Goose Bumps and Memory Loss

A 46-year-old man had an episode of loss of awareness while driving home. He was found in a cul de sac by his neighbor and was acting confused. He was brought to the emergency department; while there, he started having recurrent episodes of goose bumps (goose flesh) involving half of his body associated with a “wavelike” sensation that would typically begin in the lower extremities and spread upward. He also had some speech difficulty. Physical and neurologic examinations were unremarkable, except for mild cognitive deficits. Video electroencephalographic monitoring showed frequent independent left and right temporal ictal and interictal discharges. Magnetic resonance imaging of the brain showed fluid-attenuated inversion recovery hyperintensity in the bilateral hippocampi. Cerebrospinal fluid analysis showed a mildly increased total protein concentration but no supernumerary oligoclonal bands and normal nucleated cell count and immunoglobulin G index. Serum autoimmune epilepsy evaluation was remarkable for leucine-rich, glioma-inactivated protein 1-immunoglobulin G seropositivity. The patient was diagnosed with leucine-rich, glioma-inactivated protein 1- immunoglobulin G antibody–associated autoimmune seizures presenting with pilomotor seizures. Before autoimmune work-up, the patient had been treated with a gradual escalation of antiseizure medications. The seizures continued. He was subsequently started on intravenous methylprednisolone. He was seizure free and was transitioned to an oral prednisone taper. He was subsequently started on a 6-week regimen of intravenous immunoglobulin. He was also started on mycophenolate mofetil. On follow-up clinic visits, the patient had no recurrence of seizures and disclosed no cognitive dysfunction except for mild inattention. Three years after the patient’s initial episode, the antiseizure medications and mycophenolate mofetil were gradually tapered, without recurrence. Leucine-rich, glioma-inactivated protein 1-immunoglobulin G–associated autoimmunity is typically seen among older patients (>50 years), more commonly men. Symptoms commonly include seizures and cognitive dysfunction, presenting as memory loss and disorientation.

Pitfalls in EEG Analysis in Patients With Nonconvulsive Status Epilepticus: A Preliminary Study

Objective: Electroencephalography (EEG) interpretations through visual (by human raters) and automated (by computer technology) analysis were still not reliable for the diagnosis of nonconvulsive status epilepticus (NCSE). This study aimed to identify typical pitfalls in the EEG analysis and make suggestions as to how those pitfalls might be avoided. Methods: We analyzed the EEG recordings of individuals who had clinically confirmed or suspected NCSE. Epileptiform EEG activity during seizures (ictal discharges) was visually analyzed by 2 independent raters. We investigated whether unreliable EEG visual interpretations quantified by low interrater agreement can be predicted by the characteristics of ictal discharges and individuals’ clinical data. In addition, the EEG recordings were automatically analyzed by in-house algorithms. To further explore the causes of unreliable EEG interpretations, 2 epileptologists analyzed EEG patterns most likely misinterpreted as ictal discharges based on the differences between the EEG interpretations through the visual and automated analysis. Results: Short ictal discharges with a gradual onset (developing over 3 s in length) were liable to be misinterpreted. An extra 2 min of ictal discharges contributed to an increase in the kappa statistics of >0.1. Other problems were the misinterpretation of abnormal background activity (slow-wave activities, other abnormal brain activity, and the ictal-like movement artifacts), continuous interictal discharges, and continuous short ictal discharges. Conclusion: A longer duration criterion for NCSE-EEGs than 10 s that is commonly used in NCSE working criteria is recommended. Using knowledge of historical EEGs, individualized algorithms, and context-dependent alarm thresholds may also avoid the pitfalls.

Temporal Onset Focal Seizures Induced by Intermittent Photic Stimulation

The study aimed to review the clinical, radiological, and pathological findings and electroencephalogram (EEG) of pediatric epilepsy patients with temporal onset focal seizures induced by intermittent photic stimulation (IPS). Four patients with temporal onset photosensitivity focal seizures were analyzed. Three (75%) of the four patients were female. The average age of seizure-onset was 4.4 years. The interictal EEG showed both generalized and focal spike and waves in one patient and focal or multifocal spike and waves alone in three patients. Photoparoxysmal response (PPR) was evoked in all patients and showed generalized discharges (patients 2–4), both generalized and posterior discharges (patient 1). Both generalized and focal discharges could coexist in interictal discharges and PPR. The sensitive frequencies of PPR and photoconvulsive response (PCR) were 12–30 and 10–16 Hz, respectively, which were close to the occipital rhythm. In all patients, the onset of PCR was recorded, namely, the left anterior and mesial temporal lobe (TL), the left posterior TL, and the whole left TL, which showed two forms: the seizure of two patients was the onset of slow waves in the temporal area without spreading generalized discharges (patients 1 and 4), and the other one was fast rhythmic activities in the temporal area, spreading to the occipital area or gradually evolving into the generalized discharges (patients 2 and 3). During follow-up, except for patient 3 who had occasional seizures, the seizures of the remaining patients were under control. Temporal onset focal seizures could be induced by IPS. Temporal onset photosensitivity seizures were mostly easy to control with antiseizure drugs.

