Resective Epilepsy Surgery and Respective Histopathological Diagnoses: A Retrospective Cohort Study.

INTRODUCTION: Over recent decades, brain resection for drug-resistant epilepsy has proven to be a valuable treatment option. The histopathological classification was of paramount value for patient management. The aims of this study were to characterize our resective epilepsy surgical series including the histopathological diagnoses and to understand the differences in clinical practice between two different periods of our epilepsy surgical programme. MATERIAL AND METHODS: We performed a retrospective cohort study, including patients with drug-resistant epilepsy that underwent resective surgery between 1997 and 2021 in the Coimbra University Hospital Centre. Histopathological diagnoses were classified into seven major conventional categories. For comparison purposes, the cohort was divided into two consecutive periods of 12 years. RESULTS: A total of 259 patients were included, from which 228 (88%) were adults at the time of surgery. The median disease duration prior to surgery was 14 (interquartile range 23) years. Fifty-five (21%) patients performed pre-surgical invasive work-up. The temporal lobe was the most frequently operated region (73%). Major and minor post-surgical complications were identified in 21 (8%) patients. A reduction in the number of antiepileptic drugs was possible in 96 (37%) patients after surgery. The most common histopathological diagnosis was hippocampal sclerosis, but among children it was long-term epilepsy associated tumour. Long-term epilepsy associated tumours, hippocampal sclerosis and vascular malformations had the best post-operative outcomes. Malformations of cortical development and glial scars had the worst outcomes. Regarding differences between the two periods, the absolute number of operated patients increased (119 versus 140), and the age at surgery was higher in the second period (p = 0.04). The number of malformations of cortical development increased (p = 0.01), but the number of other tumours (p = 0.01) and specimens with no lesion (p = 0.03) decreased in the same period. CONCLUSION: This study is in line with contemporaneous research, reinforcing the previous knowledge on the underlying structural aetiologies, clinical practice, and surgical outcomes over more than two decades of experience. Our data provide realistic expectations about epilepsy surgery and highlight the need for further improvements in diagnosis and treatment paradigm for people with chronic epilepsy.

Introdução: Nas últimas décadas, a cirurgia ressectiva demonstrou ser uma opção valiosa no tratamento da epilepsia farmacorresistente. A classificação histopatológica foi de grande importância na orientação do doente. Os objetivos deste estudo foram caracterizar a nossa série de cirurgia de epilepsia ressectiva incluindo os diagnósticos histopatológicos, e compreender as diferenças na prática clínica entre dois períodos diferentes do programa de cirurgia da epilepsia. Material e Métodos: Realizou-se um estudo de coorte retrospetivo, incluindo doentes com epilepsia farmacorresistente submetidos a cirurgia ressectiva entre 1997 e 2021 no Centro Hospitalar e Universitário de Coimbra. Os diagnósticos histopatológicos foram classificados em sete categorias. Para análise comparativa, a coorte foi dividida em dois períodos consecutivos de 12 anos. Resultados: Um total de 259 doentes foram incluídos, sendo 228 (88%) adultos aquando da cirurgia. A mediana da duração da doença antes da cirurgia foi de 14 (amplitude interquartil 23) anos. Cinquenta e cinco (21%) doentes realizaram investigação invasiva pré-cirúrgica. O lobo temporal foi a região mais frequentemente operada (73%). Complicações pós-cirúrgicas major e minor foram identificadas em 21 (8%) doentes. Uma redução no número de antiepiléticos foi observada em 96 (37%) doentes após a cirurgia. O diagnóstico histopatológico mais comum foi a esclerose do hipocampo, mas nas crianças foi o tumor associado a epilepsia de longa duração. Tumores associados a epilepsia de longa duração, esclerose do hipocampo e malformações vasculares tiveram os melhores resultados pós-operatórios. Malformações do desenvolvimento cortical e cicatrizes gliais tiveram os piores resultados. Relativamente às diferenças entre os dois períodos, o número absoluto de doentes operados aumentou (119 versus 140), e a idade aquando da cirurgia foi maior no segundo período (p = 0,04). O número de malformações do desenvolvimento cortical aumentou (p = 0,01), mas o número de outros tumores (p = 0,01) e amostras sem lesão (p = 0,03) diminuiu no mesmo período. Conclusão: Este estudo está de acordo com a literatura atual, reforçando o conhecimento prévio sobre as etiologias estruturais, prática clínica e resultados cirúrgicos ao longo de mais de duas décadas de experiência. Os dados analisados fornecem expectativas realistas sobre a cirurgia de epilepsia e destacam a necessidade de melhorias no paradigma de diagnóstico e tratamento destes doentes.

