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1.
J Bodyw Mov Ther ; 37: 57-62, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38432842

RESUMEN

INTRODUCTION: Shoulder injuries in baseball players cause excessive shoulder load during pitching and scapular dyskinesis (SD). However, the characteristics of pitching kinetics in the shoulder joint with SD are unclear. This study aimed to investigate the effect of SD on pitching kinetics in the shoulder joint of baseball players. METHOD: Seventy-two college and independent league baseball players participated in the study. The pitching motion was measured using an 18-camera motion-capture system. SD was classified into four types (I-IV) using the scapular dyskinesis test (SDT). The pitching kinetics data were analyzed. RESULTS: The agreement of SD in this study was 56/72 (77.8%). SD were classified into 31 abnormal group (type I-Ⅲ) and 25 control group (type Ⅳ). Three participants with measurement failure during the pitching motion analysis were excluded from the analysis. The abnormal group showed a larger maximum value of the glenohumeral normalized anterior joint force than the control group. CONCLUSIONS: These results suggest that an increase in GH anterior force during pitching causes an excessive increase in external rotation of the GH with an insufficient posterior tilt of the scapula with SD. Therefore, baseball pitching with SD may involve shoulder injuries owing to excessive shoulder load during pitching.


Asunto(s)
Béisbol , Discinesias , Lesiones del Hombro , Articulación del Hombro , Humanos , Hombro , Escápula , Discinesias/etiología
2.
J Tradit Chin Med ; 43(4): 829-833, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37454270

RESUMEN

Nonketotic hyperglycemic hemichorea-hemiballismus is a rare syndrome in the clinic, and treatment is often delayed. Hypoglycemic therapy is the most widely used and effective treatment, but some patients experience a slower improvement. Other symptomatic treatment medicines have some degree of side effects. Acupuncture treatment is beneficial for hemichorea-hemiballismus. A male patient, aged 59 years, first visited our hospital outpatient department due to motor agitation with involuntary movements of the right limb. He had a history of type 2 diabetes mellitus and poor blood glucose control. His serum glucose was 26.5 mmol/L (normal: 4.4-6.1 mmol/L), and magnetic resonance imaging demonstrated an irregular area of high signal intensity in T1-weighted imaging, low signal intensity on T2-weighted imaging, and high signal intensity in the left corpus striatum in T2-FLAIR imaging. Hospitalization was recommended for the patient. After ruling out other possibilities, he was eventually diagnosed with nonketotic hyperglycemic hemichorea-hemiballismus. Intensive glycemic control was immediately started with subcutaneous injection and acupuncture treatment at "governor vessel 13 acupoints", and the involuntary movements completely disappeared on the ninth day of hospitalization. The pathophysiology of nonketotic hyperglycemic hemichorea-hemiballismus is unclear. Different patient histories lead to different brain tissue conditions, and relapses and uncontrolled blood glucose add difficulties to treatment. According to Traditional Chinese Medicine theory, insufficient kidney essence leads to brain dystrophy and causes the symptoms of hemichorea-hemiballismus. Research evidence has shown that acupuncture at "governor vessel 13 acupoints" has a beneficial treatment effect on nonketotic hyperglycemic hemichorea-hemiballismus.


Asunto(s)
Terapia por Acupuntura , Corea , Diabetes Mellitus Tipo 2 , Discinesias , Humanos , Masculino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/patología , Discinesias/etiología , Discinesias/terapia , Discinesias/diagnóstico , Corea/etiología , Corea/terapia , Corea/diagnóstico , Encéfalo/patología , Terapia por Acupuntura/efectos adversos
3.
Medicine (Baltimore) ; 100(10): e25036, 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33725887

