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BACKGROUND: Cervical dystonia (CD) is a form of isolated focal dystonia typically associated to abnormal head, neck, and shoulder movements and postures. The complexity of the clinical presentation limits the investigation of its pathophysiological mechanisms, and the neural networks associated to specific motor manifestations are still the object of debate. OBJECTIVES: We investigated the morphometric properties of white matter fibers in CD and explored the networks associated with motor symptoms, while regressing out nonmotor scores. METHODS: Nineteen patients affected by CD and 21 healthy controls underwent diffusion-weighted magnetic resonance imaging. We performed fixel-based analysis, a novel method evaluating fiber orientation within specific fiber bundles, and compared fiber morphometric properties between groups. Moreover, we correlated fiber morphometry with the severity of motor symptoms in patients. RESULTS: Compared to controls, patients exhibited decreased white matter fibers in the right striatum. Motor symptom severity negatively correlated with white matter fibers passing through inferior parietal areas and the head representation area of the motor cortex. CONCLUSIONS: Abnormal white matter integrity at the basal ganglia level may affect several functional networks involved, for instance, in motor preparation and execution, visuomotor coordination, and multimodal integration. This may result in progressive maladaptive plasticity, culminating in overt symptoms of dystonia. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Trastornos Distónicos , Tortícolis , Sustancia Blanca , Humanos , Tortícolis/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Imagen por Resonancia Magnética , Encéfalo , Trastornos Distónicos/diagnóstico por imagenRESUMEN
Objective: Blepharospasm is a type of dystonia where the diagnosis is often delayed because its varied clinical manifestations are not well recognized. The purpose of this study was to provide a comprehensive picture of its clinical features including presenting features, motor features, and non-motor features. Methods: This was a two-part study. The first part involved a systematic literature review that summarized clinical features for 10,324 cases taken from 41 prior reports. The second part involved a summary of clinical features for 884 cases enrolled in a large multicenter cohort collected by the Dystonia Coalition investigators, along with an analysis of the factors that contribute to the spread of dystonia beyond the periocular region. Results: For cases in the literature and the Dystonia Coalition, blepharospasm emerged in the 50s and was more frequent in women. Many presented with non-specific motor symptoms such as increased blinking (51.9%) or non-motor sensory features such as eye soreness or pain (38.7%), photophobia (35.5%), or dry eyes (10.7%). Non-motor psychiatric features were also common including anxiety disorders (34-40%) and depression (21-24%). Among cases presenting with blepharospasm in the Dystonia Coalition cohort, 61% experienced spread of dystonia to other regions, most commonly the oromandibular region and neck. Features associated with spread included severity of blepharospasm, family history of dystonia, depression, and anxiety. Conclusions: This study provides a comprehensive summary of motor and non-motor features of blepharospasm, along with novel insights into factors that may be responsible for its poor diagnostic recognition and natural history.
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INTRODUCTION: Cervical dystonia is the most frequent form of isolated focal dystonia. It is often associated with a dysfunction in brain networks, mostly affecting the basal ganglia, the cerebellum, and the somatosensory cortex. However, it is unclear if such a dysfunction is somato-specific to the brain areas containing the representation of the affected body part, and may thereby account for the focal expression of cervical dystonia. In this study, we investigated resting state functional connectivity in the areas within the motor cortex and the cerebellum containing affected and non-affected body representations in cervical dystonia patients. METHODS: Eighteen patients affected by cervical dystonia and 21 healthy controls had resting state fMRI. The functional connectivity between the motor cortex and the cerebellum, as well as their corresponding measures of gray matter volume and cortical thickness, were compared between groups. We performed seed-based analyses, selecting the different body representation areas in the precentral gyrus as seed regions, and all cerebellar areas as target regions. RESULTS: Compared to controls, patients exhibited increased functional connectivity between the bilateral trunk representation area of the motor cortex and the cerebellar vermis 6 and 7b, respectively. These functional abnormalities did not correlate with structural changes or symptom severity. CONCLUSIONS: Our findings indicate that the abnormal function of the motor network is somato-specific to the areas encompassing the neck representation. Functional abnormalities in discrete relevant areas of the motor network could thus contribute to the focal expression of CD.
