Primary Orthostatic Tremor: Experience of Perampanel Use in 20 Patients

Background: Primary orthostatic tremor (POT) is a rare disorder for which current treatments are largely ineffective. Following up on our recent report of complete resolution of POT symptoms in a patient using low doses of perampanel, we describe our experience of perampanel in 20 patients. Methods: Twenty patients whose neurologists prescribed perampanel were recruited. Initial dose was 2 mg/day, which was increased to 4 mg/day after the first month. Treatment efficacy was self-scored from +3 to −3 at 1 and 3 months. Results: Eight patients withdrew due to adverse effects. Of the 12 patients who completed the study, 92% indicated that their POT symptoms had improved after 1 month, with 75% indicating moderate to marked improvement (mean score 1.9 ± 0.9). This improvement was not sustained by follow-up at 3 months (mean score 0.9 ± 1.3). A rebound of POT symptoms that lasted 2–6 weeks was observed in most patients who withdrew. Discussion: Our experience with this series of cases points to the potential of low-dose perampanel as a treatment for POT, although poor tolerance and the possibility of a non-persistent therapeutic benefit need to be considered. Controlled studies are needed to confirm these findings

Un marcapassos incrustat al cervell

Sense fer servir el rellotge, a vegades som capaços de dir quina hora és o despertar-nos a una hora en concret. Els científics sospiten que aquesta habilitat es troba mecanitzada a algun lloc del nostre cos. Investigadors del Servei de Neurologia van estimular i inhibir parts del cervell suposadament implicades. Els resultats descarten que la producció del temps es dugui a terme al lòbul prefrontal o a l'hemisferi cerebel·lós dret.Sin necesidad de reloj a veces somos capaces de decir qué hora es o despertarnos a una hora en concreto. Los científicos sospechan que esta habilidad se encuentra mecanizada en el algún lugar de nuestro cuerpo. Investigadores del Servicio de Neurología estimularon e inhibieron partes del cerebro supuestamente implicadas. Los resultados descartan que la producción del tiempo se lleve a cabo en el lóbulo prefrontal o en el hemisferio cerebeloso derecho

Tremolor "prodròmic" : descripció d'un nou símptoma de la malaltia de Parkinson

El mal de Parkinson és una malaltia neurodegenerativa que encara planteja moltes incògnites per a la ciència mèdica. Però, gràcies a l'esforç de la comunitat científica, poc a poc aquest complicat trencaclosques va prenent la seva forma. Un bon exemple dels assoliments al quals s'ha arribat és la present investigació, la mateixa que revela un nou símptoma de la malaltia, en les seves primeres etapes.El mal de Parkinson es una enfermedad neurodegenerativa que todavía plantea muchas incógnitas para la ciencia médica. Pero, gracias al esfuerzo de la comunidad científica, poco a poco este complicado rompecabezas va tomando forma. Un buen ejemplo de los logros alcanzados es la presente investigación, que revela un nuevo síntoma de la enfermedad en sus primeras etapas.Parkinson's disease is a neurodegenerative illness that still raises many doubts for the medical and scientific world. However thanks to the efforts of the scientific community this complicated puzzle is beginning to take shape. A good example of this are the results of the present UAB research, which reveal a new symptom in the early stages of this illness

