Diagnosis Of Huntington's Disease Research Articles

Dynamic undirected graphical models for time-varying clinical symptom and neuroimaging networks.

In this work, we propose methods to examine how the complex interrelationships between clinical symptoms and, separately, brain imaging biomarkers change over time leading up to the diagnosis of a disease in subjects with a known genetic near-certainty of disease. We propose a time-dependent undirected graphical model that ensures temporal and structural smoothness across time-specific networks to examine the trajectories of interactions between markers aligned at the time of disease onset. Specifically, we anchor subjects relative to the time of disease diagnosis (anchoring time) as in a revival process, and we estimate networks at each time point of interest relative to the anchoring time. To use all available data, we apply kernel weights to borrow information across observations that are close to the time of interest. Adaptive lasso weights are introduced to encourage temporal smoothness in edge strength, while a novel elastic fused- penalty removes spurious edges and encourages temporal smoothness in network structure. Our approach can handle practical complications such as unbalanced visit times. We conduct simulation studies to compare our approach with existing methods. We then apply our method to data from PREDICT-HD, a large prospective observational study of pre-manifest Huntington's disease (HD) patients, to identify symptom and imaging network changes that precede clinical diagnosis of HD.

Dermal Fibroblast Cell Line from a Patient with the Huntington's Disease as a Promising Model for Studying Disease Pathogenesis: Production and Characterization.

Huntington's disease (HD) is an incurable hereditary disease caused by expansion of the CAG repeats in the HTT gene encoding the mutant huntingtin protein (mHTT). Despite numerous studies in cellular and animal models, the mechanisms underlying the biological role of mHTT and its toxicity to striatal neurons have notyet been established and no effective therapy for HD patients has been developed so far. We produced and characterized a new line of dermal fibroblasts (HDDF, Huntington's disease dermal fibroblasts) from a patient with a confirmed HD diagnosis. We also studied the growth characteristics of HDDF cells, stained them for canonical markers, karyotyped these cells, and investigated their phenotype. HDDF cells was successfully reprogrammed into induced striatal neurons via transdifferentiation. The new fibroblast line can be used as a cell model to study the biological role of mHTT and manifestations of HD pathogenesis in both fibroblasts and induced neuronal cells obtained from them by reprogramming techniques.

What Huntington's Disease Patients Say About Their Illness: An Online Direct-to-Participant Pilot Study.

Direct-to-participant online reporting facilitates the conduct of clinical research by increasing access and clinically meaningful patient engagement. We assessed feasibility of online data collection from adults with diagnosed Huntington's disease (HD) who directly reported their problems and impact in their own words. Data were collected online from consenting United States residents who self-identified as 1) having been diagnosed with Huntington's disease, 2) able to ambulate independently, and 3) self-sufficient for most daily needs. Data for this pilot study were collected using the Huntington Study Group myHDstory online research platform. The Huntington Disease Patient Report of Problems (HD-PROP), an open-ended questionnaire, was used to capture verbatim bothersome problems and functional impact. Natural language processing, human-in-the-loop curation of verbatim reports involving clinical and experience experts, and machine learning classified verbatim-reports into clinically meaningful symptoms. All 8 questionnaires in the online pilot study were completed by 345 participants who were 60.9% men, 34.5±9.9 (mean±SD) years old, and 9.5±8.4 years since HD diagnosis. Racial self-identification was 46.4% Caucasian, 28.7% African American, 15.4% American Indian/Alaska Native, and 9.5% other. Accuracy of verbatim classification was 99%. Non-motor problems were the most frequently reported symptoms; depression and cognitive impairment were the most common. Online research participation was feasible for a diverse cohort of adults who self-reported an HD diagnosis and predominantly non-motor symptoms related to mood and cognition. Online research tools can help inform what bothers HD patients, identify clinically meaningful outcomes, and facilitate participation by diverse and under-represented populations.

