Gene/Protein Disease Symptom Drug Enzyme Compound
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 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Besides chorea, hypokinesia is an important motor disturbance in Huntington's disease (HD) but its clinical, neuropsychiatric, and cognitive functioning correlates are largely unknown. This cross-sectional study investigates correlates of hypokinesia in HD and its effect on global functioning. Among 150 HD gene carriers, 96 patients were clinically motor manifest. Hypokinesia was assessed using the motor section of the Unified Huntington's Disease Rating Scale and global functioning was measured using the Total Functioning Capacity (TFC) scale. Neuropsychiatric measures included the Apathy Scale and the Composite International Diagnostic Interview for diagnosis of depression. The Mini Mental State Examination (MMSE) and a composite executive cognitive measure were used to assess global and executive cognitive functioning, respectively. Compared with 45 patients with no or mild hypokinesia, 51 patients with moderate to severe hypokinesia showed a significant difference in most clinical and neuropsychiatric variables and had worse cognitive functioning scores. However, using forward logistic regression analysis, poor executive cognitive functioning was the only independent correlate of hypokinesia (OR 7.33; 95% CI: 2.82-19.0; P < 0.001). Hypokinesia score was inversely associated with the TFC score (P < 0.001), also after adjusting for chorea, use of antipsychotics, apathy, and global and executive cognitive functioning. In conclusion, the presence of moderate to severe hypokinesia in HD patients co-occurs with executive cognitive dysfunction and adversely affects global functioning.
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PMID:Hypokinesia in Huntington's disease co-occurs with cognitive and global dysfunctioning. 2062 65

Huntington disease (HD) is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia. Prevalence in the Caucasian population is estimated at 1/10,000-1/20,000. Mean age at onset of symptoms is 30-50 years. In some cases symptoms start before the age of 20 years with behavior disturbances and learning difficulties at school (Juvenile Huntington's disease; JHD). The classic sign is chorea that gradually spreads to all muscles. All psychomotor processes become severely retarded. Patients experience psychiatric symptoms and cognitive decline. HD is an autosomal dominant inherited disease caused by an elongated CAG repeat (36 repeats or more) on the short arm of chromosome 4p16.3 in the Huntingtine gene. The longer the CAG repeat, the earlier the onset of disease. In cases of JHD the repeat often exceeds 55. Diagnosis is based on clinical symptoms and signs in an individual with a parent with proven HD, and is confirmed by DNA determination. Pre-manifest diagnosis should only be performed by multidisciplinary teams in healthy at-risk adult individuals who want to know whether they carry the mutation or not. Differential diagnoses include other causes of chorea including general internal disorders or iatrogenic disorders. Phenocopies (clinically diagnosed cases of HD without the genetic mutation) are observed. Prenatal diagnosis is possible by chorionic villus sampling or amniocentesis. Preimplantation diagnosis with in vitro fertilization is offered in several countries. There is no cure. Management should be multidisciplinary and is based on treating symptoms with a view to improving quality of life. Chorea is treated with dopamine receptor blocking or depleting agents. Medication and non-medical care for depression and aggressive behavior may be required. The progression of the disease leads to a complete dependency in daily life, which results in patients requiring full-time care, and finally death. The most common cause of death is pneumonia, followed by suicide.
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PMID:Huntington's disease: a clinical review. 2117 77

The neuroacanthocytoses are a group of disorders characterised by peripheral blood acanthocytes, central nervous system as well as neuromuscular symptoms. These disorders uniformly result in pathology in the basal ganglia, which account for the characteristic motor symptoms such as chorea or dystonia, but may also account for the apparent elevated rates of major mental disorders in these syndromes. Elevated rates of dysexecutive syndromes, obsessive-compulsive disorder, depression and schizophrenia-like psychosis appear to occur in chorea-acanthocytosis, McLeod's syndrome, pantothenate kinase-associated neurodegeneration, and Huntington's disease-like 2. Disruptions to key frontostriatal loops secondary to pathology in the striatum and pallidum appear to predispose individuals to major neuropsychiatric syndromes; however, treatment can be instituted for a number of these manifestations, which lessens the overall burden of disease in neuroacanthocytosis patients and their families.
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PMID:The neuropsychiatry of neuroacanthocytosis syndromes. 2123 98

A variety of neurodegenerative diseases can underlie dementia syndromes. In addition to Alzheimer's disease (AD) and its prodromal stages, these include in particular frontotemporal degeneration, Lewy body dementia and Parkinson's dementia, progressive supranuclear paresis, corticobasal degeneration and chorea Huntington. Although not classified as a neurodegenerative brain disease, for all clinical diagnoses there must be a differential diagnostic separation from vascular forms of dementia. Furthermore an exclusion of affective disorders, such as minor depression is necessary from a clinical psychiatric perspective. Moreover the preclinical stages of AD often present with uncharacteristic symptoms. Especially affective symptoms can occur in addition to initial cognitive deficits such as memory decline. In summary, clinical and neuropsychological procedures together with functional imaging techniques allow a detailed diagnostic assessment of neurodegenerative dementia syndromes which can be additionally supported by neurochemical biomarkers and innovative imaging procedures, such as diffusion imaging or magnetic resonance spectroscopy.
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PMID:[Symptoms and imaging diagnostics of neurodegenerative dementia]. 2146 5

