Neuromuscular Disorders

Question 1

Cerebral Palsy

Answer 1

• Definition:
  
  • chronic condition characterized by impaired muscle tone, strength, and coordination of movements
• Pathophys:
  
  • cerebral injury often before birth but can also occur during birth or in the perinatal and postnatal period. Maternal infections &/or fetal hypoxia is often root cause
• S/sxs:
  
  • -Spasticity (still muscles)
  • -Dyskinesia (uncontrollable movements)
  • -Ataxia (poor balance & coordination)
  • • May also have: intellectual disability; seizures; problems with vision, hearing or speech; changes in spine (scoliosis); or joint problems (contractures)
• Dx:
  
  • Cranial MRI
  • • CP can rarely be confirmed during early infancy and the specific syndrome cannot be characterized until around age 2
  • -High risk kids (e.g. kids with evidence of asphyxia, stroke, periventricular abnormalities seen on cranial ultrasonography in premature infants, jaundice, meningitis, neonatal seizures, hypertonia, hypotonia, or reflex suppression) should be followed closely
• Tx:
  
  • Early intervention for children age 0-3 years is very important!!
  • PT and OT
  • Tx the spasticity: braces, constrains, surgery and meds
  • -Benzodiazepines → myorelaxation, anxiety relief
  • -Spasmolytics → muscle-spasticity relief
  • -Anticonvulsants → seizure tx, prevention
  • -pain meds
  • -Botulinum toxin injections
  • -Intrathecal baclofen

Question 2

Types of Cerebral Palsy

Answer 2

4 types:

1. Spastic Cerebral Palsy (80% of cases): state of resistance to passive range of motion; resistance increases with the increasing speed of that motion. Due to upper motor neuron involvement
2. Athetoid or Dyskinetic CP (20% of cases): result from basal ganglia involvement; sxs = slow, writhing, involuntary movements of the proximal extremities and trunk often caused by voluntary movement or excitement
3. Ataxic Cerebral Palsy (<5% of cases): results from involvement of cerebellum; weakness, incoordination, and intention tremor that causes unsteadiness, a wide-based gait, and difficulty with rapid or fine movements
4. Mixed cerebral palsy: common→ most often with spasticity and athetosis

Question 3

Multiple Sclerosis

Answer 3

• Definition:
  
  • an autoimmune disease of the CNS characterized by chronic inflammation, demyelination, gliosis (plaques or scarring), & neuronal loss of the white matter
• Risks:
  
  • Upper Northern Hemisphere (less sunlight), women, smoking, Vitamin D deficiency, family hx, African Americans (increasing)
• Epidemiology:
  
  • most common permanently disabling disorder of the CNS in young adults; mean age onset 28-31yo
• S/sxs:
  
  • -paresthesias in the extremities
  • -Ataxia
  • -Fatigue
  • -Focal motor symptoms
  • -weakness
  • -Spasticity
  • First visit usually associated with vision symptoms followed by weakness in distal limbs, ataxia, or paresthesias over several years
• PE:
  
  • Lhermitte’s Sign: electrical shock sensation in the limbs & torso brought on by movement (usually flexion) of the neck.
• Dx:
  
  • MRI looking for plaques associated with MS (McDonald’s Diagnostic Criteria) → MRI of the brain & spinal cord
  • If MRI is non-diagnostic then next best test = lumbar puncture which would show oligoclonal bands
  • McDonald’s Diagnostic Criteria:
    
    • -2 episodes of neurologic deficits (focal weakness, sensory disturbances) separated in time & space
    • *Must occur in absence of a fever, infection or other etiologies
    • *Attacks must last >24 hours.
• Tx:
  
  • Average lifespan = 25-35 years after diagnosis
  • Acute Exacerbations:
    
    • -Corticosteroids = tx of choice, PO = IV
    • -Plasmapheresis: if unresponsive to steroids, every other day x 14 days
  • Chronic Management:
    
