Amyotrophic Lateral Sclerosis (ALS, sometimes called Maladie de Charcot, or, in the United States, Lou Gehrig's Disease By: Peter Andre Soltau Class OF 2009 What Does It Really Mean?? • A-myo-trophic comes from the Greek language. "A" means no or negative. "Myo" refers to muscle, and "Trophic" means nourishment–"No muscle nourishment." When a muscle has no nourishment, it "atrophies" or wastes away. ?? • "Lateral" identifies the areas in a person's spinal cord where portions of the nerve cells that signal and control the muscles are located. As this area degenerates it leads to scarring or hardening ("sclerosis") in the region. • “Lateral sclerosis” refers to the hardness to palpation of the lateral columns of the spinal cord in autopsy specimens, where gliosis follows degeneration of the corticospinal tracts. Definition • ALS has two meanings. 1) In one sense, it refers to several adult-onset conditions characterized by progressive degeneration of motor neurons . In the United Kingdom, the term motor neuron disease is used for these disorders. 2) In the second sense, ALS refers to one specific form of motor neuron disease in which there are both upper and lower motor neuron signs. • Is characterized by neuronal muscle atrophy (amyotrophy) and hyperreflexia due to loss of lower motor neurons in the anterior horns of the spinal cord and upper motor neurons that project in the corticospinal tracts respectively Incidence • Approx 1 in 54,400 i.e: 2 per 100,000 • Prevalence is 6 per 100,000 • Affects men slightly more often than females (60 :40%) • Becomes clinically manifest in the fifth decade or later (40 -70, peak at 55) • 5 – 10% are familial with autosomal dominant inheritance, other 90% sporadic • 93% are caucasian Pathophysiology • Etiology and pathogenesis are unknown • For a subset of the familial cases, the genetic locus has been mapped to the copper-zinc superoxide dismutase gene (SOD1) on chr 21 Clinical Features • As motor neurons degenerate, they can no longer send impulses to the muscle fibers that normally result in muscle movement. • Early symptoms often include - increasing muscle weakness, especially involving the arms and legs, speech (slurring), swallowing (dysphagia) or breathing (dyspnoea). - May present with asymmetric weakness of the hands, manifested by dropping objects, difficult fine motor tasks and cramping and spasticity of the arms and legs. • When muscles no longer receive the messages from the motor neurons that they require to function, the muscles begin to atrophy and muscle power appears much diminshded. Limbs begin to look "thinner" as muscle tissue atrophies. • Involuntary contractions of individual motor units termed fasiculations occur. • Limb weakness is predominantly distal. Weakness and atrophy of the intrinsic hand muscles are prominent. • Weakness progresses to involve the forearms and shoulder girdle muscles and the lower extremities. • In the majority of cases the disease does not impair a patient's mind, personality, intelligence, or memory. Nor does it affect a person's ability to see, smell, taste, hear, or feel touch. Control of eye muscles is the most preserved function, unlike M.S bladder and bowel function is also retained. • Involvement of both upper and lower motor neurons is characteristic. Patients develop variable hyperreflexia, clonus, spasticity, extensor plantar responses, and limb or tongue fasciculations. • Degeneration of motor neurons in the motor cortex leads to clinically apparent signs of upper motor neuron abnormalities: overactive tendon reflexes, Hoffmann signs, Babinski signs, and clonus. • Degeneration of motor neurons in the brain stem and spinal cord causes muscle atrophy, weakness, and fasciculation. • If lower motor neuron signs alone are evident, the condition is called progressive spinal muscular atrophy (progressive muscular atrophy). • In primary lateral sclerosis, only upper motor neuron signs are seen. These syndromes are considered variants of ALS because, at autopsy, there are likely to be abnormalities in both upper and lower motor neurons. • Progressive / Bulbar ALS – degeneration of the lower brainstem cranial motor nuclei occur early and rapidly Diagnosis • Lab Studies: • Serum protein immunoelectrophoresis should be done to rule out a possible monoclonal