Electroencephalogram Findings Research Articles

Nocturnal frontal lobe epilepsy presenting as sleepwalking episodes and restless leg syndrome-like symptoms

Nocturnal frontal lobe epilepsy (NFLE) is characterized by seizures with complex motor behaviors arising mainly during sleep. Varied clinical presentations and nonspecific electroencephalogram findings make it difficult to distinguish NFLE from other nocturnal paroxysmal events such as nonrapid eye movement (NREM) parasomnias and restless leg syndrome (RLS). Here, we present a case of NFLE, which had a complex clinical presentation resembling features suggestive of RLS and NREM parasomnia and posed a diagnostic challenge. Initiation of carbamazepine as the anti-epileptic led to rapid resolution of symptoms.

Risk factors of epilepsy in children with complex febrile seizures: A retrospective cohort study.

Febrile seizures are the most common seizures in children. Children with complex febrile seizures have a higher risk of subsequent epilepsy compared with children with simple febrile seizures. Multiple risks factors for epilepsy, including focal status epilepticus, family history of epilepsy, neurodevelopmental abnormalities and abnormal electroencephalogram findings, have been found with inconsistent results. The aim of this study is to identify risk factors for developing epilepsy in children with complex febrile seizures. The study included 248 children aged 3-72-months, diagnosed with complex febrile seizures at Chiang Mai University Hospital. Demographic data, seizure characteristics, electroencephalogram and neuroimaging findings were identified, and assessed to establish whether they were risk factors for subsequent epilepsy. Fifty-five patients (22.1%) had subsequent epilepsy. Using Cox regression-survival analysis, factors associated with epilepsy were prolonged seizures >15 min (P = 0.006; Hazard Ratio (HR): 2.475; 95% Confidence Interval (CI): 1.294-4.735), developmental delay (P = 0.019; HR: 4.476; 95% CI: 2.280-15.646), epileptiform discharges on electroencephalogram (P = 0.023; HR: 1.391; 95%CI: 1.174-1.876), and abnormal neuroimaging (computed tomography or magnetic resonance imaging; P = 0.028; HR: 1.355; 95% CI: 1.034-1.776). Age at onset, peak febrile temperature, duration between the onset of fever and the occurrence of seizure, recurrent seizures within 24 h, focal seizures, abnormal neurological exams and family history of febrile seizure or epilepsy were not associated with increased risk of subsequent epilepsy in this study. Risk factors associated with increased risk of epilepsy in children with complex febrile seizures are prolonged seizures or febrile status epilepticus, developmental delay, electroencephalogram epileptiform discharges, and abnormal neuroimaging. Their presence would merit close clinical monitoring.

A rare case of partially empty sella with epileptiform discharges presenting with first episode of mania.

Sir, Busch described the condition empty sella syndrome (ESS) in 1951 where the sella turcica is filled with cerebrospinal fluid (CSF) causing displacement or flattening of the normal pituitary gland.[1] It is reported to occur in 5.5%–23.5% of the population[2] which is pathophysiologically characterized by either anatomic abnormalities in the diaphragma sellae (primary ESS) or damage to the pituitary by irradiation/surgery, or autoimmunity leading to the availability of “empty” space in the sella (secondary ESS).[1] The common signs and symptoms includes headache, papilledema due to raised intracranial pressure, leakage of CSF through nose and weight gain.[1] It can also present as decreased libido, galactorrhea, amenorrhea and secondary infertility.[3] Psychiatric manifestations of ESS are rare but can occur in the form of behavioral disturbances and psychotic symptoms.[4,5] A 25-year-old male presented to us with violent behavior towards family members, reduced need for sleep, elevated self-esteem and grandiose delusions claiming himself to be the prime minister of India. It was associated with one episode of tonic–clonic movements two nights back, with urinary incontinence. Patient also complained of jerky movements in his left arm occasionally about two to three times a day following this. All the symptoms started abruptly for past 10 days, this being his first such episode in his lifetime. There was no history of any febrile illness, head injury, substance abuse; blood parameters that included serum electrolytes, serum prolactin, vitamin B12 levels, and serum osmolality were all within normal limit. He was diagnosed to be in mania as per Diagnostic and Statistical Manual of Mental Disorders (DSM 5). Young’s Mania Rating Scale (YMRS) score was 24. The patient was subjected to magnetic resonance imaging (MRI) scan which revealed empty sella [Figure 1]. 10–20 electroencephalogram findings revealed generalized periodic epileptiform discharges (GPED). The patient was placed on sodium valproate 1000mg, haloperidol 10 mg and trihexyphenidyl 4 mg in divided dosages. The symptoms reduced in severity and YMRS score came 12 on day 5 of admission and EEG was normal. This was his first episode of mania that coexisted with first lifetime episode of seizure. GPEDs results in kindling of neuronal pathways, leading to psychiatric manifestations such as mania. Lateral hypothalamic kindling can induce manic-like behavior in a rat model.[5]Figure 1: MRI scan showing empty sellaThere are reports of atypical presentations of ESS in the form of acute psychosis, sinus bradycardia, herniation of anterior cerebral artery.[5–7] The presentation of empty sella as seizure episode has been reported rarely.[8] Moreover, it is even more rare to be presenting with both seizure episode and mania.[9] In one case report mania was precipitated by hyponatremia in a patient with ESS[10] whereas in our case sodium and other electrolytes level were in normal range. The possible mechanism of such is still a gray area.[9] Even there is also a dilemma of seizure precipitating mania or vice-versa. More sample based studies is needed to establish the neurochemical events leading to the same for better diagnosis and management. Ethical concerns Proper consent was taken from the patient regarding publication of the case without revealing patient’s identity Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

