Impact of In Utero Exposure to Antiepileptic Drugs on Neonatal Brain Function

In utero brain development underpins brain health across the lifespan but is vulnerable to physiological and pharmacological perturbation. Here, we show that antiepileptic medication during pregnancy impacts on cortical activity during neonatal sleep, a potent indicator of newborn brain health. These effects are evident in frequency-specific functional brain networks and carry prognostic information for later neurodevelopment. Notably, such effects differ between different antiepileptic drugs that suggest neurodevelopmental adversity from exposure to antiepileptic drugs and not maternal epilepsy per se. This work provides translatable bedside metrics of brain health that are sensitive to the effects of antiepileptic drugs on postnatal neurodevelopment and carry direct prognostic value.

Role of High-Frequency Oscillation in Locating an Epileptogenic Zone for Radiofrequency Thermocoagulation

Radiofrequency thermocoagulation (RFTC) has been proposed as a first-line surgical treatment option for patients with drug-resistant focal epilepsy (DRE) that is associated with gray matter nodular heterotopia (GMNH). Excellent results on seizures have been reported following unilateral RFTC performed on ictal high-frequency-discharge, fast-rhythm, and low-voltage initiation areas. Complex cases (GMNH plus other malformations of cortical development) do not have good outcomes with RFTC. Yet, there is little research studying the effect of high-frequency oscillation in locating epileptogenic zones for thermocoagulation on unilateral, DRE with bilateral GMNH. We present a case of DRE with bilateral GMNH, treated using RFTC on unilateral GMNH and the overlying cortex, guided by stereotactic electroencephalogram (SEGG), and followed up for 69 months. Twenty-four-hour EGG recordings, seizure frequency, post-RFTC MRI, and neuropsychological tests were performed once yearly. To date, this patient is seizure-free, the electroencephalogram is normal, neuropsychological problems have not been found, and the trace of RFTC has been clearly identified on MRI. His dosage of antiepileptic medication has, furthermore, been significantly reduced. It is concluded that RFTC on unilateral DRE with bilateral GMNH may achieve good long-term effects, lasting up to, and perhaps longer than, 69 months. Ictal high-frequency oscillation (fast ripple) inside the heterotopia and the overlying cortex may be the key to this successful effect.

Wolf-Hirschhorn Syndrome with Hyperparathyroidism: A Case Report and a Narrative Review of the Literature

Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion condition. The WHS core phenotype includes developmental delays, intellectual disabilities, seizures, and distinctive facial features. Various other comorbidities have also been reported, such as hearing loss, heart defects, as well as eye problems and kidney problems. In this report, we present a case of WHS accompanied by hyperparathyroidism and hypercalcemia, which has not been previously reported. A girl was born at 37 weeks of gestation by vaginal delivery. She was small for the gestational age (2,045 g) and admitted to neonatal intensive care unit. She had typical WHS facial features and was found to have bilateral small kidneys associated with transient metabolic acidosis and renal insufficiency. She had right-sided sensorineural hearing loss, a small atrial septal defect, and colpocephaly and hypoplasia of corpus callosum. She had a single seizure which was well controlled with an oral antiepileptic medication. Cytogenetic studies demonstrated a large terminal chromosome 4p deletion (21.4 Mb) and 4p duplication (2.1 Mb) adjacent to the deletion. A unique finding in this patient is her consistently elevated levels of parathyroid hormone and serum calcium, suggesting hyperparathyroidism. We present this rare case along with a review of the literature and hope to draw an attention to a potential relationship between WHS and hyperparathyroidism.