RESUMEN

INTRODUCTION: Poststroke dyskinesia is the most common clinical symptom after stroke, which greatly affects the patients' daily life. Eye-acupuncture is an effective method for stroke. And the rehabilitation training has been widely used for patients suffer from stroke. However, whether eye-acupuncture combined with rehabilitation training has greater clinical efficacy for poststroke dyskinesia is still unknown. Our aim in this systematic review was to evaluate the clinical efficacy of eye-acupuncture combined with rehabilitation training (EACRT) as a treatment for dyskinesia after stroke. METHODS AND ANALYSIS: We will search the following 4 databases of registered trials and 7 electronic databases from inception to March 2021:Cochrane Stroke Group, Cochrane Central Register of Controlled, the World Health Organization International Clinical Trials Registry Platform, the Chinese Clinical Trial Registry; PubMed, MEDLINE, Embase, CNKI, VIP, WanFang, and CBM. All relevant randomized controlled trials focus on EACRT will be included. The primary outcome will be the Fugl-Meyer Assessment. The Secondary outcomes will include Activity of Daily Living, clinical effective rate and the Visual Analogue Score. Two reviewers will independently conduct the Study selection and data extraction. The data synthesis and assessment of risk of bias will be performed by RevMan5.2. ETHICS AND DISSEMINATION: The ethical approval is unnecessary that systematic review is based on published articles other than patients. The results of this meta-analysis will be published in an open access (OA) journal according to the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA). PROSPERO REGISTRATION NUMBER: CRD42020168278.


Asunto(s)
Terapia por Acupuntura/métodos , Discinesias/terapia , Ojo , Rehabilitación de Accidente Cerebrovascular/métodos , Accidente Cerebrovascular/complicaciones , Terapia Combinada/métodos , Discinesias/etiología , Humanos , Metaanálisis como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Revisiones Sistemáticas como Asunto , Resultado del Tratamiento
4.
Medicine (Baltimore) ; 99(38): e22207, 2020 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-32957353

RESUMEN

BACKGROUND: Stroke is the primary cause of adult disability in China, which causes serious personal, family, and social burden. "Central peripheral central" closed-loop rehabilitation theory is proved to be an effective neural rehabilitation model. Based on this theory, repetitive transcranial magnetic stimulation (rTMS) combined with magnetic stimulation of Neiguan (PC6) and Sanyinjiao (SP6) may be an effective treatment for limb dysfunction after stroke. However, the efficacy and mechanism of repetitive magnetic stimulation of M1 region combined with magnetic stimulation of Neiguan and Sanyinjiao points on limb dysfunction after stroke has not been confirmed. METHODS/DESIGN: This study is a prospective, randomized, controlled, open trial. We randomly divided 42 subjects, aged 35 to 80 years, diagnosed with ischemic stroke within 1 month, into 2 groups with a ratio of 1:1. On the basis of this medical treatment, patients in the experimental group received 1 Hz rTMS in M1 area on the contralateral side, and 3 Hz rTMS treatment at Neiguan point and Sanyinjiao point on the affected side. The control group was treated with acupuncture (body acupuncture). All patients were treated once a day and followed up for 10 days. The National Institute of Health Stroke Scale score, simplified fulg Meyer, modified Barthel index, and cortical excitability were evaluated on the day of enrollment and the 10th day of treatment respectively. The modified Barthe index was followed up on the 30th day of treatment, and the adverse reactions were recorded at any time. The mechanism of rTMS will be revealed by Barthe index before treatment, on the 10th day of treatment and on the 30th day of follow-up. The results were analyzed by spss19.0 software, and the quantitative indexes were analyzed by t test and rank sum test. χ test was used for non-grade counting, and rank sum test was used for grade counting. All statistical tests were performed with bilateral test. If P value is less than or equal to .05, the difference will be considered statistically significant. CONCLUSION: The purpose of this study was to determine the effect of repetitive magnetic stimulation of M1 region combined with magnetic stimulation of Neiguan and Sanyinjiao points on limb function after stroke. Through this study, we expect to explore a new scheme for the treatment of poststroke dyskinesia, and prove that compared with rTMS and acupuncture alone, the closed-loop rehabilitation theory based on "center peripheral center" can be more efficient and safe in the treatment of poststroke limb dysfunction. TRIAL REGISTRATION: The trial was registered in China clinical trial registry (http://www.chictr.org.cn/index.aspx), ID: ChiCTR1900026890 (October 25, 2019).


