Insular Role in Blood Pressure and Systemic Vascular Resistance Regulation.

OBJECTIVES: The insula is a brain area involved in the modulation of autonomic responses. Previous studies have focused mainly on its heart rate regulatory function, but its role in vascular control is not well defined. Ictal/postictal blood pressure (BP) fluctuations may have a role in the pathogenesis of sudden unexpected death in epilepsy. This study aims to characterize the insular influence on vascular regulation through direct high-frequency electrical stimulation (E-stim) of different insular regions during stereo-electroencephalographic studies. MATERIALS AND METHODS: An observational, prospective study was conducted, involving people with epilepsy who underwent E-stim of depth electrodes implanted in the insular cortex. Patients with anatomical or electrophysiological insular abnormalities, E-stim producing after discharges, or any elicited symptoms were excluded. Variations of BP and systemic vascular resistance (SVR) during the insular stimuli were analyzed, comparing them with those observed during E-stim of control contacts implanted in cortical noneloquent regions and sham stimulations. RESULTS: Fourteen patients were included, five implanted in the right insula and nine in the left. We analyzed 14 stimulations in the right insula, 18 in the left insula, 18 in control electrodes, and 13 sham stimulations. Most right insular responses were hypertensive, whereas most left ones were hypotensive. E-stim of the right insula produced a significant BP and SVR increase, whereas the left insula induced a significant BP decrease without SVR changes. The most remarkable changes were elicited in both posterior insulas, although the magnitude of BP changes was generally low. Control and sham stimulations did not induce BP or SVR changes. CONCLUSION: Our findings on insular stimulation suggest an interhemispheric difference in its vascular regulatory function, with a vasopressor effect of the right insula and a vasodilator effect of the left one.

Outcomes from a Spanish Expanded Access Program on cannabidiol treatment in pediatric and adult patients with epilepsy.

AIM: To evaluate the effectiveness and tolerability of cannabidiol (CBD) in patients with developmental and epileptic encephalopathies, including Dravet syndrome (DS), and Lennox-Gastaut syndrome (LGS), in a Spanish Expanded Access Program (EAP). METHODS: This was a multicenter, retrospective, observational study of patients treated with purified CBD in 14 hospitals across Spain. Patients with (1) written informed consent and (2) at least 6 months follow-up before the closure of the database were included. Primary effectiveness endpoints included reductions (100 %, ≥75 %, ≥50 %, ≥25 %, or 0 %) or worsening in seizure frequency (all seizure types and most disabling seizures) at 1-, 3-, 6-, and 12-month visits and at the last visit, and median relative seizure reduction between baseline and last visit. Secondary effectiveness endpoints included retention rate, reduction in seizure severity, status epilepticus, healthcare utilization, and quality of life. Primary safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation. RESULTS: One hundred and two patients (DS 12 %; LGS 59 %; other epilepsy syndromes 29 %) with a mean age of 15.9 years were enrolled. Patients were highly refractory to antiseizure medications (ASMs); mean number of prior failed ASMs was 7.5 (SD 3.7). The mean CBD dose was 13.0 mg/kg/day at the last visit. The proportion of patients with ≥50 % reduction in the total number of seizures from baseline was 44.9 % at 6 months and 38.9 % at 12 months. The median number of total seizures per month reduced by 47.6 % from baseline to the last visit. At 12 months, seizure severity was lower in 33/54 patients (61.1 %) and unchanged in 17/54 patients (31.5 %). Quality of life, based on the CAVE scale, increased from a mean score of 17.9 ± 4.7 (n = 54) at baseline to 21.7 ± 5.5 (n = 51) at the last patient visit (21.2 % improvement). The mean treatment retention time was 10.3 months. There were no statistically significant changes in the number of status epilepticus episodes, but lower healthcare utilization was observed. Adverse events occurred in sixty-eight patients (66.7 %), and the most common were somnolence (34.3 %) and diarrhea (12.7 %). Cannabidiol was discontinued exclusively due to AEs in 7.8 % of patients, increasing to 25.5 % when both lack of efficacy and AEs were considered together. CONCLUSIONS: Cannabidiol demonstrated promising effectiveness and tolerability in patients with developmental and epileptic encephalopathies taking part in a Spanish EAP.

Observational retrospective analysis of vaccination against SARS-CoV-2 and seizures: VACCI-COVID registry.

