Long term outcome of functional hemispherectomy for refractory epilepsy: Experience from a single center / Resultado a largo plazo de la hemisferectomía funcional para la epilepsia refractaria: experiencia en un único centro

Background: Hemispherectomy has an established role as a treatment of last resort in patients with unilateral hemispheric lesions suffering from refractory epilepsy. Methods: Seven patients were evaluated at our Epilepsy Unit. We compared the seizure outcome at 6 months, 1, 2, 5 years post-surgery, as well as at end follow-up (mean 7.1 years) using Engel classification. Reduction of antiepileptic drugs (AEDs) was also assessed utilizing equal time frames. Results: The mean age of seizure onset was 5.4 years. Engel I was achieved in 5 patients at 6 months (71.4%). Engel at 1 year was predicted by the Engel at 6 months (p=0.013) with a similar number of patients being classified as Engel I outcome. Engel at 2 years was also predicted by Engel at 6 months and at 1 year (p=0.030). At end follow-up only 3 patients (42.9%) remained categorized as Engel I outcome. There was a trend toward a stability in Engel classification. All patients with developmental causes for their epilepsy experienced some deterioration of the surgical outcomes. Conversely, all patients with acquired causes were stable throughout follow-up. Seizure outcome at 6 months was worse in the patients who had post-op complications (p=0.044). Adult and pediatric populations did not differ significantly in any tested variable. Conclusions: Hemispherectomy is a valuable resource for seizure control in properly selected patients. Engel patient's evolution could be predicted at 6 months interval. Hemispherectomy could be considered a useful attitude in difficult cases (AU)

Antecedentes: La hemisferectomía tiene un rol establecido como último recurso de tratamiento en pacientes con lesiones hemisféricas unilaterales que padecen epilepsia refractaria. Métodos: En nuestra Unidad de Epilepsia fueron evaluados 7 pacientes. Comparamos el resultado de la crisis epiléptica a los 6 meses, 1, 2 y 5 años posteriores a la cirugía, así como durante el seguimiento final (media 7,1 años) utilizando la clasificación de Engel. También se evaluó la reducción de fármacos antiepilépticos (FAE) utilizando marcos temporales iguales. Resultados: La edad media de aparición de la crisis fue de 5,4 años. Se logró Engel I en 5 pacientes a los 6 meses (71,4%). Engel a 1año fue predicho por Engel a 6 meses (p=0,013) con un número similar de pacientes clasificados como resultado Engel I. Engel a 2 años fue también predicho por Engel a 6 meses y 1año (p=0,030). Durante el seguimiento final solo 3 pacientes (42,9%) siguieron categorizados como resultado Engel I. Se produjo una tendencia hacia la estabilidad en la clasificación Engel. Todos los pacientes con causas evolutivas para la epilepsia experimentaron cierto deterioro de los resultados quirúrgicos. Por contra, todos los pacientes con causas adquiridas permanecieron estables a lo largo del seguimiento. El resultado de las crisis a los 6 meses fue peor en los pacientes con complicaciones posquirúrgicas (p=0,044). Las poblaciones adulta y pediátrica no difirieron significativamente en ninguna de las variables probadas. Conclusiones: La hemisferectomía es un recurso válido para el control de la crisis en pacientes debidamente seleccionados. La evolución del paciente de Engel pudo predecirse a intervalos de 6 meses. La hemisferectomía podría considerarse una actitud útil en casos difíciles (AU)

Circulating microRNAs as potential biomarkers for genetic generalized epilepsies: a three microRNA panel.

BACKGROUND AND PURPOSE: Genetic generalized epilepsies (GGEs) encompass a group of syndromes of mainly genetic causes, characterized by the involvement of both hemispheres. MicroRNAs (miRNAs) are small non-coding RNAs with a critical role in the regulation of neuronal biological processes through gene expression modulation. Dysregulated miRNA expression has been shown in epilepsy. Due to their stability in biological fluids like serum, miRNAs have assumed a prominent role in biomarker research. Our aim was to evaluate circulating levels of three miRNAs in GGE patients and assess their putative diagnostic value. METHODS: MiR-146a, miR-155 and miR-132 were quantified by real-time polymerase chain reaction in the serum of 79 GGE patients (47 women, 32 men, 35.1 ± 12.4 years) and 67 healthy individuals (41 women, 26 men, 42.4 ± 10.1 years). Relative expression values were calculated using the 2-ΔΔCt method. Receiver operating characteristic curve analysis was performed to assess diagnostic value. MiRNA expression was correlated with clinicopathological features. RESULTS: Serum levels of miR-146a and miR-155 were significantly upregulated in GGE patients relative to controls (3.13 and 6.05, respectively). Combined miR-146a, miR-155 and miR-132 serum levels performed well as a diagnostic biomarker, discriminating GGE patients from controls with an area under the curve of 0.85, 80% specificity and 73% sensitivity. CONCLUSIONS: Our results indicate that miR-146a, miR-155 and miR-132 may partake in GGE epileptogenesis. A panel of three circulating miRNAs with potential value as a GGE biomarker is reported for the first time. Novel biomarkers may help to identify new treatment targets and contribute to improved patients' quality of life through earlier diagnosis and a more precise prognosis.

Co-morbidities and sleep apnoea severity. A study in a cohort of Portuguese patients. / Comorbilidades y gravedad de la apnea del sueño. Estudio en una cohorte de pacientes portugueses.