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Trastornos Distónicos , Tortícolis , Ganglios Basales , Cerebelo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Tortícolis/diagnóstico por imagenRESUMEN
OBJECTIVE: To assess the clinical manifestations and predictors of different types of tremors in individuals with different types of isolated dystonia. METHODS: Clinical manifestations of tremor were assessed in a multicenter, international cross-sectional, cohort study of 2,362 individuals with all types of isolated dystonia (focal, segmental, multifocal, and generalized) recruited through the Dystonia Coalition. RESULTS: Methodical and standardized assessments of all participants in this cohort revealed the overall prevalence of any type of tremor was 53.3%. The prevalence of dystonic tremor varied from 36.9% to 48.4%, depending on criteria used to define it. To identify the factors associated with tremors in dystonia, the data were analyzed by generalized linear modeling and cluster analyses. Generalized linear modeling indicated 2 of the strongest factors associated with tremor included body region affected by dystonia and recruitment center. Tremor was also associated with severity of dystonia and duration of dystonia, but not with sex or race. The cluster analysis distinguished 8 subgroups within the whole cohort; defined largely by body region with dystonia, and secondarily by other clinical characteristics. CONCLUSION: The large number of cases evaluated by an international team of movement disorder experts facilitated the dissection of several important factors that influence the apparent prevalence and phenomenology of tremor in dystonia. These results are valuable for understanding the many differences reported in prior studies, and for guiding future studies of the nosology of tremor and dystonia.
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Distonía/diagnóstico , Distonía/epidemiología , Internacionalidad , Temblor/diagnóstico , Temblor/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) currently has no approved treatments. OBJECTIVES: The Fosmetpantotenate Replacement Therapy pivotal trial examined whether treatment with fosmetpantotenate improves PKAN symptoms and stabilizes disease progression. METHODS: This randomized, double-blind, placebo-controlled, multicenter study evaluated fosmetpantotenate, 300 mg oral dose three times daily, versus placebo over a 24-week double-blind period. Patients with pathogenic variants of PANK2, aged 6 to 65 years, with a score ≥6 on the PKAN-Activities of Daily Living (PKAN-ADL) scale were enrolled. Patients were randomized to active (fosmetpantotenate) or placebo treatment, stratified by weight and age. The primary efficacy endpoint was change from baseline at week 24 in PKAN-ADL. RESULTS: Between July 23, 2017, and December 18, 2018, 84 patients were randomized (fosmetpantotenate: n = 41; placebo: n = 43); all 84 patients were included in the analyses. Six patients in the placebo group discontinued treatment; two had worsening dystonia, two had poor compliance, and two died of PKAN-related complications (aspiration during feeding and disease progression with respiratory failure, respectively). Fosmetpantotenate and placebo group PKAN-ADL mean (standard deviation) scores were 28.2 (11.4) and 27.4 (11.5) at baseline, respectively, and were 26.9 (12.5) and 24.5 (11.8) at week 24, respectively. The difference in least square mean (95% confidence interval) at week 24 between fosmetpantotenate and placebo was -0.09 (-1.69 to 1.51; P = 0.9115). The overall incidence of treatment-emergent serious adverse events was similar in the fosmetpantotenate (8/41; 19.5%) and placebo (6/43; 14.0%) groups. CONCLUSIONS: Treatment with fosmetpantotenate was safe but did not improve function assessed by the PKAN-ADL in patients with PKAN. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Neurodegeneración Asociada a Pantotenato Quinasa , Actividades Cotidianas , Método Doble Ciego , Humanos , Neurodegeneración Asociada a Pantotenato Quinasa/tratamiento farmacológico , Neurodegeneración Asociada a Pantotenato Quinasa/genética , Ácido Pantoténico/análogos & derivadosRESUMEN
OBJECTIVE: Isolated focal dystonia can spread to muscles beyond the initially affected body region, but risk of spread has not been evaluated in a prospective manner. Furthermore, body regions at risk for spread and the clinical factors associated with spread risk are not well characterised. We sought here to prospectively characterise risk of spread in recently diagnosed adult-onset isolated focal dystonia patients. METHODS: Patients enrolled in the Dystonia Coalition with isolated dystonia affecting only the neck, upper face, hand or larynx at onset of symptoms were included. Timing of follow-up visits was based on a sliding scale depending on symptom onset and ranged from 1 to 4 years. Descriptive statistics, Kaplan-Meier survival curves and Cox proportional hazard regression models were used to assess clinical characteristics associated with dystonia spread. RESULTS: 487 enrolled participants (68.3% women; mean age: 55.6±12.2 years) met our inclusion/exclusion criteria. Spread was observed in 50% of blepharospasm, 8% of cervical dystonia, 17% of hand dystonia and 16% of laryngeal dystonia cases. Most common regions for first spread were the oromandibular region (42.2%) and neck (22.4%) for blepharospasm, hand (3.5%) for cervical dystonia and neck for hand (12.8%) and laryngeal (15.8%) dystonia. Increased spread risk was associated with a positive family history (HR=2.18, p=0.012) and self-reported alcohol responsiveness (HR=2.59, p=0.009). CONCLUSIONS: Initial body region affected in isolated focal dystonia has differential risk and patterns of spread. Genetic factors likely influence the risk of spread. These findings can aid clinical prognostication and inform future investigations into potential disease-modifying treatments.
