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.

The electroclinical spectrum, etiologies, treatment and outcome of nonconvulsive status epilepticus in the elderly.

BACKGROUND: Nonconvulsive status epilepticus (NCSE) in the elderly is particularly difficult to diagnose, mainly due to subtle clinical manifestations and associated comorbidities. The recently validated electroencephalography (EEG) diagnostic criteria for NCSE and the proposed operational classification of status epilepticus provide tools that can allow an earlier diagnosis and better management of NCSE in this age group, possibly contributing to reduce its high mortality. MATERIAL AND METHODS: we used these tools to identify and characterize a cohort of elderly (>60year-old) patients admitted at our institution in a 3-year period; the video-EEG and clinical files of the patients fulfilling EEG diagnostic criteria for NCSE were reviewed, being in this study described their electroclinical spectrum, etiologies, treatment, inhospital mortality, and status epilepticus severity score (STESS). RESULTS: Fourty patients (23 women; mean age 76.6years) were identified. Although dyscognitive NCSE associated with >2.5Hz of epileptiform discharges (ED) was the most frequent electroclinical phenotype, this was quite heterogeneous, ranging from patients with aura continua to patients in coma, associated with frequent ED or rhythmic slow activities. Acute symptomatic (45%) and multifactorial (27.5%) etiologies were the most common, and associated with the worst prognosis. There was a trend to use newer antiepileptic drugs in the early steps of NCSE treatment. The inhospital mortality was high (22.5%) and predicted by STESS scores ≥3. CONCLUSION: In the elderly, NCSE has heterogeneous electroclinical phenotypes and etiologies. In spite of the treatment limitations conditioned by the comorbidities, more aggressive treatments could be justified to reduce mortality in patients with high STESS scores.

Comparative 12-month retention rate, effectiveness and tolerability of perampanel when used as a first add-on or a late add-on treatment in patients with focal epilepsies: The COM-PER study.

OBJECTIVES: To compare the 12-month retention rate, effectiveness and tolerability of perampanel (PER) as a first or late add-on treatment in adult patients with focal-onset seizures (FOS), including focal to bilateral tonic-clonic seizures (FBTCS). METHODS: This retrospective, observational, multicenter study was carried out in patients with FOS that received PER as a late add-on (n = 60), after failure of > 3 AEDs, and a group that received PER as a first add-on treatment (n = 21). RESULTS: At 12 months, the retention (90.5 % vs. 48.3 %; p = 0.001), seizure-freedom (71.4 % vs. 13.3 %; p < 0.001) and responder (85.7 % vs. 28.3 %; p < 0.001) rates were significantly higher in the first add-on group compared with the late add-on group. In patients with FBTCS, the 12-month retention rate did not differ significantly between the first and late add-on groups (93.8 % vs. 66.7 %); however, seizure-freedom (81.2 % vs. 27.8 %; p = 0.002) and responder rate response (93.8 % vs. 44.4 %; p = 0.002) were significantly higher in the first add-on group. There were no significant differences in tolerability between the two groups, including in patients with FBTCS. Adverse events were reported in 54.3 % of patients (44/81), most were mild or moderate, with dizziness being the most frequent one. CONCLUSION: Overall, retention rate and effectiveness at 12 months were significantly higher in patients taking PER as a first add-on than as a late add-on, and the tolerability of PER did not differ significantly between groups. PER demonstrated high effectiveness in patients with FBTCS, even as a late add-on treatment.

Spindle Coma in the Intensive Care Unit: Different Aetiologies - Different Outcomes.

Spindle coma is an electroclinical entity that has been used to describe an EEG pattern of "sleep-like" activity in comatose patients. Although it has been associated with favourable prognosis, its aetiology is one of the key factors for patient outcome. The authors present three cases of spindle coma with different aetiologies (amitriptyline overdose, pontine myelinolysis and hypoxic-ischaemic encephalopathy) that culminated in different outcomes. LEARNING POINTS: Spindle coma (SC) is an electroclinical "sleep-like" pattern that appears in comatose patients.It implies the functional preservation of the cerebral hemispheres which can be associated with a good prognosis.The aetiology of SC is a key factor for outcome.

Sudden psychotic episode probably due to meningoencephalitis and Chlamydia pneumoniae acute infection.