Asunto(s)
Puntos de Acupuntura , Terapia por Acupuntura , Discinesias/terapia , Rehabilitación de Accidente Cerebrovascular/métodos , Estimulación Magnética Transcraneal , Discinesias/etiología , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Accidente Cerebrovascular/complicaciones
5.
J Neurol ; 267(4): 954-965, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31797086

RESUMEN

Parkinson's disease (PD) is the world's fastest growing neurological disorder disabling patients through a broad range of motor and non-motor symptoms. For the clinical management, a multidisciplinary approach has increasingly been shown to be beneficial. In Germany, inpatient Parkinson's Disease Multimodal Complex Treatment (PD-MCT) is a well-established and frequent approach, although data on its effectiveness are rare. We conducted a prospective real-world observational study in 47 subjects [age (M ± SD): 68.5 ± 9.0 years, disease duration: 8.5 ± 5.3 years, modified Hoehn and Yahr stage (median, IQR): 3, 2.5-3] aiming at evaluating the effectiveness of 14-day PD-MCT in terms of quality of life (Parkinson's Disease Questionnaire, EuroQol), motor [Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III], Timed Up and Go Test, Purdue Pegboard Test) and non-motor symptoms (revised Beck Depression Inventory). Six weeks after hospital discharge, a follow-up examination was performed. PD patients with a predominantly moderate disability level benefited from PD-MCT in terms of health-related quality of life, motor symptoms and non-motor symptoms (depression). Significant improvements were found for social support, emotional well-being and bodily discomfort domains of health-related quality of life. Sustainable improvement occurred for motor symptoms and the subjective evaluation of health state. We found a higher probability of motor response especially for patients with moderate motor impairment (MDS-UPDRS III ≥ 33). In conclusion, Parkinson's Disease Multimodal Complex Treatment improves motor symptoms, depression and quality of life. A more detailed selection of patients who will benefit best from this intervention should be examined in future studies.


Asunto(s)
Depresión/rehabilitación , Discinesias/rehabilitación , Rehabilitación Neurológica/métodos , Evaluación de Resultado en la Atención de Salud , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/rehabilitación , Calidad de Vida , Anciano , Terapia Combinada , Personas con Discapacidad , Discinesias/etiología , Terapia por Ejercicio , Femenino , Estudios de Seguimiento , Humanos , Hipertermia Inducida , Terapia del Lenguaje , Masculino , Masaje , Persona de Mediana Edad , Terapia Ocupacional , Enfermedad de Parkinson/complicaciones , Índice de Severidad de la Enfermedad
6.
Expert Opin Drug Saf ; 18(12): 1203-1218, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31619083

RESUMEN

Introduction: Dyskinesia is a motor complication of Parkinson's disease (PD) characterized by clinical heterogeneity and complex pathogenesis and associated with long-term levodopa therapy. Recent and controversial views on the management of PD patients have suggested that overall dyskinesia rates, and particularly troublesome dyskinesia, may be declining due to more conservative levodopa dosing regimens, widespread availability and early introduction of deep brain stimulation, and use of continuous drug delivery strategies. Nevertheless, anti-dyskinetic agents continue to be evaluated in clinical trials and recent efforts have focused on non-dopaminergic drugs.Areas covered: In this review, the authors discuss the clinical phenomenology and current understanding of dyskinesia in PD with a focus on up-to-date therapeutic strategies to prevent and manage these drug-related involuntary movements.Expert opinion: The way dyskinesia in PD is currently managed should be changed and attention should be focused toward a more personalized medicine rather than a one-fits-all-approach. The correct identification of dyskinesia types and tailored treatments are crucial for a better management of these involuntary movements together with a holistic approach which considers additional influencing factors. The future for dyskinesia treatment is likely to be found in non-dopaminergic approaches, first set into motion by the introduction of amantadine.


Asunto(s)
Antiparkinsonianos/administración & dosificación , Discinesias/tratamiento farmacológico , Enfermedad de Parkinson/tratamiento farmacológico , Animales , Antiparkinsonianos/efectos adversos , Estimulación Encefálica Profunda , Sistemas de Liberación de Medicamentos , Discinesia Inducida por Medicamentos/prevención & control , Discinesias/etiología , Discinesias/fisiopatología , Humanos , Levodopa/administración & dosificación , Levodopa/efectos adversos , Enfermedad de Parkinson/fisiopatología
7.
Sci Rep ; 9(1): 3602, 2019 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-30837649