Vitamin D deficiency in a Portuguese epilepsy cohort: who is at risk and how to treat.

The epilepsy-related risk factors for vitamin D deficiency, particularly the use of enzyme-inducing antiepileptic drugs (EIAEDs), and how to treat vitamin D deficiency in patients with epilepsy remain unclear. Our aims were to explore risk factors and the influence of EAIEDs in vitamin D status and to determine the efficacy of a daily dose of oral cholecalciferol (vitamin D3) in epileptic patients with vitamin D deficiency. Clinical data were collected and 25-hydroxyvitamin D (25(OH)D) serum levels were measured. All patients with vitamin D deficiency (25(OH)D ≤20 ng/mL) or insufficiency (25(OH)D from 21-29 ng/mL) were treated with 6,670 IU/day cholecalciferol for eight weeks and 25(OH)D was then remeasured. Descriptive and inferential statistics were employed. A total of 92 patients (44.6% males), with mean age of 41.0±14.8 years, were included. Measurements of 25(OH)D revealed that 79.3% patients had abnormal levels: 56.5% were vitamin D deficient and 22.8% were vitamin D insufficient. The statistically significant risk factors for vitamin D deficiency identified were: number of AEDs, treatment with EIAEDs, low sun exposure, high body mass index (BMI) and a high frequency of epileptic seizures. After treatment, 25(OH)D mean level increased by 98.99% (regardless of EIAED use or being overweight). In our sample, more than half of the adults with epilepsy showed 25(OH)D deficiency. Patients on EIAEDs had lower 25(OH)D levels. A daily dose of 6,670 IU cholecalciferol successfully led to the correction of 25(OH)D levels. A higher dose in obese patients or in patients taking EIAEDs may not be warranted and this should be considered in future guidelines for routine vitamin D deficiency treatment.

Sporadic Creutzfeldt-Jakob disease presenting as epilepsia partialis continua and non-ictal nystagmus.

BACKGROUND AND PURPOSE: Creutzfeldt-Jakob disease (CJD) is a rare form of rapidly progressive neurodegenerative disorder. Seizures are uncommon in the early stage of CJD, increasing diagnostic difficulty. METHODS: An autopsy-proven case of CJD presenting initially as an epilepsia partialis continua is reported, in which the initial workup was unremarkable. Retrospectively, the presence of nystagmus, which proved to be non-epileptic, pointed to a cerebellar lesion before a diagnosis of clinically probable CJD was made. RESULTS: A 70-year-old man presented with a 3-week history of intermittent rhythmic jerking tremors in his left limbs, interfering with his gait. Examination showed left body clonic movements. Electroencephalography revealed an ictal right centroparietal pattern of focal status epilepticus. Video-oculography revealed right-beating nystagmus (mean slow phase velocity [SPV] 3.4º/s) in the dark and left-beating nystagmus (SPV 2.6º/s) in the light, left-beating nystagmus after head shaking (SPV 4º/s) and during mastoid vibration (SPV 11º/s) and mildly hypoactive horizontal head impulses. Search for occult malignancy, serologies, cerebrospinal fluid analyses, anti-onconeural antigen, auto-immune panel and brain magnetic resonance imaging were unrevealing. Rapid neurological decline was observed. Three weeks later, cerebrospinal fluid was positive for 14.3.3 protein, electroencephalography showed generalized periodic sharp wave complexes and brain magnetic resonance imaging revealed diffusion restriction and T2/fluid-attenuated inversion recovery hyperintensities in the cerebellum, basal ganglia, thalamus and cortex. He died 1 month later. Neuropathological study confirmed the diagnosis of CJD. CONCLUSION: This case highlights that CJD should be considered in the differential diagnosis of new onset epilepsia partialis continua and that neuro-ophthalmological examination can be helpful in pointing to early asymmetric cerebellar involvement.

