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-Hajrah Gul

A medical diagnosis is the first step towards curing a disease. However, in the case of a neurodegenerative disease such as Huntington’s Disease (HD), a diagnosis is not a step towards riding oneself of HD but a step towards seeking symptomatic treatments. Once diagnosed properly a patient can take the precautions needed and seek out the treatments for a better socially, physically, and psychologically healthy life versus one whom is not diagnosed. The diagnosis will further allow for the permanent monitoring of an individual’s health status as it pertains to HD. The medical diagnosis of HD is initially based on the presence of its physical symptoms. It can be assessed through one’s family history and confirmed via genetic testing or even prenatal testing. A confirmed diagnosis will allow for either pharmaceutical treatments or rehabilitation options as remedies to particular symptoms of the disease. For symptoms like movement disorders or emotional irregularity, medication can be prescribed 1. Though the medications have proven to be successful in alleviating some symptoms, they can cause several unwanted side effects 1. Fortunately there is also another option of treatment such as therapy which encompasses multiple interventions that can aid the patient in adapting to the drastic changes in their life caused by Huntington’s disease 1.






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1.1 Clinical Assessment


The verdict of HD is initially determined by a complete clinical diagnosis. It is based on the assessment of present extrapyramidal movement disorders further confirmed via neurologic evaluation 2. The combination of physical and neurologic examination entails the detection of characteristic symptoms of HD (i.e. chorea, behavioral and emotional disturbances, and cognitive decline) 2. Available studies to date suggest a reduction of the white matter volumes in the brain of individuals predictive of pending diagnosis 3. Furthermore, the neurologic assessment relies on the Unified Huntington’s Disease Rating Scale (UHDRS). UHDRS is divided into measuring subscales including assessment of motor and cognitive function, behavioral symptoms and functional capacity 2. For the characterization of dementia the Mini-Mental State Exam and the Dementia Rating Scale have been used. These tests are also used in clinical trials to further establish the implicated biomarkers 2.

The family history is taken into consideration during clinical assessment since it allows for the prediction of whether the HD symptoms will develop earlier or later in life 2. The timeframe for the development of HD symptoms relies on the quantity of the CAG repeats. As the HTT gene is passed down through families, the quantity of CAG repeats increases and symptoms develop progressively at younger ages 4. Longer CAG repeats are indicative of an earlier onset, accounting for up to 50–70% of variance in age of onset 4.

1.2 Neuroimaging


Part of the diagnosis may also include brain-imaging tests such as computed tomography (CT scan) and magnetic resonance imaging (MRI). CT scans and MRI are important diagnostic tools that are used in conjunction with clinical symptoms and the patient’s family history. Hence by no means can the imagining tests be used to diagnose HD in isolation considering that other conditions may also cause similar changes on imaging tests 2. Furthermore, Neuroimaging techniques have proven to be successful in detecting altered structure or physiology in HD patients sometimes many years prior to the disease onset 5. In particular structural neuroimaging studies in patients with HD have demonstrated atrophy of the striatum and white matter 5. The similar atrophy is evident even 15 to 20 years before the predicted disease onset in premanifest mutation carriers 5. The neuroimaging techniques have allowed the implication of accelerated change in total brain volume including the cerebral white matter, striatal, and ventricular volume in individuals with Huntington’s disease 3,5.



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1.3 Genetic Testing


Genetic Testing is a DNA based technique used to test for genetic disorders. In the diagnosis of HD, apart from neurologic evaluation genetic testing is also pertinent. It is performed through the quantification of the CAG repeat length in the HTT gene 6. For the verification of HD presence a positive genetic test is acquired for the CAG repeat in the range of greater than 39 repeats 6. The genetic test can be further divided into the diagnostic testing and the predictive testing 6.

The diagnostic testing allows either a confirmation or refutation of the presence of HD in a patient who is already demonstrating symptoms suggestive of HD 6.

Predictive testing is done when there is an absence of symptoms suggestive of HD but the family history is indicative of HD risk in a patient. This test determines if the individual is an expanded HTT gene carrier and will develop HD in the near future 6. A positive test indicates that they will certainly develop HD at some point in the future without indicating when HD onset will occur or what the symptoms will be like 6. The test is usually done in combination with pretest and post test counselling. By use of predictive genetic testing, the chances of preventing or delaying disease onset increase since it allows the identification of individuals who carry the gene defect prior to the development of symptoms 6.


