Asunto(s)
Anticonvulsivantes/uso terapéutico , Potenciales Evocados Somatosensoriales/efectos de los fármacos , Potenciales Evocados Somatosensoriales/fisiología , Nitrilos/uso terapéutico , Piridonas/uso terapéutico , Síndrome de Unverricht-Lundborg/tratamiento farmacológico , Síndrome de Unverricht-Lundborg/fisiopatología , Anticonvulsivantes/farmacología , Femenino , Humanos , Nitrilos/farmacología , Piridonas/farmacología , Resultado del Tratamiento , Síndrome de Unverricht-Lundborg/diagnóstico , Adulto JovenRESUMEN
This long-term open-label extension (OLE) trial was conducted to evaluate the long-term safety and tolerability of brivaracetam (BRV) at individualized doses in patients with epilepsy and focal (partial-onset) or generalized onset seizures, or Unverricht-Lundborg disease (ULD). A secondary objective was to evaluate efficacy of BRV in the subgroups of patients with focal or generalized onset seizures. Patients with epilepsy were eligible to enroll in this OLE (N01125; NCT00175916) and were analyzed if they had completed a previous double-blind BRV trial (N01114 [NCT00175929], N01252 [NCT00490035], N01254 [NCT00504881], N01187 [NCT00357669], and N01236 [NCT00368251]), and were expected to obtain a reasonable benefit from long-term BRV treatment. Patients entered the OLE at the BRV dose recommended at the end of the previous trial, with dose adjustments of BRV and concomitant antiseizure medications permitted. Safety variables included treatment-emergent adverse events (TEAEs). Efficacy variables in patients with focal seizures were percent reduction in focal seizure frequency, 50 % responder rates, and 6- and 12-month seizure-freedom. Eight hundred and fifty-three patients (729 [85.5 %] with focal seizures, 30 [3.5 %] with generalized onset seizures, and 94 [11.0 %] with ULD) were enrolled and included in the Safety Set. Overall, 619 (72.6 %) patients discontinued the trial, mainly due to lack of efficacy (354 [41.5 %]), adverse events (100 [11.7 %]), and patient choice (98 [11.5 %]). During the OLE, 588 (68.9 %) patients received BRV for ≥12 months, 403 (47.2 %) for ≥36 months, and 223 (26.1 %) for ≥96 months. The most common modal dose of BRV was 150 mg/day (415 [48.7 %] patients). In the ULD subgroup, the most common modal BRV dose was 100 mg/day (44/94 [46.8 %] patients), and 37/94 (39.4 %) patients had ≥96 months of BRV exposure. Overall, 720/853 (84.4 %) patients reported TEAEs, 451 (52.9 %) had a drug-related TEAE, and 95 (11.1 %) discontinued BRV due to a TEAE. In the ULD subgroup, 87/94 (92.6 %) patients reported TEAEs, 60 (63.8 %) had a drug-related TEAE, and 16 (17.0 %) discontinued due to a TEAE. In patients with focal seizures, the median reduction in focal seizure frequency from Baseline was 43.1 % (n = 728), the 50 % responder rate was 43.6 % (n = 729), and 6- and 12-month seizure freedom rates were 22.2 % and 15.8 %, respectively (n = 595). Overall, BRV was well-tolerated as long-term adjunctive therapy in patients with focal seizures, generalized onset seizures, or Unverricht-Lundborg disease, with improvements in focal seizure frequency maintained over time.
