The etiology of ALS is unknown.

Risk factors

genetic predisposition, toxic effects of heavy metal, viral infection, environmental and occupational exposures, cigarette smoking, repeated physical trauma, military service, and participation in strenuous physical activity, such as professional athletics.3-5 Investigations into etiology have revealed a pathologic overlap between frontotemporal degeneration (FTD) and ALS; these two diseases have similar features.6,7

Two classifications of ALS have been described: familial (inherited) and sporadic. Approximately 10% of all cases of ALS are thought to be familial and due to genetic mutations.8 Numerous genetic mutations have been associated with ALS. A mutation in the superoxide dismutase gene 1 (SOD1) accounts for approximately 20% of familial cases of ALS. Superoxide dismutase is a critical enzyme involved in protecting mitochondria from oxidative stress.8 In addition, a repeated nucleotide abnormality at the 9p21 genetic locus, termed the C9orf72 mutation, has been detected in 60% of familial cases of ALS and 10% of sporadic cases.9 At the molecular level, the pathology of ALS is highly complex, and dysfunction has been found in numerous cellular components. However, the “trigger” of these cellular changes is unknown. A pathologic process of excessive glutamate excitation of motor neurons, leading to degeneration and dysfunction, is found in ALS.10 Mitochondrial abnormalities in the spinal cord, such as swelling and vacuolization, are a pathologic hallmark of ALS.11 The presence of proteinaceous aggregates in the spinal cord in ALS suggests malfunction of protein degradation and clearance.12 Diminished levels of vascular endothelial growth factor (VEGF) and angiogenin (ANG), which are involved in the maintenance of neural networks and vasculature, have also been implicated in ALS.13 A neurotoxin, β-methylamino-L-alanine, is related to ALS in some populations, including military personnel who have served in the Middle East.14 Malfunction of RNA transcription and splicing is a common causal factor in both familial and sporadic ALS, in which the accumulation and misassembly of neurofilaments disrupt neuronal axon integrity—another hallmark of ALS pathology.15

 

Amyotrophic lateral sclerosis,nervous system disease that affects nerve cells in the brain and spinal cord, causing loss of muscle control.

ALS is often called Lou Gehrig's disease, after the baseball player who was diagnosed with it.

ALS often begins with muscle twitching and weakness in a limb, or slurred speech.

Eventually, ALS affects control of the muscles needed to move, speak, eat and breathe.

 

 

 

Often referred to as Lou Gehrig's disease, is a progressive neurodegenerative disorder that is characterized by a loss of upper and lower motor neurons.

Muscle weakness and atrophy develop gradually over many years.

Motor neuron from the spinal cord containing an inclusion from ALS.

Motor neuron from the spinal cord containing an inclusion from ALS.

Pathophysiology

ALS progressively destroys the motor neurons that control voluntary muscles. Upper motor neurons, located in the brain, send messages to lower motor neurons in the spinal cord and from there to various voluntary muscle groups. In individuals affected by ALS, both the upper and lower motor neurons become sclerotic and die. Consequently, the neurons can no longer conduct impulses to the muscles, so that muscular weakness and atrophy develop. In a process called astrocytic gliosis, lost motor neurons are replaced by astrocytes, which form a kind of scar tissue that can be seen on magnetic resonance imaging (MRI) within the corticospinal tracts, brain stem, and spinal cord. Motor neuron degeneration is accompanied by a neuroinflammatory process and the proliferation of glial cells (gliosis), which do not conduct impulses.16,17

Eventually, as damage to the motor neurons increases, the brain is unable to start or adequately control voluntary muscle movement. The affected muscles become increasingly weak and atrophic, and the muscles that control speech, swallowing, and breathing slowly become impaired. Ultimately, paralysis develops, and the patient requires artificial ventilation for respiratory failure.18 ALS damages motor neurons, but the sensory neurons usually remain intact—the senses of sight, touch, hearing, taste, and smell are not affected. The eye muscles and sphincter control are spared.8 Cognitive impairment is not a major feature of ALS, and dementia does not occur in all patients. However, a link between ALS and FTD has recently been postulated because the two conditions are characterized by similar neuropathologic changes, clinical features, and genetic mutations. Some investigators refer to this overlap of features as the ALS-FTD spectrum.19-22

 

++++++++++++++++++++++++++++++++

  • f nervous system affected: The central nervous system (CNS), specifically the motor neurons.

