Demyelinating and Movement Disorders

By Gregory Eisinger

read on for a thorough review of this weeks conference small group session.

Describe the pathophysiology and clinical features related to Amyotrophic lateral sclerosis (ALS). What are some of the common complications that may lead to ED presentation?

ALS is an idiopathic progressive neurodegenerative disorder characterized by destruction of the anterior horn cells of the spinal cord. It classically presents in older males (though any sex/age can be affected) with combination of upper (spasticity, hyperreflexia, Babinski sign) and lower (wasting, atrophy, fasciculations) motor neuron signs. Extremity weakness is often first sign, though dysarthria and dysphagia may also come first. Typically there is no involvement of sensory function. Diagnosis is made clinically based on El Escorial criteria. Incidence is approximately the same as MS but prevalence is much lower since survival is so poor. May be familial or sporadic and associated with SOD1 (which normally has antioxidant function) or other genes. Higher incidence in northern latitudes. Common ED presentations include weakness, dysarthria, dysphagia, aspiration, failure to thrive, and respiratory failure. ED workup should search for cause of acute presentation (e.g. aspiration PNA). Management is supportive with focus on airway protection due to increased secretions or respiratory failure due to respiratory muscle weakness. Some patients are on riluzole which can delay development of respiratory failure. Due to the progressive essentially untreatable course of the illness, there should be a low threshold for involvement of palliative care and goals of care discussion prior to intubation.

What is myasthenia gravis, and what are some of the typical features? How should acute crises be diagnosed and treated?

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction characterized by antibody mediated destruction of postsynaptic acetylcholine receptors. It typically presents in young women with bulbar and proximal muscle weakness (dysphagia, dysarthria, diplopia, dysphonia, ptosis, chewing fatigue, neck weakness, etc) which characteristically worsens with repetitive activity. The disease course is chronic and slowly progressive with intermittent exacerbations. Myasthenic crisis is defined by respiratory failure requiring mechanical ventilation, often precipitated by infection, pregnancy, surgery, or medication changes. Common ED presentations include respiratory failure secondary to diaphragmatic weakness, inability to clear secretions, upper airway obstruction, pneumonia, pregnancy with disease exacerbation, and iatrogenic adrenal insufficiency or infection secondary to chronic steroid use. Initial workup and diagnosis often includes edrophonium stimulation test, serum anti-Ach titers, and EMG though ED evaluation is focused more on assessment of the ABCs, search for cause of exacerbation such as infection, and assessment of respiratory muscle status through parameters such as NIF (negative inspiratory force) and VC (vital capacity). Respiratory parameters should be checked on most MG patients in the ED regardless of whether they present with respiratory issues as decompensation secondary to some other trigger may ensue. In addition to standard labs and infectious workup including CXR, a blood gas to assess for hypercarbia, CK, TSH/T4, and ESR/CRP should be obtained. Remember to think about things like steroid induced myopathy (which could mimic myasthenic crisis) and cholinergic toxidrome (especially increased secretions causing respiratory failure) in patients on chronic stigmines. Cholinesterase inhibitor toxicity can also cause weakness simulating myasthenic crisis; edrophonium test is helpful in differentiating the two.


Emergency management may include intubation for respiratory failure and IVIG or plasmapheresis which are the treatments of choice. Current guidelines from the AAN state that IVIG or plasmapheresis are indicated for patients with MG and 1) acute life threatening conditions such as respiratory failure; 2) in preparation for surgery; 3) when quick response to Tx is needed; and 4) when other Txs have failed. They state that both are probably equally effective and the decision between the two should be based on pt factors (eg can’t use pheresis in sepsis, can’t use IVIG in renal failure, hypersensitivity, hypercoaguable state) but if no contraindications exist, pheresis is 1st line (expert consensus is that it’s more effective and works faster). Steroids and cholinesterase inhibitors are the backbone of chronic suppressive therapy but are not routinely recommended for the treatment of crisis. Acutely, steroids can worsen crisis so generally wait several days after IVIG/PLEX before starting.


Special consideration must be given to the use of paralytic agents when intubating these patients. Due to deficiency AChR there is typically some degree of resistance to succinylcholine.  However, those receiving plasmapheresis or taking stigmines also have deficiency of plasma cholinesterase which can lead to prolonged effect of succinyl choline. There is also typically increased sensitivity to nondepolarizing neuromuscular blockers requiring decreased dose. In addition, myasthenic pts are at heightened risk for crticial care myopathy following exposure to paralytic agents. In summary, it is important to be aware that the effects and duration of paralytic drugs may be unpredictable in MG. In much of the literature, it is recommended to avoid neuromuscular blockade whenever possible, though these recommendations come from anesthesiology literature where it is more important to have predictable duration of blockade in order to allow extubated after surgery. However, rapid sequence intubation can be safely done in myasthenic crisis in the ED with increased dose of succinylcholine (1.5 to 2.0 mg/kg) or low doses of vecuronium (approximately 0.05 mg/kg. Most patients with concern for respiratory failure should be admitted to the ICU with serial respiratory parameters. BIPAP can be helpful in reducing need for intubation, length of MV, hosp LOS, ICU LOS, etc but PaCO2>50 mmHg predicts BiPAP failure and indicates that muscle fatigue is imminent. Per Rosen’s intubation is indicated for VC < 15cc/kg or NIF worse than -15mmHg though guidelines vary on specific numbers. Definitive therapy is often by thymecotmy which often leads to improvement, even in patients without thymoma.


