Syagrus coronata fixed oil prevents rotenone-induced movement disorders and oxidative stress in Drosophila melanogaster.

One prominent aspect of Parkinson's disease (PD) is the presence of elevated levels of free radicals, including reactive oxygen species (ROS). Syagrus coronata (S. coronata), a palm tree, exhibits antioxidant activity attributed to its phytochemical composition, containing fatty acids, polyphenols, and flavonoids. The aim of this investigation was to examine the potential neuroprotective effects of S. coronata fixed oil against rotenone-induced toxicity using Drosophila melanogaster. Young Drosophila specimens (3-4 d old) were exposed to a diet supplemented with rotenone (50 µM) for 7 d with and without the inclusion of S. coronata fixed oil (0.2 mg/g diet). Data demonstrated that rotenone exposure resulted in significant locomotor impairment and increased mortality rates in flies. Further, rotenone administration reduced total thiol levels but elevated lipid peroxidation, iron (Fe) levels, and nitric oxide (NO) levels while decreasing the reduced capacity of mitochondria. Concomitant administration of S. coronata exhibited a protective effect against rotenone, as evidenced by a return to control levels of Fe, NO, and total thiols, lowered lipid peroxidation levels, reversed locomotor impairment, and enhanced % cell viability. Molecular docking of the oil lipidic components with antioxidant enzymes showed strong binding affinity to superoxide dismutase (SOD) and glutathione peroxidase (GPX1) enzymes. Overall, treatment with S. coronata fixed oil was found to prevent rotenone-induced movement disorders and oxidative stress in Drosophila melanogaster.

The effect of dyskinesia on postural control, balance, gait, and fall risk in people with Parkinson's disease: a systematic review protocol

Dyskinesia affects the limbs, trunk, and head and is more prevalent in people with Parkinson's disease (PD) and a history of falls. More evidence about the effects of dyskinesia on postural control, balance, gait, and fall risk could help improve the quality of life of individuals with PD. This review aims to examine associations between dyskinesia and postural control, balance, gait, and fall risk in individuals with PD. Such information could lead to new approaches to quality of life improvement among individuals with PD. PubMed, CINAHL, PsycInfo, Scopus, and SciELO will be searched for longitudinal, cohort, and case-control studies published in English or Portuguese in any year that investigated the association between dyskinesia and postural control, balance, gait, and fall risk in individuals with PD. Two reviewers will independently evaluate the titles, abstracts, and full texts according to PRISMA guidelines to select eligible studies for the review. Data on participants, dyskinesia, postural control, balance, gait, and fall risk will be extracted and summarized in tables. Two reviewers will independently assess the methodological quality of each study using the Newcastle Ottawa quality assessment scale. Meta-analysis will not be performed. The results of this systematic review will offer insight into the effects of dyskinesia on postural control, balance, gait, and fall risk. Such information could significantly contribute to informed decisions about early motor intervention in individuals with PD. (AU)

ATP1A2-related epileptic encephalopathy and movement disorder: Clinical features of three novel patients.

OBJECTIVE: Variants in the ATP1A2 gene exhibit a wide clinical spectrum, ranging from familial hemiplegic migraine to childhood epilepsies and early infantile developmental epileptic encephalopathy (EIDEE) with movement disorders. This study aims to describe the epileptology of three unpublished cases and summarize epilepsy features of the other 17 published cases with ATP1A2 variants and EIDEE. METHODS: Medical records of three novel patients with pathogenic ATP1A2 variants were retrospectively reviewed. Additionally, the PUBMED, EMBASE, and Cochrane databases were searched until December 2023 for articles on EIDEE with ATP1A2 variants, without language or publication year restrictions. RESULTS: Three female patients, aged 6 months-10 years, were investigated. Epilepsy onset occurred between 5 days and 2 years, accompanied by severe developmental delay, intellectual disability, drug-resistant epilepsy, severe movement disorder, and recurrent status epilepticus. All individuals had pathogenic variants of the ATP1A2 gene (ATP1A2 c.720_721del (p.Ile240MetfsTer9), ATP1A2c.3022C > T (p.Arg1008Trp), ATP1A2 c.1096G > T (p.Gly366Cys), according to ACMG criteria. Memantine was p) rescribed to three patients, one with a reduction in ictal frequency, one with improvement in gait pattern, coordination, and attention span, and another one in alertness without significant side effects. SIGNIFICANCE: This study reinforces the association between ATP1A2 variants and a severe phenotype. All patients had de novo variants, focal motor seizures with impaired awareness as the primary type of seizure; of the 11 EEGs recorded, 10 presented a slow background rhythm, 7 multifocal interictal epileptiform discharges (IED), predominantly temporal IEDs, followed by frontal IED, as well as ten ictal recordings, which showed ictal onset from the same regions mentioned above. Treatment with antiseizure medication was generally ineffective, but memantine showed moderate improvement. Prospective studies are needed to enlarge the phenotype and assess the efficacy of NMDA receptor antagonist therapies in reducing seizure frequency and improving quality of life.