L'amantadina, ineficaç contra el tremolor essencial

Tremolor involuntari de les mans, de les cames, de la veu o del cap... Són símptomes associats al tremolor essencial, una malaltia que no és greu, però que afecta la qualitat de vida dels qui la pateixen, generalment persones majors de 60 anys. Un dels fàrmacs que fins ara es barallaven com a potencialment efectius per tractar aquesta malaltia, l'amantadina, acaba de mostrar-se ineficaç i fins i tot perjudicial, en un estudi realitzat per investigadors de l'Hospital de Sant Pau.El tremolor essencial és la malaltia més comuna dintre els trastorns del moviment, amb unaincidència deu vegades superior a la malaltia de Parkinson. Aquesta malaltia tan freqüent escaracteritza per la presencia de tremolor involuntari de les mans, cames, veu i cap. Sol aparèixera partir dels 60 anys. No és una malaltia greu, però si que comporta limitacions per les activitatsde la vida diària i laboral. En l'actualitat, aquesta malaltia neurològica no disposa de bonstractaments farmacològics, donat que no aconsegueixen un control adequat dels símptomes.Cal seguir investigant noves teràpies.nvoluntary shaking of the hands, legs, voice or head. These aresymptoms associated with essential tremor, a disorder which while notsevere, affects the quality of life of those suffering from it, generally thoseover 60. One of the drugs that was, up to now, thought of as beingpotentially effective in treating the disorder, amantadine, has been shownto be ineffective and even detrimental, in a study carried out byresearchers at the Hospital de Sant Pau

Tremolor essencial : la hipòtesi gabaèrgica resta qüestionada

Un del transtorns del moviment del cos més freqüent en edat adulta, la tremolor essencial, no només descapacita greument a aquells que la pateixen, sinó que l'ajuda farmacològica existent es troba bastant limitada. Tenint present una de les hipòtesis més aceptades pel que fa a l'origen de malaltia -l'existència d'una disfunció en el sistema de neurotransmissors cerebrals GABA-, sí que ha estat possible que alguns fàrmacs amb principis gabaèrgics donin bons resultats. L'article següent però, demostra que la hipòtesi no és tan clara, i sobretot després que un altre fàrmac, la tiagabina, donés resultats negatius en quant a efectes adversos i manca de millora en els pacients estudiats. És evident, per tant, que cal continuar investigant la base farmacològica de la tremolor essencial.Temblor esencial : la hipótesis gabaérgica queda cuestionada Uno de los trastornos del movimiento del cuerpo más frecuente en edad adulta, el temblor esencial, no sólo incapacita gravemente a aquellos que la sufren, sino que la ayuda farmacológica existente es bastante limitada. Teniendo presente una de las hipótesis más aceptadas con respecto al origen de esta enfermedad -la existencia de una disfunción en el sistema de neurotransmisores cerebrales GABA-, sí ha sido posible que algunos fármacos con principios gabaérgicos den buenos resultados. El siguiente artículo, sin embargo, demuestra que la supuesta hipótesis no es tan clara, y sobre todo después de que otro fármaco, la tiagabina, diera resultados negativos en cuanto a efectos adversos y falta de mejora en los pacientes estudiados. Es evidente, por lo tanto, que hay que continuar investigando la base farmacológica del temblor esencial

Diferencias entre pacientes de Parkinson y controles en la conducta motora fina basada en la información visual y propioceptiva versus solo propioceptiva

Personality differences based on fine motor precision performance were studied in early stage Parkinson’s patients and an age-matched control group under two different test conditions: Proprioceptive + visual information and proprioceptive information alone. A comparative data analysis for deviations of three measured movement types (transversal, frontal and sagittal) was done for both hands (dominant and non-dominant) with relation to personality di-mensions. There were found significant differences between the two groups in decision making dimension and emotionality. After splitting the data for gender subgroups, some significant differences were found for men but not for women. The differences in fine motor task performance varied, being better in some directions for the Parkinson’s patients and worse in others. The findings may suggest that medication has both positive and negative effects on motor per-formance and provoke personality changes, being more pronounced in men.Las diferencias de personalidad basadas en la precisión de la ejecución motora fina fueron estudiadas en pacientes con Parkinson en la etapa inicial de la enfermedad y en un grupo control de edad similar bajo dos con-diciones de ensayo diferentes: información propioceptiva + visual y solo información propioceptiva. Se hizo un análisis de datos comparativo de las desviaciones en los tres tipos de movimiento medidos (transversal, frontal y sagital) con las dos manos (dominante y no dominante) y en relación a las dimensiones de la personalidad. Se encontraron diferencias significativas entre los dos grupos en las dimensiones toma de decisiones y emotividad. Después de dividir los datos en subgrupos según el género, se encontraron algunas diferencias significativas para los hombres pero no para las mujeres. Las diferencias en el rendimiento en estas tareas variaron, siendo mejor en algunas direcciones para los pacientes de Parkinson y peor en otras. Los hallazgos sugieren que la medicación puede tener efectos tanto positivos como negativos en el rendimiento motor y provocar cambios en la personalidad, siendo más pronunciados en los hombre