To Study the Electroencephalogram Changes in Children with Acute Encephalitis

Aim: To study the electroencephalogram changes in children with acute encephalitis. Study design: Cross-sectional study. Place and duration of study: The cases were admitted from OPD and emergency over duration of 10 months from May2009 to March 2010 in Children Hospital PIMS, Islamabad. Method: Patients with Cerebral Palsy, Degenerative Brain disease, Cerebral Malaria and Meningitis were excluded. Written informed consent was taken from parents /guardians. All patients, from both genders, age varying from 4 months to 12 years, fitting the criteria of Acute Encephalitis according to ICD 9 & 10 were included in the study, which were 56 in total. All cases had Lumbar puncture and Cerebro Spinal Fluid examination. The findings of pleocytosis (WBC count more than5 u/l), protein and sugar were recorded. EEG (Electroencecephlogram) was done in 52 patients, frequencies and percentages were calculated of the findings. Results: The mean age was 4. 6 years, (varying from 4 months to 12 years) with a standard deviation of 3. 2. From a total of fifty six patients, 38(68%) were males and 18(32%) females. All cases presented with fever (100%). Cerebro Spinal Fluid examination, showed Pleocytosis in 30(54%) while 46(46%) had normal cell count. Cerebro Spinal Fluid protein content was normal in 45(80%) and increased in 11(20%). Cerebro Spinal Fluid sugar was normal in 50(89%) and 6(11%) had low. Electroencephalogram was done in fifty-two patients out of which 30(58%) were normal, 22(42%) were abnormal. Intermittent slowing was found in 17(77%) and 5(23%) cases had focal discharges along with intermittent slowing, out of which three were unilateral temporo-frontal discharges, two cases had other focal discharges on EEG. Conclusion: In patients with Acute Encephalitis, slowing of the rhythm was the most frequent abnormal Electroencephalogram finding, followed by focal discharges in children admitted in Children’s Hospital PIMS, Islamabad. Keywords: Acute Encephalitis, Electroencephalogram (electro encephalogram), Cerebro Spinal Fluid Pleocytosis, Fever

Improving early recognition of Creutzfeldt‐Jakob disease mimics in clinical practice