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Trastornos Distónicos/complicaciones , Trastornos Distónicos/diagnóstico , Adulto , Edad de Inicio , Anciano , Estudios de Cohortes , Progresión de la Enfermedad , Trastornos Distónicos/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Análisis de Supervivencia , Evaluación de SíntomasAsunto(s)
Estimulación Encefálica Profunda , Trastornos Distónicos , Tortícolis , Marcha , Globo Pálido , HumanosRESUMEN
BACKGROUND: Whether reserve plays a role in Parkinson's disease (PD) patients has received less attention than in dementia and has been mainly examined in relation with cognitive function. OBJECTIVE: To investigate whether reserve plays a role in the severity and progression of motor, cognitive, and nonmotor PD symptoms by examining whether education level (proxy of reserve) is associated with baseline performance and rate of progression. METHODS: We used data from a longitudinal cohort of PD patients (≤5-year disease duration at baseline) annually followed up to 5 years (n = 393; 41% women; mean age = 62.3 years, standard deviation = 10.0; mean disease duration = 2.6 years, standard deviation = 1.5). We examined the relationship of education with time to reach Hoehn and Yahr stage ≥3 using Cox regression and with baseline severity and progression of motor (Movement Disorder Society-Unified Parkinson's Disease Rating Scale parts II and III, gait speed), cognitive (Mini-Mental State Examination), and nonmotor (depression, anxiety, nonmotor symptoms scale, quality of life) symptoms using mixed models. RESULTS: Education level was not associated with age at onset or diagnosis. Compared with the low-education group, the incidence of Hoehn and Yahr ≥3.0 was 0.42 times lower (95% confidence interval, 0.22-0.82, P = 0.012) in the high-education group. Higher education was associated with better baseline motor function (P < 0.001), but not with the rate of motor decline (P > 0.15). Similar results were observed for cognition. Education was not associated with nonmotor symptoms. CONCLUSIONS: Higher education is associated with better baseline motor/cognitive function in PD, but not with rate of decline, and with a lower risk of reaching Hoehn and Yahr ≥3 during the follow-up. Our observations are consistent with a passive reserve hypothesis for motor/cognitive symptoms. © 2019 International Parkinson and Movement Disorder Society.
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Cognición/fisiología , Disfunción Cognitiva/etiología , Enfermedad de Parkinson/psicología , Anciano , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/psicología , Disfunción Cognitiva/complicaciones , Demencia/complicaciones , Demencia/psicología , Depresión/etiología , Depresión/psicología , Trastorno Depresivo/complicaciones , Trastorno Depresivo/psicología , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/complicaciones , Calidad de VidaRESUMEN
The execution of coordinated hand movements requires complex interactions between premotor and primary motor areas in the two hemispheres. The supplementary motor area (SMA) is involved in movement preparation and bimanual coordination. How the SMA controls bimanual coordination remains unclear, although there is evidence suggesting that the SMA could modulate interhemispheric interactions. With a delayed-response task, we investigated interhemispheric interactions underlying normal movement preparation and the role of the SMA in these interactions during the delay period of unimanual or bimanual hand movements. We used functional MRI and transcranial magnetic stimulation in 22 healthy volunteers (HVs), and then in two models of SMA dysfunction: (a) in the same group of HVs after transient disruption of the right SMA proper by continuous transcranial magnetic theta-burst stimulation; (b) in a group of 22 patients with congenital mirror movements (CMM), whose inability to produce asymmetric hand movements is associated with SMA dysfunction. In HVs, interhemispheric connectivity during the delay period was modulated according to whether or not hand coordination was required for the forthcoming movement. In HVs following SMA disruption and in CMM patients, interhemispheric connectivity was modified during the delay period and the interhemispheric inhibition was decreased. Using two models of SMA dysfunction, we showed that the SMA modulates interhemispheric interactions during movement preparation. This unveils a new role for the SMA and highlights its importance in coordinated movement preparation.