Asunto(s)
Epilepsia Generalizada , Pirrolidinonas/uso terapéutico , Convulsiones , Síndrome de Unverricht-Lundborg , Anticonvulsivantes/uso terapéutico , Método Doble Ciego , Quimioterapia Combinada , Epilepsia/tratamiento farmacológico , Epilepsia Generalizada/tratamiento farmacológico , Estudios de Seguimiento , Humanos , Preparaciones Farmacéuticas , Pirrolidinonas/efectos adversos , Convulsiones/tratamiento farmacológico , Resultado del Tratamiento , Síndrome de Unverricht-Lundborg/tratamiento farmacológicoRESUMEN
The purpose of this paper was to present our experience following the longterm treatment of 11 patients with Unverricht-Lundborg disease (ULD) confirmed by molecular testing. METHODS: We analyzed the clinical course, cognitive state, neuroimaging and neurophysiology results. RESULTS: The data were collected from 9 unrelated families (F/M: 4/7) aged 25-49. The most frequent early manifestations of ULD include generalized tonic-clonic seizures (GTCS) accompanied by myoclonus 2 years later. Myoclonus was observed in all of the patients; its severity made it impossible for 91% to move independently. In two patients- mild atrophy of brain were observed in the MRI. More than half of the patients who underwent evoked potential presented no abnormalities. The dominant EEG-change was slow background activity in all of the patients. Seven patients had generalized seizure activity. The patients received antiepileptic therapy modifications depending on the severity of symptoms and stage of the disease. Five patients received N-acetyl-cysteine. CONCLUSIONS: ULD patients require anti-epileptic polytherapy, mostly benefitting from managing GTCS and myoclonus with valproic acid and clonazepam treatment. Patients may benefit from add-on therapy with levetiracetam or topiramate. An increase in myoclonus, resulting from the progressive nature of the disease leads to significant disability in the majority of patients.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Convulsiones/tratamiento farmacológico , Síndrome de Unverricht-Lundborg/tratamiento farmacológico , Ácido Valproico/uso terapéutico , Adulto , Encéfalo/efectos de los fármacos , Electroencefalografía/métodos , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Mioclonía/tratamiento farmacológico , PoloniaRESUMEN
We report a 32-year-old female who presented myoclonus and generalized tonic-clonic seizure since she was 9 year-old. Thereafter, she was diagnosed as Unverricht-Lundborg disease by gene analysis. Although the epileptic seizures were controlled by multiple antiepileptic drugs, her cortical myoclonus remained intractable, which severely interfered her activity of daily living. On admission to our hospital, she presented mild cognitive impairment, dysarthria, severe postural and action myoclonus in all the limbs, severe impairment of coordinative movements, inability of standing and walking by herself, and severe basophobia. After administration of perampanel, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, with initial dose of 1â mg/day, and then 16 days later it was increased up to 2â mg/day, the myoclonus dramatically improved and the basophobia also lessened about in 30 days since it started. Moreover, abnormally enlarged amplitudes of short latency somatosensory evoked potentials by median nerve stimulation decreased, which suggested the reduction of abnormal cortical hyperexcitability mainly in the primary sensori-motor cortices. We presented that perampanel is the effective drug for treating the refractory cortical myoclonus and basophobia even with small dosage.
Asunto(s)
Anticonvulsivantes/administración & dosificación , Piridonas/administración & dosificación , Síndrome de Unverricht-Lundborg/tratamiento farmacológico , Adulto , Anticonvulsivantes/farmacología , Potenciales Evocados Somatosensoriales , Femenino , Humanos , Nitrilos , Piridonas/farmacología , Receptores AMPA/antagonistas & inhibidores , Corteza Sensoriomotora/fisiopatología , Resultado del Tratamiento , Síndrome de Unverricht-Lundborg/genética , Síndrome de Unverricht-Lundborg/fisiopatologíaRESUMEN
Unverricht-Lundborg disease (ULD) is a form of progressive myoclonus epilepsy characterized by stimulation-induced myoclonus and seizures. This disease is an autosomal recessive disorder, and the gene CSTB, which encodes cystatin B, a cysteine protease inhibitor, is the only gene known to be associated with ULD. Although the prevalence of ULD is higher in the Baltic region of Europe and the Mediterranean, sporadic cases have occasionally been diagnosed worldwide. The patient described in the current report showed only abnormally enlarged restriction fragments of 62 dodecamer repeats, confirming ULD, that were transmitted from both her father and mother who carried the abnormally enlarged restriction fragment as heterozygotes with normal-sized fragments. We report the first case of a genetically confirmed patient with ULD in Korea.