Movement Disorder Perspectives on Monocarboxylate 8 Deficiency: A Case Series of 3 Colombian Patients with Allan-Herndon-Dudley Syndrome.

BACKGROUND: Deficiencies in the thyroid hormone transporter monocarboxylate 8 (MCT8) due to pathogenic variants in the SLC16A2 gene (OMIM 300095) result in a complex phenotype with main endocrine and neurologic symptoms. This rare disorder, named Allan-Herndon-Dudley syndrome (AHDS) (OMIM 300523), is inherited in an X-linked trait. One of the prominent features of AHDS is the presence of movement disorders (MD), which are complex and carry a significant burden of the disease. CASES: Patient 1: male with hypotonia since birth, developmental delay, dystonic posturing at 4 months and at 15 months, and startle reaction developed with sensory stimuli. Patient 2: male, at 2 months, shows hypotonia and developmental delay, paroxysmal episodes triggered by a stimulus with sudden blush, tonic asymmetric posture, and no epileptiform activity. At 10 months, generalized dystonic posturing. Patient 3: typical neurodevelopmental milestones until 6 months; at 24 months, dystonia, startle reaction, and upper motoneuron signs. CONCLUSIONS: We aim to describe our patients diagnosed with AHDS, focusing on MD phenomenology and strengthening the phenotype-genotype correlations for this rare condition.

MRI of the Spine in Patients who Toe Walk: Is There a Role?

BACKGROUND: Little is known about the prevalence of intraspinal pathology in children who toe walk, but magnetic resonance imaging (MRI) may be part of the diagnostic workup. The purpose of this study was to examine the role of MRI for children who toe walk with a focus on the rate of positive findings and associated neurosurgical interventions performed for children with said MRI findings. METHODS: A single-center tertiary hospital database was queried to identify a cohort of 118 subjects with a diagnosis of toe walking who underwent spinal MRI during a 5-year period. Patient and MRI characteristics were summarized and compared between subjects with a major abnormality, minor abnormality, or no abnormality on MRI using multivariable logistic regression. Major MRI abnormalities included those with a clear spinal etiology, such as fatty filum, tethered cord, syrinx, and Chiari malformation, while minor abnormalities had unclear associations with toe walking. RESULTS: The most common primary indications for MRI were failure to improve with conservative treatment, severe contracture, and abnormal reflexes. The prevalence of major MRI abnormalities was 25% (30/118), minor MRI abnormalities was 19% (22/118), and normal MRI was 56% (66/118). Patients with delayed onset of toe walking were significantly more likely to have a major abnormality on MRI ( P =0.009). The presence of abnormal reflexes, severe contracture, back pain, bladder incontinence, and failure to improve with conservative treatment were not significantly associated with an increased likelihood of major abnormality on MRI. Twenty-nine (25%) subjects underwent tendon lengthening, and 5 (4%) underwent neurosurgical intervention, the most frequent of which was detethering and sectioning of fatty filum. CONCLUSIONS: Spinal MRI in patients who toe walk has a high rate of major positive findings, some of which require neurosurgical intervention. The most significant predictor of intraspinal pathology was the late onset of toe walking after the child had initiated walking. MRI of the spine should be considered by pediatric orthopedic surgeons in patients with toe walking who present late with an abnormal clinical course. LEVEL OF EVIDENCE: Level III Retrospective Comparative Study.

