Neuromuscular disorders Flashcards
Genetic predispositions to MS
HLA-DRB1*15- increases risk
3-4% increased risk among first-degree relatives
Environmental predispositions to MS
Low vitamin D
Smoking
Infection: EBV, HHV
Early life obesity
Schilder disease
Affects children/ young adults
Large areas of demyelination
Pathological process in MS
Autoimmune, inflammatory destruction of myelin with partial preservation of axons
- T cells mediated
- Causes atrophy of oligodendrocytes and gliosis
B cell dysfunction
- synthesis of IgG bands
- Anti-CD20 agents effective in exacerbation
Marcus Gunn pupil
Unilateral relative afferent pupillary defect
- afferent pupil dilating when light swung between both eyes
Intranuclear opthalmoplegia is caused by a lesion to the __________
Medial longitudinal fasciculus
Intranuclear opthalmoplegia features
- Medial rectus palsy on same side
- Intact convergence reflex
- Lateral nystagmus in contralateral eye
Mechanism of Intranuclear opthalmoplegia
CN6 nucleus in pons (lateral rectus)
- Communicates to medial longitudinal fasciculus —> CN 3 nucleus in midbrain
CN3 innervates medial rectus
Activation of lateral gaze (CN6) alllows conjugate eye movememnt
Lesion in MLS causes palsy on medial rectus on same side
- CN6 still functioning on contralateral side- causing nystagmus
Pronator drift test showing pronation and downward arm drift is typical of what lesion?
Upper motor neuron lesion
Pronator drift test showing pronation and upward arm drift is typical of what lesion?
Cerebellar lesion
Pathophysiology of neuromyelitis optica
Anti-aquaporon-4 antibody
- Destroys membrane of astrocytes involved in humoral immune response
Causes demyelination and axonal damage of optic nerve and spinal cord
Neuromyelitis optica acute treatment
Loading steroids with tapering over 2-8 weeks
Severe= plasmaphersis
Acute disseminated encephalomyelitis is associated with…
Infection (i.e. measles)
Vaccination
Diagnostic features of Acute disseminated encephalomyelitis
Clinical- rapid progression
- motor, sensory, CN, brainstem involvement
- optic neuritis
- reduced GCS
LP
- high lymphocyte
- raised protein
MRI spine/ brain
- B/L lesions
Acute disseminated encephalomyelitis management
High-dose IV steroids
Acyclovir empirically
2nd line
- IV immune globulin
First line treatment for MS
High dose IV steroids
2nd line- plasmapheresis, ACTH gel
Lifestyle modifications for MS
Exercise
Smoking cessation
Manage sleep disorders
Most commonly used disease-modifying MS medication
Interferon- beta
Glatiramer acetate
Ocrelizumab is used in what MS phenotype
Primary, progressive MS
Adverse effects of interferon-beta
Injection site reaction
Flu-like symptoms
Liver dysfunction
Leukopenia
Depression
Glatiramer acetate (copolymer-1)
Decoy for T cells instead of myelin
- reduced Th1 inflammation and increases anti-inflammatory Th2
What disease-modifying MS medication is teratogenic?
Teriflunomide
What medication used in MS can aid mobility by blocking K channels, allowing increased AP in demyelinated axons?
Dalfampridine
Poor prognostic factors for disease progression in MS
Male
Onset >40
Multiple early motor and cerebellar involvement
Incomplete recovering after exacerbation
High relapse within first 2 years of MS onset
Effect of pregnancy on MS
Decreased exacerbation during pregnancy
Increased exacerbation risk post-partum
Effect of MS on pregnancy
Low fetal birth weight
Increased rate of C-section/ assisted deliver
Medication cautions for MS during pregnancy
Stop most-disease modifying medications at least 4 months before conception
- glatiramere acetate is the safest
Avoid steroids in 1st trimester
Avoid breastfeeding for DM medications
What are the two approved drugs for ALS?
Riluzole
Edaravone
Life-expectancy prognosis for ALS
Most (70%)- 3-5 years from onset
Common infection causes associated with GBS
Typically 2-4 weeks before:
C. jejuni
CMV
EBV
Clinical presentation of GBS
Bilateral ascending flaccid paralysis over days
Glove-stocking paraesthesia
Hypo/areflexia
CN weakness- most commonly facial nerve
Respiratory distress
Autonomic dysfunction
GBS prognosis
Most (80%) have spontaneous remission with near complete recovery in 6 months.
3-7% die from complications
Indications for IV immunoglobulins/ plasmapheresis in GBS
Severe flaccid paralysis (unable to walk unsupported for >10m
Bulbar palsy
Progressive respiratory failure/ autonomic dysfunction
Mechanical ventilation
Diagnostic features of GBS
Labs- exclude infection or electolyte disturbance
CSF- increased protein, normal WCC (<10/ mcL)
Nerve conduction studies
- Sural nerve typically intact
EMG
- Shows neuropathy instead of myopathy
- Pathological spontaneous activity= unfavourable prognosis
Monitoring in GBS
- Monitor for respiration function with PFTs
- Autonomic function: cardiac monitoring, bladder/ bowel function
- Motor/sensory function, including swallowing
What tool can be used to predict the need for mechanical ventilation in GBS?
Erasmus GBS respiratory insufficiency score
Poor prognostic factor for long-term disability in GBS
Rapid progression of symptoms
Severe symptoms at peak of disease
Older age
Axonal damage
Friedreich ataxia
- aetiology
GAA trinucleotide repeat exapnsion
- FXN gene, chromsome
- autosomal recessive
Oxidative damage of CNS and PNS (intramitochondrial iron accumulation)
Friedreich ataxia
- clinical features
neuro:
- Progressive ataxia
- Upper limb action + intentional tremors
- Impaired dorsal column sensation
- Loss of deep tendon reflexes
- Spastic paralysis
- Nystagmus
Skeletal- scoliosis, foot inversion, hammertoes
Cardiac
- Hypertrophic CMP
- palpitations,
arrhythmias
