Seizure Episodes Research Articles

Diagnostic role of serum prolactin level in different kinds of seizure and seizure-like episode in children: A hospital-based study

Background: Serum prolactin level has been previously used in distinguishing epileptic seizure from non-epileptic seizure, as prolactin level usually rises following an epileptic seizure in children. Aims and Objectives: We conducted this study to determine the role of serum prolactin as a surrogate marker of seizure disorder and whether serum prolactin level varies between different types of seizure, febrile seizure, and seizure mimics. Materials and Methods: This cross-sectional comparative study was conducted for 1 year among 113 children between 6 months and 16 years of age of either sex. They were divided into 3 groups (1) epileptic seizure, (2) febrile seizure, and (3) seizure mimics. The blood sample was collected within 1 h of the occurrence of seizure for estimation of serum prolactin level. Each child was investigated and treated according to the protocol. Results: Mean post-ictal prolactin level was found significantly higher in epileptic seizure (29.94±7.97 ng/mL) compared to febrile seizure (10.21±0.94 ng/mL), and seizure mimics (8.73±0.67 ng/mL). Among group 1, serum prolactin levels significantly elevated in children with generalized tonic-clonic seizure (GTCS) (34.18±2.76 ng/mL) and complex partial seizure (CPS) (31.38±1.59 ng/mL) compared to simple partial seizure (SPS) (14.36±2.33 ng/mL). Post-ictal serum prolactin levels remain elevated for a longer duration in GTCS (54.26±5.19 min) and CPS (45.19±1.73 min) compared to children with SPS (26.76±2.33 min). Conclusion: Estimation of serum prolactin level within 1 h after a seizure can be used for screening purposes to distinguish between epileptic and non-epileptic seizures. A high prolactin level is suggestive of GTCS or CPS whereas a low level is indicative of SPS, febrile convulsion, or seizure mimics with a prolactin cutoff taken 24 ng/mL in our study.

Depression and anxiety among patients with epilepsy: A cross-sectional study from Riyadh, Saudi Arabia.

It is well established that epileptic disorders are associated with a wide range of psychosocial issues that overburden the affected individuals and limit their lifestyle. This study aimed to determine the commonalities between depression and anxiety symptoms among patients with epilepsy (PWE). In addition, we assessed whether depression and anxiety rates varied depending on factors related to the disease. A cross-sectional study was conducted between October 2021 and March 2022 among all PWE at Prince Mohammed bin Abdulaziz Hospital, and 147 patients who responded to the questionnaires were included for analysis (65.6% response rate). Depression was measured using the Patient Health Questionnaire depression scale (PHQ-9), while anxiety levels were measured using the Generalized Anxiety Disorder scale (GAD-7). Demographic variables such as sex, age, marital status, and factors related to epilepsy were also recorded. The results showed that 39.5% and 27.9% of participants had major depressive disorder (MDD) and generalized anxiety disorder (GAD), respectively. The presence of factors that increased susceptibility to seizures was associated with a greater expression of depression (P = 0.035) and anxiety (P = 0.002) symptoms. The presence of symptoms/signs that precede seizures was associated with a higher risk of moderate and severe depression (P = 0.001) and moderate and severe anxiety (P < 0.001). Irregular use of medications was associated with a higher risk of moderate and severe depression (P = 0.037); however, lamotrigine was associated with lower rates of depression among the participants (P = 0.023). This study found that PWE had a higher prevalence of MDD and GAD than the general population. However, this accepted paradigm has yet to reflect a meaningful change in constructing condition-specific recommendations for PWE. Our study revealed that the presence of subjectively recognized signs of an impending ictal episode was significantly associated with a higher risk of moderate and severe depression and anxiety. Furthermore, factors that increase the susceptibility to seizures were associated with a higher risk of depression and anxiety. Irregular medication use was associated with a higher risk of moderate and severe depression. However, lamotrigine was associated with lower rates of depression among participants.

Global developmental delay in a child with asphyxia neonatorum: Why search for an additional explanation?

