Weight-loss is an integral part of Huntington's disease (HD) that can start before the onset of motor symptoms. Investigating the underlying pathological processes may help in the understanding of ...this devastating disease as well as contribute to its management. However, the complex behavior and associations of multiple biological factors is impractical to be interpreted by the conventional statistics or human experts. For the first time, we combine a clinical dataset, expert knowledge and machine intelligence to model the multi-dimensional associations between the potentially relevant factors and weight-loss activity in HD, specifically at the premanifest stage. The HD dataset is standardized and transformed into required knowledge base with the help of clinical HD experts, which is then processed by the class rule mining and self-organising maps to identify the significant associations. Statistical results and experts' report indicate a strong association between severe weight-loss in HD at the premanifest stage and measures of certain cognitive, psychiatric functional ability factors. These results suggest that the mechanism underlying weight-loss in HD is, at least partly related to dysfunction of certain areas of the brain, a finding that may have not been apparent otherwise. These associations will aid the understanding of the pathophysiology of the disease and its progression and may in turn help in HD treatment trials.
Parkinson’s Disease (PD) is a complex neurodegenerative disorder characterized by a spectrum of motor and non-motor symptoms, prominently featuring the freezing of gait (FOG), which significantly ...impairs patients’ quality of life. Despite extensive research, the precise mechanisms underlying FOG remain elusive, posing challenges for effective management and treatment. This paper presents a comprehensive meta-analysis of FOG prediction and detection methodologies, with a focus on the integration of wearable sensor technology and machine learning (ML) approaches. Through an exhaustive review of the literature, this study identifies key trends, datasets, preprocessing techniques, feature extraction methods, evaluation metrics, and comparative analyses between ML and non-ML approaches. The analysis also explores the utilization of cueing devices. The limited adoption of explainable AI (XAI) approaches in FOG prediction research represents a significant gap. Improving user acceptance and comprehension requires an understanding of the logic underlying algorithm predictions. Current FOG detection and prediction research has a number of limitations, which are identified in the discussion. These include issues with cueing devices, dataset constraints, ethical and privacy concerns, financial and accessibility restrictions, and the requirement for multidisciplinary collaboration. Future research avenues center on refining explainability, expanding and diversifying datasets, adhering to user requirements, and increasing detection and prediction accuracy. The findings contribute to advancing the understanding of FOG and offer valuable guidance for the development of more effective detection and prediction methodologies, ultimately benefiting individuals affected by PD.
Huntington’s disease (HD) is a neurodegenerative dementia with a well recognised genetic cause. Alcohol misuse is a major environmental factor relevant to numerous neurological presentations, ...including HD. We explored the effects of alcohol intake on clinical features of HD by means of data from the Enroll-HD, which is a global registry study. A retrospective observational study making use of the Enroll-HD periodic dataset up to 2020 (in accordance with the Enroll-HD guidelines, encompassing 16,120 subjects with the HD gene (CAG expansion > 36), was carried out. This included 180 sites in 21 countries. The study looked at the association of alcohol use with the clinical presentation of HD, specifically looking into the age of first symptoms and HD severity. We also describe a specific case with manifest HD, a participant in the Enroll-HD study, whereby the patient’s obsessionality was central to her pattern of high alcohol intake and to her successful avoidance of alcohol thereafter. A record of past problems with high alcohol intake was more common in the group with manifest HD (9.0%, n = 1121) when compared with the pre-manifest carriers of the HD genetic abnormality (2.3%, n = 339). Age at onset of symptoms was not significantly influenced by current alcohol misuse, or past misuse. The severity of clinical impairments in HD was influenced by alcohol. Patients who reported high alcohol intake in the past had a statistically significant increase in motor impairments, by the Unified Huntington’s Disease Rating Scale total motor score (Kruskal–Wallis, post hoc Dunn’s, p < 0.001), and a significantly higher burden of psychiatric symptoms by the Problem Behaviours Assessment score (Kruskal–Wallis, post hoc Dunn’s, p < 0.01) compared with those not reporting high alcohol use. However, the past alcohol group did not have a lower Mini Mental State Examination score (Kruskal–Wallis, post hoc Dunn’s, p > 0.05) The first symptom of HD, as determined by the assessing clinician, was more likely to be psychiatric disturbance in patients currently misusing alcohol or those with prior history of alcohol misuse (55% and 31% respectively) when compared with controls (5%). Individual case experience, such as that presented in this study, shows that HD and alcohol, two major genetic and environmental contributors to neurodegeneration, interact in producing clinical problems. However, the complexities of these interactions are difficult to define, and may require larger studies dedicated to exploring the various factors in this interaction.
