Amyotrophic Lateral Sclerosis


Chapter 189

Amyotrophic Lateral Sclerosis



Stephanie Cassone



Definition and Epidemiology


Amyotrophic lateral sclerosis (ALS) is the most common of the progressive motor neuron diseases. It is also often referred to as Lou Gehrig’s disease, after the New York Yankee baseball player who was diagnosed with the disease in the late 1930s. Classified as a neurodegenerative disorder, it is an incurable disease that produces progressive muscle weakness and ultimately death.1


ALS is a progressive motor neuron disease characterized by dysfunction of both upper motor neurons (UMNs) and lower motor neurons (LMNs) in the corticospinal and corticobulbar tracts, anterior motor horn cells, and bulbar motor nuclei. Most cases (90% to 95%) of ALS are sporadic, appearing at random with no clearly defined risk factors. Approximately 10% are familial, with about one third thought to be caused by a defect in the gene known as C9orf72, and another 20% of familial cases from mutations in the superoxide dismutase 1 (SOD1) gene.1 There are also a variety of clinical variants, including progressive muscular atrophy and progressive bulbar palsy, affecting LMNs in limb and bulbar muscles, respectively. Primary lateral sclerosis and progressive pseudobulbar palsy affect UMNs in limb and bulbar muscles. Although these clinical variants may manifest differently early on, they all eventually affect both LMNs and UMNs.2 Symptoms of autonomic, ocular movement, sensation, and cognitive dysfunction may also occur from degenerative involvement of other cortical areas.2 The prevalence rate of ALS in the United States is 3.9 cases per 100,000 population.2


imageNeurology consultation is indicated for all patients with suspected ALS.



Pathophysiology


The cause of ALS remains unknown, although the recent literature suggests several major hypotheses. There are rare familial cases of ALS (5% to 10% of cases) in which mutations in the SOD1 gene have been discovered. Many cases of ALS, however, are sporadic, not familial, and several theories of cause are postulated. The first describes excitotoxic stimulation as a result of accumulation of glutamate in the central nervous system. It appears that the excess glutamate is toxic to motor neurons. The second hypothesis suggests an autoimmune process with autoantibodies to the calcium channels in motor neurons. The third is a familial hypothesis that neuronal injury is secondary to altered function of the enzyme SOD1 and subsequent accumulation of free oxygen radicals.3


There is evidence that this oxidative stress, mediated by free radicals, is important in the initiation of the disease. The role of abnormal protein aggregation has also been gaining recognition in neurodegenerative diseases including ALS. Research into the role of environmental exposures and viral agents as risk factors for the disease continues.3


The proposed causative mechanisms all lead to neuronal damage of both UMNs and LMNs. The UMNs are initially altered in the motor cortex, thereby affecting the corticospinal and corticobulbar tracts. The LMNs are affected at the anterior motor horn cells in the spinal cord and at the respective motor nuclei in the brainstem. Death of the motor neurons in the brainstem and spinal cord leads to denervation and atrophy of muscle fibers.



Clinical Presentation and Physical Examination


A precise documentation of the history of symptoms and a complete physical examination highlighting the neurologic examination are essential. Early LMN cell death leads to an insidious onset of asymmetric weakness that is evident initially in the limbs, usually in the arms. Early findings include foot drop, difficulty walking, and weakness with lifting arms.4 It is important to assess UMNs and LMNs as well as bulbar signs and symptoms.


UMN dysfunction may manifest as hyperreflexia, spasticity, Babinski signs, incoordination, and weakness. LMN dysfunction may manifest as weakness, muscle atrophy, and fasciculations (spontaneous twitching). Fasciculations may be focal, multifocal, or diffuse. Fasciculations are accompanied by UMN signs and weakness in patients with ALS. Bulbar signs and symptoms include dysarthria, dysphagia, sialorrhea, tongue atrophy, and tongue fasciculations. Bulbar presentation is often closely related to reduced vital capacity resulting from difficulty in speaking and swallowing and carries a poor prognosis compared with limb onset.5


As the disease progresses, both UMN and LMN involvement becomes evident, with a more symmetric distribution of the disease. Yet even in the late stages of disease, sensation and bowel and bladder function are spared. There is a known link between ALS and executive dysfunction of the frontal and temporal lobes that may manifest as subtle cognitive dysfunction or, in about 15%, as frontotemporal dementia.4



Diagnostics


The diagnosis of ALS is usually made when there are widespread UMN and LMN signs in the absence of any electrophysiologic and pathologic signs of other disease processes as well as absence of neuroimaging evidence of other disease processes. In 1994, the World Federation of Neurology presented diagnostic criteria for ALS. These were subsequently revised in 1998 and renamed Airlie House criteria. Awaji-Shima criteria were introduced in 2008, which improved diagnostic sensitivity without increasing false positives.2 These criteria include signs of LMN degeneration by clinical, electrophysiologic, or neuropathologic examination; signs of UMN degeneration by clinical examination; and progression of the motor syndrome within a region or to other regions. The four regions are bulbar, cervical, thoracic, and lumbosacral.2


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Oct 12, 2016 | Posted by in CRITICAL CARE | Comments Off on Amyotrophic Lateral Sclerosis

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