Children presenting neurological problems and a history of “not cried immediately at birth” are labeled to have cerebral palsy due to birth asphyxia. Although this may be true in many situations, the presence of some additional features may help determine an alternate diagnosis. We present such a case with an alternate diagnosis. A child with a history of birth asphyxia was labeled as a case of global developmental delay or a case of cerebral palsy by the treating doctors. However, the child had certain dysmorphic features such as bulbous nose, depressed nasal bridge, low-set ears, high-arched palate, squint, and flat feet. The child was initially treated in the Neonatal Intensive Care Unit after birth. Later, she developed various neurological features, with frequent episodes of aspiration pneumonia and seizures which were managed with anticonvulsant drugs and antimicrobial agents. She also had some additional non-specific features. On detailed evaluation, the child was diagnosed to have 1q43q44 microdeletion. Search for an alternate or additional diagnosis should be carried out if a child presenting with global developmental delay has some additional syndromic features. This will help in the prognostication of child and help parents in future pregnancy.

The Spectrum of First-onset Seizures in Children Presenting at a Tertiary Care Centre

Abstract Introduction: Seizure is the most common paediatric neurological condition with an increased predilection for early childhood. The recent definition of epilepsy includes first-onset seizures with an increased probability of future episodes. Thus, stringent evaluation of the initial episode of seizure is essential. Hence, this study estimated the aetiology, clinical profile, treatment and outcome of the first seizure episode in children at a tertiary hospital. Materials and Methods: This prospective observational study was carried out at a tertiary hospital in Barabanki, India. Children in the age group of 1 month to 12 years who presented with the first seizure episode and those admitted for other illnesses and developed the first seizure episode during hospital stay were included. Data collected were sociodemographics, clinical presentations, laboratory tests, brain imaging studies, electroencephalography (EEG), diagnosis, treatment and short-term outcomes. Results: A total of 113 patients were enrolled presenting with first-onset seizures. There were 78 (69%) males, 86 (76.1%) were below 5 years of age and 60 (53.1%) presented with fever. Most seizures had a generalised onset (58.4%). Febrile seizures (29.2%) were the most common type, followed by neurocysticercosis (20.3%). Central nervous system (CNS)-infective aetiology (58.7%) was the most common etiological classification. Abnormal findings were observed in cerebrospinal fluid examination of 24 out of 56, in brain imaging of 53 out of 80 and in EEG of 70 out of 113 cases examined. Anti-seizure medication (ASM) was prescribed to 68 patients, of which 10 had a recurrence in the 6-month follow-up period. Conclusion: The first episode of seizure in children usually had a generalised onset, with younger children of the male sex at an increased risk. CNS infections and febrile seizures were common causes. Complete history and neurological evaluation can guide the relevant investigations. ASM tailored to the aetiology controls the seizures in most cases.

Idiopathic Hypoparathyroidism Presenting with Erythrodermic Psoriasis and Fahr’s Syndrome: A Case Report

Idiopathic hypoparathyroidism may remain asymptomatic or present with hypocalcaemic neuromuscular manifestations. Dermatological manifestations like exfoliative dermatitis, pustular psoriasis and symmetrical brain calcification known as Fahr’s syndrome are uncommon in clinical practice. Even in absence of neuromuscular symptoms, hypocalcaemia associated with exfoliative skin lesions and symmetrical brain calcification should prompt investigation for hypoparathyroidism. A 40-year-old male presented with diffuse erythematous pruritic plaques and fever of 10 days duration. Auspitz sign was positive on examination. Investigations showed leucocytosis with neutrophilic predominance. He was admitted with a diagnosis of erythrodermic psoriasis with secondary infection. On the second day of admission he developed an episode of generalised tonic clonic seizure for the first time. Investigations into the cause of seizure revealed low serum calcium while computerised tomography of head revealed symmetrical calcification of bilateral basal ganglia. Further, he was found to have a low level of intact Parathyroid Hormone (PTH) level and hyperphosphataemia. Based on clinical, biochemical and radiological findings, a diagnosis of idiopathic hypoparathyroidism, psoriasis and Fahr’s syndrome was made. Serum calcium was corrected with infusions of calcium gluconate followed by oral calcium carbonate. The patient was kept under observation for seizure recurrence. Calcium and vitamin D supplements and hydrochlorothiazide were started and psoriasis treatment was continued. His skin lesions resolved over the next two weeks, serum calcium levels returned to normal level and no seizure episodes were reported over three months of follow-up.

