Characterization and quantification of epilepsy patients with hospital episodes in Portugal: A multicenter retrospective study from Liga Portuguesa Contra a Epilepsia.

INTRODUCTION: Epilepsy affects around 50 million people worldwide and is associated with lower quality of life scores, an increased risk of premature death, and significant socio-economic implications. The lack of updated evidence on current epidemiology and patient characterization creates considerable uncertainty regarding the epilepsy burden in Portugal. The study aims to characterize and quantify the epilepsy patients who have been hospitalized, with medical or surgical procedures involved, and to analyze their associated comorbidities and mortality rates. METHODS: A multicenter retrospective study was conducted using hospital production data of epilepsy patients. The study included all patients diagnosed with epilepsy-related International Classification of Diseases-9/10 codes between 2015 and 2018 in 57 Portuguese National Health Service (NHS) hospitals (n = 57 institutions). Patient characterization and quantification were done for all patients with an epilepsy diagnosis, with specific analyses focusing on those whose primary diagnosis was epilepsy. Baseline, demographic, and clinical characteristics were analyzed using descriptive statistics. RESULTS: Between 2015 and 2018, a total of 80,494 hospital episodes (i.e., patient visit that generates hospitalization and procedures) were recorded, with 18 % to 19 % directly related to epilepsy. Among these epilepsy-related hospital episodes, 13.0 % led to short term hospitalizations (less than 24 h). Additionally, the average length of stay for all these epilepsy-related episodes was 8 days. A total of 49,481 patients were identified with epilepsy based on ICD-9/10 codes. The median age of patients was 64 years (min: 0; max: 104), with a distribution of 4.8 patients per 1,000 inhabitants. From the total of deaths (9,606) between 2015 and 2018, 14% were associated with patients whose primary diagnosis was epilepsy, with 545 of these being epilepsy-related deaths. Among patients with a primary diagnosis of epilepsy, the most common comorbidities were hypertension (24%) and psychiatric-related or similar comorbidities (15%), such as alcohol dependance, depressive and major depressive disorders, dementia and other convulsions. CONCLUSION: This study showed similar results to other European countries. However, due to methodological limitations, a prospective epidemiological study is needed to support this observation. Furthermore, the present study provides a comprehensive picture of hospitalized epilepsy patients in Portugal, their comorbidities, mortality, and hospital procedures.

Metabolic lesion-deficit mapping of human cognition.

In theory the most powerful technique for functional localization in cognitive neuroscience, lesion-deficit mapping is in practice distorted by unmodelled network disconnections and strong 'parasitic' dependencies between collaterally damaged ischaemic areas. High-dimensional multivariate modelling can overcome these defects, but only at the cost of commonly impracticable data scales. Here we develop lesion-deficit mapping with metabolic lesions-discrete areas of hypometabolism typically seen on interictal 18F-fluorodeoxyglucose PET imaging in patients with focal epilepsy-that inherently capture disconnection effects, and whose structural dependence patterns are sufficiently benign to allow the derivation of robust functional anatomical maps with modest data. In this cross-sectional study of 159 patients with widely distributed focal cortical impairments, we derive lesion-deficit maps of a broad range of psychological subdomains underlying affect and cognition. We demonstrate the potential clinical utility of the approach in guiding therapeutic resection for focal epilepsy or other neurosurgical indications by applying high-dimensional modelling to predict out-of-sample verbal IQ and depression from cortical metabolism alone.

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.

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].

The utility of 18F-fluorodeoxyglucose PET (FDG PET) in epilepsy surgery.

PURPOSE: To investigate the utility of 18F-fluorodeoxyglucose Positron Emission Tomography (FDG PET) in helping decision making for epilepsy surgery. METHODS: All patients with medically refractory focal epilepsy and MRI that was normal or discordant with clinical and EEG data underwent FDG PET. FDG PET scans were reported by two investigators blinded to clinical data using visual assessment aided by the semiquantitative assessment. All clinical, MRI and FDG PET data were reviewed in the multidisciplinary patient management conferences for the localization and further decisions, which were recorded in the electronic database. For this study, we reviewed the charts of all these patients to decide the usefulness of PET in further decision making. FDG PET was considered to be useful if led directly to surgery, helped in planning intracranial EEG or helped in excluding patients from further evaluation. RESULTS: 194 consecutive adult patients (median age, 32.5 years) underwent FDG PET; 158 had normal MRI, 12 had subtle MRI abnormalities and 24 had discordant non-invasive data. Final localization was temporal lobe epilepsy (TLE, n=64), frontal lobe epilepsy (FLE, n=66), temporal-plus epilepsy (n=26) and other extratemporal lobe epilepsies (ETE, n=38). PET scans were normal in 72 (37%) patients, showed unifocal hypometabolism in 98 (50.5%) and bilateral hypometabolism in 24 (12%) patients. The TLE group had a higher proportion of abnormal PET scans (67%) than FLE (52%) and ETE (61%). PET data were useful in 103 (53%) patients, more in TLE (63%) than FLE (38%) or ETE (50%). It led directly to surgery in 12 (6%) cases, helped in planning intracranial EEG in 67 (35%) patients and excluded 24 (12%) patients from further evaluation. Focal hypometabolism on FDG PET increased the odds of being selected for surgery or intracranial EEG by five fold [odds ratio, 5.1 (2.8-9.4); p<0.0001]. CONCLUSIONS: FDG PET scan can help decision making in 53% of presurgical patients with normal or discordant MRI. PET findings need to be evaluated in conjunction with other data.