Dysphagia in Indivuduals with Huntington's Disease: A Narrative Review

Huntington's disease (HD) is a neurodegenerative autosomal dominant condition characterized by motor, behavioral, and cognitive symptoms. Aspiration pneumonia stands out as a leading cause of death in HD, primarily attributed to dysphagia, which gets more noticeable as the disease progresses. Dysphagia symptoms in individuals with HD are compounded by noticeable movement problems, including Chorean or rigid-bradykinetic patterns. These symptoms manifest in every phase of swallowing and fluctuate with the progression of HD. Lingual chorea, delayed swallowing initiation, and impaired swallowing-respiratory coordination are key indicators of dysphagia in HD individuals. The negative impact on eating behaviors is further exacerbated by concurrent cognitive and sensory deficits. Consequently, dysphagia leads to social isolation, restrictions on activities and involvement, and a diminished quality of life for individuals with HD. To minimize these adverse effects, a referral to a speech-language therapist (SLT) for swallowing assessment should be initiated immediately upon the diagnosis of HD by a neurologist. Starting from the earliest stages of the disease, both clinical and instrumental swallowing assessments should be employed to minimize the detrimental consequences of dysphagia. Depending on the assessment results, compensatory and/or rehabilitative (restitutive) strategies can be recommended for treatment. Furthermore, the SLT actively collaborates with other team members, including individuals with HD, caregivers, neurologists, otolaryngologists, gastroenterologists, and others, contributing collectively to the decision-making process regarding both oral and non-oral feeding considerations. Despite negative impact of dysphagia on individuals with HD and its significant role in individuals’ deterioration, the evidence for specific dysphagia interventions remains limited. Clinicians, therefore, rely on well-established general swallowing therapy practices. There is a pressing need for evidence-based research on dysphagia in HD. In this study, the literature on dysphagia in HD will be examined, with a focus on its pathophysiology and the role of SLT in diagnostic and intervention techniques.

Exploring Huntington's Disease Diagnosis via Artificial Intelligence Models: A Comprehensive Review.

Huntington's Disease (HD) is a devastating neurodegenerative disorder characterized by progressive motor dysfunction, cognitive impairment, and psychiatric symptoms. The early and accurate diagnosis of HD is crucial for effective intervention and patient care. This comprehensive review provides a comprehensive overview of the utilization of Artificial Intelligence (AI) powered algorithms in the diagnosis of HD. This review systematically analyses the existing literature to identify key trends, methodologies, and challenges in this emerging field. It also highlights the potential of ML and DL approaches in automating HD diagnosis through the analysis of clinical, genetic, and neuroimaging data. This review also discusses the limitations and ethical considerations associated with these models and suggests future research directions aimed at improving the early detection and management of Huntington's disease. It also serves as a valuable resource for researchers, clinicians, and healthcare professionals interested in the intersection of machine learning and neurodegenerative disease diagnosis.

Differential diagnosis of chorea (guidelines of the German Neurological Society)

IntroductionChoreiform movement disorders are characterized by involuntary, rapid, irregular, and unpredictable movements of the limbs, face, neck, and trunk. These movements often initially go unnoticed by the affected individuals and may blend together with seemingly intended, random motions. Choreiform movements can occur both at rest and during voluntary movements. They typically increase in intensity with stress and physical activity and essentially cease during deep sleep stages. In particularly in advanced stages of Huntington disease (HD), choreiform hyperkinesia occurs alongside with dystonic postures of the limbs or trunk before they typically decrease in intensity.Summary or definition of the topicThe differential diagnosis of HD can be complex. Here, the authors aim to provide guidance for the diagnostic process. This guidance was prepared for the German Neurological Society (DGN) for German-speaking countries.RecommendationsHereditary (inherited) and non-hereditary (non-inherited) forms of chorea can be distinguished. Therefore, the family history is crucial. However, even in conditions with autosomal-dominant transmission such as HD, unremarkable family histories do not necessarily rule out a hereditary form (e.g., in cases of early deceased or unknown parents, uncertainties in familial relationships, as well as in offspring of parents with CAG repeats in the expandable range (27–35 CAG repeats) which may display expansions into the pathogenic range).ConclusionsThe differential diagnosis of chorea can be challenging. This guidance prepared for the German Neurological Society (DGN) reflects the state of the art as of 2023.

