Infantile Neurodegeneration and Hair Changes: A Rare Case of Menkes Disease

A 4-month-old, previously healthy boy presented with acute onset of prolonged, recurrent seizure activity followed by neurodevelopmental deterioration and concurrent hair shaft hypopigmentation with fragility. Initial evaluation revealed significant low serum copper and ceruloplasmin, electrical status epilepticus on electroencephalography, and generalized subcortical white matter changes with diffuse tortuosity of intracranial vessels on MRI brain. In addition, a genetic study with whole-genome sequencing demonstrated a hemizygous pathogenic variant at c.2179G>A p(Gly727Arg) on ATP7A, thereby confirming the diagnosis of Menkes disease. Symptomatic treatment with antiepileptic medications was provided along with an urgent referral to an advanced center for multidisciplinary care and copper histidine replacement therapy.

Escalation to Barbiturate-Induced Coma for Refractory Seizures after Liver Transplantation

Seizures after liver transplantation were previously thought to be a reliable harbinger of catastrophe, but more recent studies have found seizure activity to be relatively common, and most cases do not result in a poor outcome. Generalized seizures are the most common, and they typically occur de novo within the first two weeks after transplantation. The underlying cause for seizure activity in these patients may be complex, with potential etiologies including metabolic, infectious, cerebrovascular, and medication-induced causes. Identification of the underlying cause and the use of antiepileptic drugs (AEDs) is crucial for minimizing risk to the patient’s neurologic and overall health. In this report, we present the case of a patient with refractory seizures unresponsive to conventional treatment, requiring prolonged barbiturate burst suppression with ventilator support. Seizure activity eventually ceased, and the patient made a full recovery.

Examining the role of astrogliosis and JNK signaling in post-traumatic epilepsy

Objective Post-traumatic epilepsy is a devastating complication of traumatic brain injury that has no targeted pharmacological therapy. Previous literature has explored the role of the c-Jun N-terminal kinase (JNK) pathway in epilepsy and the creation of epileptogenic foci by reactive astrogliosis; however, the relationship between reactive astrogliosis and the c-Jun N-terminal kinase signaling pathway in the development of post-traumatic epilepsy has not been thoroughly examined. Methods Four experimental groups, consisting of c57/b16 male mice, were examined: (1) control, (2) traumatic brain injury of graded severity (mild, moderate, severe), (3) sub-convulsive kainic acid alone without traumatic brain injury (15 mg/kg i.p.), and (4) sub-convulsive kainic acid administered 72 h after moderate traumatic brain injury. Modified Racine scale from 1 to 72 h and total beam breaks at 72 h were used to assess seizure activity. Immunohistochemistry and western blot were utilized to examine astrogliosis (GFAP), microglia activation (IBA-1), and phosphorylated JNK in prefrontal cortex samples collected from the contracoup side at 72 h post-injury. Results Astrogliosis, measured by GFAP, was increased after traumatic brain injury and increased commensurately based on the degree of injury. Mice with traumatic brain injury demonstrated a four-fold increase in phosphorylated JNK: p < 0.001. Sub-convulsive kainic acid administration did not increase seizure activity nor phosphorylation of JNK in mice without traumatic brain injury; however, sub-convulsive kainic acid administration in mice with moderate traumatic brain injury did increase phosphorylated JNK. Seizure activity was worse in mice, with traumatic brain injury, administered kainic acid than mice administered kainic acid. Conclusions Reactive astrocytes may have dysfunctional glutamate regulation causing an increase in phosphorylated JNK after kainic acid administration. Future studies exploring the effects of JNK inhibition on post-traumatic epilepsy are recommended.

Anticonvulsive Effects and Pharmacokinetic Profile of Cannabidiol (CBD) in the Pentylenetetrazol (PTZ) or N-Methyl-D-Aspartate (NMDA) Models of Seizures in Infantile Rats

In spite of use of cannabidiol (CBD), a non-psychoactive cannabinoid, in pediatric patients with epilepsy, preclinical studies on its effects in immature animals are very limited. In the present study we investigated anti-seizure activity of CBD (10 and 60 mg/kg administered intraperitoneally) in two models of chemically induced seizures in infantile (12-days old) rats. Seizures were induced either with pentylenetetrazol (PTZ) or N-methyl-D-aspartate (NMDA). In parallel, brain and plasma levels of CBD and possible motor adverse effects were assessed in the righting reflex and the bar holding tests. CBD was ineffective against NMDA-induced seizures, but in a dose 60 mg/kg abolished the tonic phase of PTZ-induced generalized seizures. Plasma and brain levels of CBD were determined up to 24 h after administration. Peak CBD levels in the brain (996 ± 128 and 5689 ± 150 ng/g after the 10- and 60-mg/kg doses, respectively) were reached 1–2 h after administration and were still detectable 24 h later (120 ± 12 and 904 ± 63 ng/g, respectively). None of the doses negatively affected motor performance within 1 hour after administration, but CBD in both doses blocked improvement in the bar holding test with repeated exposure to this task. Taken together, anti-seizure activity of CBD in infantile animals is dose and model dependent, and at therapeutic doses CBD does not cause motor impairment. The potential risk of CBD for motor learning seen in repeated motor tests has to be further examined.

