1,721,133 research outputs found
Parkinson disease in Gaucher disease
No full textGaucher disease (GD) is an inborn error of metabolism caused by mutations in the gene (GBA) coding for glucocerebrosidase (GCase), inherited in an autosomal recessive pattern. GD patients have up to 9% risk of developing PD
Essential pitfalls in "essential" tremor.
No full textAlthough essential tremor has been considered the most common movement disorder, it has largely remained a diagnosis of exclusion: many tremor and nontremor features must be absent for the clinical diagnosis to stand. The clinical features of "essential tremor" overlap with or may be part of other tremor disorders and, not surprisingly, this prevalent familial disorder has remained without a gene identified, without a consistent natural history, and without an acceptable pathology or pathophysiologic underpinning. The collective evidence suggests that under the rubric of essential tremor there exists multiple unique diseases, some of which represent cerebellar dysfunction, but for which there is no intrinsic "essence" other than a common oscillatory behavior on posture and action. One approach may be to use the term essential tremor only as a transitional node in the deep phenotyping of tremor disorders based on historical, phenomenological, and neurophysiological features to facilitate its etiologic diagnosis or serve for future gene- and biomarker-discovery efforts. This approach deemphasizes essential tremor as a diagnostic entity and facilitates the understanding of the underlying disorders to develop biologically tailored diagnostic and therapeutic strategies. © 2017 International Parkinson and Movement Disorder Society
Diagnostic criteria for camptocormia in parkinson's disease. a consensus-based proposal
No full textIntroduction: Camptocormia is defined as an involuntary, marked flexion of the thoracolumbar spine appearing during standing or walking and resolving in the supine position or when leaning against a wall. However, there is no established agreement on the minimum degree of forward flexion needed to diagnose camptocormia. Likewise, the current definition does not categorize camptocormia on the basis of the bending fulcrum. Methods: We performed a survey among movement disorders experts to identify camptocormia using images of patients with variable degrees and types of forward trunk flexion by fulcrum (upper and lower fulcra). We tested the subsequently generated diagnostic criteria in a sample of 131 consecutive patients referred for evaluation of postural abnormalities. Results: Experts reached full consensus on lower camptocormia (L1-Sacrum, hip flexion) with a bending angle ≥30° and upper camptocormia (C7 to T12-L1) with a bending angle ≥45°. This definition detected camptocormia in 9/131 consecutive PD patients (2 upper/7 lower) but excluded camptocormia in 71 patients considered to have camptocormia by the referring neurologist. Conclusions: Camptocormia can be defined as “an involuntary flexion of the spine appearing during standing or walking and resolving in the supine position of at least 30° at the lumbar fulcrum (L1-Sacrum, hip flexion, i.e. lower camptocormia) and/or at least 45° at the thoracic fulcrum (C7 to T12-L1, i.e. upper camptocormia)”. Strict criteria for camptocormia are met by 7% of patients with abnormal posture. The ascertainment of upper and lower camptocormia subtypes could improve the validity of epidemiological studies and assist future therapeutic trials
Levodopa-responsive progressive encephalomyelitis with rigidity and myoclonus associated with glycine receptor antibodies
No full textProgressive Ataxia with Hemiplegic Migraines: a Phenotype of CACNA1A Missense Mutations, Not CAG Repeat Expansions
No full textWe report a 52-year-old woman presenting with autosomal dominant progressive cerebellar ataxia and familial hemiplegic migraine type 1 whose genetic evaluation, negative for spinocerebellar ataxia (SCA) types 1, 2, 3, and 6, revealed instead a heterozygous pathogenic missense mutation in CACNA1A (NM_001127221:c.1748G > A:p.Arg583Gln). A systematic literature review showed that Arg583Gln is associated predominantly with progressive ataxia combined with episodic disorders (overwhelmingly hemiplegic migraine) whereas Thr666Met, the other most common CACNA1A missense mutation, with a combination of progressive ataxia and episodic disorders in half the cases and episodic disorders only in