Behavioral Arrest Research Articles

Antisense oligonucleotide therapy in an individual with KIF1A-associated neurological disorder.

KIF1A-associated neurological disorder (KAND) is a neurodegenerative and often lethal ultrarare disease with a wide phenotypic spectrum associated with largely heterozygous de novo missense variants in KIF1A. Antisense oligonucleotide treatments represent a promising approach for personalized treatments in ultrarare diseases. Here we report the case of one patient with a severe form of KAND characterized by refractory spells of behavioral arrest and carrying a p.Pro305Leu variant in KIF1A, who was treated with intrathecal injections of an allele-specific antisense oligonucleotide specifically designed to degrade the mRNA from the pathogenic allele. The first intrathecal administration was complicated by an epidural cerebrospinal fluid collection, which resolved spontaneously. Otherwise, the antisense oligonucleotide was safe and well tolerated over the 9-month treatment. Most outcome measures, including severity of the spells of behavioral arrest, number of falls and quality of life, improved. There was little change in the 6-min Walk Test distance, but qualitative changes in gait resulting in meaningful reductions in falls and increasing independence were observed. Cognitive performance was stable and did not degenerate over time. Our findings provide preliminary insights on the safety and efficacy of an allele-specific antisense oligonucleotide as a possible treatment for KAND.

Understanding of Consciousness in Absence Seizures: A Literature Review.

Absence seizures are classically associated with behavioral arrest and transient deficits in consciousness, yet substantial variability exists in the severity of the impairment. Despite several decades of research on the topic, the pathophysiology of absence seizures and the mechanisms underlying behavioral impairment remain unclear. Several rationales have been proposed including widespread cortical deactivation, reduced perception of external stimuli, and transient suspension of the default mode network, among others. This review aims to summarize the current knowledge on the neural correlates of impaired consciousness in absence seizures. We review evidence from studies using animal models of absence epilepsy, electroencephalography, functional magnetic resonance imaging, magnetoencephalography, positron emission tomography, and single photon emission computed tomography.

Posterior cingulate epilepsy: Seizure semiology and intracranial electrical stimulation using SEEG

PurposeThis study aimed to explore seizure semiology and the effects of intracerebral electrical stimulation on the human posterior cingulate cortex (PCC) using Stereoelectroencephalography (SEEG) to deepen our comprehension of posterior cingulate epilepsy (PCE). MethodsThis study examined the characteristics of seizures through video documentation, by assessing the outcomes of intracranial electrical stimulation (iES) during SEEG. We further identified the connection between the observed semiology and precise anatomical locations within the PCC subregions where seizure onset zones (SOZ) were identified. ResultsAnalysis was conducted on 59 seizures from 15 patients recorded via SEEG. Behavioural arrest emerged as the predominant manifestation across the PCC subregions. Where ictal activity extended to both the mesial and lateral temporal cortex, automatism was predominantly observed in seizures originating from the ventral PCC (vPCC). The retrosplenial cortex (RSC) is associated with complex motor behaviour, with seizure discharges spreading to the temporal lobe. Seizures originating from the PCC include axial tonic and autonomic seizures. Only one case of positive clinical seizures was documented. High frequencies of iES within the PCC induced various clinical responses, categorised as vestibular, visual, psychological, and autonomic, with vestibular reactions primarily occurring in the dorsal PCC (dPCC) and RSC, visual responses in the left RSC, and autonomic reactions in the vPCC and RSC. ConclusionThe manifestations of seizures in PCE vary according to the SOZ and the patterns of seizure propagation. The occurrence of seizures induced by iES is exceedingly rare, indicating that mapping of the PCC could pinpoint the primary sector of PCC.