Characteristics of Patient with Status Epilepticus at the Emergency Department of Sanglah General Hospital

Introduction: Status epilepticus is a neurological condition caused by a failure of body mechanism to terminate the seizures or the onset of abnormal seizure activity resulting in prolonged seizure’s duration for more than five minutes. The available research data on status epilepticus in Indonesia is still limited. The purpose of this study was to determine the profile of patients with status epilepticus at Sanglah General Hospital from 2020 to 2021. Methods: This was a descriptive study with a retrospective approach. The study populations were patients with status epilepticus who were treated at Sanglah General Hospital in 2019-2020 who had no missing data in the medical records. Results: There were 117 patients with status epilepticus, 63 males (53.8%) and 54 females (46.2%). There are 41 patients>60 years (35%), general onset in 63 patients (53.8%), and focal onset in 54 patients (46.2%). Etiology from cerebral was 68 patients (58.1%), followed by metabolic in 28 patients (23.9%). The most common OAE therapy was phenytoin (86.3%) and the longest length of stay status epilepticus patients was 8 days (55.6%). Patients with status epilepticus had leukocytosis (73.5%), increased NLR (66.7%), and decreased mean platelet volume (53.8%). Conclusion: The highest incidence of status epilepticus is in women, above 60 years, general onset type of seizure, and etiology from cerebral. Initial therapy in 117 patients was intravenous diazepam followed by phenytoin for maintenance. NLR increased in most of the patients showing signs of inflammation which further worsened the patient's outcome with a mortality rate of 47%. Keywords: Status epilepticus, seizure duration, anticonvulsant, neutrophil-lymphocyte ratio.

Sleep Disruption Worsens Seizures: Neuroinflammation as a Potential Mechanistic Link

Sleep disturbances, such as insomnia, obstructive sleep apnea, and daytime sleepiness, are common in people diagnosed with epilepsy. These disturbances can be attributed to nocturnal seizures, psychosocial factors, and/or the use of anti-epileptic drugs with sleep-modifying side effects. Epilepsy patients with poor sleep quality have intensified seizure frequency and disease progression compared to their well-rested counterparts. A better understanding of the complex relationship between sleep and epilepsy is needed, since approximately 20% of seizures and more than 90% of sudden unexpected deaths in epilepsy occur during sleep. Emerging studies suggest that neuroinflammation, (e.g., the CNS immune response characterized by the change in expression of inflammatory mediators and glial activation) may be a potential link between sleep deprivation and seizures. Here, we review the mechanisms by which sleep deprivation induces neuroinflammation and propose that neuroinflammation synergizes with seizure activity to worsen neurodegeneration in the epileptic brain. Additionally, we highlight the relevance of sleep interventions, often overlooked by physicians, to manage seizures, prevent epilepsy-related mortality, and improve quality of life.

Regulation and Intervention of Intracranial Pressure

Intracranial pressure is the total amount of pressure exerted by the brain, blood and cerebrocinal fluid in the rigid cranial space. Compliance is an indicator of the brain's tolerance for increased ICP, when compliance is exceeded, there will be a dramatic increase in the pressure/volume curve so that ICP will increase rapidly. In the injured brain, cerebral blood flow (CBF) is regulated to supply sufficient oxygen and substrates to the brain. Certain physiological factors such as hypercarbia, acidosis and hypoxemia cause vasodilation which causes an increase in CBF, seizure activity and fever will increase the level of brain metabolism and CBF. Cerebral edema is the most common cause of non-traumatic brain injury such as central nervous system infections, metabolic and systemic encephalopathy. Vasogenic brain edema occurs due to injury to the blood-brain barrier and increased capillary permeability in the area around the injury, or to inflammation, especially in CNS infections. Medical management of elevated intracranial pressure includes sedation, cerebrospinal fluid drainage, and osmotherapy with either mannitol or hypertonic salts.

P.129 Bi-insular Responsive Neurostimulation Artifact on Scalp Electroencephalogram

Background: Background: Responsive Neurostimulation (RNS) has proven efficacy in treating medically resistant epilepsy as an intracranial system detecting, recording and treating seizures automatically. No information exists pertaining to artifact characteristics of RNS findings in scalp EEG. Methods: A 30 year-old female was diagnosed using intracranial electroencephalography(iEEG), with bi-insular epilepsy, of unknown cause. She presented large number of focal unaware non-motor seizures and seizures with progression to bilateral tonic-clonic. She was implanted with bi-insular RNS. Results: During scalp EEG recordings, a prominent artifact was seen corresponding to an automatized discharge suspectedly evoked by the RNS trying to minimize the frequent epileptiform activity in her case. Figure 1 and 2 depict these findings. Conclusions: Artifact seen by the RNS in scalp EEG has not been previously described in scientific literature. These findings must be identified to better characterize the role of the RNS in EEG and treatment of seizure activity visible on scalp recordings.