Presenting Status Epilepticus Research Articles

Reversible Cytotoxic Edema in Patients with COVID-19 Associated Encephalitis Presenting Status Epilepticus

Coronavirus disease 2019 (COVID-19) is a serious infectious disease with multisystem alteration including neurological complications. COVID-19 associated encephalitis is a potentially fatal viral infection of the brain. Diffusion-weighted images (DWI) are a useful evaluation modality of cytotoxic edema in patients with encephalitis. We report on the reversible DWI change in a patient with COVID-19 associated encephalitis, who had diffused cytotoxic edema in the affected temporal lobe and accompanied status epilepticus. Sequential imaging showed that the cytotoxic edema in DWI confirmed recovery to normal after 12 days in the presence of cortical edema in fluid-attenuated inversion recovery image after aggressive neurocritical management. Thus, prompt, proper management is indispensable during the acute period and DWI may be a valuable tool for reflecting the clinical course of COVID-19 associated encephalitis.

Non-convulsive status epilepticus as the initial manifestation in a family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant small-vessel disease caused by mutations of the NOTCH3 gene. It typically presents with migraine, recurrent brain ischaemia, and cognitive disorders. Seizures rarely present as the initial manifestation, with non-convulsive status epilepticus being even less frequent. We present a series of 3 related patients with this arteriopathy, 2 of whom presented status epilepticus as a manifestation of the disease.

Status epilepticus secondary to hypocalcemia due to vitamin D deficiency

Vitamin D deficiency is becoming more common around the world, owing to reduced sunshine exposure and an imbalanced diet. However, severe hypocalcemia as a result of vitamin D insufficiency is a rare occurrence, and it seldom leads to seizures in children. We present such a case in a 6-month-old infant who presented status epilepticus secondary to hypocalcemia due to vitamin D deficiency, which was first misdiagnosed as epilepsy. Thereby we want to emphasize that hypocalcemia secondary to vitamin D deficiency can lead to convulsion and the importance of vitamin D supplementation.

Variante patogénica en el gen PCDH19 en una paciente con epilepsia y discapacidad cognitiva

La asociación de casos familiares de epilepsia y discapacidad intelectual (DI) en mujeres fue reportada en 1971. El año 2008, se identificó el rol de variantes patogénicas del gen PCDH19 en algunas familias. La enfermedad se presenta con crisis febriles en cluster, DI y rasgos autistas. La mayoría se debe a variantes de novo, pero hay algunos casos heredados por un modo peculiar de transmisión ligada X.Objetivo: Comunicar el caso de una paciente con epilepsia portadora de una variante patogénica en el gen PCDH19, revisando la historia natural de la enfermedad y la evidencia disponible para su manejo.Caso Clínico: Paciente femenina, con antecedentes de embarazo y período perinatal normal. A los 6 meses, estando febril, presentó crisis focales motoras en cluster que repitieron a los 14, 18, 21 meses y 3 años siempre asociadas a fiebre, presentando incluso estatus epiléptico. Mantiene biterapia con topiramato y ácido valproico, completando 13 años sin crisis. El estudio del gen SCN1A no mostró anomalías y el estudio del gen PCDH19 reveló una variante patogénica en heterocigosis, “de novo”. La paciente ha evolucionado con DI y alteraciones conductuales severas que requieren atención de salud mental.Conclusiones: Las variantes patogénicas PCDH19 tienen expresión fenotípica variada. El diagnóstico genético debe sospecharse con la clínica. La morbilidad psiquiátrica a largo plazo puede ser incapacitante.