Asunto(s)
Cistatina B/genética , Convulsiones/fisiopatología , Síndrome de Unverricht-Lundborg/diagnóstico , Síndrome de Unverricht-Lundborg/genética , Adulto , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/uso terapéutico , Southern Blotting , Femenino , Predisposición Genética a la Enfermedad , Humanos , Isoxazoles/administración & dosificación , Isoxazoles/uso terapéutico , Levetiracetam , Piracetam/administración & dosificación , Piracetam/análogos & derivados , Piracetam/uso terapéutico , República de Corea , Resultado del Tratamiento , Síndrome de Unverricht-Lundborg/tratamiento farmacológico , Ácido Valproico/administración & dosificación , Ácido Valproico/uso terapéutico , ZonisamidaRESUMEN
OBJECTIVE: To explore the course of Unverricht-Lundborg disease (EPM1) and identify the risk factors for severity, we investigated the time course of symptoms and prognostic factors already detectable near to disease onset. METHODS: We retrospectively evaluated the features of 59 Italian patients carrying the CSTB expansion mutation, and coded the information every 5 years after the disease onset in order to describe the cumulative time-dependent probability of reaching disabling myoclonus, relevant cognitive impairment, and inability to work, and evaluated the influence of early factors using the log-rank test. The risk factors were included in a Cox multivariate proportional hazards regression model. RESULTS: Disabling myoclonus occurred an average of 32 years after disease onset, whereas cognitive impairment occurred a little later. An age at onset of less than 12 years, the severity of myoclonus at the time of first assessment, and seizure persistence more than 10 years after onset affected the timing of disabling myoclonus and cognitive decline. Most patients became unable to work years before the appearance of disabling myoclonus or cognitive decline. CONCLUSIONS: A younger age at onset, early severe myoclonus, and seizure persistence are predictors of a more severe outcome. All of these factors may be genetically determined, but the greater hyperexcitability underlying more severe seizures and myoclonus at onset may also play a role by increasing cell damage due to reduced cystatin B activity.
Asunto(s)
Síndrome de Unverricht-Lundborg/diagnóstico , Síndrome de Unverricht-Lundborg/fisiopatología , Adolescente , Adulto , Edad de Inicio , Análisis de Varianza , Anticonvulsivantes/uso terapéutico , Catepsina B/genética , Electroencefalografía , Potenciales Evocados Somatosensoriales/efectos de los fármacos , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Fenitoína/uso terapéutico , Pronóstico , Estudios Retrospectivos , Síndrome de Unverricht-Lundborg/tratamiento farmacológico , Síndrome de Unverricht-Lundborg/genética , Ácido Valproico/uso terapéutico , Adulto JovenRESUMEN
OBJECTIVE: Perampanel (PER) was used in 12 patients with Unverricht-Lundborg disease (ULD) to evaluate its efficacy against myoclonus and seizures. METHODS: We treated 11 patients with EPM1 mutations (6 F, 5 M, aged 13-62 years) and a 43-year-old man with de novo KCNC1 mutation. PER was introduced by 2 mg steps at 2-4 week intervals until 6 mg/day, with a possible dose reduction or dose increase. RESULTS: Ten patients had a clear clinical response of myoclonus, and five were able to reduce concomitant therapy. Improvement was noted sometimes as soon as with 2 mg/day. Epileptic seizures stopped on PER in the six patients who still had experienced generalized tonic-clonic or myoclonic seizures (100%). Some abatement of efficacy on myoclonus was seen in two patients who still retained some benefit. Weight gain was reported in six patients (50%). Psychological and behavioral side-effects were observed in six patients (50%) and led to withdrawal of PER in three cases and dose reduction in three, with abatement of the problems. SIGNIFICANCE: This study provides evidence that for ULD patients, PER may show marked efficacy even in severe cases, particularly against myoclonus, but also against seizures. PER should thus be tried in ULD patients whose seizures are not satisfactorily controlled. Its use is limited because of psychological and behavioral side effects, with higher doses of approximately 6 mg/day or greater likely risk factors.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Piridonas/uso terapéutico , Síndrome de Unverricht-Lundborg/tratamiento farmacológico , Adolescente , Adulto , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Proteínas de Neoplasias/genética , Nitrilos , Receptores de Superficie Celular/genética , Canales de Potasio Shaw/genética , Resultado del Tratamiento , Síndrome de Unverricht-Lundborg/genética , Adulto JovenRESUMEN
OBJECTIVES: To describe the EEG characteristics of patients with Unverricht-Lundborg disease (ULD) and their changes during the long-term evolution of the disease. METHODS: A retrospective study including all patients with ULD confirmed by molecular biology and more than 15 years' duration of disease progression at the time of inclusion. EEGs were recorded at inclusion, 2 years and 5 years of follow-up. Patients who discontinued treatment during follow-up had an EEG monitoring 1 year after reintroduction of therapy. RESULTS: Forty-seven EEGs were performed in 17 patients. The mean age at onset was 12.0±5.5 years. The mean duration of follow-up was 26.5±6.9 years. The average background rhythm was 8.2 c/s, and was normal in 30 EEGs (64%), slow in 17 (36%) and disorganized in 11 (23%). Epileptic abnormalities were found in 22 EEGs (47%). Myoclonic jerks were found in 13 EEGs (28%). After re-adaptation of antiepileptic medication in patients who had previously stopped treatment, control EEG showed a normal background rhythm with no epileptic abnormalities throughout the monitoring period. CONCLUSION: This study shows that the progressive disappearance of EEG abnormalities is rather due to antiepileptic treatment than a gradual spontaneous tendency to decrease over time.
