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

Introduction: Choreiform 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.

Symptomatic treatment options for Huntington's disease (guidelines of the German Neurological Society).

Introduction: Ameliorating symptoms and signs of Huntington's disease (HD) is essential to care but can be challenging and hard to achieve. The pharmacological treatment of motor signs (e.g.

Generation of two human iPSC lines from dermal fibroblasts of adult- and juvenile-onset Huntington's disease patients and two healthy donors.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a mutation in the HTT gene. To generate human-induced pluripotent stem cells (hiPSCs), we used dermal fibroblasts from 1 healthy adult control (K-Pic2), 1 HD manifest patient (M-T2), 1 healthy juvenile control (jK-N1), and 1 juvenile HD patient (jHD-V1). HD stage of patients was assessed by neurological tests and donors were without comorbidities and were non-smokers.

Generation of three human iPSC lines from patients with Huntington's disease with different CAG lengths and human control iPSC line from a healthy donor.

Huntington's disease (HD) is a progressive neurodegenerative disorder with autosomal-dominant heritability that affect the central nervous system and peripheral tissues. The human-induced pluripotent stem cells (hiPSC) lines were generated from dermal fibroblasts of patients without comorbidities, non-smokers, at the pre-manifest (IIMCBi004-A), early-manifest (IIMCBi005-A), and manifest (IIMCBi006-A) HD stage assessed by neurological tests, as well as from a healthy donor (IIMCBi003-A). Characterization showed that the obtained hiPSC lines contained different CAG repeats consistent with the number of CAG repeats in original fibroblasts.

Cerebrospinal fluid levels of proenkephalin and prodynorphin are differentially altered in Huntington's and Parkinson's disease.

Background: Proenkephalin (PENK) and prodynorphin (PDYN) are peptides mainly produced by the striatal medium spiny projection neurons (MSNs) under dopaminergic signaling. Therefore, they may represent candidate biomarkers in Huntington's disease (HD) and Parkinson's disease (PD), two neurodegenerative diseases characterized by striatal atrophy and/or dysfunction.

Methods: Using an in-house established liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in multiple reaction monitoring mode (MRM) we measured cerebrospinal fluid (CSF) levels of PENK- and PDYN- derived peptides in patients with HD (n = 47), PD (n = 61), Alzheimer's disease (n = 11), amyotrophic lateral sclerosis (n = 14) and in 92 control subjects.

Effect of Body Weight on Age at Onset in Huntington Disease: A Mendelian Randomization Study.

Objective: Weight loss is associated with clinical progression in Huntington disease (HD), but whether body weight causally affects disease onset or progression is unknown. Therefore, we aimed to assess whether genetically determined variations in body weight are causally related to age at onset in HD.

Methods: Using data from different recent genome-wide association studies, we performed a 2-sample mendelian randomization (MR) analysis to assess whether genetic markers of body mass index (BMI) are causally related to residual age at onset in HD, i.

Identification of symbol digit modality test score extremes in Huntington's disease.

Studying individuals with extreme phenotypes could facilitate the understanding of disease modification by genetic or environmental factors. Our aim was to identify Huntington's disease (HD) patients with extreme symbol digit modality test (SDMT) scores. We first examined in HD the contribution of cognitive measures of the Unified Huntington's Disease Rating Scale (UHDRS) in predicting clinical endpoints.

FDG-PET underscores the key role of the thalamus in frontotemporal lobar degeneration caused by C9ORF72 mutations.

C9ORF72 mutations are the most common cause of familial frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). MRI studies have investigated structural changes in C9ORF72-associated FTLD (C9FTLD) and provided first insights about a prominent involvement of the thalamus and the cerebellum. Our multicenter, F-fluorodeoxyglucose positron-emission tomography study of 22 mutation carriers with FTLD, 22 matched non-carriers with FTLD, and 23 cognitively healthy controls provided valuable insights into functional changes in C9FTLD: compared to non-carriers, mutation carriers showed a significant reduction of glucose metabolism in both thalami, underscoring the key role of the thalamus in C9FTLD.