Variante patogénica en el gen PCDH19 en una paciente con epilepsia y discapacidad cognitiva

The association of family cases of epilepsy and intellectual disability in women was reported in 1971. In 2008, the role of pathogenic variants of the PCDH19 gene in some families were identified. The disease presents with febrile seizure clusters, intellectual disability, and autistic features. Most cases are due to de novo variants, however, there are some inherited cases, with an atypical way of X-linked transmission. To report the case of a patient with epilepsy carrier of a pathogenic variant of the PCDH19 gene, reviewing the natural history of this condition and the available evidence for its management. Female patient, with normal history of pregnancy and perinatal period. At 6 months, while febrile, she presented focal motor seizure clusters that repeated at 14, 18, 21 months and 3 years old, always associated with fever, even presenting status epilepticus. She is on therapy with topiramate and valproic acid, achieving 13 seizure-free years. The analysis of the SCN1A gene showed no abnormalities and the study of the PCDH19 gene revealed a de novo heterozygous pathogenic variant. The patient evolved with intellectual disability and severe behavioral disorders that require mental health team support. PCDH19 pathogenic variants have varied phenotypic expression. The genetic diagnosis should be guided with the clinical features. Long-term psychiatric morbidity can be disabling.

Status epilepticus no convulsivo como manifestación inicial en una familia con arteriopatía autosómica dominante cerebral con infartos subcorticales y leucoencefalopatía (CADASIL)

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant small-vessel disease caused by mutations of the NOTCH3 gene. It typically presents with migraine, recurrent brain ischaemia, and cognitive disorders. Seizures rarely present as the initial manifestation, with non-convulsive status epilepticus being even less frequent. We present a series of 3 related patients with this arteriopathy, 2 of whom presented status epilepticus as a manifestation of the disease.

Should Postanoxic Status Epilepticus be Treated Aggressively?-No!

Electrographic status epilepticus and myoclonus represent frequent findings in patients surviving cardiac arrest; both features have been related to poor clinical outcome. Recent data have outlined that status epilepticus appearing during therapeutic hypothermia and sedation is practically and invariably related to a fatal issue, as opposed to some patients presenting status epilepticus and/or myoclonus after return to normothermic conditions. Although it seems reasonable to give a chance of awakening to the latter patients by administering consequent antiepileptic treatment, especially if other favorable prognostic markers are observed, an aggressive treatment of status epilepticus arising during hypothermia seems futile in view of the existing evidence.

Neurological outcome in newborns with congenital heart disease and seizures

Background: Newborns with congenital heart disease have a high risk of seizures, associated to developmental delay, cerebral palsy, and epilepsy.In this study we analyzed the etiology of seizures, electroencephalographic findings and outcome of newborns with congenital heart disease and seizures.Methods: We retrospectively identified 29 newborns with congenital heart disease, who presented with at least one seizure during their admission to the Neonatal Intensive Care Unit of the Hospital Italiano.Results: All newborns had structural/metabolic seizures. Median gestational age was 38 weeks (30-40 weeks, four pre-term) and median birth weight was 3100 g. (range: 1200-4375). Neurological exam was normal in seven neonates (24%), fourteen had only one seizure and four developed status epilepticus. The EEGs were abnormal in 21 newborns (72%). Ten showed focal paroxysms, ten showed minimal alterations with low amplitude and one had a burst-suppression pattern.Nine newborns (31%) died, due to hemodynamic decompensation. They all had an abnormal EEG (p=0.027), an abnormal neurological exam (p: 0.05) and four presented status epilepticus. (p=0.0053).At six months, two more newborns died and two had refractory epilepsy. Of the 18 patients, six had a normal neurological exam. These 6 patients, had had a normal neonatal neurological exam before hospital discharge and four had had only one seizure. Of the six newborns, five had a normal EEG (p= 0.03).Conclusions: In this population we observed a high mortality and an adverse neurological outcome. Abnormal EEG, abnormal neurological exam and status epilepticus were significantly related to mortality.