INTRODUCTION: Obstructive sleep apnoea syndrome (OSAS) is frequently associated to other morbid conditions that act as risk factors influencing OSAS morbidity and mortality. AIM: To analyse the presence of co-morbidities in OSAS patients, recruited from a sleep outpatient clinic in Northern Portugal, stratified as a function of OSAS severity. PATIENTS AND METHODS: A cohort of 319 sleep-disordered patients was assessed by clinical and sleep video-polygraphic recording. Patients (n = 209) with sleep respiratory distress had OSAS (n = 145) and severity defined according to Apnoea/Hypopnea Index (AHI); 64 had primary snoring or respiratory distress with AHI < 5; and 110 had other sleep disorders. A full individual background study was possible in 128 OSAS patients. The association to unique or multiple co-morbidities was assessed by clinical and analytical studies in general group or as a function of OSAS severity. RESULTS: The presence of co-morbidities was of 75% in all OSAS patients and of 79.5% in the severe group of OSAS. Forty seven of patients had only one co-morbidity. The most common was obesity (56.3%) followed by high blood pressure, diabetes and other cardiovascular disorders. Obesity was present in 84% among the most severe OSAS cases and always present in those with multiple co-morbidities. When compared with the group of patients without sleep respiratory distress the co-morbidity condition was more frequently related to OSAS (p = 0.0196). CONCLUSION: Comorbidities are commonly associated to OSAS independently of disease severity. Among the comorbidities present obesity was the most common in the most severe OSAS cases.

TITLE: Comorbilidades y gravedad de la apnea del sueño. Estudio en una cohorte de pacientes portugueses.Introduccion. El sindrome de apnea obstructiva del sueño (SAOS) se asocia frecuentemente a otras enfermedades que actuan como factores de riesgo que influyen en la morbilidad y mortalidad del SAOS. Objetivos. Analizar la presencia de comorbilidades en pacientes con SAOS, seleccionados en una clinica del sueño ambulatoria en el norte de Portugal y clasificados atendiendo a la gravedad del SAOS. Pacientes y metodos. Una cohorte de 319 pacientes con trastornos del sueño fueron evaluados mediante estudios clinicos y registro videopoligrafico durante el sueño. Del total de pacientes (n = 209) con distres respiratorio durante el sueño, 145 tenian SAOS con gravedad definida segun el indice de apnea/hipopnea (IAH); 64 presentaban ronquidos primarios o distres respiratorio con IAH < 5; y 110 tenian otros trastornos del sueño. Resultados. La presencia de comorbilidades fue del 75% en todos los pacientes con SAOS y del 79,5% en el grupo de pacientes con SAOS grave; 47 pacientes presentaban una unica comorbilidad, la mas comun de las cuales fue la obesidad (56,3%), seguida de hipertension, diabetes y otros trastornos cardiovasculares. La obesidad estuvo presente en el 84% de los casos mas graves de SAOS y en el 100% de casos con multiples comorbilidades. En comparacion con el grupo de pacientes con distres respiratorio durante el sueño, la comorbilidad aparece normalmente relacionada con el SAOS (p = 0,0196). Conclusion. Las comorbilidades se asocian con frecuencia al SAOS, independientemente de la gravedad de la enfermedad. Entre las comorbilidades presentes, la obesidad resulto ser la mas comun en los casos mas graves de SAOS.

Variant Creutzfeldt-Jakob [corrected] disease: the second case in Portugal and in the same geographical region.

We present the second variant Creutzfeldt-Jacob patient in the same district of northwest Portugal as was previously reported. A 14-year-old previously healthy girl had unexplained pain in the left leg, as well as psychiatric disturbances. This was shortly followed by progressive cognitive impairment, ataxia and generalised choreoatethosis. Neuropsychological assessment revealed severe frontal and medial temporal dysfunction, the posterior cortices being spared. An electroencephalogram was normal. CSF 14.3.3 protein was slightly positive. Magnetic resonance imaging showed the "hockey stick sign" and hyperintensities in the periaquedutal grey matter and in the right parietal cortex, the last with restriction to water molecule movement. SPECT revealed perfusion defects in the left frontotemporal and right parietal regions. PRNP gene sequencing showed no mutations, the patient being homozygous to methionine in codon 129. Five months after onset, immunocytochemical and immunoblotting analysis confirmed deposition of prion protein and a PrP4t electrophoretic pattern. The patient never travelled outside Portugal or received blood transfusions. She had surgical herniorrhaphy in 1998 (when catgut was used) and 2003. This is the second case in Portugal in a 2-year period and 20 km apart from each other, with no known common exposure apart from ingestion of cow meat. We discuss these case peculiarities and underline its epidemiological significance.

A study of 159 Portuguese patients with familial amyloidotic polyneuropathy (FAP) whose parents were both unaffected.

We reviewed 1233 cases of familial amyloidotic polyneuropathy (FAP) from 489 Portuguese families registered at the Centro de Estudos de Paramiloidose, Porto, Portugal. It was found that in 159 cases, neither parent had shown symptoms of this hereditary dominant form of peripheral neuropathy. These cases appear to form a distinct group, with a later age at onset (mean 45.1 years, SD 12.0) than the group of patients with one affected parent (mean 31.2 years, SD 6.9) and a geographical origin not quite in the areas where the disease is most prevalent. Though this group is not significantly different from the general group of patients in clinical presentation at onset and severity of the disease, the average interval between onset and diagnosis (mean 4.5 years, SD 3.2) reflects the difficulties in diagnosing these patients in the absence of a positive family history. From the analysis of pedigrees and in spite of a large number of isolated cases, the occurrence of new mutations could not be proven, and it seems more likely that, in some families, the FAP gene may result in a milder expression or even remain "silent" for several generations. Further investigation of this discrepancy may prove to be important in elucidating the mechanisms involved in the pathogenetic process.