Non-epileptic Paroxysmal Events Research Articles

Impacto asistencial de la electroencefalografía realizada durante la guardia de Neurofisiología Clínica en un hospital de tercer nivel

IntroductionThe electroencephalogram (EEG) is a useful tool in the diagnosis of pathologies such as non-convulsive status epilepticus (NCSE) or brain death (BD), cardiac arrest (CA), and status epilepticus (SE) treatment monitoring. In addition, it provides irreplaceable information depending on the time it is performed, as is the case with the diagnosis of epilepsy after a first epileptic seizure (ES) or to differentiate these from non-epileptic paroxysmal events (NEPE). Its usefulness is maintained outside the usual working day, but it is not available in many centers. Subjects and methodsRetrospective observational study based on the clinical history of 86 patients who underwent an on-call EEG (ocEEG) at our hospital during 2020. ResultsOne hundred two records requested by Intensive Care (41.1%), Neurology (37.3%), Pediatrics (17.6%) or other services (4%) were made. Suspected NCSE represented 56.7%, followed by treatment monitoring in EE (21.6%). The ME accounted for only 6.9% of the total. The ocEEG avoided potential iatrogenesis in a 56.3% of cases with therapeutic implications, allowed to treat 27.58% of patients who would have remained without treatment until the conventional EEG. An increase in the level of care was required in only 22.2% of all cases. The ocEEG was anticipated a mean of 31.6h to the next conventional EEG that would have been available. ConclusionsThe availability of ocEEG is beneficial in terms of diagnosis, therapy, and hospital management, advancing decision-making and avoiding iatrogenesis. Its availability should become widespread.

Epilepsy in inmate patients seen in a high complexity reference hospital in Colombia: A cross-sectional study.

To describe the sociodemographic and clinical characteristics of imprisoned patients with epilepsy seen at Samaritana University Hospital (HUS) in Bogotá D.C., between January 2017 and November 2020. Cross-sectional cohort study of inmate patients over 18 years of age seen at HUS between January 2017 and November 2020, with a discharge diagnosis of epilepsy. A descriptive univariate analysis of patient sociodemographic and clinical characteristics was carried out. Overall, 92 patients were included, 95.7% were males with a median age of 32 years (IQR: 26-44); 65% were assessed in the outpatient clinic; median hospital length of stay was 2 days (IQR: 0) and 7.6% required admission to the intensive care unit; 75% had focal onset epilepsy, 63.04% with undetermined etiology 31.52% with structural causes. Polytherapy was found in 53.3%, valproic acid being the most frequently used antiseizure medication in 59.78%; lack of adherence was reported in 15.22% and inadequate seizure control in 81.52%; status epilepticus occurred in 5.34%. A total of 31 EEG recordings and 53 brain images were performed, of which, 29% and 39.62%, respectively, were abnormal. Non-epileptic paroxysmal events were diagnosed in 5.34%, while organic or psychiatric comorbidities were found in 25%, and the use of psychoactive substances was documented in 17.39%. Upon discharge, 93.47% had no disability, and only 45.65% returned for outpatient follow-up. The clinical profile was of men in the fourth decade of life with focal onset epilepsy characterized by high seizure frequency, most of whom were receiving antiseizure medication, with a high proportion of polytherapy. The results are a point of departure for prospective studies designed to identify points to intervene and improve healthcare for inmates with epilepsy. Inmates are a vulnerable proportion of persons with epilepsy. In this group there are significant differences compared to the general population, especially with greater psychiatric comorbidity and worse control of epileptic seizures due to difficulties in accessing medical care, antiseizure medication and diagnostic tests. We found that the most characteristic population is made up of men in the fourth decade of life with a high frequency of seizures, most of whom were receiving multiple antiseizure medication This study is the first of its kind in Latin America and it is an initial approach to epilepsy in inmates.

Diagnostic Value of Intermittent Photic Stimulation Among Adult Patients in a Tertiary Referral Epilepsy Center: A Retrospective Study.