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Lateralidad Funcional/fisiología , Intención , Corteza Motora/diagnóstico por imagen , Corteza Motora/fisiología , Movimiento/fisiología , Desempeño Psicomotor/fisiología , Adolescente , Adulto , Potenciales Evocados Motores/fisiología , Femenino , Voluntarios Sanos , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Trastornos del Movimiento/diagnóstico por imagen , Trastornos del Movimiento/fisiopatología , Estimulación Magnética Transcraneal/métodos , Adulto JovenRESUMEN
Abnormalities of eye movements have been reported in patients with Parkinson's disease (PD). However, it is unclear if they occur in the prodromal stage of synucleinopathy represented by idiopathic rapid eye movement sleep behaviour disorder (iRBD). We thus aimed to study eye movements in subjects with iRBD and in de novo PD, to assess if their abnormalities may serve as a clinical biomarker of neurodegeneration. Fifty subjects with polysomnography-confirmed iRBD (46 male, age 40-79 years), 18 newly diagnosed, untreated PD patients (13 male, age 43-75 years) and 25 healthy controls (20 male, age 42-79 years) were prospectively enrolled. Horizontal and vertical ocular prosaccades and antisaccades were investigated with video-oculography. All patients completed the MDS-UPDRS and the Montreal Cognitive Assessment. In addition, a neuropsychological battery was performed on iRBD subjects. When compared with healthy controls, both de novo PD patients and iRBD subjects showed increased error rates in the horizontal antisaccade task (p < 0.01, p < 0.05 respectively). In the iRBD group, the error rates in horizontal and vertical antisaccades correlated with performances in the Prague Stroop Test and the Grooved Pegboard Test, as well as with motor scores of the MDS-UPDRS. De novo PD patients showed a lower gain (p < 0.01) compared with controls. In conclusion, the increased error rate in the antisaccade task of iRBD and PD patients reflects a dysfunction of the dorsolateral prefrontal cortex and is related to the impairment of executive functions and attention.
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Movimientos Oculares/fisiología , Enfermedad de Parkinson/fisiopatología , Polisomnografía/métodos , Corteza Prefrontal/anomalías , Trastorno de la Conducta del Sueño REM/complicaciones , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastorno de la Conducta del Sueño REM/fisiopatologíaRESUMEN
BACKGROUND: Good short-term results of pallidal deep brain stimulation have been reported in myoclonus-dystonia. Efficacy and safety in the long term remain to be established. In addition, the actual impact of DBS treatment on social inclusion is unknown. The objective of this study was to assess the long-term clinical outcome, quality of life, and social adjustment of GPi-DBS in patients with ε-sarcoglycan (DYT11)-positive myoclonus-dystonia. METHODS: Consecutive myoclonus-dystonia patients with ε-sarcoglycan mutations who underwent GPi-DBS were evaluated at least 5 years postoperatively. Motor symptoms were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale including the Disability Scale, a composite score combining the rest and action parts of the Unified Myoclonus Rating Scale and modified Abnormal Involuntary Movement Scale. Standardized video-protocols were assessed by a blinded and external movement disorder specialist. Social adjustment, cognition, and mood were evaluated. RESULTS: Nine patients (5 women) with long-term GPi-DBS (8.7 ± 3.1 years) were included. There was significant improvement in the composite myoclonus score (94.1% ± 4% improvement; P = 0.008). Dystonia severity was also markedly improved (71.4% ± 28.33% improvement; P = 0.008) as well as motor disability (88.3% ± 20% improvement; P = 0.008) and abnormal involuntary movement score (71.1% ± 15.0% improvement; P = 0.008). No patients experienced postoperative speech or gait problems or any permanent adverse effects. Eight of the 9 patients had fully enhanced social adjustment and personal achievement, with little or no mood or behavioral disorders. CONCLUSIONS: GPi-DBS seems to be a safe and efficacious treatment for medically refractory É-sarcoglycan myoclonus-dystonia, with sustained motor benefit, good quality of life, and social adjustment in long-term follow-up. © 2018 International Parkinson and Movement Disorder Society.