RESUMEN

Aldehyde dehydrogenase 1A1 (ALDH1A1), a retinoic acid (RA) synthase, is selectively expressed by the nigrostriatal dopaminergic (nDA) neurons that preferentially degenerate in Parkinson's disease (PD). ALDH1A1-positive axons mainly project to the dorsal striatum. However, whether ALDH1A1 and its products regulate the activity of postsynaptic striatal neurons is unclear. Here we show that µ-type opioid receptor (MOR1) levels were severely decreased in the dorsal striatum of postnatal and adult Aldh1a1 knockout mice, whereas dietary supplement of RA restores its expression. Furthermore, RA treatment also upregulates striatal MOR1 levels and signaling and alleviates L-DOPA-induced dyskinetic movements in pituitary homeobox 3 (Pitx3)-deficient mice that lack of ALDH1A1-expressing nDA neurons. Therefore, our findings demonstrate that ALDH1A1-synthesized RA is required for postsynaptic MOR1 expression in the postnatal and adult dorsal striatum, supporting potential therapeutic benefits of RA supplementation in moderating L-DOPA-induced dyskinesia.


Asunto(s)
Familia de Aldehído Deshidrogenasa 1/fisiología , Cuerpo Estriado/efectos de los fármacos , Neuronas Dopaminérgicas/patología , Discinesias/prevención & control , Proteínas de Homeodominio/fisiología , Receptores Opioides mu/metabolismo , Retinal-Deshidrogenasa/fisiología , Factores de Transcripción/fisiología , Tretinoina/farmacología , Animales , Cuerpo Estriado/patología , Dopamina/metabolismo , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/metabolismo , Discinesias/etiología , Discinesias/metabolismo , Discinesias/patología , Femenino , Masculino , Ratones , Ratones Noqueados , Receptores Opioides mu/genética
8.
Medicine (Baltimore) ; 97(48): e13387, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30508935

RESUMEN

Motor dysfunction is a common and severe complication of stroke that affects the quality of life of these patients. Currently, motor function rehabilitation predominantly focuses on active movement training; nevertheless, the role of sensory input is usually overlooked. Sensory input is very important to motor function. Voluntary functional movement necessitates preparation, execution, and monitoring functions of the central nervous system, while the monitoring needs the participation of the sensory system. Sensory signals affect motor functions by inputting external environment information and intrinsic physiological status as well as by guiding initiation of the motor system. Recent studies focusing on sensory input-based rehabilitation training for post-stroke dyskinesia have demonstrated that sensory function has significant effects on voluntary functional movements. In conclusion, sensory input plays a crucial role in motor function rehabilitation, and the combined sensorimotor training modality is more effective than conventional motor-oriented approaches.


Asunto(s)
Discinesias/terapia , Rehabilitación de Accidente Cerebrovascular/métodos , Animales , Ganglios Basales/fisiología , Cerebelo/fisiología , Discinesias/etiología , Humanos , Musicoterapia , Calidad de Vida , Sensación/fisiología , Corteza Sensoriomotora/fisiología , Accidente Cerebrovascular/complicaciones
10.
Neurotox Res ; 34(3): 375-387, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29629512

RESUMEN

Reserpine (RES)-induced orofacial dyskinesia (OD) has been used as an animal model for human tardive dyskinesia (TD) for decades, due to its strong pathophysiological association with striatal oxidative stress and neural cytoarchitecture alteration. L-Theanine (LT), one of the major amino acid components in green tea, has potent antioxidative, anti-inflammatory, and neuroprotective effects. In this study, we examined the potential protective effects of LT on RES-induced behavioral and neurochemical dysfunction in rats. RES treatment (1 mg/kg s.c., 3 injections 1 day apart) induced significant increases (p < 0.001) in the frequency of vacuous chewing movements (VCM), tongue protrusion (TP), as well as the duration of facial twitching (FT). LT treatment (100, 300 mg/kg orally for 14 days, starting 10 days before RES injection) was able to prevent most of the RES-induced OD. Moreover, LT treatment reduced the RES-induced lipid peroxidation (LPO) production, increased the antioxidation power and catecholamines in the striatum, and significantly reduced the levels of neuroinflammatory and apoptotic markers. Our results indicated that LT was able to counteract the increased oxidative damage, neurotransmitter deficiency, neuroinflammation, and apoptosis induced by RES, and these results have demonstrated the possible neuroprotective effects of LT against RES-induced OD, including antioxidation, neurochemical deficiency prevention, antineuroinflammation, and antiapoptosis. These findings, therefore, suggest a potential role for LT to have a clinically relevant therapeutic effect in delaying or treating human TD.