019 — (DAS0163) Prognostic significance of interictal spikes and high-frequency oscillations in ECoG acutely recorded during temporal lobe epilepsy surgery

rectal temperature was measured again before and until 4 h after the female rats received 4% pilocarpine i.p. The temperature measures obtained during the pilocarpine injection of OVX (n= 10) female rats were compared with NO OVX (n= 18) female rats submitted to the pilocarpinemodel. The female rats that presented status epilepticus (SE) and those that did not present status epilepticus (NO SE) were compared. Results: Female Wistar rat temperature did not change significantly during the estrous cycle. Nevertheless, these female rats showed a significant temperature reduction after the ovariectomy procedure (p b 0.01). Besides that, NO OVX female rats showed a significantly higher rectal temperature (p b 0.01) before pilocarpine injection compared with the OVX group and still presented significantly lower rectal temperature (p b 0.05) until 4 h after pilocarpine injection. At 1 h after the pilocarpine injection, the significance between the two groups was higher, p b 0.01. Our preliminary results also show that 60% of OVX female rats presented SE after receiving pilocarpine injection, 30% died after a tonic–clonic seizure, and only 10% did not show SE. In NO OVX female rats, only 22% showed SE after pilocarpine injection, and 78% did not. Discussion/conclusions:Our previous results confirm that the absence of reproductive hormones alters the gonadal–hypothalamic–pituitary axis, and this may lead to changes in the temperature that might influence the brain response to pilocarpine and protect it from seizures.

NK1 receptors antagonism of dorsal hippocampus counteract the anxiogenic-like effects induced by pilocarpine in non-convulsive Wistar rats

Recent evidence supports a role for the substance P (SP) in the control of anxiety and epilepsy disorders. Aversive stimuli alter SP levels and SP immunoreactivity in limbic regions, suggesting that changes in SP-NK1 receptor signaling may modulate the neuronal excitability involved in seizures and anxiogenesis. The involvement of NK1 receptors of the dorsal hippocampus and lateral septum in the anxiogenic-like effects induced by a single injection of pilocarpine (PILO) was examined in non-convulsive rats evaluated in the elevated plus-maze (EPM). Male Wistar rats were systemically injected with methyl-scopolamine (1mg/kg) followed 30min later by saline or PILO (350mg/kg) and only rats that did not present status epilepticus were used. One month later, vehicle or FK888 (100pmol) – an NK1 receptor antagonist – were infused in the dorsal hippocampus or the lateral septum of the rats and then behaviorally evaluated in the EPM. Previous treatment with PILO decreased the time spent in and the frequency of entries in the open arms of the EPM, besides altering risk-assessment behaviors such as the number of unprotected head-dipping, protected stretch-attend postures and the frequency of open-arms end activity, showing thus a long-lasting anxiogenic-like profile. FK888 did not show any effect per se but inhibited the anxiogenic responses induced by PILO when injected into the dorsal hippocampus, but not into the lateral septum. Our data suggest that SP-NK1 receptor signaling of the dorsal hippocampus is involved in the anxiogenic-like profile induced by PILO in rats evaluated in the EPM test.

MRI abnormality of the pulvinar in patients with status epilepticus

Recently, magnetic resonance imaging (MRI) abnormalities of the pulvinar in patients with epilepsy have received greater attention, but their occurrence and features have not been fully elucidated. Therefore, we investigated the clinical and radiological features of patients with epilepsy who presented MRI abnormalities of the pulvinar. We retrospectively investigated 225 consecutive patients who came to our institute because of seizures and underwent an MRI within 24h. The patients who exhibited pulvinar MRI abnormalities, their profile, seizure type, efficacy of medication, and chronological changes of MRI findings were examined. Out of the 225 patients who underwent MRI within 24h of seizure, 17 exhibited MRI abnormalities of the pulvinar. All of these 17 patients presented status epilepticus. Bilateral pulvinar diffusion-weighted imaging (DWI) hyperintensity was observed in 3 patients and unilateral pulvinar DWI hyperintensity in the other 14. Out of these 14 patients, 7 exhibited DWI hyperintensity in the ipsilateral cerebral cortex, and 10 patients presented an old lesion due to stroke or trauma. Our results demonstrated that the involvement of the pulvinar in status epilepticus is more frequent than expected and consisted of unilateral or bilateral DWI hyperintensities that may completely normalize. These pulvinar MRI abnormalities possibly reflect the epileptogenic hyperexcitation of different cortical areas through their connections with the pulvinar.