The Huntington's Disease Gene Discovery.

The gene for Huntington's disease (HD) was discovered in 1993, after an international collaborative initiative that led researchers to remote regions of South America. It was the most remarkable milestone, since George Huntington's initial description. Through the phenomenological discussions led by Jean-Martin Charcot and Willian Osler, and finally Americo Negrette's reports, which served as the inspiration for the Venezuela Project led by Nancy Wexler, the journey toward discovering the Huntington's disease (HD) gene was marked by substantial efforts. This monumental achievement involved the analysis of more than 18,000 blood samples and gathered dozens of researchers in an integrated effort, enabling the mapping of the gene on chromosome 4 in 1983 and leading, a decade later, to the precise localization and identification of the HTT gene. The discovery of the HD mutation represented a pivotal moment in the field of genetics and neurology, significantly enhancing our understanding of the disease and creating opportunities for future treatments. The progress made and the knowledge gained during this journey catalyzed the development of many innovative molecular techniques that have advanced research in other medical conditions. In this article, the authors celebrate three decades of this memorable event, revisiting the historical aspects, providing insights into the techniques developed, and delving into the paths that ultimately led to the discovery of the HD gene. © 2024 International Parkinson and Movement Disorder Society.

Movement disorders in hereditary spastic paraplegias.

BACKGROUND: Hereditary or familial spastic paraplegias (SPG) comprise a group of genetically and phenotypically heterogeneous diseases characterized by progressive degeneration of the corticospinal tracts. The complicated forms evolve with other various neurological signs and symptoms, including movement disorders and ataxia. OBJECTIVE: To summarize the clinical descriptions of SPG that manifest with movement disorders or ataxias to assist the clinician in the task of diagnosing these diseases. METHODS: We conducted a narrative review of the literature, including case reports, case series, review articles and observational studies published in English until December 2022. RESULTS: Juvenile or early-onset parkinsonism with variable levodopa-responsiveness have been reported, mainly in SPG7 and SPG11. Dystonia can be observed in patients with SPG7, SPG11, SPG22, SPG26, SPG35, SPG48, SPG49, SPG58, SPG64 and SPG76. Tremor is not a frequent finding in patients with SPG, but it is described in different types of SPG, including SPG7, SPG9, SPG11, SPG15, and SPG76. Myoclonus is rarely described in SPG, affecting patients with SPG4, SPG7, SPG35, SPG48, and SPOAN (spastic paraplegia, optic atrophy, and neuropathy). SPG4, SPG6, SPG10, SPG27, SPG30 and SPG31 may rarely present with ataxia with cerebellar atrophy. And autosomal recessive SPG such as SPG7 and SPG11 can also present with ataxia. CONCLUSION: Patients with SPG may present with different forms of movement disorders such as parkinsonism, dystonia, tremor, myoclonus and ataxia. The specific movement disorder in the clinical manifestation of a patient with SPG may be a clinical clue for the diagnosis.

ANTECEDENTES: As paraplegias espásticas hereditárias ou familiares (SPG) compreendem um grupo de doenças geneticamente e fenotipicamente heterogêneas caracterizadas por degeneração progressiva dos tratos corticospinais. As formas complicadas evoluem com vários outros sinais e sintomas neurológicos, incluindo distúrbios do movimento e ataxia. OBJETIVO: Resumir as descrições clínicas de SPG que se manifestam com distúrbios do movimento ou ataxias para auxiliar o clínico na tarefa de diagnosticar essas doenças. MéTODOS: Realizamos uma revisão da literatura, incluindo relatos de casos, séries de casos, artigos de revisão e estudos observacionais publicados em inglês até dezembro de 2022. RESULTADOS: O parkinsonismo juvenil ou de início precoce com resposta variável à levodopa foi relatado principalmente em SPG7 e SPG11. A distonia pode ser observada em pacientes com SPG7, SPG11, SPG22, SPG26, SPG35, SPG48, SPG49, SPG58, SPG64 e SPG76. O tremor não é um achado frequente em pacientes com SPG, mas é descrito em diferentes tipos de SPG, incluindo SPG7, SPG9, SPG11, SPG15 e SPG76. A mioclonia é raramente descrita em SPG, afetando pacientes com SPG4, SPG7, SPG35, SPG48 e SPOAN (paraplegia espástica, atrofia óptica e neuropatia). SPG4, SPG6, SPG10, SPG27, SPG30 e SPG31 podem raramente apresentar ataxia com atrofia cerebelar. E SPG autossômico recessivo, como SPG7 e SPG11, também pode apresentar ataxia. CONCLUSãO: Indivíduos com SPG podem apresentar diferentes formas de distúrbios do movimento, como parkinsonismo, distonia, tremor, mioclonia e ataxia. O distúrbio específico do movimento na manifestação clínica de um paciente com SPG pode ser uma pista clínica para o diagnóstico.