Photosensitivity is a phenomenon that may be elicited by standardized intermittent photic stimulation during EEG recording and is detected more frequently in children and adolescents. Nevertheless, at our Epilepsy Center, we routinely assess photosensitivity in all newly referred adult patients. In this investigation, we sought to address the diagnostic yield under the prerequisites described. We reanalyzed all routine EEG recordings among referrals to the department of adults during the first six months of 2019, including a simultaneous video that is always coregistered in our center. The prevalence of abnormal findings during photic stimulation was assessed. Intermittent photic stimulation was performed on 344 patients. Photoparoxysmal response were detected in five subjects (1.5%). All patients were female. Four patients were diagnosed with idiopathic generalized epilepsy, and one with Doose syndrome. Photomyogenic responses were recorded in 1.1% and only in patients with psychogenic nonepileptic seizures. In two subjects with psychogenic nonepileptic seizures, the typical seizure was provoked by intermittent photic stimulation (8.7% of all subjects with psychogenic nonepileptic seizures in this cohort). Photoparoxysmal response was not detected in any subject with focal epilepsy, syncope, or other nonepileptic paroxysmal events. In every case of photoparoxysmal responses, increased photosensitivity had already been reported before recording. In our study, photoparoxysmal responses was a rare phenomenon among adults with a preponderance of females and idiopathic generalized epilepsies. Intermittent photic stimulation may be helpful in provoking typical psychogenic nonepileptic seizures and thus abbreviate the diagnostic process. Provided a careful history, routine intermittent photic stimulation in adults with epilepsy does not appear to be mandatory.

Paroxysmal nonepileptic events in children and adolescents admitted to the epilepsy monitoring unit: A retrospective study

Several patients are referred to the epilepsy monitoring unit (EMU) to evaluate episodic events that can be challenging to differentiate from epileptic events. The current study aimed to determine the prevalence of non-epileptic events (NEEs) among children and adolescents admitted to the EMU, and the clinical and demographic features of such events. MethodsWe retrospectively evaluated all patients aged 18 years and below who were admitted to the EMU of King Fahad Medical City, Riyadh, KSA, from January 2014 to March 2020. ResultsThe prevalence of NEEs in children & adolescents admitted to the EMU was 25%. Psychogenic events (PNESs, 30%) were the most common type. Movement disorders occurred more often in younger age group, while migraine was seen more often in school-aged children. ConclusionThe prevalence of NEEs was 25%, and this result is similar to that reported in the literature. The distribution of events is mainly based on age. Clinical and video-based assessments are essential in identifying such events to prevent unnecessary treatment with anti-seizure medications.

Non-epileptic paroxysmal events at pediatric video-electroencephalography monitoring unit over a 15-year period

ObjectiveNon-epileptic paroxysmal events (NEPEs) are common in pediatric patients and may be misdiagnosed as epileptic seizures. We aimed to study the distribution of NEPEs across age groups and with different comorbidities, and to correlate the patients' presenting symptoms with their final diagnosis after video-EEG. MethodsWe retrospectively analyzed video-EEG recordings of children aged one month to 18 years who were admitted between March 2005 and March 2020. Patients who experienced any NEPE while under video-EEG monitorization were evaluated in this study. Subjects with concomitant epilepsy were also included. The patients were first divided into 14 groups according to the basic characteristics of symptoms they reported at admission. The events captured on video-EEG were then classified into six NEPE categories based on the nature of the events. These groups were compared according to video-EEG results. ResultsWe retrospectively evaluated 1338 records of 1173 patients. The final diagnosis was non-epileptic paroxysmal event in 226 (19.3%) of 1173 patients. The mean age of the patients was 105.4 ± 64.4 months at the time of the monitoring. The presenting symptoms were motor in 149/226 (65.9%) patients, with jerking being the most common (n = 40, 17.7%). Based on video-EEG, the most common NEPE was psychogenic non-epileptic seizures (PNES) (n = 66, 29.2%), and the most common PNES subtype was major motor movements (n = 19/66, 28.8%). Movement disorders (n = 46, 20.4%) were the second most common NEPE and the most common NEPE (n = 21/60, 35%) in children with developmental delay (n = 60). Other common NEPEs were physiological motor movements during sleep (n = 33, 14.6%), normal behavioral events (n = 31, 13.7%), and sleep disorders (n = 15, 6.6%). Almost half of the patients had a prior diagnosis of epilepsy (n = 105, 46.5%). Following the diagnosis of NEPE, antiseizure medication (ASM) was discontinued in 56 (24.8%) patients. ConclusionNon-epileptiform paroxysmal events can be difficult to distinguish from epileptic seizures in children, especially in patients with developmental delay, epilepsy, abnormal interictal EEG, or abnormal MRI findings. Correct diagnosis of NEPEs by video-EEG prevents unnecessary ASM exposure in children and guides appropriate management of NEPEs.

