Neuropsychiatric phenomena in Huntington’s disease

This thesis describes a study on neuropsychiatric symptoms in Huntington’s Disease (HD). This cohort study was performed in HD mutation carriers (both pre-motor symptomatic and motor symptomatic), and a control group of non-carriers that had an a-priori 50% risk for HD. The study started in may 2004 and a second measurement was performed 2 years later. The aim of this study was to study the presence and course of both formal psychiatric disorders and neuropsychiatric symptoms, and to find correlates and predictors associated with the psychiatric phenomena. This cohort study confirms that neuropsychiatric symptoms   frequently occur in patients with HD. We expected a diminished insight in patients with a neuropsychiatric symptoms like irritability, but most patients were aware of their irritability. A strong relationship was found between the presence of psychopathology, cognitive functioning and global daily functioning. Irritability may be an early sign of the disease, but only apathy was closely related to the progression of HD indicating a relationship with the progressive neurodegenerative nature of the disease. However, we also found associations with apathy and irritability, and the use of psychotropic medications.  LUMC / Geneeskund

Self reported stressful life events and exacerbations in multiple sclerosis: prospective study

OBJECTIVE: To study the relation between self reported stressful life events not related to multiple sclerosis and the occurrence of exacerbations in relapsing-remitting multiple sclerosis. DESIGN: Longitudinal, prospective cohort study. SETTING: Outpatient clinic of department of neurology in the Netherlands. PARTICIPANTS: Patients aged 18-55 with relapsing-remitting multiple sclerosis, who could walk with a cane or better (score of 0-6.0 on the expanded disability status scale), and had had at least two exacerbations in 24 months before inclusion in the study. Patients with other serious conditions were excluded. MAIN OUTCOME MEASURE: The risk of increased disease activity as measured by the occurrence of exacerbations after weeks with stressful events. RESULTS: Seventy out of 73 included patients (96%) reported at least one stressful event. In total, 457 stressful life events were reported that were not related to multiple sclerosis. Average follow up time was 1.4 years. Throughout the study, 134 exacerbations occurred in 56 patients and 136 infections occurred in 57 patients. Cox regression analysis with time dependent variables showed that stress was associated with a doubling of the exacerbation rate (relative risk 2.2, 95% confidence interval 1.2 to 4.0, P = 0.014) during the subsequent four weeks. Infections were associated with a threefold increase in the risk of exacerbation, but this effect was found to be independent of experienced stress. CONCLUSION: Stressful events were associated with increased exacerbations in relapsing-remitting multiple sclerosis. This association was independent of the triggering effect of infections on exacerbations of multiple sclerosis

Rating scales for behavioural symptoms in Huntington's Disease: critique and recommendations

Behavioral symptoms are an important feature of Huntington’s disease and contribute to impairment in quality of life. The Movement Disorder Society commissioned the assessment of the clinimetric properties of rating scales in Huntington’s disease in order to make recommendations regarding their use, following previously used standardized criteria. A systematic literature search was conducted to identify the scales used to assess behavioral symptoms in Huntington’s disease. For the purpose of this review, seven behavioral domains were deemed significant in Huntington’s disease: irritability, anxiety, depression, apathy, obsessive-compulsive behaviors, psychosis and suicidal ideation. We included a total of 27 behavioral rating scales, 19 of which were of a single behavioral domain, and the remaining 8 scales included multiple behavioral domains. Three rating scales were classified as “recommended” exclusively for screening purposes: the Irritability Scale for irritability, and the Beck Depression Inventory-II and the Hospital Anxiety and Depression Scale for depression. There were no “recommended” scales for other purposes such as diagnosis, severity or change in time or to treatment. The main challenges identified for assessment of behavioral symptoms in Huntington’s disease are the co-occurrence of multiple behavioural symptoms, the particular features of a behavioral symptom in Huntington’s disease, as well as the need to address stage- and disease-specific features, including cognitive impairment and lack of insight. The committee concluded that there is a need to further validate currently available behavioral rating scales in Huntington’s disease to address gaps in scale validation for specific behavioral domains and purpose of use

Neuropsychiatric phenomena in Huntington’s disease

This thesis describes a study on neuropsychiatric symptoms in Huntington’s Disease (HD). This cohort study was performed in HD mutation carriers (both pre-motor symptomatic and motor symptomatic), and a control group of non-carriers that had an a-priori 50% risk for HD. The study started in may 2004 and a second measurement was performed 2 years later. The aim of this study was to study the presence and course of both formal psychiatric disorders and neuropsychiatric symptoms, and to find correlates and predictors associated with the psychiatric phenomena. This cohort study confirms that neuropsychiatric symptoms   frequently occur in patients with HD. We expected a diminished insight in patients with a neuropsychiatric symptoms like irritability, but most patients were aware of their irritability. A strong relationship was found between the presence of psychopathology, cognitive functioning and global daily functioning. Irritability may be an early sign of the disease, but only apathy was closely related to the progression of HD indicating a relationship with the progressive neurodegenerative nature of the disease. However, we also found associations with apathy and irritability, and the use of psychotropic medications.  </p

Direct Amplification and Genotyping of Dientamoeba fragilis from Human Stool Specimens

Dientamoeba fragilis is a globally occurring parasite that has been recognized as a causative agent of gastrointestinal symptoms. A single-round PCR was developed to detect D. fragilis DNA directly from human stool samples. The genetic diversity of D. fragilis from 93 patients and 6 asymptomatic carriers was examined by PCR followed by restriction fragment length polymorphism and sequencing of part of the small-subunit rRNA gene. The data show that D. fragilis sequences can be studied directly from fecal specimens despite the absence of a cyst stage and without the need for prior culturing. In addition, the results suggest strongly that D. fragilis shows remarkably little variation in its small-subunit rRNA gene

COURSE OF IRRITABILITY, DEPRESSION, AND APATHY IN HUNTINGTON'S DISEASE DURING A 2-YEAR FOLLOW-UP PERIOD

Stress-related psychiatric disorders across the life spa

Hypokinesia in Huntington's Disease Co-occurs with Cognitive and Global Dysfunctioning

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. (C) 2010 Movement Disorder SocietyStress-related psychiatric disorders across the life spa

Correlates of Apathy in Huntington's Disease

The authors aim to study prevalence and clinical correlates of apathy in Huntington's disease. Apathy was defined as an Apathy Scale score >= 14 points in 152 Huntington's disease mutation carriers and 56 noncarriers. Correlates of apathy were analyzed cross-sectionally in mutation carriers using multivariable logistic regression analysis. Forty-nine (32%) Huntington's disease mutation carriers showed apathy compared to none of the noncarriers. After exclusion of 10 depressed patients, apathy was independently associated with male sex, worse global functioning, and higher use of neuroleptics and benzodiazepines. (The Journal of Neuropsychiatry and Clinical Neurosciences 2010; 22:287-294)Stress-related psychiatric disorders across the life spa