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| Amyotrophic Lateral Sclerosis (ALS) |
| Overview |
 | Also known as: Motor neuron disease, Lou Gehrig's disease
 | a number of overlapping syndromes such as pseudobulbar palsy, progressive
bulbar palsy, progressive muscular atrophy and primary lateral sclerosis.
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| Annual incidence is approximately 1/100,000 population |
| Pockets of high incidence in Guam (ALS-Parkinson-dementia complex), the
Kii peninsula of Japan, and western New Guinea. |
| 95% of cases in the US are of the sporadic variety, but a few families
have several members with the typical clinical picture of sporadic ALS arising in an
autosomal dominant pattern. |
| Onset of the disease can be as early as the third decade of life, most
cases begin after age 40, and the incidence increases into the eighth decade. |
| Etiology: unknown |
| Male = Female |
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| Symptoms |
| Slowly progressive muscle weakness involving the limbs, trunk,
respiratory muscles, throat, and tongue. |
| Onset is insidious, and initial symptoms may be confined to a single
limb, especially the distal muscles. |
| Gradually weakness becomes widespread |
| Weight loss: result of muscle atrophy and impaired swallowing. |
| Speech difficulty and respiratory difficulty. |
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| Signs |
| Both lower and upper motor neuron signs, either may predominate.
| Lower motor neuron: muscle weakness, wasting, fasciculations, and cramps. |
| Upper motor neuron: stiffness and slowness of movement, slow and clumsy
speech, and pseudobulbar palsy. Babinski signs are often present.
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| There is no impairment of bladder, bowel, or sexual function.
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| Diagnosis |
| Principles of diagnosis
| upper motor neuron signs |
| lower motor neuron signs |
| progression of weakness |
| absence of an alternative explanation |
| Spares cognitive, oculomotor, sensory and autonomic functions. |
| Anti GM1 autoantibodies in low titer commonly found |
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| Lambert's EMG criteria for ALS:
| fibrillation and fasciculation potentials in the upper and lower limbs,
or the head plus either the upper or lower limbs |
| increased amplitude and duration motor unit potentials (MUPs) with
reduced recruitment and normal nerve conduction studies, allowing reduced compound muscle
action potential amplitudes and related slowing of motor nerve conduction velocities.
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| World
Federation of Neurology - Revised criteria for the diagnosis of ALS
| Requires the presence of each of the following:
 | LMN signs in at least two limbs |
| UMN signs in at least one region (bulbar, cervical, or lumbosacral) |
| Progression of the disease defined as increasing symptomatic impairment
by history. This may involve the same or new regions. |
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| Requires the absence of each of the following:
| Sensory signs (except those attributable to aging) |
| Neurogenic sphincter abnormalities |
| Clinically evident CNS disease apart from ALS, with a natural history of
progression (e.g., Parkinson's disease, dementia) |
| Clinically evident peripheral nervous system disease with natural history
of progression (e.g., diabetic polyneuropathy, hereditary polyneuropathy) |
| ALS-like syndromes
| Structural spinal cord lesions including spondylotic myelopathy |
| Multifocal motor neuropathy |
| Hyperthyroidism |
| Hyperparathyroidism |
| Monoclonal gammopathy with an associated hematologic malignancy (e.g.,
lymphoma, myeloma [monoclonal gammopathy alone permitted]) |
| Lead poisoning |
| History of radiation to the brain or spinal cord |
| Hexosaminidase A deficiency (patients under age 30)
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| Prognosis |
| Death occurs from pulmonary infection and insufficiency. |
| Average survival of the ALS patient is 3 years after onset of symptoms;
few will live for 10 years or longer. |
| Shorter survival was associated with
| greater age |
| lower percent-predicted forced vital capacity (FVC%) |
| lower serum chloride reflecting the degree of respiratory acidosis |
| shorter interval from symptom onset to diagnosis |
| greater weight loss in the 2 months before study entry also predicted
shortened survival times |
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| Treatment |
| Riluzole |
| 2 well-controlled trials:
| The time to tracheostomy or death was longer for patients randomized to
riluzole than placebo. |
| No statistical difference in mortality at the end of the study period of
about 18 months. |
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| Dose: 50 mg q 12 hours. No increased benefit with higher doses, but
adverse events are increased.
| should be taken 1 hour ac or 2 hour pc |
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| Avoid use in patient with evidence or history of abnormal liver function. |
| 3 cases of marked neutropenia out of 4000 patients, all seen within the
first 2 months of treatment. |
| Most common side effects: asthenia, nausea, dizziness, decreased lung
function, diarrhea, abdominal pain, pneumonia, vomiting, vertigo, circumoral paresthesia,
anorexia, and somnolence. |
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| Symptomatic treatment |
| Sialorrhea:
| Poor handling of saliva appears to be the major cause. |
| Distinguish between sialorrhea and thick mucus production. |
| Medications that may be useful for sialorrhea:
| Lycopyrrolate (Robinul) |
| Amitriptyline (Elavil) |
| Benztropine (Cogentin), trihexyphenidyl hydrochloride (Artane) and
transdermal hyoscine (Scopolamine) |
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| Beta blocker: propranolol (Inderal) or metoprolol (Toprol) may reduce
thick mucus production. |
| Physical measures:
| Suction machines |
| Manually assisted coughing techniques |
| Mechanical insufflation-exsufflation (In-Exsufflator cough machine)
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| External beam irradiation (3 to 30 Gy, 3 to 10 fractions) to a single
parotid gland |
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| Pseudobulbar affect:
| Pathologic crying or laughing is not a mood disorder, occurs in as many
as 50% of patients. |
| Reasearch trial in patients with MS supported the use of amitriptyline. |
| A single study in a mixed population of patients including ALS reported
satisfactory results with fluvoxamine (Luvox).
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| Nutrition & dysphagia:
| Initial management:
| modification of food and fluid consistency. |
| coaching by a speech pathologist. |
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| Need for PEG
| Preferably before forced vital capacity (VC) falls to 50% of predicted. |
| Or, when patients have symptomatic dysphagia with accelerated weight loss
due to insufficient caloric intake, dehydration, or ending meals prematurely. |
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| Risk of PEG placement
| onset of dysphagia may coincide with the development of respiratory
insufficiency, which is the major determinant of survival. |
| PEG tube insertion employs procedural sedation, knowledge of a patient's
respiratory capacity and monitoring of oxygen saturation are essential. |
| To minimize risks, place PEG before VC falls below 50% of predicted. |
| Complications: transient laryngeal spasm (7.2%), localized infection
(6.6%), gastric hemorrhage (1 to 4%), failure to place PEG. |
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| PEG or jejunostomy does not prevent aspiration pneumonia.
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| Cisapride may enhance gastric emptying and reduce the incidence of
post-PEG aspiration. |
| Recurrent aspiration pneumonia in aphonic patients may be treated with
conservative laryngectomy or laryngeal diversion. |
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| Resiratory insufficiency:
| Offer noninvasive ventilatory support |
| Physicians should respect the right of the patient to refuse or withdraw
any treatment, including mechanical ventilation. |
| When withdrawing ventilation, use adequate opiates and anxiolytics to
relieve dyspnea and anxiety. |
| Bioethics statement from the ALS Task Force and the Quality Standards
Subcommittee of the AAN: It is a strong consensus of both that during withdrawal of
ventilation, paralyzing drugs should not be used. |
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| References & further readings |
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| Information for patient and family |
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