Intracerebroventricular baclofen therapy improves function and quality of life in a child with severe cerebral palsy.

Limited therapies are available for severe cerebral palsy children (CP) with complex movement disorders, especially when both dystonia and spasticity are present. In this publication, we present the improvement of a child with severe CP after intracerebroventricular baclofen therapy. The treatment can impact not just the movement disorders but also on the quality of life of the child and caregivers. Global functional improvements can be observed on the 6-month follow-up.

Development and Validation of the Dystonia-Pain Classification System: A Multicenter Study.

BACKGROUND: Dystonia is associated with disabling nonmotor symptoms like chronic pain (CP), which is prevalent in dystonia and significantly impacts the quality of life (QoL). There is no validated tool for assessing CP in dystonia, which substantially hampers pain management. OBJECTIVE: The aim was to develop a CP classification and scoring system for dystonia. METHODS: A multidisciplinary group was established to develop the Dystonia-Pain Classification System (Dystonia-PCS). The classification of CP as related or unrelated to dystonia was followed by the assessment of pain severity score, encompassing pain intensity, frequency, and impact on daily living. Then, consecutive patients with inherited/idiopathic dystonia of different spatial distribution were recruited in a cross-sectional multicenter validation study. Dystonia-PCS was compared to validated pain, mood, QoL, and dystonia scales (Brief Pain Inventory, Douleur Neuropathique-4 questionnaire, European QoL-5 Dimensions-3 Level Version, and Burke-Fahn-Marsden Dystonia Rating Scale). RESULTS: CP was present in 81 of 123 recruited patients, being directly related to dystonia in 82.7%, aggravated by dystonia in 8.8%, and nonrelated to dystonia in 7.5%. Dystonia-PCS had excellent intra-rater (Intraclass Correlation Coefficient - ICC: 0.941) and inter-rater (ICC: 0.867) reliability. In addition, pain severity score correlated with European QoL-5 Dimensions-3 Level Version's pain subscore (r = 0.635, P < 0.001) and the Brief Pain Inventory's severity and interference scores (r = 0.553, P < 0.001 and r = 0.609, P < 0.001, respectively). CONCLUSIONS: Dystonia-PCS is a reliable tool to categorize and quantify CP impact in dystonia and will help improve clinical trial design and management of CP in patients affected by this disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Web version of the protocol of the orofacial myofunctional evaluation with scores: usability and learning.

PURPOSE: The Orofacial Myofunctional Evaluation with Scores (OMES) protocol has been validated and used in clinical practice and research. The goals of this study were to develop, analyze and improve a version of OMES for the Web and to investigate the relationship between the usability judgments and the prior experience of the evaluators and whether using the interface promotes learning, as shown by the task completion time (TCT). METHODS: Study steps: 1) inspection of the prototype by the team; 2) evaluation of usability by three experienced speech-language pathologists (SLPs); and 3) evaluation of its usability by 12 SLPs with varying levels of experience in the use of OMES. Participants answered the Heuristic evaluation (HE), the Computer System Usability Questionnaire (CSUQ), and expressed free comments. The TCT was recorded. RESULTS: The OMES-Web reached excellent usability levels, and the participants were highly satisfied. The correlations between the participants' experience and the HE and CSUQ scores were not significant. The TCT decreased significantly throughout the tasks. CONCLUSION: OMES-Web meets the usability criteria, and participants feel satisfied with the system regardless of their level of experience. The fact that it is easy to learn favors its adoption by professionals.