Knowledge and Attitude of School Teachers toward Epilepsy in Al-Baha City, Saudi Arabia- A Cross-sectional Study

Introduction: Epilepsy is a neurological disorder characterised by recurrent unprovoked episodes of seizures. A seizure is a frightening event, especially when it lasts more than five minutes, known as status epilepticus, which, if not treated promptly, can lead to brain injury. Understanding first aid for a seizure is crucial and may save the patient’s life. Aim: To assess school teachers’ knowledge about epilepsy, their attitudes toward epileptic patients, and the factors that affect teachers’ knowledge in Al-Baha City. Materials and Methods: This cross-sectional study was conducted in Al-Baha City, Saudi Arabia, from November 2021 to May 2022. A total of 305 teachers working in various randomly selected schools, equally distributed between male and female schools, were enrolled. Data were collected through an electronic questionnaire to evaluate teachers’ knowledge and attitudes toward epilepsy. Statistical analysis was performed using the Chi-square test, with data considered statistically significant when the p-value was less than 0.05. Results: In the present study, out of 305 subjects, 167 (54.8%) were male, and the majority, 137 (44.9%), were aged between 35-44 years. Of the participants, 214 (70.2%) were found to have poor knowledge about epilepsy, particularly regarding its etiology, impact on learning, and treatment options. There was a positive attitude among 211 (69.2%) participants toward hiring epileptic patients in their businesses and 240 (78.7%) responded positively to allowing their children to play with epileptic patients. However, 125 (41%) participants had a negative attitude toward allowing their offspring to marry an epileptic patient. Conclusion: The school teachers’ knowledge about epilepsy was poor. While their attitudes were positive regarding hiring epileptic patients and allowing their children to play with them, their attitude was negative regarding allowing their offspring to marry an epileptic patient.

Dynamic topological data analysis: a novel fractal dimension-based testing framework with application to brain signals.

Topological data analysis (TDA) is increasingly recognized as a promising tool in the field of neuroscience, unveiling the underlying topological patterns within brain signals. However, most TDA related methods treat brain signals as if they were static, i.e., they ignore potential non-stationarities and irregularities in the statistical properties of the signals. In this study, we develop a novel fractal dimension-based testing approach that takes into account the dynamic topological properties of brain signals. By representing EEG brain signals as a sequence of Vietoris-Rips filtrations, our approach accommodates the inherent non-stationarities and irregularities of the signals. The application of our novel fractal dimension-based testing approach in analyzing dynamic topological patterns in EEG signals during an epileptic seizure episode exposes noteworthy alterations in total persistence across 0, 1, and 2-dimensional homology. These findings imply a more intricate influence of seizures on brain signals, extending beyond mere amplitude changes.

Terapia com cães para crianças com síndrome do zika: percepção de mães e profissionais

ABSTRACT Objective: To assess the perceptions of mothers and health professionals about the dog-assisted therapy for children with congenital Zika Virus syndrome. Method: Qualitative, descriptive-exploratory research, with six mothers of children with congenital Zika Virus syndrome and six health professionals. Data were obtained at a Brazilian Specialized rehabilitation center in Paraíba, through semi-structured interviews, between February and October 2019. The empirical material was subjected to Inductive Thematic Analysis and interpreted using the Bronfenbrenner’s Bioecological Theory. Results: Dog-Assisted Therapy allowed the enhancement of skills that were previously not performed by children, such as: spontaneous hand opening, head control, improved social interaction, reduction of seizure episodes and disruption of spasticity patterns. Final considerations: Dog-Assisted Therapy was perceived as qualified, humanized and satisfactory support for the evolution of the neuropsychomotor development of children with congenital Zika Virus syndrome.

