Old neurology 2 notes

Last updated on June 3, 2021 at 21:57

These are the old neurology 2 notes I wrote during the semester. I’ll leave them here for a bit in case anyone prefer them, but the other notes I wrote in separate pages are better.

Table of Contents

1. The most common types of myopathies and myositis

  • In this topic you should explain generally about myopathies and myositis, the symptoms, investigations, and then mention the rough details of the most common types
  • Most common types of myopathies and myositis
    • Inherited
      • Progressive muscular dystrophies – start in certain age and then progress
        • Duchenne muscular dystrophy
        • Becker muscular dystrophy
        • Myotonic dystrophy
        • Facioscapulohumeral muscular dystrophy (FSHD)
        • Limb-girdle muscular dystrophy
      • Congenital dystrophies – poor prognosis, associated with CNS malformation
        • With normal mental development
        • With mental deficiency
      • Congenital myopathies – good prognosis, slow development
      • Metabolic myopathies
        • Mitochondrial diseases
        • Glycogen storage disease
          • Pompe disease is rare but treatable, so important to recognize
    • Acquired
      • Rhabdomyolysis
      • Myositis
        • Polymyositis
        • Dermatomyositis
        • Inclusion body myositis
      • Myopathy due to endocrine disease
        • Hypothyroidism – must always be ruled out in myopathy
        • Hyperthyroidism
      • Toxic myopathy
        • Statins
        • Steroids
        • Alcohol
      • Critical illness myopathy
        • Patients on respirator, in sepsis, ICU, etc.
  • Clinical features of myopathies and myositis
    • Negative symptoms
      • Weakness
      • Fatigue
      • Muscle atrophy
    • Positive symptoms
      • Pain
      • Cramps
      • Muscle contracture
      • Myoglobinuria
    • Distribution of muscle involvement
      • Proximal muscles – most frequent
      • Distal muscles – rarely, more commonly polyneuropathy
  • Investigations in myopathies and myositis
    • Serum creatine kinase (CK)
      • Almost always elevated, released from damaged muscle
      • Normal CK does not exclude myopathy
    • EMG
      • Differentiates neurogenic and myopathic problems
      • Shows typical myopathic features (small, short motor potentials)
    • MRI
      • Very good for muscle involvement, can see inflammation, atrophy, oedema
      • Can see the distribution and extent of myopathy
      • Can guide location for biopsy
    • Muscle biopsy
      • Indicated in typical features + typical EMG findings
      • Required for diagnosis of the specific type of myositis
      • MHC-I is usually absent on skeletal muscle, but present in myositis
      • MHC-I is absent in muscular dystrophy
      • Shows inflammation in myositis
      • Shows necrosis in dystrophy
    • Molecular genetic studies
      • Can eliminate the need for muscle biopsy in certain genetic diseases
      • Duchenne, myotonic dystrophy, FSHD, etc.
  • Duchenne muscular dystrophy
    • 1/3500 male births
    • X-linked recessive deletion of dystrophin gene
    • Clinical features
      • Onset 3 – 5 years
      • Progressive muscle paresis and atrophy of proximal limbs
      • Calf hypertrophy
      • Hyporeflexia
      • Bilateral Trendelenburg gait
      • Gower sign (Patient stands up by supporting themselves on their thighs and then using their hand to “walk up” the body)
      • Cardiac and respiratory muscle involvement
        • Dilated cardiomyopathy
        • Arrhythmia
    • Diagnosis
      • Increased serum creatine kinase and aldolase
      • Confirmatory test: genetic analysis or muscle biopsy
        • Biopsy shows absent dystrophin
        • Genetic analysis shows deleted dystrophin gene
    • Treatment
      • Steroids – delay wheelchair by 2 years
      • Physiotherapy
      • Assist devices
    • Prognosis
      • Wheelchair-bound at 10 – 15 years
      • Life expectancy ~30 years
      • Death by cardiac or respiratory failure
  • Becker muscular dystrophy
    • 1/30 000 male births
    • X-linked recessive in-frame mutation of dystrophin gene
    • Clinical features same as Duchenne, but less severe, begins later, and more slowly progressing
    • Diagnosis same as Duchenne, but biopsy shows reduced dystrophin, not absent
    • Treatment same as Duchenne
    • Prognosis better than Duchenne
  • Myotonic dystrophy
    • 5 – 10/100 000 births
    • Autosomal dominant inheritance
    • Begins in adolescence or early adulthood
    • Clinical features
      • Myotonia (impaired muscle relaxation after voluntary contraction)
      • Weakness – first of face, eyes, then distal limb
      • Narrow face
      • Frontal balding
      • Cataract
      • Arrhythmias
      • Low intelligence
      • Endocrine problems
    • Diagnosis
      • EMG – shows myopathy, myotonia
      • Genetic test – definitive diagnosis
    • Treatment
      • Symptomatic
  • Dermatomyositis
    • Epidemiology
      • 8/100 000 prevalence
      • Affects children and adults
      • Females > males
    • Can be primary or secondary to adenocarcinoma
    • Autoantibody-mediated myositis
    • Clinical features
      • Proximal, symmetrical muscle weakness
      • Skin symptoms (heliotrope rash, Gottron papules)
      • Progression over weeks/months
    • Diagnosis
      • High CK
      • Myositis-specific antibodies may also be present
      • Inflammation on biopsy
      • Malignancy must be ruled out
    • Treatment
      • Steroids or other immunosuppressants
      • Physical therapy
  • Polymyositis
    • Epidemiology
      • 7/100 000 prevalence
      • Affects adults
      • Females > males
    • Idiopathic
    • CD8+ T-cell-mediated myositis
    • Clinical features
      • Proximal, symmetrical muscle weakness
      • No skin symptoms
      • Progression over weeks/months
    • Diagnosis
      • High CK
      • Inflammation on biopsy
      • Myositis-specific antibodies may also be present
    • Treatment
      • Steroids or other immunosuppressants
      • Physical therapy
  • Necrotizing myositis
    • Similar to dermatomyositis and polymyositis but more severe
    • Can be primary or secondary to adenocarcinoma
    • Clinical features
      • Proximal symmetric muscle weakness
    • Diagnosis
      • High CK
      • Necrosis on biopsy
    • Treatment
      • Stronger or multiple immunosuppressants necessary
  • Inclusion body myositis
    • Epidemiology
      • 2/100 000 prevalence
      • Affects elderly
      • Males > females
    • Idiopathic
    • Clinical features
      • Distal, asymmetrical muscle weakness of upper extremity
      • No skin symptoms
      • Slow progression over years
    • Diagnosis
      • High CK
      • Vacuoles on biopsy
    • Treatment
      • No specific treatment, but progression is slow
      • Physiotherapy

Accidental (provoked) seizures

  • Provoked seizures
    • A provoked seizure is one invariably caused by well-defined provoking factors and not by a disorder
    • Etiology
      • Febrile seizures in childhood
      • Sleep deprivation
      • Photic stimulation with a stroboscope
      • Alcohol withdrawal
      • Drug withdrawal
    • Almost always generalized tonic-clonic
    • Treated by avoiding the provoking factor
      • Sometimes require antiepileptics acutely, but not long-term
  • Symptomatic seizures (= accidental seizures)
    • A symptomatic seizure is one caused by a serious acute illness affecting the CNS
    • Etiology
      • HSV encephalitis
      • Autoimmune encephalitis
      • Intracranial tumour (esp. meningioma)
      • Head trauma
        • Severe contusion
        • Subdural haematoma
      • Sinus thrombosis
      • Stroke
      • Metabolic disturbances (hypoglycaemia, hyponatraemia, hypernatraemia, …)
      • Drug intoxication
      • Sepsis
    • Usually focal, sometimes progresses to generalized tonic-clonic
    • Treated by antiepileptics, often lifelong (even if underlying condition is treated)

2. Benign positional paroxysmal vertigo

  • Epidemiology
    • Peak incidence in 50s
    • Female > male
  • Pathomechanism
    • Otoliths dislodging in endolymph into semi-circular canals
  • Clinical features
    • Paroxysmal episodes of vertigo lasting < 1 minute
    • Triggered by specific movements (hence positional)
    • Nystagmus toward affected side
  • Diagnosis
    • Positive Dix-Hallpike manoeuvre
  • Treatment
    • Epley repositioning manoeuvre
  • Dix-Hallpike manoeuvre
    • Used in suspected BPPV
    • Procedure:
      • Patient sits on the examination table
      • Rotate the head 45 degrees to the side of the suspected BPPV
      • Keeping the neck rotated, quickly lay the patient in a supine position so that their head hangs slightly off the short end of the table
      • Hold this position for 20 seconds
      • Slowly reposition patient into the original seated position
    • Negative:
      • Patient experiences no vertigo
      • No nystagmus appears
    • Positive:
      • Patient experiences vertigo and nystagmus when supine, which spontaneously resolve within the 20 seconds
  • Epley repositioning manoeuvre
    • Indicated if Dix-Hallpike is positive
    • This procedure moves the stone from the posterior semicircular canal into the utricle, improving symptoms
    • Procedure:
      • Patient sits on the examination table
      • Rotate the head 45 degrees to the side of the suspected BPPV
      • Keeping the neck rotated, quickly lay the patient in a supine position so that their head hangs slightly off the short end of the table
      • Hold this position for 30 seconds, or until the nystagmus disappears
      • Turn patient’s head by 90° towards the unaffected side
      • Hold this position for 30 seconds, or until the nystagmus disappears
      • Turn patient’s head another 90° towards the unaffected side, so that the patient is lying on their side with they head facing the ground
      • Hold this position for 30 seconds, or until the nystagmus disappears
      • Slowly bring patient back to a seated, upright position with the head in a neutral position
      • Ask patient to remain in this position for about 15 minutes

Transient ischemic attack

  • Definition
    • Old, classic definition: full resolution of symptoms within 24 hours
    • New definition: transient neurological dysfunction caused by ischaemia without infarction
      • New definition requires MRI with DWI sequence for diagnosis
  • Clinical features
    • Similar to those of ischaemic stroke (see topic 60)
    • Most symptoms resolve within 1 hour
    • Most patients present after symptoms have resolved
    • Most often acute
    • Amaurosis fugax
      • In case of involvement of ophthalmic artery
      • Sudden, painless loss of vision
      • Lasts for second to minutes but recovers spontaneously
      • Usually unilateral
  • Differential diagnosis
    • Migraine with aura
    • Todd’s paralysis (post-seizure neurologic deficit)
    • Hypoglycaemia
    • Intracranial structural lesions (tumour, haemorrhage, etc.)
    • Syncope
    • BPPV, labyrinthitis, Meniere disease
    • Brain abscess, encephalitis
    • Demyelinating disorders (multiple sclerosis)
  • ABCD2 score
    • Used to estimate risk of stroke in the next two days
    • Can be a help to guide whether patient should be hospitalised or not
    • Each factor gives 1 or 2 points
    • Age > 60 years – 1 point
    • BP – SBP > 140 mmHg or DBP > 90 mmHg – 1 point
    • Clinical features
      • Speech impairment – 1 point
      • Unilateral weakness – 2 points
    • Duration
      • 10 – 59 minutes – 1 point
      • > 60 minutes – 2 points
    • Diabetes – 1 point
    • 0 – 3 points: low risk (1%)
    • 4 – 5 points: moderate risk (4%)
    • 6 – 7 points: high risk (8%)

3. Differential diagnosis of tremors

  • Classification
    • Resting tremor – occurs in rest
    • Action tremor – occurs during voluntary movement
      • Kinetic tremor – occurs when moving toward a target, low amplitude
      • Intention tremor – occurs when moving toward a target, high amplitude
      • Postural tremor – when holding arms out against gravity
  • Physiological tremor
    • A type of postural tremor
    • Occurs in healthy people when exposed to certain factors
    • Etiology
      • Stress
      • Sympathetic activation
      • Hyperthyroidism
      • Caffeine
      • Alcohol withdrawal
    • Clinical features
      • Fine tremor (low amplitude)
    • Treatment
      • Avoid triggers
      • Benzodiazepines in severe cases
  • Essential tremor
    • A type of postural tremor
    • Etiology
      • Hereditary (autosomal dominant)
      • Worsens with stress, fatigue, caffeine
    • Clinical features
      • Fine tremor
      • Affects the hands and the head
      • Symmetric
      • Improves with alcohol
    • Treatment
      • Pharmacological treatment
        • Treatment usually doesn’t improve symptoms a lot
        • Propranolol
        • Antiepileptics
      • Deep brain stimulation
        • In very severe cases
        • Stimulation of thalamic nuclei
        • Can be effective for any kind of disabling tremor
  • Intention tremor
    • Due to cerebellar injury
    • Etiology
      • Cerebellar stroke
      • Trauma
      • Multiple sclerosis
      • Chronic alcohol abuse
    • Clinical features
      • Occurs during voluntary movements
      • Coarse (low frequency) tremor
      • Slow “zigzag” movement towards a target
      • Tremor is biggest right before reaching target
  • Resting tremor
    • In parkinsonism
    • Etiology
      • Parkinson disease
      • Dopamine antagonist drugs (antipsychotics, etc.)
      • Parkinson-plus syndromes
    • Clinical features
      • Occurs during rest
      • Asymmetric
      • Special movement of the thumb and index finger as if you were rolling a pill between them (pill-rolling tremor)
    • Treat underlying parkinsonism
  • Neuropathic tremor
    • Etiology
      • Diabetes
      • Etc.
    • Clinical features variable
  • Psychogenic tremor
    • Etiology
      • Psychiatric disease
    • Clinical features
      • Features change when patient is distracted
  • Flapping tremor (asterixis)
    • Etiology
      • Hepatic encephalopathy
    • Clinical features
      • Characteristic “flapping” motion of hands

(Diagnostic steps in acute stroke)

  • Ensuring medical stability (airways, breathing, circulation)
  • ECG
  • Labs
    • CBC
    • INR
    • Glucose
    • Electrolytes
    • ABG
    • Infectious parameters
    • Toxicology
  • Diagnostic imaging
    • Purpose
      • To exclude haemorrhage as a cause of stroke
        • If patient has clinical symptoms of stroke and no haemorrhage on imaging, they have ischaemic stroke until proven otherwise
    • ECG and labs should not delay diagnostic imaging!
    • Non-contrast CT (first choice)
      • Can not detect ischaemia in the first 6 hours
      • Can sometimes detect hyperdense vessels, a sign of a clot in the vessel
    • MRI with DWI sequence (alternative)
      • Is superior to non-contrast CT but is less available and more often contraindicated
      • Can detect ischaemia after 30 minutes
  • Vascular imaging
    • After initial diagnostic imaging
    • Purpose
      • To detect occlusion of large artery
        • If present, patient may be eligible for mechanical thrombectomy
      • To evaluate collateral circulation
        • Good collateral -> better outcome of revascularization therapy
      • To evaluate whether there is atherosclerosis present, which would suggest a thrombotic etiology
    • Modalities
      • Carotid ultrasound
      • CT or MRI angiography
  • Perfusion imaging
    • Indicated if the findings may influence the decision to perform thrombectomy after the initial 6 hour window
    • Can be performed simultaneously with vascular imaging
    • Purpose
      • To determine the size of the penumbra, the brain area which is potentially salvageable by revascularization
    • Modalities
      • MRI with DWI and PWI
      • CT perfusion
  • Cardiological investigation
    • Done if a cardiac etiology of stroke is suspected, or there is cryptogenic stroke
    • Not performed in the acute phase – only later
    • Modalities
      • Transthoracic echocardiography
        • Can not detect PFO
      • Transoesophageal echocardiography
        • Can detect PFO
      • Holter ECG
        • Normal ECG at admission does not exclude paroxysmal AF
        • Sensitivity of Holter to detect paroxysmal AF increases with the duration of the ECG monitoring