Potential Adverse Consequences of Combination Therapy with Gabapentin and Pregabalin

Gabapentinoids comprise the medications gabapentin and pregabalin. These were designed to not only look chemically like the central inhibitory neurotransmitter gamma-aminobutyric acid (GABA) but also act like it. The prototype gabapentin was primarily introduced to be used as antiepileptic medication. Today, both chemicals are not only utilized as adjunct antiepileptics in focal (aware and impaired awareness) seizures but are also used in several neuropathic pain conditions and other clinical indications. Their use has skyrocketed in the past few years and this has brought forward more instances of adverse effects and errors in prescribing practices. We describe here a case of a female patient with a history of diabetes, diabetic neuropathy, and hypertension being prescribed both gabapentin and pregabalin concomitantly which led to adverse effects like drowsiness, dizziness, fatigue, and ataxia. Once the patient medication profile was revisited, the pharmacy staff was able to identify the therapeutic duplications (gabapentin and pregabalin). The physician was contacted and pregabalin was discontinued. This led to the disappearance of the adverse effects. The dose of the existing gabapentin was increased to control the symptoms of diabetic neuropathy. This report sheds light on the importance of responsible prescribing, efficient checking of medication profiles on the level of dispensing pharmacies, and timely follow-up to patients to keep the patients safe and their medical conditions under check.

Black stone poisoning with a unique complication of posterior reversible encephalopathy syndrome (PRES)

A 25-year-old woman presented to the emergency department with difficulty in breathing, within 12 hours of intentional black stone ingestion, that is, para-phenylenediamine (p-PD), a chemical component of hair dye. Video laryngoscopy was done which showed laryngeal oedema and got intubated immediately to prevent respiratory failure. She got admitted to the intensive care unit and rigorous fluid resuscitation was done due to acute kidney injury secondary to rhabdomyolysis. On the 5th day, she got extubated after a successful spontaneous breathing trial, and step down to the high dependency unit, where she had four episodes of seizures in a day. After antiepileptic medication initiation, seizures were settled, brain imaging done to rule out stroke showed a finding suggestive of posterior reversible encephalopathy syndrome. Adequate intravenous fluid resuscitation was performed and blood pressure monitored closely. She remained vitally stable and clinically better hence discharge home with clinic follow-up on the 9th day of hospitalisation.

Refractory status epilepticus – a major problem for the practitioners

Introduction: Status epilepticus (SE) is a life-threatening neurological emergency requiring immediate medical intervention and is associated with high mortality and morbidity. The aim of this research was evaluation of clinical and etiological profile of refractory status epilepticus (RSE) among children aged between 1 month and 18 years. Material and methods: The study was done between January 1, 2017 and December 24, 2019. All children with the age limits mentioned above, who presented convulsive SE, subsequently with development in refractory status epileptic (RSE), were included in the study. Patients were investigated and evaluated according to a standard protocol. Subsequently, the characteristics of children with RSE and those without an evolution in RSE were compared. Results: 55 children, out of whom 32 boys with SE were enrolled in the study, of which 20 children (36%) developed RSE. Central nervous system (CNS) infections were the most common causes of SE and development of RSE (51% in SE and 53% in RSE, p > 0.05). Noncompliance of antiepileptic medication served as the second cause for evolution of RSE. The overall mortality rate was 10.9%, the chances of death in RSE (20%) being higher than in SE (5.7%). The unfavorable prognosis was seven times higher in children with RSE, compared to children who developed SE. Conclusions: In the management of CNS infections, pediatricians should be aware of the high risk of developing RSE. In addition, the possibility of developing RSE should be considered and promptly managed in an intensive care unit in order to reduce the risk of mortality and morbidity of this severe neurological condition