Stress-induced Late Onset Adult Section Idiopathic Epilepsy after Snakebite: A Rare Case Report

Viper snake bites are associated with haemorrhagic qualities and bleeding disorders, including intracerebral haemorrhage. However, idiopathic epilepsy resulting from viper venom is considered a rare condition. Here is a case of a 30-year-old female who developed idiopathic epilepsy following a snake bite within two hours of the incident. Based on her clinical symptoms and laboratory investigations, the patient was immediately treated with Anti-Snake Venom (ASV) and supportive care. She then experienced an idiopathic seizure upon admission, and her Electroencephalography (EEG) showed generalised epileptiform activity. Subsequently, she was treated with anticonvulsant agents. After being discharged, the patient was readmitted one month later for the same condition, experiencing multiple seizure episodes, each lasting about 40 to 50 seconds. Her MRI of the brain was normal. She was then treated with two anticonvulsant agents and discharged with regular follow-up. This case highlights the importance of maintaining a high suspicion for seizures in patients presenting after envenomation. Early diagnosis and aggressive management may help prevent further neuromuscular damage to the patient.

Biochemical Findings of Neonatal Seizures: a hospital-based study

Background: Neonatal seizures are seizures that happen within the first 28 days of life; they are serious emergency that need to be quickly diagnosed in order to start immediate treatment. Methodology: This cross-sectional study was conducted in the Department of Paediatrics of the Jalalabad Ragib-Rabeya Medical College Hospital in Sylhet. The study* was done from July 2013 to December 2013. The study included 100 neonates who experienced seizure episodes. A detailed history was taken and thorough physical examinations were performed after acquiring written consent. A complete blood count, urine R/M/E (routine microscopic examination), blood glucose, total serum calcium, and serum electrolytes (sodium, potassium, and chloride) levels were done in all 100 neonates. Results: 100 hospitalized newborns were evaluated, of which 43% were born to primi mothers and 57% to multipara mothers, 37% of newborns were delivered at home while 63% were born in a hospital. The majority (60%) of births were through normal vaginal delivery (NVD) and 73% of the mothers reported being in good health in the antenatal period. Biochemical study of these patients revealed that 20% of newborns experienced hypoglycemia, 13% of patients had hypokalemia, 30% had hypornatremia, 27% of newborns had hypochloremia, while 43% had hypocalcaemia. Conclusion: The most frequent biochemical abnormality in neonatal seizure according to this study was hypocalcemia (43%) and hyponatremia (30%).

Posterior Reversible Encephalopathy Syndrome Associated with Late onset Eclampsia: A Case Report

We describe a case of 25 year old women who had full term pregnancy, presented with symptoms of headache, loss of vision and seizure episodes after 7th postpartum day. There were no findings of pre-eclampsia in antenatal stage. The diagnosis of posterior reversible encephalopathy syndrome was made after magnetic resonance imaging. Imaging findings include vasogenic edema of bilateral occipital lobe and parietal lobe. Hypertension and endothelial injury seems to be involved in pathophysiology of the syndrome. After appropriate management, the syndrome resolved. Early diagnosis and proper treatment plays a key role in management of posterior reversible encephalopathy syndrome.

Tramadol use and seizure: A case report

Opioids are commonly used and abused substance worldwide. Tramadol hydrochloride is a synthetic, centrally acting, opiate-like analgesic. Seizure is a rare side effect of tramadol. Tramadol-related seizures are short, tonic-clonic seizures that, like other drug-related seizures, are self-limiting. This epileptogenic effect of tramadol occurs at both low and high doses. We, herein, report the development of seizures after the use of tramadol with increasing dose. We report a 19-year-old man who had opioid dependence syndrome with regular use resulting into multiple episodes of seizures diagnosed as epilepsy for which Sodium valproate had been started.

