Familial association of genetic generalised epilepsy with limb-girdle muscular dystrophy through a mutation in CAPN3

Muscular dystrophies are a heterogeneous group of inherited dis-eases that cause progressive muscle weakness. The association of epi-lepsy with some of these diseases has been previously described andhas most commonly been found for Fukuyama-type muscular dystro-phy due to alterations in cerebral neuronal migration[1]. Among mus-cular dystrophies, limb-girdle muscular dystrophies (LGMDs)represent the fourth most common group, with a prevalence of 1.63per 100, 000 individuals[2]. The diseases in this group share a commonphenotype involving progressive weakness of the scapular and pelvicgirdles that starts after 2 years of age and can be accompanied by differ-ent degrees of elevation in blood creatine kinase (CK) levels and by var-ious anatomic pathologicalfindings. LGMDs are subdivided into LGMD1and LGMD2 depending on whether the inheritance is dominant or re-cessive, respectively. LGMD2A, which is caused by deficiency of thecalpain 3 protein owing to mutations in theCAPN3gene, is the mostcommon form of LGMD in Europe and America[2]. Its associationwith epilepsy has been described in only two isolated cases[1, 3], bothof them on the spectrum of genetic generalised epilepsies (GGEs). Thelatter are the most common group of epilepsies with genetic aetiology, accounting for 15–20% of all epilepsy cases[4]. Nonetheless, none of thegenes usually involved in monogenic epilepsies seem to play a majorrole in GGE, probably indicating a polygenic predisposition to GGE andtherefore a complex inheritance pattern[5]. Here, we describe a family..

Epilepsia mioclónica juvenil: Pronóstico a largo plazo y retirada de tratamiento

Fundamento. La epilepsia mioclónica juvenil (EMJ) es un síndrome epiléptico clásico que carece de consenso pleno sobre la posibilidad de suspensión de tratamiento con fármacos antiepilépticos (FAE). Método. Estudio observacional, retrospectivo de una serie de pacientes con diagnóstico de EMJ de más de 20 años de evolución, atendiendo a la evolución de aquellos con retirada de FAE. Resultados. Se estudiaron veinte pacientes (edad media 44, 1 años, 55% hombres) con EMJ de 30 años de evolución media y edad media al inicio de 14, 2 años. El tipo de crisis motora más frecuente fue la combinación de mioclónicas y tónico-clónicas (70%); el 60% de los pacientes llevan más de cinco años libres de crisis. A cuatro pacientes (20%) se les suspendieron los FAE, a dos de ellos con edad media 23 años y un tiempo medio libre de crisis de 7, 5 años, que recayeron, y a los otros dos con edad media 39 años y tras 23, 5 años libres de crisis, que llevan dos y nueve años sin crisis en la actualidad. Conclusiones. Existe la posibilidad de suspender FAE en pacientes con EMJ con libertad de crisis mantenida en el tiempo. Sugerimos tener en cuenta la edad de suspensión y la existencia previa de un tiempo prolongado de libertad de crisis. Background. Juvenile myoclonic epilepsy (JME) is a classic epileptic syndrome that lacks consensus on the possibility of suspending treatment with antiepileptic drugs (AD). Method. Retrospective observational study of a series of patients diagnosed with JME with 20 years or more of evolution, focusing on those with withdrawal from AD. Results. The study involved twenty patients (average age 44.1 years, 55% men) with JME of 30 years average evolution and average age at its outset of 14.2 years. The most frequent type of motor crisis was the com-bination of myoclonic and tonic-clonic seizures (70%); 60% of the patients have been free of seizures for more than five years. Four patients (20%) were withdrawn from AD, two of them with an average age of 23 years and an average time free of seizures of 7.5 years, who relapsed, and the other two with an average age of 39 years and following 23.5 years free of seizures, who currently have been without seizures for two and nine years. Conclusions. The possibility of withdrawing AD in patients with JME who have been free of seizures over an extended time seems feasible. We suggest taking into account age at withdrawal and prior existence of a prolonged period of time free of seizures

Epilepsy in elderly patients: does age of onset make a difference?