Asunto(s)
Corteza Cerebral/fisiopatología , Progresión de la Enfermedad , Electroencefalografía , Síndrome de Unverricht-Lundborg/diagnóstico , Síndrome de Unverricht-Lundborg/fisiopatología , Adulto , Anticonvulsivantes/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Síndrome de Unverricht-Lundborg/tratamiento farmacológicoRESUMEN
OBJECTIVE: To evaluate efficacy, tolerability, and safety of adjunctive brivaracetam (BRV) in patients with Unverricht-Lundborg disease (EPM1). METHODS: Two prospective, multicenter, double-blind, phase III trials (N01187/NCT00357669; N01236/NCT00368251) in patients (≥16 years) with genetically ascertained EPM1, showing moderate-severe myoclonus (action myoclonus score ≥30/160), randomized (1:1:1) to twice-daily BRV (N01187: 50 or 150 mg/day; N01236: 5 or 150 mg/day), or placebo. Both studies comprised a baseline period (2 weeks), 2-week up-titration period, 12-week stable-dose maintenance period, and down-titration or entry into long-term follow-up study. Symptoms of myoclonus were assessed by Unified Myoclonus Rating Scale (UMRS). Primary efficacy end point was percent reduction from baseline in action myoclonus score (UMRS section 4) at last treatment visit. Safety assessments included treatment-emergent adverse events (TEAEs). RESULTS: N01187: 50 patients randomized, 47 completed; N01236: 56 patients randomized, 54 completed. Median (min-max) percent reduction from baseline in action myoclonus score is the following-N01187: placebo 5.6 (-81.3 to 53.8), pooled BRV group (primary efficacy analysis) 21.4 (-50.0 to 73.6), BRV 50 mg/day 26.3 (-35.8 to 69.2), BRV 150 mg/day 16.9 (-50.0 to 73.6); N01236: placebo 17.5 (-170 to 61.5), BRV 5 mg/day -4.6 (-430 to 81.8), BRV 150 mg/day (primary efficacy analysis) 12.3 (-58.3 to 96.9). Estimated differences versus placebo were not statistically significant. TEAEs were reported by 72-75% placebo-treated and 56-83% BRV-treated patients. SIGNIFICANCE: Effect of BRV on action myoclonus was not statistically significant. However, action myoclonus score showed wide intrapatient variability and may not have been the optimal tool to measure severity of myoclonus in EPM1. Both studies had very high completion rates (95.3% overall), and a high percentage of patients (88.7% overall) entered long-term follow-up; both likely to be influenced by good tolerability. These studies demonstrate the feasibility of rigorous trials in progressive myoclonic epilepsy.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Pirrolidinonas/uso terapéutico , Síndrome de Unverricht-Lundborg/tratamiento farmacológico , Adolescente , Adulto , Clonazepam/uso terapéutico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Quimioterapia Combinada , Femenino , Fructosa/análogos & derivados , Fructosa/uso terapéutico , Humanos , Isoxazoles/uso terapéutico , Levetiracetam , Masculino , Persona de Mediana Edad , Fenobarbital/uso terapéutico , Piracetam/análogos & derivados , Piracetam/uso terapéutico , Topiramato , Resultado del Tratamiento , Ácido Valproico/uso terapéutico , Adulto Joven , ZonisamidaAsunto(s)
Electroencefalografía/métodos , Epilepsia/diagnóstico , Síndrome de Unverricht-Lundborg/diagnóstico , Adulto , Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Epilepsia/fisiopatología , Potenciales Evocados Somatosensoriales , Femenino , Humanos , Síndrome de Unverricht-Lundborg/tratamiento farmacológico , Síndrome de Unverricht-Lundborg/fisiopatologíaAsunto(s)
Trastornos del Movimiento/diagnóstico , Mioclonía/diagnóstico , Síndrome de Unverricht-Lundborg/diagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Resultado del Tratamiento , Síndrome de Unverricht-Lundborg/tratamiento farmacológico , Ácido Valproico/uso terapéutico , Adulto JovenRESUMEN