Huntington Study Group's Neuropsychology Working Group: Implementing Non‐Motor Diagnostic Criteria

AbstractBackgroundThe clinical diagnosis of manifest Huntington's disease (HD) relies on a high level of clinical confidence (99% confidence) of HD‐consistent motor signs. Longitudinal data have reliably identified cognitive and behavioral dysfunction predating clinical motor diagnosis by up to 15 years. Reliance on motor signs to establish a diagnosis of HD increases risk of early misdiagnosis or delayed diagnosis. Clinical neuropsychologists are uniquely positioned to advise on the clinical application of the Movement Disorder Society Task Force's recently proposed non‐motor diagnostic criteria for HD.ObjectivesTo provide (1) a recommended clinical approach toward non‐motor diagnostic criteria in persons with HD and facilitation of accurate diagnosis; (2) recommended practices for medical treatment providers to screen and longitudinally monitor non‐motor signs of HD.MethodsThe Huntington Study Group re‐established the Neuropsychology Working Group, then recruited a multi‐disciplinary group of neuropsychologists, neurologists, and psychiatrists to conduct an unstructured literature review and discuss expert opinions on practice, to facilitate an informal consensus opinion to accomplish the objectives.ResultsThe opinion and an example protocol for medical treatment providers to screen, monitor, and triage non‐motor signs and symptoms of Huntington's disease is provided.ConclusionsClinical diagnosis of non‐motor HD is empirically justified and clinically important. Screening and triage by non‐neuropsychologist clinicians can aid in detecting and monitoring non‐motor Huntington's disease manifestation. The Neuropsychology Working Group consensus advances good clinical practice, clinical research, and quality of life. A companion position paper presenting the details of our consensus opinion regarding evidence‐based guidelines for neuropsychological practice is forthcoming.

Graphomotor Dysfluency as a Predictor of Disease Progression in Premanifest Huntington's Disease.

Prior studies have relied on conventional observer-based severity ratings such as the Unified Huntington's Disease Rating Scale (UHDRS) to identify early motor markers of decline in Huntington's disease (HD). The present study examined the predictive utility of graphomotor measures handwriting and drawing movements. Seventeen gene-positive premanifest HD subjects underwent comprehensive clinical, cognitive, motor, and graphomotor assessments at baseline and at follow-up intervals ranging from 9-36 months. Baseline graphomotor assessments were subjected to linear multiple regression procedures to identify factors associated with change on the comprehensive UHDRS index. Subjects were followed for an average of 21.2 months. Three multivariate regression models based on graphomotor variables derived from a complex loop task, a maximum speed circle drawing task and a combined task returned adjusted R2 coefficients of 0.76, 0.71, and 0.80 respectively accounting for a significant portion of the variability in cUHDRS change score. The best-fit model based on the combined tasks indicated that greater decline on the cUHDRS was associated with increased pen movement dysfluency and stroke-stroke variability at baseline. Performance on multiple measures of graphomotor dysfluency assessed during the premanifest or prodromal stage in at-risk HD individuals was associated with decline on a multidimensional index on HD morbidity preceding an HD diagnosis.

Nursing Homes Underreport Antipsychotic Use but Overreport Diagnoses Qualifying for Appropriate Use.

Antipsychotic drug use in U.S. nursing homes remains a priority concern, but less is understood about the characteristics associated with reporting. Using linked Medicare claims and Minimum Data Set (MDS) assessments for long-stay nursing home residents from January 2018 to December 2019, we assessed the consistency of antipsychotic drug reporting and diagnosis of conditions (schizophrenia, Tourette's syndrome, and Huntington's disease) which qualify as appropriate drug use across data sources by calculating reporting rates in facility-reported MDS and Medicare claims. The antipsychotic reporting outcome is conditional on claims reporting while the condition reporting outcomes are conditional on MDS reporting. We found underreporting (87% reporting rate) in facility-reported antipsychotic use relative to Medicare claims. In contrast, we found overreporting of the qualifying conditions with a number of facility-reported diagnoses unsupported by a corresponding claims diagnosis. Only 54.8% of schizophrenia, 46.5% of Tourette's syndrome, and 72.4% of Huntington's disease diagnoses reported in the MDS had a claims diagnosis. There was also variation in reporting odds for antipsychotic drug use by dual-eligibility status and race, with higher odds for dual-eligible and lower odds for Black residents These findings suggest CMS should continue investigating the source of reporting discrepancies in antipsychotic drug use and qualifying diagnoses.

