What is the difference between Parkinson’s Disease and Huntington’s Disease?
Parkinson’s disease and Huntington’s disease both result in progressive damage to parts of the brain responsible for coordinated movement. However, there are some major differences:
Huntington’s is largely inherited, whereas Parkinson’s is not. The main difference between Huntington’s disease and Parkinson’s disease is the extent of neurodegeneration: Parkinson’s symptoms are limited mostly to problems with movement, while Huntington’s symptoms also progress into severe cognitive decline. Further, while there are successful treatments for Parkinson’s, there are very few options for treating the symptoms and progression of Huntington’s disease.
How are the symptoms of Parkinson’s Disease and Huntington’s Disease different?
Parkinson’s disease and Huntington’s disease both have similar motor symptoms, characterized by uncontrolled or involuntary movements. However, PD motor symptoms are referred to as “tremors,” while Huntington’s symptoms are twitching movements. Both will experience rigidity in the limbs with the progression of the disease, but cognitive decline and memory loss experienced by Huntington’s patients is far more pronounced.
Motor Symptoms of Parkinson’s Disease
Parkinson's disease is characterized by motor symptoms such as uncontrolled shaking, especially in the hands, referred to as tremors [1]. Bradykinesia, or the slowing down of movements, is another common symptom in Parkinson's patients [1, 2]. Patients often experience stiffness on one or both sides of their body, a symptom known as rigidity [1].
Parkinson's disease can also cause changes in the way a person walks, referred to as changes in gait [1]. Trouble with balance and coordination, and falls, known as postural instability, are common symptoms of Parkinson's disease [3]. Some people with Parkinson's disease may have "flat" facial expressions [1].
Non-motor Symptoms of Parkinson’s Disease
Non-motor symptoms of Parkinson's disease include memory problems, loss of smell, constipation, trouble urinating, temperature sensitivity, excessive sweating or salivating, sleep disorders, mood disorders, and changes in handwriting or voice [1].
Motor Symptoms of Huntington’s Disease
The early motor symptoms of Huntington's disease include unusual clumsiness, lack of coordination or precision in movements, and difficulty in maintaining balance and stability [4]. As the disease progresses to its advanced stages, involuntary twitching or jerking movements, known as chorea, become a hallmark symptom of Huntington's disease [4]. Patients may experience stiffness and inflexibility in their muscles, similar to the rigidity in PD [4]. Mobility becomes increasingly challenging, and patients may have difficulty moving around [4].
Non-Motor Symptoms of Huntington's Disease
The early non-motor symptoms of Huntington's disease include anxiety, mood changes and irritability, depression, memory issues, difficulty understanding new information, and trouble making decisions [4]. As the disease advances, patients may experience slurred speech and difficulty speaking, trouble swallowing, significant changes in personality traits and behavior, breathing issues, cognitive decline, hallucinations, and paranoia [4].
Is Parkinson’s Disease or Huntington’s Disease more common?
Parkinson’s disease is far more common than Huntington’s disease. Since both diseases have a genetic component, this also varies greatly across regions.
Prevalence of Parkinson's Disease
The prevalence of Parkinson’s Disease varies across different regions and populations. In Europe and Asia, the prevalence of PD was found to be 1.5% [5, 6, 7, 8, 9]. In the United States, the prevalence of PD was 347 per 100,000 inhabitants [10]. In total, according to the Parkinson’s Foundation, more than 10 million people live with Parkinson’s disease worldwide [11].
Prevalence of Huntington's Disease
The prevalence of Huntington’s Disease varies globally and is influenced by factors such as ethnicity. Globally, the prevalence of HD is significantly lower in Asian populations, estimated at 0.41 per 100,000, compared to Europe and North America, where prevalence is up to 8.87 per 100,000 [12, 13].
Pathology of Parkinson's Disease and Huntington's Disease: What are the causes and mechanisms of disease?
What causes Parkinson’s Disease?
Parkinson’s Disease is characterized by the progressive loss of dopamine neurons in the substantia nigra, a region of the brain that plays a crucial role in coordinating muscle movement and emotional functions [19].
A key feature of PD is the presence of intra-neuronal inclusions, or inside of brain cells, known as Lewy bodies. These inclusions are primarily composed of a protein called alpha-synuclein (α-SYN), which is important for synaptic function and inter-cell communication [19, 21, 22].