AbstractBackgroundDiagnostic criteria emphasize the use of real‐time quaking‐induced conversion (RT‐QuIC) assays in cerebrospinal fluid (CSF) to identify patients with rapidly progressive dementia (RPD) due to for Creutzfeldt‐Jakob disease (CJD; CDC Diagnostic Criteria; Oct‐2018). Yet, this test is often performed in specialized centers, leading to delays in return of results. There is a need to leverage clinical features and the results of readily available tests to distinguish patients with CJD from those with other causes (‘CJD mimics’), including patients with potentially treatment‐responsive RPD.MethodPatients with definite (pathology‐confirmed) or probable CJD (clinical features with positive RT‐QuIC) were identified through retrospective review of Mayo Clinic Enterprise (n=91) and Washington University in St. Louis records (n=14; Jan‐2014 to Dec‐2020). Demographic, clinical details and results of common investigations (e.g., neuroimaging, CSF analyses and electroencephalogram) were compared between CJD cases and ‘mimics’ who met clinical criteria for probable CJD but did not have CJD.ResultCJD mimics were diagnosed with autoimmune encephalitis (n=8), neurosarcoidosis (n=1), FTLD/MND (n=1) and unknown dementia (n=1), comprising 11/155 (7%) patients enrolled with RPD at study sites. Median [range] ages‐at‐presentation (65.6 [21.9‐81.5] vs 62.4 [32.8‐76.4] years; p=0.09), % females (51% vs 46%; p>0.99) and symptoms/signs were similar between groups, with the exception of motor complaints (e.g., spasms, focal weakness), which were more common in mimics (11/11 vs 55/105; p<0.01). Electroencephalogram findings did not differ between groups. MRI findings compatible with CJD (i.e., restricted diffusion within deep nuclei/cortical ribbon) predominated in cases (80/105 vs 4/11; p<0.01), while elevations in CSF leukocytes (>5 cells/hpf: 6/11 vs 5/103; p<0.01) and protein >45 mg/dL (10/11 vs 43/103; p<0.01) were more common in mimics. Total‐tau levels >1150 pg/mL (76/84 vs 2/10; p<0.01) and ‘positive’ 14‐3‐3 (67/98 vs 3/10; p=0.03) were frequent in cases. Autoantibodies associated with autoimmune encephalitis were detected in 5/10 mimics but 0/87 cases (p<0.01). Immunosuppressant therapies were provided to 10 mimics and 24 cases, with response limited to mimics.ConclusionsAutoimmune encephalitis, neurosarcoidosis and select neurodegenerative diseases may mimic CJD at presentation. Findings from brain MRI and commonly available CSF tests may facilitate early recognition of mimics, providing an opportunity for early treatment.

Prognostic implications of persistent interictal epileptiform discharges on antiseizure medication withdrawal in patients with epilepsy in five-year remission

PurposeWhether patients with epilepsy in long-term remission and interictal epileptiform discharges (IEDs) can stop antiseizure medication (ASM) remains a challenging topic even though multiple studies have investigated ASM withdrawal. This study aimed to estimate seizure relapse and its risk factors in patients with epilepsy in five-year remission and persistent IEDs. MethodsPatients with epilepsy and persistent IEDs were prospectively recruited from the Affiliated Nanjing Brain Hospital of Nanjing Medical University from Dec.1, 2010 to Dec.30, 2019. All enrolled patients achieved seizure remission for over five years and were divided into the ASM withdrawal and continuous treatment groups according to their personal preference. Seizure outcomes and 24 h video electroencephalogram findings were obtained through clinical visits or telephone interviews every three months until March 31, 2021. The cumulative recurrence rate and its diversity between the ASM withdrawal and continuous treatment groups were tested using Kaplan–Meier analysis. Multivariate Cox regression analysis was performed to explore the independent predictors for seizure recurrence. Relapsed patients were further monitored for their seizure control and prognosis. ResultsA total of 83 patients with epilepsy in five-year remission and persistent IEDs were enrolled in this study, including 41 (49.4%) in the ASM withdrawal group and 42 (50.6%) in the continuous ASM treatment group. During the follow-up with a median time of 36.8 months (range from 18.7 to 104.6 months), the seizure relapse in off-medication patients (43.9%, 18/41) was higher than that in on-medication patients (21.4%, 9/42; P = 0.031). In the multivariate analysis model, independent predictors for seizure recurrence were structural-metabolic epilepsy or unknown cause (HR = 6.185, 95% CI 1.166–32.805) and multiple seizure types (HR = 2.807, 95% CI 1.051–7.502). ASM withdrawal was not found to be an independent risk factor for seizure recurrence. Of 27 patients with seizure recurrence, 25 were given reinstitution or continuous ASM therapy, whereas two chose sustained observation without medication. At the end of the follow-up, 70.4% (19/27) of recurrence patients were completely free from seizures for at least one year again, and only one patient developed refractory epilepsy. ConclusionFor patients with epilepsy in five-year remission and persistent IEDs, drug withdrawal may be a rational choice after the individualized assessment of benefits and risks. Furthermore, the independent risk factors for the seizure relapse were structural-metabolic epilepsy or an unknown cause, and multiple seizure types. Finally, patients with epilepsy relapsing after ASM withdrawal could achieve seizure remission again after ASM retreatment.

