Motor Deficits

Anatomy

• Motor deficits can be caused by central nervous system or peripheral nervous system dysfunction.
• The motor unit is composed of an anterior horn cell, its motor axon, and muscle fibers. The motor nerve fibers and the muscle fibers make up the presyntaptic and postsynaptic components of the neuromuscular junction, respectively.
• Muscle contraction involves an action potential at the motor axon, causing an influx of calcium that releases acetylcholine into the synaptic cleft; this results in an action potential at the motor end plate, and subsequent depolarization of the postsynaptic membrane and contraction of the muscle cell.

Scope of the Problem

• Based on the anatomy of the neuromuscular system, peripheral nervous system causes of motor weakness correlate with involvement at 1 of 4 levels: the anterior horn cells, peripheral nerve, neuromuscular junction, or the muscle fiber itself.
• Progressive motor weakness may be accompanied by sensory and autonomic dysfunction, requiring rapid respiratory or hemodynamic stabilization.

Etiology

The following list is not exhaustive, but includes most etiologies encountered on an emergency basis. The patient may have a known neurologic disease and present with an exacerbation or deterioration, or may have new-onset symptoms without a prior diagnosis.
• CNS
• Multiple sclerosis (MS)
• Motor Neuron
• Amyotrophic lateral sclerosis (ALS)
• Poliomyelitis
• Peripheral Nerve
• Guillain-Barre syndrome (GBS)
• Tick paralysis
• Porphyric polyneuropathy
• Arsenic poisoning
• Paralytic shellfish poisoning
• Hypophosphatemia
• Neuromuscular Junction
• Myasthenia gravis (MG)
• Botulism
• Lambert-Eaton (LEMS)
• Hypermagnesemia
• Muscle
• Myoglobinuric myopathy
• Hypo- or hyperkalemia
• Toxic myopathy
• Dermato- and polymyositis
• Guillain-Barre syndrome is the most common form of acute inflammatory demyelinating polyradiculoneuropathy (AIDP). The most frequent impairment results from immunologic reaction against nerve roots, peripheral nerves, and cranial nerves. The typical clinical manifestation is motor weakness beginning in the legs and ascending to the arms, with symptoms evolving over a few days. Approximately 14% of patients will present with symptoms beginning in the cranial nerves or arms, descending to the legs.
• Myasthenia gravis (MG) is characterized by the formation of antibodies to the acetycholine receptor of the post-synaptic component of the neuromuscular junction.
  Weakness and fatiguability are the predominant symptoms, with a predilection for the ocular muscles. The proximal muscles of the limbs are affected more than distal muscles.
  Oropharyngeal muscle involvement may impair speech, swallowing, or chewing. Respiratory muscles (i.e., intercostals and diaphragm) are affected in one-third of patients, leading to respiratory failure.
• Multiple sclerosis (MS) is a demyelinating disease of the axons in the CNS. Clinical symptoms wax and wane and are attributed to discrete lesions in the CNS which are "scattered in time and space." In the presence of demyelinated axons, action potentials are not conducted normally: edema and inflammation may impair action potential propagation leading to "negative" symptoms (e.g., diplopia from CN VI paresis), while hyperexcitable demyelinated axons may produce "positive" symptoms (e.g., Lhermitte’s sign).
• Idiopathic dysfunction of both upper and lower motor neurons (in the anterior horn cells) contributes to the motor weakness seen in patients with amyotrophic lateral sclerosis (ALS).

Risk Factors

Two-thirds of patients with GBS recall an antecedent event, approximately 1 to 3 weeks prior to symptom onset. The most common is infectious (e.g., URI, flulike symptoms, or diarrhea), but immunizations or surgery may predate the disorder.
• Myasthenic crisis (i.e., exacerbation requiring ventilatory support) is often precipitated by infection, changes in medications, pregnancy (or just before menses), or surgery.
• Lambert-Eaton Myasthenic syndrome (LEMS) is an autoimmune disorder affecting presynaptic nerve terminals. Like myasthenia gravis, the characteristic weakness, fatiguability, and pain primarily affects proximal muscles; unlike myasthenia gravis, cranial nerves are only mildly impaired. An underlying malignancy (usually squamous cell carcinoma of the lung) is present in 75% of male and 25% of female patients.
• First-degree relatives of patients with MS have a 15- to 20-fold greater risk of developing the disease. Hyperthermia (resulting from underlying infection) may exacerbate previous neurologic deficits, or precipitate new symptoms.