Treatment of the acute stroke

  • Management of acute ischaemic stroke
    • Admission to stroke unit
    • ASPECTS score
      • 10-point scale scored based on native CT
      • Used to quantify the size of ischaemic lesion
      • 10 points = normal native CT
      • 0 points = ischaemic changes throughout the MCA territory
      • Low score – lower chance of good clinical outcome after revascularisation. Might influence the decision to perform revascularisation
    • IV thrombolysis
      • With a rtPA (recombinant tissue plasminogen activator)
        • Alteplase, duteplase, tenecteplase
      • Can be used for both large artery and small artery occlusion
        • But it is less effective for large artery occlusion, therefore it should be combined with thrombectomy
      • Time window: Within 4,5 hours of symptom onset
        • The sooner, the better
      • Risk
        • Relatively safe
        • May increase risk of haemorrhage
        • Haemorrhage as cause of stroke must be ruled out first
      • Contraindications
        • INR > 1,7
    • Mechanical thrombectomy
      • If there is large artery occlusion on CT angiography
        • Large artery means internal carotid, basilar, vertebral arteries, or large segments of middle or anterior cerebral artery
        • 10% of ischaemic stroke are due to large artery occlusion
        • Thrombolysis has poor effect on large artery occlusion
      • Time window: Within 6 hours of symptom onset
        • Can be extended to up to 24 hours if there is a large penumbra (salvageable brain area) or there is basilar artery occlusion
        • MRI with perfusion sequencing necessary to determine the size of the penumbra
      • Should be combined with thrombolysis if within the 4,5 hour time window
    • Aspirin
      • For all cases of acute ischaemic stroke
      • Given within 48 hours of symptom onset and continued indefinitely
      • In patients given thrombolysis aspirin should be delayed until after the 24 hour post-thrombolysis imaging has excluded haemorrhage
      • Aspirin decreases recurrence rate
    • Decompressive hemicraniectomy
      • If there is malignant MCA infarction
      • Within 48 hours of symptom onset
      • Reduces mortality substantially, but has high risk of disability
    • Blood pressure management
      • Blood pressure during stroke is usually high
      • Purpose
        • Decrease blood pressure
        • But don’t treat too aggressively! Avoid too low blood pressure
      • If patient does not receive thrombolytics
        • Target BP < 220/120 mmHg
      • If patient does receive thrombolytics
        • Target BP < 185/110 mmHg
      • Drugs
        • Labetalol
        • Enalapril
        • Nitroprusside
        • Nitropaste
    • Blood glucose management
      • Insulin titration if serum glucose > 10 mM
    • Fluid replacement therapy
      • Patients with stroke are often fluid deprived
      • Isotonic saline is recommended if needed
  • Management of acute haemorrhagic stroke
    • Admission to stroke unit
    • Reverse anticoagulation (if patient was on it)
    • Blood pressure management
      • Systolic target BP varies from 140 to 160 mmHg
        • Depending on type of haemorrhage and original BP
    • Blood glucose management
      • Insulin titration if serum glucose > 10 mM
    • Surgical evacuation of haemorrhage
      • On certain indications
        • Large cerebellar haemorrhage
        • Brainstem compression
        • Hydrocephalus
    • Prevent vasospasm
      • With nimodipine
      • For SAH
    • Aneurysm repair
      • For aneurysmal SAH
      • Methods
        • Surgical clipping
        • Endovascular coiling

4. Myasthenia gravis

  • Myasthenia gravis (MG)
    • Etiology
      • Idiopathic
      • Thymoma
      • Other autoimmune conditions
    • Pathomechanism
      • Autoantibodies against the acetylcholine receptor (AChR) causes competitive inhibition of acetylcholine at the neuromuscular junction
      • -> decreased receptor density -> weakness and fatigue
      • -> activation of complement -> muscle cell lysis
      • Some patients with myasthenia gravis have autoantibodies against another antigen, which produces different clinical picture
        • Anti-muscle-specific kinase (anti-MuSK)
        • Anti-voltage-gated Ca channel (anti-VGCA)
    • Clinical features of “normal” myasthenia gravis
      • Muscle weakness which worsens with increased muscle use and improve with rest
        • Symptoms are usually worse in the evening
      • Symptoms worsen with certain drugs (the list is endless)
        • Muscle relaxants
        • Aminoglycosides
        • Fluoroquinolones
        • Macrolides
        • Beta blockers
        • Hydroxychloroquine
      • Smaller muscles are affected first, larger muscles later
      • Progresses over months, years
      • Many patients have “ocular” MG (only eye muscles affected), but some develop “generalized” MG
      • Weakness of eye muscles
        • Usually first symptom
        • Ptosis
        • Diplopia
        • Blurred vision
      • Weakness of muscles of mouth and throat
        • Slurred speech
        • Difficulty chewing or swallowing
      • Proximal limb weakness
      • Respiratory muscle weakness
    • Diagnosis
      • Serology for anti-AChR antibodies
      • ENG, EMG
      • Imaging for thymoma
    • Treatment
      • Symptomatic (acetylcholinesterase inhibitor)
        • Usually pyridostigmine
      • Immunosuppressive
        • If symptomatic therapy alone isn’t enough
        • Steroids
        • Azathioprine, mycophenolate mofetil, etc
      • Thymectomy
        • For all patients with thymoma
        • For certain patients without thymoma but generalized MG
  • MuSK-positive myasthenia gravis
    • Much less frequent than AChR-positive MG
    • Caused by anti-muscle-specific kinase (anti-MuSK) antibodies
    • More severe type of myasthenia gravis, worse response to treatment, similar clinical features
  • Lambert-Eaton myasthenic syndrome
    • Much less frequent than AChR-positive MG
    • Caused by anti-voltage-gated Ca channel (anti-VGCA) antibodies
    • Associated with lung cancer
    • Muscle weakness usually beginning in proximal lower limbs. Ocular involvement is rare

Convulsive syncope

  • = Form of syncope which is accompanied by myoclonic jerks and tonic stretching
  • Must be differentiated from epileptic seizures
  • It’s not difficult to differentiate them if you witness them and you’ve seen what both types look like – the difficulty comes from trying to differentiate them if you don’t witness them personally
  • Etiology
    • Vasovagal syncope
    • Cardiogenic syncope
      • Arrhythmia
      • Myocardial infarction
      • Pulmonary embolism
    • Hypoglycaemia
    • Antihypertensive drugs
  • Pathomechanism
    • > 10 second globally decreased CBF
  • Clinical features
    • Usually brief (< 20 seconds)
    • Myoclonic jerk
    • Tonic stretching
    • Tongue bite on the apex of the tongue (not on the lateral side)
    • Never starts with tonic phase
    • Always starts with a clonic phase
    • No post-convulsive confusion
    • Eyes remain open
  • Must be differentiated from true seizure based on clinical features and history
    • Family history of sudden death or heart disease
    • Personal history of syncope
    • Occurs immediately after blood-taking, standing for a long time, pain, coughing, etc.

5. Polyneuropathies

  • General
    • Etiology
      • Genetic (most common)
      • Medical illness
      • Deficiency
      • Endocrine
      • Toxic
      • Inflammatory
      • Infectious
        • Lyme disease
        • Hepatitis B, C
      • Paraneoplastic (topic 24)
    • Types according to pathomechanism
      • Demyelinating neuropathy
        • Damage to myelin sheath
        • Causes slow conduction or conduction block
        • Progressive but better response to treatment
      • Axonal neuropathy
        • Idiopathic in 50% of cases
        • Damage to axon
        • Causes degeneration of distal nerve, denervation
        • Worse response to treatment
    • ENG
      • Shows slow conduction in demyelinating neuropathy
      • Shows denervation in axonal neuropathy
  • Diabetic neuropathy
    • Most common polyneuropathy
    • An axonal neuropathy
    • Types
      • Distal symmetric sensory or sensorimotor neuropathy (most common)
        • Sensory loss of distal lower extremities which progresses upwards
        • Burning sensation
      • Autonomic neuropathy
      • Painful diabetic neuropathy
      • Cranial neuropathy
      • Radiculoplexus neuropathy
    • Treatment
      • Some types spontaneously resolve
      • Tight blood glucose control
      • Neuropathic pain management
        • SNRI
        • Tricyclic antidepressants
        • Gabapentin/pregabalin
        • Capsaicin
  • Alcoholic polyneuropathy (topic 21b)
    • Second most common polyneuropathy
    • Due to alcohol and thiamine deficiency
    • Treatment
      • Abstinence from alcohol
      • Thiamine supplementation
  • Hereditary polyneuropathies
    • Hereditary motor sensory neuropathies (HMSN)
      • Charcot-Marie-Tooth disease (HMSN type I)
        • Calf atrophy
        • Foot drop
        • Pes cavus
      • Refsum disease (HSMN type IV)
    • Hereditary sensory autonomic neuropathies (HSAN)
    • Distal hereditary motor neuropathies (dHMN)
  • Inflammatory neuropathies
    • Account for 30% of neuropathies
    • Immune-mediated infiltration of peripheral nerves causes destruction of myelin sheath and/or axons
    • Types
      • Acute = Guillain-Barre syndrome (own topic)
      • Intermediate
        • Subacute inflammatory demyelinating polyradiculoneuropathy
        • Vasculitic neuropathies
        • Infections (HBV, HCV, HIV)
        • Malignancy
        • Paraneoplastic
      • Chronic
        • Multifocal motor neuropathy (MMN)
          • Asymmetric muscle weakness of upper limb
        • Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
        • Distal acquired demyelinating sensorimotor neuropathy (DADS)
        • Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM)
        • Etc.
    • These neuropathies are treatable
      • For GBS, see its topic
      • Chronic neuropathies are treated with methylprednisolone, plasma exchange and/or IVIG
  • Small fibre neuropathy
    • Symptoms: Pain, autonomic dysfunction
    • Biopsy necessary to diagnose (ENG only measures large fibres)

Subarachnoid haemorrhage (SAH)

  • Can be nontraumatic and traumatic – will write about nontraumatic here. For traumatic, see topic 19
    • Traumatic SAH is more common than non-traumatic
  • 6 – 10% of all strokes
  • Etiology
    • Rupture of intracranial aneurysm in the circle of Willis (70% of cases)
      • Risk factors for developing aneurysm: smoking, female, hypertension, alcoholism, family history
      • Risk factors for rupturing aneurysm: acute hypertension, strain
    • Rupture of arteriovenous malformation or angiomas
    • Idiopathic (no cause is found)
  • Most aneurysms are found in the anterior circulation
  • Clinical features
    • “Warning” symptoms before
      • 20% have them in the days or weeks before
      • Transient diplopia or headache
    • Thunderclap headache
      • Characteristically described as the worst headache of their lives
      • Sudden
    • Loss of consciousness
    • Seizure
    • Nausea, vomiting
    • Meningism (stiff neck, photophobia, etc.)
    • Focal neurological symptoms
  • Diagnosis
    • First-line: Native CT -> shows hyperdense blood in subarachnoid space
    • MRi if CT is negative but suspicion remains high
    • Lumbar puncture
      • If CT is negative but suspicion remains high
      • Shows yellowish/reddish CSF with increased RBC
    • DSA or CT angiography -> to identify source of ongoing bleeding before treatment
  • Treatment
    • The goal is to treat and prevent complications, especially rebleeding
    • Admission to ICU, supportive care
    • Decreased BP to < 160 mmHg but not much lower
    • CCB (nimodipine) to prevent vasospasm
    • If caused by aneurysm -> endovascular coiling (or surgical clipping) of the aneurysm within 72h
      • A coil is inserted into the aneurysm which completely obstructs it
    • If caused by AVM or angioma -> irradiation/surgery/endovascular
    • Long-term follow-up for complications
  • Complications
    • Rebleeding (common)
    • Vasospasm leading to ischaemia
    • Hydrocephalus
    • Epilepsy
    • Hypopituitarism (can occur long time after)
  • Prognosis
    • 10% don’t reach the hospital at all
    • 30-day mortality rate is 46%
    • Many of those who survive sustain severe disability and decrease in quality of life

6. Neuroimaging

  • Structural neuroimaging – gives diagnosis of gross intracranial disease, like tumour or injuries
  • Functional neuroimaging – used to examine certain functions
  • CT
    • Indications
      • Mostly used for neurological emergencies
      • Stroke – to differentiate ischaemic from haemorrhagic
      • Traumatic injury of brain and spine
    • Advantages
      • Fast (few minutes)
      • Cheap
      • No contraindications except pregnancy
      • Patient cooperation not required
    • Disadvantages
      • Radiation
      • Not good for soft tissue imaging
    • Specific techniques
      • Native:
        • Blood is hyperdense
        • Ischaemic lesions hypodense after 24h
      • Contrast media: Cancer shows enhancement
      • CT angiography: To find occluded vessels and examine collateral blood supply
      • CT perfusion – can differentiate salvageable ischaemic brain from infarcted brain in ischaemic stroke
  • MRi
    • Indications
      • Soft tissue imaging
      • Demyelinating disorders
      • Infectious CNS disorders
      • Inflammatory CNS disorders
      • Neurodegenerative disorders
      • General imaging of brain, spinal cord, peripheral nerves, cranial nerves
      • Epilepsy
      • Muscle atrophy, fatty degeneration of muscle
    • Advantages
      • No radiation
      • Good for soft tissue imaging
    • Disadvantages
      • Patient cooperation is required – anxiolytic or anaesthetic may be required
      • Slow (20-30 minutes)
      • Expensive
      • Contraindicated for metals, pacemakers
      • Claustrophobic
    • Modalities
      • T1: good for anatomical structures (brain, spine, muscles)
      • T2: grey and white matter lesions
      • Contrast-enhanced T1: shows BBB damage
      • FLAIR: more sensitive for white matter lesion
      • DWI: very sensitive for recent lesions (ischaemia, oedema, inflammation)
      • SWI: visualization of deposition of metals
      • Tractography: visualizes main tracts before neurosurgery or in ALS
      • MR angiography: same as CT angiography, but doesn’t require contrast
      • MR spectroscopy: measure metabolites like NAA (marker of neuronal loss) or lactate (marker of metabolic disease)
      • Functional MRI: localizes certain functional areas (speech centre, motor centre) before neurosurgery
  • US
    • Indications
      • Extracranial vessels
        • Screening patients with high risk (dyslipidaemia, ASCVD, DM, etc.)
        • After TIA or stroke
      • Intracranial vessels (transcranial doppler)
        • Monitor vasospasm in subarachnoid haemorrhage
        • Monitor embolism in cryptogenic stroke
    • Advantages
      • Fast
      • Cheap
      • No radiation
    • Disadvantages
      • Result depends on operator experience
  • DSA
    • To visualize extracranial or intracranial vessels
      • Narrowing, occlusion, or aneurysm
    • Interventional neurology – stenting, thrombectomy, aneurysm closure
  • SPECT – measures CBF
    • Indications
      • Epilepsy imaging – CBF increases during seizure
      • Alzheimer disease
      • Parkinson disease (DAT scan) – asymmetric uptake in basal ganglia
  • PET – measures metabolic activity
    • Indications
      • Epilepsy imaging – metabolic activity increases during seizure
      • Alzheimer disease (amyloid PET imaging)
      • Tumours in whole body

Guillain-Barre syndrome

  • Guillain-Barre syndrome (GBS) is no longer classified as a single disease, but rather a group of disorders
    • Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) accounts for 90% of Guillain-Barre in the western hemisphere, and so is the most important one for us
    • Other types
      • Acute motor axonal neuropathy (AMAN)
        • Pure motor symptoms
        • Most common in Asia, Mexico
      • Acute motor and sensory axonal neuropathy (AMSAN)
        • Motor, sensory, and autonomic symptoms
      • Miller Fisher syndrome (MFS)
        • Involves cranial nerves
        • Sensory ataxia, areflexia, ophthalmoplaegia, ptosis
      • Functional variants of GBS
      • Etc.
  • Etiology
    • Upper respiratory tract or gastrointestinal infection 1 – 4 weeks earlier
      • Especially campylobacter jejuni infection
  • Pathomechanism (of AIDP)
    • Immune reaction against an earlier infection forms antibodies which, due to molecular mimicry, target antigens on Schwann cells, causing demyelination
  • Clinical features (of AIDP)
    • Symptoms progress over the course of 2 – 4 weeks
      • Most patients peak at week 2
    • Symmetric flaccid muscle weakness
      • Weakness usually begins in legs and ascend from there
    • Absent deep tendon reflexes
    • Paraesthesia in hands and feet
    • Cranial nerve signs may be present (facial palsy, ptosis)
    • 10 – 30% develop severe respiratory muscle weakness, requiring ventilatory support
    • Dysautonomia
      • Diarrhoea/constipation
      • Arrhythmia
  • Diagnosis
    • Based on typical clinical picture as well as:
    • CSF showing albuminocytologic dissociation (high protein, normal cell count)
    • ENG and EMG show demyelination
    • Enhancement of nerve roots on MRI (rarely used)
  • Treatment
    • All patients should be admitted for monitoring
      • Respiratory and cardiac monitoring
      • General supportive care
    • Intravenous immunoglobulin or plasma exchange
      • To all patients
      • Both are equally effective
    • Never give steroids!
  • Prognosis
    • Mortality increases with age and those with underlying pulmonary disease