Generalized onset seizures with focal evolution (GOFE) – a largely unknown ictal variation in genetic generalized epilepsies

PurposeAt onset of generalized seizures, focal electroclinical features are commonly seen, while generalized onset seizures with focal evolution (GOFE) are largely unknown bearing the risk of misclassification. MethodsIn two German epilepsy-centers, patients with GOFE documented by video-EEG monitoring (VEM) between 2017 and 2022 were identified retrospectively. In addition to analysis of ictal electroclinical features, detailed epilepsy and family history, response to antiseizure medication (ASM), and findings from neuroimaging were considered. ResultsWe identified five patients with GOFE, three females, age 14 to 22 years. All patients developed genetic generalized epilepsy in childhood or adolescence, each presenting with two or three generalized seizure types. In each of the five patients, one GOFE was recorded by VEM. At onset, EEG seizure patterns were characterized by generalized spike-wave discharges at 2.5 to 3.5/sec for 9 to 16 sec followed by focal evolution of the discharges. Interictally, all patients presented with generalized spike-wave discharges without focal abnormalities. Semiology at onset was behavioral arrest in two patients and generalized increase in tone in one, while two onsets were clinically inapparent. Semiological signs during focal evolution were variable, comprising head and body version, figure 4 sign, unilateral arm clonic activity, and staring with oral automatisms. In one case, focality involved both hemispheres successively. ConclusionProminent focal semiological features in GOFE carry a high risk of misclassification as focal seizures and epilepsy and thus wrong choice of ASM. This calls for low-threshold VEM if any doubts of focal genesis of seizures exist.

Abstract 117: Digitally Subtracted Angiogram & Biopsy Negative Recurrent Spontaneous Bilateral Anterior Cerebral Artery Territory Intracranial Hemorrhage

Introduction Up to 18% of spontaneous intracerebral hemorrhages are cryptogenic despite a thorough workup, usually noted in a lobar location. Although undetected on DSA, a significant proportion of these represent ruptured micro‐AVM/AVF or cavernous malformations that ultimately are amenable to surgical resection if detected on biopsy. However, occult cerebral amyloid angiopathy can also present similarly, and their management is markedly different. Methods We present a case of recurrent bilateral medial frontal hemorrhage in a patient without known cerebrovascular disease that evaded diagnosis despite hematologic evaluation, MRI, CTA, two DSAs, three clot evacuations with pathology, and brain biopsy. Results The patient is a 60‐year‐old previously healthy woman who presented with sudden onset right hemiparesis and speech arrest. CT revealed a left parasagittal hemorrhage. She was brought to the OR for clot evacuation. Pathology from the clot revealed blood vessels of multiple sizes consistent with meningeal vessels or underlying AVM/AVF. A 6‐vessel cerebral angiogram as unremarkable. The patient’s inpatient course was complicated by new onset Afib with RVR and asymptomatic DVT with PE, however no etiology of coagulopathy was detected. MRI brain showed no evidence of cerebral microbleed or other underlying pathology, noting only DWI + FLAIR hyperintensity in the left ACA territory. The patient was diagnosed with ACA territory stroke complicated by PH2‐type hemorrhagic conversion. She was initially placed on IV Heparin, before transition to apixaban uneventfully. She continued to recover in the hospital and was eventually discharged to rehab. She re‐presented 1 month later with worsening behavioral arrest and right hemiparesis. CT head revealed recurrence of left parasagittal ICH. She underwent clot evacuation in the OR again and repeat pathology was unrevealing. A repeat MRI showed only the evident bleed and a subtle hyperintensity in the right occipital cortex suspicious for an interval subacute occipital lobe stroke with laminar necrosis, ostensibly from Afib. She improved clinically and was discharged to rehab with a diagnosis of recurrent hemorrhage attributed to anticoagulant use and recent stroke. She was discharged this time on no anticoagulant or antiplatelets. She re‐presented 1 month later with sudden onset speech arrest, but now with left hemiparesis. CT revealed a right parasagittal hemorrhage. She was brought to the OR for emergent clot evacuation and parenchymal biopsy – which was initially normal. A repeat 6‐vessel DSA was again unremarkable as was repeat brain MRI. The patient’s parenchymal biopsy was sent for specific congo‐red and immunohistochemistry for beta‐amyloid. IHC revealed beta‐amyloid plaques in the parenchyma and vessel walls, confirming a diagnosis of CAA. Conclusion Apparently cryptogenic lobar hemorrhage may be caused by both occult micro‐AVM/fistula and CAA. As in this case, when a patient experiences recurrent DSA negative lobar hemorrhages, biopsy should be pursued. This case was particularly challenging given the anatomical plausibility of parasagittal AVM/fistula given its midline location and venous drainage, considering the patient’s evident predisposition to systemic venous thrombosis hemorrhagic venous infarction mimicking lobar ICH is also possible. We present this case to raise awareness of the potential need for early biopsy, especially in patients who may also require anticoagulation or antiplatelet medications.