Biological and clinical manifestations of juvenile Huntington's disease: a retrospective analysis.

Background: Huntington's disease is a rare, neurodegenerative disease caused by an expanded CAG repeat mutation in the huntingtin gene. Compared with adult-onset Huntington's disease, juvenile Huntington's disease (onset ≤20 years) is even rarer and has not been studied extensively. We aimed to further characterise juvenile Huntington's disease by examining the effect of CAG repeat size on disease presentation, progression, and survival.

Data Analytics from Enroll-HD, a Global Clinical Research Platform for Huntington's Disease.

Background: The study of complex neurodegenerative diseases is moving away from hypothesis-driven biological methods toward large scale multimodal approaches, requiring standardized collaborative efforts. Enroll-HD exemplifies such an integrated clinical research platform, designed and implemented to meet the research and clinical needs of Huntington's disease (HD). The aim of this study was to describe the unique organization of Enroll-HD and report baseline data analyses of its core study.

A randomized, placebo-controlled trial of AFQ056 for the treatment of chorea in Huntington's disease.

Background: This study investigated the hypothesis that AFQ056 (mavoglurant), a selective metabotropic glutamate receptor 5 antagonist, reduces chorea in Huntington's disease (HD).

Methods: This 32-day randomized, double-blind, parallel-group, proof-of-concept study investigated AFQ056 (25-150 mg [incremental doses], twice-daily) versus placebo in patients with HD. Primary efficacy assessments were the chorea-sum score and orientation index (nondominant hand) from the quantitative motor (Q-Motor) grasping task at day 28.

Altered Ca(2+) signaling in skeletal muscle fibers of the R6/2 mouse, a model of Huntington's disease.

Huntington's disease (HD) is caused by an expanded CAG trinucleotide repeat within the gene encoding the protein huntingtin. The resulting elongated glutamine (poly-Q) sequence of mutant huntingtin (mhtt) affects both central neurons and skeletal muscle. Recent reports suggest that ryanodine receptor-based Ca(2+) signaling, which is crucial for skeletal muscle excitation-contraction coupling (ECC), is changed by mhtt in HD neurons.

Cortical dysfunction in patients with Huntington's disease during working memory performance.

Previous functional neuroimaging studies on executive function suggested multiple functionally aberrant cortical regions in patients with Huntington's disease (HD). However, little is known about the neural mechanisms of working memory (WM) function in this patient population. The objective of this study was to investigate the functional neuroanatomy of WM in HD patients.

Myopathy as a first symptom of Huntington's disease in a Marathon runner.

A semi professional marathon runner at risk for Huntington's disease (HD) (43 CAG repeats) developed signs of a slowly progressive myopathy with exercise-induced muscle fatigue, pain, elevated creatine kinase level, and worsening of his running performance many years before first signs of chorea were detected. Muscle biopsy displayed a mild myopathy with mitochondrial pathology including a complex IV deficiency and analysis of the patient's fibroblast culture demonstrated deficits in mitochondrial function. Challenging skeletal muscle by excessive training might have disclosed myopathy in HD even years before the appearance of other neurological symptoms.

Neurofilament heavy-chain NfH(SMI35) in cerebrospinal fluid supports the differential diagnosis of Parkinsonian syndromes.

We aimed to evaluate the potential of the cerebrospinal fluid (CSF) axonal damage biomarker NfH(SMI35) in the laboratory-supported differential diagnosis of parkinsonian syndromes. Patients with idiopathic Parkinson's disease (PD; n = 22), multiple-system atrophy (MSA; n = 21), progressive supranuclear palsy (PSP; n = 21), corticobasal degeneration (CBD; n = 6), and age-matched controls (n = 45) were included. CSF levels of NfH(SMI35) were measured using ELISA.