Diagnosis

History

• Determine the time course and the distribution of symptoms.
• Toxic or metabolic disturbances may have an abrupt onset; neoplastic, infective, or inflammatory disorders may progress over days to weeks; hereditary, endocrinologic, degenerative, or other neoplastic processes may cause symptoms which develop over a period of months to years.
• Proximal muscle weakness causes difficulty getting up from a squatting position, climbing or descending stairs, or washing or brushing the hair. Distal weakness of the upper limbs may manifest as clumsiness or loss of fine motor skills (e.g., tying shoelaces or buttoning).
• Patients with cranial nerve involvement may present with diplopia, dysarthria, or impaired chewing or swallowing, with nasal regurgitation.
• Does the patient have a preexisting neuromuscular or systemic disorder? Have there been any recent infections or immunizations?
• Patients with dystrophies may present with clinical deterioration; likewise, ALS symptoms tend to worsen with concurrent illness (especially pneumonia). In addition, patients with neuromuscular junction disorders (e.g., myasthenia gravis) suffer exacerbations with illness or addition of pharmacologic agents. A history of similar symptoms suggests familial periodic paralysis or myoglobinuria. Finally, patients with connective tissue disorders are at risk for vasculitic neuropathy.
• The patient’s medications, social history, and recent diet should be ascertained.
• Ingestion of shellfish containing saxitoxin—specifically, mussels and clams from both U.S. coasts during the summer months—may produce sensory deficits and ascending paralysis within 30 min. Home-canned goods may contain botulinum toxin. Symptom onset temporally related to new medications (e.g., oral contraceptives, anti-epileptic drugs) may suggest porphyria. Patients on diuretics may become hypokalemic. In the setting of renal insufficiency, a patient with a neuromuscular junction disorder may experience increasing weakness after ingesting magnesium-containing antacids. Myotoxicity has been attributed to several medications, including cholesterol-lowering agents, colchicine, chloroquine, cyclosporine, and L-tryptophan.
• Determine whether the patient has had any known exposure to toxins, chemicals, solvents, or tick bites (e.g., in wooded areas).
• Are there any associated symptoms?
• Patients with GBS commonly report dysesthesias in the hands and feet prior to the onset of weakness. They may also experience transient bladder paralysis (resulting in urinary retention) and paralytic ileus. Abdominal pain and mental status changes in the presence of motor weakness suggests porphyric polyneuropathy. Arsenic poisoning causes an encephalopathy, in addition to systemic signs and symptoms. The pure motor weakness attributed to polymyelitis is accompanied by fever and meningeal signs.
• Is there a family history of neuromuscular disease?

Vital Signs

• Patients with sensory GBS are at increased risk for autonomic nervous system instability, manifesting as arrhythmias, orthostatic hypotension, and hypertension.

Physical Exam

• Note the patient’s general appearance. Confusion, in a tachypneic patient using accessory muscles of respiration, suggests impending neuromuscular respiratory failure.
• Neck: The strength of the patient’s neck flexors (and the trapezius, responsible for shoulder elevation) parallels that of the diaphragm.
• Chest exam may reveal clear breath sounds in a patient in respiratory distress from motor weakness. A patient’s vital capacity can be grossly measured by asking him to count as high as possible with one breath (normal >50).
• Paradoxical abdominal movements indicate diaphragm weakness.
• Neurologic Exam
• Upper motor neuron lesions are associated with weakness (or paralysis), spasticity, increased deep tendon reflexes (DTRs), and a Babinski response. Lower motor neuron lesions are characterized by weakness (or paralysis), hypotonia, loss of DTRs, and normal plantar reflexes. Disorders of neuromuscular transmission exhibit normal or reduced muscle tone; normal or diminished DTRs; and waxing and waning weakness in a patchy distribution (i.e., not attributed to a single, discrete lesion) with cranial nerve involvement; there are no sensory deficits. Myopathic processes typically cause proximal >distal weakness; DTRs are normal until late in the course; there is no impairment in sensation or sphincter function.
• Patients with GBS generally have symmetric limb weakness, and decreased or absent deep tendon reflexes. Despite subjective paresthesias, there is minimal objective sensory loss.
• Patients with myasthenia gravis who have ocular involvement have ptosis and extraocular muscle weakness. Fatiguability can be measured by asking the patient to look upwards for 2 min or by repeatedly testing the proximal muscles (e.g., deltoids and iliopsoas).
• In contrast to myasthenia gravis, patients with LEMS show improvement with repeated testing. The extraocular muscles are spared.