Status Epilepticus as Manifestation of Posterior Reversible Encephalopathy Syndrome in a Healthy Child

Posterior reversible encephalopathy syndrome is a recently described cliniconeuroradiological syndrome reported in children with several predisposing conditions such as transplantation, autoimmune, hematological, infectious, renal, and neoplastic diseases or administration of chemotherapeutic immunosuppressive drugs. Seizures are one of the most frequent manifestations of posterior reversible encephalopathy syndrome; status epilepticus has been described more frequently in adults but rarely in children. We report on the case of a 6-year-old healthy boy who presented status epilepticus as the main manifestation of posterior reversible encephalopathy syndrome in the absence of other underlying conditions. This is the first report of posterior reversible encephalopathy syndrome in a previously healthy child. Our case reminds us that pathogenesis of this condition is far from being completely understood and may include both genetic and environmental factors. Moreover, posterior reversible encephalopathy syndrome should always be suspected by clinicians in cases of status epilepticus with a prolonged neurological failure.

Pathophysiology and Long‐Term Outcome of Reversible Tumor‐Like Lesions Induced by Presenting Status Epilepticus

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. 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. 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. 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.

Cocaine-induced status epilepticus and death generate oxidative stress in prefrontal cortex and striatum of mice

Oxidative stress (OS) has been related to cocaine's actions and also to numerous nervous system pathologies, including seizures. The purpose of this work was to determine the alterations in glutathione (GSH) content, nitrite/nitrate and MDA levels after cocaine-induced toxicity. Male Swiss mice were injected (i.p.) with cocaine 90 mg/kg and observed during 1 h. After this cocaine overdose some animals presented status epilepticus (SE) while some died after seizures. These animals were divided in two groups, SE and death. A group with an association of the antioxidant Vitamin E (Vit E, 400 mg/kg, i.p.) plus Coc 90 (Vit E plus Coc 90) was undertaken to assess the neuroprotective effect of Vit E. Neurochemical analyses were carried out in prefrontal cortex (PFC) and striatum (ST). GSH levels increased only after cocaine-induced death in both areas studied. Cocaine-induced SE has increased nitrite/nitrate content in PFC and ST, while after death the increase was only in PFC. MDA (the lipid peroxidation marker) was elevated after SE and death in ST and only after death in PFC. Antioxidant treatment significantly reduced the GSH, nitrite/nitrate in ST and MDA levels. Only nitrite/nitrate content in PFC has not been decreased by Vit E pretreatment. The results relate that oxidative stress occurs after cocaine-induced toxicity mainly after death indicating that probably the increase of OS in the animal's brain leads to seizures and death, also showing a protective effect of Vit E in this process. Together with previous results this study contributes to the knowledge of cocaine-induced toxicity and possible in the near future to the use of antioxidants in the prevention of cocaine-induced CNS toxicity.

État de mal épileptique de la personne âgée. Étude rétrospective de 63 patients hospitalisés

Introduction Status epilepticus is quite frequent in the elderly but rarely studied despite the poor functional prognosis and significant mortality. Methods We retrospectively evaluated the clinical manifestations and electroencephalogram findings observed over a two-year period in 63 consecutive inpatients aged over 70 years presenting status epilepticus. The variables studied included age, sex, the number of concomitant chronic active diseases, previous neurological disorders, brain lesions on CT or MRI, the use and withdrawal of medications and outcome. Results The incidence of status epilepticus was 1%; two-thirds in women and one-third in men. The mean age was 83 years. Complex partial status epilepticus was noted in 91% with predominant features of confusion (89%), impairment of consciousness (75%) or psychiatric symptoms (46%). Etiologies were often multifactorial and acute symptomatic. Etiology was metabolic in 60%, drug-induced in 51%, demential in 44%, cerebrovascular in 37%, infectious in 30% and other neurological disorders in 28% of the cases. Antiepileptic drugs used to treat status epilepticus were benzodiazepine (60%), often in association with lamotrigine (51%), valproate (46%) or phenytoin (25%). Maintenance of an antiepileptic drug was found in 70% of cases. Complications were loss of autonomy (86%), malnutrition (67%), infections (51%), dementia (30%), pressure sores (14%), and recurrent epilepsy (13%). Mortality was 32% of cases and it was higher in men. Conclusion These findings have shown some special features of status epilepticus among the elderly but other prospective studies are needed to confirm these results and to identify optimal management to decrease mortality, and improve the poor functional prognosis.