Brain abscess as an otorhinolaryngological complication

Introduction: A brain abscess can be fatal if not diagnosed or treated promptly. It is more common in children than in adults and has a high mortality rate. Respiratory infections, such as otitis and sinusitis, usually precede brain abscesses. In most cases, double treatment, antibiotics, and surgery are necessary. Complications can be fatal even with proper treatment. Clinical case: This was a 3-year-old girl with a history of respiratory infection. His parents took her to the emergency room due to a severe headache and a seizure episode. Clinical examination revealed left ear otalgia associated with pain and sensitivity to palpation of the mastoid region. Laboratory tests revealed leukocytosis of 18,770/MMC with neutrophilia, thrombocytosis of 628,000/MMC, elevated C-reactive protein of 8.35 mg/dl (average value 0.10-0.30 mg/dl) and elevated ferritin of 250.20 ng/dl (standard value 7-140 ng/dl). Due to the patient’s history and clinical findings, the skull's computed tomography (CT) was performed, revealing an image of evident hypodensity in the left hemisphere. MRI was also performed and revealed that the lesion was previously associated with left breast thrombosis. She received antibiotics and low-molecular-weight heparin with neurosurgical therapy, which produced good results. Evolution: Despite the extent of the injury, he had two episodes of seizures. He promptly received appropriate antibiotic therapy and surgical treatment, which produced good results. Three months later, during the follow-up, he looked normal and had no long-term complications. Conclusions: Complications of brain abscess, even with adequate treatment, can be severe and include epilepsy or death. Early treatment minimizes lethal risks.

Extreme synchronization events in a model neuron-astrocyte network

The examination of synchronization in neural networks is essential to comprehend how the brain functions in normal and pathological states. The synchronization of signals between groups of neurons is paramount for brain activity and associated with various brain functions, including memory, movement, sleep, and attention. However, a balance between synchronization and desynchronization must be maintained for proper brain function. During epilepsy, spontaneous transitions occur between two states of brain activity: synchronous and asynchronous. These transitions can be induced by various factors, including imbalances in chemical signals, changes in network activity, and other mechanisms that are not yet fully understood. Understanding these spontaneous transitions and the underlying mechanisms is a crucial aspect of epilepsy research. It will lead to the development of novel treatment approaches and strategies for inhibiting synchronized activity and averting seizure episodes. A neuron-astrocyte network model was constructed in this study, which displayed spontaneous and induced transitions between asynchronous and synchronous states triggered by external stimuli. The network model utilized 1000 Izhikevich neurons [1] interconnected with excitatory synapses and organized according to a scale-free graph. Each neuron had a bidirectional interaction with a single astrocyte, resulting in a total of 1000 astrocytes in the network. The Ullah model [2] simulated intracellular calcium ion concentration dynamics in a single astrocyte. The action potential generated by a neuron causes the release of neurotransmitters into the synaptic cleft, which triggers the corresponding astrocyte to release calcium ions from its endoplasmic reticulum into the cytoplasm, generating a calcium impulse. The calcium pulse within the astrocyte led to the release of a gliotransmitter. This gliotransmitter has the potential to regulate the synaptic transmission efficiency of both presynaptic and postsynaptic terminals associated with the respective astrocyte. The study simulated the effect of astrocytic suppression on neurotransmitter release. The strength of the synaptic input connection to the neuron that interacts with the astrocyte decreased in proportion to the amplitude of the calcium pulse in the astrocyte. Within the context of the implemented model study, we analyzed the global order parameter’s dependence on the maximum synaptic weight. Our bifurcation analysis showed the presence of hysteresis within a specific range of parameter values for connection weight maximums. In this range, the system under consideration is capable of displaying both synchronous and asynchronous regimes. However, an asynchronous regime was the only observed outcome below the lower boundary of the range, and only a synchronous regime was observed above the upper boundary. A statistical analysis was carried out on the duration of the model’s asynchronous states, specifically for the parameter value of the maximum synaptic weight near the upper boundary of the hysteresis region. The network dynamics were simulated for a prolonged period, and a histogram of the asynchronous state durations was plotted on a double logarithmic scale. The resulting data points were approximated using linear regression, which yielded a power-law exponent of –3/2. Based on the obtained results, the neuron-astrocyte network can exhibit spontaneous transitions between two states: synchronous and asynchronous, similar to pathological processes in the brain. More precisely, the power-law exponent of –3/2 aligns with values discovered in experimental recordings of epileptic activity in rodent brains [3–5]. Detailed modeling of biophysical processes revealed the spontaneous emergence of global order in the network induced by noise. Astrocytic effects mediated the disruption of synchronization in the neural network by reducing the efficiency of synaptic transmission.