Electroencephalogram Abnormalities and Epilepsy in Autism Spectrum Disorders: Clinical and Electroencephalogram Findings

AbstractIt has been known for several decades that epilepsy and autism spectrum disorders (ASD) are related to each other. Epilepsy frequently accompanies ASD. The purpose of this study was to investigate relationship between clinical and electroencephalogram (EEG) findings in ASD patients and to identify EEG characteristics that may create a disposition to epilepsy in ASD by examining differences in clinical and EEG findings between patients diagnosed with ASD without epilepsy and ASD with epilepsy. A total of 102 patients aged 2 to 18 years and diagnosed with ASD based on Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) diagnostic criteria between January 2017 and June 2019 were included in the study. Patients were assigned into two groups: (1) ASD with epilepsy and (2) ASD without epilepsy. Clinical findings were retrieved from patients' files, and EEG findings from first EEG records in the EEG laboratory at the time of diagnosis. EEG findings were defined as central, parietal, frontal, temporal, or generalized, depending on the location of rhythmic discharges. The incidence of epilepsy in our ASD patients was 33.7% and that of febrile convulsion was 4%. Generalized motor seizures were the most common seizure type. Epileptic discharges most commonly derived from the central and frontal regions. These abnormalities, especially frontal and central rhythmic discharges, may represent a precursor for the development of epilepsy in ASD patients.

Relationship Between Anesthesia Depth and Quality of Seizures in Patients Undergoing Electroconvulsive Therapy: A Prospective Observational Study.

Electroconvulsive therapy under general anesthesia is an established treatment for mood disorders, such as therapy-resistant depression. As most anesthetic drugs used for induction of anesthesia increase the seizure threshold, adequate depth of anesthesia without diminishing the therapeutic efficacy of interventions is crucial. The aim of this study was to investigate whether anesthesia depth as assessed by Narcotrend (NCT) monitoring correlates with maximum seizure quality. An observational study was performed in psychiatric patients undergoing multiple interventions of electroconvulsive therapy. Seizure quality of each attendance was assessed evaluating electroencephalogram end point, electromyogram end point, postictal suppression index, the midictal amplitude, and a 3-step overall graduation. Narcotrend was used to assess anesthesia depth according to index-based electroencephalogram findings. Measurements were obtained before induction of anesthesia, before stimulation, and after arousal. Data were analyzed by means of linear mixed models and generalized estimating equations models. A total of 105 interventions in 12 patients were analyzed. Anesthesia depth before stimulation was significantly associated with seizure quality (standardized β = 0.244, P = 0.010), maximum sustained coherence (β = 0.207, P = 0.022), and electroencephalogram duration (β = 0.215, P = 0.012). A cutoff value of 41 or greater versus 40 or less for the NCT index was found appropriate to differentiate between good and less satisfactory overall seizure quality. Anesthesia depth index assessed by NCT monitoring was positively associated with seizure quality. Narcotrend monitoring may be useful in assessment of optimal anesthesia depth before stimulation.

Electroclinical Features in MECP2 Duplication Syndrome: Pediatric Case Series.

MECP2 duplication syndrome (MECP2DS) is an x-linked recessive syndrome characterized by infantile hypotonia, severe neurodevelopmental delay, intellectual disability, progressive spasticity, recurrent infections, and seizures. More than 50% of cases have been associated with epilepsy. Seizure semiology and electroencephalogram (EEG) findings in these patients are poorly described. In this case series, the authors describe the electroclinical features of children with MECP2DS presenting to their institution. In addition, they reviewed seizure types and therapies used. Eight out of 9 patients with MECP2DS developed epilepsy, with 56% having normal initial EEG. Generalized slowing with generalized and focal/multifocal discharges was the most common EEG pattern which is consistent with prior studies. Atonic seizure was the most common semiology. Majority were pharmacoresistant (63%). The goal of this case series is to better define the clinical and electrophysiological aspects of the epilepsy associated with MECP2 duplication syndrome and provide practical guidance regarding management.