Musicogenic seizures - STXBP1 encephalopathy with reflex seizures.

Mutations in the gene encoding syntaxin binding protein 1 (STXBP1) have been implicated in a wide variety of epileptic encephalopathies. Although the recognized phenotypes of patients with STXBP1 encephalopathies have broadened in recent years, no case of reflex seizures, particularly musicogenic seizures, has been reported in the literature. We present an 18-year-old woman with STXBP1 encephalopathy and seizures that are stereotypically reproducible in response to a variety of audible stimuli. An 18-year-old woman with a history of profound intellectual disability, confirmed STXBP1 genetic defect via genetic testing, and seizures beginning as infantile spasms during childhood, who presented to the epilepsy monitoring unit for seizure characterization. Her mother reported reproducible seizures triggered by a particular cell phone ringtone, music from a certain automobile television commercial and certain beeping alarm sounds. In response, the patient had clinically stereotyped seizures associated with staring, behavioral arrest, followed by eye deviation to the left, tonic stiffening in upper and lower extremities and labored breathing, lasting between 30 seconds and 2 minutes. These seizures were reliably reproducible within a few seconds of exposure to the auditory stimulus. During hospitalization, mother played one of the cell phone ringtones known to trigger seizures for the patient, which resulted in induction of a seizure characterized by diffuse electrodecrement, subsequent emergence of frontal-predominant theta which was followed by progressive diffuse attenuation and semi-rhythmic slowing over the right posterior quadrant. This is the first case to describe musicogenic or other reflex seizures in a patient with STXBP1 encephalopathy.

Bilateral Rasmussen Encephalitis: Good Outcome Following Hemispherotomy

BackgroundBilateral Rasmussen encephalitis is a rare variant of a debilitating, typically unihemispheric disease with limited treatment options. Few cases with bilateral histopathology have been reported, all with poor seizure control following surgery. Here we report a favorable outcome following hemispherotomy in a four-year-old male with biopsy-confirmed bilateral disease. CaseThe patient presented with right hemispheric focal seizures with behavioral arrest and over a year progressed to left lower extremity clonic seizures, epilepsia partialis continua, and loss of ambulation, with transient response to steroids and tacrolimus. Histopathology confirmed bilateral disease. The patient developed super-refractory status epilepticus and underwent right functional hemispherotomy 4.5 years after initial presentation. In a 2.5-year follow-up period, an Engel 1D outcome classification was observed with substantially improved quality of life. ConclusionPrevious reports of bilateral Rasmussen encephalitis describe universally poor outcomes, and hemispherotomy is often considered contraindicated. However, hemispherotomy in a patient with bilateral Rasmussen encephalitis may have a good outcome if seizures are unihemispheric.

Pedunculopontine Chx10+ neurons control global motor arrest in mice

Arrest of ongoing movements is an integral part of executing motor programs. Behavioral arrest may happen upon termination of a variety of goal-directed movements or as a global motor arrest either in the context of fear or in response to salient environmental cues. The neuronal circuits that bridge with the executive motor circuits to implement a global motor arrest are poorly understood. We report the discovery that the activation of glutamatergic Chx10-derived neurons in the pedunculopontine nucleus (PPN) in mice arrests all ongoing movements while simultaneously causing apnea and bradycardia. This global motor arrest has a pause-and-play pattern with an instantaneous interruption of movement followed by a short-latency continuation from where it was paused. Mice naturally perform arrest bouts with the same combination of motor and autonomic features. The Chx10-PPN-evoked arrest is different to ventrolateral periaqueductal gray-induced freezing. Our study defines a motor command that induces a global motor arrest, which may be recruited in response to salient environmental cues to allow for a preparatory or arousal state, and identifies a locomotor-opposing role for rostrally biased glutamatergic neurons in the PPN.