Action myoclonus frequently remains the primary cause of disability in Unverricht-Lundborg disease (EPM1) patients. Pharmacological treatment of myoclonus in these patients continues to be challenging; indeed conventional AEDs may be poorly effective in monotherapy or even in combination. We carried out a pilot, open-label trial of add-on zonisamide (ZNS) in patients with EPM1. Twelve EPM1 patients with epilepsy and action myoclonus were included in the study. Oral ZNS was gradually titrated until the target dose of 6 mg/Kg/day. Unified Myoclonus Rating Scale was obtained in each subject before and after ZNS add-on. A significant reduction of myoclonus severity was reached after ZNS introduction. ZNS was generally well tolerated and only two patients withdrew due to mild adverse effects. Our trial suggests that ZNS may be a valuable therapeutic option in EPM1 patients.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Isoxazoles/uso terapéutico , Mioclonía/tratamiento farmacológico , Síndrome de Unverricht-Lundborg/tratamiento farmacológico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Resultado del Tratamiento , ZonisamidaAsunto(s)
Síndrome de Unverricht-Lundborg/genética , Síndrome de Unverricht-Lundborg/fisiopatología , Anticonvulsivantes/uso terapéutico , Cistatina B/genética , Electroencefalografía , Humanos , Mutación Puntual/genética , Índice de Severidad de la Enfermedad , Síndrome de Unverricht-Lundborg/tratamiento farmacológicoAsunto(s)
Agonistas de Dopamina/farmacología , Agonistas de Dopamina/uso terapéutico , Indoles/farmacología , Indoles/uso terapéutico , Mioclonía/etiología , Mioclonía/prevención & control , Equilibrio Postural/efectos de los fármacos , Desempeño Psicomotor/efectos de los fármacos , Síndrome de Unverricht-Lundborg/complicaciones , Síndrome de Unverricht-Lundborg/tratamiento farmacológico , Adulto , Femenino , Humanos , Grabación de Cinta de VideoRESUMEN
We conducted a search for white matter changes (WMCs) in 13 Unverricht-Lundborg disease patients and compared the prevalence of WMCs in these patients to age-matched long-term epileptics and healthy controls. ULD patients had significantly more T2-weighted high-intensity signals on MRI than control subjects, due to the increased prevalence of these signals in the basal ganglia. Interestingly, ULD patients with the basal ganglia changes were overweight. Basal ganglia T2-weighted high-intensity signals are novel findings in ULD.
Asunto(s)
Ganglios Basales/patología , Síndrome de Unverricht-Lundborg/patología , Adolescente , Adulto , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Ganglios Basales/efectos de los fármacos , Índice de Masa Corporal , Mapeo Encefálico , Estudios de Casos y Controles , Femenino , Humanos , Aumento de la Imagen/métodos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Síndrome de Unverricht-Lundborg/tratamiento farmacológico , Ácido Valproico/farmacología , Ácido Valproico/uso terapéutico , Adulto JovenRESUMEN
Unverricht-Lundborg disease (ULD), progressive myoclonic epilepsy type 1 (EPM1, OMIM254800), is an autosomal recessively inherited neurodegenerative disorder characterized by age of onset from 6 to 16 years, stimulus-sensitive myoclonus, and tonic-clonic epileptic seizures. Some years after the onset ataxia, incoordination, intentional tremor, and dysarthria develop. Individuals with EPM1 are mentally alert but show emotional lability, depression, and mild decline in intellectual performance over time. The diagnosis of EPM1 can be confirmed by identifying disease-causing mutations in a cysteine protease inhibitor cystatin B (CSTB) gene. Symptomatic pharmacologic and rehabilitative management, including psychosocial support, are the mainstay of EPM1 patients' care. Valproic acid, the first drug of choice, diminishes myoclonus and the frequency of generalized seizures. Clonazepam and high-dose piracetam are used to treat myoclonus, whereas levetiracetam seems to be effective for both myoclonus and generalized seizures. There are a number of agents that aggravate clinical course of EPM1 such as phenytoin aggravating the associated neurologic symptoms or even accelerating cerebellar degeneration. Sodium channel blockers (carbamazepine, oxcarbazepine) and GABAergic drugs (tiagabine, vigabatrin) as well as gabapentin and pregabalin may aggravate myoclonus and myoclonic seizures. EPM1 patients need lifelong clinical follow-up, including evaluation of the drug-treatment and comprehensive rehabilitation.
