National plans and awareness campaigns as priorities for achieving global brain health.

Neurological conditions are the leading cause of death and disability combined. This public health crisis has become a global priority with the introduction of WHO's Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders 2022-2031 (IGAP). 18 months after this plan was adopted, global neurology stakeholders, including representatives of the OneNeurology Partnership (a consortium uniting global neurology organisations), take stock and advocate for urgent acceleration of IGAP implementation. Drawing on lessons from relevant global health contexts, this Health Policy identifies two priority IGAP targets to expedite national delivery of the entire 10-year plan: namely, to update national policies and plans, and to create awareness campaigns and advocacy programmes for neurological conditions and brain health. To ensure rapid attainment of the identified priority targets, six strategic drivers are proposed: universal community awareness, integrated neurology approaches, intersectoral governance, regionally coordinated IGAP domestication, lived experience-informed policy making, and neurological mainstreaming (advocating to embed brain health into broader policy agendas). Contextualised with globally emerging IGAP-directed efforts and key considerations for intersectoral policy design, this novel framework provides actionable recommendations for policy makers and IGAP implementation partners. Timely, synergistic pursuit of the six drivers might aid WHO member states in cultivating public awareness and policy structures required for successful intersectoral roll-out of IGAP by 2031, paving the way towards brain health for all.

Alterations of Plasma Pro-Inflammatory Cytokine Levels in Children with Refractory Epilepsies.

Paediatric epilepsy is a multifaceted neurological disorder with various aetiologies. Up to 30% of patients are considered drug-resistant. The background impact of interfering inflammatory and neuronal pathways has been closely linked to paediatric epilepsy. The characteristics of the inflamed state have been described not only in epilepsies, which are considered prototypes of an inflammatory pathophysiology, but also in patients with drug-resistant epilepsy, especially in epileptic encephalopathies. The imbalance of different cytokine levels was confirmed in several epileptic models. Chemokines are new targets for exploring neuroimmune communication in epileptogenesis, which control leukocyte migration and have a possible role in neuromodulation. Additionally, prostaglandin E2 (PGE2) is an important effector molecule for central neural inflammatory responses and may influence drug responsiveness. We measured the serum interictal quantitative levels of chemokines (CCL2, CCL4, CCL11) and PGE2 in correlation with the seizure frequency and severity in controlled and intractable childhood epilepsies. Our refractory seizure group demonstrated significantly increased concentrations of eotaxin (CCL11) compared to the controlled epilepsy group. The higher level of CCL11 was correlated with an increased seizure frequency, while the PGE2 levels were associated with the severity of seizure and epilepsy, supporting the findings that proinflammatory cytokines may contribute to epileptogenesis and possibly have a role in developing seizure resistance.

Vaccination and childhood epilepsies.

INTRODUCTION: The evidence relating vaccination to febrile seizures and epilepsy is evaluated with an emphasis on febrile seizures (FS), Dravet syndrome (DS), West syndrome, and other developmental and epileptic encephalopathies. METHODS: A systematic literature review using search words vaccination/immunization AND febrile seizures/epilepsy/Dravet/epileptic encephalopathy/developmental encephalopathy was performed. The role of vaccination as the cause/trigger/aggravation factor for FS or epilepsies and preventive measures were analyzed. RESULTS: From 1428 results, 846 duplicates and 447 irrelevant articles were eliminated; 120 were analyzed. CONCLUSIONS: There is no evidence that vaccinations cause epilepsy in healthy populations. Vaccinations do not cause epileptic encephalopathies but may be non-specific triggers to seizures in underlying structural or genetic etiologies. The first seizure in DS may be earlier in vaccinated versus non-vaccinated patients, but developmental outcome is similar in both groups. Children with a personal or family history of FS or epilepsy should receive all routine vaccinations. This recommendation includes DS. The known risks of the infectious diseases prevented by immunization are well established. Vaccination should be deferred in case of acute illness. Acellular pertussis DTaP (diphtheria-tetanus-pertussis) is recommended. The combination of certain vaccine types may increase the risk of febrile seizures however the public health benefit of separating immunizations has not been proven. Measles-containing vaccine should be administered at age 12-15 months. Routine prophylactic antipyretics are not indicated, as there is no evidence of decreased FS risk and they can attenuate the antibody response following vaccination. Prophylactic measures (preventive antipyretic medication) are recommended in DS due to the increased risk of prolonged seizures with fever.