Asunto(s)
Antipsicóticos/toxicidad , Discinesias/tratamiento farmacológico , Discinesias/etiología , Glutamatos/uso terapéutico , Reserpina/toxicidad , Análisis de Varianza , Animales , Caspasa 3/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Glutatión/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Neurotransmisores/metabolismo , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo
12.
Exp Neurol ; 302: 155-168, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29339052

RESUMEN

Recently, the biased and highly selective 5-HT1A agonists, NLX-112, F13714 and F15599, have been shown to alleviate dyskinesia in rodent and primate models of Parkinson's disease, while marginally interfering with antiparkinsonian effects of levodopa. To provide more detailed information on the processes underlying the alleviation of dyskinesia, we have here investigated changes in the spectral contents of local field potentials in cortico-basal ganglia-thalamic circuits following treatment with this novel group of 5-HT1A agonists or the prototypical agonist, 8-OH-DPAT. Dyskinetic symptoms were consistently associated with 80 Hz oscillations, which were efficaciously suppressed by all 5-HT1A agonists and reappeared upon co-administration of the antagonist, WAY100635. At the same time, the peak-frequency of fast 130 Hz gamma oscillations and their cross-frequency coupling to low-frequency delta oscillations were modified to a different extent by each of the 5-HT1A agonists. These findings suggest that the common antidyskinetic effects of these drugs may be chiefly attributable to a reversal of the brain state characterized by 80 Hz gamma oscillations, whereas the differential effects on fast gamma oscillations may reflect differences in pharmacological properties that might be of potential relevance for non-motor symptoms.


Asunto(s)
Ganglios Basales/fisiología , Ondas Encefálicas/efectos de los fármacos , Corteza Cerebral/fisiología , Discinesias/tratamiento farmacológico , Potenciales Evocados/fisiología , Agonistas del Receptor de Serotonina 5-HT1/uso terapéutico , Tálamo/fisiología , Animales , Ganglios Basales/efectos de los fármacos , Ondas Encefálicas/fisiología , Corteza Cerebral/efectos de los fármacos , Modelos Animales de Enfermedad , Discinesias/etiología , Estimulación Eléctrica/efectos adversos , Femenino , Levodopa/efectos adversos , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiología , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson Secundaria/tratamiento farmacológico , Piperazinas/uso terapéutico , Piperidinas/farmacología , Piperidinas/uso terapéutico , Piridinas/farmacología , Piridinas/uso terapéutico , Ratas , Ratas Sprague-Dawley , Receptor de Serotonina 5-HT1A/metabolismo , Agonistas del Receptor de Serotonina 5-HT1/farmacología , Antagonistas de la Serotonina/uso terapéutico , Tálamo/efectos de los fármacos
13.
Schizophr Bull ; 43(5): 982-992, 2017 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-28911049

RESUMEN

Motor abnormalities are frequently observed in schizophrenia and structural alterations of the motor system have been reported. The association of aberrant motor network function, however, has not been tested. We hypothesized that abnormal functional connectivity would be related to the degree of motor abnormalities in schizophrenia. In 90 subjects (46 patients) we obtained resting stated functional magnetic resonance imaging (fMRI) for 8 minutes 40 seconds at 3T. Participants further completed a motor battery on the scanning day. Regions of interest (ROI) were cortical motor areas, basal ganglia, thalamus and motor cerebellum. We computed ROI-to-ROI functional connectivity. Principal component analyses of motor behavioral data produced 4 factors (primary motor, catatonia and dyskinesia, coordination, and spontaneous motor activity). Motor factors were correlated with connectivity values. Schizophrenia was characterized by hyperconnectivity in 3 main areas: motor cortices to thalamus, motor cortices to cerebellum, and prefrontal cortex to the subthalamic nucleus. In patients, thalamocortical hyperconnectivity was linked to catatonia and dyskinesia, whereas aberrant connectivity between rostral anterior cingulate and caudate was linked to the primary motor factor. Likewise, connectivity between motor cortex and cerebellum correlated with spontaneous motor activity. Therefore, altered functional connectivity suggests a specific intrinsic and tonic neural abnormality in the motor system in schizophrenia. Furthermore, altered neural activity at rest was linked to motor abnormalities on the behavioral level. Thus, aberrant resting state connectivity may indicate a system out of balance, which produces characteristic behavioral alterations.