7. Carpal tunnel-syndrome

  • Median nerve lesion
    • Sensory symptoms (pain, paraesthesia)
      • Middle of the palm
      • Palmar aspect of first, second, and third fingers
      • Lateral half of the fourth finger
    • Motor symptoms (less common)
      • Weak pinching
      • Weak grip
      • Thenar atrophy
  • Carpal tunnel syndrome
    • Most common cause of median nerve lesion
    • Etiology
      • Obesity
      • Female > male
      • Diabetes
      • Pregnancy
      • Certain repetitive wrist movements at work
    • Diagnosis
      • Carpal tunnel is a clinical diagnosis
      • Tinel sign
        • Applying pressure to the palmar side of the wrist causes paraesthesia in the area of the median nerve
      • Nerve conduction studies or electromyography can help the diagnosis
    • Treatment
      • Splinting
      • Glucocorticoid injection
      • Surgical decompression

Secondary headaches

  • = those headaches which occur as a symptom of an underlying disease
  • Also called symptomatic headaches
  • Causes
    • Mass-occupying lesions
      • Epidural haemorrhage
      • Subdural haemorrhage
      • Subarachnoid haemorrhage
      • Intracerebral haemorrhage
      • Tumour
      • Brain abscess
    • Other CNS pathology
      • Meningitis/encephalitis
      • Cerebral venous sinus thrombosis
      • Ischaemic stroke/TIA
      • Dissection of carotid/vertebral artery
      • Post head trauma
    • Extracranial disorders
      • Infections near to the CNS (sinusitis, etc.)
      • Systemic infection
      • Hypertensive emergency
      • Acute glaucoma
      • Temporal arteritis and other vasculitides
      • Substance abuse (alcohol, etc.)
      • Substance withdrawal (caffeine, etc.)
      • Medication side effect
        • Nitrates
        • Analgesic overuse – overuse of analgesics can cause headache
  • Red flags of secondary headache
    • Non-specific symptoms like fever – rule out metastasis, infection
    • Neurological symptoms – rule out stroke, CNS lesion, encephalitis
    • Age > 50 at onset – rule out temporal arteritis, glaucoma, tumour
    • Sudden onset (esp. thunderclap) – rule out haemorrhagic stroke
    • Papilloedema or precipitated by Valsalva or exertion – rule out raised ICP
    • Positional – rule out intracranial hypotension
    • Progressive worsening or significant change in symptom pattern – rule out all secondary causes

(Brain tumours in general)

  • In adults, secondary brain tumours are 10x as common as primary
  • Pathophysiology
    • Symptoms constantly progress without significant remission
    • Focal neurological symptoms progress from one region to multiple
    • According to the Monroe-Kellie doctrine, a brain tumour must decrease CSF flow and cerebral blood flow
      • In the beginning phase, CSF and CBF flow can decrease to compensate for the increased ICP
      • Eventually the compensatory mechanisms are exhausted, causing large increase in ICP
  • Clinical features
    • Headache
    • Vertigo
    • Increased ICP
      • Nausea, vomiting
      • Papilloedema
    • Focal neurological symptoms
    • Focal epilepsy
  • Most common tumours in childhood
    • Craniopharyngioma
    • Medulloblastoma
    • Cerebellar astrocytoma
  • Most common tumours in adulthood
    • CNS metastases
    • Meningioma
    • Glioblastoma
    • Pituitary tumours
  • Prognostic factors
    • Tumour grade, which depends on the histological type
    • Biogenetical markers of tumour
    • Karnofsky Performance Status (KPS)
    • Age of patient
    • Comorbidities
    • Presence of metastasis of CSF
  • Diagnosis
    • Imaging
      • Gold standard is contrast-enhanced MRI
        • CT is second choice
      • DSA
        • For vascularised tumours
        • May allow for tumour embolization therapy
      • PET/CT
    • Majority of cases undergo biopsy and histopathology
      • In many of the cases the biopsy isn’t conclusive or diagnostic -> repeat biopsy, or the precise histologic type of the tumour won’t be known until surgical removal
      • Brainstem tumours can’t be biopsied
      • Histopathology is repeated after surgical removal
  • Treatment
    • Complete surgical resection is required for cure
      • Surgical resection in brainstem is rarely possible
    • Cytoreduction/debulking may improve prognosis
    • Chemotherapy is not much used in CNS tumours
      • CNS metastasis is the exception – it’s as sensitive to chemotherapy as the primary tumour

8. Gliomas

  • On this topic you should first talk about brain tumours in general and then a bit about gliomas specifically (according to my teacher)
  • These tumours originate from glial cells like astrocytes, oligodendrocytes, and ependymal cells
  • Gliomas are the second most common primary brain tumours in adults (after meningioma)
  • Pathology
    • Types
      • Astrocytoma
      • Oligodendroglioma
      • Ependymoma
    • Testing for isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion are important as they have a better prognosis than wildtype
      • IDH mutated and 1p/19q codeleted tumours are more sensitive to chemotherapy
    • Grading of astrocytoma
      • Grade I astrocytoma = pilocytic astrocytoma
      • Grade II astrocytoma = diffuse astrocytoma
      • Grade III astrocytoma = anaplastic astrocytoma
      • Grave IV astrocytoma = glioblastoma
      • Higher grades have more mitosis, more atypia, worse prognosis
  • Glioblastoma is the most common glioma in adults
  • Pilocytic astrocytoma is the most common glioma in children

Parkinson’s disease

  • (I went a little overboard with the details for the diagnosis and treatment. All the details aren’t necessary)
  • Parkinson disease (PD) = Idiopathic cause of parkinsonism
  • Clinical features
    • Unilateral onset
    • Slow progression
    • Parkinsonism (bradykinesia, rest tremor, rigidity, postural instability)
    • Expressionless face
    • Hypokinetic gait
    • Small handwriting
    • Cognitive dysfunction (dementia)
    • Psychosis
    • Mood disorders
    • Olfactory loss
  • Diagnosis
    • In typical presentations, only anamnesis and physical examination are necessary
    • In less typical presentations an MRI or MIBG scintigraphy can be used to exclude many other causes of parkinsonism
    • Parkinson disease is a clinical diagnosis based on the MDS diagnostic criteria
    • A definitive diagnosis requires:
      • Diagnosis of parkinsonism
      • Two supportive criteria
      • No absolute exclusion criteria
      • No red flags
    • A probable diagnosis requires:
      • Presence of bradykinesia plus resting tremor or rigidity
      • No absolute exclusion criteria
      • Presence of red flags counterbalanced by supportive criteria
    • Supportive criteria
      • Beneficial response to dopaminergic therapy
      • Presence of levodopa-induced dyskinesia
      • Resting tremor
      • Olfactory loss
      • Cardiac sympathetic denervation on MIBG scintigraphy
    • Absolute exclusion criteria
      • Cerebellar symptoms
      • Concomitant anti-dopamine drug therapy
      • Cortical sensory loss
      • Diagnosis of another condition known to cause parkinsonism
      • +++
    • Red flags
      • Rapid progression of gait impairment
      • Absence of progression of motor symptoms
      • Severe dysphonia, dysarthria, or dysphagia
      • +++
  • Differential diagnosis of parkinsonism
    • Parkinson disease
    • Secondary parkinsonism
      • Drug-induced (antipsychotics, antiemetics, etc.)
      • Metabolic (Wilson disease, chronic liver failure, etc.)
      • Infections (HIV, encephalitis lethargica, etc.)
      • Structural brain lesions
        • Hydrocephalus
        • Tumour
        • Chronic subdural haematoma
        • +++
      • Trauma
      • Cerebrovascular disease
      • Toxins
    • Parkinson-plus syndromes
      • They all cause parkinsonism but have other clinical features as well
        • Can usually be distinguished from PD by imaging and clinical features
      • Dementia with Lewy-bodies
        • Dementia (occurs earlier than in PD)
        • Visual hallucinations
        • Fluctuating cognitive function
      • Multiple system atrophy
        • Autonomic dysfunction
        • Cerebellar symptoms
        • Symmetrical symptoms at onset
      • Corticobasal degeneration
        • Dementia
        • Motor symptoms affecting only one limb at onset
        • Alien limb phenomenon – patient feels that the affected limb does not belong to them
      • Progressive supranuclear palsy
        • Vertical gaze palsy
        • Frontal lobe symptoms
  • Choice of therapy depends on age and symptom severity
    • In mild cases treatment may not be necessary
  • Non-medical therapy
    • Physiotherapy
    • Speech therapy
  • Levodopa + carbidopa/benserazide
    • Most potent antiparkinsonian drug
    • Has effect in virtually all patients with PD
      • If the patient experiences no effect, they most likely have don’t have PD
    • Preferred in patients with moderate or severe symptoms at any age
    • The lowest dose which gives adequate benefit should be used
      • Rather than using a higher dose to eradicate all symptoms
    • Patients initially have very good effect, the so-called “honeymoon period”, with no motor fluctuations or dyskinesias
    • The patient experiences dyskinesias and motor fluctuations more and more often over time
      • It was previously believed that levodopa increases the rate of progression of PD, and so it should be started as late as possible to “ration” its effects
      • Nowadays we’re pretty sure that that’s not true. Instead, we now know that it is the natural progression of PD which reduces the effect of levodopa, and not the levodopa treatment itself
        • As the PD progresses and the brain’s dopamine production decreases, the fluctuations in plasma levels of levodopa cause larger and larger fluctuations in brain dopamine levels
      • So, the choice and timing of initial therapy does not impact the long-term incidence of dyskinesia and motor fluctuations, and there’s no reason not to start levodopa early
      • When the patient begins to experience these late side effects, a specialist should re-evaluate dosage, dosing schedules, choice of drugs, etc., in order to reduce them
    • Levodopa exists in immediate release (normal) and controlled release formulations
      • Controlled release formulations may decrease the incidence of dyskinesias and motor fluctuations
    • Side effects
      • Nausea
      • Somnolence
      • Headache
      • Psychiatric symptoms
        • Hallucination
        • Agitation
        • Psychosis
      • Dyskinesia
        • Usually occurs 30 – 90 minutes after taking a dose, as the action of the drug peaks (so-called “peak dose dyskinesia”)
      • Motor fluctuations (= “on – off phenomenon”)
        • “Wearing off” = symptoms return as the dose of levodopa diminishes, 3 – 4 hours after a dose
        • “Unpredictable off” = symptoms return with no obvious relationship to the time of levodopa dosing
        • “Dose failure” or “no-on response” = a dose fails to improve symptoms
  • Dopamine agonists
    • Agents
      • Pramipexole
      • Ropinirole
      • (Bromocriptine is associated with fibrosis and so is rarely used)
    • Less effective than levodopa
    • More non-motor side effects but fewer motor side effects
      • Rarely cause dyskinesia or motor fluctuations
    • Withdrawal syndrome occurs in case of abrupt cessation
      • Anxiety
      • Panic attack
      • Nausea
      • Dizziness
  • Monoamine oxidase type B (MAO-B) inhibitors
    • Agents
      • Selegiline
      • Rasagiline
      • Safinamide
    • Low effectiveness
    • Generally well tolerated – few side effects
    • Good first choice in mild PD
  • Amantadine
    • Has antiviral, dopaminergic, anticholinergic, anti-NMDA, and amphetamine-like effects
    • Low effectiveness
      • Effect decreases over time
    • Good second choice in mild PD
    • Effective in reducing dyskinesia of levodopa treatment
    • Non-severe side effects
      • Leg oedema
      • Livedo reticularis
  • Catechol-O-methyl transferase (COMT) inhibitors
    • Agents
      • Entacapone
      • Opicapone
    • These drugs prolong effect of levodopa
    • Effective in reducing motor fluctuations of levodopa treatment
  • Anticholinergics
    • Agents
      • Trihexyphenidyl
      • Benztropine
    • Effective against tremor but not for other symptoms
    • Not used in older (> 65 years) patients due to increased side effects
    • Side effects
      • Dry mouth
      • Blurred vision
      • Constipation
      • Urinary retention
      • Impaired memory
      • Confusion
  • Apomorphine
    • A dopamine agonist
    • Used for “rescue therapy” for “off periods” in levodopa treatment
    • Given as subcutaneous injection
      • Onset within 15 minutes
    • May also be given as a continuous subcutaneous apomorphine infusion (CSAI) via a pump
  • Deep brain stimulation (DBS)
    • Most frequently performed surgical procedure for PD
    • Involves placing electrodes in the subthalamic nucleus or internal globus pallidus
    • Highly effective, but carries risk for surgical complications, equipment complications, and stimulation-related complications
    • Reserved for patients who have reduced quality of life despite optimal medical treatment
  • Levodopa-carbidopa intestinal gel (LCIG) infusion
    • Involves a percutaneous gastrojejunostomy tube which infuses a levodopa-carbidopa gel into the jejunum continuously
      • A pump gives a morning bolus followed by a continuous maintenance dose during the day
    • Usually used in patients who don’t want DBS
    • Complications
      • Polyneuropathy
      • Postoperative wound infection
      • Abdominal pain
  • Older surgical procedures
    • Pallidotomy, thalamotomy, subthalamotomy
    • Effective, but invasive and destructive
    • Rarely performed nowadays

9. Peripheral facial palsy (Bell-paresis)

  • 50% of all facial palsies are idiopathic and peripheral
  • Bell’s palsy is the name of idiopathic peripheral facial palsy
  • Etiology
    • Idiopathic (= Bell’s palsy)
      • Idiopathic inflammation of CN VII in facial canal
      • Might be due to virus
    • Lyme disease
    • Infiltrative disease (lymphoma, sarcoidosis)
    • Parotid tumour
    • Schwannoma
    • Trauma (involving pyramidal bone)
    • Brainstem lesion (involving facial nucleus)
  • Clinical features
    • All symptoms on ipsilateral side
      • Can be bilateral in Lyme disease
    • Motor symptoms
      • Frowning, eye-closing, blinking is impaired
      • Inability to close the eye
      • Drooping corner of mouth
      • Disappearance of nasolabial fold
    • Pain in ear
    • Hyperacusis
    • Abnormal lacrimation
    • Abnormal taste
    • Symptoms of underlying disease (not in case of Bell’s palsy)
  • Diagnosis
    • If peripheral facial palsy is the only symptom, Bell’s palsy is assumed and no investigation is needed
    • If other symptoms are present, investigate with MRi, LP, etc.
  • Treatment and prognosis
    • In most cases Bell’s palsy resolves completely in a few weeks without treatment
      • Steroids hastens resolution if given within the first days of symptoms
      • Acyclovir can be used if viral etiology is suspected
    • Physiotherapy of the face – patient should actively move facial muscles to prevent atrophy
    • Artificial eye drops to prevent dry eyes
    • Treat underlying disease if any