gammopathy syndrome. • Lyme disease serology • HIV testing – HIV testing in appropriate only if the history is highly suggestive of exposure. – A chronic, inflammatory, demyelinating polyradiculoneuropathy (CIDP) syndrome in HIVinfected patients can resemble ALS. – However, a clinical history of sensory signs is helpful in excluding this possibility. INVESTIGATION Imaging Studies: • Brain or cervical spine MRI should be done to rule out dysmyelinative lesions (eg, in family history of Tay-Sachs disease) or to rule out cervical myelopathy. • The cervical spinal cord is often normal in appearance in ALS. Cord atrophy is generally a late manifestation of this disease. • The most common finding noted in ALS is signal hyperintensity on T2-weighted images in the posterior limbs of the internal capsule and extending into the adjacent frontoparietal white matter. The phenomenon is caused by secondary degenerative changes related to the neuronal abnormality in the anterior horn cells of the spinal cord. • Other Tests: • Needle EMG and nerve conduction studies are the tests of choice for confirming the diagnosis of ALS. • Electrophysiological studies in the diagnosis of ALS - El Escorial criteria MANAGEMENT • Medical care in ALS is primarily palliative. • Patients should be involved in regular exercise and a physical therapy program. • Medications such as baclofen and tizanidine may be used to relieve severe spasticity. • Riluzone is an FDA-approved medication for prolonging tracheostomy-free survival. • Riluzole, a glutamate antagonist, is the only drug approved by the Food and Drug Administration for the treatment of ALS . In two therapeutic trials, riluzole prolonged survival by three to six months. In one of these trials, treatment slightly slowed the decline in the strength of limb muscle; there was no benefit with respect to many measures of function in either trial. In one retrospective analysis, patients who received riluzole remained in a milder stage of disease longer than did controls. For patients, the effects are invisible • Agents that are currently being evaluated include xaliproden (which may foster the release of neurotrophic factors), creatine, coenzyme Q10, intrathecally administered (by lumbar puncture) brainderived neurotrophic factor, and orally administered brain-derived neurotrophic factor. • Inhibitors of cyclooxygenase-2  and caspase inhibitors are being considered, and “high-throughput” drug development is on the horizon. • Surgical Care: • Early consideration for elective tracheostomy should be considered in patients with early signs of respiratory difficulty. • Home health aides can be helpful in managing secretions and feeding. • Computerized aids for writing and communication also can be helpful. Consultations Surgeon or gastroenterologist - To perform elective tracheostomy or G-tube placement Pulmonologist and respiratory therapist - For ventilator assistance and management of intercurrent infections and tracheostomy Physical and respiratory therapists - To enhance muscle function and manage spasticity Secretion management - For chest percussion therapy and suctioning Diet: Evaluate swallowing to quantify any dysphagia. Modify the patient’s diet to prevent aspiration. Consider a gastrostomy tube when patient cannot swallow fluids or soft foods. Activity: No activity restriction is necessary. Patients should maintain a regular exercise regimen if the degree of weakness allows. FOLLOW-UP Complications: • Aspiration pneumonia • Respiratory insufficiency • Progressive inability to perform activities of daily living (ADLs), including handling utensils for selffeeding • Deterioration of ambulation • Complications from wheelchair-bound or bedridden states, including decubitus ulcers and skin infections Prognosis • At the time of writing this, no treatment significantly prolongs survival in ALS. • Prognosis is grim, but new medications that counteract neuronal apoptosis, oxidative stress, mitochondrial dysfunction, or excitotoxicity show significant promise. Prognosis • ALS leads to death within a decade, and in most cases, within 5 years • Some patients with familial, juvenile-onset ALS have been reported to survive for longer periods (2-3 decades). • FOR FURTHER QUESTIONS PLEASE SPEAK WITH THE PERSON TO YOUR RIGHT !!!