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Background: Huntington's Disease (HD) is an autosomal dominant, progressive neuropsychiatric illness caused by CAG repeat expansion. The high penetrance of the mutation and limited treatment options make it challenging for patients and caretakers. Proper counseling enables families to cope better and make informed life choices., Objective: To explore some complex issues in genetic counseling and testing (GCAT) in HD., Materials and Methods: Vignettes of patients who underwent genetic testing along with pre and post-test counseling at our GCAT clinic., Results: Case 1: Diagnosis of juvenile HD meant that the healthy parent was an obligate carrier of the mutation. Case 2: Consanguinity resulted in a dense prevalence of HD and >50% risk for the progeny. Case 3: Predictive testing in youth with healthy parents but affected uncles and aunts revealed a HD expansion., Conclusions: HD can present with complex inheritance patterns and proper counseling is necessary for better outcomes., Competing Interests: None

Background: Huntington's disease (HD) is a progressive neurodegenerative disorder characterised by chorea, cognitive impairment, psychiatric and behavioral disturbances. Sleep disturbances including reduced REM sleep have been observed in HD., Objectives: The aim of the study was to study the polysomnography findings in HD and to assess whether oculomotor abnormalities are associated with poor REM sleep., Methods: Twenty-nine genetically confirmed HD patients underwent clinical evaluation including extraocular movement and OKN examination. Twenty-six patients and 15 controls underwent overnight video polysomnography (VPSG)., Results: VPSG of 23 HD patients and 13 controls were considered for analysis. Compared to controls, HD patients had higher median wake period and higher WASO percentage (p = 0.005). REM sleep percentage was reduced significantly in HD in comparison to controls (p < 0.001). Out of 23 patients, only two patients had REM sleep above 20% while 14 patients had REM sleep percentage less than 15%. Poor horizontal OKN (grades 2 and 3) was associated with the presence of low REM sleep percentage (REM sleep less than 15%) (p = 0.02). Low REM sleep was also associated with severe illness (UHDRS) (p = 0.038)., Conclusion: An association between decreased REM sleep and OKN abnormalities indicate that EOM abnormalities seen in HD could lead to errors in scoring REM sleep. To understand the actual degree of decreased REM sleep percentage will require additional parameters in AASM guidelines to score REM sleep in patients with EOM abnormalities like that seen in HD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Huntington's disease (HD), an inherited, often late-onset, neurodegenerative disorder, is considered to be a rare, orphan disease. Research into its genetic correlates and services for those affected are inadequate in most low-middle income countries, including India. The apparent 'incurability' often deters symptomatic and rehabilitative care, resulting in poor quality of life and sub-optimal outcomes. There are no studies assessing disease burden and outcomes from India., Methods: We attempted to evaluate individuals diagnosed to have HD at our tertiary-care center between 2013 and 2016 for clinical symptoms, functionality, mortality, follow up status through a structured interview, clinical data from medical records and UHDRS-TFC scoring., Results: Of the 144 patients, 25% were untraceable, and another 17 (11.8%) had already died. Mean age at death and duration of illness at the time of death, were 53 years and 7 years respectively, perhaps due to suicides and other comorbidities at an early age. The patients who could be contacted (n = 81) were assessed for morbidity and total functional capacity (TFC). Mean CAG repeat length and TFC score were 44.2 and 7.5 respectively. Most individuals (66%) were in TFC stage I and II and could perhaps benefit from several interventions. The TFC score correlated inversely with duration of illness (p < 0.0001). The majority were being taken care of at home, irrespective of the physical and mental disability. There was a high prevalence of psychiatric morbidity (91%) including suicidal tendency (22%). Three of the 17 who died had committed suicide, and several other families reported suicidal history in other family members. Only about half the patients (57%) maintained a regular clinical follow-up., Conclusions: This study demonstrates the poor follow-up rates, significant suicidality and other psychiatric symptoms, sub-optimal survival durations and functional outcomes highlighting the need for holistic care for the majority who appear to be amenable to interventions.

Background: Recent advances in neurophysiological techniques have contributed to our understanding of the pathophysiology of Huntington's disease (HD). Studies of the motor cortical excitability and central motor pathways have shown variable results., Objectives: Our aims were to evaluate the cortical excitability changes in HD using transcranial magnetic stimulation (TMS) and correlate the changes with cognitive impairment., Methods: The study included 32 HD patients and 30 age- and gender-matched controls. The demographic and clinical profiles of the patients were recorded. All subjects were evaluated by TMS and resting motor threshold (RMT), central motor conduction time (CMCT), silent period (SP), short-interval intracortical inhibition (SICI), and intracortical facilitation were determined. A battery of neuropsychological tests was administered to all subjects., Results: The mean age of the patients was 42.1±14.1 years, and that of controls 39.4±12.4 years (p=0.61). There was no significant difference in RMT and CMCT between the two groups. There was a mild prolongation of the contralateral SP in HD, but it was not significant. SICI was significantly reduced in HD (p<0.0001). A significant impairment in attention, verbal fluency, executive function, visuospatial function, learning, and memory was observed in HD patients. However, there was no correlation between cortical excitability changes and cognitive impairment., Conclusions: TMS is a valuable method of evaluating cortical excitability changes in HD. These patients have reduced SICI and significant impairment of cognition in multiple domains.