Asunto(s)
Catatonia/fisiopatología , Cerebelo/fisiopatología , Corteza Cerebral/fisiopatología , Conectoma/métodos , Discinesias/fisiopatología , Esquizofrenia/fisiopatología , Núcleo Subtalámico/fisiopatología , Tálamo/fisiopatología , Adulto , Catatonia/diagnóstico por imagen , Catatonia/etiología , Cerebelo/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Discinesias/diagnóstico por imagen , Discinesias/etiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Corteza Motora/diagnóstico por imagen , Corteza Motora/fisiopatología , Esquizofrenia/complicaciones , Esquizofrenia/diagnóstico por imagen , Núcleo Subtalámico/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Adulto Joven
15.
Mult Scler ; 23(13): 1791-1795, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28397579

RESUMEN

Secondary paroxysmal dyskinesias (SPDs) are short, episodic, and recurrent movement disorders, classically related to multiple sclerosis (MS). Carbamazepine is effective, but with risk of adverse reactions. We identified 7 patients with SPD among 457 MS patients (1.53%). SPD occurred in face ( n = 1), leg ( n = 2), or arm +leg ( n = 4) several times during the day. Magnetic resonance imaging (MRI) showed new or enhancing lesions in thalamus ( n = 1), mesencephalic tegmentum ( n = 1), and cerebellar peduncles ( n = 5). Patients were treated with clonazepam and then acetazolamide ( n = 1), acetazolamide ( n = 5), or levetiracetam ( n = 1) with response within hours (acetazolamide) to days (levetiracetam). No recurrences or adverse events were reported after a median follow-up of 33 months.


Asunto(s)
Anticonvulsivantes/farmacología , Cerebelo/diagnóstico por imagen , Discinesias , Distonía , Esclerosis Múltiple , Tegmento Mesencefálico/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Acetazolamida/farmacología , Adulto , Anticonvulsivantes/administración & dosificación , Clonazepam/farmacología , Discinesias/diagnóstico por imagen , Discinesias/tratamiento farmacológico , Discinesias/etiología , Discinesias/fisiopatología , Distonía/diagnóstico por imagen , Distonía/tratamiento farmacológico , Distonía/etiología , Distonía/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Levetiracetam , Imagen por Resonancia Magnética , Masculino , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/fisiopatología , Piracetam/análogos & derivados , Piracetam/farmacología , Resultado del Tratamiento
16.
Hum Gene Ther ; 28(6): 510-522, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28132521

RESUMEN

GM2 gangliosidoses, including Tay-Sachs disease and Sandhoff disease, are lysosomal storage disorders caused by deficiencies in ß-N-acetylhexosaminidase (Hex). Patients are afflicted primarily with progressive central nervous system (CNS) dysfunction. Studies in mice, cats, and sheep have indicated safety and widespread distribution of Hex in the CNS after intracranial vector infusion of AAVrh8 vectors encoding species-specific Hex α- or ß-subunits at a 1:1 ratio. Here, a safety study was conducted in cynomolgus macaques (cm), modeling previous animal studies, with bilateral infusion in the thalamus as well as in left lateral ventricle of AAVrh8 vectors encoding cm Hex α- and ß-subunits. Three doses (3.2 × 1012 vg [n = 3]; 3.2 × 1011 vg [n = 2]; or 1.1 × 1011 vg [n = 2]) were tested, with controls infused with vehicle (n = 1) or transgene empty AAVrh8 vector at the highest dose (n = 2). Most monkeys receiving AAVrh8-cmHexα/ß developed dyskinesias, ataxia, and loss of dexterity, with higher dose animals eventually becoming apathetic. Time to onset of symptoms was dose dependent, with the highest-dose cohort producing symptoms within a month of infusion. One monkey in the lowest-dose cohort was behaviorally asymptomatic but had magnetic resonance imaging abnormalities in the thalami. Histopathology was similar in all monkeys injected with AAVrh8-cmHexα/ß, showing severe white and gray matter necrosis along the injection track, reactive vasculature, and the presence of neurons with granular eosinophilic material. Lesions were minimal to absent in both control cohorts. Despite cellular loss, a dramatic increase in Hex activity was measured in the thalamus, and none of the animals presented with antibody titers against Hex. The high overexpression of Hex protein is likely to blame for this negative outcome, and this study demonstrates the variations in safety profiles of AAVrh8-Hexα/ß intracranial injection among different species, despite encoding for self-proteins.


