This is the first large series, comprising 50 patients who suffered a total of 164 episodes, of pseudomigraine with temporary neurological symptoms and lymphocytic pleocytosis (PMP syndrome). Onset of PMP was between the ages of 14 and 39 years and was most frequent in males (68%). Eight males (24%) and five females (31%) had a personal history of migraine. One-quarter had had a viral-like illness up to 3 weeks prior to the onset of the syndrome. The clinical picture consisted of one to 12 episodes of changing variable neurological deficits accompanied by moderate-to-severe headache and occasionally fever. The headaches were described as predominantly throbbing and bilateral with variable duration (mean, 19 h). The mean duration of the transient neurological deficits was 5 h. Sensory symptoms were most common (78% of episodes), followed by aphasic (66%) and motor (56%) symptoms. Visual symptoms appeared in only 12% of episodes. The most frequent combinations were motor aphasia plus sensory and motor right hemibody symptoms (19% of episodes), motor aphasia plus right sensory symptoms (10%) and isolated right (9%) or left (9%) sensory symptoms. All patients were asymptomatic between episodes and following the symptomatic period (maximum duration 49 days). Lymphocytic pleocytosis ranged from 10 to 760 lymphocytic cells/mm3 CSF (mean, 199). In CSF, protein was increased in 96% of patients, IgG was normal in 80% of cases and oligoclonal bands were not found. Adensoine deaminase values were slightly above normal in two out of 16 patients tested. Extensive microbiological determinations, including viral HIV and borrelia serologies, were negative. Brain CT and MRI were always within normal limits, while EEG frequently showed focal slowing. Conventional cranial angiography was performed on 12 patients. In only one were there abnormalities suggestive of localized vascular inflammation, coincident with the focal neurological symptoms. Two patients developed PMP symptoms immediately after angiography. SPECT, performed on only three patients in the symptomatic period, revealed focal areas of decreased uptake consistent with the clinical symptoms. PMP aetiology remains a mystery; chronic arachnoiditis, viral meningoencephalitis or migraine are not plausible aetiological explanations. Because a number of patients had had a prodromic viral-like illness, we hypothesize here that such a viral infection could activate the immune system, thereby producing antibodies that would induce an aseptic inflammation of the leptomeningeal vasculature, possibly accounting for this clinical picture.

SARS-CoV-2 was first detected in December 2019 in the Chinese city of Wuhan and has since spread across the world. At present, the virus has infected over 1.7 million people and caused over 100 000 deaths worldwide. Research is currently focused on understanding the acute infection and developing effective treatment strategies. In view of the magnitude of the epidemic, we conducted a speculative review of possible medium- and long-term neurological consequences of SARS-CoV-2 infection, with particular emphasis on neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin, based on the available evidence on neurological symptoms of acute SARS-CoV-2 infection. We systematically reviewed the available evidence about the pathogenic mechanisms of SARS-CoV-2 infection, the immediate and lasting effects of the cytokine storm on the central nervous system, and the consequences of neuroinflammation for the central nervous system. SARS-CoV-2 is a neuroinvasive virus capable of triggering a cytokine storm, with persistent effects in specific populations. Although our hypothesis is highly speculative, the impact of SARS-CoV-2 infection on the onset and progression of neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin should be regarded as the potential cause of a delayed pandemic that may have a major public health impact in the medium to long term. Cognitive and neuropsychological function should be closely monitored in COVID-19 survivors.

Inositols are sugar-like compounds that are widely distributed in nature and are a part of membrane molecules, participating as second messengers in several cell-signaling processes. Isolation and characterization of inositol phosphoglycans containing myo- or d-chiro-inositol have been milestones for understanding the physiological regulation of insulin signaling. Other functions of inositols have been derived from the existence of multiple stereoisomers, which may confer antioxidant properties. In the brain, fluctuation of inositols in extracellular and intracellular compartments regulates neuronal and glial activity. Myo-inositol imbalance is observed in psychiatric diseases and its use shows efficacy for treatment of depression, anxiety, and compulsive disorders. Epi- and scyllo-inositol isomers are capable of stabilizing non-toxic forms of β-amyloid proteins, which are characteristic of Alzheimer’s disease and cognitive dementia in Down’s syndrome, both associated with brain insulin resistance. However, uncertainties of the intrinsic mechanisms of inositols regarding their biology are still unsolved. This work presents a critical review of inositol actions on insulin signaling, oxidative stress, and endothelial dysfunction, and its potential for either preventing or delaying cognitive impairment in aging and neurodegenerative diseases. The biomedical uses of inositols may represent a paradigm in the industrial approach perspective, which has generated growing interest for two decades, accompanied by clinical trials for Alzheimer’s disease.