BACKGROUND: We aimed to assess the risk of developing new-onset seizures or seizure decompensations in people with epilepsy (PWE) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. METHODS: A retrospective observational study in a tertiary hospital was conducted. Clinical records of all patients attended because of seizures or epilepsy at outpatient clinics, emergency department, or admitted to our hospital from January to December 2021 were reviewed, including patients older than 16 years who received some dose of coronavirus disease 2019 (COVID-19) vaccines. RESULTS: A total of 418 vaccinated PWE were analyzed: 6.2% presented an increase in seizure frequency and 1% reported different seizure types during the next month after vaccination. However, 61.5% had another possible cause for this decompensation. Having monthly seizures (1-3/month) was the only associated risk factor (OR 4.9, p < 0.001) while being seizure free > 1 year had a protective role (OR 0.36, p = 0.019). Patients with epileptic encephalopathies or a history of COVID-19 infection were not at increased risk of seizure decompensation. Besides this, 15 patients presented new-onset seizures within the first month post-vaccination, mean time from vaccination 15 ±â€¯8 days, 67% after the second dose. Again, 53.3% had another possible trigger for seizures. Eight debuted with status epilepticus or cluster of seizures. CONCLUSIONS: A small proportion of PWE (6.2%) had an increase in seizure frequency after COVID-19 vaccination and 15 patients had new-onset seizures during the first month after vaccination, though another reason for seizure exacerbation was identified in 61.5% and 53.3%, respectively. Severe acute respiratory syndrome COVID-19 vaccines appear to have little impact on the generation or decompensation of seizures.

COVID-19 prevalence and mortality in people with epilepsy: A nation-wide multicenter study.

BACKGROUND: To assess the prevalence, severity, and mortality of COVID-19 in people with epilepsy (PWE) and evaluate seizure control in PWE during and after COVID-19. METHODS: Retrospective, observational, multicenter study conducted in 14 hospitals. Medical records of randomly selected PWE followed at neurology outpatient clinics were reviewed. Proportion of PWE with a positive test for SARS-CoV-2 during 2020 was calculated. Risk factors associated with COVID-19 and its morbimortality were evaluated. RESULTS: 2751 PWE were included, mean age 48.8 years (18-99), 72.4% had focal epilepsy, and 35% were drug-refractory. COVID-19 prevalence in PWE was 5.53%, while in the Spanish population was 4.26%. Proportion of admissions to hospital, ICU, and deaths in PWE were 17.1%, 2%, and 4.61% of COVID-19 cases, while in Spanish population were 10.81%, 0.95%, and 2.57%, respectively. A severe form of COVID-19 occurred in 11.8%; dyslipidemia, institutionalization at long-term care facilities, intellectual disability, and older age were associated risk factors. Older age, hypertension, dyslipidemia, cardiac disease, and institutionalization were associated with mortality from COVID-19. Seizure control was stable in 90.1% of PWE during acute COVID-19, while 8.6% reported an increase in seizure frequency. During post-COVID-19 follow-up, 4.6% reported seizure control worsening. CONCLUSIONS: COVID-19 was moderately prevalent in PWE. One out of 5 patients required medical attention and 4.6% died due to COVID-19. Older age, dyslipidemia, institutionalization, and intellectual disability were significant risk factors associated with severe COVID-19. Seizure control remained stable during COVID-19 and throughout long-term follow-up in most PWE who contracted the infection.

Neurological Symptoms of COVID-19: The Zonulin Hypothesis.

The irruption of SARS-CoV-2 during 2020 has been of pandemic proportions due to its rapid spread and virulence. COVID-19 patients experience respiratory, digestive and neurological symptoms. Distinctive symptom as anosmia, suggests a potential neurotropism of this virus. Amongst the several pathways of entry to the nervous system, we propose an alternative pathway from the infection of the gut, involving Toll-like receptor 4 (TLR4), zonulin, protease-activated receptor 2 (PAR2) and zonulin brain receptor. Possible use of zonulin antagonists could be investigated to attenuate neurological manifestations caused by SARS-CoV-19 infection.

Characterization of the Insular Role in Cardiac Function through Intracranial Electrical Stimulation of the Human Insula.