Huntington's disease (HD) is characterised by movement disorders, cognitive impairments, and psychiatric problems. The abnormal generation of reactive oxygen species and the resulting oxidative stress-induced mitochondrial damage in neurons upon CAG mutations in the HTT gene have been hypothesized as the contributing factors of neurodegeneration in HD. The potential use of antioxidants against free radical toxicity has been an emerging field in the management of ageing and many neurodegenerative disorders. Neural stem cells derived adult neurogenesis represents the regenerative capacity of the adult brain. The process of adult neurogenesis has been implicated in the cognitive functions of the brain and is highly modulated positively by different factors including antioxidants. The supportive role of antioxidants to reduce the severity of HD via promoting the functional neurogenesis and neuroprotection in the pathological adult brain has great promise. This review comprehends the recent studies describing the therapeutic roles of antioxidants in HD and other neurologic disorders and highlights the scope of using antioxidants to promote adult neurogenesis in HD. It also advocates a new line of research to delineate the mechanisms by which antioxidants promote adult neurogenesis in HD., Competing Interests: The authors have declared that no competing interests exist.

Background: Huntington's disease (HD) is a genetically mediated neurodegenerative disorder characterized by presence of involuntary movements, behavioral problems and cognitive dysfunctions. Though few patients with HD may have behavioral symptoms at onset of the disease, studies comparing patients with behavioral symptoms at the onset of HD with those having motor symptoms are sparse., Objective: Objective of this study is to determine the differences in the demographic and genetic characteristics of patients with behavioral symptom at the onset of HD from those with motor symptoms., Methods: A chart review of 92 patients with HD who had attended the neurology outpatient clinics of National Institute of Mental Health and Neurosciences, India was done. Demographic and genetic characteristics of HD patients with onset of the disease with initial behavioral symptoms (HD-iB) were compared with patients with onset of the disease with initial motor symptoms (HD-iM)., Results: The principal findings in our study were (i) higher proportion of patients with HD-iB had a positive family history of HD, (ii) maternal inheritance of HD was more frequent among those with HD-iB, and (iii) There is no significant difference between the CAG repeat length between HD-iB and HD-iM groups., Conclusion: Presence of family history of HD especially inheritance of HD from mother may be associated with behavioral symptoms at the onset of HD. CAG repeat length in patients with HD-iB does not differ from those with HD-iM.

Repetitive transcranial magnetic stimulation (rTMS) has been used therapeutically for reducing choreiform movements in patients with Huntington disease. There have been case studies reporting improvement in choreiform movements with administration of low-frequency rTMS lasting for a brief period. We report a case series where application of 7 consecutive sessions of bilateral low-frequency rTMS over the scalp area corresponding to supplementary motor area in patients with severe Huntington chorea did not reduce the intensity of choreiform movements even transiently. Hence, the proposed role of rTMS in reducing intensity of choreiform movements by altering neuronal plasticity may not hold true in severe cases.

Objective: Genetic counseling for individuals undergoing presymptomatic testing is lacking in India although testing is easily available. This has an impact on family members of Huntington's disease (HD), an autosomal dominant disease, wherein the age at onset of symptoms varies., Aim: We examine if attitudes differ towards presymptomatic testing for HD amongst HD family members, physicians and laypersons., Materials and Methods: A modified questionnaire enquiring about opinions on various personal, family, social and future health care with regards to presymptomatic testing of HD was designed. A physician explained briefly about HD and presymptomatic testing of HD and recorded responses of unaffected family members of HD (n=25) and laypersons (n=50). Medical doctors (n=50) answered the questionnaire based on their knowledge of HD., Results: HD family members, Medical doctors and laypersons were similar in their opinion to undergo the testing. Majority (60%) of HD family members did not wish to communicate test results with their friends when compared to the other two groups. Medical doctors and HD family members were more concerned about certainty of developing disease when the test results are positive. Majority (80%) of Medical doctors and less than half in the other groups felt that their decision to have a child would strongly depend on test results. Large proportion (80%) of HD family members did not wish to report their test results to their employers., Conclusions: Individuals with knowledge about HD and the test differ in their decision of sharing test results and reproductive choices.

Huntington's disease is characterized by choreic movements, psychiatric disorders, striatal atrophy with selective small neuronal loss, and autosomal dominant inheritance. The genetic abnormality is CAG expansion in Huntingtin gene. Newer therapeutic strategies are evolving to treat this progressive disorder. The neuroprotective agents are one such group of drugs being tried. Lithium has been used to treat Huntington's disease in the past due to its neuroprotective effects. Though the precise mechanism of action is not clear, Lithium can directly or indirectly modulate proteins involved in neuronal survival/differentiation which may account for its neuroprotective effects. We report three patients with Huntington's disease in whom Lithium prevented the progression of chorea and also helped stabilize mood. [ABSTRACT FROM AUTHOR]