Amyotrophic Lateral Sclerosis (ALS) (Lou Gehrig's Disease)
Diagnosis and Conventional Treatment of ALS
Like many neuromuscular diseases, it can be difficult to make an early diagnosis of ALS. Depending on which muscle group is affected first, its symptoms vary from person to person and can include:
- tingling in the fingers or toes
- cramping in the arms or legs
- trouble with tongue and facial movements, including chewing and swallowing.
As the disease progresses, it spreads through the affected limb until eventually all muscle groups become involved. This spread into all muscle groups is the defining characteristic of ALS. In fact, the term amyotrophy refers to the atrophy (wasting) of muscle tissue, while lateral sclerosis refers to the hardening of the spinal column from the buildup of scar tissue (Rowland 2001). The diagnosis of ALS is primarily a clinical one and requires the appearance of both upper (increased tone and reflexes) and lower (fasciculations and muscle atrophy) motor neuron involvement in many segments of the body. Electromyography, nerve conduction studies, and transcranial magnetic stimulation can all be used to support the diagnosis of amyotrophic lateral sclerosis.
Riluzole, an FDA approved drug for the treatment of ALS, blunts the effects of glutamate by decreasing its release and blocking the ability of glutamate to bind to its receptors, thereby decreasing the excitotoxicity that leads to cell death. Albeit small, its two to three month increase in survival time (Miller 2007) indicates that controlling glutamate levels in the brain could be an essential component in fighting ALS and provides valuable information toward ultimately finding a more effective treatment for the disease (Carlesi 2011).
Edaravone (Radicava) was approved by the FDA in 2017 to treat ALS patients (FDA 2017). Edaravone has free radical-scavenging abilities and may reduce oxidative stress, an important aspect of ALS pathogenesis. Edaravone was shown in two controlled clinical trials to slow functional deterioration in a certain subset of ALS patients. The first was a randomized trial of 206 subjects treated with intravenous infusions of either edaravone or placebo for 24 weeks (Abe 2014). While there was no significant difference in overall ALS functional rating scores (ALSFRS-R) between the groups after treatment, post-hoc analysis revealed that subjects in earlier stages of the disease showed a greater treatment effect (Edaravone [MCI-186] ALS 16 Study Group 2017). In order to demonstrate the efficacy in this subgroup, a second trial including 137 subjects in early stages of ALS was conducted. The edaravone group experienced a 33% slower decline in function than the placebo group (Writing Group 2017). Edaravone is generally recommended in addition to riluzole as an adjuvant therapy.
Concerns have been raised regarding the safety and efficacy of edaravone treatment (Turnbull 2018). The majority of patients in the second study experienced treatment-related adverse events, likely due to the nature of drug delivery (ie, intravenous infusion). Edaravone has also only been shown to be effective in a small subset of patients with ALS.
The remainder of conventional medical treatment for ALS patients focuses on relieving symptoms and improving quality of life. For example, non-invasive positive pressure ventilation is often used to help patients with ALS breathe, especially at night (Mustfa 2006; Lo Coco 2006). Physicians frequently recommend prescription medications to relieve painful muscle cramps (e.g. carbamazepine and phenytoin) (Andersen 2005), excessive salivation (e.g. atropine, amitriptyline, hyoscamine, and injections of botulinum toxin into the salivary glands) (Giess 2000; Lipp 2003; Stone 2009), and other symptoms. ALS patients are often advised to engage in moderate exercise and seek physical therapy to maintain muscle strength and function. As the disease progresses, splints, braces, and wheelchairs are used to help with mobility. Also, higher toilet seats, headrests and specialized utensils may help improve the quality of life for ALS patients (Borasio 2001). Occupational and speech therapy help patients as their motor control gradually deteriorates.