OBJECTIVE: The link between brain function and cardiovascular dynamics is an important issue yet to be elucidated completely. The insula is a neocortical brain area that is thought to have a cardiac chronotropic regulatory function, but its role in cardiac contractility is unknown. We aimed to analyze the variability in heart rate and cardiac contractility after functional activation of different insular regions through direct electrical stimulation (E-stim) in humans. METHODS: This was an observational, prospective study, including patients admitted for stereo-electroencephalographic recording because of refractory epilepsy, in whom the insular cortex was implanted. Patients with anatomical or electrophysiological insular abnormalities and those in whom E-stim produced subjective symptoms were excluded. Variations in heart rate (HR), stroke volume (SV), and cardiac output (CO) were analyzed during insular E-stim and compared with control E-stim of non-eloquent brain regions and sham stimulations. RESULTS: Ten patients were included, 5 implanted in the right insula (52 E-stim) and 5 in the left (37 E-stim). Demographic and clinical characteristics of both groups were similar. E-stim of both right and left insulas induced a significant decrease of the CO and HR, and an increase of the SV. E-stim of control electrodes and sham stimulations were not associated with variations in cardiac function. Blood pressure and respiratory rate remained unaltered. INTERPRETATION: Our results suggest a direct chronotropic and inotropic cardiac depressor function of the right and left insulas. The evidence of an insular direct cardiac regulatory function might open a path in the prevention or treatment of heart failure, arrhythmias, and sudden unexpected death in epilepsy. ANN NEUROL 2021;89:1172-1180.

Influence of the COVID-19 outbreak in people with epilepsy: Analysis of a Spanish population (EPICOVID registry).

BACKGROUND: The aim of this study was to have a better understanding of the influence of the coronavirus disease 2019 (COVID-19) pandemic in people with epilepsy (PWE) and to assess whether there have been changes in seizure control during the current COVID-19 outbreak, exploring the possible causes thereof. METHODS: This is an observational, retrospective study based on prospective data collection of 100 successive patients who attended an epilepsy outpatient clinic either face-to-face or telephonically during the months of the COVID-19 outbreak and national state of emergency. RESULTS: One hundred patients were included, 52% women, mean age 42.4 years. During the COVID-19 period, 27% of the patients presented an increase of >50% of seizure frequency. An increase of stress/anxiety (odds ratios (OR): 5.78; p = 0.008) and a prior higher seizure frequency (OR: 12.4; p = 0.001) were associated with worsening of seizures. Other risk factors were exacerbation of depression, sleep deprivation, less physical activity, and history of epilepsy surgery. Three patients had status epilepticus (SE) and one a cluster of seizures. Likewise, 9% of patients improved their seizure control. Reduction in stress/anxiety (OR: 0.05; p = 0.03) and recent adjustment of antiepileptics (OR: 0.07; p = 0.01) acted as protecting factors. CONCLUSIONS: A high proportion of PWE suffered a significant worsening of their seizure control during the months of the COVID-19 pandemic. Emotional distress due to home confinement was the main factor for the change in seizure control. Promoting physical activity and adequate sleep may minimize the potential impact of the pandemic in PWE. Ensuring correct follow-up can prevent decompensation in those PWE at high risk.

Neurologic manifestations in hospitalized patients with COVID-19: The ALBACOVID registry.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) has spread worldwide since December 2019. Neurologic symptoms have been reported as part of the clinical spectrum of the disease. We aimed to determine whether neurologic manifestations are common in hospitalized patients with COVID-19 and to describe their main characteristics. METHODS: We systematically reviewed all patients diagnosed with COVID-19 admitted to the hospital in a Spanish population during March 2020. Demographic characteristics, systemic and neurologic clinical manifestations, and complementary tests were analyzed. RESULTS: Of 841 patients hospitalized with COVID-19 (mean age 66.4 years, 56.2% men), 57.4% developed some form of neurologic symptom. Nonspecific symptoms such as myalgias (17.2%), headache (14.1%), and dizziness (6.1%) were present mostly in the early stages of infection. Anosmia (4.9%) and dysgeusia (6.2%) tended to occur early (60% as the first clinical manifestation) and were more frequent in less severe cases. Disorders of consciousness occurred commonly (19.6%), mostly in older patients and in severe and advanced COVID-19 stages. Myopathy (3.1%), dysautonomia (2.5%), cerebrovascular diseases (1.7%), seizures (0.7%), movement disorders (0.7%), encephalitis (n = 1), Guillain-Barré syndrome (n = 1), and optic neuritis (n = 1) were also reported, but less frequent. Neurologic complications were the main cause of death in 4.1% of all deceased study participants. CONCLUSIONS: Neurologic manifestations are common in hospitalized patients with COVID-19. In our series, more than half of patients presented some form of neurologic symptom. Clinicians need to maintain close neurologic surveillance for prompt recognition of these complications. The mechanisms and consequences of severe acute respiratory syndrome coronavirus type 2 neurologic involvement require further studies.