Thrombosis of the intracranial sinuses

  • = Cerebral venous sinus thrombosis (CVST)
  • Etiology
    • Non-infectious
      • Hypercoagulable state
        • Contraceptives
        • Blood clotting disorders (Leiden mutation, antiphospholipid syndrome)
        • Polycythaemia
        • Cancer
      • Head trauma
      • Iatrogenic after lumbar puncture
    • Infectious (septic cerebral venous sinus thrombosis)
      • Spread from nearby local bacterial or fungal infections
      • Rhinosinusitis
      • Dental infection
      • Acute otitis media, mastoiditis
      • Meningitis
      • Pharyngitis
      • Cellulitis
  • Pathophysiology
    • Thrombosis -> decreased cerebral venous drainage -> increased intracranial pressure
    • Thrombosis -> decreased cerebral venous drainage -> ischaemia of brain parenchyme
  • Clinical features
    • Highly variable. Can be acute, subacute, or chronic
    • Headache
      • In almost all patients
      • Gradual, acute, or thunderclap-like
    • Symptoms of increased ICP
      • Papilloedema
      • Diplopia
      • Nausea, vomiting
      • Altered mental status
    • Focal neurological symptoms
    • Seizures
    • Cavernous sinus syndrome
      • Compression of cranial nerves passing through the cavernous sinus
      • CN III, IV, V1, and V2 palsy
  • Diagnosis
    • First choice: MR venography – shows absent flow and thrombus
    • Alternative: CT venography
    • Screen for blood clotting disorder in those with high risk for it
    • CRP, blood culture – if infectious etiology is suspected
  • Treatment
    • Anticoagulation
      • For all patients
      • Initially LMWH, transition to VKA long-term
      • VKA for at least 3 months. Up to 12 months, depending on the risk for recurrence
    • Empiric antibiotics
      • Indicated in suspected septic CVST
      • Vancomycin + ceftriaxone + metronidazole
    • Endovascular thrombolysis or thrombectomy
      • In case of absolute contraindication to anticoagulation, or insufficient effect of anticoagulation
    • Antiepileptic drugs – in cases of seizures
    • Surgical drainage of abscess
  • Prognosis – good. 80% recover completely or have minor residual symptoms

10. Acute meningitis

  • Types according to etiology and onset
    • Acute meningitis = onset over hours to days
    • Subacute meningitis = onset over days but < 4 weeks
    • Chronic meningitis = symptoms persisting > 4 weeks
    • Purulent meningitis = bacterial meningitis
    • Aseptic meningitis = viral meningitis
  • Epidemiology
    • Bacterial: 4 – 10/100 000
  • Etiology
    • Infectious
      • Bacteria
        • Streptococcus pneumoniae
        • Neisseria meningitidis
        • Group B streptococcus (in neonates)
      • Virus
        • Enteroviruses
        • HSV, VZV, and other herpesviruses
    • Non-infectious
      • Lymphoma, leukaemia
      • Granulomatous disorders (sarcoidosis, etc.)
      • Vasculitis
      • Systemic autoimmune diseases
  • (Types according to affected area)
    • Leptomeningitis – inflammation of leptomeninges (arachnoid and pia)
    • Pachymeningitis – inflammation of dura mater
    • Meningoencephalitis – inflammation of meninges and parenchyme
  • Clinical features
    • Acute onset headache
    • Fever
    • Light sensitivity (photophobia)
    • Mental status change
    • Meningeal signs
      • These signs have very low sensitivity (5 – 30%)
      • Neck stiffness
      • Kernig sign
      • Brudzinski sign
    • Petechial rash (in case of meningococcus)
    • Focal neurological symptoms and seizures are rare
  • Diagnosis
    • Examination of CSF by lumbar puncture
      • ASAP
Normal Bacterial Viral
Colour Clear fluid Cloudy, purulent fluid Clear fluid
Pressure 6 – 20 cmH2O ↑↑
WBC 0 – 5 /µL ↑↑

Mostly granulocytes

Mostly lymphocytes

Protein 0,18 – 0,45 g/L Normal
Glucose 0,45 – 0,80 g/L Normal or ↓
Culture Negative Gram positive in 60 – 80% Negative
    • Head CT before LP
      • In cases where LP could cause tonsillar herniation, like:
      • Symptoms of increased ICP: Papilloedema, decreased level of consciousness, etc.
      • Focal neurological symptoms
      • Immunocompromised state
      • History of focal brain disease (abscess, tumour)
      • New onset seizure
  • Treatment
    • Bacterial meningitis
      • If head CT is not required before LP -> give ABs immediately after LP
      • If head CT is required before LP -> give ABs ASAP
      • Empiric drug regimen depends on age, immunocompromised state, community vs hospital setting, etc.
      • Usually vancomycin + third generation cephalosporin ± ampicillin
      • Give dexamethasone if strep. Pneumoniae or meningococcus is possible cause
        • Discontinue if culture shows other pathogens
        • Dexamethasone improves outcome only in strep. Pneumo and meningococcus meningitis
    • Viral meningitis
      • Mostly self-limiting
      • Treatment usually supportive
      • Unless there is also encephalitis (topic 12)

Intracerebral haemorrhage (ICH)

  • = bleeding into the brain parenchyma
  • 10 – 15% of all strokes
  • Etiology
    • Hypertensive vasculopathy
    • Vascular malformation (mostly in younger patients)
    • Cerebral amyloid angiopathy (mostly in older patients)
    • Anticoagulant therapy or coagulation disorders
  • Types
    • The distinction is important because if a person has features of atypical ICH additional tests must be performed to determine the etiology
    • “Typical” ICH
      • Affects basal ganglia, thalamus, pons, and/or cerebellum
      • Due to chronic hypertension -> forms Charcot-Bouchard microaneurysms which are prone to rupture
      • Most common
    • “Atypical” ICH
      • Affects cortical lobes, usually the surface
      • Due to vascular malformation, coagulation disorders, cerebral amyloid angiopathy
      • More common in younger patients
      • Usually don’t have hypertension
      • Rare, accounts for only 14%
  • Clinical features
    • Symptoms progress gradually over minutes or hours
    • For ICH in any location
      • Focal neurological deficit
      • Headache
      • Vomiting
      • Loss of consciousness
    • Specific for cerebellar ICH
      • Cerebellar symptoms
      • Brainstem symptoms (respiratory depression, etc.)
      • Hydrocephalus
    • Specific for pontine ICH
      • Tetraplaegia
      • Brainstem symptoms
      • Pinpoint pupils
      • Skewed/dysconjugate eye movements
    • Specific for lobar ICH
      • Seizure
  • Diagnosis
    • By native CT, shows haemorrhage almost immediately
    • If lobar haemorrhage on CT, young age, normotension -> atypical ICH is assumed and additional tests must be performed to determine etiology
      • CT or MR angiography can show vascular malformation, cavernous angioma
      • Screen for bleeding disorder
  • Treatment
    • Conservative
      • Reverse any anticoagulation
      • Decrease blood pressure
      • Stabilize
    • Craniotomy, surgical haematoma evacuation – in case of brain herniation, large cerebellar haematoma
    • Ventricular drainage – in case of hydrocephalus
  • Prognosis: approx. 50% of patients die within 30 days

11. Types of epilepsy

  • Epileptic seizures
    • Epileptic seizures are transient events caused by excessive or synchronous neuronal activity in the brain
    • Types
      • Partial or focal seizures – those which originate from a circumscribed brain region, lobe, or hemisphere
        • Simple partial seizure
        • Complex partial seizure
      • Generalized seizures – those which originate from the entire brain
        • Absence seizure
        • Myoclonic seizure
        • Generalized tonic-clonic seizures (grand mal)
    • Simple partial seizures
      • Consciousness preserved
      • Clinical features
        • Usually short
        • Focal motor signs
        • Autonomic symptoms (flushing, sweating, vomiting)
        • Somatosensory symptoms
        • Special sensory symptoms (flashing lights, unpleasant taste, paraesthesia)
        • Psychiatric symptoms (Déjà vu, hallucinations)
      • Jacksonian seizures: when the seizure spreads to other areas, causing progressive involvement of muscle groups
      • May have a postictal phase called Todd’s paralysis, with paralysis or weakness of the affected muscle groups
    • Complex partial seizures
      • Consciousness impaired
      • Can be preceded by a simple partial seizure
      • Clinical features
        • Usually longer (minutes)
        • Manual automatisms (fumbling, lip smacking, chewing, swallowing)
      • Has a postictal phase with confusion and amnesia
    • Absence seizure
      • Occur mostly in childhood and adolescents
      • Consciousness impaired
      • Clinical features
        • Patient’s motion or activity is suddenly interrupted. They might stare blankly and be unresponsive
        • Usually lasts a few seconds
        • Can occur hundreds of times a day
        • Patient is often unaware of the interruption
      • No postictal phase
    • Myoclonic seizure
      • Consciousness impaired
      • Clinical features
        • Abrupt, brief myoclonus of entire body or parts of it
      • No postictal phase
    • Generalised tonic-clonic seizure
      • All types of seizures can progress into this type
      • Consciousness impaired
      • Begins with a tonic phase
        • Generalised tonic muscle contraction, usually causing extension of limbs
        • A “cry” as air is expelled
        • Rotated eyes
        • Apnoea (due to tonic contraction of respiratory muscles) -> cyanosis
        • Biting the lateral aspect of the tongue
        • Bladder incontinence
      • Then a clonic phase with rhythmic muscle twitching
      • Has a postictal phase with the following symptoms:
        • Unresponsiveness
        • Confusion
        • Amnesia
        • Muscle pain
  • Epilepsy
    • Epilepsy is a disease where a person has recurrent unprovoked seizures
    • A patient has epilepsy if they have any of the following:
      • Two unprovoked seizures more than 24 hours apart
      • One unprovoked seizure and a high probability (> 60%) of further seizures in the next 10 years due to an underlying predisposition to seizures
      • Diagnosis of an epilepsy syndrome
    • Etiology of epilepsy
      • Genetic disorders (idiopathic epilepsy syndromes)
      • Developmental malformations
        • Arteriovenous malformations
        • Haemangioma cavernosum
        • Malformations of the cortex
        • Hippocampal sclerosis
      • Chronic neurological disorders
        • Tumours
        • Chronic encephalitis
      • Post-acute disorders
        • Post-stroke
        • Post-trauma
        • Post-encephalitis
        • Post-birth asphyxia
    • EEG abnormalities
      • Interictal spikes (characteristic EEG spikes which are present outside seizures)
        • Not always present
      • Ictal epileptiform potentials (characteristic waves during seizures)
        • Provoking factors like sleep deprivation or stroboscope may be used to trigger a seizure
    • Treatment of epilepsy
      • 70% of epileptic patients become seizure-free on chronic drug treatment
      • Focal or partial epilepsy is treated with focal antiepileptic drugs
        • Carbamazepine, oxcarbazepine, phenytoin
      • Generalised epilepsy is treated with broad-spectrum antiepileptic drugs
        • Valproate, lamotrigine, levetiracetam
        • Remember that valproate is foetotoxic
      • Epilepsy surgery
        • Indicated if the epilepsy is related to a specific location and it is refractory to 2 – 3 antiepileptic drugs
        • 60 – 90% of these patients become seizure-free after surgery
      • Neuromodulation
        • These are last-resort modalities
        • Deep brain stimulation of anterior nucleus of thalamus
        • Vagus nerve stimulation
  • Epilepsy syndromes
    • = chronic conditions with typical clinical features, typical age of onset, typical types of seizures, typical etiology
    • Classified according to whether they’re focal or generalized, and whether they’re idiopathic (genetic) or non-idiopathic (symptomatic or cryptogenic)
    • Focal epilepsy syndromes
      • Idiopathic focal epilepsy syndromes
        • Benign centro-temporal epilepsy
      • Non-idiopathic focal epilepsy syndromes
        • Temporal lobe epilepsy
        • Frontal lobe epilepsy
        • Parietal lobe epilepsy
        • Occipital lobe epilepsy
    • Generalised epilepsy syndromes
      • Idiopathic generalised epilepsy syndromes
        • Absence epilepsy
        • Juvenile myoclonic epilepsy
        • Grand mal epilepsy on awakening
      • Non-idiopathic generalised epilepsy syndromes
        • West syndrome
        • Lennox-Gastaut syndrome
    • Temporal lobe epilepsy
      • A non-idiopathic focal epilepsy syndrome
      • Starts at 5 – 18 years of age
      • Febrile seizures in childhood may be a risk factor
      • Clinical features
        • Auras related to the temporal lobe
          • Weird sensations in the stomach
          • Déjà vu
          • Uncinate symptoms/seizures
        • Auras usually followed by complex partial seizures
        • Memory disturbances are characteristic
      • Diagnosis
        • EEG shows epileptic focus in temporal lobe
        • MRI usually shows hippocampal sclerosis, tumour or developmental malformation
      • Refractory to drug treatment in most cases, but responsive after epilepsy surgery (partial anterior temporal lobectomy)
    • Idiopathic generalised epilepsy syndromes
      • Includes many types (see earlier)
      • There is often family history of seizures
      • Seizures can be triggered by sleep deprivation, alcohol, photic stimuli
      • Responsive to valproate in almost all cases

(Dementia)

  • Definition of dementia
    • Dementia is an outdated term, nowadays called major neurocognitive disorder (MCD)
    • This topic will use the term MCD instead
    • Mild neurocognitive disorder is a milder form of MCD
  • Definition and clinical features of major neurocognitive disorder
    • Significant decline in cognitive abilities from a previous level
      • Often causes concern by family or the doctor
      • Patient scores poorly on neuropsychological testing
    • The cognitive deficits interfere with independence in everyday activities
      • Causing them to require assistance in activities like paying bills or managing medications
    • The cognitive deficits do not occur exclusively during delirium
    • The cognitive deficits are not better explained by another mental disorder like depression, schizophrenia

Potentially reversible dementias

  • (Nonreversible MCDs:)
    • Alzheimer disease
    • Frontotemporal lobar degeneration
    • Lewy body disease
    • Vascular disease
    • Traumatic brain injury
    • Etc.
  • The potentially reversible MCDs are:
    • Subdural haematoma – treatable by surgery
    • Normal-pressure hydrocephalus – treatable by shunt surgery
    • Obstructive sleep apnoea syndrome – treatable by CPAP/BiPAP
    • Endocrine disorders
      • Hypothyroidism
      • Hypercalcaemia
      • Hypoglycaemia
    • Thiamine deficiency
    • Niacin deficiency
    • B12 deficiency
    • Liver failure
    • Kidney failure
    • Major depression
    • Epilepsy
    • Alcohol abuse
    • Drugs and medications
  • Evaluation of MCD
    • It’s important to screen for the most common causes of reversible MCD
    • Evaluation of mental status by the use of quick screening tests
      • Montreal cognitive assessment (MOCA) or Mini-mental state examination (MMSE) – take 10 – 15 minutes and are good first-choices for GPs
      • Quicker, less thorough tests (MIS, MINI-COG) and slower, more thorough tests (Addenbrooke, Mattis) are also available
    • History
      • Very important to get history from the family
      • Drug history – many drugs may impact cognition
        • Anticholinergics
        • Antidepressants
        • Antipsychotics
        • Sedative-hypnotics
        • Opioids
        • Etc. (the list is endless)
    • In all patients
      • CBC
      • Electrolytes
      • TSH level
      • B12 and folic acid
      • Creatinine for kidney failure
      • Liver function tests
      • Screen for depression and anxiety
      • Neuroimaging with native MRI or CT
    • In those patients with suspicion
      • VDRL for syphilis
      • Antinuclear antibodies for CNS vasculitis
      • HIV
      • CSF analysis for paraneoplastic syndromes
      • Toxic screen for metals, poisons, drugs
      • EEG for epilepsy
      • Genetic testing for Huntington, Alzheimer, frontotemporal, etc.
      • ECG for atrial fibrillation