Asunto(s)
Dependovirus/genética , Discinesias/etiología , Gangliosidosis GM2/terapia , Vectores Genéticos/efectos adversos , Necrosis/etiología , Neuronas/metabolismo , beta-N-Acetilhexosaminidasas/genética , Animales , Apatía , Dependovirus/metabolismo , Modelos Animales de Enfermedad , Discinesias/genética , Discinesias/metabolismo , Discinesias/patología , Femenino , Gangliosidosis GM2/genética , Gangliosidosis GM2/metabolismo , Gangliosidosis GM2/patología , Expresión Génica , Terapia Genética/métodos , Vectores Genéticos/química , Vectores Genéticos/metabolismo , Sustancia Gris/metabolismo , Sustancia Gris/patología , Inyecciones Intraventriculares , Macaca fascicularis , Masculino , Necrosis/genética , Necrosis/metabolismo , Necrosis/patología , Neuronas/patología , Subunidades de Proteína/efectos adversos , Subunidades de Proteína/genética , Subunidades de Proteína/metabolismo , Tálamo/metabolismo , Tálamo/patología , Transgenes , Sustancia Blanca/metabolismo , Sustancia Blanca/patología , beta-N-Acetilhexosaminidasas/efectos adversos , beta-N-Acetilhexosaminidasas/metabolismo
17.
Behav Brain Res ; 320: 400-411, 2017 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-27816557

RESUMEN

Chronic use of typical antipsychotic haloperidolis related to movement disturbances such as parkinsonism, akathisia and tardive dyskinesia which have been related to excitotoxicity in extrapyramidal brain areas, requiring their prevention and treatment. In the current study we evaluated the influence of the magnesium on prevention (for 28days before-), reversion (for 12days after-) and concomitant supplementation on haloperidol-induced movement disorders in rats. Sub-chronic haloperidol was related to orofacial dyskinesia (OD) and catalepsy development, increased generation of reactive species (RS) and levels of protein carbonyl (PC) in cortex, striatum and substantia nigra (SN) in all experimental protocols. When provided preventatively, Mg reduced the increase of OD and catalepsy time 14 and 7days after haloperidol administration, respectively. When supplemented after haloperidol-induced OD establishment, Mg reversed this behavior after 12days, while catalepsy was reversed after 6days of Mg supplementation.When Mg was concomitantly supplemented with haloperidol administration, OD and catalepsy were prevented. Moreover, Mg supplementation was able to prevent the RS generation in both cortex and SN, reducing PC levels in all brain areas evaluated. When supplemented after haloperidol, Mg reversed RS generation in cortex and striatum, decreasing PC levels in SN and striatum.The co-administration of haloperidol and Mg supplementation prevented RS generation in cortex, striatum and SN, and PC levels in the SN.These outcomes indicate that Mg supplementation may be a useful alternative to prevent movement disturbances resulting of classic antipsychotic pharmacotherapy as haloperidol.


Asunto(s)
Antipsicóticos/farmacología , Catalepsia/inducido químicamente , Catalepsia/tratamiento farmacológico , Discinesias/tratamiento farmacológico , Haloperidol/farmacología , Magnesio/farmacología , Análisis de Varianza , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Embrión de Pollo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Discinesias/etiología , Haloperidol/administración & dosificación , Masculino , Carbonilación Proteica/efectos de los fármacos , Ratas , Ratas Wistar , Factores de Tiempo
18.
PM R ; 9(7): 732-735, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27840300

RESUMEN

We report a case of a patient with profound right-sided hemiballismus resulting from an acute unilateral left thalamic lesion. The hemiballismus was significant and persistent, resulting in profound functional disability. We discuss the use of low-dose haloperidol in conjunction with acute rehabilitation in the treatment of hemiballismus, resulting in decreased amplitude and frequency of adventitious movements and leading to substantial functional gains in our patient. To our knowledge, this is the first extensive report of successful rehabilitation of a patient with functionally disabling hemiballismus. LEVEL OF EVIDENCE: V.