Effectiveness and safety of perampanel monotherapy for focal and generalized tonic-clonic seizures: Experience from a national multicenter registry.

OBJECTIVE: To assess the effectiveness and tolerability of perampanel (PER) monotherapy in routine clinical practice for the treatment of focal onset and generalized tonic-clonic seizures (GTCS). METHODS: This multicenter, retrospective, observational study was conducted in patients aged ≥12 years treated with PER as primary monotherapy or converted to PER monotherapy by progressive reduction of background antiepileptic drugs. Outcomes included retention, responder, and seizure-free rate after 3, 6, and 12 months and tolerability throughout the follow-up. RESULTS: A total of 98 patients (mean age = 49.6 ± 21.7 years, 51% female) with focal seizures and/or GTCS were treated with PER monotherapy for a median exposure of 14 months (range = 1-57) with a median dose of 4 mg (range = 2-10). The retention rates at 3, 6, and 12 months and last follow-up were 93.8%, 89.3%, 80.9%, and 71.4%, respectively. The retention rates according to the type of monotherapy (primary vs conversion) did not differ (log-rank P value = .57). Among the 98 patients, 61.2% patients had seizures throughout the baseline period, with a median seizure frequency of 0.6 seizures per month (range = 0.3-26). Responder rates at 3, 6, and 12 months were 79.6%, 70.1%, and 52.8%, respectively, and seizure freedom rates at the same points were 62.7%, 56.1%, and 41.5%. Regarding the 33 patients who had GTCS in the baseline period, 87.8% were seizure-free at 3 months, 78.1% at 6 months, and 55.1% at 12 months. Over the entire follow-up, PER monotherapy was generally well tolerated, and only 16% of patients discontinued PER due to adverse events (AEs). Female patients were found to be at a higher risk of psychiatric AEs (female vs male odds ratio = 2.85, 95% confidence interval = 1-8.33, P = .046). SIGNIFICANCE: PER demonstrated good effectiveness and a good safety profile when used as primary therapy or conversion to monotherapy at relatively low doses, in a clinical setting with patients with focal seizures and GTCS.

SUDEP in Spain: An Epilepsy Monitoring Unit based case series.

PURPOSE: SUDEP is the first cause of mortality related to epilepsy. However, in Spain there are no published cases or series from Epilepsy Monitoring Units that could expose the characteristics of SUDEP in our population. METHOD: We reviewed all patients treated at our Spanish Epilepsy Reference Centre who died between 2010-2018. SUDEP cases were classified as definite, probable, possible or near-SUDEP. Epilepsy type, demographics and case detection issues were described. RESULTS: From 1250 evaluated patients, 102 died during the study period. Seven patients were diagnosed with SUDEP or near-SUDEP: two definite SUDEP, one definite SUDEP plus, two probable SUDEP and two near-SUDEP. Specific problems for detection and registration of SUDEP inherent to the Spanish healthcare system and the legal framework were defined. Only 43% of cases were known by the referral neurologist. SUDEP incidence was 1.3 per 1000 patient/year, comprising 0.56% of all deaths in our cohort. Two cases were female, the average age was 36 years (18-61). All patients had focal epilepsy and suffered from generalized tonic-clonic seizures. All witnessed cases occurred after a focal to bilateral tonic-clonic seizure. Four cases occurred during sleep and all non-witnessed cases were found in prone position. One case occurred during video-EEG monitoring. CONCLUSIONS: Our casuistic represents the first Epilepsy Monitoring Unit based case series of SUDEP conducted in Spain. The incidence in our population agrees with the reported in other countries. However, in our population, SUDEP is probably underdiagnosed due to administrative and legal issues.