1.4 Prenatal Testing


The prenatal diagnosis is carried out for a fetus by obtaining the fetal genetic material via chronic villus sampling between 11 and 13 weeks of pregnancy 6. This test is done in conjunction with pretest counselling to ensure that the potential parents consent to the termination of the pregnancy if their fetus is found to carry an expanded HTT gene 6.





Treatments
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2.1 Therapy Treatment


2.1a Psychotherapy



Psychotherapy can be conducted by a psychiatrist or a clinical psychologist. It can aid in minimizing the effects of many psychiatric symptoms such as depression, anxiety, compulsive behaviour and emotional dysregulation pertaining to HD 7. The therapist can provide coping strategies for behavioral problems. The therapist can facilitate quality communication of the individual with family members and peers 7. Psychotherapy can overall help manage subjective distress caused by the disease 7.

2.1b Physical Therapy


Physical therapy can be helpful in several aspects of HD treatment. It can aid in walking and balance to preserve mobility and to reduce the occurrence of falls 8. If an individual is experiencing immense trouble in movement, physical therapy can allow for the assessment of specific walking aids and wheelchairs. The physiotherapist can further provide recommendations for a long term exercise routine 8. Although it is difficult for patients to learn new exercises due to progressive cognitive decline new exercises can still be helpful if started earlier in the disease. It is necessary to achieve long term maintenance from physical therapy rather than short term improvement 8.

2.1c Speech therapy


Dysarthria and dysphagia are prominent conditions of HD, and aspiration pneumonia is a leading cause of death for these patients 8. The speech therapist can educate on possible beneficial dietary modifications and swallowing strategies in order to lessen the prevalence of dysphagia 8. It is also important to seek speech therapy since it aids the preservation of clear articulation for successful communication. The speech therapist can further evaluate the action of swallowing and recommend when a feeding tube is to be considered 8.

2.1d Occupational Therapy


An occupational therapist can make suggestions to ensure the safety of an HD patient by assessing their need for assistive devices and evaluating their accommodation to prevent excessive falls 8. Occupational therapist is needed since the spatial awareness in an HD patient is impaired and once the impairment occurs in combination with involuntary movements and imbalance it increases the risk for trauma 8.


2.2 Drug Treatment


2.2a Movement disorder medication


The initiation of treatment for motor symptoms is taken into consideration once they become tedious and start to interfere with everyday functioning. The treatment is not aimed to completely eradicate the involuntary movements but it is to decrease their severity. Totally abolishing the movements may cause worsening of imbalance and further impairment 8.

The main drug used to treat chorea is Tetrabenazine, it is the only agent approved by the FDA for the treatment of HD 8. In a study, it was shown that the use of tetrabenazine (≤100 mg/day) was associatedwith a 23.5% reduction (from baseline) in chorea, using theUnified Huntington Disease Rating Scale 9.

2.2b Psychiatric disorder medication


Antipsychotics are the top option for reducing psychosis associated with movement disorder. Antipsychotics serve as a multi-purpose remedy for anxiety, weight loss, sleep dysfunction and irritability in conjunction with chorea 8.
  • Olanzapinen—can be used to control movement disorders, anxiety, irritability, weight loss, depression and sleep dysfunction 8. In a study conducted on nine patients with HD, the use of olanzapine (≤30 mg/day) showed a significant improvement according to the UHDRS 10. In another study of 11 patients with HD, the use of olanzapine (5 mg/day) resulted in a reduction of depression, irritability, anxiety, and obsessive behavior 11.
  • Risperidone—is proven to reduce abnormal movements and cause a general improvement in everyday activities. It is as well used to treat anxiety, obsessive symptoms, depression, psychosis, and sleep dysfunction 8. In a retrospective chart review for the course of a year, treatment effects of risperidone were recorded for 17 patients versus 12 patients that were not being treated. The results showed that an average dosage of 2.5mg resulted in a significant improvement of psychosis and allowed the stabilization of chorea while the untreated patients showed worsening of motor symptoms and no psychiatric improvement 12.
  • Haloperidol—is useful in the treatment of cognitive disorders such as aggression, delusions, hallucinations and agitation. Haloperidol is proved to be similar to tetrabenazine in regards to improvement in chorea 8.
  • Clonazepam—is used in management of myoclonus (muscle jerks), dystonia, rigidity, spasticity, and rapid eye movement (REM) behavior disorder 8. Clonazepam has a potential for abuse and so it should be used infrequently for the treatment of temporary stress associated worsening of chorea and anxiety 8.
  • Valproic acid—is used as a remedy for irritability, myoclonus and seizures 8. In a case series of eight HD patients, valproic acid (900–2,700mg/day) was found to stabilize dramatic mood in five patients and it was also found to reduce myoclonus, with UHDRS score improvement 13.
  • Quetiapine—is generally used to treat psychiatric symptoms and not chorea 8. In a study, quetipine (dosage of 600mg/day) was found to reduce irritability, agitation, and delusions without worsening motor symptoms in HD patients 14.
  • Antidepressants—SSRIs and velafaxine are commonly used to treat HD depression 8. In a study evaluating venlafaxine effect on HD depression, it revealed that the depression scores for the HD patients had improved from baseline 15.