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Estimulación Encefálica Profunda , Trastornos Distónicos/terapia , Trastornos Motores/terapia , Ajuste Social , Adolescente , Adulto , Anciano , Estimulación Encefálica Profunda/métodos , Personas con Discapacidad/psicología , Trastornos Distónicos/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Motores/psicología , Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To investigate the longitudinal dose-effect relationship between dopamine replacement therapy and impulse control disorders (ICDs) in Parkinson disease (PD). METHODS: We used data from a multicenter longitudinal cohort of consecutive patients with PD with ≤5 years' disease duration at baseline followed up annually up to 5 years. ICDs were evaluated during face-to-face semistructured interviews with movement disorder specialists. Generalized estimating equations and Poisson models with robust variance were used to study the association between several time-dependent definitions of dopamine agonist (DA) use, taking dose and duration of treatment into account, and ICDs at each visit. Other antiparkinsonian drugs were also examined. RESULTS: Among 411 patients (40.6% women, mean age 62.3 years, average follow-up 3.3 years, SD 1.7 years), 356 (86.6%) took a DA at least once since disease onset. In 306 patients without ICDs at baseline, the 5-year cumulative incidence of ICDs was 46.1% (95% confidence interval [CI] 37.4-55.7, DA ever users 51.5% [95% CI 41.8-62.1], DA never users 12.4% [95% CI 4.8-30.0]). ICD prevalence increased from 19.7% at baseline to 32.8% after 5 years. ICDs were associated with ever DA use (prevalence ratio 4.23, 95% CI 1.78-10.09). Lifetime average daily dose and duration of treatment were independently associated with ICDs with significant dose-effect relationships. Similar analyses for levodopa were not in favor of a strong association. ICDs progressively resolved after DA discontinuation. CONCLUSION: In this longitudinal study of patients with PD characterized by a high prevalence of DA treatment, the 5-year cumulative incidence of ICDs was ≈46%. ICDs were strongly associated with DA use with a dose-effect relationship; both increasing duration and dose were associated with ICDs. ICDs progressively resolved after DA discontinuation. CLINICALTRIALSGOV IDENTIFIER: NCT01564992.
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Antiparkinsonianos/efectos adversos , Trastornos Disruptivos, del Control de Impulso y de la Conducta/inducido químicamente , Trastornos Disruptivos, del Control de Impulso y de la Conducta/diagnóstico , Agonistas de Dopamina/efectos adversos , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/tratamiento farmacológico , Anciano , Estudios de Cohortes , Trastornos Disruptivos, del Control de Impulso y de la Conducta/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiologíaRESUMEN
BACKGROUND: Depression and anxiety frequently accompany the motor manifestations of isolated adult-onset focal dystonias. Whether the body region affected when this type of dystonia first presents is associated with the severity of these neuropsychiatric symptoms is unknown. OBJECTIVES: The aim of this study was to determine whether depression, anxiety and social anxiety vary by dystonia onset site and evaluate whether pain and dystonia severity account for any differences. METHODS: Patients with isolated focal dystonia evaluated within 5 years from symptom onset, enrolled in the Natural History Project of the Dystonia Coalition, were included in the analysis. Individual onset sites were grouped into five body regions: cervical, laryngeal, limb, lower cranial and upper cranial. Neuropsychiatric symptoms were rated using the Beck Depression Inventory, Hospital Anxiety and Depression Scale and Liebowitz Social Anxiety Scale. Pain was estimated using the 36-Item Short Form Survey. RESULTS: Four hundred and seventy-eight subjects met our inclusion criteria. High levels of depression, anxiety and social anxiety occurred in all groups; however, the severity of anxiety and social anxiety symptoms varied by onset site group. The most pronounced differences were higher anxiety in cervical and laryngeal, lower anxiety in upper cranial and higher social anxiety in laryngeal. Increases in pain were associated with worse neuropsychiatric symptom scores within all groups. Higher anxiety and social anxiety in laryngeal and lower anxiety in upper cranial persisted after correcting for pain and dystonia severity. CONCLUSION: Anxiety and social anxiety severity vary by onset site of focal dystonia, and this variation is not explained by differences in pain and dystonia severity.