  • Fasciculations: ALS is a progressive, neurodegenerative disease affecting motor neurons, which are cells within the CNS that control voluntary muscle movement. The loss of signal communication to the muscles caused by the degeneration of these cells leads to muscle atrophy, which manifests itself in fasciculations.

  • Pathology: Loss of motor neurons in the brainstem nuclei and the anterior horns of the spinal cord, along with degeneration of the corticospinal tracts in the spinal cord.

Clinical Correlation

ALS is a progressive degenerative disorder of the motor neurons of the spinal cord, brainstem nuclei, and corticospinal tracts. In its classical presentation, patients in their sixth decade initially complain of difficulty with fine finger movements and stiffness and weakness of the fingers and hands. The patients can also experience cramps or fasciculations of the muscles in the upper extremities. As time progresses, atrophic weakness involves both upper extremities, and spasticity and hyperreflexia develops in the lower extremities. The muscles of the neck, tongue, pharynx, and larynx may also become involved. Depending on the extent of involvement of the various motor neurons, a mixed upper and lower motor neuron disease becomes evident. There are no cognitive, sensory, or autonomic disturbances in this disease. An electromyelogram (EMG) obtained for confirmatory purposes reveals widespread fibrillations and fasciculations, evidence of active denervation and reinnervation of the muscles. Analysis of cerebrospinal fluid (CSF) may reveal normal or slightly elevated protein levels. Unfortunately, the etiology of ALS is unknown. As the disease reaches its ultimate conclusion, the patient is left with flaccid paralysis of all voluntary muscles with the exception of the extraocular and sphincter muscles. Treatment is directed toward minimizing the disability. For instance, medications such as baclofen and diazepam can be used to treat spasticity. The median survival from onset of symptoms is 3-4 years, although individuals can live a normal life span if proper care is available.

Save Answers

 

 

 

It is difficult to estimate the incidence and prevalence of ALS because it is not a reportable disease. According to the Mehta et al, the estimated incidence of ALS across all ages is approximately 4 to 5 persons per 100,000.1ALS is diagnosed each year in the United States in an estimated 5000 persons, with an estimated prevalence of 12,000 to 15,000 cases. ALS is more prevalent in men than in women, with a typical age at diagnosis of 55 to 75 years.1,2 

 

 No cure is available for ALS. However, riluzole is believed to reduce the damage to motor neurons by decreasing the release of the excitatory neurotransmitter glutamate. Another drug, edaravone, is a free radical scavenger that is thought to decrease oxidative stress on neurons in ALS. Both drugs claim to slow the progression of ALS, and studies reveal modest results.34,35

 neurologist and a multidisciplinary team are required for the management of ALS. Whenever possible, primary care clinicians should refer the patient to a specialized ALS clinic. Treatments to manage the various symptoms can improve the quality of life (Table 2). Medications to reduce fatigue, relieve muscle cramps, control spasticity, and reduce excessive oral secretions can be beneficial. Gentle, low-impact aerobic activity and range-of-motion and stretching exercises can help to prevent painful muscle spasticity and contractures. When respiratory muscles weaken, intermittent positive pressure ventilation may be used to ease the work of breathing during sleep. Most patients remain asymptomatic until the forced vital capacity (FVC) is less than 50% of the predicted level as a result of respiratory muscle weakness. The patient's preferences regarding life-sustaining treatment and approaches to palliative care should be discussed soon after the diagnosis of ALS, and any decisions should be reconsidered on several occasions before respiratory failure occurs. 


The primary care clinician may be involved early in the ALS disease process. Often, the diagnosis is delayed because the clinical presentation is unclear at an early stage. The primary care clinician may be involved in managing the symptoms of a patient with ALS and serve as a source of support for the caregiver(s). Patients require multidisciplinary care and rehabilitative interventions; maximizing independent function and quality of life are the goals. Family members, particularly spouses, commonly care for patients with ALS. The caregiver role frequently causes strain, which generally increases as the disease process progresses. Continued support and education from the primary care provider are essential for caregivers. Currently, numerous investigations into the genetic basis of ALS and the development of drugs to diminish the progressive degeneration associated with this disease are under way. 

Teri Capriotti, DO, MSN, CRNP, is a clinical associate professor, Erin Donnelly is an honors student, and Simone Brissenden is an honors student at Villanova University, PA.

References

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