Recurrence rate of the first nonfebrile seizure in children with autism spectrum disorder

ObjectiveEpilepsy prevalence is higher in children with Autism Spectrum Disorder (ASD) and is a contributor to morbidity and mortality. Little is known about the recurrence rate after the first nonfebrile seizure in this population, specifically in regard to seizure type and electroencephalogram (EEG) findings. MethodsWe reviewed pediatric medical records at our institution between 2006 and 2016 for subjects with ASD who had a first seizure. We then looked for risk of a recurrent non-provoked seizure within the next two years. ResultsOverall, the recurrence rate in this study was 70.9%. This is much higher than the general population. The recurrence rate was higher in patients who had a generalized convulsion compared to those who had a behavioral arrest. When the first seizure was a generalized convulsion, there was an 84% chance of developing a second convulsion, whereas the recurrence rate was 59% for behavioral arrest type seizures (p = 0.002). The odds of having recurrence when the first seizure is a generalized convulsion was 5.36 higher than when it was a behavioral arrest (95% CI 2.14–13.42, p < 0.001). An abnormal EEG was a strong predictor of seizure recurrence in both seizure types. However, even with a normal EEG, generalized convulsions were more likely to recur within 2 years compared to behavioral arrest (OR 6.3, 95% CI 2.1–19). SignificanceThe recurrence rate for nonfebrile seizures in children with ASD is much higher than the general population, especially for generalized convulsions. An abnormal EEG has a strong predictive value for seizure recurrence. However, even when the EEG is normal, the recurrence rate for generalized convulsions is quite high. This is an important finding as epilepsy contributes to morbidity and mortality in this group and may impact clinical decisions about when to start anti-seizure medications.

P-EP030. Epilepsy in a child with a history of maternal thyroid dysfunction: A case report

Introduction. Thyroid hormones (THs) are crucial for brain development. Though the underlying molecular mechanism is yet known, the effects of THs on inhibitory and excitatory neurons may affect brain seizure activity through GABAergic and glutamatergic neuron transmission. There are hypothesis showing THs dysfunction in pregnancy may affect neurocognitive development with increased the risk of neonatal seizure, febrile seizure and epilepsy in children. Results. We report a 2-year-old male patient admitted to the outpatient department with a history of repeated seizures since 3 months ago. Seizures had recurred three times, with generalized tonic clonic seizure as its semiology. Patient was the third child, prematurely born with a mother diagnosed with hyperthyroid during her antenatal period. He had complete immunization schedule. History of developmental delay was seen. Physical examination showed open anterior fontanelle, negative meningeal signs. Routine lab examination and thyroid levels were unremarkable. Electroencephalogram findings revealed intermittent slowing on the right temporal region, and brain MRI showed cerebral atrophy with no mesial temporal sclerosis. Patient was treated with valproic acid and was seizure free since. Conclusion. Maternal thyroid dysfunction may have an effect on seizures and brain development in neonates. Therefore, antenatal care and screening of thyroid levels in maternal patients may be vital in the future. To our knowledge, there are still limited amount of study available regarding this condition, thus study with abundant amount of samples needed to procure further information.

Neurodevelopmental Findings and Epilepsy in Malformations of Cortical Development.