Progressive generalized tonic-clonic seizures in a transgenic mouse model of adult-onset epilepsy: Implications for morphological changes in cortico-limbic and brainstem structures

Video/cortical electroencephalography (EEG) is monitored to assess progressive severity of generalized tonic clonic seizures (GTCSs) in a transgenic mouse model of adult-onset epilepsy with increased death risk. The mice overexpress the brain derived neurotrophic factor (BDNF) in the forebrain under the calcium/calmodulin dependent protein kinase 2a (termed TgBDNF) and develop GTCSs in response to tail suspension/cage agitation stimulation at 3–4 months of age. With successive GTCSs (a total of 16 across 10 weeks of assessment), seizures became more severe as evidenced by increased duration of postictal generalized EEG suppression (PGES) associated with loss of posture/consciousness. Mice also developed spike wave discharges with behavioral arrest during the seizure recovery that increased in duration as a function of number of GTCSs. Overall seizure duration (from preictal spike to offset of PGES) and ictal spectral power (full spectra) were also increased. Half of the TgBDNF mice expired following a long period of PGES at the last recorded GTCS. Seizure-evoked general arousal impairment was associated with a striking decrease in total number of gigantocellular neurons of the brainstem nucleus pontis oralis along with increase in volumes of the anterior cingulate cortex and dorsal dentate gyrus in severely convulsive TgBDNF mice compared to litter-matched WT controls and non-convulsive TgBDNF mice. The latter effect was accompanied with an increase in total number of hippocampal granule neurons. These results provide structure-function associations in an animal model of adult-onset GTCSs that progressively increase in severity with clinical relevance for sudden unexpected death following generalized seizures.

EEG Findings in a Pediatric Patient with 3q29 Microdeletion Syndrome (P13-1.005)

<h3>Objective:</h3> 3q29 microdeletion syndrome is a rare genetic disorder which results from interstitial microdeletion of a segment on the long arm of chromosome 3. The syndrome is characterized by neurodevelopmental and psychiatric manifestations including intellectual disability, autism spectrum disorder, anxiety, executive function deficits, and psychosis/schizophrenia. Systemic manifestations include ocular issues, gastrointestinal disorders, dental anomalies, and congenital heart defects. <h3>Background:</h3> We present a 7-year-old boy with a history of intellectual disability including delayed speech and fine motor abilities, and autism spectrum disorder, who presented with frequent and new onset of complete behavioral arrest, staring, grunting and pulling movements lasting several minutes that were described by his teachers. Spells did not progress to tonic-clonic activity and were not associated with urine loss. His physical examination revealed down slanted eyes, epicanthal folds, wide mouth, long and thin philtrum, thin upper lip and axial and appendulicar tone were decreased. EEG while off ASM revealed excessive beta activity of the background, frontally dominant generalized spike/polyspike and wave discharges, and focal spike/polyspike and wave activity seen independently over the left and right frontocentral regions. MRI showed reduced cerebral white matter hemispheric volume involving the frontoparietal lobes with no obvious seizure focus. He was subsequently started on levetiracetam, which resulted in a cessation of staring spells. <h3>Design/Methods:</h3> NA <h3>Results:</h3> NA <h3>Conclusions:</h3> Seizures have been reported in 13% of patients with 3q29 microdeletion syndrome and are generally mild and responsive to ASM. Previously reported EEG abnormalities in patients with 3q29 microdeletion syndrome include focal epileptiform discharges in the left occipital region and slow waves in the frontotemporal regions. To our knowledge, generalized spike/polyspike wave activity has not previously been reported in this syndrome. Whether the independent focal frontocentral epileptiform discharges represent a forme fruste of the generalized discharges, or the latter represent a rapid secondary bisynchrony phenomenon, remains to be determined. <b>Disclosure:</b> Dr. Sheikh has nothing to disclose. Dr. Nascimento has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zogenix. The institution of Dr. Nascimento has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biocodex. Dr. Nascimento has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. The institution of Dr. Nascimento has received research support from Zogenix. The institution of Dr. Nascimento has received research support from Biocodex. The institution of Dr. Nascimento has received research support from Greenwich. Dr. Nascimento has received publishing royalties from a publication relating to health care. Dr. Nascimento has a non-compensated relationship as a Editorial Team Member with Neurology RFS that is relevant to AAN interests or activities. Dr. Nascimento has a non-compensated relationship as a Production Team with Neurology Podcast that is relevant to AAN interests or activities. Dr. Waite has nothing to disclose. Dr. Lam has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage Therapeutics. Dr. Lam has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurona Therapeutics. Dr. Lam has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Cognito Therapeutics. The institution of Dr. Lam has received research support from Sage Therapeutics.