Paroxysmal Nonepileptic Events in Children With Epilepsy and Cerebral Palsy.

To determine the frequency of paroxysmal nonepileptic events in children with cerebral palsy due to brain injury who have epilepsy and to describe the factors associated with paroxysmal nonepileptic events. Methods: Retrospective, population-based study of children from the Victorian CP Register born 1999-2006. Neuroimaging, medical records, electroencephalograms (EEG), and EEG requests were analyzed. Results: Of the included 256 children, 87 had epilepsy. EEGs (with video correlation) were available for 82 of 87. Eighteen (18/82, 22%) had epileptic events captured on EEG. Twenty-one (21/82, 26%) had paroxysmal nonepileptic events captured on EEG. The majority (13/18, 77%) of children with epileptic events also had paroxysmal nonepileptic events captured. Ten parents and carers continued to report events as epileptic despite there being no ictal EEG correlate for specific events on multiple EEGs. There were no clear associations to identify which children would have ongoing paroxysmal nonepileptic events reported. Conclusions: Paroxysmal nonepileptic events were captured on EEG in one-fourth of children from this cerebral palsy cohort with epilepsy and available EEG. Half the parents and carers reported previously identified paroxysmal nonepileptic events as epileptic on subsequent EEGs, highlighting the need for clearer counseling so that parents better understand seizure semiology in children with EEG-proven paroxysmal nonepileptic events.

The Diagnostic Utility of Short-Term Video Electroencephalography at a Tertiary Care Center in North India: A Retrospective Study

Purpose: This study investigated the diagnostic utility of short-term video electroencephalography (EEG) recordings at a tertiary care centre in North India. Methods: A retrospective analysis was conducted of 30 minutes of video EEG recordings done between January 2021 and January 2022 in children between 1 and 10 years of age. Demographic and clinical data were collected from the EEG register. Age, sex, the clinical diagnosis, the number of anti-seizure medicines (ASMs), the activation procedures used, and EEG abnormalities were recorded. Results: Data from 100 children (male-to-female ratio, 1.9:1) were analysed. The mean age was 5.39±2.02 years. The indications for EEG recordings were epileptic disorders, neurodevelopmental disorders, paroxysmal non-epileptic events, and miscellaneous in 66%, 18%, 9%, and 7% of children, respectively. EEG abnormalities were seen in 50 children (50%) and about 45% of children were on two or more ASMs. EEG abnormalities in sleep were seen in 35 of 66 (53%) children, whereas abnormalities were observed on awake recordings with activation procedures (hyperventilation and photic) in 23 of 34 (68%) children; this difference was not statistically significant (P=0.16) Conclusion: EEG abnormalities were significantly more common in children taking multiple ASMs; however, there was no statistically significant difference in the EEG yield between asleep and awake records with activation procedures. A better selection of patients for routine EEG, through an assessment of their clinical history and comorbidities, is warranted to increase its diagnostic yield.