BACKGROUND: Since 9% to 20% of all cases of acute psychosis presenting to an Emergency Department (ED) are due to a general medical condition, cautious medical workup should be mandatory in such patients. Differential diagnosis must consider conditions as diverse as renal failure or CNS infection. Acute Chlamydia pneumoniae infection usually causes a self-limited respiratory syndrome. Rarely, acute neurological complications occur, with acute meningoencephalitis most frequently reported. Diagnosis requires a high level of suspicion and is difficult to confirm. CASE REPORT: We describe a 22 year-old female Caucasian who, three days after a mild pharingitis, developed an acute psychosis with exuberant symptoms interspersed with periods of lucidity, in a background of normal consciousness and orientation. Initial medical and imagiological workup were inconclusive. After 20 days of unsuccessful treatment with antipsychotics she developed a high fever and was re-evaluated medically. Lumbar puncture revealed an inflammatory cerebrospinal fluid. MRI showed irregular thickening and nodularity of the lateral ventricles' lining. An anti-Chlamydia pneumoniae IgM antibody titter of 85 IU/ml was detected. All symptoms cleared after treatment with antibiotics and corticosteroids. CONCLUSION: This is, to our knowledge, the first reported case of acute CP-associated meningoencephalitis manifesting as an acute psychotic episode. It illustrates the principle that non-organic psychiatric syndromes must remain a diagnosis of exclusion in first-time acute psychosis.

Brain-derived neurotrophic factor facilitates glutamate and inhibits GABA release from hippocampal synaptosomes through different mechanisms.

Brain-derived neurotrophic factor (BDNF) has an acute excitatory effect on rat hippocampal synaptic transmission. To compare the action of BDNF upon the release of excitatory and inhibitory neurotransmitters in the hippocampus, we studied the effect of acutely applied BDNF on the K+-evoked glutamate and on the K+-evoked gamma-aminobutyric acid (GABA) release from rat hippocampal nerve terminals (synaptosomes). The acute application of BDNF (30-100 ng/ml) enhanced the K+-evoked [3H]glutamate release. This effect involved tyrosine-kinase B (TrkB) receptor phosphorylation and Ca2+ entry into synaptosomes through voltage-sensitive calcium channels, since it was abolished by K252a (200 nM), which prevents TrkB-mediated phosphorylation, and by CdCl2 (0.2 mM), a blocker of voltage-sensitive calcium channels. In contrast, BDNF (3-100 ng/ml) inhibited K+-evoked [3H]GABA release from hippocampal synaptosomes. This action was also mediated by phosphorylation of the TrkB receptor, but was independent of Ca2+ entry into synaptosomes through voltage-sensitive calcium channels. Blockade of transport of GABA with SKF 89976a (20 microM) prevented the inhibitory action of BDNF upon GABA release, indicating that BDNF influences the activity of GABA transporters. It is concluded that BDNF influences in an opposite way, through distinct mechanisms, the release of glutamate and the release of GABA from hippocampal synaptosomes.

N170 asymmetry as an index of inferior occipital dysfunction in patients with symptomatic occipital lobe epilepsy.

OBJECTIVE: Localizing epileptic foci in posterior brain epilepsy remains a difficult exercise in surgery for epilepsy evaluation. Neither clinical manifestations, neurological, EEG nor neuropsychological evaluations provide strong information about the area of onset, and fast spread of paroxysms often produces mixed features of occipital, temporal and parietal symptoms. We investigated the usefulness of the N170 event-related potential to map epileptic activity in these patients. METHODS: A group of seven patients with symptomatic posterior cortex epilepsy were submitted to a high-resolution EEG (78 electrodes), with recordings of interictal spikes and face-evoked N170. Generators of spikes and N170 were localized by source analysis. Range of normal N170 asymmetry was determined in 30 healthy volunteers. RESULTS: In 3 out of 7 patients the N170 inter-hemispheric asymmetry was outside control values. Those were the patients whose spike sources were nearest (within 3cm) to the fusiform gyrus, while foci further away did not affect the N170 ratio. CONCLUSIONS: N170 event-related potential provides useful information about focal cortical dysfunction produced by epileptic foci located in the close neighborhood of the fusiform gyrus, but are unaffected by foci further away. SIGNIFICANCE: The N170 evoked by faces can improve the epileptic foci localization in posterior brain epilepsy.

Pathophysiology and long-term outcome of reversible tumor-like lesions induced by presenting status epilepticus.