Objective: This study investigated early, real‐world outcomes with cenobamate (CNB) in a large series of patients with highly drug‐resistant epilepsy within a Spanish Expanded Access Program (EAP).Method: This was a multicenter, retrospective, observational study in 14 hospitals. Inclusion criteria were age ≥18 years, focal seizures, and EAP authorization. Data were sourced from patient clinical records. Primary effectiveness endpoints included reductions (100%, ≥90%, ≥75%, and ≥50%) or worsening in seizure frequency at 3‐, 6‐, and 12‐month visits and at the last visit. Safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation.Results: The study included 170 patients. At baseline, median epilepsy duration was 26 years and median number of seizures/month was 11.3. The median number of prior antiseizure medications (ASMs) and concomitant ASMs were 12 and 3, respectively. Mean CNB dosages/day were 176 mg, 200 mg, and 250 mg at 3, 6, and 12 months. Retention rates were 98.2%, 94.5%, and 87% at 3, 6, and 12 months. At last available visit, the rate of seizure freedom was 13.3%; ≥90%, ≥75%, and ≥50% responder rates were 27.9%, 45.5%, and 63%, respectively. There was a significant reduction in the number of seizures per month (mean: 44.6%; median: 66.7%) between baseline and the last visit (P < 0.001). Responses were maintained regardless of the number of prior or concomitant ASMs. The number of concomitant ASMs was reduced in 44.7% of patients. The cumulative percentage of patients with AEs and AEs leading to discontinuation were 68.2% and 3.5% at 3 months, 74.1% and 4.1% at 6 months, and 74.1% and 4.1% at 12 months. The most frequent AEs were somnolence and dizziness.Significance: In this highly refractory population, CNB showed a high response regardless of prior and concomitant ASMs. AEs were frequent but mostly mild‐to‐moderate, and few led to discontinuation.

Objective This article estimates the incidence and fatality of coronavirus disease 2019 (COVID-19) and identifies potential risk factors for fatality in patients with active epilepsy. Methods This is a cross-sectional observational study of patients with active epilepsy and COVID-19. A control group was used to compare the cumulative incidence and case-fatality rate (CFR). The main outcomes of the study were cumulative incidence, defined as number of patients with active epilepsy and COVID-19 admitted to an emergency department divided by the total number of patients with epilepsy at risk, and CFR based on the number of deaths during the enrollment period. Multiple logistic regression analysis was performed to investigate risk factors for fatality in patients with active epilepsy. Results Of the 1,537 patients who fulfilled the inclusion criteria, 21 (1.3%) had active epilepsy. The cumulative incidence (95% confidence interval [CI]) of COVID-19 in patients with epilepsy was higher (1.2% [0.6–2.4]) compared to the population without epilepsy (0.5% [0.5–0.5]). In reverse transcription PCR–positive patients, there were no significant differences in CFR in patients with active epilepsy compared to patients without epilepsy (33.3% vs 8.3%; p = 0.266). Of the 21 patients with active epilepsy, 5 (23%) died. In multivariate analysis, the factor associated with fatality in patients with active epilepsy was hypertension (odds ratio [OR] 2.8 [95% CI 1.3–21.6]). In another model, age (OR 1.0 [95% CI 1.0–1.1]) and epilepsy (OR 5.1 [95% CI 1.3–24.0]) were associated with fatality during hospitalization. Conclusion COVID-19 cumulative incidence was higher in patients with active epilepsy. Epilepsy was associated with fatality during hospitalization. Hypertension was associated with fatality in patients with epilepsy.