The role of orexin neuron activity in sleep/wakefulness regulation

Orexin (also known as hypocretin) is a neuropeptide exclusively synthesized in the neurons of the lateral hypothalamus (LH). Initially orexin was thought to be involved in the regulation of feeding behavior. However, it is now known to also be a critical regulator of sleep/wakefulness, especially the maintenance of wakefulness. Although the somas of orexin neurons are exclusively located in the LH, these neurons send axons throughout the brain and spinal cord. Orexin neurons integrate inputs from various brain regions and project to neurons that are involved in the regulation of sleep/wakefulness. Orexin knockout mice have a fragmentation of sleep/wakefulness and cataplexy-like behavior arrest, which is similar to the sleep disorder narcolepsy. Recent progress with manipulation of neural activity of targeted neurons, using experimental tools such as optogenetics and chemogenetics, has emphasized the role of orexin neuron activity on the regulation of sleep/wakefulness. Recording of orexin neuron activity in vivo using electrophysiological and gene-encoded calcium indicator proteins revealed that these cells have specific activity patterns across sleep/wakefulness state changes. Here, we also discuss not only the role of the orexin peptide, but also the role of other co-transmitters that are synthesized and released from orexin neurons and involved in sleep/wakefulness regulation.

Decreased but diverse activity of cortical and thalamic neurons in consciousness-impairing rodent absence seizures

Absence seizures are brief episodes of impaired consciousness, behavioral arrest, and unresponsiveness, with yet-unknown neuronal mechanisms. Here we report that an awake female rat model recapitulates the behavioral, electroencephalographic, and cortical functional magnetic resonance imaging characteristics of human absence seizures. Neuronally, seizures feature overall decreased but rhythmic firing of neurons in cortex and thalamus. Individual cortical and thalamic neurons express one of four distinct patterns of seizure-associated activity, one of which causes a transient initial peak in overall firing at seizure onset, and another which drives sustained decreases in overall firing. 40–60 s before seizure onset there begins a decline in low frequency electroencephalographic activity, neuronal firing, and behavior, but an increase in higher frequency electroencephalography and rhythmicity of neuronal firing. Our findings demonstrate that prolonged brain state changes precede consciousness-impairing seizures, and that during seizures distinct functional groups of cortical and thalamic neurons produce an overall transient firing increase followed by a sustained firing decrease, and increased rhythmicity.

Early onset developmental and epileptic encephalopathy and Rett-like phenotype in a 15-year-old girl affected by Cornelia de Lange syndrome type 2 due to a SMC1A gene mutation

Developmental and epileptic encephalopathies (DEE) are conditions in which a mutated gene may cause abnormal functioning of the central nervous system, resulting in both encephalopathy and epileptogenesis. We present a case of a girl with a DEE characterized by a Rett-like phenotype in association with febrile and afebrile clusters of focal seizures. The girl presented typical development until the age of 18 months, followed by regression. The first febrile bilateral tonic-clonic seizure was observed at 30 months of age, and the following month seizures recurred in clusters of several episodes per day every 10 days. These seizures were characterized by behavioural arrest, emotional symptoms, head turning, and followed by bilateral tonic-clonic seizures. The administration of valproic acid and levetiracetam led to prolonged seizure control. However, from the age of 7 years, she had monthly recurrent clusters of focal seizures and non-convulsive status epilepticus which occurred at different ages. Brain and spinal cord MRI showed mild non-progressive hemispheric cerebellar atrophy. A next generation sequencing panel for epilepsy identified the de novo splicing mutation c.2973+1G>A of the SMC1A gene.