Progressive Spinal Cord Degeneration in Friedreich's Ataxia: Results from ENIGMA-Ataxia.

BACKGROUND: Spinal cord damage is a hallmark of Friedreich's ataxia (FRDA), but its progression and clinical correlates remain unclear. OBJECTIVE: The objective of this study was to perform a characterization of cervical spinal cord structural damage in a large multisite FRDA cohort. METHODS: We performed a cross-sectional analysis of cervical spinal cord (C1-C4) cross-sectional area (CSA) and eccentricity using magnetic resonance imaging data from eight sites within the ENIGMA-Ataxia initiative, including 256 individuals with FRDA and 223 age- and sex-matched control subjects. Correlations and subgroup analyses within the FRDA cohort were undertaken based on disease duration, ataxia severity, and onset age. RESULTS: Individuals with FRDA, relative to control subjects, had significantly reduced CSA at all examined levels, with large effect sizes (d > 2.1) and significant correlations with disease severity (r < -0.4). Similarly, we found significantly increased eccentricity (d > 1.2), but without significant clinical correlations. Subgroup analyses showed that CSA and eccentricity are abnormal at all disease stages. However, although CSA appears to decrease progressively, eccentricity remains stable over time. CONCLUSIONS: Previous research has shown that increased eccentricity reflects dorsal column (DC) damage, while decreased CSA reflects either DC or corticospinal tract (CST) damage, or both. Hence our data support the hypothesis that damage to the DC and damage to CST follow distinct courses in FRDA: developmental abnormalities likely define the DC, while CST alterations may be both developmental and degenerative. These results provide new insights about FRDA pathogenesis and indicate that CSA of the cervical spinal cord should be investigated further as a potential biomarker of disease progression. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Movimiento escapular, distancia acromiohumeral, rango y fuerza rotacional glenohumeral en deportistas femeninas de handball de élite / Scapular motion, acromiohumeral distance, range and glenohumeral rotational strength in elite female handball athletes

Antecedentes: El handball es un deporte "overhead" que expone al hombro a demandas elevadas de carga durante la práctica, lo que puede llevar a esta articulación a sufrir adaptaciones específicas. La comprensión de estas adaptaciones es importante y puede ayudar a los clínicos a crear protocolos de prevención y a desarrollar programas de condicionamiento y rehabilitación para esta población. Objetivos: Generar un perfil descriptivo de:1) movimiento escapular durante la elevación y descenso de la extremidad superior en el plano escapular, 2) distancia acromiohumeral y 3) rango de movimiento y fuerza rotacional glenohumeral en deportistas femeninas de handball de élite. Métodos: Se realizo un estudio transversal observacional y descriptivo en 23 jugadoras (Edad = 22±4.3 años; Años de practica 9.7±3.5) de handball de élite, libres de dolor. Se valoró el movimiento escapular bilateral durante la elevación y el descenso del brazo, la distancia acromiohumeral durante la abducción activa y pasiva, y el rango de movimiento articular y la fuerza rotacional GH en rotación interna y externa. Se describen estas variables, comparándolas entre ambos brazos, y entre los grupos formados en función del déficit de rotación interna GH. Resultados: No se detectaron diferencias significativas en el movimiento escapular 3D ni en la distancia acromiohumeral entre los brazos. Se observó una disminución del rango de rotación interna (Diferencia Media (DM)= -11.09°; Intervalo Confianza 95% (IC)= -17.70,-4.47) y un incremento del rango de rotación externa (DM= 12.82°; IC= 6.07°,19.58°) en el hombro dominante. El torque rotacional GH en rotación externa fue mayor (DM= 0.36 Nm/kg; IC=-0.008 Nm/kg, -0.81Nm/kg) en el hombro dominante. Las participantes con déficit de rotación interna mostraron mayores rangos de rotación superior y tilt posterior escapular durante la elevación, mayor distancia acromiohumeral en reposo y mayor disminución de esta durante la elevación de la extremidad Conclusión: Los resultados sugieren que no existen diferencias en el movimiento escapular durante la elevación y descenso de la extremidad superior, ni en la distancia acromiohumeral en las diferentes posiciones de elevación GH activa y pasiva entre el brazo dominante y no dominante de las deportistas femeninas de handball de élite. Los hallazgos indican que el brazo lanzador de estas deportistas presenta diferencias en el rango rotacional y en la fuerza, que podrían representar un factor de riesgo lesional, siendo detectables en el ambiente clínico. Las deportistas que presentan GIRD, muestran mayor movimiento escapular 3D durante la elevación, mayor DAH en reposo y mayor disminución de esta durante la elevación de la ES