Increased hippocampal excitability in miR-324-null mice

MicroRNAs are non-coding RNAs that act to downregulate the expression of target genes by translational repression and degradation of messenger RNA molecules. Individual microRNAs have the ability to specifically target a wide array of gene transcripts, therefore allowing each microRNA to play key roles in multiple biological pathways. miR-324 is a microRNA predicted to target thousands of RNA transcripts and is expressed far more highly in the brain than in any other tissue, suggesting that it may play a role in one or multiple neurological pathways. Here we present data from the first global miR-324-null mice, in which increased excitability and interictal discharges were identified in vitro in the hippocampus. RNA sequencing was used to identify differentially expressed genes in miR-324-null mice which may contribute to this increased hippocampal excitability, and 3′UTR luciferase assays and western blotting revealed that two of these, Suox and Cd300lf, are novel direct targets of miR-324. Characterisation of microRNAs that produce an effect on neurological activity, such as miR-324, and identification of the pathways they regulate will allow a better understanding of the processes involved in normal neurological function and in turn may present novel pharmaceutical targets in treating neurological disease.

Premature Ovarian Failure and Epilepsy

Premature ovarian failure (POF) or premature menopause refers to development of amenorrhoea due to cessation of ovarian function before the age of 40 years. The diagnosis is based on elevated FSH levels in menopausal range (usually above 40 IU/l) detected on at least two occasions a few weeks apart. The term “epilepsy” defines a group of disorders characterized by an enduring predisposition of the brain to produce seizures. The hypothalamic-pituitary-ovarian axis regulation is affected by the abnormal neurophysiology of seizures, and the hypothalamic-pituitary-ovarian associated hormones are affected by medications used to treat seizures in women with epilepsy. Ictal and interictal discharges can disrupt the normal activity of brain structures, including the limbic system, amygdala, hypothalamus, and pituitary gland. Management of epilepsy in women requires not only knowledge of epilepsy, but also recognition of the various roles and priorities women have in their lives (education, career development, child rearing, the role as carer within the extended family), and attention to gender-specific issues and their impact on patients’ wellbeing throughout life.Keywords: premature ovarian failure (POF), epilepsy

Prenatal alcohol exposure affects developmental differentiation of interictal discharges in septal and temporal hippocampus

Prenatal alcohol exposure (PAE) provokes lifelong CNS dysfunction, including an increased susceptibility to seizure disorders. We investigated hippocampal excitability in vitro in the offspring of dams exposed to a mild ethanol concentration throughout pregnancy (ethanol 15%v/v in drinking water). Hippocampal slices were prepared from the offspring at a Young (Y, 21-30 Postnatal Days, PND) or Adult (A, 60 PND) age, with controls from same age Normal rats (N). Synchronous spontaneous interictal-type epileptiform discharges (IEDs) were induced by bathing the slices in Mg2+-free ACSF or in 4-Aminopyridine (4-AP, 50µM) and were recorded from CA1 pyramidal layer of Temporal (T) and Septal slices (S). Hippocampal slices readily generated IEDs following NMDA receptor activation or K+ conductance block, with frequency and duration depending on location (septal or temporal), age, the activating mechanism, and prior conditioning (N or PAE). From the two media, 4-AP induced higher frequency (always), shorter duration (mostly) IEDs compared to Mg 2+-free ACSF. Temporal IED frequency increased with age, whereas Septal was stable, indicating an earlier maturation of the latter part. The hippocampal "T to S" (high to low) excitability gradient appeared at/later than the end of the first postnatal month and concerned mostly discharge frequency. Discharge duration generally decreased with maturation but appeared to depend on many factors including conditioning. Prenatal alcohol exposure differentiated the control of synchronous discharges by NMDA receptors and K+ conductances, and their developmental evolution, thus suggesting potential mechanisms for aberrant hippocampal neuronal network function.