A Case of Pembrolizumab (Anti-PD-1) Induced Encephalitis

Objective N/A. Background PD-1 Immune checkpoint inhibitors (ICI) have been associated with neurologic immune-related adverse events including meningoencephalitis and limbic encephalitis that can manifest as paraneoplastic syndromes. We present a case of suspected pembrolizumab (anti PD-1) induced limbic encephalitis presenting as episodic aphasia. Design/Methods N/A. Results A 62-year-old man with poorly differentiated papillary thyroid carcinoma with extensive brain, lung, lymphatic metastases post thyroidectomy, radioiodine therapy, chemotherapy with dabrafenib and trametinib, and stereotactic radiation surgery presented with recurrence of brain metastases one year after the diagnosis of a 2.1 cm metastatic lesion in the left parieto-occipital region causing right homonymous hemianopsia. The metastases initially improved in size and number with radiation and serial brain MRIs were stable. Biopsy of the mets revealed a poorly differentiated carcinoma. He was subsequently treated with pembrolizumab for six months. Two months after treatment initiation, he reported episodic behavioral arrest, confusion, and expressive aphasia concerning for seizures. Continuous EEG monitoring revealed a left-sided focus without seizures, and the episodes persisted despite levetiracetam and clobazam. Four lumbar punctures revealed lymphocytic pleocytosis (10-14 cells), elevated protein (48–68 mg/dl), negative cytology, flow cytometry and viral studies including JC virus. Paraneoplastic panels in serum and cerebrospinal fluid were negative. Repeat MRIs findings were most consistent with radionecrosis and noted improvement of the metastatic lesions. Suspicion was raised for pembrolizumab-induced encephalitis and he received high-dose steroids with minimal response however, clinical improvement noted with reduced episode frequency after intravenous immunoglobulin induction therapy and rituximab maintenance therapy. Conclusions PD-1 ICI-related encephalitis is a diagnosis of exclusion that should be considered in patients with encephalopathy or other neurological deficits following 3 months of treatment initiation and response to immunosuppressive therapy. Higher incidences are reported in males. Early recognition is crucial to prevent long-term neurologic damage. Outcomes are depend on patient characteristics and clinical presentation.

"Generalized-to-focal" epilepsy: stereotactic EEG and high-frequency oscillation patterns

We aimed to clarify the pathophysiology of epilepsy involving seizures with apparently generalized onset, progressing to focal ictal rhythm through stereotactic EEG (SEEG) implantation, recording, stimulation and high-frequency oscillation (HFO) analysis. We identified two patients with seizures with bilateral electrographic onset evolving to focal ictal rhythm, who underwent SEEG implantation. Patients had pre-surgical epilepsy work-up, including prolonged video scalp EEG, brain MRI, PET, ictal/interictal SPECT, MEG, and EEG-fMRI prior to SEEG implantation. Both patients had childhood-onset seizures involving behavioural arrest and left versive head and eye deviation, evolving to bilateral tonic-clonic convulsions. Seizures were electrographically preceded by diffuse, bilateral 3-Hz activity resembling absence seizures. Both had suspected focal lesions based on neuroimaging, including 3T MRI and voxel-based post-processing in one patient. Electrode stimulation did not elicit any habitual electroclinical seizures. HFO analysis showed bilateral focal regions with high fast-ripple rates. “Generalized-to-focal” seizures may occur due to a diffuse, bilateral epileptic network, however, both patients showed ictal evolution from a generalized pattern to a single dominant focus which may explain why the focal aspect of their seizures had a consistent clinical semiology. Patients such as these may have a unique form of generalized epilepsy, but focal/multifocal cerebral abnormalities are also a possibility.