Background: Handball is an overhead sport that exposes the shoulder to high demands of load during the practice, which may lead this joint to sport-specific adaptions. Understanding these adaptions is important and may help clinicians to create preventive protocols and further develop conditioning and rehabilitation program to this population. Objectives: To generate a descriptive profile of:1) scapular motion during upper extremity raising and lowering along the scapular plane, 2) acromiohumeral distance, and 3) GH rotational range of motion and rotational strength in elite female handball athletes. Methods: This is observational and descriptive cross-sectional study. Twenty-three (22±4.3 years and 9.7±3.5 years of practice) pain free elite female handball players were assessed. Outcome measures included bilateral 3D scapular movement during raising and lowering of the arm, acromiohumeral distance during passive and active abduction, GH range of motion of internal and external rotation, and strength of the internal and external rotators. These variables were described by comparing them between both arms, and among the groups according to the GH internal rotation deficit. Results: No significant differences were detected in 3D scapular motion or acromiohumeral distance between the arms. A decrease in internal rotation range of motion (Mean Difference (MD) =-11.09°;95% Confidence Interval (CI)= -17.70°, -4.47°) and an increase in external rotation range of motion (MD= 12.82°; CI=6.07°, 19.58°) and in GH rotational torque in external rotation (MD=0.36 Nm/kg; CI=-0.008Nm/kg, -0.81Nm/kg) were observed in the dominant shoulder. Participants with internal rotation deficit showed greater ranges of superior rotation and scapular posterior tilt during raising, greater acromiohumeral distance at rest and greater decrease of this during limb elevation. Conclusion: The findings suggest there are no differences in in the scapular movement during upper extremity raising and lowering along the scapular plane, nor in the acromiohumeral distance during passive and active GH between the dominant and non-dominant arm of elite female handball athletes. The findings indicate that there are differences in rotational range of motion and strength between both arms, which could represent an injury risk factor, being detectable in the clinical sports environment. Participants with internal rotation deficit showed greater scapular 3D movement, greater DAH at rest and greater decrease of it during arm elevation

Dystonia, Chorea, and Ataxia: Three Challenging Cases.

Movement disorders comprise a heterogeneous and complex group of neurological disorders that increase (hyperkinetic) or decrease (hypokinetic) the speed or amplitude of movements, or disrupt their coordinated sequencing. In this article, we describe three instructive cases, exemplifying classic movement disorders, namely dystonia, chorea, and ataxia. We highlight the diagnostic approach based on clinical clues, syndromic reasoning, evaluation, and management recommendations. Each case ends with key messages for the clinicians.

Parkinsonism-Plus Syndrome Secondary to Neurosyphilis: Case Report and Literature Review.