the other half. While uncertainties remain in the genotype-phenotype correlation of all CACNA1A mutations, the accumulated evidence suggests that that the co-occurrence of hemiplegic migraine and autosomal dominant progressive cerebellar ataxia should guide the clinician to test for CACNA1A missense mutation rather than CAG expansions or truncating mutations.Fil: Duque, Kevin R.. University of Cincinnati; Estados UnidosFil: Marsili, Luca. University of Cincinnati; Estados UnidosFil: Sturchio, Andrea. University of Cincinnati; Estados UnidosFil: Mahajan, Abhimanyu. University of Cincinnati; Estados UnidosFil: Merola, Aristide. Ohio State University; Estados UnidosFil: Espay, Alberto J.. University of Cincinnati; Estados UnidosFil: Kauffman, Marcelo Andres. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Centro Universitario de Neurología "Dr. José María Ramos Mejía".; Argentin
Holmes Tremor‐Like Phenotype in DYT1 Dystonia
Get PDFHolmes tremor is characterized by a combination of a flexion‐extension resting postural and action tremor, most often due to mesencephalic lesions affecting the nigrostriatal and cerebello‐thalamo‐cortical pathways. On the other hand, dystonic tremor represents a jerky postural and action tremor, which if severe enough may include a resting component and may arise from cerebellar and nigrostriatal dysfunction. Here, we present a patient with a four‐decade history of progressive tremor, initially interpreted as Holmes tremor with a dystonic (pseudospastic) gait, in whom whole exome sequencing (WES) demonstrated a pathogenic TOR1A deletion. This case highlights two important clinical points, (1) the need for proper semiologic interpretation: direct DYT1 testing could have been entertained if tremor was properly categorized as dystonic rather than cerebellar at the outset; and (2) the phenotypic variability of DYT1 dystonia, with tremor as a presenting and disabling feature separate from the body part affected by dystonia (“tremor associated with dystonia”).Fil: Rodríguez Quiroga, Sergio Alejandro. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: González Morón, Dolores. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Espay, Alberto J. University of Cincinnati; Estados UnidosFil: Kauffman, Marcelo Andres. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentin
Analyzing the 'Bradykinesia Complex' in Parkinson's Disease
No full textBackground: Bradykinesia is the hallmark sign of parkinsonism. We recently proposed redefining bradykinesia as a complex of motor abnormalities, each reflecting separate pathophysiological elements. Objective: To analyze the 'bradykinesia complex' in Parkinson's disease (PD) and healthy elderly individuals. Methods: We conducted a finger-tapping kinematic analysis in 350 individuals (192 PD patients OFF medication and 158 healthy controls). A subsample of 129 patients was also tested ON medication. Group comparisons were followed by unsupervised clustering. Receiver operating characteristic (ROC) analyses defined optimal kinematic cut-offs to detect individual motor abnormalities. We then quantified the prevalence and combinations of these features per subject. Using Bayes' theorem, we estimated the probability of PD based on the observed combination of bradykinesia features. Regression analyses served to identify predictors of kinematic alterations. Results: Patients exhibited reduced velocity and amplitude as well as altered rhythm and sequence effect compared with controls (all P-values < 0.001). Cluster analysis revealed substantial group overlap. ROC analyses showed that bradykinesia (movement slowness) was the most common and accurate feature for distinguishing PD, with its diagnostic power improving when combined with other motor abnormalities (hypokinesia, dysrhythmia, sequence effect). The likelihood of correctly identifying PD increased with the number of observed abnormalities, reaching up to 95% when all features were present. Levodopa improved motor performance, but the motor abnormality patterns remained unchanged. Conclusions: The detailed bradykinesia features assessment was crucial for differentiating PD individuals from controls. Diagnostic accuracy requires considering multiple motor abnormalities together, irrespective of the specific combination. Advancing our understanding of the 'bradykinesia complex' has clinical and pathophysiological implications. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
- …