    • *Disease-modifying agents suppress T-cell autoimmune cascade → EARLY treatment instigated by neurologist
    • -Disease modifying agents: interferon beta, Glatiramer, fingolimod, teriflunomide, dimethyl fumarate, natalizumab, alemtuzumab, ocrelizumab, mitoxantrone
    • -Symptom-Specific tx for neurogenic bladder (oxybutynin)
• Tx of spasticity (Baclofen, tizanidine, diazepam, dantrolene)

Question 4

Multiple Sclerosis: Pathophys and Course of Disease

Answer 4

• Pathophys:
  
  • -Plaques develop at different times & in different CNS locations
  • -T cells & B cells cross damaged BBB & release inflammatory mediators & immunoglobulins that target myelin nerve sheath
  • -Macrophages expose axonal surfaces & release NO & oxygen free radicals
  • -Surviving oligodendrocytes partially remyelinate → gliotic plaques (Sclerosis)
• Course of Disease:
  
  • Relapsing-Remitting (90%): discrete attacks evolving over days-weeks followed by recovery
  • -Secondary progressive: initial relapsing-remitting followed by gradual deterioration
  • -Primary progressive: steady functional decline from onset

Question 5

Myasthenia Gravis

Answer 5

• Definition:
  
  • an autoimmune disease involving the postsynaptic membrane in the neuromuscular junction
• Epidemiology:
  
  • most commonly acquired disorder of neuromuscular transmission, but rare. Peaks bimodal at~30 (young women) & ~50yo (old men), African descent
• S/sxs:
  
  • Hallmark = fatigability ⇒ weakness in everyday activities like brushing hair
  • Sitting to Standing weakness: generalized or localized, more proximal than distal, symmetric
  • Fatigability: fluctuating weakness, worsens with exercise & throughout the day
  • Ocular Weakness: asymmetric, ptosis, horizontal/vertical/diagonal diplopia
  • Bulbar Weakness: weakness in jaw muscles, difficult chewing, dysphagia, nasal regurgitation of fluids, aspiration, loss of facial expression, inability to fully close eyelids
  • -Respiratory muscle weakness: dyspnea with exertion, orthopnea
• PE:
  
  • Ice Pack Test:
  • -Place ice cube over eyelid for 2 minutes → improvement of ptosis suggests neuromuscular transmission disorder
• Dx:
  
  • -Antibody tests: Standard of diagnosis, AChR, MuSK, LRP4
  • -Single-fiber EMG: most sensitive diagnostic test that shows decremental response to repetitive stimulation of motor nerves
  • -CT contrast/MRI chest: to look for thymoma or residual thyroid tissue
  • -TSH & Free T4: look for thyroid dx
  • -Forced vital capacity: determine extent of respiratory muscle involvement
• Tx:
  
  1. Symptomatic treatment (acetylcholinesterase inhibition): pyridostigmine, neostigmine, ambenonium chloride, only tx needed if mild dx
  2. Immunosuppression: prednisone or prednisone/azathioprine = 1st line, most MG patients
  3. Immunomodulation: monoclonal antibodies (rituximab, eculizumab), cyclosporine, mycophenolate mofetil
  4. Thymectomy: for all MG patients with thymoma, mild-moderate AChR antibody positive generalized disease, risk of acute myasthenic crisis
  5. Co-Existing Disorders: thyroiditis = most common, SLE, RA, thymoma

Question 6

Myasthenic Crisis

Answer 6

• Definition:
  
  • serious complication of MG characterized by worsening muscle weakness. May involve the respiratory muscles, bulbar muscles, or both
  • Precipitated by a wide range of physical stressors and meds
• S/sxs:
  
  • -Respiratory Arrest
  • -Muscle Weakness
• Drugs that Worsen MG:
  
  • neuromuscular blocking agents, botulinum toxin, beta-blockers, fluoroquinolones, aminoglycosides
  • **There are many more so make sure to take a thorough med history
• Tx:
  
  • **ICU admission
  • -Respiratory Support: endotracheal intubation & mechanical ventilation, non-invasive ventilation
  • -Plasmapheresis
  • -IV immune globulin
  • -High-dose corticosteroids
  • -Monitoring & correcting of abnormal electrolytes