Glue Sniffing Among the Street Children Residing at Pokhara Metropolitan, Nepal: A Descriptive Cross-sectional Study

Introduction: Glue sniffing usually refers to volatile substance abuse (VSA) for psychoactive effects. Street children are the children who live, work, and earn their livelihood through the streets of urban settlements. Street children are mostly attracted to substance abuse and more particularly towards volatile substances as they are cheap, easy to access and have psychoactive effects as alcohol intoxication. This study aimed to assess the general characteristics of street children of Pokhara Metropolitan, Nepal who are addicted to glue sniffing. Methods: A cross-sectional study was conducted among street children who were addicted to glue sniffing through the snowball sampling method in Pokhara Metropolitan, Nepal. Results: All 88 children who were addicted to glue sniffing were males. Of the total children, 59 (67%) children started glue-sniffing at the age of five to ten years of age while nine (10.2%) children started sniffing even before they were five years old. Addiction to glue (n = 33, 37.5%), pleasure (n = 18, 20.5%)), coping with hunger (n = 14, 15.9%), and being a part of street children group (n = 13, 14.8%) were the major reasons to sniff glue for these children. Conclusions: It has been observed that the majority of street children are at increased risk of getting involved in glue sniffing. It has resulted in different ill outcomes such as self-destruction and problematic behavior, fights and police arrest. There is a need to focus on the issue of glue sniffing among the street children to save and ensure the quality of life of these vulnerable children.

NCOG-38. PEMBROLIZUMAB (ANTI-PD-1) INDUCED LIMBIC ENCEPHALITIS PRESENTING AS EPISODIC APHASIA

Abstract PD-1 immune checkpoint inhibitors (ICI) have been associated with neurological immune-related adverse events including meningioencephalitis and limbic encephalitis that can manifest as paraneoplastic syndromes. We present a case of pembrolizumab (Anti-PD-1) induced limbic encephalitis presenting as episodic aphasia. A 62-year-old man with poorly differentiated papillary thyroid carcinoma with extensive brain, lung, lymphatic metastases, post total-thyroidectomy, radioiodine therapy, chemotherapy with dabrafenib and trametinib, and stereotactic radiation presented with recurrence of brain metastasis 1 year after diagnosis of a 2.1 cm metastatic lesion in the left parieto-occipital region. The metastases had initially improved in size and number with radiation, followed on serial MRI Brain - that were stable. Biopsy of recurrence revealed a poorly differentiated cancer. He was subsequently treated with pembrolizumab for 6 months for refractory carcinoma. Two months after treatment initiation, he reported episodic behavioral arrest, confusion, and expressive aphasia, initially concerning for seizures. Continuous EEG monitoring revealed non-epileptogenic left-sided foci and no seizures were captured. Patient empirically started on levetiracetam and clobazam - however, episodes persisted. Lumbar puncture revealed lymphocytic pleocytosis (10-14 cells), elevated protein (48-68 mg/dL), negative cytology, flow cytometry, and viral studies including JC virus. Paraneoplastic panel in serum and cerebrospinal fluid were negative. Repeat MRI findings were most consistent with radionecrosis and on contrary improvement of the previous metastatic lesions. This rose suspicion for pembrolizumab-induced encephalitis and he received high dose steroids with minimal response but great clinical improvement with IVIG and induction/maintenance therapy with rituximab. Marked reduction in aphasic episodes were noticed thereafter. PD-1 ICI-related encephalitis is diagnosis of exclusion that should be considered in patients with encephalopathy or neurological deficit following 3 months of treatment initiation and response to immunosuppressive therapy. Higher incidences reported in males. Early recognition is crucial to prevent long-term neurological damage. Outcomes depend on patient characteristics and timeline of presentation.

A machine-learning approach for predicting impaired consciousness in absence epilepsy.