Multiple Daily Seizures in a Pregnant Woman - A Case Report

A seizure is a brief disturbance of cerebral function, lasting from seconds to a few minutes, caused by an abnormal electrical discharge. Epilepsy is the tendency to have seizures on a chronic, recurrent basis, not resulting from a temporary condition. The term, epilepsy, does not presuppose a cause; there are many causes. Essentially, anything that disturbs the normal functioning of the cerebral cortex can cause seizures, and if this abnormality is enduring, it can result in epilepsy.1 Epilepsy is a common neurological condition with a global prevalence of 1.2 %. Most women with epilepsy who become pregnant or are planning to conceive are recommended to continue taking antiepileptic drugs (AEDs) to minimise seizure recurrence during pregnancy, adverse effects to the fetus, and unintended ill consequences during labour and / or delivery.2,3 The seizure pattern during pregnancy may be influenced by variations in ovarian hormones, blood levels of antiepileptic drugs, and metabolic changes.4 Status epilepticus occurs in only 1 – 2 % of pregnancies,5 and if treated appropriately and aggressively carries a fairly low risk of morbidity and mortality. Structural and metabolic changes may precipitate new-onset seizures during pregnancy. The structural causes include intracranial haemorrhage of multiple types, cerebral venous sinus thrombosis, and ischemic stroke. Metabolic causes include hyperemesis gravidarum; acute hepatitis (due to fatty liver of pregnancy or viral hepatitis); metabolic diseases, such as acute intermittent porphyria; infections, such as malaria; and eclampsia.5 Evaluation and management should be performed in a stepwise fashion and may require a multidisciplinary approach with other specialties such as neurology.6 The threat of seizures during pregnancy and the consequences that they might have on the developing foetus are fundamental reasons for the prescription of daily antiepileptic medication to a pregnant woman with epilepsy (WWE).7 We present an original case of 3 episodes of seizures, of 22-year-old female who was 16 weeks pregnant. This study was approved by Sree Uthradom Thirunal Hospital, Pattom, Trivandrum, Kerala (ethics committee).

Epileptic phenotype in late-onset hyperinsulinemic hypoglycemia successfully treated by diazoxide

Objectives Serious hyperinsulinemic hypoglycemia (HH) is generally the main initial symptom of hyperinsulinism. Epilepsy, without any overt feature of hypoglycemia, might be a very rare initial presentation of late-onset isolated hyperinsulinism. Case presentation We describe a case of late-onset HH in a 15-year-old boy with a history of idiopathic generalized epilepsy, now named genetic generalized epilepsy (IGE/GGE), beginning with a tonic–clonic seizure at the age of 11 years. Subsequently, absences with rare eyelid myoclonia were recorded on electroencephalogram (EEG), followed by episodes of impaired consciousness with facial myoclonia. Neurological status was normal except attention-deficit hyperactivity disorder (ADHD). At the age of 15 years, an episode of slight alteration of consciousness with neurovegetative signs could be recorded, which did not correspond to an absence status. Hypoglycemia due to hyperinsulinism was documented (clinically, biologically, and genetically). Diazoxide treatment resolved the glycopenic symptoms, the non-hypoglycemic seizures and normalized brain electrical activity allowing complete withdrawal of antiepileptic medication. Conclusions Epilepsy can be a very rare initial feature of HH starting in childhood. The occurrence of atypical features in the context of GGE as “absence statuses” with unusual vegetative symptoms and facial myoclonia might be suggestive for HH. Careful assessment and specific treatment are necessary to prevent hyperinsulinism related brain damage. Our case showed that diazoxide might also resolve seizures and normalize EEG.

Brain Injury and Neuroinflammation of the Gut-Brain Axis in Subjects with Cerebral Palsy

Cerebral Palsy (CP) is a limiting deficiency, characterized by a permanent neuromotor disorder which affects movements, resulting in non-progressive lesions of the immature brain during the neuro psychomotor stages. Epidemiological studies of premature births correlated with the presence of high levels of inflammation in the umbilical cord, amniotic fluid, and fetal blood, being that one of the most relevant underlying physiopathological mechanisms includes inflammation and intra-amniotic infection, with inflammatory response and damage to the developing brain. Recently attributed to the excessive production of cytokines, CP inflammation is mostly modulated through diet restriction, intestinal dysfunction, and drug intake. The high prevalence of convulsive crises in individuals with CP (77%) on its own does not bring about post inflammatory and post convulsive cytokine synthesis, treated with antiepileptic medication. In these individuals, there is high incidence of intestinal constipation (47%), besides oral dysbiosis, gingival bleeding and even greater increase in chronic inflammation. The dysbiosis causes an increase in mucous permeability (leaky-gut) of the gut-brain axis, and increase in seric endotoxin, demonstrating a persistent inflammatory state, and supporting the emergence of new side effects, which can become the object of future research.