Vaccination in acute immune-mediated/inflammatory disorders of the central nervous system.

This review article covers the vaccination related issues in autoimmune disorders of central nervous system (CNS) including narcolepsy, anti-NMDAR encephalitis, Rasmussen encephalitis and febrile infection related epilepsy syndrome (FIRES). Beyond these conditions the immune mediated epilepsies related with autoimmune CNS disorders are discussed and indications and contraindications of vaccinations in these cases are also considered.

Effect of EEG Biofeedback on Cognitive Flexibility in Children with Attention Deficit Hyperactivity Disorder With and Without Epilepsy.

Attention deficit hyperactivity disorder (ADHD) is one of the most common developmental disorders in school-aged children. Symptoms consistent with ADHD have been observed in 8-77 % of children with epilepsy. Researchers have been motivated to search for alternative forms of treatment because 30 % of patients with ADHD cannot be treated by psychostimulants. Several studies support the use of a multimodal treatment approach that includes neurofeedback (NF) for the long-term management of ADHD. These studies have shown that NF provides a sustained effect, even without concurrent treatment with stimulants. We aimed to assess cognitive flexibility in ADHD children with and without temporal lobe epilepsy (TLE), and to evaluate the effects of NF on cognitive flexibility in these groups of children. We prospectively evaluated 69 patients with ADHD aged 9-12 years. The control group was 26 ADHD children without TLE who received no treatment. The first experimental group comprised 18 children with ADHD. The second experimental group comprised 25 age-matched ADHD children with TLE. This group was further divided in two subgroups. One subgroup comprised those with mesial temporal lobe epilepsy (16 patients, 9 with hippocampal sclerosis and 7 with hippocampal atrophy), and the other with lateral temporal lobe epilepsy (9 patients, 5 with temporal lobe dysplasia, 3 with temporal lobe cysts, and 1 with a temporal lobe cavernoma). We treated their ADHD by conducting 30 sessions of EEG NF. Reaction time and error rates on the Trail Making Test Part B were compared before and after treatment, and significant differences were found for all groups of patients except those who had mesial temporal lobe epilepsy with hippocampal atrophy. Our results demonstrate that in most cases, NF can be considered an alternative treatment option for ADHD children even if they have TLE. Additional studies are needed to confirm our results.

Neuroprotective treatment of cerebral infarction: an experimental study.

We investigated the effect of the amniotic-derived peptide Plaferon-LB on cerebral tissue damage during photochemical insults in rats. Plaferon-LB (US patent number: 20070123467 A1) was extracted from the amniochorionic membrane of a human placenta and showed a relatively strong antihypoxic effect compared to other interferon. Thrombotic infarction was induced by photochemical illumination after intravenous injection of Rose Bengal. The infarct volume, cerebral tissue oxygen tension, cerebral blood flow, and capillary damage were measured in the following groups: untreated control rats, Plaferon-LB-alone rats, insult-alone rats, and insult in Plaferon-LB pretreated rats. The technique of electron paramagnetic resonance (EPR) spectroscopy was used to study free-radical metabolites in the blood and brain tissue ex vivo. Plaferon-LB alone had no effect on systemic blood pressure, cerebral blood flow, and reactive metabolites in the brains of intact animals. In the insult-alone group, a focal hemorrhage was observed in the ischemic area. The cerebral blood flow and tissue oxygen pressure declined to zero within an hour and remained at this level throughout the insult. The treatment with Plaferon-LB 0.5 hr before illumination resulted in a significant reduction of the median infarct size in the insult-alone group. The total length and percentage ratio of thrombotic vessels were significantly diminished in the infarct area. The intensity of Fe2+, Mn2+ -, Mo5+ -xanthinoxidase-containing complexes, and nitric oxide EPR signals was decreased, and the electron transport in the mitochondria was normalized. The results indicate a significant beneficial effect of Plaferon-LB on cerebral infarct, which is likely due to its antioxidative properties.