Evaluation

• Forced vital capacity is recommended to determine a patient’s respiratory status.
• Laboratory
• Arterial blood gas is helpful in determining ventilatory status.
• Urinalysis, BUN, and creatinine may reveal myglobin and renal insufficiency in the clinical setting of rhabdomyolysis. Likewise, the creatine kinase (CK) may be elevated in myopathies.
• Electrolytes, including calcium, phosphorus, and magnesium should be obtained.
• Patients with exacerbation of myasthenia gravis or MS should have a urinalysis and urine culture, as well as a CBC.
• Lumbar puncture (generally not required in the ED) may be helpful in the diagnosis of GBS. The CSF may benormal in the first 48 h after symptom onset; however, within 1 wk, elevated CSF protein is noted (without pleocytosis).
• EKG
• EKG may reveal evidence of hypo- or hyperkalemia or an arrhythmia resulting from the autonomic dysfunction associated with GBS.
• Radiography
• Chest radiography may show evidence of pneumonia, atelectasis, an elevated hemidiaphragm (resulting from weakness), or a malignancy. Occult respiratory infection should be sought in any patient with MG or MS exacerbation.
• Consider head CT in patients with presumed myasthenia gravis (especially patients with ocular symptoms) to exclude an intracranial mass producing similar symptoms.
• Tensilon test
• Edrophonium (Tensilon) is a short-acting acetylcholinesterase inhibitor; patients with myasthenia gravis generally have transient improvement in their motor strength within minutes.
• Cholinergic side effects of edrophonium include excessive salivation, bradycardia, and nausea. Cautious use (with atropine at the bedside) is warranted in patients with heart or lung disease.
• An initial test dose of 2 mg is given intravenously. If the patient tolerates the medication but shows no improvement over 1 min, an 8 mg dose is given and the patient is observed for the next 3 to 5 min for a response. Patients in myasthenic crisis will show improvement, while patients in cholinergic crisis will be worse.

Treatment

A rapid assessment of the patient’s airway, breathing, and circulation is critical in patients presenting with motor weakness.

• Specific Treatment
• Guillain-Barre syndrome
• Hypotension generally responds to isotonic fluids. Hypertension should only be treated if severe and persistent. Short-acting, a-adrenergic blockers are recommended.
• Plasmapheresis and intravenous immune globulin (IVIG) have been shown to be equally effective, and both are superior to supportive care alone.
• Myasthenia gravis
• Patients with myasthenia gravis may present in cholinergic crisis; in response to increasing weakness, the patient increases his anticholinesterase medications, which worsens the weakness. The presence of cholinergic signs—pallor, miosis, sweating, nausea/vomiting and diarrhea, salivation, and bradycardia—helps to distinguish cholinergic crisis from myasthenic crisis.
• Patients with mild exacerbation of MG (i.e., no respiratory or oropharyngeal compromise) may be treated with prednisone, pyridostigmine, and an eye patch (for diplopia).
• Moderate or severe MG is an indication for plasmapheresis (or IVIG), in addition to predisone. If the vital capacity is < 12 to 15 mL/kg, the patient should be intubated. A source of infection should be sought and treated.
• Multiple sclerosis
• Any identifiable infection should be aggressively treated; in the presence of infection, corticosteroids are not warranted. Symptoms will generally resolve when the fever or infection is treated.
• Clinical deterioration without an identifiable cause (e.g., infection) is an indication for high-dose corticosteroids (PO or IV). Optic neuritis warrants IV methylprednisolone.

Disposition

• Patients at risk for respiratory compromise should be admitted to the ICU. This includes patients with vital capacity < 35 mL/kg, or other evidence of diaphragmatic weakness (e.g., weak neck flexors or trapezius muscles).
• Patients with any other evidence of autonomic nervous system instability should be admitted to the ICU.
• Patients with worsening symptoms of myasthenia gravis should be observed in the ICU for respiratory and bulbar difficulties, including nasal regurgitation and choking on food.
• Patients with MS exacerbations who are unable to tolerate oral medications or liquids, require parenteral medications (i.e., antibiotics or steroids), or lack home support should be admitted.
• Patients with mild MS exacerbations who are candidates for oral steroids or do not require treatment (e.g., viral infections), and those with mild infections amenable to outpatient management, may be discharged home. This decision should be made in consult with the patient’s neurologist.