Encéphalite limbique paraneoplasique et carcinome épidermoïde du poumon

Paraneoplastic limbic encephalitis is a rare clinical entity, most often associated with small cell lung cancer. We report a case of a 54-year-old man presenting status epilepticus, cognitive dysfunction and loss of short term memory associated with epidermoid lung carcinoma. CT scan was normal whereas MRI revealed hyperintensities on T2WI and FLAIR images in the temporolimbic regions. Treatment of the primary tumour was followed by neurological improvement.

Early development destructive brain lesions and their relationship to epilepsy and hippocampal damage

Fifty-one consecutive adult patients with epilepsy and early development destructive brain lesions were divided into three main groups according to the topographic distribution of the lesion on magnetic resonance imaging: hemispheric ( H) ( n=9); main arterial territory ( AT) ( n=25) and arterial borderzone ( Bdz) ( n=17). Eight (89%) patients from group H presented status epilepticus in the first 5 years of life, five of them associated with fever. Seventeen of the 25 patients from group AT (76%) had an obvious hemiparesis observed early in life. In addition, major prenatal events were significantly more common in the group AT compared with the other two groups. Among patients from group Bdz, prenatal or postnatal events were not identified, except for one patient. Conversely, nine patients from group Bdz (60%) showed a history of perinatal complications. Hippocampal atrophy (HA) was determined by visual analysis in 74.5% of all patients and by volumetry in 92%. The frequency of HA was comparable among groups, but patients from group H presented the most severe atrophy and more frequent hyperintense T2 hippocampal signal. In conclusion, these three groups of patients with early destructive lesions and epilepsy ( H, AT and Bdz), appear to have distinct pathogenic mechanisms. Our data show that there is a striking association of HA with different patterns of neocortical destructive lesions of early development. This association seems to be related to a common and synchronic pathogenic mechanism. The recognition of the pattern and degree of HA among these patients with intractable seizures may influence the surgical rationale.

Selective alterations of glycosaminoglycans synthesis and proteoglycan expression in rat cortex and hippocampus in pilocarpine-induced epilepsy

Proteoglycans and glycosaminoglycans are elements of matrix. In the nervous system, glycosaminoglycans modulate neurite outgrowth and are co-receptors for growth factors playing a crucial role in cell differentiation and synaptogenesis. The receptor of protein tyrosine phosphatase β (RPTPβ) is a chondroitin sulphate proteoglycan which plays an important role in neural morphogenesis and axon guidance mechanisms. Pilocarpine-treated rats present status epilepticus, which is followed by a seizure-free period (silent), by a period of spontaneous recurrent seizures (chronic), and the hippocampus of these animals exhibits cell loss and mossy fiber sprouting. Thus, the synthesis of heparan sulphate and chondroitin sulphate and the time course of RPTPβ immunoreactivity were studied in the hippocampus and cerebral cortex during these phases of pilocarpine-induced epilepsy. The results showed decreased synthesis of heparan sulphate during the acute phase and an increased synthesis of chondroitin sulphate during the silent period in the cortex and hippocampus. In control rats RPTPβ immunoreactivity was detected only in glial cells. After 6 h of status epilepticus the RPTPβ immunoreactivity was no longer detectable in the glial cells in both tissues and intense staining became evident in the matrix, surrounding CA3 and dentate gyrus and piriform cortex neurones. In the silent and chronic periods RPTPβ immunoreactivity was mainly detected in neuronal somata and fibers of neurones of hippocampus and cortex. These changes show a selective variation of synthesis and expression of glycosaminoglycans and RPTPβ in relation to epilepsy suggesting a molecular interplay between glia and neurones during seizures.