Inflammatory and Autoimmune

Question 1

What is multiple sclerosis?

Answer 1

Inflammatory demyelinating disease of the CNS, defined by neurological dysfunction in at least two areas of the CNS (brain, spinal cord, OPTIC NERVES), that are separated in time and space (McDonald criteria).

Question 2

What are the types of MS? (x4)

Answer 2

• RELAPSING-REMITTING: clinical attacks of demyelination with complete recovery in between attacks
• CLINICALLY ISOLATED SYNDROME: single attack of demyelination (does not qualify as MS)
• PRIMARY PROGRESSIVE: stead accumulation of disability with no clear relapsing-remitting pattern
• MARBURG VARIANT: severe fulminant variant leading to advanced disability of death within weeks

Question 3

What is the aetiology of MS?

Answer 3

Autoimmune with environmental trigger in genetically pre-disposed individual

Question 4

What are the risk factors of MS? (x3)

Answer 4

EBV, prenatal vitamin D levels and deficiency, smoking

Question 5

What is the pathophysiology of MS?

Answer 5

T cells access CNS through BBB infiltration. Immune-mediated damage to CNS myelin results in impaired conduction along axons, with eventual axonal damage from autoimmune and inflammatory damage. There is also associated grey matter atrophy (CNS cell bodies).

Question 6

What is the epidemiology of MS: Type? Gender? Age?

Answer 6

Most common type is relapsing-remitting. More common in females. Presents 20-40.

Question 7

What are the optic signs and symptoms of MS? (x6)

Answer 7

• OPTIC NEURITIS (swelling that affects optic nerve; most common symptom): unilateral deterioration in visual acuity and colour perception.
• There may be pain on eye movement.
• Fundoscopy shows swollen optic nerve head, with optic atrophy in chronic disease
• Visual field testing shows central scotoma (optic nerve affected) or field defects (optic radiations affected)
• Relative afferent pupillary defect: both pupils dilate when light shone in affected eye
• Internuclear ophthalmoplegia: lateral horizontal gaze produces a failure of adduction of the contralateral eye, indicating lesion of contralateral medial longitudinal fasciculus

Question 8

What are the extra-ocular signs and symptoms of MS? (x6)

Answer 8

• SENSORY: paraesthesia, burning pain
• MOTOR: paraplegia and UMN signs such as spasms, stiffness, brisk reflexes
• CEREBELLAR: limb ataxia (intention tremor, past-pointing and dysmetria on finger-nose test and heel-shin test), dysdiadochokinesis, ataxic wide-based gait
• UHTHOFF’S PHENOMENON: transient increase or recurrence of symptoms due to conduction block precipitated by rise in body temperature
• LHERMITTE’S PHENOMENON: electric shock-like sensation in arms and legs precipitated by neck flexion
• Constipation and urinary frequency

Question 9

What are the investigations for MS? (x3)

Answer 9

• MRI BRAIN, CERVICAL AND THORACIC SPINE: gadolinium (contrast)-enhancing inflammatory lesions with limited oedema in brain, grey matter atrophy, and spinal hypo-intensity (or black holes)
• LP: microscopy to exclude other infective/inflammatory causes. CSF electrophoresis shows unmatched oligoclonal bands
• EVOKED POTENTIALS: delayed conduction velocity

Question 10

What is Guillain-Barre syndrome?

Answer 10

Acute inflammatory demyelinating polyneuropathy.

Question 11

What is the aetiology of GBS? (x3)

Answer 11

• Idiopathic in 40%
• Post-infection (1-3 weeks): bacterial (e.g., Campylobacter jejuni), HIV, herpes viruses, Zika virus outbreaks
• Malignancy (lymphoma, Hodgkin’s)
• Post-vaccination

Question 12

What is the pathophysiology of Guillain-Barre syndrome?

Answer 12

Inflammatory process where antibodies react with self-antigen on myelin or neurons leading to demyelination. Rare axonal variants of GBS may be associated with no demyelination.