It is generally believed that treatments are available to manage chorea in Huntington's disease (HD). However, lack of evidence prevents the establishment of treatment guidelines. The HD chorea research literature fails to address the indications for drug treatment, drug selection, drug dosing and side effect profiles, management of inadequate response to a single drug, and preferred drug when behavioral symptoms comorbid to chorea are present. Because there is lack of an evidence base to inform clinical decision-making, we surveyed an international group of experts to address these points. Survey results showed that patient stigma, physical injury, gait instability, work interference, and disturbed sleep were indications for a drug treatment trial. However, the experts did not agree on first choice of chorea drug, with the majority of experts in Europe favoring an antipsychotic drug (APD), and a near equal split in first choice between an APD and tetrabenazine (TBZ) among experts from North America and Australia. All experts chose an APD when comorbid psychotic or aggressive behaviors were present, or when active depression prevented the use of TBZ. However, there was agreement from all geographic regions that both APDs and TBZ were acceptable as monotherapy in other situations. Perceived efficacy and side effect profiles were similar for APDs and TBZ, except for depression as a significant side effect of TBZ. Experts used a combination of an APD and TBZ when treatment required both drugs for control of chorea and a concurrent comorbid symptom, or when severe chorea was inadequately controlled by either drug alone. The benzodiazepines (BZDs) were judged ineffective as monotherapy but useful as adjunctive therapy, particularly when chorea was exacerbated by anxiety. There was broad disagreement about the use of amantadine for chorea. Experts who had used amantadine described its benefit as small and transient. In addition to survey results, this report reviews available chorea studies, and lastly presents an algorithm for the treatment of chorea in HD which is based on expert preferences obtained through this international survey.
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PMID:An International Survey-based Algorithm for the Pharmacologic Treatment of Chorea in Huntington's Disease. 2197 81

OPINION STATEMENT: There is no specific treatment for Huntington's disease (HD). Its many symptoms of motor, psychiatric, and cognitive deterioration are managed with symptomatic relief, rehabilitation, and support. The only drug approved by the US Food and Drug Administration (FDA) for the treatment of HD is an antichoreic agent, tetrabenazine, but this drug is used sparingly because of uneasiness regarding its propensity to cause depression and suicidality in this population, which is already at risk for these complications. Neuroleptics are still first-line treatments for chorea accompanied by comorbid depression and/or behavioral or psychotic symptoms, as is often the case. Psychiatric features, which have a significant impact on a patient's professional and personal life, often become the major focus of management. In addition to neuroleptics, commonly used medications include antidepressants, mood stabilizers, anxiolytics, and psychostimulants. In contrast, few treatment options are available for cognitive impairment in HD; this remains an important and largely unmet therapeutic need. HD patients typically lack insight into their disease manifestations, failing to recognize their need for treatment, and possibly even arguing against it. Multipurpose medications are employed advantageously to simplify the medication regimen, so as to facilitate compliance and not overwhelm the patient. For example, haloperidol can be prescribed for a patient with chorea, agitation, and anorexia, rather than targeting each symptom with a different drug. This approach also limits the potential for adverse effects, which can be difficult to distinguish from the features of the disease itself. With HD's complexity, it is best managed with a multidisciplinary approach that includes a movement disorders specialist, a genetic counselor, a mental health professional, a physical therapist, and a social worker for support and coordination of services. As the disease progresses, there may be need for other specialists, such as a speech and occupational therapist, a nutritionist for weight loss, and ultimately, a palliative care specialist.
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PMID:Therapeutics in Huntington's Disease. 2231 29

