Neuromuscular Disorders

This week in conference we covered a broad range of topics, from multiple sclerosis and Parkinson’s disease to TIA and stroke. As a review, lets focus on some of the key learning points of neuromuscular disorders.

The neuromuscular unit has four components: anterior horn cells in the spinal cord, the peripheral nerve, the neuromuscular junction, and the muscle innervated. The pathology based on what component is impacted determines the associated signs and symptoms (i.e. myelopathy – spinal cord, radiculopathy – nerve root as it exits the spinal cord, neuropathy – peripheral nerve, myopathy – muscle). Moreover, the location of the pathology leads to signs and symptoms that can help us locate the pathologic process and help with diagnosis:

Upper motor neuron involved (i.e. spinal cord) – increased deep tendon reflexes, muscle tone increased, positive Babinski/Hoffman’s signs, clonus

Lower motor neuron involved (ie. peripheral nerve) – decreased deep tendon reflexes, decreased muscle tone, muscle atrophy notable with chronicity, fasiculations may be present

When discussing presenting symptoms in patients with neuromuscular complaints, differentiate weakness from fatigue:

Weakness – inability to exert a normal force

Fatigue – decreased force with repetitive use

Also, as a focus of the physical examination, pay particular attention to the things we really care about in the ED, such as the patient’s ability to ventilate. Muscles used to lift the head off the bed may weaken before those of respiration and so should be assessed. Frequent measurements and reassessment of respiratory parameters such as forced vital capacity (FVC) and negative inspiratory force (NIF) should be used early and rechecked often if there is concern. Normal FVC is 60-70 mL/kg. When it approaches a reduction towards 15 mL/kg, ventilator support is likely necessary. Similarly, if the NIF is approaching a less negative value (i.e. -20 mmHg), this should raise alarm. Blood gasses are NOT helpful, as by the time the patient has developed hypercarbia or hypoxia from their neuromuscular weakness leading to ventilatory failure you’re too late.

On to a brief review of the main topics covered:

Myasthenia Gravis

Epidemiology: affects women 20-40 years old and men 50-70 years old typically.

Pathophysiology: autoantibodies to the nicotinic acetylcholine receptor (i.e. anti-ACh-R) or muscle specific tyrosine kinase leading to destruction of acetylcholine receptors with a decrease in the total number available and competition with acetylcholine for binding sites on the remaining available receptors. Repeated stimulation leads to fewer and fewer receptor sites available for acetylcholine binding, leading to fatigue and weakness (contrast this to Lambert-Eaton syndrome, in which weakness improves with activity).

Presentation: fatigue, progressive weakness with repetitive activity with ocular symptoms often as the first manifestation and ocular muscle weakness as a first sign in up to 40% (i.e. ptosis, diplopia, blurred vision). Symptoms typically worse at the end of the day. Pay particular attention to bulbar involvement leading to dysarthria and dysphagia. Respiratory failure is rarely a first presentation but does happen. Furthermore, the patient may not manifest normal signs of impending respiratory failure, such as accessory muscle use, so look for other features, such as tachypnea. Also, be aware of patient’s with myasthenic crisis, defined as respiratory failure leading to mechanical ventilation. It occurs in 15-20% of patient’s, usually within the first 2 years, typically with an underlying provocative event (i.e. infection, non-compliance, medication change or new medication, etc.).

Diagnosis: edrophonium stimulation test (less often used) or the ice bag test, serologic testing for anti-ACh-R or anti-MuSK (probably not done in the ED). Most importantly, ALL patient’s with a history of myasthenia gravis should get respiratory parameters (FVC and/or NIF) regardless of reason for presention. Importantly, search for underlying processes that might have led to the exacerbation (i.e. infectious work-up, thorough history to include medications, recent medication changes, etc.)

Treatment: ABCs! As with anything, focus on the things acutely that can kill the patient, such as respiratory failure. Non-invasive ventilation (i.e. BiPAP) can be tried, but this should be done in conjunction with close monitoring and serial respiratory parameters (typically every 2 hours). Neostigmine or pyridostigmine can be given but may increase secretions and worsen weakness or even stimulate myasthenic crisis. As such, they are typically avoided in the acute period, as patients with respiratory failure or impending failure benefit most from plasmapheresis or IVIG with the addition of steroids. Treat associated exacerbating causes (i.e. infection, etc.)

Other things that may benefit the patient that we will not be involved in include thymectomy for those with thymoma and consideration for thymectomy in those without thymoma but <60 years old as well as immunosuppressant drugs, which patient’s presenting to the ED may already be on. Also critical is knowing what drugs to avoid.

Multiple Sclerosis

Epidemiology: peak age of onset is 25-30 years old, women > men with proposed genetic and environmental factors. More common in temperate climates.

Pathophysiology: proposed mechanism is that of an autoimmune disease with autoreactive T cells stimulated by environmental (i.e. viral infection or superantigen) leading to inflammatory response involving CNS demyelination in the brain and spinal cord.

Presentation: optic neuritis may be the initial presenting symptom with painful unilateral vision loss affecting the central vision. Other symptoms are variable, as white matter anywhere in the brain and spinal cord can be involved to include motor, sensory, and bulbar complaints as well as neurocognitive complaints such as poor memory, distractibility, etc. Bowel and bladder dysfunction are common. Uhthoff’s phenomenon (temporary worsening of signs/symptoms secondary to an increase body temperature, such as a hot bath). A comprehensive neurological exam is key

Diagnosis: key to the diagnosis is description of TWO different neurological complaints at different times (i.e. neurological complaints scattered in time and space). CSF studies are abnormal in 90% of cases, with 50% having pleiocytosis, 70% with elevated IgG gamma globulin level, and the presence of IgG oligoclonal bands and/or myelin basic protein. Importantly, IgG oligoclonal bands may also be seen in other disorders, such as neurosyphillis. If sending off CSF studies, send off serum oligoclonal bands at the same time.   Gadolinium enhanced MRI is also important in the work-up. Lesions are bright on T2 signal or FLAIR and are commonly found in the periventricular white matter.

Treatment: for our purposes, acute exacerbations require HIGH DOSE intravenous methylprednisone. Long-term treatment may include interferon-beta, glatiramer, or other immunosuppressant medications. Many patients require baclofen (orally, intrathecally) for spasticicty, and pain is managed with a range of medications. Amantadine may help with fatigue.

Two other disease topics discussed during conference included amyotrophic lateral sclerosis (ALS) and Parkinson’s disease. While important, we don’t often see these present as primary complaints, obviously, but rather patient’s present with complications of the underlying disease. Briefly, ALS is a progressive disease involving destruction of the upper and lower motor neuron units, leading to muscle atrophy and weakness. Ultimately, patient’s often succumb to respiratory failure or other complications such as aspiration pneumonia and other infectious processes. Parkinson’s disease is caused by loss of pigmented dopaminergic neurons in the substantia nigra and development of Lewy bodies leading to symptoms to include tremor, (cogwheel) rigidity, akinesia, and postural instability. The most common reasons for patients presenting to the ED include infection, trauma (think falls), cardiovascular and cerebrovascular events, gastrointestinal complaints, and electrolyte abnormalities. Orthostatic hypotension is a common reason for falls and can be secondary to medication side effects. Treatment really depends on the underlying cause for the presentation. An important point brought up by Dr. Kman is that drugs (i.e. antipsychotics) can lead to Parkinsonian features (or Parkinsonism) and are managed in a different manner.