Question 13

What are the signs and symptoms of Guillain-Barre syndrome? (x6) Disease course? Consideration of alternative diagnosis?

Answer 13

• COURSE: progressive symptoms of less than 1 month duration of:
• Ascending symmetrical limb weakness (lower > upper) associated with FLACCID PARALYSIS on examination and bilateral hypotonia
• Ascending paraesthesia
• Arreflexia
• There may also be cranial nerve involvement (dysphagia, dysarthria, facial weakness (LMN), bulbar symptoms). If there is pupil constriction, consider botulism
• Respiratory muscles affected if severe and affects 30% who will need ventilation
• Autonomic dysfunction: postural hypotension and arrythmias
• Back or leg pain is reported in most patients

Question 14

What is the Miller-Fisher variant of Guillain-Barre syndrome?

Answer 14

Associated with ophthalmoplegia, ataxia and arreflexia.

Question 15

What is dysarthria?

Answer 15

Motor speech disorder of slurring words due to loss of control of larynx and tongue

Question 16

What are the investigations for Guillain-Barre syndrome? (x5)

Answer 16

• LP: raised CSF protein, normal cell count (called albuminocytological dissociation), and to exclude other aetiologies such as meningitis
• NERVE CONDUCTION STUDY: reduced conduction velocity or conduction block
• BLOOD: anti-ganglioside antibodies are positive in Miller-Fisher, and 25% of GBS cases. Consider C. jejuni serology
• SPIROMETRY: indicates ventilator weakness
• ECG: arrythmias in autonomic dysfunction

Question 17

What is myasthenia gravis?

Answer 17

Autoimmune disease affecting NMJ producing weakness of skeletal muscles

Question 18

What is the pathophysiology of myasthenia gravis? (x2)

Answer 18

• Auto-antibodies against nAChR at NMJ
• Lambert-Eaton myasthenic syndrome is a paraneoplastic subtype caused by autoantibodies against pre-synaptic calcium ion channels, impairing Ach release

Question 19

What is the aetiology of myasthenia gravis? (x2)

Answer 19

Associated with other autoimmune conditions such as pernicious anaemia and thymoma (malignancy leading to breakdown of immune balance thought to arise in thymus)

Question 20

What is the epidemiology of myasthenia gravis: Gender?

Answer 20

More common in females at younger ages, but equal gender distribution in middle age.

Question 21

What are the signs and symptoms of myasthenia gravis? (x4)

Answer 21

• Muscle weakness: worsens with repetitive use or towards end of day
• Ocular symptoms: diplopia, bilateral ptosis (may be asymmetrical)
• Bulbar symptoms: facial weakness (myasthenic snarl), disturbed hyper-nasal speech, difficulty in smiling, chewing, or swallowing (nasal regurgitation of fluids)
• SOB if severe enough to impair mechanical ventilation

Question 22

How do you test for ocular symptoms? (x2)

Answer 22

Test for ocular fatigue by asking patient to sustain upward gaze for 1 minute and watch for progressive ptosis. OR ‘ice on eyes’ test which, for two minutes, can improve NMJ transmission (considered positive when ptosis improved by at least 2mm from baseline)

Question 23

How do symptoms differ in Lambert-Eaton syndrome?

Answer 23

Muscle weakness IMPROVES after repeated use.

Question 24

What are the investigations for myasthenia gravis? (x5)

Answer 24

• BLOOD: CK (exclude myopathies), serum AChR antibody (positive in 80%), TFT (associated disorders). Atypical features warrant anti-MuSK antibody (uncommon variant) and anti-voltage-gated-calcium-channel antibody (in Lambert-Eaton syndrome)
• TENSION TEST: short-acting anti-cholinesterase increases ACh levels, causing rapid and transient improvement in symptoms
• NERVE CONDUCTION STUDY: repetitive stimulation associated with decrements in muscle action potential. Differentiate between MG and LES
• EMG: demonstrates ‘jitter’ (variability in latency from stimulus to muscle potential) indicating fluctuation in NMJ conduction
• CT THORAX/CXR: visualise thymoma in mediastinum