BACKGROUND AND PURPOSE: Within the spectrum of reversible neuroimaging abnormalities induced by status epilepticus (SE) tumor-like lesions (TLL) have been rarely described. Their etiology, pathophysiology, and long-term outcome remain uncertain. These issues could be clarified by long-term magnetic resonance imaging (MRI) studies in TLL induced by presenting SE. METHODS: Prospective multi-sequence MRI and clinical and electroencephalographic long-term (18 to 60 months) follow-up studies were performed in 3 patients with reversible TLL induced by presenting SE. RESULTS: In the peri-ictal MRI, TLL are hypointense in T1-weighted, hyperintense in T2-weighted, and fluid-attenuated inversion recovery images with a marked subcortical component and sulci effacement. The diffusion and MR-spectroscopy studies disclosed intermixed areas of increased/decreased diffusivity associated with a lactate peak and a decreased N-acetylaspartate. At long-term follow-up, none of the patients had seizure recurrence or electroencephalographic epileptiform abnormalities; MRI showed residual focal atrophy and gliosis associated with neuronal loss/dysfunction. CONCLUSIONS: SE per se may induce TLL. MRI multi-sequence studies disclosed that they are mainly formed by focal vasogenic and cytotoxic edema resulting from the hypermetabolism associated with seizure activity. In spite of a clinical favorable long-term outcome, the demonstration of irreversible brain damage argues in favor of immediate treatment of SE.

The electroclinical-imagiological spectrum and long-term outcome of transient periictal MRI abnormalities.

The electroclinical-imagiological spectrum and long-term outcome of transient periictal MRI abnormalities (TPMA) remains largely unclear. This prompted us to perform a prospective observational cohort study, including electroencephalography (EEG) and multi-sequence MRI, in 19 consecutive patients (8 female, mean age 51.7 years) with TPMA induced by convulsive and non-convulsive status epilepticus (n=14) or isolated seizures. TPMA were associated with focal, lateralized or diffuse EEG abnormalities, and were mostly focal unilateral and cortico-subcortical (n=11), less frequently cortically restricted, bilateral, hemispheric and with remote lesions (pulvinar, cerebellum); 66.7% had cortico-pial contrast enhancement and 93.7% restriction on diffusion-weighted imaging, with cortical cytotoxic edema on apparent-diffusion coefficient, only tumor-like TPMA (n=5) presenting noticeable subcortical vasogenic edema. The heterogeneity of clinical, EEG and MRI findings contributed to a 38.6% strict focal topographic concordance between them, with the more widespread findings also attributable to the time lag between studies, seizure dynamics/etiologies and cerebral reserve. At follow-up (mean duration 29.6 months, 3-120), the brain damage induced by TPMA was responsible for a high incidence of clinical and MRI sequelae (63.2%), only tumor-like/small TPMA induced by acute symptomatic seizures presenting good clinical outcomes. Our findings may contribute to a better definition and comprehension of the TPMA electroclinical-imagiological spectrum, pathophysiology and long-term outcome.

[Post-malaria neurologic syndrome]. / Síndrome neurológico agudo pós-malária.

The neurologic symptoms in malaria are usually associated with a severe infection by Plasmodium falciparum. Less frequently, the presence of impaired consciousness, seizures and visual and auditory deficits is related with hypoglycemia (by malaria or quinine) or with the toxicity of anti-malarial drugs. In the last years, it was recognized a rare neurologic complication after the efficient treatment of Plasmodium falciparum malaria - post-malaria neurologic syndrome (PMNS). PMNS occurs days to weeks after the parasite clearance, presenting as an encephalopathy of variable severity. The pathogenic mechanisms involved in PMNS are not well understood, being admitted a possible immunological cause. We describe a case of a 61-year-old man presenting with a severe encephalopathy (delirium, cerebellar ataxia and ophthalmoparesis ), 2 days after complete recovery from Plasmodium falciparum malaria. Peripheral blood smears were repeatedly negative for malaria parasites. MRI during acute phase showed extensive multifocal white matter abnormalities. He was treated with high-dose methylprednisolone with complete resolution of neurological deficits. After 9 months the MRI showed minimal residual lesions.

[Thyrotoxic periodic paralysis: a case report]. / Paralisia periódica tireotóxica.

Thyrotoxic periodic paralysis (TPP) is characterized by recurrent episodes of muscle weakness and hypokalemia associated with thyroid hyperactivity. Reported predominantly among individuals of Asian descent, TPP is a rare manifestation of hyperthyroidism in western populations. We describe a typical case of TPP in a 33-year-old portuguese male, who presented with acute tetraparesis associated with hypokalemia (K+ 2.6 mEq/L). The patient had a 8-week history of several episodes of paraparesis of variable intensity; these attacks were usually nocturnal, preceded by strenuous exercise and resolved spontaneously after a few hours. The presence of tachycardia, weight loss, and goiter led to the diagnosis of Graves's disease. The correction of the hyperthyroid function with metimazol and propranolol prevented further episodes of muscle weakness. Thyrotoxic periodic paralysis should be considered in the differential diagnosis of acute episodes of motor paralysis in young patients. The maintenance of a euthyroid status is an essential part of management as this prevents the paralytic episodes.