12. Encephalitis

  • Encephalitis = damage to the blood-brain barrier + CNS damage
  • Etiology
    • Viral
      • HSV – topic 19B
      • HZV – topic 19B
      • Tick-borne encephalitis
      • HIV
      • Enterovirus
      • Rabies
      • Measles
    • Bacterial, autoimmune (less common)
  • HSV and HZV are the most common causes
  • Clinical features
    • Prodromal phase with flu-like symptoms
    • Meningeal signs
    • Focal neurological symptoms
    • Epileptic seizures
    • Altered mental state
  • Diagnosis
    • EEG: diffuse slowing, focal epileptic discharges
    • MRI: focal or multifocal lesions, oedema
    • CSF: lymphocytes, high protein, oligoclonal bands
  • Types
    • Polioencephalitis = grey matter affected
    • Leukoencephalitis = white matter affected
    • Panencephalitis = grey and white matter affected
  • Polioencephalitis
    • Herpes simplex encephalitis (topic 19B)
    • Tick-borne encephalitis
      • A tick-borne flavivirus
      • Present in central and eastern Europe, but the European variant of TBE is generally mild
      • Predilection for cervical spinal cord motoneurons and temporal lobe
      • Prevention by vaccine
      • Doesn’t require treatment
    • Acute anterior poliomyelitis
      • Very rare outside certain countries like Pakistan and Afghanistan
      • Predilection of motoneurons in lumbar spinal cord and brainstem
      • GI infection followed by asymmetric flaccid weakness, usually of legs
      • Prevention by vaccine
    • Lyssavirus, rabies
      • Transmitted by bite of a rabid animal
      • Incubation takes weeks or months as the virus travels from the peripheral nerve to the CNS
      • Lethal in 100% as soon as symptoms appear
      • Urgent post exposure prophylaxis with passive and active immunization after bite is necessary to prevent death
  • Leukoencephalitis
    • Parainfectious and postvaccination encephalomyelitis (= acute disseminated encephalomyelitis)
      • Autoimmune demyelinating disease
      • Very rare (a few per million per year)
      • Can occur after any infection and after any vaccination
      • Severe and acute symptoms
      • Symptoms similar to MS, these patients are usually thought to have MS
      • Treatment: high dose steroid
      • Good prognosis with treatment
    • Progressive multifocal leukoencephalopathy (PML)
      • Demyelinating disease
      • Caused by reactivation of JC virus in immunosuppressed
      • Subacute changes in personality, pyramidal signs, ataxia
      • No treatment, death within a few months
  • Panencephalitis
    • Subacute sclerotizing panencephalitis
      • Occurs >7 years after childhood infection with measles
      • Usually affects children 8 – 11
      • Progressive dementia, myoclonus -> death
    • Rubeola panencephalitis
      • Develops within days of measles infection
      • Affects 1 per 1000
      • Many retain permanent neurological complications

Primary prevention of stroke

  • Primary prevention of all cardiovascular disease is similar, so this will be familiar
  • Many major risk factors for CVD are modifiable. 90% of stroke burden globally is due to modifiable risk factors
  • Healthy diet – increase intake of
    • Fruits and vegetables
    • Fibre
    • Foods with low glycaemic index and low glycaemic load
    • Monounsaturated fat rather than trans or saturated fat
    • Omega-3 fatty acids from foods
  • Smoking cessation
  • Hypertension – treat
  • Dyslipidaemia – treat
  • Increase physical activity
    • Moderate intensity exercise for 150 minutes/week OR:
    • Vigorous intensity exercise for 75 minutes/week
  • Weight loss – in cases of overweight or obesity
  • Treatment of type 2 diabetes
  • Anticoagulation for atrial fibrillation
    • Anticoagulation is indicated if CHA2DS2-VASC score is:
      • 2 or more in men
      • 3 or more in women
    • DOACs is the recommended anticoagulant
    • CHA2DS2-VASC score
      • Congestive heart failure – 1 point
      • Hypertension – 1 point
      • Age > 75 years – 2 points
      • Diabetes mellitus – 1 point
      • Stroke, TIA, or thromboembolism – 2 points
      • Vascular disease (CAD, PAD, etc.) – 1 point
      • Age 65 – 74 years – 1 point
      • Sex Category: female – 1 point

13. Ischias syndrome and cervicobrachialgia (symptoms, warning signs)

  • Introduction
    • Ischias, cervicobrachialgia, chronic back pain (23A) and lumboischialgia (23A) are all different clinical manifestations of spinal cord disease
    • They’re all different manifestations of diseases of the spine and spinal cord
    • Etiology
      • Trauma to the back
      • Spondylosis (age-related arthritis of the spine)
      • Spinal disc herniation
      • Spinal stenosis
      • Spinal tumour
    • Chronic back pain means only local pain with no neurological symptoms
    • Ischias means back pain + radiating pain down the leg, but no other neurological symptoms
    • Lumboischialgia means back pain + neurological symptoms like radiating pain, weakness, sensory loss, reflex loss in the lumbar spine and lower limbs
    • Cervicobrachialgia means neck pain + neurological symptoms like radiating pain, weakness, sensory loss, reflex loss in the cervical spine and upper limbs
  • Ischias syndrome
    • = sciatica
    • (Ischias and sciatica are outdated terms and are rarely used)
    • Caused by compression of L4 – S1 roots
    • Clinical features
      • Pain in the distribution of the sciatic nerve, radiating down the posterior or lateral aspect of the leg, usually to the foot or ankle
      • May be accompanied by lower back pain
    • Diagnosis
      • Positive Lasegue sign
      • Diagnostic imaging only necessary in case severe symptoms
    • Treatment
      • Physical therapy
      • NSAIDs
      • If severe, surgical treatment may be possible
  • Cervicobrachialgia
    • = cervicobrachial syndrome/cervicobrachial neuralgia/brachialgia
    • (These terms are outdated and are rarely used)
    • Caused by compression of the cervical nerve roots C5-C8
      • C8 is most commonly affected
    • Clinical features
      • Neurological symptoms present which correspond to a nerve root
        • Motor weakness, atrophy
        • Sensory loss in a dermatome
        • Reflex loss
        • Radicular pain (sharp, radiating pain)
      • If C8
        • Sensory symptoms on little finger
        • Motor symptoms of the hand muscles
        • Loss of triceps reflex
    • Diagnostic imaging only necessary in case severe symptoms
    • Treatment
      • Physical therapy
      • NSAIDs
      • If severe, surgical treatment may be possible
  • Warning signs
    • These signs are suspicious for spinal cord compression, conus medullaris syndrome or cauda equina syndrome. Because these syndromes are medical emergencies any patient with these signs must undergo imaging and surgery immediately
    • Most common warning signs
      • Saddle anaesthesia
      • Paraplaegia
      • Urinary retention or incontinence
      • Loss of lower extremity reflexes
    • Conus medullaris syndrome
      • A type of upper motor neuron lesion
      • Symmetric symptoms
      • Motor symptoms rare
      • Sensory loss of S3 – S5
        • Pelvic region, perianal region (saddle anaesthesia)
        • No pain!
      • Vegetative
        • Urinary retention
        • Faecal incontinence
        • Erectile dysfunction
        • Loss of anal and bulbocavernosus reflexes
    • Cauda equina syndrome
      • A type of lower motor neuron lesion
      • Asymmetric symptoms
      • Motor symptoms
        • Paraparesis
        • Loss of patellar and Achilles reflex
      • Sensory symptoms
        • Pelvic region, perianal region (saddle anaesthesia)
        • Radicular pain may be present
      • Vegetative symptoms
        • Same as conus

Clinical features of multiple sclerosis

  • Clinical course
    • Usually presents with an attack of neurological symptoms which last for days, but then improve over weeks
    • In the most common subtype (relapsing-remitting MS), the patient will experience more relapses in the future
    • Patients with relapsing-remitting MS may eventually develop secondary progressive MS, where there is a gradual increase in neurological symptoms with superimposed relapses
    • 10 – 20% present with primary progressive MS, where there is a gradual progression with no remission or relapse
    • A “clinically isolated syndrome” (CIS) is the first attack of MS-like symptoms which has yet to fulfil the criteria for MS
  • Clinical features
    • Unilateral optic neuritis
      • -> impaired vision unilaterally
      • Retrobulbar pain
    • Internuclear ophthalmoplaegia -> limited adduction, nystagmus of abducted contralateral eye -> horizontal diplopia
    • Cerebellar symptoms
      • Gait disturbance
      • Vertigo
      • Balance problems
    • Spinal cord symptoms
      • Absent superficial reflexes
      • Upper motor neuron lesion
      • Sensory loss in limbs or face
    • Fatigue
    • Bladder incontinence
    • Lhermitte sign (electric shock-like sensation down the back when flexing the neck)
    • Uhthoff phenomenon – reversible worsening of symptoms after increased body temperature
      • Warm bath, fever, exercise, etc.

14. Motor neuron diseases

  • General
    • Diseases which selectively affect motor neurons
    • Progressive, lead to severe disability and death
    • Most important types
      • Amyotrophic lateral sclerosis
      • Progressive bulbar palsy
      • Primary lateral sclerosis
      • Progressive muscular atrophy
  • Amyotrophic lateral sclerosis
    • Begins in 50 – 70 years
    • Idiopathic
    • An unknown mechanism causes degeneration of both upper and lower motor neurons
    • Clinical features
      • Often begins with asymmetric weakness in hands or feet (80%)
      • Bulbar symptoms (dysarthria, dysphagia) (20%)
      • Muscle atrophy
      • Muscle fasciculations
      • “Drop head” due to weak neck muscles
      • Eventually, patient dies due to severe dysphagia causing problems with eating, or neuromuscular respiratory failure
    • Diagnosis
      • Physical examination shows features of both upper and lower motor neuron lesion
        • Upper – hyperreflexia, spasticity
        • Lower – atrophy, fasciculations
      • EMG, ENG show denervation, fibrillation, axonal loss, chronic reinnervation
      • MRI findings on FLAIR, DTI – shows impaired pyramidal tract
    • Treatment
      • Multidisciplinary – social workers, physiotherapy, speech therapy
      • Supportive therapy
      • Ventilatory support – when respiratory muscles start to fail
      • Percutaneous gastrostomy – when dysphagia becomes severe
      • Riluzole – prolongs survival
      • Edaravone – slows progression of symptoms – not available in EU
    • Prognosis
      • Most die with 3 – 5 years
  • Other motor neuron diseases
    • Progressive muscular atrophy
      • Progressive lower motor neuron disorder of spinal muscles
      • Symptoms of lower motor neuron lesion in arms, legs
      • Often progresses to ALS, but may remain isolated
      • Mean survival 5 years
    • Progressive bulbar palsy
      • Progressive upper and lower motor neuron disorder of cranial (bulbar) muscles
      • Bulbar symptoms (same as ALS)
      • Often progresses to ALS, but may remain isolated to bulbar muscles
      • Mean survival 2 years
    • Primary lateral sclerosis
      • Progressive upper motor neuron disorder of spinal muscles
      • Symptoms include abnormal gait, spasticity, hyperreflexia
      • Often progresses to ALS, but may remain isolated
      • Mean survival 20 years
  • SMA
  • Hereditary spastic paraplaegia

Diagnosis of multiple sclerosis

  • Diagnosis
    • Diagnosis is made when the patient fulfils the so-called McDonald criteria
      • These criteria require evidence of lesions in the CNS in different places and at different times (so-called “dissemination in space and time”)
    • In some patients, the diagnosis can be made after a single attack, If they have evidence of dissemination in both space and time
      • If the diagnosis can not be made (yet) after a single attack that attack is known as a “clinically isolated syndrome”
    • In most patients, the diagnosis is made after the patient has multiple attacks
    • Dissemination in space is evidenced when either of the following apply
      • Lesions on MRI in two MS-typical regions in the CNS (periventricular white matter, corpus callosum, spinal cord)
      • Clinical features which suggest lesions in multiple sites in the CNS
    • Dissemination in time is evidenced when either of the following apply
      • Presence of both gadolinium-enhancing and non-enhancing lesions on a gadolinium contrast MRI
        • Gadolinium-enhancing lesions are maximum a few weeks old, while non-enhancing lesions are older than that
      • Presence of a new gadolinium-enhancing lesion on a follow-up contrast MRI
      • Development of an additional clinical attack
      • (Presence of oligoclonal bands in CSF can act as a substitute for dissemination in time)
    • Modalities used in diagnosis
      • MRI (with and without gadolinium contrast)
      • Lumbar puncture (shows oligoclonal bands in CSF)
      • Visually evoked potentials (VEP)
        • Shows slowed nerve conduction
        • Used if other tests are inconclusive
  • Differential diagnosis
    • Neuromyelitis optica (Has similar symptoms as MS but worse prognosis and different treatment, so important to distinguish them)
      • NMOD has normal brain MRI, no oligoclonal bands, etc.
    • Systemic lupus erythematosus
    • Sarcoidosis
    • Behcet disease
    • Neuroborreliosis
    • Neurosyphilis

15. Trigeminal neuralgia

  • Epidemiology
    • Age of onset > 60
    • Females > males
  • Etiology
    • Classic
      • (Due to compression of the trigeminal nerve root by a vessel, most commonly superior cerebellar artery)
    • Secondary
      • (Due to MS or tumour)
    • Idiopathic
  • Clinical features
    • Attacks of very severe facial pain in the area of one or more branches of CN V
    • Sharp, stabbing pain lasting for seconds
    • Many episodes each day (up to 100)
    • Can occur at rest or in association with movements like chewing, talking, touching, etc.
  • Diagnosis
    • Clinical
    • MR angiography can give information on cause
  • Treatment
    • Pharmacological therapy
      • First-line
      • Antiepileptics (especially carbamazepine)
    • Surgical therapy
      • If pharmacological therapy is insufficient
      • Mainly for classical type
      • Microvascular decompression to separate the blood vessel from the trigeminal nerve root

Neuromyelitis optica (Devic-disease)

  • Nowadays called neuromyelitis optica spectrum disease (NMOSD) because it’s a spectrum not one disease
  • Has similar symptoms as MS but worse prognosis and different treatment, so important to distinguish them
  • Epidemiology
    • More often in Africans and Asians than whites
    • Peak onset in 40 – 60 years
  • Pathophysiology
    • Immune-mediated chronic inflammatory disorders of the CNS
    • Mainly affect optic nerve and spinal cord
    • Anti-aquaporin-4 antibodies bind to AQP-4 on astrocytes
    • Causes demyelination and axonal damage
  • Clinical features
    • Very similar to MS
    • Recurrent attacks which become worse and worse
    • Symptoms of optic neuritis
      • Impaired vision
      • Retrobulbar pain
    • Symptoms of transverse myelitis
      • Symmetric paraplaegia
      • Sensory loss
      • Bladder dysfunction
    • Area postrema syndrome (severe nausea, vomiting, and hiccups)
  • Diagnosis
    • Based on presence of anti-AQP4 and typical clinical features
    • Longitudinal lesions in spinal cord which span 3 or more vertebral segments
    • Slightly elevated WBC in CSF
    • MS should be excluded (no oligoclonal CSF bands, brain MRI normal)
  • Treatment
    • During relapse: steroids for 3 – 5 days. Plasmapheresis if severe
    • Maintenance: Azathioprine, biological therapy
    • Axonal damage is not reversible (unlike demyelination), so early treatment is important to prevent permanent injury
  • MOG-antibody-associated disease (MOGAD)
    • Very similar to NMOSD, but with anti-MOG antibodies instead of anti-AQP4

16. Clinical symptoms of insufficient blood supply in territory of carotid and vertebral artery

  • I assume vertebral artery is a mistake here, and it was supposed to be only the carotid. See also topic 26
  • Anterior territory stroke = stroke involving the territory of the internal carotid system, including the anterior and middle cerebral arteries
    • Middle cerebral artery infarct is most common, 2/3 of all strokes
    • Anterior cerebral artery infarct is rare, ~2% of all strokes
  • Contralateral hemiparesis
    • If anterior cerebral artery is affected -> lower limbs more affected
  • Contralateral hemisensory loss
  • Contralateral homonymous hemianopia
  • Aphasia (if dominant hemisphere is affected)
  • Contralateral hemineglect (if nondominant hemisphere is affected)
  • Gaze deviation toward side of lesion

Differential diagnosis of short-term loss of consciousness

  • Differentiate between syncope and neurological causes
    • 90% are non-neurological
    • Syncope
      • Causes
        • Cardiac syncope
        • Reflex syncope
        • Autonomic dysfunction
        • Recent change in drugs
      • Suspicious features
        • Prodromal symptoms
          • Blurry vision, sight goes dark
          • Sweating
        • Lasts seconds
        • Patient is oriented immediately after
    • Neurological causes
      • Almost always seizures
      • Suspicious features
        • Prodromal symptoms
          • Often sudden blackout, no prodromal symptoms
          • Aura
        • Lasts minutes
        • Enuresis
        • Muscle soreness
        • Bitten tongue on lateral part
        • Patient has postictal period of tenebrosity and disorientation after

17. Types and etiology of unconsciousness. Coma

  • Types of unconsciousness
    • Hypnoid – sleep-like
      • Somnolence
        • Patient is superficially sleeping but can be awakened by sensory stimuli or verbal stimuli
      • Sopor
        • Patient can only be awakened by painful stimuli
      • Coma
        • Patient cannot be awakened at all
    • Non-hypnoid
      • Tenebrosity
        • Decreased state of awareness after seizure
      • Delirium
        • Due to drug withdrawal, meningitis, dehydration, dementia
        • Disorientation, agitation, restlessness, sweating, tachycardia
      • Decortication
        • Due to diffuse cortical lesion (like cardiac arrest), with subcortical areas intact
        • Flexion of upper extremities + extension of lower extremities
      • Akinetic mutism
        • No voluntary activity, no communication, no speech
        • Due to frontal lobe lesion
      • Locked-in
        • Normal brain activity and consciousness, eye-lid movements are preserved, but rest of the body is paralysed
        • Due to severe brainstem lesion
  • Etiology of hypnoid unconsciousness
    • Brain herniation
    • High intracranial pressure
    • Intoxication
    • Brainstem lesion

Status epilepticus

  • Definition:
    • Any of the two:
    • A single seizure lasting longer than 5 minutes
    • More than one seizure without recovery of consciousness in-between
  • Etiology
    • Provoked epileptic seizure
    • Symptomatic seizure
    • Epilepsy (rare)
  • Clinical significance
    • Life-threatening!
    • 20% mortality
    • May cause cerebral oedema, aspiration, cardiovascular failure, rhabdomyolysis, hyperthermia, etc.
  • Treatment
    • Ensure stability (ABC)
    • 1 ampulla IV lorazepam or other BZD
      • Alternative if no IV access: IM or buccal or rectal midazolam
      • If no response within 1 minute -> give another dose
    • If no resolution after 2 doses of BZD = refractory status epilepticus:
      • IV valproate or levetiracetam
      • If antiepileptics does not work, give narcosis with propofol or midazolam infusion
    • Look for cause
      • Electrolytes, glucose, inflammatory markers, etc.

