Amyothrophic Lateral Sclerosis (ALS)
Rapidly progressive upper/lower motor neuron weakness. Thought to be genetic mutation.
Upper motor neuron demyelination: limb spasticity, hyperreflexia, emotional lability. Positive Babinski sign (fans out)
Lower motor neuro demyelination: limb muscle weakness, atrophy, fasiculations, dysarthria, mastication difficulty.
Cognition and sensory findings usually still intact. Progression over weeks/months to the point of respiratory failure.
Tx: supportive; prevent aspiration, look for signs of impending respiratory failure. Riluzole is a excitotixin glutamate modulation medication that can increase survival.
Autoimmune disease; Acetylcholine receptor antibodies (AChR) form; proximal muscle weakness. Thymus abnormal in 75% of patients.
General weakness of proximal muscle groups including neck extensors, facial/bulbar muscles, ptosis (eyelid drooping), diplopia, dysphagia/dysarthria, dysphonia.
Diagnosis: Edrophonium chloride administration (improvement in symptoms after receiving medication though can cause worsening weakness if given to someone with other disorder of neuromuscular impairment). EMG does repetitive nerve stimulation. AChR antibody testing is blood test, though early MG will have 15% false negative.
Treatment: Thymus removal. Patients usually on pyridostigmine 60-90mg q4hrs and should get it scheduled. If miss a dose, double the next. If need to give IV, give 1/30th dose (2-3mg). Neostigmine is usually 0.5mg.
Avoid neuromuscular blockers (paralytics) since it will last 2-3x longer. Consider using 1/2 regular dose.
Myasthenic Crisis vs Cholinergic Crisis: give 1-2mg slow IV push of edrophonium (rapid onset of 30s, duration 5-10m). If showing improvement, continue giving up to 10mg, then give neostigmine 0.5-2mg IM/SC which will last for 4 hours. If worsening with edrophonium, likely cholinergic and consider giving atropine or intubating.
Inflammatory disorder; scattered neuron demyelination. Can affect multiple areas including cerebrum, brainstem, spinal cord, and cranial nerves.
Lower extremity symptoms more severe than upper extremity. Young person with multiple neuro systems of different areas over time. Lhermitte sign: electrical shock sensation/pain down back/arms/legs with flexion of the neck. Dysautonomias: urinary retention, urgency/frequency, stress incontinence. Paresthesais, gait disturbances, extremity weakness, poor coordination, visual disturbances.
Optic neuritis: 30% initial sign. Unilateral vision loss, retrobulbar pain, afferent pupillary defect (Marcus Gunn pupil).
Symptoms worse with body temp increases (fever, exercise, hot bath). Diagnosed by T2 weight MRI findings of multiple discrete lesions on white matter, including in spinal cord.
Treatment: glucocorticoids, interferon-B. High dose steroids for exacerbations. Exclude causes of stress/infection. Due to post void residual, very common to have UTI/pyelo.
Lambert-Eaton Myasthenic Syndrome
Autoimmune disorder like MG causing flucutating weakness/fatigue in proximal limb muscles. Show some improvement in strength with sustained/repeated exercises like MG. Lambert sign: squeeze strength increases over a few seconds.
Associated with malignancy (50% has small cell lung cancer). Predominant in older men with hx/o smoking.
Treatment supportive, though can be similar to MG (tx cancer, neostigmine, steroids).
Lewy bodies: cellular cytoplasmic inclusions; in the midbrain, particularly in the substantia nigra. Results in loss of fucntional dopaminergic receptors, resulting in lower dopamine levels.
TRAP: resting tremor (pill rolling, not with movement), cogwheel rigidity (intermittent stiffness with passive ROM of the extremities), bradykinesia or akinesia (slowness, inability to perfom), impairment of posture/equilibrium (hard time turning/changing directions, lose balance). Clinical diagnosis primarily.
Treatment: Reduce symptoms: anticholinergics (benztropine), central dopamine increasing medicatiosn (levodopa, carbidopa), dopamine receptor agonists (bromocriptine).
Levodopa SE: anorexia, nausea/vomiting. Carbidopa decrease these SE. Effects of medications will decrease overtime. On-off phenomenon can occur where patient pretty debilitated in the morning before receiving medications. Drug holiday (off medication for 1 week) can sometimes increase effect of medication when it is started again.
Dopaminergic therapy toxicities: cardiac dysrhytmias, orthostatic hypotension, dyskinesias, dystonia. Psychosis/hallucinations can be caused by dose and having reduction in medications can help reduce these symptoms.
Psychotropics (haldol) can have increased likelihood of tardive dyskinesia.
Poliomyelitis and Postpolio Syndrome
Poliomyelitis: enterovirus infection, causing striated muscle paralysis in <5% of patients. Usually just GI viral illness in most patients affected. After typical viral illness, asymeetric proximal limb weakness in lower extremities. Flaccid/weak muscles, absent tendon reflexes, fasiculations. Sensory deficits usually not present. Usually occurs over 5 days, then wasting occurs over several weeks. CSF will show pleocytosis. Throat/rectal swaps for disease are more accurate in early course of disease.
Postpolio syndrome can occur 20-35 years after initial benign infection (though would usually be in patients > 50-60yo). Muscle fatigue, joint pain, worsening skeletal deformities. Patients usually had neuro symptoms with initial infection 30 years ago. Lamictal can sometimes help recovery in postpolio syndrome.
GBS usually presents very similar, though symmetric muscle weakness unlike polio which is unilateral.
Tintinalli, Chapter 167: Chronic Neurologic Disorders