Are you angry? Neural basis of impaired facial expression recognition in pre-manifest Huntington's

IntroductionEarly non-motor symptoms in Huntington's disease (HD), including visual perceptual difficulties, can have profound negative impacts on quality of life. In particular, deficits in emotion recognition may contribute to misinterpretation of social cues, and may adversely affect interpersonal relationships, work relationships and/or general well-being. This may be particularly salient during the pre-manifest period, a period prior to the onset of motor symptoms. We sought to evaluate impairments in emotion recognition in gene-positive individuals who did not meet criterial for a diagnosis of HD; we also sought to determine associations between emotion recognition processing and altered cortico-striatal circuitry. MethodsWe used a standardized battery to evaluate performance on a facial expression recognition task in a cohort of motor pre-manifest HD (Pre-HD) individuals (N = 21). Functional MRI (fMRI) was then used to assess the face processing network in a subset (N = 15). ResultsWe found significantly decreased response accuracy to certain facial expressions, particularly of negative emotions (p < 0.001) in Pre-HDs. When Pre-HDs viewed faces with different emotions, activation within the Superior Temporal Sulcus (fSTS) was reduced compared to controls; in contrast, the level of evoked response within other face-selective cortical regions was comparable. ConclusionEarly deficits in emotion recognition in Pre-HD appear to be associated with alterations in the fSTS response, a distinctly different pathway from that involved in face perception and provide support for early cognitive and behavioral interventions.

Alternations of Lipoprotein Profiles in the Plasma as Biomarkers of Huntington's Disease.

Alterations in lipid composition and disturbed lipoprotein metabolism are involved in the pathomechanism of Huntington's disease (HD). Here, we measured 112 lipoprotein subfractions and components in the plasma of 20 normal controls, 24 symptomatic (sympHD) and 9 presymptomatic (preHD) HD patients. Significant changes were found in 30 lipoprotein subfractions and components in all HD patients. Plasma levels of total cholesterol (CH), apolipoprotein (Apo)B, ApoB-particle number (PN), and components of low-density lipoprotein (LDL) were lower in preHD and sympHD patients. Components of LDL4, LDL5, LDL6 and high-density lipoprotein (HDL)4 demonstrated lower levels in preHD and sympHD patients compared with controls. Components in LDL3 displayed lower levels in sympHD compared with the controls, whereas components in very low-density lipoprotein (VLDL)5 were higher in sympHD patients compared to the controls. The levels of components in HDL4 and VLDL5 demonstrated correlation with the scores of motor assessment, independence scale or functional capacity of Unified Huntington's Disease Rating Scale. These findings indicate the potential of components of VLDL5, LDL3, LDL4, LDL5 and HDL4 to serve as the biomarkers for HD diagnosis and disease progression, and demonstrate substantial evidence of the involvement of lipids and apolipoproteins in HD pathogenesis.

Recent approaches on Huntington's disease (Review).

Huntington's disease (HD) is a neurodegenerative disorder characterized by severe motor, cognitive and psychiatric symptoms. Patients of all ages can present with a dysfunction of the nervous system, which leads to the progressive loss of movement control and disabilities in speech, swallowing, communications, etc. The molecular basis of the disease is well-known, as HD is related to a mutated gene, a trinucleotide expansion, which encodes to the huntingtin protein. This protein is linked to neurogenesis and the loss of its function leads to neurodegenerative disorders. Although the genetic cause of the disorder has been known for decades, no effective treatment is yet available to prevent onset or to eliminate the progression of symptoms. Thus, the present review focused on the development of novel methods for the timely and accurate diagnosis of HD in an aim to aid the development of therapies which may reduce the severity of the symptoms and control their progression. The majority of the therapies include gene-silencing mechanisms of the mutated huntingtin gene aiming to suppress its expression, and the use of various substances as drugs with highly promising results. In the present review, the latest approaches on the diagnosis of HD are discussed along with the need for genetic counseling and an up-to-date presentation of the applied treatments.