18. Migraine and other primary headaches

  • Migraine
    • Epidemiology
      • 12% of the population
      • Women/men 3:1
      • Without aura > with aura
    • Types
      • Migraine without aura
      • Migraine with aura
      • Chronic migraine – daily mild-moderate headaches with exacerbations with migranious features
    • Pathophysiology
      • Cortical spreading depression
        • A wave of electrophysiological hyperactivity across the brain followed by inhibition
        • Implicated in both migraine with and without aura
      • Trigeminovascular system
        • = trigeminal sensory neurons that innervate large cerebral vessels, vessels of the meninges, large venous sinuses, and the dura mater
        • Cortical spreading depression may activate meningeal nociceptors in the trigeminovascular system, leading to pain and sensitisation of these neurons
    • Clinical features
      • (Non-chronic) migraine is a disorder of recurrent migranious attacks
      • Attacks can be triggered by factors like stress, menstruation, nitrates, fasting, wine, sleep disturbances, smoking, certain foods, etc.
      • Attacks typically have three or four phases:
      • Prodromal phase
        • With affective or vegetative symptoms 1 – 2 days before attack
        • Excessive yawning
        • Euphoria
        • Depression
        • Irritability
      • Aura phase
        • Usually visual – vision loss or bright spots
        • Can also be sensory (tingling or numbness of a limb or the face), verbal, or motor
        • Develops gradually over minutes
        • Lasts < 1 hour
      • Headache or attack phase
        • Often occurs simultaneously as the aura
        • Often unilateral
        • Throbbing or pulsatile
        • May be accompanied by nausea, photophobia, phonophobia
        • Lasts for hours, sometimes up to days
      • Postdromal phase
        • Feeling of exhaustion or being drained
        • Residual headache during head movements
    • Migraine prophylaxis
      • Tricyclic antidepressants
        • Amitriptyline
        • Nortriptyline
      • Antiepileptics
        • Topiramate
        • Valproate
      • Antihypertensives
        • Propranolol, metoprolol
        • Flunarizine, verapamil
        • Lisinopril
        • Candesartan
      • Anti-CGRP antibodies
    • Acute treatment of episodic migraine
      • Triptans
        • Eletriptan
        • Rizatriptan
        • Zolmitriptan
        • Sumatriptan
      • Other analgesics
        • Paracetamol
        • NSAIDs
        • Opioids should not be used
      • Antiemetics
        • Domperidone
        • Metoclopramide
  • Tension headache
    • Most common type of primary headache
    • Pericranial tenderness (in neck muscles, etc.) may be involved
    • Can be episodic or chronic
    • Clinical features
      • Dull, non-pulsating, band-like pain
      • Usually bilateral
      • Only one or no autonomic symptoms
      • No aura
    • Prophylactic treatment
      • Amitriptyline
      • Gabapentin
    • Acute treatment
      • Aspirin, NSAIDs
      • Paracetamol has poor response
  • Cluster headache
    • A type of trigeminal-autonomic cephalgia
    • 80% of patients are smokers
    • Clinical features
      • Often called “the worst pain a human can experience”
      • Unilateral, periorbital and/or temporal pain
      • Ipsilateral autonomic symptoms
        • Conjuctival injections and tearing
        • Rhinorrhoea and nasal congestion
        • Ptosis
        • Miosis
      • Short (15 minutes – 3 hours)
      • Typically 1 – 3 times a day, up to 8
      • May have months or years without attacks
    • Prophylactic treatment
      • Verapamil
      • Lithium
      • Steroids
    • Acute treatment
      • Sumatriptan injection
      • 100% oxygen inhalation

Types of disturbances of urinary bladder innervation

  • Innervation of bladder
    • Parasympathetic fibres from sacral spine innervate:
      • Detrusor muscle, causing contraction
    • Sympathetic fibres from lower thoracic level innervate:
      • Detrusor muscle, causing relaxation
      • Internal sphincter, causing contraction
    • Somatic (pudendal nerve) fibres from sacral spine innervate:
      • External sphincter, causing contraction
    • Three centres of bladder control
      • Frontal cortex – which inhibits the PMC
      • Pontine micturition centre (PMC)
      • Onuf-nucleus in sacral spine
  • Disturbance of urinary bladder innervation is sometimes called neurogenic bladder
  • Types according to neuroanatomical location
    • Suprapontine lesion (lesion of cortex, usually frontal lobe)
      • Due to stroke, tumour, dementia, multiple system atrophy
      • Usually causes detrusor hyperreflexia -> urge incontinence
      • Central (UMN) lesion
    • Spinal cord lesion (between pons and Onuf-nucleus)
      • Most frequent type
      • Due to multiple sclerosis, myelitis, trauma, herniation
      • Initially causes urinary retention (spinal shock)
      • Later -> detrusor hyperreflexia or detrusor sphincter dyssynergy -> urge incontinence
      • Central (UMN) lesion
    • Subsacral lesion (below Onuf-nucleus)
      • Due to trauma, herniation
      • Usually causes bladder hypoactivity -> overflow incontinence
      • Peripheral (LMN) lesion
  • Types according to clinical features
    • Urge incontinence
      • Urinary leak preceded by strong urge to urinate
      • Can be due to intravesicular problems like stone, inflammation, tumour of bladder, or neurological problems
      • Due to hyperactivity of the bladder
      • Treatment
        • Anticholinergics
        • TCAs with strong anticholinergic effect (imipramine)
        • Alpha blockers (alfuzosin, doxazosin)
        • Beta blockers
        • Patient self-catheterization
    • Stress incontinence
      • Usually not neurologic, rather urological or gynaecological
      • Due to inadequate tone of pelvic floor muscles, causing urine loss in cases where intraabdominal pressure increases, like when coughing
      • Treatment
        • TCAs with strong anticholinergic effect (imipramine)
        • Duloxetine
        • Surgery
    • Overflow incontinence
      • Due to peripheral neurological lesion causing hypoactivity of the bladder (or bladder obstruction)
      • Bladder fills up, causing urine to dribble out
      • Treatment
        • Patient self-catheterization
  • Types according to pathomechanism
    • Detrusor sphincter dyssynergy
      • Only seen in spinal cord lesion
      • Due to the urethral sphincter not relaxing when detrusor contracts
      • Usually causes urge incontinence
    • Detrusor hyperreflexia (hyperactive bladder)
      • Usually seen in suprapontine or spinal cord lesion
      • Usually causes urge incontinence
    • Detrusor areflexia (hypoactive bladder)
      • Usually seen in subsacral lesion
      • Usually causes overflow incontinence or residual urine

19. Traumatic brain injuries

  • Traumatic brain injury (TBI) = external force applied to skull which cause alteration of function and/or morphology of brain
    • Altered function: Loss of consciousness, amnesia, altered mental state
  • Epidemiology
    • “Silent epidemic”
    • One of the most common causes of death in the active population
    • Usually from motor vehicle accident in younger adults
    • Usually from falls in elderly
  • Primary brain injury = occurs at the time of impact
    • Causes immediate clinical effects
    • Preventable but not treatable
  • Secondary brain injury = occurs some time after the impact
    • Caused by hypoperfusion, altered autoregulation, oedema
    • Causes gradual clinical effects
    • Both preventable and treatable
  • “Anatomical” classification
    • Closed TBI – dura is maintained – low risk for infection
    • Penetrating TBI – dura is penetrated – high risk for infection
  • “Pathomorphologic” classification
    • Focal TBI
      • Contusion
      • Epidural haemorrhage
      • Subdural haemorrhage
    • Diffuse TBI
      • Diffuse axonal injury
      • Diffuse neuronal somatic injury
  • Diagnosis
    • CT is gold standard
    • Skull x-ray is never indicated for TBI!
  • Complications
    • Epilepsy
    • Hydrocephalus
    • Hypopituitarism (can occur long time after the injury)
    • Cognitive issues
    • Neurodegenerative disease
  • Epidural haematoma
    • = bleeding between the skull and the dura
    • Generally a disease of young people due to trauma
    • Etiology
      • Classically due to rupture of meningeal artery, most frequently the middle
      • Can also be due to rupture of diploic veins -> less severe
    • Clinical features
      • Patient loses consciousness then regains it
      • Headache then progressively worsens until consciousness is lost again – this period is called the lucid interval
    • Diagnosis
      • CT shows lens-shaped (biconvex) lesion
    • Treatment
      • Venous epidural haematoma does not always need surgery
    • Prognosis
      • Usually good prognosis if treated in time
  • Subdural haematoma
    • = bleeding between the dura and the arachnoid layer
    • Generally a disease of older people
    • Etiology
      • Classically due to rupture of bridging veins
      • Can also be due to rupture of cortical arteries -> more severe
    • Clinical features
      • Symptoms progress
    • Diagnosis
      • CT shows concave/linear lesion
    • Prognosis
      • High mortality rate
  • (traumatic) Subarachnoid haematoma
    • See topic 5 for nontraumatic SAH
    • = bleeding under the arachnoid layer
    • Accounts for 80% of subarachnoid haemorrhages
    • Pathophysiology
      • Classically due to rupture of small vessels on the brain surface
  • Contusion
    • = haematoma in the brain parenchyma
    • Usually due to acceleration-deceleration injury
    • Both coup and countercoup lesions on the brain

Herpes infection, postherpetic neuralgia

  • Herpes simplex encephalitis
    • Almost all HSV-1
    • Always causes haemorrhagic necrosis of temporal lobe
    • Clinical features
      • Often preceded by a flu-like phase
      • Progressive loss of consciousness
      • Aphasia
      • Fever
      • Hemiparesis
      • Focal epileptic seizures
    • Diagnosis
      • Progresses very fast and has much better prognosis if treatment is started early, so treatment should begin upon clinical suspicion even before diagnosis
      • MRI shows inflammation and necrosis of temporal lobe
        • Only present after day 3
      • EEG shows slow activity and epileptic discharges over temporal regions
        • Only present after day 2
      • Lumbar puncture
        • Analysis of CSF and PCR for HSV
        • Can be performed after treatment has started
        • CSF shows increased lymphocytes and protein
        • PCR of CSF gives definitive diagnosis
    • Treatment
      • Acyclovir should be initiated immediately in case of clinical suspicion
        • 30 mg/kg/day IV for weeks
      • Antiepileptics
    • Prognosis
      • 70% mortality if untreated
      • 20% mortality if treated
        • 50% have permanent deficits
  • Herpes zoster encephalitis
    • Mostly seen in immunocompromised people with herpes zoster
    • Manifests as delirium within days of the rash
  • Postherpetic neuralgia
    • = chronic neuropathic pain an area where there was a previous herpes zoster rash
    • Epidemiology
      • Occurs in 10 – 20% of herpes zoster cases
      • More frequent in elderly
    • Clinical features
      • Severe shooting, burning, or stabbing pain
      • Pain persisting for > 3 months
      • Allodynia, paraesthesia, etc. may also occur
    • Treatment
      • Antiepileptics (pregabalin, gabapentin)
      • Carbamazepine
      • Tricyclic antidepressants (amitriptyline)
      • Duloxetine, venlafaxine
      • Lidocaine patch
      • Capsaicin patch

20. Traumatic spinal cord injuries (TSCI)

  • Extent of damage depends on the level of the injury
  • Etiology
    • Motor vehicle accidents
    • Falls
    • Violence
    • Sport injuries
  • Primary injury
    • Occurs at the time of injury
    • May cause spinal cord compression, direct spinal cord injury, interruption of cord blood supply
  • Secondary injury
    • Occurs after the initial injury
    • May occur due to oedema, inflammation, ischaemia, moved body fragments, etc.
  • Classification according to the type of injury
    • Spinal cord concussion/contusion – temporary loss of function
    • Spinal cord compression – decompression required to reduce permanent injury
    • Spinal cord laceration – permanent injury unavoidable
  • Classification according to the level of the injured spinal cord segment
    • 50% of cases involve the cervical spinal cord
    • If cervical level – tetraparesis
    • If above C4 – diaphragm paralysis, loss of spontaneous breathing
    • If thoracic or lumbar level – paraparesis
  • Classification according to the severity of the spinal cord injury – the various cord syndromes
    • Complete cord injury/transection
      • Complete paralysis and anaesthesia below the level of the injury
      • Urinary retention
      • Bulbocavernosus reflex absent
    • Incomplete cord injury
      • Variable degree of motor and sensory function below the level of the injury
      • Motor function is usually more affected because the motor tracts are located in the more vulnerable areas of the cord
      • Bulbocavernosus reflex present
      • Anterior cord syndrome
        • Due to compression of anterior spinal artery, by bone fragment, AAA, etc.
        • Dissociated sensory loss below the level of the lesion
        • Loss of motor and spinothalamic tract modalities
        • Dorsal column sensory modalities intact
      • Central cord syndrome
        • Due to hyperextension of cervical spine
        • Weakness of upper extremities
        • Normal strength in lower extremities
      • Hemisection syndrome (Brown-Sequard syndrome)
        • Ipsilateral paralysis
        • Ipsilateral loss of dorsal column sensory modalities
        • Contralateral loss of spinothalamic modalities
  • Spinal shock
    • Sometimes after spinal cord injury, reversible loss of all spinal cord function below the level of the injury may occur
      • Areflexia
      • Paralysis
      • Anaesthesia
      • Urinary retention
      • Circulatory instability
    • May last hours to weeks
    • May or may not completely resolve
  • Diagnosis
    • CT – initial imaging, shows bony structures and any fractures
    • MRI – if damage to spinal cord is suspected
  • Management
    • ABCD, monitoring, stabilisation
    • Immobilisation – All patients with suspected spinal injury must be immobilised until imaging can be performed!
    • Urinary catheterisation to prevent rupture due to overfilling
    • Methylprednisolone to decrease spinal cord oedema
    • Surgery
      • In cases of spinal cord compression, progressive neurological deficits, unstable spine, etc.
    • (Prevention of DVT due to immobility: LMWH)
    • (Prevention of stress ulcer: PPI)
  • Prognosis
    • Prognosis is worse the higher the level of the injury
    • 4 – 20% early death
    • Most retain severe and permanent disability

Alzheimer disease (AD)