2.2c Side Effects


Unfortunately, all the drugs required to treat symptoms of Huntington's Disease have moderate to severe adverse secondary effects. The following side effects have been implicated with the drugs mentioned 8:

Tetrabenazine
Depression, anxiety, sedation, extrapyramidal symptoms, insomnia, imbalance.
Olanzapine
Sedation, weight gain, extrapyramidal symptoms, elevated prolactin and transaminases, postural hypotension, risk of metabolic syndrome
Risperidone
Increased appetite, extrapyramidal symptoms, insomnia, vomiting, headache, coughing, constipation, postural hypotension
Haloperidol
Extrapyramidal symptoms, anticholinergic effects, weight gain
Clonazepam
Somnolence, decreased coordination, cognitive impairment. This drug has a potential for abuse and should be taken with caution
Quetiapine
Somnolence, headache, agitation, hypotension, weight gain, dry mouth, increased triglycerides and cholesterol
Valproic acid
Vomiting, abdominal pain, weight gain, somnolence, headache, blood dyscrasia, hyperammonemia, dizziness
Antidepressants
Nausea and irritability are common





References

  1. Huntington's disease: Treatments and drugs - MayoClinic.com. (n.d.). Mayo Clinic. Retrieved March 6, 2012, from http://www.mayoclinic.com/health/huntingtons-disease/DS00401/DSECTION=treatments-and-drugs
  2. Paulsen, J. (2011). Cognitive Impairment in Huntington Disease: Diagnosis and Treatment. Current neurology and neuroscience reports,11(5), 474-483.
  3. Paulsen, J. (2009). Functional imaging in Huntington's disease. Experimental Neurology, 216, 272-277.
  4. Ross, C., & Tabrizi, S. (2011). Huntington’s disease: from molecular pathogenesis to clinical treatment.Lancet Neurol, 10, 83-98.
  5. Weir, D., Sturrock, A., & Leavitt, B. (2011). Development of biomarkers for Huntington’s disease. The Lancent Neurology, 10(6), 573-590.
  6. Brotchie, J., & Bezard, E. (2011).Pathophysiology, pharmacology and biochemistry of dyskinesia. Burlington: Elsevier Science.
  7. Psychotherapy Facts, information, pictures | Encyclopedia.com articles about psychotherapy. (n.d.).Encyclopedia.com | Free Online Encyclopedia. Retrieved April 2, 2012, from http://www.encyclopedia.com/topic/psych
  8. Killoran, A., & Biglan, K. (2012). Therapeutics in Huntington’s Disease.Current Treatment Options in Neurology, 14, 137-149.
  9. Huntington Study Group. (2006). Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology, 66, 366-72.
  10. Bonelli RM, Mahnert FA, Niederwieser G. (2002). Olanzapine for Huntington’s disease: an open label study. Clin Neuropharmacol, 25, 263–5.
  11. Squitieri F, Cannella M, Piorcellini A, et al. (2001). Shortterm effects of olanzapine in Huntington’s disease. Neuropsychiatry Neuropsychol Behav Neurol, 14, 69–72.
  12. Duff K, Beglinger LJ, O’Rourke ME, et al. (2008). Risperidone and the treatment of psychiatric, motor, and cognitive symptoms in Huntington’s disease. Ann Clin Psychiatry, 20, 1–3.
  13. Saft C, Lauter T, Kraus PH, et al. (2006). Dose-dependent improvement of myoclonic hyperkinesia due to Valproic acid in eight Huntington’s Disease patients: a case series. BMC Neurol, 6, 11.
  14. Alpay M, Koroshetz WJ. (200). Quetiapine in the treatment of behavioral disturbances in patients with Huntington’s disease. Psychosomatics, 47, 70–2.
  15. Holl AK, Wilkinson L, Painold A, et al. (2010). Combating depression in Huntington’s disease: effective antidepressive treatment with venlafaxine XR. Int Clin Psychopharmacol, 25, 46–50.