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Trastornos de Ansiedad/epidemiología , Trastorno Depresivo/epidemiología , Trastornos Distónicos/diagnóstico , Fenotipo , Trastornos de Ansiedad/diagnóstico , Trastorno Depresivo/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor , Escalas de Valoración Psiquiátrica , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
To identify progressive supranuclear palsy (PSP), we combined voxel-based morphometry (VBM) and support vector machine (SVM) classification using disease-specific features in multicentric magnetic resonance imaging (MRI) data. Structural brain differences were investigated at four centers between 20 patients with PSP and 20 age-matched healthy controls with T1-weighted MRI at 3T. To pave the way for future application in personalized medicine, we applied SVM classification to identify PSP on an individual level besides group analyses based on VBM. We found a major decline in gray matter density in the brainstem, insula, and striatum, and also in frontomedian regions, which is in line with current literature. Moreover, SVM classification yielded high accuracy rates above 80% for disease identification in imaging data. Focusing analyses on disease-specific regions-of-interest (ROI) led to higher accuracy rates compared to a whole-brain approach. Using a polynomial kernel (instead of a linear kernel) led to an increased sensitivity and a higher specificity of disease detection. Our study supports the application of MRI for individual diagnosis of PSP, if combined with SVM approaches. We demonstrate that SVM classification provides high accuracy rates in multicentric data-a prerequisite for potential application in diagnostic routine.
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BACKGROUND: Primary orthostatic tremor (POT) is a movement disorder characterized by unsteadiness upon standing still due to a tremor affecting the legs. It is a gradually progressive condition with limited treatment options. Impairments in health-related quality of life (HQoL) seem to far exceed the physical disability associated with the condition. METHODS: A multi-center, mixed-methodology study was undertaken to investigate 40 consecutive patients presenting with POT to four movement disorder centers in France. HQoL was investigated using eight quantitative scales and a qualitative study which employed semi-structured interviews. Qualitative data were analyzed with a combination of grounded-theory approach. RESULTS: Our results confirm that HQoL in POT is severely affected. Fear of falling was identified as the main predictor of HQoL. The qualitative arm of our study explored our initial results in greater depth and uncovered themes not identified by the quantitative approach. CONCLUSION: Our results illustrate the huge potential of mixed methodology in identifying issues influencing HQoL in POT. Our work paves the way for enhanced patient care and improved HQoL in POT and is paradigmatic of this modern approach for investigating HQoL issues in chronic neurological disorders.
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OBJECTIVE: To evaluate the efficacy and safety of zonisamide in patients with myoclonus-dystonia. METHODS: We conducted a randomized, double-blind, placebo-controlled crossover trial of zonisamide (300 mg/d) in 24 patients with myoclonus-dystonia. Each treatment period consisted of a 6-week titration phase followed by a 3-week fixed-dose phase. The periods were separated by a 5-week washout period. The co-primary outcomes were action myoclonus severity (section 4 of the Unified Myoclonus Rating Scale [UMRS 4]) and myoclonus-related functional disability (UMRS 5). Secondary outcomes included dystonia severity, assessed with the movement and disability subscales of the Burke-Fahn-Marsden-Dystonia Rating Scale (BFM), the Clinical Global Impression-Improvement scale (CGI), and safety measures. Wilcoxon signed-rank tests for paired data were used to analyze treatment effects. RESULTS: Twenty-three patients (11 men, 12 women) were analyzed in the intention-to-treat analysis. Zonisamide significantly improved both action myoclonus (median improvement [95% confidence limits] -5 [-9.25 to -1.44], p = 0.003) and myoclonus-related functional disability (median improvement [95% confidence limits] -2 [-2.58 to -2.46], p = 0.007) compared to placebo. Zonisamide also significantly improved dystonia (BFM movement) compared to placebo (median improvement [95% confidence limits] -3 [-8.46 to 0.03], p = 0.009). No difference was found between zonisamide and placebo with respect to the CGI (median improvement [95% confidence limits] -1 [-1.31 to 0.09], p = 0.1). Zonisamide was well-tolerated. CONCLUSIONS: Zonisamide is well-tolerated and effective on the motor symptoms of myoclonus-dystonia. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that zonisamide improves myoclonus and related disability in patients with myoclonus-dystonia.