  • The most common neurodegenerative disease
  • Definitions
    • There exists possible AD, probably AD, and definite AD
    • Definite AD = typical clinical features + histopathologic confirmation
      • Histopathologic confirmation can only be performed at autopsy, so diagnosis of AD in live patients can only be probable or possible
    • Probable AD = major neurocognitive disorder + typical clinical features
    • Possible AD = major neurocognitive disorder + not all typical clinical features OR minor neurocognitive disorder + typical clinical features
  • Risk factors
    • Old age
    • Family history
    • Head trauma
    • Vascular risk factors (same as for stroke)
    • Genetics
      • APOE e4 genotype
      • Mutations in amyloid precursor protein (APP) gene
      • Mutations in presenilin-1 and -2
  • Protective factors
    • Higher education
    • Good diet
    • Exercise
    • Oestrogen
    • Statins
    • NSAIDs
    • APOE e2 genotype
  • Pathology
    • Transmembranous APP is cleaved into Aβ peptides, which aggregate and form senile plaques extracellularly, which may have a neurotoxic effect
    • Hyperphosphorylated tau protein in the cells form neurofibrillary tangles, which may have a neurotoxic effect
    • Degeneration of cholinergic neurons causes acetylcholine deficiency
    • Degeneration of noradrenergic, serotoninergic, glutaminergic, and GABAergic systems also occur but to a lesser extent
  • Clinical features
    • Typically presents with impairment in memory and learning
    • Later, impairment of executive function, perceptual motor ability and language occurs
    • At the mild stage
      • Depression
      • Apathy
    • At the moderate stage
      • Psychotic features
      • Irritability
      • Agitation
      • Combativeness
      • Wandering
    • At the late stage noncognitive neurologic deficits occur too
      • Gait disturbance
      • Dysphagia
      • Incontinence
      • Myoclonus
      • Seizures
  • Diagnosis
    • Diagnosis of probable or possible AD is based on diagnostic criteria
    • Diagnostic markers which may aid diagnosis
      • Decreased amyloid β-42 in CSF
      • Increased total tau and phosphorylated tau in CSF
      • Presence of amyloid plaques on PET
      • Mutations in presenilin-1 or -2
      • Mutations in APP
  • Treatment
    • No treatment is curative, but they can slow progression
    • We can also treat symptoms
    • Nonpharmacological treatment
      • Mediterranean diet
      • Social and mental activity
      • Exercise
    • Cholinesterase inhibitors
      • Used in mild-moderate cases
      • Improve symptoms, but have cholinergic side effects (nausea, diarrhoea, dizziness, bradycardia)
      • Donepezil
      • Rivastigmine
      • Galantamine
    • Memantine, an NMDA receptor antagonist
      • Used in moderate-severe cases
      • Can be used in addition to cholinesterase inhibitors
      • Slows progression
    • Atypical antipsychotics in case of agitations, hallucinations

21. Meningiomas

  • Epidemiology
    • Accounts for 1/3 of primary CNS tumours
    • Mostly in elderly (> 65 years)
  • Etiology
    • Mostly idiopathic
    • Some cases are related to NF2 or previous radiation exposure
  • Pathology
    • Arise from arachnoid layer cells, 90% occur in the skull, 10% in the spine
    • Very slowly growing
    • > 90% are benign
  • Clinical features
    • Most are slowly growing and asymptomatic, only discovered incidentally
    • Headache
    • Seizure
    • Focal neurological deficits
    • Visual defects
    • Most common locations and their specific symptoms
      • Falx cerebri and parasagittal area – personality changes, contralateral weakness
      • Convex brain surface – seizures
      • Sphenoid wing – visual defects, loss of sensation in face
      • Olfactory groove – anosmia, visual defects
      • Suprasellar – visual defects
      • Posterior cranial fossa – cerebellar symptoms
      • Spinal cord – back pain, lumboischialgia
  • Diagnosis
    • MRI with contrast
      • Shows round, sharply demarcated, extra-axial lesion with a “dural tail”
      • Shows tumour with strong contrast enhancement
    • Most meningiomas are diagnosed on imaging and never biopsied because of the characteristic appearance
  • Treatment
    • Active surveillance – if slow-growing, asymptomatic, in elderly
    • Surgical removal
      • If close to the surface
      • Tumour itself and later the surgical scar may cause symptomatic seizures, many patients require lifelong antiepileptics
    • Radiotherapy if inoperable

Neurological disorders related to alcoholism

  • Wernicke encephalopathy
    • Acute and reversible
    • Due to thiamine (B1) deficiency, most commonly due to alcoholism
    • Clinical features
      • Classical triad
        • Confusion
        • Oculomotor dysfunction (nystagmus, diplopia, gaze palsy)
        • Gait ataxia
      • Autonomic dysfunction
      • Peripheral neuropathy
    • Diagnosis by clinical features
      • If in doubt: serum thiamine levels
    • A medical emergency, must be treated with IV thiamine
    • Later, long-term supplementation of B vitamins and alcohol abstinence
    • Glucose must never be infused in thiamine-deficient persons before administering thiamine, because it can worsen encephalopathy
  • Korsakoff syndrome
    • Chronic and irreversible
    • Due to long-term thiamine (B1) deficiency, most commonly due to alcoholism
    • Clinical features
      • Personality changes
      • Anterograde and retrograde amnesia
      • Confabulation
      • Hallucination
      • Disorientation
    • Diagnosis by clinical features
      • If in doubt: serum thiamine levels or MRI showing periventricular haemorrhage and mammillary body atrophy
    • Treatment
      • Long-term supplementation of B vitamins
      • Alcohol abstinence
      • Therapy
  • Alcoholic neuropathy
    • Second most common neuropathy
    • Due to alcoholism and thiamine deficiency
    • Clinical features
      • Involves sensory, motor, and autonomic nerves
      • Usually symmetric and distal symptoms of polyneuropathy
    • Treatment
      • Abstinence from alcohol
      • Thiamine supplementation
      • See treatment of neuropathic pain
  • Alcoholic cerebellar degeneration
    • Due to alcoholism and thiamine deficiency -> degeneration of Purkinje cells
    • Clinical features
      • Gait ataxia
      • Limb ataxia
      • Dysarthria
    • Treatment
      • Abstinence from alcohol
      • Thiamine supplementation
  • Alcoholic myopathy
    • Due to alcoholism
    • Usually more severe in proximal muscles
    • Can affect cardiac muscle -> heart failure
    • Treatment: Abstinence
  • Delirium tremens

22. Hydrocephalus

  • = increased CSF, often causing increased ICP
  • Types
    • Obstructive (non-communicating) hydrocephalus = increased CSF due to mechanical blockage of CSF flow within the ventricular system -> increased ICP
    • Communicating (non-obstructive) hydrocephalus = increased CSF due to impaired absorption of CSF or due to increased CSF production -> increased ICP
    • Hydrocephalus ex vacuo = not a true hydrocephalus, only there is brain atrophy which makes the ventricles appear dilated
  • There is often overlap between obstructive and communicating types!
    • The same etiology can cause features of both
  • Epidemiology
    • 60% of hydrocephalus are congenital
    • Communicating more common than obstructive
  • Etiology according to type
    • Obstructive hydrocephalus
      • CNS tumour
      • Congenital stenosis of cerebral aqueduct
    • Communicating hydrocephalus
      • Choroid plexus tumour
      • Genetic syndromes (trisomies, triploidy, etc.)
    • Either or both obstructive and communicating hydrocephalus
      • Subarachnoid haemorrhage
      • Intraventricular haemorrhage
      • CNS infection (bacterial meningitis, etc.)
      • Neural tube defect -> Chiari II malformation
  • Clinical features of ICP and herniation (see topic 24b)
    • If occurring before the cranial sutures have closed it can give infants large head
  • Diagnosis
    • MRI or CT -> shows dilated ventricles
    • If communicating hydrocephalus -> all ventricles are dilated
    • If obstructive hydrocephalus -> ventricles upstream of the obstruction are dilated
  • Treatment
    • Supportive
      • While waiting for surgery
      • Diuretics, acetazolamide
    • Ventriculoperitoneal (VP) shunt
      • A one-way shunt which drains CSF into the peritoneum
      • Complications (shunt infection, shunt malfunction) are unfortunately not rare
    • Endoscopic third ventriculostomy
      • Opens a floor in the third ventricle, allowing CSF flow into the prepontine cistern
      • Only effective for obstructive hydrocephalus
  • Normal pressure hydrocephalus (NPH)
    • = a form of idiopathic chronic communicating hydrocephalus without increased ICP
    • Can also be secondary to subarachnoid haemorrhage or meningitis
    • NPH mostly affects adults > 60 years
    • Clinical features: classic triad of wet, wacky, and wobbly:
      • Urinary incontinence
      • Dementia
      • Ataxic gait, frequent falls
    • Diagnosis
      • Exclude other causes of gait dysfunction
      • MRI or CT -> shows dilated ventricles without enlargement of the sulci
      • Lumbar puncture and release of CSF improves symptoms
    • Treatment: VP shunt

Secondary prevention of stroke

  • Secondary prevention of ischaemic stroke
    • Antiplatelet therapy
      • For patient with established atherosclerosis
      • Aspirin or P2Y12 antagonist (clopidogrel, etc.)
      • Start within 48 hours of ischaemic stroke onset and continue indefinitely
        • Should not be started for 24 hours after thrombolysis
    • Cholesterol management
      • For all patients who had ischaemic stroke
        • Statin therapy is beneficial even for patients without high LDL
      • Statins
      • Target LDL < 1,4 mM or at least 50% reduction from baseline
    • Blood pressure management
      • For patients with hypertension without diabetes, the target is < 140/90 mmHg
      • For patients with hypertension and diabetes, the target is < 120/80 mmHg
    • Blood glucose management
      • For patients with diabetes
      • Target HbA1c < 7% (53 mmol/mol)
    • Anticoagulation
      • For patients with atrial fibrillation
      • NOAC is preferred over VKA
    • Carotid surgery
      • Indicated in patients with 70 – 99% carotid stenosis
      • As soon as possible after ischaemic event
      • Carotid endarterectomy or carotid artery stenting
  • Secondary prevention of haemorrhagic stroke
    • Blood pressure management
      • Specific target depends on presence of other risk factors, etc.

23. Lumboischialgia and chronic back pain

  • See also topic 13A
  • Lumboischialgia
    • Caused by compression of the cervical nerve roots L5 and/or S1
    • Clinical features
      • Neurological symptoms present which correspond to a nerve root
        • Motor weakness, atrophy
        • Sensory loss in a dermatome
        • Reflex loss
        • Radicular pain (sharp, radiating pain)
      • If L5
        • Sensory symptoms on lateral surface of thigh, anterior surface of calf
        • Motor symptoms of extensor hallucis longus -> foot drop
        • Loss of tibialis posterior reflex
      • If S1
        • Sensory symptoms on lateral surface of calf
        • Motor symptoms of peroneus muscle, triceps surae
        • Loss of Achilles reflex
      • Lasegue sign positive
      • May be accompanied by lower back pain
    • Diagnostic imaging only necessary in case of vegetative symptoms or severe motor symptoms
    • Treatment
      • Physical therapy
      • NSAIDs
      • If severe, surgical treatment may be possible
  • Chronic back pain
    • Caused by muscle spasm, spondylosis, etc.
    • Clinical features
      • Pain only in the back
      • No neurological symptoms present
      • Lasegue sign negative
    • No diagnostic investigations necessary
    • Treatment
      • Physiotherapy
      • NSAIDs

Nervous system metastases

  • Epidemiology
    • Brain metastases are the most common form of adult brain tumour
    • 70% are multiple rather than solitary
    • Brain metastases occurs in few paediatric cancers, only 6%
  • Etiology
    • Lung cancer
    • Breast cancer
    • Melanoma
    • Lymphoma
  • Clinical features
    • Change in cognitive status
    • Headache
    • Focal neurological symptoms
    • Seizures
  • Diagnosis
    • Contrast-enhanced MRI is gold standard
    • Biopsy in most cases
    • Metastases are usually multifocal and have large perifocal oedema
  • Treatment and prognosis
    • Steroids to reduce oedema
    • Depending on the primary tumour, chemotherapy and immunotherapy may be options
    • Whole brain radiation therapy (WBRT) for many lesions
    • Radiosurgery (gamma knife), or surgical resection with curative intent if good prognosis and few lesions
    • These tumours are less often treated surgery compared to primary tumours
    • Presence of CNS metastases equals a much worse prognosis
    • Cure may be achieved if the primary tumour is chemosensitive, or if there are few, resectable metastases
      • However, most cases are palliative
  • Meningeal carcinomatosis
    • Metastasis to meninges from any carcinoid tumour
    • Mostly cause cranial nerve symptoms
    • Tumour cells in CSF samples
  • Spinal metastases
    • = metastases to vertebral column -> compress the spinal cord
    • Relatively frequent
    • Metastasis from any thoracic or abdominal cancer
      • Prostate cancer
      • Lung cancer
      • Breast cancer
    • Clinical features
      • Back pain (in early stage)
      • Sensory and/or motor loss below level of lesion (in later stage)
      • Ischias/lumboischialgia
    • Diagnosis – MRi
    • Treatment
      • Irradiation
      • Decompressive surgery

24. Paraneoplastic nervous system diseases

  • Epidemiology
    • Occurs in 1 – 3% of patients with malignancies
    • Commonly develop before the cancer diagnosis
  • Etiology
    • Small cell lung cancer
    • Breast cancer
    • Ovarian cancer
    • Lymphoma
    • Neuroendocrine tumours
  • Pathophysiology
    • Occurs when tumours express antigens which are structurally similar to antigens on neurons (molecular mimicry)
    • Antineuronal antibodies present in serum and CSF
  • Diagnosis
    • CSF changes
      • Increased protein
      • Lymphocytic pleocytosis (increased lymphocytes)
      • Oligoclonal bands
    • EEG may show abnormality
    • MRI may show abnormality
  • Importance
    • Can give earlier diagnosis of tumour
    • Recognising paraneoplastic syndromes early gives best chance for its management
  • Treatment
    • Treatment with steroids, IVIG, plasmapheresis, other immunosuppressants
    • Treatment response depends on specific type
  • Types
    • Onconeuronal antibody-associated types
      • Antibodies against intracellular antigens
      • Respond poorly to therapy
      • Includes
        • Paraneoplastic cerebellar degeneration
        • Paraneoplastic sensory neuronopathy
        • Limbic encephalitis caused by anti-Ma2
    • Neuronal surface antibody-associated types
      • Antibodies against surface antigens
      • Respond better to therapy
      • Not all causes are paraneoplastic, can be autoimmune as well
      • Includes
        • Anti-NMDA receptor encephalitis
        • Limbic encephalitis caused by other antibodies
  • Paraneoplastic cerebellar degeneration
    • Subacute (< 12 weeks) onset of cerebellar symptoms
      • Trunk and limb ataxia
      • Dysarthria
      • Nystagmus
    • Causes irreversible T-cell mediated destruction of Purkinje cells
    • Does not respond to therapy, most patient become wheelchair-bound
  • Paraneoplastic sensory neuronopathy
    • (Neuronopathy = damage to nerve cell body of dorsal root ganglia)
    • Subacute onset of paraesthesia and heavy pain
    • Asymmetric symptoms
    • Mostly affect upper limbs
    • Poor response to therapy
  • Anti-NMDA receptor encephalitis
    • Almost always after ovarian teratoma
    • Mostly affects young women and children
    • Commonly starts with behavioural changes, memory deficits
    • Later comes seizures, abnormal movements, autonomic dysfunction
    • Antibodies against NMDA receptor are present in serum and CSF
    • Good response to therapy
  • Anti-Ma2 encephalitis
    • Mostly after testicular cancer
    • Subacute onset of memory deficit, seizure, irritability, cognitive decline
    • Poor response to therapy