Tardive dystonia is a potential side effect of antipsychotic medications and certain other dopamine antagonists. It is characterized by sustained muscle contractions that lead to abnormal postures ...and movements. It is generally a permanent side effect that has a significant impact on a patient's physical, psychological, and social well-being, decreasing overall quality of life. The authors present the case of a patient with severe tardive dystonia due to metoclopramide that illustrates the profound physical, psychological, and social impact of this condition. It is important for clinicians to be knowledgeable about tardive dystonia so that they can take active steps to prevent its development and have a positive impact on its prognosis when it does develop by recognizing the condition early. Treatment of tardive dystonia should follow a biopsychosocial approach that combines an array of treatment modalities, depending on the individual presentation. Incorporating a quality of life questionnaire specific to dystonia into clinical practice can help clinicians tailor care to the needs of the individual patient.
A man in his 20s presented following a generalised tonic-clonic seizure on a background of a recent diagnosis of hepatitis B (HBV). During admission, he was severely hypertensive and imaging findings ...confirmed a diagnosis of posterior reversible leukoencephalopathy syndrome (PRES). The patient subsequently developed multiorgan involvement with an axonal sensorimotor neuropathy, vascular cutaneous lesions and multiple bilateral renal and splenic infarcts. Based on the 2012 Revised International Chapel Hill Consensus Criteria, a diagnosis of polyarteritis nodosa (PAN) with secondary PRES was made. The patient was given intravenous methylprednisolone, followed by a prolonged course of oral prednisolone, and tenofovir antiviral therapy to target HBV seroconversion. He made a good neurological recovery with resolution of imaging changes. This case highlights the importance of a low threshold for systemic screening for young patients presenting with PRES secondary to uncontrolled hypertension and the importance of viral screening, particularly for HBV.
Seronegative autoimmune limbic encephalitis is a rare clinical syndrome defined by a rapid onset of cognitive impairment with neuropsychiatric features and an absence of associated autoantibodies ...that often lead to diagnostic uncertainty, delayed treatment and ultimately, poor prognosis. Here a case is presented that highlights the benefits of implementing a multidisciplinary approach to treating the psychiatric manifestations, including a cautious use of therapeutic home leave for patients where the clinical course is prolonged.
premutation cytosine-guanine-guanine repeat expansion alleles are relatively common mutations in the general population that are associated with a neurodegenerative disease (fragile X-associated ...tremor/ataxia syndrome), reproductive health problems and potentially a wide range of additional mental and general health conditions that are not yet well-characterised. The International Fragile X Premutation Registry (IFXPR) was developed to facilitate and encourage research to better understand the
premutation and its impact on human health, to facilitate clinical trial readiness by identifying and characterising diverse cohorts of individuals interested in study participation, and to build community and collaboration among carriers, family members, researchers and clinicians around the world. Here, we describe the development and content of the IFXPR, characterise its first 747 registrants from 32 countries and invite investigators to apply for recruitment support for their project(s). With larger numbers, increased diversity and potentially the future clinical characterisation of registrants, the IFXPR will contribute to a more comprehensive and accurate understanding of the fragile X premutation in human health and support treatment studies.
OBJECTIVETo assess the effect of stereotactic lesional surgery for treatment of tremor in multiple sclerosis on cognition. METHODSEleven patients (3 males, 8 females) with multiple sclerosis ...participated in the study. Six subjects comprised the surgical group and five the matched control group. All patients were assessed at baseline and three months using a neuropsychological test battery that included measures of intellectual ability, memory, language, perception and executive function. RESULTSThere were no significant differences between the surgical and control groups and no change from pre to post testing except for a decline in scores on the Mini-Mental State Examination (MMSE), WAIS-R Digit Span and Verbal Fluency in the surgical group. CONCLUSIONSThe results indicate that stereotactic lesional surgery does not result in major cognitive impairment in multiple sclerosis. However, the decline in MMSE scores, digit span and verbal fluency require further investigation in a larger sample.
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