Journal of Neuroinfectious Diseases
Open Access

Huntington’s disease (HD) is a rare, inherited neurodegenerative disorder that causes the progressive breakdown of nerve cells in the brain. This disorder leads to severe motor, cognitive, and psychiatric impairments, significantly affecting a person's quality of life. HD is caused by a genetic mutation in the HTT gene, leading to the production of an abnormal huntingtin protein, which is toxic to neurons. Symptoms usually appear in adulthood, typically between the ages of 30 and 50, though a juvenile form of the disease can develop earlier. HD is an autosomal dominant disorder, meaning that an individual only needs to inherit one copy of the faulty gene from a parent to develop the disease. As the disease progresses, individuals experience uncontrolled movements (chorea), difficulty with coordination, cognitive decline, and psychiatric disturbances such as depression, anxiety, and personality changes. This article explores the pathophysiology, clinical symptoms, diagnosis, treatment options, and ongoing research efforts aimed at finding a cure or more effective therapies for Huntington’s disease. Early symptoms often include subtle personality changes, mood swings, and difficulties with coordination. As the disease advances, patients experience chorea (involuntary movements), difficulty speaking and swallowing, and a decline in cognitive abilities. Psychiatric symptoms, such as depression and anxiety, are also common. Although there is currently no cure for Huntington’s disease, ongoing research in gene therapy, neuroprotection, and symptomatic treatments offers hope for future interventions [1,2]. This article explores the pathophysiology, clinical symptoms, diagnostic methods, current treatment approaches, and emerging research in the field of Huntington’s disease. HD is an autosomal dominant disorder, meaning that an individual need only one defective copy of the HTT gene to develop the disease [3,4].

Pathophysiology

Huntington’s disease is caused by a CAG trinucleotide repeat expansion in the HTT gene located on chromosome 4. The number of CAG repeats determines the severity and onset of the disease: individuals with 40 or more repeats will inevitably develop symptoms, while those with 36-39 repeats may or may not develop the disease. This mutation leads to the production of mutant huntingtin protein (mHTT), which forms toxic aggregates in neurons, leading to progressive neuronal dysfunction and cell death, particularly in the striatum and cortex [5,6].

The neurodegeneration associated with HD results in a loss of motor control, cognitive function, and emotional regulation. The basal ganglia, a brain region involved in movement control, is particularly affected, leading to the characteristic involuntary movements seen in HD patients. Over time, the damage extends to other parts of the brain, worsening cognitive and psychiatric symptoms [7,8].

Clinical symptoms

HD symptoms typically progress through three stages: early, middle, and late. The severity and progression rate vary between individuals but generally follow a predictable course:

Early Stage: Subtle changes in coordination, difficulty concentrating, irritability, mild involuntary movements, and depression.

Middle Stage: More pronounced movement difficulties, slurred speech, difficulty swallowing, cognitive impairments, and worsening psychiatric symptoms [9].

Late Stage: Severe motor dysfunction, inability to walk or speak, profound cognitive decline, and total dependence on caregivers.

The combination of motor, cognitive, and psychiatric symptoms makes HD a particularly challenging disorder for patients and caregivers.

Diagnosis

Diagnosing Huntington’s disease involves a combination of clinical evaluation, family history assessment, genetic testing, and imaging studies.

Genetic testing: A blood test can confirm the presence of the HTT gene mutation, making genetic testing the definitive diagnostic tool for HD.

Neurological examination: A physician assesses motor function, reflexes, muscle strength, balance, and cognitive abilities.

Imaging studies: MRI and CT scans may reveal brain atrophy, particularly in the striatum, though these changes often appear later in the disease.

Psychiatric evaluation: Screening for depression, anxiety, and other mental health conditions is essential for comprehensive care.

Genetic testing can also identify individuals at risk before symptoms appear, though ethical considerations play a role in deciding whether to test asymptomatic individuals [10].

Treatment and management

Currently, there is no cure for Huntington’s disease, and treatment focuses on managing symptoms and improving quality of life.

Pharmacological treatments:

Tetrabenazine and deutetrabenazine: Used to reduce chorea by depleting dopamine levels.

Antipsychotic medications: Such as risperidone and olanzapine, help manage psychiatric symptoms.

Antidepressants and mood stabilizers: Used to treat depression, anxiety, and irritability.

Supportive therapies:

Physical therapy to improve mobility and prevent falls.