Behavior during 3–4 Hz spike‐wave discharges (SWDs) in absence epilepsy can vary from obvious behavioral arrest to no detectible deficits. Knowing if behavior is impaired is crucial for clinical care but may be difficult to determine without specialized behavioral testing, often inaccessible in practice. We aimed to develop a pure electroencephalography (EEG)‐based machine‐learning method to predict SWD‐related behavioral impairment. Our classification goals were 100% predictive value, with no behaviorally impaired SWDs misclassified as spared; and maximal sensitivity. First, using labeled data with known behavior (130 SWDs in 34 patients), we extracted EEG time, frequency domain, and common spatial pattern features and applied support vector machines and linear discriminant analysis to classify SWDs as spared or impaired. We evaluated 32 classification models, optimized with 10‐fold cross‐validation. We then generalized these models to unlabeled data (220 SWDs in 41 patients), where behavior during individual SWDs was not known, but observers reported the presence of clinical seizures. For labeled data, the best classifier achieved 100% spared predictive value and 93% sensitivity. The best classifier on the unlabeled data achieved 100% spared predictive value, but with a lower sensitivity of 35%, corresponding to a conservative classification of 8 patients out of 23 as free of clinical seizures. Our findings demonstrate the feasibility of machine learning to predict impaired behavior during SWDs based on EEG features. With additional validation and optimization in a larger data sample, applications may include EEG‐based prediction of driving safety, treatment adjustment, and insight into mechanisms of impaired consciousness in absence seizures.

Absence-like Seizures, Cortical Oscillations Abnormalities and Decreased Anxiety-like Behavior in Wistar Audiogenic Rats with Cortical Microgyria

Wistar Audiogenic Rats (WAR) is an inbred rodent strain susceptible to acute auditory stimulation-induced seizures. However, spontaneous epileptic seizures (SES) and their associated electroencephalogram (EEG) abnormalities have not been reported in WAR kindled animals. The same is true for naïve WARs (without sound-induced seizures). An approach to increment epileptogenesis and SES is to use a second insult to be added to the genetic background. Here, we used adult naïve WARs with microgyria induced by neonatal cortical freeze-lesion (FL) to evaluate the occurrence of SES and the modification in cortical oscillation patterns and behavior. The neonatal cortical FL was performed in Wistar and naïve WARs (Wis-FL and WAR-FL). Sham animals were used as controls (Wistar-S and WAR-S). Video-EEG recordings and behavioral tasks were performed during adulthood. Surprisingly, spike-waive discharges (SWD) events associated with behavior arrest were detected in WAR-S rats. Those events increased in duration and number in WAR-FL animals. The EEG quantitative analysis showed decreased power of cortical delta, theta and beta oscillations in WAR-S, decreased power of cortical fast gamma (FG) oscillations in WARs, independent of microgyria, and decreased interhemispheric synchrony for delta and FG with stronger coupling in delta and theta-FG oscillations in FL animals. The WARs, regardless of microgyria, had reduced locomotor activity, but only WAR-FL animals had reduced anxiety-like behavior. Microgyria in naïve WARs intensified SWD events associated with behavior arrest that could reflect absence-like seizures and abnormal cortical oscillations, and reduced anxiety-like behavior indicating that WAR-FL could be a reliable model to study epileptogenesis.

Neonatal seizures: diagnostic updates based on new definition and classification.

Neonatal seizures are the most common neurological symptoms caused by various etiologies in the neonatal period, but their diagnosis and treatment are challenging because their pathophysiology and electroclinical manifestations differ from those of patients in older age groups. Many seizures present as electrographic-only events without clinical signs or as obscure clinical manifestations that are difficult to distinguish from other neonatal behaviors. Accordingly, a new definition and classification of neonatal seizures was recently proposed by the International League Against Epilepsy Task Force on neonatal seizures, highlighting the role of electroencephalography in diagnosing and treating neonatal seizures. Neonatal seizures are defined as electrographic events with sudden, paroxysmal, and abnormal alteration of activity and divided into electroclinical seizures and electrographic-only seizures according to their clinical signs, thus excluding clinical events without an electrographic correlation. Seizure types are described by their predominant clinical features and divided into motor (automatisms, clonic, epileptic spasms, myoclonic, tonic, and sequential), nonmotor (autonomic and behavioral arrest), and unclassified. Although many neonatal seizures are acute reactive events caused by hypoxic-ischemic encephalopathy or vascular insults, structural, genetic, or metabolic etiologies of neonatal-onset epilepsy should also be thoroughly evaluated to determine their appropriate management.