How are the symptoms of ALS and Huntington’s disease different?
ALS Symptoms
Amyotrophic Lateral Sclerosis, sometimes known as Lou Gehrig’s disease, is the most common “motor neuron disease” and primarily affects neurons in the spinal cord, brain stem, and motor cortex of the brain. These are all very important for muscle control and accurate movement, and taken together, the degeneration of these cells results in progressive muscle weakness and atrophy.
Eventually, motor symptoms develop into difficulties walking, speaking, swallowing, and breathing. In the final stages of ALS, patients are often completely paralyzed [1].
About 10-15% of patients will experience cognitive decline. These patients are then classified as having ALS-FTD (frontotemporal dementia) [2].
In the case of bulbar onset ALS, the symptoms are characterized by the weakining of facial, head and neck muscles.
Huntington’s Disease Symptoms
Huntington’s Disease primarily affects the basal ganglia and cortex of the brain, which are crucial for emotional processing, learning, and controlled movements [3].
A mutated Huntingtin gene interacts with various cellular processes and causes malfunction and degeneration. Symptoms of HD include impaired coordination, difficulties with movement, and “chorea,” which are involuntary movements that often develop into constant jerky movements [3].
Additionally, patients with Huntington's disease experience significant cognitive decline, affecting short and long-term memory, as well as problems with decision-making and impulse control.
What are the causes of ALS and Huntington's? How is the onset of ALS and Huntington's different?
What causes ALS?
A majority of ALS cases are sporadic, where only 10% of cases are hereditary, or have been passed down from a family member. This makes it very difficult to diagnose and treat. ALS is most common between the ages of 50 and mid-60’s. Onset is about 10 years later in European patients when compared to all other populations [4].
There are some known risk factors for developing ALS: a personal history of smoking and exposure to some environmental toxins such as heavy metals have been associated with increased risk for development of ALS [1].
Additionally, ALS is more-often developed by males, and has a different onset of symptoms [5]. In males, symptoms begin as a result of spinal degeneration, causing difficulties controlling limbs, whereas in females symptoms begin as a result of bulbar degeneration, causing difficulties in controlling facial muscles [5]. The life expectancy is approximately 2-5 years after diagnosis.
Some recent research is exploring a possible link between ALS and the gut micriobiome.
What Causes Huntington’s Disease?
Contrary to ALS, Huntington's disease has a clear genetic component, where an inherited Huntingtin (Htt) gene mutation from one’s parents can pose a 50% risk of developing HD. Only around 10% of HD cases are caused by a random, or de novo, Htt gene mutation. Further, there are virtually no identified life-style risk factors [6]. It is thought that these random gene mutations are contributed from the father's genetic pool, and are more likely to occur when the father is older [7].
Most patients with Huntington's develop symptoms in adulthood, between 30 and 50 years of age, depending on how mutated the gene is. Smaller mutations may not even cause symptoms, whereas greater mutations may even result in “juvenile” Huntington's disease, with symptoms developing at around 20 years of age [8].
A majority of Huntington's disease patients will have a life-expectancy of 15-20 years after diagnosis.
Is ALS or Huntington's more common?
Huntington's disease is slightly more common, globally, than ALS, though the differences in prevalence are very regionally-dependent. There is a slight increase in prevalence of both ALS and Huntington's reported in the last decade, however this is most-likely due to longer life expectancies and the random occurrence of de novo, non-inherited, gene mutations [5, 9].
Prevalence of Amyotrophic Lateral Sclerosis
The prevalence of ALS has been reported between 4.1 to 8.4 per 100,000, depending on region and ethnicity. For example, prevalence among European-American ALS patients is nearly double that of African-American ALS patients [4]. Males are thought to be twice as likely to develop ALS, but only in sporadic cases: inherited (familial) cases of ALS have no sex differences [4, 10].
Prevalence of Huntington’s Disease
The global prevalence of Huntington's disease has been reported to be around 4.8 per 100,000, again depending on the region. Prevalence of Huntington's is nearly 20 times higher in Europe and North America, where prevalence is up to 8.87 per 100,000, than it is in Asia and Africa, where prevalence is 0.41 per 100,000 [11]. This is thought to be due to a completely distinct genetic origin of the mutations causing HD.
How do treatments differ between ALS and Huntington's?
ALS Treatment
Since there is no known genetic cause of ALS, it is difficult to diagnose early and treat before symptoms arise. Recently, a new medication Tofersen has been approved for treatment of inherited ALS caused by the gene SOD1 [12], but unfortunately this only applies to a select handful of ALS patients.
ALS treatment plans tend to focus on symptom management (including prescription of muscle relaxants). The medication riluzole helps relieve breathing difficulties, and has been shown to extend life by at least three months.
ALS patients are also treated with edaravone, which may delay progression of symptoms for some time [13]. When ALS patients become unable to breathe easily on their own, they will get a tracheostomy, or a breathing tube, and be transferred to palliative or hospice care.
Huntington’s Disease Treatment
Though Huntington's disease is genetically inherited, there is still no cure. Medications include tetrabenazine [14] and deutetrabenazine [15], which help decrease jerky and involuntary movements for some time.
Clinical trials are currently testing gene-therapies for HD. Additionally, there is one current clinical trial experimenting with delivering a therapy directly to the basal ganglia in the brain, where the majority of HD-related neurodegeneration occurs [16].
Huntington's disease patients are also treated with antipsychotics and antidepressants throughout the development of the disease, to help manage and improve cognitive symptoms. Once physical symptoms become more severe, patients are also referred to physiotherapy and occupational therapy to improve quality of life.
Similarly to ALS, the final years of life are usually spent in palliative or hospice care.
Can ALS and Huntington's be mistaken for each other?
Both ALS and Huntington's have similar motor symptoms at first, specifically the poor control or coordination of muscle movements. It is possible that an ALS or an Huntington's disease patient may initially receive a list of possible diagnoses, prior to an official diagnosis, in which a doctor could suspect the wrong condition.
However, due to the genetic nature of Huntington's disease, the greater prevalence of early cognitive decline in HD, and the very characteristic “chorea” experienced by most HD patients, it is unlikely that Huntington's would be mistaken for ALS. Additionally, since HD affects the basal ganglia and ALS affects the spinal cord, a standard series of diagnostic tests performed early-on during the progression of the disease should quickly rule out one or the other and avoid misdiagnosis.
Importantly, recent research points to a possibility for motor neuron damage in the spinal cord of Huntington's disease patients, which is otherwise characteristic of ALS. However, this is found largely in patients with the greatest gene mutations and only in the later stages of HD [17], which should not pose challenges to diagnosis when symptoms first arise.
Is it possible to have both Huntington's and ALS?
Cases of both Huntington's disease and ALS are rare, but where present, there are some notable differences in the genetic expression of HD.
Since Huntington's is a hereditary condition, it is important to note that in ALS patients, the genetic carrier rate is over four times greater than in HD-only patients, specifically in the patients with the most-mutated copy of the gene.
Additionally, while HD patients typically show brain atrophy and cell death in the striatum, a large part of the basal ganglia controlling emotion and cognition, ALS-and-HD patients show no damage to the striatum [18].
The reason for this is poorly understood, but it is thought that many ALS patients may also have misdiagnosed underlying HD that may reduce their life expectancy.
For these reasons, it is important that patients with a suspected neurodegenerative disease undergo comprehensive genetic testing to ensure a complete and accurate diagnosis.
