Workup

The El Escorial World Federation of Neurology diagnostic criteria are considered the clinical gold standard for diagnosing ALS.15 The criteria state that an ALS diagnosis requires the absence of other disease processes that could be responsible for the clinical signs and the presence of 3 benchmarks: lower motor neuron degeneration, upper motor neuron degeneration, and symptoms that progressively spread either within one body region or from one region to another.15

The Awaji criteria16 use electrodiagnostic studies to allow an earlier diagnosis of ALS and to decrease the number of patients who fail to meet the El Escorial criteria.15-17 Since publication of the Awaji criteria, electromyography (EMG) and nerve conduction studies are routinely employed by providers for evaluation of ALS.16,17

EMG studies document the presence of denervation: fibrillations and positive sharp waves, as well as large-amplitude, long-duration, and complex motor unit action potentials.16,17  Nerve conduction studies assess the number of viable motor axons innervating the muscles of the hands and feet and can identify decreases prior to patients experiencing weakness. This information can assist providers in gauging areas of progressing weakness.2 Both studies prove to be most beneficial when bolstering limited clinical findings to support a diagnosis of ALS.16

Treatment

Treatment options for ALS are limited, and currently there are no pharmacologic cures for the disease.  The US Food and Drug Administration (FDA) has approved 3 drugs for the treatment of ALS: riluzole, edaravone, and a combination of dextromethorphan and quinidine. The approval of riluzole, an oral glutamate blocker, was based on its positive impact on survival rates for patients with ALS.4,18 Along with inhibiting glutamate release, riluzole deactivates the voltage-dependent sodium channels and interferes with cellular events to inhibit binding at excitatory amino acid receptors.18  Early diagnosis of ALS is critical when considering the initiation of riluzole therapy and its role in decelerating the inevitable progression of ALS symptoms. 

Adverse events associated with riluzole include dizziness, fatigue, abdominal pain, diarrhea, headaches, and muscle weakness.19 Riluzole can cause an increase in liver enzymes; therefore, patients who are prescribed riluzole should undergo monthly liver function tests for the first 3 months of therapy, and then quarterly from that point forward.19 Patients being treated with riluzole require monitoring for neutropenia and interstitial lung disease, which are 2 additional side effects of the drug.20 Because the drug’s absorption is decreased by meals with high fat content, patients must take riluzole at least 1 hour before or 2 hours after a meal.18

The FDA approved edaravone as an adjunct therapy to riluzole with the intention to reduce oxidative stress and slow functional deterioration in patients with ALS.21,22  Edaravone 60 mg is administered via intravenous infusion over 60 minutes daily for 14 days, followed by a 14-day infusion-free period.22 Adverse effects associated with edaravone include headaches, gait disturbances, and injection-site contusions.21

A third FDA-approved treatment is a combination of dextromethorphan and quinidine (Nuedexta®). The combination is indicated for the treatment of pseudobulbar affect in patients with ALS.23

As the number of prescribed pharmacologic treatments specifically targeting ALS is limited, over-the-counter medications are often employed to relieve secondary complications including pain, acid reflux, and insomnia.

Multidisciplinary Approach

Patients with ALS benefit from a multidisciplinary approach to care. Physical therapists, respiratory therapists, occupational therapists, psychiatrists, and dietitians improve patients’ quality of life.24  Respiratory therapists use noninvasive positive pressure ventilation to assist patients who are experiencing respiratory distress.24  Physical therapists engage to maintain muscle function, and occupational therapists aid in easing the transition as patients experience worsening symptoms with disease progression.24 

Many patients with ALS suffer from depression and anxiety. Patients may benefit from speaking with a psychiatrist, psychologist, and chaplain throughout the course of their disease.24 As swallowing becomes more of a challenge, dietitians can educate patients about foods that are easier to swallow as well as how to thicken foods. However, most patients will eventually need a percutaneous endoscopic gastrostomy tube for nutrition.2,11 

Pharmacologic and therapeutic regimens for ALS are individualized according to each patient and constantly evolve with disease progression; therefore, primary care providers should collaborate with all specialists involved in the care of the ALS patient to ensure all clinicians are fully informed about the patient’s care plan.

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Prognosis

The outlook for patients with ALS is poor; life expectancy for most patients is 2 to 5 years from diagnosis, and patients typically die from respiratory failure.1,2 A subset of patients with ALS have been reported to experience improved survival rates: when at age of onset was 40 years, the mean duration of disease was 8.2 ± 5.0 years compared with 2.6 ± 1.4 years for patients aged 61 to 70 years (P > .001).Contributors to these long-term survival rates include the rationale that younger age at onset translates to living longer with the disease.25 

In conclusion, patients with ALS require appropriate education regarding their diagnosis and specific prognosis. Every patient’s experience with ALS is unique, and providers should ensure their patients are supported both medically and emotionally through each stage of this devastating disease.