Efficacy and Safety of Brivaracetam in Persons With Epilepsy in a Real-World Setting: A Prospective, Non-Interventional Study.

Epilepsy stands out as one of the most prevalent neurological conditions. Brivaracetam (BRV) is a noteworthy antiseizure medication (ASM) distinguished by its pronounced and selective interaction with the synaptic vesicle protein 2A (SV2A) within the brain. Prior investigations, including regulatory trials, post-marketing assessments, and comparative meta-analyses, have consistently underscored BRV's equivalency in efficacy and superior tolerability when pitted against other antiseizure drugs. This study aimed to evaluate the effectiveness, safety, and acceptability of BRV in treating epileptic patients in the Pakistani population. This prospective observational study, conducted in Pakistan from February to December 2022, employed a non-probability consecutive sampling technique. This study included 368 adult patients diagnosed with epilepsy, with a focus on those aged 18 and above experiencing focal seizures. Demographic data, clinical history, seizure types, and epilepsy profiles were recorded. Patients were administered BRV (Brivera; manufactured by Helix Pharma Pvt Ltd., Sindh, Pakistan) monotherapy therapy under physician guidance and followed up for three months. The study assessed changes in seizure frequency, side effects, and drug resistance at baseline, 14th day, and 90th day. Safety aspects were monitored, including documenting any adverse effects associated with BRV therapy. A total of 368 epileptic patients were included in this study, of which 287 (61.3%) were males and 181 (38.7%) were females. The mean age was 32.91±17.11 years. The mean number of seizures at the baseline visit was 5.74±6.21, at 14 days was 2.89±3.84 and at 90 days was 1.73±5.01 (p<0.001). Overall, a more than 50% reduction in seizure episodes was achieved in 178 (56.3%) patients at day 90, and less than 50% reduction in seizure episodes was achieved by 95 (26.8%) patients on Day 14, with a highly significant association between them (p<0.001). Among 316 patients, only 41 (4.4%) of all BRV-treated patients experienced adverse events; Of these 41 patients, 17 (41.7%) reported dizziness and 14(34.2%) reported behavioral issues. Epileptic patients receiving BRV demonstrated a substantial reduction of greater than 50% seizure episodes at the end of follow-up visits. Moreover, BRV exhibited fewer adverse effects in individuals with epilepsy.

MCC950 alleviates seizure severity and angiogenesis by inhibiting NLRP3/ IL-1β signaling pathway-mediated pyroptosis in mouse model of epilepsy

Epilepsy is one of the most common serious chronic brain disorders, affecting up to 70 million people worldwide. Vascular disruption, including blood–brain barrier impairment and pathological angiogenesis, exacerbates its occurrence. However, its underlying mechanisms remain elusive. MCC950 is a specific small-molecule inhibitor that selectively blocks NLRP3 inflammatory vesicle activation across the blood–brain barrier, limits downstream IL-1β maturation and release, and exerts therapeutic effects across multiple diseases. In the present study, an epilepsy model was established by intraperitoneal administration of Kainic acid to adult male C57BL/6J wild-type mice. The results revealed that the epilepsy susceptibility of MCC950-treated mice was decreased, and neural damage following seizure episodes was reduced. In addition, immunofluorescence staining, RT-qPCR, and Western blot demonstrated that MCC950 inhibited the expression of the NLRP3 inflammasome and its related proteins in microglia, whereas microangiogenesis was found to be increased in the cerebral cortex and hippocampus of epileptic mice, and these effects could be reversed by MCC950. Furthermore, neurobehavioral impairment was observed in the epileptic mouse model, and MCC950 similarly alleviated the aforementioned pathological process. To the best of our knowledge, this is the first study to establish that pathological microangiogenesis is associated with NLRP3/IL-1β signaling pathway activation in a Kainic acid-induced epilepsy mouse model and that MCC950 administration attenuates the above-mentioned pathological changes and exerts neuroprotective effects. Therefore, MCC950 is a promising therapeutic agent for the treatment of epilepsy.