Introduction: Epilepsy is most frequent in children and elderly people. Today\u27s population is ageing and epilepsy prevalence is increasing. The type of epilepsy and its management change with age. Methods: We performed a retrospective, observational study comparing patients aged ≥ 65 years with epilepsy diagnosed before and after the age of 65, and describing epilepsy characteristics and comorbidities in each group. Results: The sample included 123 patients, of whom 61 were diagnosed at \u3c 65 years of age (group A), 62 at ≥ 65 of age (group B). Sex distribution was similar in both groups, with 39 men (62.9%) in group A and 37 (60.7%) in group B. Mean age was 69.97 ± 5.6 years in group A and 77.29 ± 6.73 in group B. The most common aetiology was unknown in group A (44.3%, n = 27) and vascular in group B (74.2%, n = 46). History of stroke was present in 12 patients from group A (19.7%) and 32 (51.6%) in group B. Antiepileptic drugs were prescribed at lower doses in group A. Statistically significant differences were found between groups for history of ischaemic stroke, cognitive impairment, psychiatric disorders, and diabetes mellitus; degree of dependence; and number of antiepileptic drugs. Conclusion: Age of onset ≥ 65 years is closely related to cardiovascular risk factors; these patients require fewer antiepileptic drugs and respond to lower doses. Some cases initially present as status epilepticus

Relación entre el trastorno de conducta del sueño REM y el trastorno de control de impulsos en pacientes con enfermedad de Parkinson

Resumen: Introducción: La relación entre el trastorno del control de impulsos (TCI) y el trastorno de conducta del sueño REM (TCSR) no se ha aclarado todavía y los resultados de la literatura son contradictorios. Nuestro objetivo es valorar la asociación entre estos 2 trastornos y, a su vez, su presencia en dependencia de la terapia dopaminérgica. Métodos: Un total de 73 pacientes diagnosticados de enfermedad de Parkinson, en tratamiento con un único agonista dopaminérgico, fueron incluidos en el estudio, tras valoración clínica y habiendo completado el cuestionario de pregunta única para el TCSR y el cuestionario abreviado para los trastornos impulsivo-compulsivos en la enfermedad de Parkinson. Resultados: La edad media ± desviación estándar de los pacientes fue de 68,88 ± 7,758 años. De ellos, 26 pacientes (35,6%) se clasificaron dentro de un TCSR-probable, presentando mayor prevalencia de síndrome rígido acinético no tremórico, más años de tratamiento con levodopa y con agonistas dopaminérgicos, y una relación significativa con el TCI (p = 0,001) en comparación con el grupo sin TCSR-probable.En cuanto al tratamiento con agonistas dopaminérgicos, se demostró la asociación significativa de la administración por vía oral con una mayor prevalencia de TCI, mientras que esta vía también se relacionó con mayor tendencia a desarrollar TCSR, diferencias en este caso no significativas. Conclusiones: Nuestros datos confirman que el TCSR se relaciona con el TCI en la enfermedad de Parkinson. Abstract: Introduction: The relationship between impulse control disorder (ICD) and REM sleep behaviour disorder (RBD) has not yet been clarified, and the literature reports contradictory results. Our purpose is to analyse the association between these 2 disorders and their presence in patients under dopaminergic treatment. Methods: A total of 73 patients diagnosed with Parkinson's disease and treated with a single dopamine agonist were included in the study after undergoing clinical assessment and completing the single-question screen for REM sleep behaviour disorder and the short version of the questionnaire for impulsive-compulsive behaviours in Parkinson's disease. Results: Mean age was 68.88  ±  7.758 years. Twenty-six patients (35.6%) were classified as probable-RBD. This group showed a significant association with ICD (P=.001) and had a higher prevalence of non-tremor akinetic rigid syndrome and longer duration of treatment with levodopa and dopamine agonists than the group without probable-RBD. We found a significant correlation between the use of oral dopamine agonists and ICD. Likewise, patients treated with oral dopamine agonists demonstrated a greater tendency toward presenting probable-RBD than patients taking dopamine agonists by other routes; the difference was non-significant. Conclusions: The present study confirms the association between RBD and a higher risk of developing symptoms of ICD in Parkinson's disease. Palabras clave: Enfermedad de Parkinson, Trastorno de conducta del sueño REM, Trastorno de control de impulsos y conductas relacionadas, Agonistas dopaminérgicos, Single-Question Screen for REM Sleep Behavior Disorder, Parkinson's Disease Impulsive-Compulsive Disorders Questionnaire, Keywords: Parkinson's disease, REM sleep behaviour disorder, Impulse control disorder and related behaviours, Dopamine agonists, Single-Question Screen for REM Sleep Behavior Disorder, Parkinson's Disease Impulsive-Compulsive Disorders Questionnair