Aim:The purpose of this study is to classify the malformations of cortical development in children according to the embryological formation, localization, and neurodevelopmental findings. Seizure/epilepsy and electrophysiological findings have also been compared.Material and Methods:Seventy-five children (age: 1 month-16.5 years; 56% male) followed with the diagnosis of malformation of cortical development, in Marmara University Pendik Research and Educational Hospital Department of Pediatric Neurology, were included in the study. Their epilepsy characteristics, electroencephalogram (EEG) findings, and prognosis were reported. Neurodevelopmental characteristics were evaluated by the Bayley Scales of Infant and Toddler Development (Bayley-III) for the ages of 0-42 months (n = 30); the Denver Developmental Screening Test-II (DDST-II) for ages 42 months-6 years (n = 11); and the Wechsler Intelligence Scales for Children (WISC-R), used for children 6 years and older (n = 34).Results:The patients were classified as 44% premigrational (14.6% microcephaly, 24% tuberous sclerosis, 2.7% focal cortical dysplasia, 1.3% hemimegalencephaly, and 1.3% diffuse cortical dysgenesis); 17.3% migrational (14.6% lissencephaly, 2.7% heterotopia); and 38.6% postmigrational (14.6% schizencephaly, 24% polymicrogyria) developmentally. According to involved area, the classification was 34.7% hemispheric/multilobar, 33.3% diffuse, and 32% focal. Seventy-five percent of the patients had a history of epilepsy, and 92% were resistant to treatment. The seizures started before the age of 12 months in diffuse malformations, and epileptic encephalopathy was more common in microcephaly with a rate of 80% and lissencephaly with a rate of 54.5% in the first EEGs. Ninety-five percent of patients had at least one level of neurodevelopmental delay detected by DDST/Bayley-III; this was more common in patients with accompanying epilepsy (P < .05). As seen more commonly in patients with diffuse pathologies and intractable frequent seizures, mental retardation was detected by WISC-R in 64.5% of patients (P < .05).Conclusion:In cases with cortical developmental malformation, epilepsy/EEG features and neurodevelopmental prognosis can be predicted depending on the developmental process and type and extent of involvement. Patients should be followed up closely with EEG.

Genetic and Metabolic Neonatal Epilepsies.

Seizures are a common neonatal neurological disorder with an incidence of 1 to 5 in 1,000 live births. Genetic and metabolic epilepsies account for 10% to 12% of all neonatal seizures. Correct identification and diagnosis are important factors, as they carry treatment and management implications. Clinical history, neurological examination, seizure types, epilepsy syndromes, and electroencephalogram findings can be used to guide the diagnosis of epilepsy. Genetic and metabolic epilepsies in neonates can be categorized practically into two groups: amenably treatable disorders, and the most common genetic epilepsies. The treatable disorders primarily consist of inborn errors of metabolism that have a specific therapy. The most common genetic epilepsies include monogenic disorders, which usually result from channelopathies, synaptic vesicle docking/release defect, or dysfunction of cell signaling. A step-wise diagnostic approach to genetic and metabolic epilepsies is proposed in this article to aid clinicians in providing care for newborns with seizures. [Pediatr Ann. 2020;50(6):e245-e253.].

High prevalence of psychiatric comorbidities in children and adolescents at a tertiary epilepsy center.

Epilepsy is highly comorbid with psychiatric disorders and a significant amount of the morbidity related to epilepsy is in fact a result of psychiatric comorbidities. To investigate the frequency of different psychiatric comorbidities in children with refractory epilepsy. We present preliminary observational data from a series of patients (n=82) examined in the psychiatric branch of a tertiary epilepsy center in Rio de Janeiro, Brazil. Patients were classified as presenting autism spectrum disorders, mood disorders, anxiety disorders, disruptive disorders, attention deficit hyperactivity disorder (ADHD), intellectual development disorder, psychotic episode, dissociative/conversive disorders or others. We determined the frequency of each disorder, along with demographic data, medications prescribed, electroencephalogram findings and additional medical examinations and consultations. The most common comorbidities in our sample were autism spectrum disorders and ADHD. Antipsychotics and selective serotonin uptake inhibitors were the most commonly prescribed psychiatric medications. Knowledge about the prevalence of such comorbidities may provide more targeted interventions in Psychiatry and Psychology services linked to epilepsy centers.