Exceptional response to brivaracetam in a patient with refractory idiopathic generalized epilepsy and absence seizures.

Brivaracetam is currently indicated as adjunctive therapy for patients with focal-onset seizures with or without secondary generalization. However, it has been suggested that it could provide broad-spectrum efficacy given its similarity to levetiracetam and based on the results from preclinical studies and others of patients with generalized epilepsy. We present the case of a woman with refractory idiopathic generalized epilepsy and absence seizures with dramatic response to brivaracetam. Our report supports a consideration of treatment with this new antiepileptic drug on a case-by-case basis in patients with refractory generalized epilepsy, while we await further studies on this topic.

Cerebral vasospasm and wernicke encephalopathy secondary to adult cyclic vomiting syndrome: the role of magnesium.

BACKGROUND: Magnesium has a regulatory role in the excitability of cell membranes, and is also a cofactor in the phosphorylation of thiamine. Hypomagnesemia has been associated with coronary vasospasm, but its role in cerebrovascular pathology is controversial, and cerebral vasospasm exclusively attributable to hypomagnesemia has not been reported in humans. CASE PRESENTATION: We report the case of a 51-year-old man in whom uncontrollable vomiting, treatment with omeprazole and thiazide, and renal impairment lead to a severe hypomagnesemia (magnesium below the level of detection in blood tests), which secondarily caused Wernicke's encephalopathy and vasospasm in multiple cerebral arteries (seen with cerebral angiography and CT angiography) that presented with a complete right hemisphere neurological deficit. These disturbances completely resolved when magnesium levels were normalized and subsequent neuroimaging tests confirmed the resolution of angiographic changes. CONCLUSION: Our case suggests that hypomagnesemia should be considered in the differential diagnosis of patients with neurological symptoms and predisposing causes.

[Giant racemose subarachnoid and intraventricular neurocysticercosis: A case report]. / Neurocisticercosis racemosa subaracnoidea gigante y ventricular: a propósito de un caso.

Neurocysticercosis is the most frequent parasitic disease of the central nervous system. It is caused by the larvae of Taenia solium, which can affect different anatomical sites. In Spain there is an increasing prevalence mainly due to immigration from endemic areas. The extraparenchymal forms are less common, but more serious because they usually develop complications. Neuroimaging plays a major role in the diagnosis and follow-up of this disease, supported by serology and a compatible clinical and epidemiological context. First-line treatments are cysticidal drugs such as albendazole and praziquantel, usually coadministered with corticosteroids, and in some cases surgery is indicated. We here report a case of neurocysticercosis with simultaneous intraventricular and giant racemose subarachnoid involvement.

Neurocisticercosis racemosa subaracnoidea gigante y ventricular: a propósito de un caso / Giant racemose subarachnoid and intraventricular neurocysticercosis: A case report

La neurocisticercosis es la enfermedad parasitaria más frecuente del sistema nervioso central. Es causada por las larvas de Taenia solium, las cuales pueden estar alojadas en distintas localizaciones anatómicas. En países como España existe una prevalencia en ascenso debido, principalmente, a la inmigración desde regiones endémicas. Las formas extraparenquimatosas son menos frecuentes, pero más graves por su tendencia a producir complicaciones. La neuroimagen desempeña un papel primordial en el diagnóstico y seguimiento de esta enfermedad, apoyada en la serología y un contexto clínico-epidemiológico compatible. El tratamiento de elección son los fármacos cisticidas albendazol y praziquantel, habitualmente se asocian a estos corticoides y, cuando corresponde, la cirugía. Se presenta un caso de neurocisticercosis con afectación simultánea intraventricular y subaracnoidea en su forma racemosa gigante.

Neurocysticercosis is the most frequent parasitic disease of the central nervous system. It is caused by the larvae of Taenia solium, which can affect different anatomical sites. In Spain there is an increasing prevalence mainly due to immigration from endemic areas. The extraparenchymal forms are less common, but more serious because they usually develop complications. Neuroimaging plays a major role in the diagnosis and follow-up of this disease, supported by serology and a compatible clinical and epidemiological context. First-line treatments are cysticidal drugs such as albendazole and praziquantel, usually coadministered with corticosteroids, and in some cases surgery is indicated. We here report a case of neurocysticercosis with simultaneous intraventricular and giant racemose subarachnoid involvement.