Edrophonium test: measure distance from upper to lower lid. Give 1 to 2 mg test dose. If no adverse and no dramatic improvement in 30 to 90 seconds, give 3mg, and if still no response, 5 mg. Have atropine available and watch for Ach mediated increased airway secretions. Alternatively, use ice pack test: measure ptosis as above before and after applying ice pack to the eye for 2-3 minutes.


Describe the pathophysiology behind multiple sclerosis (MS) and how it is typically treated. What is one of the most common initial presentations of MS?


MS is a chronic inflammatory demyelinating polyneuropathy of the CNS with a course which may be primary progressive, relapsing-remitting (most common), or secondary progressive. A single episode of symptoms consistent with MS that does not recur likely represents a different disease process (likely postviral) and is called acute demyelinating encephalomyelitis (ADEM). Incidence is higher in females, especially young females of reproductive age, though it may occur in any age/sex group, including pediatric patients. Presentation may be mono- or multi-focal. Symptoms correspond to the location of the lesions and may include vision loss (optic neuritis), gaze palsy (internuclear ophthalmoplegia, nystagmus, etc), sensory deficits, gait abnormality, weakness, spasticity, cognitive deficits, heat intolerance, speech difficulty, Lhermitte sign (electric shock-like sensations that run down the back and/or limbs upon flexion of the neck), bowel/bladder dysfunction, vertigo, pain, depression, fatigue, or transverse myelitis. Some of the most common initial presentations are paresthesia (33%), optic neuritis (20%), weakness (13%), diplopia (7%), and gait abnormality (5%). Diagnosis is typically made by characteristic presentation (McDonald criteria may be helpful), MRI findings of demyelinating lesions “separated in time and space,” and CSF analysis (oligoclonal bands). Optic neuritis typically presents as unilateral (bilateral in ~10%) acute to subacute painful vision loss with afferent pupillary defect on swinging flashlight test and papillitis on funduscopic exam. The etiology of MS is not known but is thought to be initiated by autoreactive lymphocytes and later by microglial activation. IgG and IgM oligoclonal bands are often seen in the CSF and many patients have serum Ab’s directed against the inward rectifier K channel Kir4 which is expressed by oligodendrocytes and astrocytes, suggesting this as a possible target of the immune system. Many drugs including interferon beta, glatiramer acetate, natalizumab, alemtuzumab, dimethyl fumarate, teriflunomide, and fingolimod are available which may help to decrease frequency of relapses and slow disease progression. Corticossteroids are the mainstay of therapy for acute exacerbations. A typical course is 3-7 days of either iv methylprednisolone 500-1000mg daily or po prednisone 625-1250mg daily, with or without a subsequent taper. For severe relapses refractory to steroid Tx, the AAN recommends consideration of plasma exchange.

What are some of the common features of Parkinson’s disease (PD)? How is it typically treated?

PD is a chronic neurodegenerative disorder characterized by the triad of: bradykinesia, pill rolling tremor, rigidity. Bradykinesia is the most common symptom but is often described by patients as weakness, fatigue, or difficulty arising. In the arms it often starts distally and manifests as decreased dexterity while in the legs it typically manifests as slow, stooped, shuffling gait. The tremor of PD is a high amplitude, low frequency, resting tremor which classically decreases with purposeful movement. Rigidity is evident as cogwheeing on exam. Other symptoms which commonly develop later in the course include postural instability, dysphagia, dysarthria, cognitive decline, hallucinations, and autonomic dysfunction. When onset of parkinsonism is seen in combination with dementia and hallucinations, a diagnosis of Lewy-body dementia is likely. Parkinsonism in the absence of PD may be seen in a variety of conditions, most notably as a side effect of antidopaminergic medications (such as antipsychotics). The etiology is poorly understood but the pathophysiology is secondary to destruction of dopaminergic neurons in the basal ganglia (specifically the substantia nigra) by atposis with accumulation of intracellular inclusions called Lewy bodies. Treatment is symptomatic and aimed at increasing CNS dopaminergic neurotransmission. The most well-established and effective agent is levodopa, a precursor to dopamine, in combination with carbidopa which prevents peripheral decarboxylation and thus activation of levodopa outside of the CNS. Other classes of agents frequently used include dopamine receptor agonists (bromocriptine, pramipexole, ropinirole), MAOi’s (such as selegeline), anticholinergic agents (eg benztropine), COMT inhibitors (eg entacapone), and amantadine. Some pts with advanced disease may also have implantable deep brain stimulators and may present with infection or surgical complications thereof. Common ED presentations include: infection (particularly aspiration PNA, UTI), falls, cardiovascular or cerebrovascular events, or medication side effects.