It is generally believed that treatments are available to manage chorea in Huntington's disease (HD). However, lack of evidence prevents the establishment of treatment guidelines. The HD chorea research literature fails to address the indications for drug treatment, drug selection, drug dosing and side effect profiles, management of inadequate response to a single drug, and preferred drug when behavioral symptoms comorbid to chorea are present. Because there is lack of an evidence base to inform clinical decision-making, we surveyed an international group of experts to address these points. Survey results showed that patient stigma, physical injury, gait instability, work interference, and disturbed sleep were indications for a drug treatment trial. However, the experts did not agree on first choice of chorea drug, with the majority of experts in Europe favoring an antipsychotic drug (APD), and a near equal split in first choice between an APD and tetrabenazine (TBZ) among experts from North America and Australia. All experts chose an APD when comorbid psychotic or aggressive behaviors were present, or when active depression prevented the use of TBZ. However, there was agreement from all geographic regions that both APDs and TBZ were acceptable as monotherapy in other situations. Perceived efficacy and side effect profiles were similar for APDs and TBZ, except for depression as a significant side effect of TBZ. Experts used a combination of an APD and TBZ when treatment required both drugs for control of chorea and a concurrent comorbid symptom, or when severe chorea was inadequately controlled by either drug alone. The benzodiazepines (BZDs) were judged ineffective as monotherapy but useful as adjunctive therapy, particularly when chorea was exacerbated by anxiety. There was broad disagreement about the use of amantadine for chorea. Experts who had used amantadine described its benefit as small and transient. In addition to survey results, this report reviews available chorea studies, and lastly presents an algorithm for the treatment of chorea in HD which is based on expert preferences obtained through this international survey.
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PMID:An International Survey-based Algorithm for the Pharmacologic Treatment of Chorea in Huntington's Disease. 0

Huntington's disease (HD) is a genetically neurodegenerative disease, affecting the central nervous system and leading to mental and motor dysfunctions. To date, there is no cure for HD; as a result, HD patients gradually suffer devastating symptoms, such as chorea, weight loss, depression and mood swings, until death. According to previous studies, the exon 1 region of the huntingtin (HTT) gene with expanded CAG trinucleotide repeats plays a critical role in causing HD. In vitro studies using exon 1 of HTT fused with green fluorescent protein (GFP) gene have facilitated discovering several mechanisms of HD. However, whether this chimera construct exerts similar functions in vivo is still not clear. Here, we report the generation of transgenic mice carrying GFP fused with mutant HTT exon 1 containing 84 CAG trinucleotide repeats, and the evaluation of phenotypes via molecular, neuropathological and behavioral analyses. Results show that these transgenic mice not only displayed neuropathological characteristics, observed either by green fluorescent signals or by immunohistochemical staining, but also progressively developed pathological and behavioral symptoms of HD. Most interestingly, these transgenic mice showed significantly differential expression levels of nuclear aggregates between cortex and striatum regions, highly mimicking selective expression of mutant HTT in HD patients. To the best of our knowledge, this is the first report showing different nuclear diffusion profiling in mouse models with transgenic mice carrying the exon 1 region of mutant HTT. Our model will be beneficial for tracing the expression of mutant HTT and accelerating the understanding of selective pathological progression in HD.
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PMID:Significantly differential diffusion of neuropathological aggregates in the brain of transgenic mice carrying N-terminal mutant huntingtin fused with green fluorescent protein. 2242 49

The management of choreic disorders presents significant challenges, including identifying the etiology of the disorder, treating and preventing motor symptoms, and managing a range of other neurologic and behavioral complications. Chorea may occur in several neurodegenerative, genetic, or drug-related conditions, and a thorough diagnostic evaluation is needed to identify the specific underlying causes. Some choreic disorders have specific treatable underlying etiologies, such as vitamin B(12) deficiency or drug-induced dyskinesia. Autoimmune disorders such as Sydenham chorea may be treated with penicillin, corticosteroids, intravenous immunoglobulin, or plasma exchange. Heredodegenerative choreas such as Huntington disease often respond to treatment with tetrabenazine or amantadine. Many other agents may be used nonspecifically for symptom control, including benzodiazepines, neuroleptics, and antiepileptic medications. In addition to motor symptoms, patients with Huntington disease or other choreic disorders often experience increasing depression, bradykinesia, cognitive impairment, aggressive behaviors, and other complications as the disease progresses. Caring for the caregiver is also a significant concern in the long-term treatment of choreic disorders.
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PMID:Comprehensive treatment of Huntington disease and other choreic disorders. 2276 Dec 68

Spinocerebellar ataxias are a group of rare and heterogeneous autosomal dominant disorders characterized by progressive ataxia and other features. Spinocerebellar ataxia 17 (SCA17) is one of the 32 subtypes described to date and is secondary to CAG/CAA repeat expansion in the gene coding for the TATA-box binding protein (TBP). SCA17 is clinically heterogeneous and typically presents with slowly evolving ataxia, dysarthria, dementia, depression, and other movement disorders such as chorea. More than 41 CAG/CAA repeats are considered diagnostic of SCA17, with more than 49 being associated with full penetrance. We report one patient presenting with isolated rapidly evolving ataxia who was found to have 44 CAG/CAA repeats in the TBP gene. This suggests that, while SCA17 typically slowly progresses over years, its repertoire of presentations should be expanded to include rapidly progressive isolated ataxia resembling paraneoplastic disorders or prion disease.
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PMID:From normal gait to loss of ambulation in 6 months: a novel presentation of SCA17. 2347 85


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