Gelastic seizures: a retrospective study in five tertiary hospital centres.

This study aimed to characterize, clinically and neurophysiologically, a series of patients with gelastic seizures (GS), including both adults and children. We retrospectively collected patients with GS from epilepsy clinics of five tertiary hospital centres within a single country. Patients were selected through relatives'/caregivers' descriptions, home video and/or video-EEG monitoring. GS were identified through ictal semiology. Thirty-five patients were enrolled; 62.9% had initial GS in infancy, 14.3% in adolescence and 22.8% at adult age. Twenty-six had abnormal MRI: eight presented with hypothalamic hamartoma (HH) and 16 non-HH lesions that included different structural aetiologies and genetic, metabolic and immune aetiologies. All patients with HH had their first GS in infancy or adolescence. For the remaining aetiologies, GS started in infancy in 59.3%, in adolescence in 11.1% and at adult age in 29.6%. Video-EEG data was available for analysis in 11 patients, including seven patients with a non-HH MRI lesion. The ictal onset topography on scalp video-EEG was usually concordant with the MRI lesion (in 6/7 patients) and the most frequent ictal onset was fronto-temporal. In two patients, both video-EEG and MRI suggested a parietal and occipital epileptogenic zone. Aetiologies and patterns of affected topography unrelated to HH are common in patients with GS, and all age groups may manifest with this type of ictal semiology. This ictal manifestation has no lateralizing value and, despite a clear preponderance for hypothalamic, frontal and temporal lobe origins, other brain areas, namely the parietal and occipital lobes, should be considered.

Increased CSF tau is associated with a higher risk of seizures in patients with Alzheimer's disease.

INTRODUCTION: Neurofibrillary tangles and tau protein, the neuropathological hallmarks of Alzheimer's disease (AD), have been identified in patients with epilepsy. Tau protein was also associated with the modulation of neuronal excitability in animal models of AD. MATERIALS AND METHODS: We evaluated in 292 patients with AD the association between the risk of seizure development and AD cerebrospinal fluid (CSF) biomarkers, demographic characteristics, baseline Mini-Mental State Examination (MMSE) score, comorbidities, and apolipoprotein E status. RESULTS: The development of seizures was associated with younger age at dementia's onset, lower baseline MMSE, and higher CSF total tau protein levels, but only MMSE (hazard ratio [HR] = 0.935; 95% confidence interval [CI] = [0.903, 0.968]; p < 0.001) and CSF tau (HR = 1.001; 95%CI = [1.001, 1.002]; p = 0.001) were independent predictors on multivariate analysis. DISCUSSION: While CSF tau and lower baseline MMSE association with seizure development could in part be explained by a greater degree of cortical damage, the role of tau in the modulation of neuronal excitability may also play a role and should be further investigated.

Negative myoclonus secondary to paroxetine intake.

Outside the context of overdose and serotonin syndrome, seizures and myoclonic movements attributed to selective serotonin reuptake inhibitors (SSRIs) are rare and poorly documented. We present a 77-year-old man, with no history of epilepsy, presenting in the emergency department with whole body jerks since that morning. Two days earlier, due to a prescription mistake, he was started on paroxetine 20 mg instead of his usual fluoxetine 20 mg. The patient's electroencephalogram (EEG), performed in the emergency department, revealed a bilateral synchronous parieto-occipital fast spike activity pattern, which correlated consistently with negative myoclonus. Two days after stopping paroxetine, the patient presented no seizures and no abnormalities in the EEG. We present an EEG documented case of drug-induced seizures, with a bilateral parieto-occipital pattern, secondary to paroxetine intake. A hyperexcitability of the primary somatosensory cortex inhibiting primary motor cortex output could explain the electroclinical correlation.

Ocular neuromyotonia.