Symptoms of raised intracranial pressure

  • Signs of increased ICP
    • Cushing triad/reflex
      • Hypertension
      • Bradycardia
      • Irregular respiration
    • Reduced level of consciousness
    • Headache
    • Vomiting
    • Papilloedema
    • Abducent palsy -> diplopia
  • Types of intracranial herniation
    • Subfalcine (cingulate) herniation
      • Cingulate gyrus herniates under falx cerebri
      • Clinical features
        • Usually asymptomatic, discovered incidentally
    • Uncal transtentorial herniation
      • Uncus herniates at tentorial incisure
      • Often caused by a unilateral mass effect
        • Haemorrhage
        • Infarct (-> swelling)
      • Clinical features
        • Impaired consciousness
        • Ipsilateral CN III palsy
          • Fixed, dilated pupil (Hutchinson’s pupil)
          • Later, downward and outer deviation of eye occurs
        • Contralateral motor deficit
        • Ipsilateral motor deficit (Kernohan’s sign)
          • Due to compression of the contralateral cerebral peduncle
          • One of the rare cases where a cortical lesion causes ipsilateral motor signs
    • Central transtentorial herniation
      • Hemispheres, basal ganglia and diencephalon herniate through tentorial notch into the midbrain
      • Often caused by diffuse or bilateral mass effect
        • Diffuse or multifocal swelling
        • Bilateral haematomas
      • Clinical features
        • Impaired consciousness
        • Compression of the vein of Galen
          • Venous congestion
          • Cerebral oedema
        • Compression of cerebral aqueduct -> obstructive hydrocephalus
        • Stretching of the basilar artery -> potential rupture
    • Foramen magnum (tonsillar) herniation
      • Cerebral tonsils herniate through foramen magnum
      • Causes compression of brainstem
        • -> Impaired consciousness
        • -> Impaired circulation
        • -> Impaired respiration -> apnoea

25. Focal dystonias

  • Dystonia = a movement disorder with sustained or intermittent muscle contractions causing abnormal movements or postures
  • Types according to age
    • Early-onset dystonia
      • Onset < 20 years
      • Usually generalized
    • Adult-onset dystonia
      • Onset > 20 years
      • Usually focal or segmental
  • Types according to cause
    • Primary dystonia
      • Idiopathic or familial
      • Normal brain MRI
      • Dystonia is the only symptom
    • Secondary dystonia
      • Antiparkinsonian drugs
      • Antipsychotic drugs
      • Huntington disease
      • Wilson disease
      • Stroke
  • Types according to distribution
    • Focal dystonia
      • Affects a single region
      • Most are idiopathic
    • Segmental dystonia
      • Affect multiple regions
    • Generalized dystonia
      • Affect the whole body or close to it
      • Usually early-onset
    • Hemidystonia
      • Affects one body side
  • Specific dystonias
    • Cervical dystonia (= torticollis)
      • A focal, primary dystonia
      • Sudden, painful contraction of sternocleidomastoid causing the head to turn, tilt, or flex
    • Hand dystonia
      • A focal, primary dystonia
      • Non-painful contractions in the hand or arm
      • Occurs when writing or playing instrument (writer’s cramp or musician’s cramp)
    • Eye dystonia (= blepharospasm)
      • A focal, primary dystonia
      • Spasm of periocular muscles, causing involuntary twitching or blinking
      • Can be isolated or part of Meige syndrome
    • Laryngeal dystonia (= spastic dysphonia)
      • A focal, primary dystonia
      • Spasm of vocal cord muscles, causing voice breaks and strained voice
    • Oromandibular dystonia
      • A focal, primary dystonia
      • Spasm of muscles of mouth and jaw, causing chomping movements
      • Can be isolated or part of Meige syndrome
    • Meige syndrome
      • A segmental (not focal), primary dystonia
      • Presence of both blepharospasm and oromandibular dystonia
    • Early-onset isolated dystonia
      • Begins in childhood
      • Usually begins in the leg, eventually progressing to becoming generalized
  • Treatment of focal or segmental dystonia
    • Botulinum toxin injection in affected muscle
      • Very effective
      • Toxin prevents release of Ach into NMJ
    • Deep brain stimulation
      • If botulinum toxin injection is insufficient
  • Treatment of generalized dystonia
    • Medical treatment
      • Not very effective
      • Dopamine antagonists (tiapride)
      • Antipsychotics
      • Antiepileptics
      • May improve symptoms in all dystonias, but will also confirm or exclude the diagnosis of dopa-responsive dystonia
    • Deep brain stimulation
      • Very effective

Creutzfeldt-Jakob disease (CJD)

  • Epidemiology
    • Incidence: 1 / 1 000 000
    • Usually affect elderly
    • In 85% of cases the source is not identified
  • Pathomechanism
    • Due to a misfolded protein called PrP = prion proteins
      • Normal prion proteins are in the PrPC conformation
      • Prion proteins in the PrPSc conformation cause other proteins in PrPC conformation to change to PrPSc
      • PrPSc accumulate and cause neuron death
    • Can be familial, due to mutations in the PRNP gene
    • Can be acquired
      • Due to consumption of meat infected with bovine spongiform encephalopathy = variant CJD
      • Due to transmission during medical procedures = iatrogenic CJD
  • Clinical features
    • Typical symptoms:
      • Rapidly progressing dementia
      • Myoclonus
    • Cerebellar symptoms
    • Extrapyramidal signs
    • Sleep disorder
    • Headache
    • Fatigue
    • Seizures
  • Diagnosis
    • CSF analysis – increased 14-3-3 protein
    • MRI – hyperintense signal in basal ganglia, thalamus, cortex outline
    • EEG – periodic sharp wave complexes are highly specific, but not sensitive
  • No available treatment – most die within a year
  • Other prion diseases
    • Fatal familial insomnia
      • Autosomal dominant mutation in PRNP gene
      • Progressively worse insomnia
      • Always deadly
    • Gertsmann-Straussler-Scheinker disease
      • Autosomal dominant
      • Progressive ataxia, pyramidal signs, dementia
      • Always deadly

26. Symptoms of insufficient blood circulation in vertebrobasilar territory

  • Posterior territory stroke = stroke involving the territory of the vertebrobasilar arterial system
    • 20% of stroke cases
  • Cranial nerve involvement
    • Ipsilateral diplopia
    • Ipsilateral facial sensory loss
    • LMN facial palsy
    • Vertigo
    • Dysphagia
    • Dysarthria
  • Ipsilateral limb ataxia – if cerebellum affected
  • Ipsilateral Horner syndrome
  • Contralateral or bilateral hemiparesis (= tetraparesis)
    • (There’s no such thing as bilateral hemiparesis, of course)
  • Contralateral or bilateral hemisensory loss
  • Contralateral homonymous hemianopia
  • Cortical blindness (blindness with an otherwise normal ophthalmological examination)

Subacute combined degeneration of the spinal cord (funicular myelosis)

  • Subacute combined degeneration is the neurological consequence of chronic B12 deficiency
  • Chronic B12 deficiency -> demyelination and degeneration of dorsal and lateral white matter in the spinal cord
    • Spinocerebellar, lateral corticospinal, and dorsal columns are affected
  • Not all patients with this also have (megaloblastic) anaemia
  • Clinical features
    • Symptoms are progressive
    • Weakness
    • Sensory ataxia
    • Paraesthesia
    • Later -> spasticity, paraplaegia, incontinence
  • Diagnosis
    • Low serum B12
    • High serum methylmalonic acid (MMA), homocysteine
    • CBC -> megaloblastic anaemia, pancytopaenia
    • Improvement of symptoms during supplementation confirms diagnosis
  • Treatment
    • IM B12, later oral supplements or dietary changes
    • It may take long for symptoms to improve, and they may not be completely reversible

27. Ischemic stroke

  • 80% of strokes
  • Large artery occlusion stroke
    • 20 – 25% of ischaemic strokes
    • Due to occlusion of large arteries
      • Middle cerebral artery > internal carotid > vertebral, ACA, etc
      • Often due to atherosclerotic rupture with thrombosis
    • Worst subtype
    • Causes large infarct (> 1,5 cm diameter)
    • Can affect both cortex and subcortical regions
  • Small artery occlusion/lacunar stroke
    • 25% of ischaemic strokes
    • Due to occlusion of penetrating small arteries
      • Also called lenticulostriate arteries
      • These are small arteries which arise at acute angles from large cerebral arteries
      • Chronic hypertension causes lipohyalinosis of these arteries, causing occlusion
    • Causes small infarct (< 1,5 cm diameter)
    • Mostly affect subcortical regions (basal ganglia, brainstem)
    • Clinical features
      • No cortical symptoms
      • Pure hemiparesis
      • Pure hemisensory loss
      • Ataxic hemiparesis
      • Dysarthria-clumsy hand syndrome
  • Cardioembolic stroke
    • 20% of ischaemic strokes
    • Arterial occlusion presumably due to embolus from heart
    • A cardiac source of embolus must be identified
      • AF, MI, endocarditis, etc.
  • Cryptogenic stroke
    • 25 – 30% of ischaemic stroke
    • Ischaemic stroke in which the etiology can not initially be determined
    • Most commonly due to
      • Paroxysmal AF
      • PFO with paradoxical embolism
      • Non-atherosclerotic vasculopathy

Wilson’s disease

  • An autosomal recessive disorder where copper accumulates in the liver and brain
  • Epidemiology
    • Age of onset 5 – 35 years
    • Prevalence 1/30 000
  • Pathomechanism
    • Autosomal recessive
    • Mutation in the ATP7B gene, a copper transporter -> decreased copper excretion, decreased incorporation of copper into apoceruloplasmin -> increased free serum copper
    • Copper accumulates in the liver, CNS, cornea, kidneys, enterocytes
  • Clinical features
    • Hepatitis/cirrhosis -> jaundice, ascites, etc.
      • Can manifest as acute liver failure, acute hepatitis, chronic hepatitis, etc.
    • Psychiatric symptoms
      • Dementia
      • Depression
      • Personality change
    • Neurological symptoms
      • Parkinsonism and other extrapyramidal symptoms
      • Dysarthria
      • Gait ataxia
      • Tremor
    • Kayser-Fleischer rings – green-brown rings on the periphery of the iris (in 95% of patients)
  • Diagnosis
    • Presence of typical symptoms, especially Kayser-Fleischer rings
    • Decreased liver function tests
    • Decreased serum ceruloplasmin
    • Increased urinary copper excretion
    • Genetic testing for definitive diagnosis
    • Liver biopsy (not usually needed)
  • Treatment
    • Copper chelator – trientine or penicillamine
      • Penicillamine have more side effects so trientine is preferred
    • Initially high dose to remove excess copper, then life-long lower dose to prevent accumulation
    • Diet low in foods which are rich in copper
  • Prognosis
    • Fatal if untreated
    • Excellent if treated

28. Obstructive sleep apnoea syndrome

  • Epidemiology
    • 15 – 30% of males
    • 5 – 15% of females
  • Risk factors
    • Smoking
    • Obesity
    • Family history
    • Nasal congestion
    • Pregnancy
    • Alcohol
  • Pathophysiology
    • Apnoea because of upper airway obstruction, usually because the pharyngeal muscles have so low tone that they collapse and close the oropharynx
    • Apnoea causes hypoxaemia, hypercapnia
      • -> pulmonary vasoconstriction -> cor pulmonale
      • -> sympathetic activity -> secondary hypertension
      • -> respiratory acidosis
  • Clinical features
    • Daytime sleepiness
    • Partner reports loud snoring, choking, or interruptions in breathing while sleeping
    • Impaired cognitive function
    • Depression
  • Diagnosis
    • The patient needs to have their cardiopulmonary parameters and EEG measured during sleep, either by
    • Polysomnography – Conducted in a lab
    • Home sleep apnoea testing – Conduced at home
    • Results
      • O2 saturation decreased
      • Arousal events on EEG
      • Pulse pressure increased
      • Bradycardia
      • Fragmentation of sleep, decreased REM sleep phases
  • Treatment
    • Weight loss
    • Avoid risk factors
    • Sleeping on the side
    • Oral appliances which keep the upper airway open
    • Severe cases:
      • Surgery (uvulopalatopharyngoplasty)
      • Continuous positive airway pressure (CPAP) – holds the oropharynx open

Choreas, Huntington disease

  • Chorea
    • = involuntary, sudden, irregular, nonrepetitive, arrhythmic movements of limbs or head
    • Due to increased dopaminergic transmission in the basal ganglia
    • Most commonly caused by Huntington disease, but can be caused by other conditions as well
      • Sydenham chorea
      • Wilson disease
      • Ataxia-telangiectasia
      • Dopaminergic drugs (esp. levodopa)
      • Stroke
      • Paraneoplastic syndrome
    • Sydenham chorea
      • A CNS manifestation of rheumatic fever, so it occurs after streptococcus infection
      • Usually effect children, especially girls
      • Rare nowadays (just like RF)
  • Huntington disease (HD)
    • Epidemiology
      • Prevalence 3/100 000
      • Begins in 30s, 40s
    • Pathomechanism
      • Autosomal dominant
      • Increased number of CAG repeats in the huntingtin (HTT) gene increases risk for Huntington disease
      • 10 – 35 CAG repeats are physiological, 36 – 39 is high risk for HD, while > 40 invariably causes HD
      • The higher the number of repeats, the earlier the onset and more severe
    • Clinical features
      • Initially chorea -> hypokinesia in advanced stages
      • Psychiatric symptoms
        • Irritability
        • Depression
        • Paranoia
        • Psychosis
        • Delusions
        • Hallucinations
      • Dementia
    • Diagnosis
      • Based on presence of family history and clinical features
      • Genetic testing for definitive diagnosis
    • Treatment
      • No cure, only symptomatic and slowing progression
      • Multidisciplinary care
      • Tetrabenazine – improve chorea but worsens psychiatric symptoms
      • Second generation antipsychotics – improve chorea and psychosis but cause sedation and parkinsonism
    • Prognosis
      • Average lifespan after onset of signs and symptoms 15 – 20 years
      • Cause of death: respiratory insufficiency, aspiration pneumonia

29. Restless-legs syndrome

  • = Willis-Ekbom disease
  • Very common, affects 15% of the US
  • Etiology
    • Primary
      • Idiopathic
      • Familial (40 – 60% of cases)
    • Secondary
      • Iron deficiency
      • Uraemia
      • Spinal cord disease
      • Peripheral neuropathy
      • Parkinson disease
      • Autoimmune disease
      • Certain drugs
  • Clinical features
    • Unpleasant sensations in the legs which give a strong urge to move them
    • Usually occurs during periods of rest, esp. evening and night
  • Diagnosis
    • Based on clinical features, and after excluding other causes
    • Iron studies
    • ENG, EMG
  • Treatment
    • Abstinence from coffee, nicotine, alcohol
    • Treat underlying disease
    • Medical therapy
      • Dopamine agonists (pramipexole, ropinirole)
      • Gabapentin, pregabalin

Conversion disorders

  • = functional neurological symptom disorder
  • Patient has neurological symptoms that cannot be fully explained by a neurological disorder, but are rather due to a psychiatric problem
  • The patient subconsciously “converts” their psychiatric problems (trauma, anxiety, etc.) into a neurological symptom
  • Clinical features
    • Can be any neurological symptom
      • Unilateral symptoms usually affect the left side
      • Headache (especially tension headache)
      • Vertigo
      • Hemiparesis or hemiplaegia
        • Usually affect the whole half of the body, from head to toe (which is rare in organic disease)
      • Sensory loss
      • Abnormal speech
      • Mutism
      • Blindness
      • Nonepileptic seizures
    • La belle indifference – patient is unbothered and calm when describing their neurological symptoms, even if they are severe
      • This is because conversion symptoms usually relieve the mind of some underlying anxiety or psychiatric problem
    • Neurological signs and investigations are inconsistent with the symptoms
      • For example, a patient may have weakness during physical examination but not show the same weakness when not formally examined
  • Is diagnosed when the patient has debilitating symptoms which cannot be fully explained by a neurological disorder
  • Treatment
    • Patient education
    • Psychotherapy
    • Management of underlying psychiatric disease

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4 thoughts on “Old neurology 2 notes”

  1. Hello 🙂 you should add toxicology, infections and ABG (hypoxia) in the lab investigations for acute treatment of ischemic stroke.

    Thank you for amazing notes like always ❤️

    1. Glad you like the notes!

      Regarding the other things, I can understand that toxicology and infectious parameters could play a role in the DD of stroke, but I don’t think they’re very important. But I’ll add them either way

  2. Why is it called “old neuro 2” ? Is it just a merged version of all topics and same as what u put in every single topic separately ?

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