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Fármacos del Sistema Nervioso Central/uso terapéutico , Trastornos Distónicos/tratamiento farmacológico , Isoxazoles/uso terapéutico , Adolescente , Adulto , Fármacos del Sistema Nervioso Central/efectos adversos , Fármacos del Sistema Nervioso Central/sangre , Estudios Cruzados , Evaluación de la Discapacidad , Método Doble Ciego , Trastornos Distónicos/sangre , Trastornos Distónicos/genética , Femenino , Humanos , Isoxazoles/efectos adversos , Isoxazoles/sangre , Masculino , Sarcoglicanos/genética , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto Joven , ZonisamidaAsunto(s)
Convergencia Ocular/fisiología , Distonía/fisiopatología , Trastornos Neurológicos de la Marcha/fisiopatología , Trastornos de la Motilidad Ocular/fisiopatología , Movimientos Sacádicos/fisiología , Temblor/fisiopatología , Adulto , Comorbilidad , Distonía/epidemiología , Medidas del Movimiento Ocular , Movimientos Oculares/fisiología , Femenino , Trastornos Neurológicos de la Marcha/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Trastornos de la Motilidad Ocular/epidemiología , Temblor/epidemiología , Adulto JovenRESUMEN
INTRODUCTION: Currently, AIDS is the worldwide leading cause of death among 15- to 59-year-old individuals. This trend has had particularly harsh social and economic consequences in sub-Saharan Africa, where more than half of global AIDS deaths take place. In the United States, an estimated 1.2 million people are infected with HIV. In 2012, a worldwide estimate of 1.7 million deaths due to AIDS-related causes was reported.About 10% to 12% of all AIDS patients will develop intracranial tumors. Differential diagnosis should rule out brain tumors such as central nervous system lymphoma and gliomas, as well as infectious processes such as toxoplasmosis, tuberculosis, and cryptococcosis. CASE REPORT: A 27-year-old homosexual man was referred to our care center after 2 months of disabling left frontal headache. Upon AIDS diagnosis, the patient was given abacavir (ABC), lamivudine (3TC), and efavirenz (EFV), but he discontinued the treatment after 9 months and failed to attend follow-up appointments. Three years later, the patient returned to the hospital and received ABC, 3TC, and lopinavir/ritonavir (LPV/r). On admission, computed tomographic scan reported multiple contrast-enhancing lesions compatible with meningiomas. The patient underwent uncomplicated surgical resection of the frontal basal lesion originating in the left olfactory bulb. No new neurological deficits were reported during the postoperative stay. CONCLUSIONS: According to a literature revision, it is likely that associated meningiomas are more aggressive in AIDS patients. Severe immunosuppression and the HIV-Tat protein may be involved in the pathogenesis of tumoral growth.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Terapia Antirretroviral Altamente Activa/métodos , Neoplasias Meníngeas , Meningioma , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Adulto , Humanos , Masculino , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/etiología , Neoplasias Meníngeas/cirugía , Meningioma/diagnóstico por imagen , Meningioma/etiología , Meningioma/cirugíaRESUMEN
OBJECTIVE: To present a retrospective study from patients with spinal cysticercosis (SC), diagnosed within the last 30 years in Mexican and Indian neurological referral centers. METHODS: This is a retrospective and comparative study of the clinical and radiological profile between Mexican and Indian patients with spinal neurocysticercosis during a 30-year period and a review of the literature during the same period. RESULTS: Twenty-seven SC patients were included: 19 from Mexico and 8 from India. SC presented predominantly with motor symptoms (21/27 patients): paraparesis and paraplegia were the most common signs; one-third of patients presented sphincter dysfunction. Imaging studies showed that parasites in vesicular stage were more frequent in patients from Mexico, while degenerative stages predominated in India. Association of subarachnoid cysticerci and hydrocephalus was observed only in Mexican patients. CONCLUSIONS: Despite the limitations of this study, the collected information supports the existence of differences in the clinical and radiological traits of SC patients between Asian and Latin-American hospitals. The possible biological factors that may underlie these differences are discussed.