Longitudinal Clinical and Biological Characteristics in Juvenile-Onset Huntington's Disease.

Juvenile-onset Huntington's disease (JOHD) is a rare form of Huntington's disease (HD) characterized by symptom onset before the age of 21 years. Observational data in this cohort is lacking. Quantify measures of disease progression for use in clinical trials of patients with JOHD. Participants who received a motor diagnosis of HD before the age of 21 were included in the Kids-JOHD study. The comparator group consisted of children and young adults who were at-risk for inheriting the genetic mutation that causes HD, but who were found to have a CAG repeat in the non-expanded range (gene non-expanded [GNE]). Data were obtained between March 17, 2006, and February 13, 2020. There were 26 JOHD participants and 78 GNE participants who were comparable on age (16.03 vs. 14.43, respectively) and sex (53.8% female vs. 57.7% female, respectively). The mean annualized decrease in striatal volume in the JOHD group was -3.99% compared to -0.06% in the GNE (mean difference [MD], -3.93%; 95% confidence intervals [CI], [-4.98 to -2.80], FDR < 0.0001). The mean increase in the Unified Huntington's Disease Rating Scale Total Motor Score per year in the JOHD group was 7.29 points compared to a mean decrease of -0.21 point in the GNE (MD,7.5; 95% CI, [5.71-9.28], FDR < 0·0001). These findings demonstrate that structural brain imaging and clinical measures in JOHD may be potential biomarkers of disease progression for use in clinical trials. Collaborative efforts are required to validate these results in a larger cohort of patients with JOHD. © 2022 International Parkinson and Movement Disorder Society.

Health care resource utilization and costs among individuals with vs without Huntington disease in a US population.

BACKGROUND: Quantifying the extent of health care resource utilization (HCRU) and costs associated with Huntington disease (HD) is vital for providers, decisionmakers, and payers to understand unmet treatment needs and to ensure limited resources can be used to benefit the maximum number of people with HD. OBJECTIVE: To quantify HCRU and costs for people with HD, overall and by disease stage, and compare these with non-HD controls. METHODS: This was a retrospective cohort study using administrative claims data from the IBM MarketScan Commercial, Multi-State Medicaid, and Medicare Supplemental Databases from January 1, 2009, to December 31, 2018. People with an HD claim between January 1, 2010, and December 31, 2017, were selected for this analysis and matched with non-HD controls for comparison. The HD cohort and the non-HD controls were exact matched on their follow-up duration and propensity score matched 1:4 to create the final analytical cohort. Index date was the first HD diagnosis for the HD cohort (proxy index date assigned to controls), and all individuals were required to have continuous enrollment for 12 or more months pre-index (baseline) and 3 or more months post-index. Proportions of all-cause HCRU (ie, outpatient visits, inpatient visits, emergency department visits, pharmacy fills, radiology visits, and physical/occupational therapy visits) in the 6-months post-index and HCRU counts and costs per patient per month (PPPM) over the entire follow-up were calculated for each cohort. RESULTS: A total of 2,473 individuals with HD and 9,522 matched non-HD controls were identified. HCRU in 6 months post-index was significantly greater in people with HD compared with non-HD controls for all health care service categories; P < 0.0001. The mean number of HCRU PPPM for all measured healthcare services was significantly higher in people with HD compared with non-HD controls (P < 0.001). Mean total costs (2018 USD PPPM) for the HD cohort ($2,260 [SD = $4,682]) were twice the total costs in the non-HD cohort ($1,056 [SD = $3,078]) (P < 0.0001) and were highest across all disease stages. CONCLUSIONS: This study provides current comprehensive HCRU and cost estimates in individuals with HD relative to those without the disease, thus demonstrating the high economic burden imposed by HD. DISCLOSURES: Dr Ta: Employment with Genentech (at time of study) and stock options with Roche; Dr To: Employment and stock options/dividends with Genentech; Dr Patel: Employment and stock options with Roche/Genentech; Dr Fuller: Employment with CHDI Management/CHDI Foundation; Mr Surinach: Employment with Genesis Research (which receives consulting fees from Genentech/Roche); Dr Abbass: Employment and stock options with Genentech; Dr Exuzides: Employment and stock options with Roche/Genentech; and Ms Luo: Employment with CHDI Management/CHDI Foundation. This study was funded by Genentech Inc. The authors thank Greg Rowe of Chrysalis Medical Communications for providing medical writing support, which was funded by F. Hoffmann-La Roche Ltd, in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).