Genetic factors also play a role in PD, with approximately 10-15% of all cases linked to some form of hereditary mutations. Among the most common mutations in PD patients are those in the genes LRRK2 and SNCA [20, 23]. In addition, some genes have been identified as risk factors for sporadic Parkinson's disease [14].
Environmental factors have also been implicated in the development of Parkinson's disease. Exposure to certain chemicals, such as pesticides, herbicides, and fungicides, has been suggested as a possible link to the condition [16]. Occupational exposure to agents such as manganese, carbon disulfide, carbon monoxide, and MTPT have also been associated with PD [17]. Other factors that have been associated with PD include advanced age and elements of rural living [18].
There are some studies suggesting a link between Parkinson's disease and head injury, but the causal relationship between the two remains clear.
What causes Huntington’s Disease?
In contrast to Parkinson’s, Huntington's disease is most-commonly caused by a genetic mutation characterized by an expansion of a CAG trinucleotide repeat in the first exon of the Huntingtin (HTT) gene [15]. This mutation leads to neurodegeneration, predominantly in the basal ganglia, including the striatum, and the cortex [24, 25, 26]. Only around 10% of HD cases are caused by a random, or de novo, Htt gene mutation.
Development of HD eventually affects the hippocampus (required in memory), the thalamus (involved in inter-brain region communication), and the cerebellum (controlling instinctive and learned movements). In HD patients, these brain areas all contain the mutant huntingtin protein, mHtt, and are all sites of severe inflammation, cellular dysfunction, and cell death [27].
Though there have been no identified environmental risk factors, it is thought that the random, de novo, gene mutations are more likely to occur when the father is older at the time of conception [28].
How do treatments differ between Parkinson’s Disease and Huntington’s Disease?
Though there is no cure for neither Parkinson’s Disease nor for Huntington’s Disease, there are some major differences in the treatment plans. For PD, there are a variety of treatments that allow patients to maintain normal or near-normal lives, with normal life expectancies [29]. Unfortunately, for Huntington’s disease the pharmaceutical interventions are not as successful: treatments exist that allow management of symptoms, but HD patients typically are prescribed palliative hospice care within 20 years of diagnosis.
Parkinson’s Disease treatment
There are a few treatment options for Parkinson’s patients. PD patients are frequently treated with L-DOPA, thought to be the “gold standard” for treating symptoms of Parkinson’s, as well as monoamine oxidase type B (MAOB) inhibitors, Catecgol-O-methyltransferase (COMT) inhibitors, and dopamine agonists [29]. Additionally, deep-brain electrical stimulation or continuous dopamine stimulation are often prescribed and demonstrate great success at removing parkinsonian-like motor symptoms [29], though these are invasive procedures.
For improved mobility, PD patients are often referred to physiotherapists and massage therapists to improve balance and loosen tension in their muscles. The progression of PD is very slow, and often these treatments allow a patient to maintain their former independence for many years.
Huntington’s Disease treatment
There is unfortunately no successful cure for Huntington’s disease. Medications include tetrabenazine [30] and deutetrabenazine [31], which help manage the motor symptoms for some time. However, these are unable to slow the progressive neurodegeneration, and only add a couple of years to the life expectancy.
However, there is currently one clinical trial experimenting with delivering a gene therapy directly to the basal ganglia in the brain, where the majority of this neurodegeneration occurs [32].
HD patients are also treated with antipsychotics and antidepressants to help manage and improve cognitive symptoms, as well as to help maintain some normalcy in day-to-day life. In middle- and advanced-stage Huntington’s, patients are also referred to physiotherapy and occupational therapy to improve quality of life. The final years of life are typically spent in palliative hospice care.
Is it possible to have both Parkinson’s Disease and Huntington’s Disease? Can Parkinson’s Disease and Huntington’s Disease be mistaken for each other?
It is, in theory, possible to have both Parkinson’s disease and Huntington’s disease, though it is extremely rare. It is likely that there are such cases, but the onset of PD symptoms will not be detected after the onset of HD.
Similarly, since both PD and Huntington’s have similar motor symptoms, there are a few reported cases where a Huntington’s patient is initially misdiagnosed as having Parkinson’s disease. This is largely because the bradykinesia in PD is very characteristic and developed late in life, making it unlikely to be HD [33, 34]. However, cases like these are extremely rare. Patients are typically diagnosed correctly following attempts at treatment, where the parkinsonian-like symptoms do not respond to L-DOPA [29, 33], as well as comprehensive genetic testing for Huntington’s disease.