Amyotrophic Lateral Sclerosis

Degenerative motor neuron disease evolving to progressive muscle weakness resulting in paralysis.

ALS; Lou Gehrig Disease (named after a famous American baseball player with New York Yankees who succumbed to amyotrophic lateral sclerosis in 1941).

Described in 1869 by Jean-Martin Charcot, a French neurologist.

Annually, approximately five new cases per 100,000 in the general population, mainly male patients (male-to-female ratio 1.5:1) age 40 to 60 years.

Etiology is not known. Approximately 10% of cases are inherited in an autosomal dominant fashion. The remaining cases are believed to be caused by an unknown slow virus infection. Despite extensive searches for infectious causative agents, no viral or bacterial etiology has been identified. Oxidative stress may be relevant.

Degenerative motor neuron disease may include cortical neuron degeneration (primary lateral sclerosis), central nuclei (pseudobulbar palsy), and/or motor neurons (progressive spinal amyotrophia). The hypothesis that excitotoxicity, oxidative stress, and mitochondrial dysfunction are involved in the process of neuronal cell death is supported at least in part by research reporting discovery of mutations of superoxide dismutase-1 in approximately 10% of patients with familial ALS. Anterior horn cells in the spinal cord and cranial motor nerves are predominantly involved in ALS. Patients may present with bulbar palsy or (commonly symmetrical and distal) weakness of single or multiple muscle groups of the limbs. The primarily bulbar form of ALS is associated with a worse prognosis with regard to severity and survival time. Fasciculations of the intrinsic hand muscles, which are an early and characteristic sign, later progress to weakness and atrophy and eventually spread proximally to the forearms and shoulder girdle muscles. Typically, both upper and lower motor neurons are affected. Clinically limb or tongue fasciculations, hyperreflexia, clonus, and spasticity are found. An inflammatory response with activated microglia, reactive astrocytes, and IgG antibodies can be found in affected areas of the spinal cord. However, how these changes are related to neuronal cell death is not known. Autoimmune phenomena may be involved in the pathogenesis of ALS. Corticospinal and corticobulbar tracts may show signs of wallerian degeneration.

Progressive adult-onset muscular weakness with muscular spasms and fasciculations (although a few cases have been reported in children). Initially, the disease is localized but rapidly spreads to all muscles. In addition to the clinical examination, electromyography studies are used to identify lower motor neuron dysfunction. Long-lasting, polyphasic fasciculation potentials and signs of chronic partial denervation are characteristic of ALS.

Initially the disease may present with fasciculations of the intrinsic hand muscles, which later change to weakness and atrophy and then spread proximally to the shoulder girdle. However, involvement of the various muscle groups is inhomogeneous. As the disease progresses, atrophy and weakness involve most of the skeletal muscles, including those of the tongue, pharynx, larynx, and chest. Swallowing problems, with frequent choking and bronchopulmonary aspirations, are common. The sensibility is not affected. Serum creatine phosphokinase levels are normal, no cardiac involvement is seen, and intellectual function remains unchanged. Loss of autonomic control with orthostatic hypotension and tachycardia has been described. Extraocular muscles, bladder, and anal sphincter muscles typically are spared. Some patients with cancer exhibit a symptom complex similar to ALS as part of a paraneoplastic syndrome. Some researchers have reported decreased levels of insulin-like growth factor-1 (IGF-1) in patients with ALS. Patients with ALS may benefit from treatment with recombinant human IGF-1, although survival remains the same. Riluzole is a benzothiazole glutamate antagonist medication that may prolong tracheostomy-free survival but not overall survival. Because no effective therapy exists to date, the prognosis remains grim. Death usually results from pulmonary complications within 5 to 10 years after the first symptoms.

Impairment of respiration, altered response to muscle relaxants, and predisposition of aspiration affect anesthetic management. Obtain a complete history, particularly with regard to muscle wasting and previous complications, especially respiratory failure and anesthesia-related complications. Obtain lung function tests (vital capacity, maximum minute ventilation, forced expiratory flow). Assess cardiac function and request a cardiology consultation if pulmonary hypertension cannot be ruled out. Blood workup should include serum electrolytes (potassium). Consider regional anesthesia (when indicated) if lung function is significantly jeopardized; however, keep in mind that an epidural anesthesia with a sensory level at T5 will decrease the vital capacity by almost 15% and may impede respiratory function and gas exchange. Postoperative mechanical ventilatory support almost always is required after major surgery and should be arranged beforehand.

There is a very high incidence of respiratory complications because of neuromuscular dysfunction. Although respiratory drive is considered normal in ALS, respiratory function and reserve are significantly compromised. Because the disease involves several cranial nerves, airway protection may not be adequate. Patients should always be considered high-risk candidates for aspiration. Consequently, a rapid sequence induction is recommended. The trachea should not be extubated before the patient is fully awake because of poor airway control and ventilatory muscles.

Avoid succinylcholine because an exaggerated hyperkalemic response is possible. The sensitivity and duration of action of nondepolarizing muscle relaxants is markedly increased, so reduced doses are required and relaxation should be controlled with a peripheral nerve stimulator. To avoid using neuromuscular blocking agents, small doses of volatile anesthetic agents often are sufficient to achieve adequate surgical relaxation in ALS patients. Hemodynamic instability has been reported with halogenated agents. Because of autonomic nervous system involvement, the dose of atropine may be higher than normal to successfully treat bradycardia. Riluzole is primarily metabolized by liver isoenzyme cytochrome P-450. Metabolism and elimination of other drugs using the same pathway may be altered.

Dermatomyositis and Polymyositis: Both diseases belong to a group of connective tissue disorders known as idiopathic inflammatory myopathies. They are a multisystem disease characterized by necrotizing inflammatory myopathy of striated muscles and a skin rash, both of unknown etiology.

Myasthenia Gravis: Neuromuscular disorder characterized by muscle weakness and rapid muscle fatigue. Usually apparent during adulthood, but onset can occur at any age. Most individuals present with eyelid ptosis, diplopia, and excessive muscle fatigue following exercise. Other features commonly include dysarthria, dysphagia, and proximal limb weakness. Approximately 10 percent develop potentially life-threatening complications resulting from severe respiratory depression (myasthenic crisis).

Progressive Bulbar Palsy of Childhood: Motor neuropathy affecting lower six cranial nerves but sparing the limbs. Deafness. X-linked or autosomal recessive. Age of onset is late childhood. Other features include excessive drooling, dysarthria, recurrent pulmonary aspiration, and pneumonia evolving to pulmonary failure. Limb involvement and pyramidal tract signs may develop later. Mortality within the first 2 decades of life.