Background/Objective: Neurosyphilis can be associated with a variety of clinical manifestations. There are only a few cases of neurosyphilis associated with parkinsonism-plus syndromes (PPSs) that have been reported in the literature. We describe a case of an elderly woman who presented with abnormal gait and progressive visual disturbance, probably secondary to neurosyphilis. Methods: Literature search was performed in Embase, Google Scholar, Medline, Scielo, and ScienceDirect using a set of terms that included parkinsonism, tremor, and syphilis. Case Report: A 64-year-old female was admitted because of vision problems, gait disturbances, and cognitive impairment. The neurological examination revealed bradykinesia, rigidity, and rest tremor. The pupils were bilaterally small and reacted in size to a near object but did not constrict when exposed to bright light. The conjugate eye movements showed a defective downward gaze. On neuropsychological examination, the mini-mental state exam showed a moderate cognitive impairment. Reduced phonemic fluency was observed. A positive serum venereal disease research laboratory (VDRL) test was noted. A cerebrospinal fluid analysis showed positive VDRL. Brain and cervical spine magnetic resonance imaging was normal. An electro-encephalogram showed diffused slow waves. Penicillin G was started. Six months after, the patient had a full recovery of her conjugate eye movements and cognitive functions. Upon further questioning, the patient reported no response with a levodopa attempt. Conclusions: To the authors' knowledge, two individuals developed progressive supra-nuclear palsy (PSP), and one presented corticobasal degeneration (CBD), probably associated with neurosyphilis. This is the second case to document the occurrence of a progressive supra-nuclear palsy because of syphilis.

Nueva mutación en el gen KMT2B como causa de distonía generalizada de inicio temprano: reporte de caso / Early-onset generalized dystonia caused by a new mutation in the KMT2B gene: Case report

La distonía por mutación en el gen KMT2B es un subtipo recientemente descrito del inicio focal de la enfermedad en los miembros inferiores que, posteriormente, evoluciona a una forma generalizada con compromiso cervical y orofaríngeo, disartria, trastorno secundario de la deglución y discapacidad intelectual. Se describe el caso de una escolar de 10 años de edad, sin antecedentes de consanguinidad ni historia familiar de enfermedad neurológica, que presentó alteración de la marcha y distonía de inicio focal, de curso progresivo a una forma generalizada que afectó sus músculos orofaciales y bulbares con alteración significativa del lenguaje y la deglución. Los estudios metabólicos y sistémicos, incluidas las neuroimágenes, no evidenciaron anormalidades. Se hizo una secuenciación genómica completa y se identificó una nueva variante, probablemente patogénica heterocigota, en el gen KMT2B, la c.1205delC, p.(Pro402Hisfs*5), que causa desplazamiento en el marco de lectura. Este hallazgo explica el fenotipo de la paciente y la distonía de inicio temprano autosómica dominante. Se reporta una nueva mutación heterocigota del gen KMT2B como causa de distonía generalizada de inicio temprano, no reportada en la literatura especializada hasta el momento. El diagnóstico de esta afección tiene implicaciones en el tratamiento y el pronóstico de los pacientes, porque las estrategias terapéuticas tempranas pueden prevenir su rápido deterioro y un curso más grave de la enfermedad.

Introduction: KMT2B-related dystonia is a recently described subtype of focal-onset dystonia in the lower limbs, evolving into a generalized form with cervical, oropharyngeal involvement, dysarthria, swallowing disorder and intellectual disability. Clinical case: We describe the case of a 10-year-old female patient, without a history of consanguinity or neurological disease. She manifested abnormal gait and dystonia with focal onset and progressive course with evolution into generalized dystonia, affecting orofacial and bulbar muscles, significant alteration of language and swallowing. Metabolic and systemic studies, including neuroimaging, were found to be normal. A complete genomic sequencing study was performed identifying a new, probably pathogenic, heterozygous variant in the KMT2B gene, c.1205delC, p. (Pro402Hisfs*5), causing displacement in the reading frame, a finding that explains the patient's phenotype and it is associated to autosomal dominant childhood-onset dystonia-28. Conclusion: We report a new heterozygous mutation in the KMT2B gene as a cause of generalized early-onset dystonia not reported in the literature until the date. The diagnosis of this pathology has implications for the treatment and prognosis of patients, given that therapeutic strategies implemented early can prevent the fast deterioration and severe course of this disease.

"On Chorea": 150 Years of the Beginning of Hope.

"On Chorea" by George Huntington was published on April 13, 1872, in The Medical and Surgical Reporter of Philadelphia. Despite being a milestone in the recognition of the disease that later would bear his name, some myths and curiosities continue to surround the history of this publication and its author. In this History, the authors pay tribute to the 150th anniversary of the publication of this iconic article. © 2022 International Parkinson and Movement Disorder Society.