Speech therapy to assist with communication and swallowing difficulties.

Occupational therapy to help with daily activities and adaptive techniques.

Lifestyle and supportive care:

A structured routine, social support, and mental health counseling can help manage the psychological impact of HD.

Nutritional support is essential, as difficulty swallowing and involuntary movements can lead to weight loss.

Research and future directions

Significant research efforts are underway to find disease-modifying treatments for Huntington’s disease. Some promising areas of study include:

Gene silencing therapies:

Antisense oligonucleotides (ASOs) such as tominersen aim to reduce the production of mutant huntingtin protein.

RNA interference (RNAi) approaches are also being explored to silence the faulty gene.

Stem cell therapy:

Research is being conducted to explore how stem cells could potentially replace damaged neurons and restore lost functions.

Neuroprotective agents:

Drugs targeting mitochondrial function, oxidative stress, and inflammation are being tested to slow disease progression.

CRISPR gene editing:

Early-stage research suggests CRISPR may offer a potential way to correct the genetic mutation responsible for HD.

Conclusion

Huntington’s disease is a devastating neurodegenerative disorder that affects movement, cognition, and mental health. Its genetic basis makes it unique, allowing for definitive diagnosis through genetic testing, yet no cure exists. Current treatment strategies focus on symptom management, with a combination of medication, supportive therapies, and lifestyle modifications aimed at improving quality of life. Ongoing research, particularly in gene therapy and neuroprotection, offers hope for disease-modifying treatments in the future. Increased awareness, early diagnosis, and comprehensive care plans are essential in managing HD effectively. As medical advancements continue, there is optimism that effective treatments—and potentially a cure—will emerge to transform the lives of those affected by Huntington’s disease. Despite the absence of a cure, ongoing research offers hope for disease-modifying treatments. Advances in gene therapy, neuroprotection, and stem cell research hold the potential to slow disease progression or even correct the underlying genetic mutation. Additionally, increased awareness, early intervention, and comprehensive care plans remain vital in supporting individuals affected by HD.

1. Mizuguchi M (1997) Acute necrotizing encephalopathy of childhood: a novel form of acute encephalopathy prevalent in Japan and Taiwan.Brain Dev19:  81-92.  

Indexed at, Google Scholar, Crossref

2. Narra R, Mandapalli A, Kamaraju SK (2015) Acute necrotizing encephalopathy in an adult.J clin l imaging sci 5:  20.  

Indexed at, Google Scholar

3. Wu X, WuW, PanW, WuL, Liu K, et al. (2015) Acute necrotizing encephalopathy: an underrecognized clinicoradiologic disorder.Mediators Inflamm 792578.   

Indexed at, Google Scholar, Crossref

4. Abbas Q, Jafri S, Ishaque S, Jamil M (2017) Acute necrotizing encephalopathy of childhood secondary to dengue infection: A case report from Pakistan. J Pediatr Neurosci 12:165.

Indexed at, Google Scholar, Crossref

5. ItoY, Ichiyama T, Kimura H, Shibata M, Ishiwada N, et al. (1999) Detection of influenza virus RNA by reverse transcription-PCR and proinflammatory cytokines in influenza-virus-associated encephalopathy.J Med Virol58:  420-425.  

Indexed at, Google Scholar, Crossref

6. Neilson DE, Adams MD, Orr CM, Schelling DK, Eiben RM, et al.  (2009) Infection-triggered familial or recurrent cases of acute necrotizing encephalopathy caused by mutations in a component of the nuclear pore, RANBP2.Am J Hum Genet 84: 44-51.   

Indexed at, Google Scholar, Crossref

7. WHO. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control. Geneva: World Health Organization. 2009  

Google Scholar

8. Verma R, SahuR, Holla V (2014) Neurological manifestations of dengue infection: a review.J Neurol Sci 346: 26-34.  

Indexed at, Google Scholar, Crossref

9. Cam BV, Fonsmark L, Hue NB, Phuong NT, Poulsen A, et al.  (2001) Prospective case-control study of encephalopathy in children with dengue hemorrhagic fever.Am J Trop Med Hyg65: 848-851.  

Indexed at, Google Scholar, Crossref

10. Misra UK, Kalita J, Syam UK, Dhole TN (2006) Neurological manifestations of dengue virus infection.Journal of the neurological sciences 244: 117-122.   

               Indexed at, Google Scholar