Lacosamide serum concentrations in adult patients with epilepsy: the influence of gender, age, dose, and concomitant antiepileptic drugs.

OBJECTIVE: Lacosamide (LCM), a new antiepileptic drug (AED) approved as adjunctive therapy for the treatment of patients with partial-onset seizures, has limited pharmacokinetic and drug interaction data. The main objectives of the present study were to investigate the effects of dose, age, gender, and hepatic enzyme-inducing AEDs on the pharmacokinetics of LCM as assessed by steady state serum LCM values. METHODS: An LCM AED therapeutic drug monitoring database was analyzed with regard to LCM serum concentrations and other relevant patient and AED drug information. One hundred twenty eight sera were identified. These were collected from 68 women and 61 men aged 19-66 years, who were prescribed a median LCM dose of 300 mg (range 50-600 mg). RESULTS: Serum LCM concentrations were observed in the following main groupings: LCM monotherapy (n = 5), LCM with nonenzyme-inducing AEDs (n = 50), LCM with enzyme-inducing AEDs (n = 49), LCM with valproic acid (n = 20), and LCM with enzyme-inducing AEDs plus valproic acid (n = 4). Analysis of variance showed a correlation of dose with LCM concentrations (r = 0.53, P < 0.001), and women had statistically higher mean LCM concentration than did men, 37.2 ± 23.6 versus 26.8 ± 12.9 µmol/L (P = 0.001). Serum LCM concentrations were significantly lower (P = 0.002) in the enzyme-inducing AED group (carbamazepine and phenytoin) compared with the LCM monotherapy group and the nonenzyme-inducing group, 23.5 ± 11.0, 34.5 ± 7.7, and 32.7 ± 17.9 µmol/L, respectively. CONCLUSIONS: Serum LCM concentrations increased dose dependently, were age independent, and were higher in women compared with men. Carbamazepine and phenytoin can significantly decrease serum LCM concentrations, probably via induction of LCM metabolism.

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.

Ictal unilateral hyperkinetic proximal lower limb movements: an independent lateralising sign suggesting ipsilateral seizure onset.

Our aim was to determine the lateralising value of ictal repetitive unilateral hyperkinetic proximal lower limb movements. Among 16 patients with ictal hyperkinetic features who underwent intracranial EEG between 2008 and 2011 in our centre, three had repetitive unilateral hyperkinetic proximal lower limb movements, sometimes associated with "hemiballic-like" movements of the ipsilateral upper limb. There were no other consistent lateralising signs. In all patients, these movements were ipsilateral to the ictal onset zone and started a few seconds after electroencephalographic seizure onset. In two patients, intracranial EEG showed seizure onset within the parietal lobe and mesial temporal ictal onset was recorded in a third. Two patients underwent resection and became seizure-free. Our results suggest that unilateral ictal repetitive hyperkinetic proximal lower limb movements may be an independent lateralising sign to the ipsilateral hemisphere.

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.

Views of patients with epilepsy on seizure prediction devices.

Patients views on the relevance, performance requirements, and implementation of seizure prediction devices have so far not been evaluated in a standardized form. We here report views of outpatients with uncontrolled epilepsy from the epilepsy centers at Freiburg, Germany, and Coimbra, Portugal, based on a questionnaire. Interest in the development of methods for seizure prediction both for warning and for closed-loop interventions is high. High sensitivity of prediction is regarded as more important than specificity. Short prediction time windows are preferred, but the indication of seizure-prone periods is also considered worthwhile. Only a few patients are, however, willing to wear EEG electrodes for signal acquisition on a long-term basis. These data support the view that seizure prediction is of high interest to patients with uncontrolled epilepsy. Improvements in the performance of presently available prediction algorithms and technical improvements in EEG recording will, however, be necessary to meet patients requirements.