Five Novel Hemizygous Variants in the PGK1 Gene Associated with Neurological Dysfunction and Mild Hemolytic Anemia in Five Indian Patients

Introduction Phosphoglycerate kinase (ATP: 3-phosphoglycerate 1-phosphotransferase; EC 2.7.2.3; PGK) is the crucial enzyme of the glycolytic pathway, catalyzing1, 3 bis-phosphoglycerate to 3-Phosphoglycerate, generating one molecule of ATP [1]. PGK enzyme is encoded by the PGK1 gene located at Xq13.3, measures 23kb in size, and spans into 11 exons. PGK deficiency is an X-linked disorder associated with a very rare cause of hereditary non-spherocytic hemolytic anemia (HNSHA). PGK1 gene is ubiquitously expressed but the patients exhibit three major symptoms -1) haemolytic anemia 2) myopathy (rhabdomyolysis), 3) mental retardation and various neurological manifestations[1]. The severity of symptoms varies among patients with PGK deficiency. PGK deficiency is reported worldwide, although to our knowledge no case with Indian ancestry has been reported. Method Genomic DNA was extracted from the EDTA blood sample and processed for targeted Next Generation Sequencing (t-NGS) as per the manufacturer's protocol. The t-NGS panel broadly consists of 80 genes of the spectrum of the disorder including congenital hemolytic anemia, bone marrow failure disorders, and iron deficiency anemia. The libraries were sequenced to &amp;gt;80-100X mean coverage on the Illumina sequencing platform. The variants were classified based on ACMG guidelines. The impact of non-synonymous variations was estimated using PolyPhen-2, SIFT, MutationTaster2, CADD Phred, and Mutpred2. In silico effect of the variant was studied by PyMol. Latter the enzyme deficiency was confirmed by standard protocol and parental segregation analysis was performed. Relative quantification (qPCR) was evaluated based on the comparative CT method ( 2 − ΔΔCT). Result We report five male children of &amp;lt;4 years of age with PGK deficiency from Indian origin. Clinically, all of them manifest global development delay and no speech. Autism spectrum disorder is observed in two of the cases, incidence of seizure and convulsion are present in two cases. None except one, presented with haemolytic anaemia and was given one transfusion post an episode of seizure at the age of 2 years. Additionally, a family history of haemolytic anemia with developmental delay and seizure was present in only one case although the patient himself required no transfusion requirement to date. All the patients are routinely followed up for any evidence of a haemolytic crisis, transfusion requirement, or any other clinical symptoms. Detailed phenotypes of all the patients are listed in Table 1. t-NGS revealed five novel hemizygous variants in the PGK1 gene - p. Cys50Trp, p. Gly137Trp, p. Val140Ile, p. Asp159Asn, and p. Arg330Trp. These variants have not been reported in the literature or available databases. DNA Sanger sequencing confirmed the heterozygous state in the mothers. In silico tools confirmed the pathogenicity of the variants. The PGK enzymatic activity was markedly reduced. The PGK1 transcript levels were reduced to 60% in patients as compared to the healthy controls. Discussion To date, only 34 mutations are known to be associated with PGK enzyme deficiency. Amongst them, 50% of variants exhibit symptoms of anaemia whereas the remaining show neurological and /or myopathy. Figure 1 illustrates all 39 mutations reported with PGK deficiency. Only four mutations p.E120K, p.G158R, p.A354P, and p.I371K are known to exhibit all three categories of symptom (PGK-anaemia-neurological-myopathy)[2]. Conclusion NGS allows for the identification of novel genetic variants that may contribute to the development of rare disorders, expanding our knowledge of their underlying mechanisms. This advanced technology also enables researchers to analyze multiple genes simultaneously, increasing the efficiency and speed of diagnosis in unexplained cases of HNSHA.