SCN8A and Its Related Epileptic Phenotypes

AbstractSodium channelopathies are among the most common single-gene causes of epilepsy and have been considered model disorders for the study of genetic epilepsies. Epilepsies due to SCN8A pathogenic variants can present with a broad range of phenotypes varying from a severe epileptic encephalopathy with multiple types of drug-resistant seizure to neurodevelopmental delay, mental retardation, and electroencephalogram (EEG) findings of multifocal spike and waves (mostly in the temporal/parietal/occipital areas). In rare cases, benign familial infantile seizures and developmental delay with/without ataxia have been reported. A first-level, specific SCN8A Sanger's sequencing, although available, is rarely performed because the clinical phenotype is not strictly characteristic and several overlaps with other genetic epilepsies may occur. Given its indistinctive phenotype, diagnosis is usually performed through a specific gene panel for epileptic encephalopathies, early epilepsies, or genetic epilepsy in general, or through whole exome sequencing (WES) and more rarely through whole genome sequencing (WGS). Mutations in SCN8A occur as an autosomal dominant trait. The great majority of individuals diagnosed with SCN8A epilepsy do not have an affected parent, because usually SCN8A patients do not reproduce, and mutations are inherited as a “de novo” trait. In rare cases, SCN8A mutations may be inherited in the setting of parental germline mosaicism. SCN8A-related epilepsies have not shown a clear genotype–phenotype correlation, the same variants have been described with different clinical expressivity and this could be due to other genetic factors or to interacting environmental factors. There is no standardized treatment for SCN8A-related epilepsy because of the rarity of the disease and the unavailability of specific, targeted drugs. Treatment is based mainly on antiepileptic drugs which include classic wide-spectrum drugs such as valproic acid, levetiracetam, and lamotrigine. Sodium-channel blockers (phenytoin, carbamazepine, oxcarbazepine, and lamotrigine) have shown appreciable results in terms of seizure reduction, in particular, in patients presenting gain-of-function mutations. Nowadays, new potentially transformative gene therapy treatment approaches are currently being explored, allowing in the next future, a precision-based treatment directed against the gene defect and protein alterations.

Blood concentration of levetiracetam after bolus administration in patients with status epilepticus

Purpose: We aimed to evaluate the blood concentration of levetiracetam (LEV), as a second-line drug, in patients with status epilepticus (SE) in an emergency clinical setting.Methods: We prospectively evaluated 20 consecutive patients with SE admitted to our department between July 2017 and July 2019. LEV (2500 mg) was administered via bolus infusion after diazepam infusion, followed by 500 mg every 12 h for 48 h and then 500 mg orally. The primary outcomes were LEV blood concentration 15 min, 12 h, 48 h, and 96 h after administration and the proportion of patients showing trough LEV concentration within the therapeutic range. The secondary outcomes were the discontinuation of apparent convulsive seizure, epileptic wave on electroencephalogram, tracheal intubation, adverse events related to blood parameters, and abnormal findings in vital signs examination.Results: Median blood LEV (2500 mg) concentration at 15 min after administration was 81.6 μg/mL. The median trough concentration after 12, 48, and 96 h was 28.8, 10.5, and 9.1 μg/mL, respectively. Moreover, 95% of patients had trough concentration above the lower limit of the therapeutic blood concentration (>12 μg/mL) after 12 h. Regarding secondary outcomes, endotracheal intubation, seizure suppression, and abnormal electroencephalogram findings were observed in approximately 40%, 90%–95%, and 41% of patients, respectively. No abnormal findings were noted in blood tests and vital sign examination, although the AST/ALT levels increased in 10% of the patients.Conclusion: After bolus administration of 2500 mg, the blood LEV concentration reached the therapeutic window in patients with early-stage SE.

Efficacy of Rituximab on Rheumatoid Leptomeningitis as the First Symptom of Rheumatoid Arthritis

Rheumatoid meningitis may occur in the disease course of rheumatoid arthritis with varied and non-specific symptoms.Cerebrospinal fluid examination, MRI and tests for rheumatoid factor or anti-citrullinated protein antibodies in serum or in cerebrospinal fluid are key examinations for diagnosing rheumatoid meningitis.Rituximab has good efficacy in rheumatoid meningitis.

Clozapine-induced stuttering in the absence of known risk factors: a case report

BackgroundStuttering is a rare side effect of clozapine. It has been shown to occur in the presence of one or more factors such as abnormal electrophysiological findings and seizures, extrapyramidal symptoms, brain pathology, and a family history of stuttering. Few case reports have documented the occurrence of clozapine-induced stuttering in the absence of these risk factors.Case presentationA 29-year-old African male on clozapine for treatment-resistant schizophrenia presented with stuttering at a dosage of 400 mg/day that resolved with dose reduction. Electroencephalogram findings were normal, and there was no clinical evidence of seizures. The patient had no prior history or family history of stuttering, had a normal neurological examination, and showed no signs of extrapyramidal symptoms.ConclusionClinicians ought to be aware of stuttering as a side effect of clozapine, even in the absence of known risk factors. Further research should investigate the pathophysiology of clozapine-induced stuttering.