Ocular neuromyotonia is a rare, albeit treatable, ocular motor disorder, characterised by recurrent brief episodes of diplopia due to tonic extraocular muscle contraction. Ephaptic transmission in a chronically damaged ocular motor nerve is the possible underlying mechanism. It usually improves with carbamazepine. A 53-year-old woman presented with a 4-month history of recurrent episodes of binocular vertical diplopia (up to 40/day), either spontaneously or after sustained downward gaze. Between episodes she had a mild left fourth nerve palsy. Sustained downward gaze consistently triggered downward left eye tonic deviation, lasting around 1 min. MR scan of the brain was normal. She improved on starting carbamazepine but developed a rash that necessitated stopping the drug. Switching to lacosamide controlled her symptoms.

Amoxicillin, a potential epileptogenic drug.

Beta-lactams are known to cause a wide spectrum of neurotoxic manifestations including epileptic seizures. The neurotoxicity of penicillin was first reported in 1945 by Johnson and Walker and is believed to exert an inhibitory effect on gamma-aminobutyric acid transmission of cortical pyramidal cells, due to its beta-lactam ring structure. Epileptogenicity is also a feature of the semisynthetic beta-lactams including aminopenicillins. In this report, we present a patient with a recurrent history of discrete body twitching/jerks of epileptic nature in the context of amoxicillin exposure. The EEG revealed intermittent generalized short bursts of beta-frequency polyspikes. This electro-clinical picture was reversed by amoxicillin discontinuation.

A-phases subtype detection using different classification methods.

Cyclic alternating patterns (CAPs) occur during normal sleep, but higher CAP rates are associated with abnormal conditions, such as epilepsy. Efficient automatic classification of CAP A-phase sub-types would be of remarkable importance for the consideration of CAP as a disease bio-marker. This paper reports a multi-step methodology for the classification of A-phases subtypes. The methodology encompasses: feature extraction, feature ranking, and classification (Support Vector Machine (SVM), k-Nearest Neighbor (k-NN) and Discriminant Analysis (DA)). The study was carried out on 30 subjects with nocturnal frontal lobe epilepsy. The best classifier is based on a SVM that achieved an accuracy of 71%. For each Aphase subtype, i.e. A1, A2, and A3, the sensitivities were 55%, 37% and 25%, respectively. The classifiers developed are an innovation compared to what is found on literature, because they are designed to detect all subtypes and achieved better performance values. However, the performance values still need to be improved to achieve a reliable classifier that would not need a human technician supervision.

Epilepsia partialis continua of the abdominal muscles due to cerebrovascular disease.

Two elderly men, with previous history of cerebrovascular disease, were admitted to the emergency department due to focal motor status epilepticus with persistent myoclonic jerks of one side of the body. In both cases, the clinical picture evolved into a unilateral and isolated arrhythmic myoclonus of the abdominal muscles with preserved consciousness. These involuntary movements resolved with antiepileptic drugs. Although cerebrovascular disease is one of the most common causes of epilepsia partialis continua, reported cases in the literature with predominant abdominal involvement have a different aetiology. The neuroimaging and electroencephalographic findings showed a wide spectrum of different localizations and aetiologies associated with this particular type of epileptic seizure. Indeed, the pathophysiology of focal motor seizures involving the abdominal muscles is still a matter of discussion. In our second case, we present a patient with epilepsia partialis continua of the abdominal wall with an occipital focus, which, to the best of our knowledge, has not been previously reported. [Published with video sequences].

Automatic identification of Cyclic Alternating Pattern (CAP) sequences based on the Teager Energy Operator.

The Cyclic Alternating Pattern (CAP) is a periodic cerebral activity prevalent during Non-Rapid Eye Movement (NREM) sleep-stages. The CAP is composed by A-phases that are related to a change in amplitude, frequency or both from the background activity epochs, called B-phases. Depending on the type of increase the A-phase could be classified as A1, A2 or A3 subtype. This paper proposes the usage of the Teager Energy Operator (TEO) to analyze the amplitude changes in the different frequency-bands to detect A-phases subtypes. The TEO classification performance is compared with the performance of a state-of-the art EEG feature, applied previously for CAP scoring and referred as the macro-micro structure descriptor (MMSD). In general, the TEO is the best feature and the improved results were obtained in the delta band for the A1 and A2 sub-types. More precisely, a sensitivity and specificity of 80.31% and 82.93% were obtained for the A1 subtype, respectively. A2 phases were detected with 76.96% of sensitivity and 73.22% of specificity. The two features detected A3 subtype with approximately the same sensitivity (approx. 70%) and specificity (approx. 75%), however the results were improved by considering the highest frequency band. These results are consistent with the frequency content of the different sub-phases.