Decorticate posturing in a 9-year-old boy: An interesting clinical image

In this case 8 year old boy presented with a complaint of fever for 4 days 8-10 episodes of seizure in 2 days, and semiconscious. The parents brought the patient in with these complaints, during the examination the physician noticed the flexion at the elbow and lower extremity in extension and hypotonia in all limbs.

Expanding the spectrum of gene-associated reflex seizures: A case report of a “bidet-induced” reflex epilepsy

In this case report, we present the case of a 20-month-old girl who manifested paroxysmal &amp;ldquo;bidet-induced&amp;rdquo; episodes characterized by impaired awareness, pallor, and hypotonia, with a duration of less than a minute. Initial neurological examination yielded unremarkable results, prompting further investigation. A video-electroencephalogram recording documented the epileptic nature of these episodes, revealing an ictal discharge originating from the right central-temporal region. A brain magnetic resonance imaging exhibited a sulcal/gyral asymmetry within the central sulci, along with the presence of the &amp;ldquo;power button sign&amp;rdquo; within the right central sulcus. These findings were indicative of a focal cortical dysplasia type-2. Subsequent genetic analysis through a gene panel identified the presence of an NPRL2 variant. Mutations affecting this particular gene are known to disrupt the normal functioning of the GATOR1 complex, potentially causing focal cortical dysplasia and various forms of epilepsy, including familial focal epilepsy with variable foci. On the diagnosis, the patient received levetiracetam, and the ictal episodes promptly ceased. At the most recent follow-up (at 4 years old), the patient remained free of seizures without the need for any treatment, and her neurodevelopment so far had exhibited no abnormalities. Considering the landscape of epilepsy-related GATOR1 variants, it is conceivable that this gene family may play a significant role in the pathogenesis of benign forms of focal reflex seizures, including bathing epilepsy.

Patient with multifocal pancreatic insulinoma: a rare presentation of functional pancreatic neuroendocrine neoplasm

Insulinoma is a type of neuroendocrine tumour with an incidence of 1—4 cases per million. Multiple insulinomas constitute less than 10% of all insulinomas. Surgery is the treatment of choice for insulinoma. The operation can be done with an open or laparoscopic approach, with cure rates ranging from 77% to 100%. Pancreatic resection is recommended for tumours larger than 2 cm in size, while enucleation is advised for lesions smaller than 2cm if the tumour is at least 2—3 mm away from the main pancreatic duct to prevent the formation of a fistula. For better intraoperative localization of lesions, bimanual palpation together with intraoperative ultrasonography (IOUS) is advised. Palpation alone has 70% sensitivity, but together with IOUS, it reaches 85—95%&#x0D; A young female patient in her late 20s with non‑specific complaints and a medical history of epilepsy dating back to the age of 17 underwent a physical examination. Blood test results indicated severe hypoglycemia, and magnetic resonance imaging (MRI) revealed an 11‑mm neoplasia in the body of the pancreas. A 72‑hour fasting test confirmed the diagnosis of insulinoma, and the patient underwent laparoscopic surgery. IOUS was done for the precise localization of the lesion, and another tumour in the pancreatic tail was found. A spleen‑preserving laparoscopic distal pancreatectomy was performed. Histologic reports confirmed multifocal Grade 1 insulinoma. The postoperative course was uneventful. After 4 months of follow‑up, computed tomography (CT) was done, and there were no signs of recurrence of insulinoma, pancreatic pseudocysts, or other signs of postoperative complications. Since the operation, the patient has not had any episodes of hypoglycemia or seizures.&#x0D; The wide spectrum of symptoms, which are not specific to insulinomas, in particular seizures, can make it difficult to establish a correct diagnosis and can be mistaken for other psychiatric or neurologic disorders. This case clearly shows the advantages of IOUS‑guided surgery in achieving better visualization and outcomes. After enucleation of the smaller lesion without the use of IOUS, other insulinomas would be missed and left in place because they were located deeply in the parenchyma. Simple visualization and palpation would not be enough.&#x0D;