The GABA Hypothesis in Essential Tremor : Lights and Shadows

The gamma-aminobutyric acid (GABA) hypothesis in essential tremor (ET) implies a disturbance of the GABAergic system, especially involving the cerebellum. This review examines the evidence of the GABA hypothesis. The review is based on published data about GABA dysfunction in ET, taking into account studies on cerebrospinal fluid, pathology, electrophysiology, genetics, neuroimaging, experimental animal models, and human drug therapies. Findings from several studies support the GABA hypothesis in ET. The hypothesis follows four steps: 1) cerebellar neurodegeneration with Purkinje cell loss; 2) a decrease in GABA system activity in deep cerebellar neurons; 3) disinhibition in output deep cerebellar neurons with pacemaker activity; and 4) an increase in rhythmic activity of the thalamus and thalamo-cortical circuit, contributing to the generation of tremor. Doubts have been cast on this hypothesis, however, by the fact that it is based on relatively few works, controversial post-mortem findings, and negative genetic studies on the GABA system. Furthermore, GABAergic drug efficacy is low and some GABAergic drugs do not have antitremoric efficacy. The GABA hypothesis continues to be the most robust pathophysiological hypothesis to explain ET. There is light in all GABA hypothesis steps, but a number of shadows cannot be overlooked. We need more studies to clarify the neurodegenerative nature of the disease, to confirm the decrease of GABA activity in the cerebellum, and to test more therapies that enhance the GABA transmission specifically in the cerebellum area

Ethosuximide for Essential Tremor : An Open-Label Trial

T-type calcium channel activation has been postulated to underlie rhythmicity in the olivo-cerebellar system that is implicated in ET. Ethosuximide reduces T-type calcium currents and can suppress tremor in two animal models of ET. We explored the effects of ethosuximide in subjects with ET in an open-label trial using both clinical scales and accelerometric recordings measures. We initially planned to conduct the trial with 15 patients, but due to lack of efficacy and a high incidence of adverse effects, the trial was stopped after seven patients had participated. Seven patients diagnosed with ET were included in the study. The ethosuximide dose was 500 mg daily (BID). The main outcome measures were: 1) tremor clinical rating scale (TCRS) score, 2) accelerometric recordings, and 3) self-reported disability scale score. Five patients completed the study, and two dropped out due to adverse effects. There were no significant changes in clinical scores in motor task performance (TCRS 1+2), daily living activities (TCRS 3), or in the patients' subjective assessment (TCRS 4) and global appraisal. There were no differences observed for accelerometry data or disability scale scores. Anxiety, nervousness, headache, and dizziness were reported by two patients while on ethosuximide, causing them to stop the trial. No patient preferred to continue ethosuximide treatment. The results of our exploratory study suggest that ethosuximide is not an effective treatment for ET

Complete Resolution of Symptoms of Primary Orthostatic Tremor with Perampanel

Primary orthostatic tremor (POT) is an infrequent disorder whose physiopathology is unknown. Current medication is largely ineffective or only offers mild benefits. A 75-year-old female with refractory POT treated with 4 mg/day of perampanel achieved complete symptom resolution. Owing to adverse effects, the patient reduced intake to 2 mg/day, but even at this lower dose the benefit was maintained. We report the complete resolution of POT symptoms using low doses of perampanel, an antiepileptic drug that blocks glutamate-mediated post-synaptic excitation. Further controlled studies are necessary to confirm this finding