Anti-NMDA receptor encephalitis presenting with total insomnia--a case report.

Fatal insomnia (FI) is the first diagnosis to be considered by most neurologists when approaching a patient presenting with total insomnia followed by personality and cognitive changes, disturbance of alertness, autonomic hyperactivation and movement abnormalities. We report the case of a 30 year-old male patient who presented with total insomnia followed by episodes of psychomotor restlessness resembling anxiety attacks. Twenty days later, he developed refractory convulsive status epilepticus with admission to Intensive Care Unit. He progressed to a state of reduced alertness and responsiveness, presenting periods of agitation with abnormal dyskinetic movements, periods of autonomic instability and central hypoventilation. Workup revealed antibodies against N-methyl-d-aspartate receptor (NMDAR). Immunotherapy treatment led to a very significant improvement with the patient presenting only slight frontal lobe dysfunction after one year of recovery. To the best of our knowledge this is the first report of a patient with anti-NMDAR encephalitis first presenting with total insomnia. Our aim is to alert that anti-NMDAR encephalitis must be considered in the differential diagnosis of FI, especially in sporadic cases. Distinguishing the two conditions is very important as, contrarily to the fatal disclosure of FI, anti-NMDAR encephalitis is potentially reversible with adequate treatment even after severe and prolonged disease.

Posterior reversible encephalopathy syndrome: the importance of early diagnosis.

A 14-year-old boy was submitted to cardiac transplant due to a dilated cardiomyopathy. On the fourth day of immunosuppression (corticosteroids, mycophenolate mofetil and tacrolimus), he developed right focal seizures and drowsiness. Blood pressure was in the normal range and laboratory findings in cerebral spinal fluid and blood were unremarkable, with drugs in non-toxic levels. The EEG showed a slow background rhythm more pronounced on the right and a seizure onset in the right occipital region. MRI revealed a diffuse hyperintense subcortical white-matter lesion on fluid attenuated inversion recovery, with lesser involvement of left temporal-occipital region. There was no enhancement with gadolinium and MRI diffusion-weighted imaging was consistent with vasogenic oedema. Tacrolimus was stopped with regression of MRI abnormalities and clinical recovery. Posterior reversible encephalopathy associated with tacrolimus is a rare but potentially serious complication of solid organ transplants. A prompt diagnosis and correct treatment is essential to avoid irreversible brain damage.

A escrita e o sujeito: uma leitura à luz de Lacan / The writing and the subject: a reading from a lacanian point of view

O texto procura analisar a relação do homem com a escrita. Nesse trajeto escolhemos Lacan como interlocutor. Suas investigações sobre o traço reforçam a nossa idéia. Esta toma a escrita como um dos possíveis constituintes do homem. Se a leitura e análise de Lacan não nos parecem fáceis, elas são, no entanto, instigantes e abrem um viés importante nas discussões sobre o papel da escrita. Ele transcende as abordagens meramente instrumentais, que a vêem como uma forma de comunicar-se ou de inserir-se no mercado de trabalho, e a relaciona ao desejo e ao gozo

A escrita e o sujeito: uma leitura à luz de Lacan / The writing and the subject: a reading from a lacanian point of view

O texto procura analisar a relação do homem com a escrita. Nesse trajeto escolhemos Lacan como interlocutor. Suas investigações sobre o traço reforçam a nossa idéia. Esta toma a escrita como um dos possíveis constituintes do homem. Se a leitura e análise de Lacan não nos parecem fáceis, elas são, no entanto, instigantes e abrem um viés importante nas discussões sobre o papel da escrita. Ele transcende as abordagens meramente instrumentais, que a vêem como uma forma de comunicar-se ou de inserir-se no mercado de trabalho, e a relaciona ao desejo e ao gozo (AU)