Leucine-rich glioma-inactivated protein 1 antibody-mediated autoimmune encephalitis in a 4-year-old girl: a case report

BackgroundLeucine-rich glioma-inactivated protein 1 (LGI1) antibody-mediated encephalitis is a rare subtype of autoimmune encephalopathy, which is associated with autoimmunity against the neuronal plasma membrane proteins. The characteristic symptoms of this disease are memory dysfunction, seizures, faciobrachial dystonic seizures, cognitive deficits, neuropsychiatric disturbances, and intractable hyponatremia. The diagnosis of this disease mainly depends on the presence of anti-LGI1 antibody in serum or cerebrospinal fluid of patients. LGI1 antibody encephalitis has been reported mostly in adults, with rare occurrences in children.Case presentationIn this report, we described a 4-year-old girl with typical seizures. Seizure types included focal seizures and generalized tonic-clonic seizures. The electroencephalogram findings showed focal discharges. Brain magnetic resonance imaging (MRI) showed normal. The cerebrospinal fluid (CSF) levels of cells, glucose, and chloride were within the normal range, and the culture did not reveal growth of any pathogen. Test of serum LGI1-Ab was positive, while the tests for autoimmune encephalitis antibody series in CSF were negative. The seizures of the patient were completely controlled after the therapy of immunoglobulin, methylprednisolone and antiepileptic drugs (AEDs), and the mental state almost returned to normal.ConclusionTo our knowledge, the patient described here may be the youngest case of LGI1 antibody encephalitis reported to date. Children with the LGI1 antibody-associated encephalitis may present only with single symptoms such as epileptic seizures and have good response to the therapy of immunoglobulin, methylprednisolone and antiepileptic drugs. Our case report will provide hints for pediatricians in the diagnosis and treatment of LGI1-antibody encephalitis.

Epilepsy in Nicolaides-Baraitser Syndrome: Review of Literature and Report of 25 Patients Focusing on Treatment Aspects.

Nicolaides-Baraitser syndrome (NCBRS), caused by a mutation in the SMARCA2 gene, which goes along with intellectual disability, congenital malformations, especially of face and limbs, and often difficult-to-treat epilepsy, is surveyed focusing on epilepsy and its treatment. Patients were recruited via "Network Therapy of Rare Epilepsies (NETRE)" and an international NCBRS parent support group. Inclusion criterion is NCBRS-defining SMARCA2 mutation. Clinical findings including epilepsy classification, anticonvulsive treatment, electroencephalogram (EEG) findings, and neurodevelopmental outcome were collected with an electronic questionnaire. Inclusion of 25 NCBRS patients with epilepsy in 23 of 25. Overall, 85% of the participants (17/20) reported generalized seizures, the semiology varied widely. EEG showed generalized epileptogenic abnormalities in 53% (9/17), cranial magnetic resonance imaging (cMRI) was mainly inconspicuous. The five most frequently used anticonvulsive drugs were valproic acid (VPA [12/20]), levetiracetam (LEV [12/20]), phenobarbital (PB [8/20]), topiramate (TPM [5/20]), and carbamazepine (CBZ [5/20]). LEV (9/12), PB (6/8), TPM (4/5), and VPA (9/12) reduced the seizures' frequency in more than 50%. Temporary freedom of seizures (>6 months) was reached with LEV (4/12), PB (3/8), TPM (1/5, only combined with PB and nitrazepam [NZP]), and VPA (4/12). Seizures aggravation was observed under lamotrigine (LTG [2/4]), LEV (1/12), PB (1/8), and VPA (1/12). Ketogenic diet (KD) and vagal nerve stimulation (VNS) reduced seizures' frequency in one of two each. This first worldwide retrospective analysis of anticonvulsive therapy in NCBRS helps to treat epilepsy in NCBRS that mostly shows only initial response to anticonvulsive therapy, especially with LEV and VPA, but very rarely shows complete freedom of seizures in this, rather genetic than structural epilepsy.