Asunto(s)
Discinesias/rehabilitación , Haloperidol/uso terapéutico , Accidente Cerebrovascular/complicaciones , Tálamo/patología , Terapia Combinada , Discinesias/diagnóstico por imagen , Discinesias/tratamiento farmacológico , Discinesias/etiología , Estudios de Seguimiento , Humanos , Pacientes Internos , Masculino , Persona de Mediana Edad , Enfermedades Raras , Medición de Riesgo , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Factores de Tiempo , Resultado del Tratamiento
19.
Ideggyogy Sz ; 68(11-12): 417-21, 2015 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-26821516

RESUMEN

Hyperglycaemia induced movement disorders, such as hemiballism are rare disorders. The syndrome is characterised by the triad of hemiballism, contralateral T1-hyperintense striatal lesion and non-ketotic hyperglycaemia. Here we report a patient with untreated diabetes presenting with acute onset of hemiballism. MRI revealed T1 hyperintensity of the head of the caudate nucleus and the anterior putamen. The patient also had acantocytosis. Based on the detailed examination of the neuroradiological results and earlier findings we will discuss the pathomechanism. Based on previous findings microhemorrhages, extensive mineralisation, gemistocytic astrocytosis might play a role in the development of the imaging signs. The connectivity pattern of the striatal lesion showed extensive connections to the frontal cortex. In coexistence with that the most severe impairment was found on the phonemic verbal fluency task measuring frontal executive functions.


Asunto(s)
Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/patología , Cuerpo Estriado/patología , Discinesias/etiología , Función Ejecutiva , Lóbulo Frontal/patología , Hiperglucemia/complicaciones , Trastornos del Habla/etiología , Abetalipoproteinemia/etiología , Abetalipoproteinemia/patología , Adulto , Núcleo Caudado/patología , Complicaciones de la Diabetes/patología , Discinesias/patología , Humanos , Hiperglucemia/patología , Imagen por Resonancia Magnética , Masculino , Memoria a Corto Plazo , Putamen/patología , Trastornos del Habla/patología
20.
Mov Disord ; 30(2): 198-205, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24919927

RESUMEN

Hemichorea-hemiballism (HC-HB) in uncontrolled diabetes mellitus is an uncommon manifestation of hyperglycemia. The pathophysiology of hyperglycemic HC-HB is not well understood. A previous report showed increased intracortical inhibition in the motor cortex in a patient with diabetes with HC-HB. The objective of this study is to investigate motor cortex excitability in patients with hyperglycemic HC-HB. We hypothesized that intracortical inhibition measured with transcranial magnetic stimulation, which likely reflects the excitability of cortical γ-aminobutyric acid (GABA)ergic circuits, would be impaired in patients with hyperglycemic HC-HB. We studied 15 patients with mean age 71.5 years (range, 48-94 y) and 12 age-matched healthy subjects. The motor cortex contralateral to the hemichorea was tested. Transcranial magnetic stimulation measures included motor evoked potential, recruitment curve, GABAA mediated short interval intracortical inhibition, intracortical facilitation, and GABAB mediated silent period duration and long interval intracortical inhibition. No significant difference was found in motor threshold, recruitment curve response, short interval intracortical inhibition, or intracortical facilitation in both rest and active conditions between patients with hyperglycemic HC-HB and normal subjects. However, long interval intracortical inhibition was significantly increased during muscle activation but not at rest in patients with hyperglycemic HC-HB. The silent period duration is also increased in patients with hyperglycemic HC-HB. We concluded that long interval intracortical inhibition and silent period are increased in the motor cortex contralateral to the hemichorea in hyperglycemic HC-HB, but only during muscle activation. Hemichorea-hemiballism may be associated with increased GABAB receptor-mediated inhibitory activity in the motor cortex.


Asunto(s)
Discinesias/terapia , Hiperglucemia/terapia , Ácido gamma-Aminobutírico/uso terapéutico , Anciano , Anciano de 80 o más Años , Corea/terapia , Discinesias/etiología , Potenciales Evocados Motores/efectos de los fármacos , Femenino , Humanos , Hiperglucemia/complicaciones , Masculino , Persona de Mediana Edad , Corteza Motora/efectos de los fármacos , Corteza Motora/cirugía , Agitación Psicomotora/terapia , Estimulación Magnética Transcraneal/métodos
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