Utilidad del electroencefalograma en el manejo de la epilepsia en el Servicio de Urgencias

Introducción: El electroencefalograma (EEG) es una prueba diagnóstica esencial en epilepsia. Su uso en los Servicios de Urgencias (SU) es limitado, estando habitualmente restringido al diagnóstico y el manejo del estado epiléptico no convulsivo (EENC). Sin embargo, pueden existir otras situaciones en las que, por su perfil temporal, el EEG puede ser una herramienta útil en este entorno. Métodos: Estudio observacional retrospectivo, sobre la base de la historia clínica, de los pacientes atendidos en el SU de nuestro hospital por crisis epilépticas (CE) y sospecha de EENC a los que se realizó un EEG, en el periodo 2015-2016, recogiendo variables demográficas y clínicas. Resultados: Se reclutó a 87 pacientes, con una edad media de 44 años. El motivo de consulta más frecuente fue CE, el 59, 8% por primera CE (pCE) y el 27, 6% por CE en paciente con epilepsia; en 12, 6% la sospecha era EENC. Se observaron descargas epileptiformes interictales (DEI) en el 38, 4% de los pacientes atendidos por pCE y en el 33, 3% de los epilépticos conocidos; el 36, 4% de los posibles EENC se confirmaron mediante EEG. El EEG con DEI supuso un inicio o cambio de tratamiento crónico en el 59, 8% de los pacientes. Conclusiones: El EEG es una herramienta útil en el manejo de las CE en los SU, tanto de situaciones agudas graves como el EENC, como en el estudio diagnóstico de la epilepsia de debut o no filiada

Clinical manifestations of intermediate allele carriers in Huntington disease

Objective: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry. Methods: We assessed a cohort of participants at risk with <36 CAG repeats of the huntingtin (HTT) gene. Outcome measures were the Unified Huntington's Disease Rating Scale (UHDRS) motor, cognitive, and behavior domains, Total Functional Capacity (TFC), and quality of life (Short Form-36 [SF-36]). This cohort was subdivided into IA carriers (27-35 CAG) and controls (<27 CAG) and younger vs older participants. IA carriers and controls were compared for sociodemographic, environmental, and outcome measures. We used regression analysis to estimate the association of age and CAG repeats on the UHDRS scores. Results: Of 12,190 participants, 657 (5.38%) with <36 CAG repeats were identified: 76 IA carriers (11.56%) and 581 controls (88.44%). After correcting for multiple comparisons, at baseline, we found no significant differences between IA carriers and controls for total UHDRS motor, SF-36, behavioral, cognitive, or TFC scores. However, older participants with IAs had higher chorea scores compared to controls (p 0.001). Linear regression analysis showed that aging was the most contributing factor to increased UHDRS motor scores (p 0.002). On the other hand, 1-year follow-up data analysis showed IA carriers had greater cognitive decline compared to controls (p 0.002). Conclusions: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling. ClinicalTrials.gov identifier: NCT01590589

Clinical and genetic characteristics of late-onset Huntington's disease

Background: The frequency of late-onset Huntington's disease (&gt;59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive. Objective: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients from the Registry database. Methods: Participants with late- and common-onset (30–50 years)were compared for first clinical symptoms, disease progression, CAG repeat size and family history. Participants with a missing CAG repeat size, a repeat size of ≤35 or a UHDRS motor score of ≤5 were excluded. Results: Of 6007 eligible participants, 687 had late-onset (11.4%) and 3216 (53.5%) common-onset HD. Late-onset (n = 577) had significantly more gait and balance problems as first symptom compared to common-onset (n = 2408) (P &lt;.001). Overall motor and cognitive performance (P &lt;.001) were worse, however only disease motor progression was slower (coefficient, −0.58; SE 0.16; P &lt;.001) compared to the common-onset group. Repeat size was significantly lower in the late-onset (n = 40.8; SD 1.6) compared to common-onset (n = 44.4; SD 2.8) (P &lt;.001). Fewer late-onset patients (n = 451) had a positive family history compared to common-onset (n = 2940) (P &lt;.001). Conclusions: Late-onset patients present more frequently with gait and balance problems as first symptom, and disease progression is not milder compared to common-onset HD patients apart from motor progression. The family history is likely to be negative, which might make diagnosing HD more difficult in this population. However, the balance and gait problems might be helpful in diagnosing HD in elderly patients