Prolonged psychosis before onset of neurological symptoms; an atypical clinical manifestation of Huntington’s disease

Huntington's disease (HD) is a rare, autosomal dominant, progressive neurodegenerative disorder. HD manifests with a triad of progressive motor, cognitive, and psychiatric symptoms. Our patient, a 39-years-old married female with over a nine-year history of psychotic symptoms. The patient was diagnosed and treated for schizophrenia. Over the last 2-3 years, the patient had a progressive decline in her Activities of Daily Living, instrumental activities of daily living, and psychotic symptoms. She developed slurred speech, gait disturbances, frequent falls, involuntary movements of the trunk and distal extremities, bowel and bladder incontinence, and severe weight loss. Her genetic test for Huntington’s gene confirmed the diagnosis of HD. She was prescribed Olanzapine, fluoxetine, and clonazepam. Psychotic symptoms are rare in HD and usually appear well after the motor and cognitive symptoms. Our case highlights an unusual clinical presentation of HD, which can be diagnostically challenging and lead to diagnostic delays.&#x0D;

Complexities in Genetic Counseling and Testing of Huntington's Disease: A Perspective from India.

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. To explore some complex issues in genetic counseling and testing (GCAT) in HD. Vignettes of patients who underwent genetic testing along with pre and post-test counseling at our GCAT clinic. 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. HD can present with complex inheritance patterns and proper counseling is necessary for better outcomes.

A probable cis-acting genetic modifier of Huntington disease frequent in individuals with African ancestry.

SummaryHuntington disease (HD)is a dominantly inherited neurodegenerative disorder caused by the expansion of a polyglutamine encoding CAG repeat in the huntingtin gene. Recently, it has been established that disease severity in HD is best predicted by the number of pure CAG repeats rather than total glutamines encoded. Along with uncovering DNA repair gene variants as trans-acting modifiers of HD severity, these data reveal somatic expansion of the CAG repeat as a key driver of HD onset. Using high-throughput DNA sequencing, we have determined the precise sequence and somatic expansion profiles of the HTT repeat tract of 68 HD-affected and 158 HD-unaffected African ancestry individuals. A high level of HTT repeat sequence diversity was observed, with three likely African-specific alleles identified. In the most common disease allele (30 out of 68), the typical proline-encoding CCGCCA sequence was absent. This CCGCCA-loss disease allele was associated with an earlier age of diagnosis of approximately 7.1 years and occurred exclusively on haplotype B2. Although somatic expansion was associated with an earlier age of diagnosis in the study overall, the CCGCCA-loss disease allele displayed reduced somatic expansion relative to the typical HTT expansions in blood DNA. We propose that the CCGCCA loss occurring on haplotype B2 is an African cis-acting modifier that appears to alter disease diagnosis of HD through a mechanism that is not driven by somatic expansion. The assessment of a group of individuals from an understudied population has highlighted population-specific differences that emphasize the importance of studying genetically diverse populations in the context of disease.