Asunto(s)
Síndrome de Unverricht-Lundborg/diagnóstico , Adolescente , Adulto , Edad de Inicio , Animales , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Clonazepam/uso terapéutico , Cistatina B , Cistatinas/genética , Análisis Mutacional de ADN , Diagnóstico Diferencial , Electroencefalografía/estadística & datos numéricos , Humanos , Levetiracetam , Ratones , Mutación/genética , Piracetam/análogos & derivados , Piracetam/uso terapéutico , Síndrome de Unverricht-Lundborg/tratamiento farmacológico , Síndrome de Unverricht-Lundborg/genética , Ácido Valproico/uso terapéuticoRESUMEN
Change in severity of myoclonus as an outcome measure of antiepileptic drug (AED) treatment in patients with Unverricht-Lundborg Disease (ULD) has been estimated by utilizing the Unified Myoclonus Rating Scale (UMRS). In this study, we measure treatment effects through EEG analysis using mutual information approach to quantify interdependence/coupling strength among different electrode sites. Mutual information is known to have the ability to capture linear and non-linear dependencies between EEG time series with superior performance over the traditional linear measures. One subject with ULD participated in this study and 1-hour EEG recordings were acquired before and after treatment of AED. Our results indicate that the mutual information is significantly lower after taking the add-on AED for four weeks at least. This finding could lead to a new insight for developing a new outcome measure for patient with ULD, when UMRS could potentially fail to detect a significant difference.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Electroencefalografía/efectos de los fármacos , Síndrome de Unverricht-Lundborg/tratamiento farmacológico , Femenino , Humanos , Persona de Mediana Edad , Modelos Neurológicos , Mioclonía/tratamiento farmacológico , Resultado del TratamientoRESUMEN
We present three unrelated cases of genetically confirmed progressive myoclonic epilepsy of the Unverricht-Lundborg type who were treated with Levetiracetam as adjunctive therapy for their myoclonus. All cases responded with decrease of their myoclonus and improvement of quality of life. Two were able to return to or continue their employment. Patients tolerated the drug well without side effects reported. Levetiracetam appears to be a useful antimyoclonic agent in cases of progressive myoclonic epilepsy and should be considered for adjunctive therapy.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Piracetam/análogos & derivados , Calidad de Vida , Síndrome de Unverricht-Lundborg/tratamiento farmacológico , Actividades Cotidianas , Adulto , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/farmacología , Quimioterapia Combinada , Femenino , Humanos , Levetiracetam , Masculino , Piracetam/efectos adversos , Piracetam/farmacología , Piracetam/uso terapéutico , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
We studied changes in event-related desynchronization/synchronization (ERD/ERS) patterns in patients with Unverricht-Lundborg disease (ULD), presenting with prominent action myoclonus. We analyzed the movement-related ERD/ERS in alpha and beta frequency bands in 15 patients using self-paced finger extension as a motor paradigm and we compared the results with those obtained in 12 healthy volunteers. In all ULD patients, alpha- and beta-ERD regularly occurred with onset and location similar to that found in healthy controls, but the desynchronization of alpha activity was significantly greater than in controls (C3: -64.4+/-9.8% vs. -49.7+/-14.8%; p=0.004). Moreover, in the patients, both alpha- and beta-ERD spread toward frontal electrodes. In controls, the post-movement beta-ERS regularly occurred; it was absent in eight patients with severe action myoclonus, while, in seven patients with mild or moderate myoclonus, the beta-peak was significantly smaller with respect to that measured in controls (55.6+/-15.1% vs. 153.9+/-99.8%, p=0.006). The failure of beta-ERS well-correlated with motor impairment resulting from action myoclonus, whereas SSEPs and long-loop reflexes performed to detect signs of cortical hyperexcitability showed inconsistent changes. In ULD patients, ERD/ERS changes indicate an increased activation of motor cortex during movement planning and a great reduction of post-excitatory inhibition of motor cortex. The changes involving beta-ERS had a significant relationship with the functional disability in individual patients and might play a pathogenic role in the motor dysfunction.