Postural control and gait measures derived from wearable inertial measurement unit devices in Huntington's disease: Recommendations for clinical outcomes

BackgroundPostural control impairments begin early in Huntington's disease yet measures most sensitive to progression have not been identified. The aims of this study were to: 1) evaluate postural control and gait in people with and without Huntington's disease using wearable sensors; and 2) identify measures related to diagnosis and clinical severity. Methods43 individuals with Huntington's disease and 15 age-matched peers performed standing with feet together and feet apart, sitting, and walking with wearable inertial sensors. One-way analysis of variance determined differences in measures of postural control and gait between early and mid-disease stage, and non-Huntington's disease peers. A random forest analysis identified feature importance for Huntington's disease diagnosis. Stepwise and ordinal regressions were used to determine predictors of clinical chorea and tandem walking scores respectively. FindingsThere was a significant main effect for all postural control and gait measures comparing early stage, mid stage and non-Huntington's disease peers, except for gait cycle duration and step duration. Total sway, root mean square and mean velocity during sitting, as well as gait speed had the greatest importance in classifying disease status. Stepwise regression showed that root mean square during standing with feet apart significantly predicted clinical measure of chorea, and ordinal regression model showed that root mean square and total sway standing feet together significantly predicted clinical measure of tandem walking. InterpretationsRoot mean square measures obtained in sitting and standing using wearable sensors have the potential to serve as biomarkers of postural control impairments in Huntington's disease.

Predictors of malnutrition risk in neurodegenerative diseases: The role of swallowing function.

Background and purposeOropharyngeal dysphagia is generally recognized to increase the risk of malnutrition; however, its role in patients with neurodegenerative disease has yet to be determined. This cross‐sectional study aimed to investigate the impact of swallowing function on malnutrition risk in patients with neurodegenerative diseases.MethodsPatients with oral nutrition and diagnosis of Huntington disease (HD), Parkinson disease (PD), or amyotrophic lateral sclerosis (ALS) were recruited. Demographic and clinical data were collected. The swallowing assessment included a fiberoptic endoscopic evaluation of swallowing, an oral phase assessment, and a meal observation scored with the Mealtime Assessment Scale (MAS). Malnutrition risk was assessed with the Mini Nutritional Assessment.ResultsOverall, 148 patients were recruited (54 HD, 33 PD, and 61 ALS). One hundred (67.6%) patients were considered at risk of malnutrition. In the multivariate analysis, age ≥ 65 years (odds ratio [OR] = 3.16, p = 0.014), disease severity (moderate vs mild OR = 3.89, severe vs mild OR = 9.71, p = 0.003), number of masticatory cycles (OR = 1.03, p = 0.044), and MAS safety (OR = 1.44, p = 0.016) were significantly associated with malnutrition risk.ConclusionsProlonged oral phase and signs of impaired swallowing safety during meals, together with older age and disease severity, are independent predictors of malnutrition risk in neurodegenerative diseases. This study broadens the focus on dysphagia, stressing the importance of early detection not only of pharyngeal signs, but also of oral phase impairment and meal difficulties through a multidimensional swallowing assessment.

Teaching Video NeuroImage: Peculiar Hobby Horse Gait in Huntington Disease-like 2.

A 59-year-old woman presented at age 48 years with abnormal hand movements, which became generalized 1 year later, along with a clumsy gait. Two years later, severe apathy and minor auditory hallucinations ensued. Her father died undiagnosed with involuntary movements at age 82 years, and 2 of her 6 sisters have also had a similar clinical picture. Neurologic examination revealed generalized chorea and an unusual dystonic gait pattern remarkably similar to the hobby horse gait, described in DYT-TUBB4A (DYT-4), which is characterized by a toe walking stiff-legged and skipping gait1 (Video 1). Walking backward improved the gait. Diagnostic workup revealed acanthocytes and mild caudate atrophy (Figure 1). A pathogenic 46 CTG/CAG repeat expansion on the JPH3 gene allowed the diagnosis of Huntington disease–like 2, an autosomal dominant Huntington disease phenocopy characterized by chorea, dystonia, and parkinsonism.2 This case expands underlying conditions recognized to cause the HHG (please see the Supplement, [links.lww.com/WNL/B931][1]). [1]: http://links.lww.com/WNL/B931