Routine Interictal EEG Recording Should be Performed Together with Simultaneous Two-Lead ECG Recording

AbstractWe aimed to evaluate the contribution of simultaneous electrocardiography (ECG) recording during routine interictal electroencephalography (EEG) recording in patients with seizures or epilepsy and therefore to provide evidence-based data on this subject. Patients with interictal cardiac arrhythmia on routine EEG-ECG recordings were determined and evaluated based on cardiologic and neurologic findings. Out of 1,078 patients aged between 5 and 16 years (mean: 10.2 ± 3.2), 9 (0.08%) patients were found to have an arrhythmia. Six patients had both epilepsy and cardiac arrhythmia (premature ventricular contractions [PVCs] in 5; Wolff-Parkinson-White [WPW] in 1 patient) and the remaining three patients had nonepileptic paroxysmal events (NPEs) and arrhythmia (PVC in 2; WPW in 1). Three patients had other diseases (neurofibromatosis type 1, tuberous sclerosis, and congenital heart disease status postsurgery). Cardiac arrhythmia required radiofrequency ablation or antiarrhythmic drug treatment in two patients with epilepsy and also two patients with NPE; however, it improved with no specific treatment in the remaining five patients. NPE was not related to arrhythmia in one of three patients with NPE. Our study suggests that routine interictal EEG-ECG recording provides a valuable and feasible opportunity to reveal unnoticed or new-onset cardiac arrhythmias. Therefore, ECG should be recorded simultaneously during routine interictal EEG recordings. Cardiac arrhythmias detected by routine interictal EEG-ECG recordings would require arrhythmia treatment in nearly half of the patients.

Predictive value of video alone in diagnosis of epileptic vs paroxysmal nonepileptic events in children

ObjectivePrevious studies examined the use of video-based diagnosis and the predictive value of videos for differentiation of epileptic seizures (ES) from paroxysmal nonepileptic events (PNEE) in the adult population. However, there are no such published studies strictly on the pediatric population. Using video-EEG diagnosis as a gold standard, we aimed to determine the diagnostic predictive value of videos of habitual events with or without additional clinical data in differentiating the PNEE from ES in children. MethodsConsecutive admissions to our epilepsy monitoring unit between June 2020 and December 2020 were analyzed for events of interest. Four child neurologists blinded to the patient’s diagnosis formulated a diagnostic impression based upon the review of the video alone and again after having access to basic clinical information, in addition to the video. Features of the video which helped to make a diagnosis were identified by the reviewers as a part of a survey. ResultsA total of 54 patients were included (ES n = 24, PNEE n = 30). Diagnostic accuracy was calculated for each reviewer and combined across all the ratings. Diagnostic accuracy by video alone was 74.5% (sensitivity 80.8%, specificity 66.7%). Providing reviewers with basic clinical information in addition to the videos significantly improved diagnostic accuracy compared to viewing the videos alone. Inter-rater reliability between four reviewers based on the video alone showed moderate agreement (κ = 0.51) and unchanged when additional clinical data were presented (κ = 0.51). The ES group was significantly more likely to demonstrate changes in facial expression, generalized stiffening, repetitive eye blinks, and eye deviation when compared with the PNEE group, which was more likely to display bilateral myoclonic jerking. ConclusionsVideo review of habitual events by Child Neurologists may be helpful in reliably distinguishing ES from PNEE in children, even without included clinical information.

The Importance of Long-Term Video Electroencephalography Monitoring in the Differential Diagnosis of Epilepsy in Children.

Objective: Epilepsy is a condition in which abnormal, recurring, and excessive neuronal discharges caused by many different disorders in the central nervous system are observed. The rate of detecting epileptiform activity in the first interictal electroencephalography (EEG) of patients with epilepsy is around 40%, even when routine activation methods are applied. Video recordings simultaneously with EEG recordings enable the establishment of correlations between abnormalities.Patients and methods: The long-term video-EEG monitoring (VEM) reports and images of 87 patients hospitalized in the video EEG service in the Pediatric Neurology Clinic of İnönü University between 2016 and 2020 were retrospectively analyzed in this study. Demographic information of the patients, such as age, gender, diagnosis/history, and length of hospital stay, was analyzed.Results: A total of 87 patients were included in the study. Of the patients, 54 (62.1%) were male and 33 (37.9%) were female. The mean age was 107.57 ± 64.40 months. While 10 (11.5%) patients followed up with non-epileptic paroxysmal events (NEPE) were taking antiepileptic drugs (AEDs), AED treatments were discontinued after VEM. The diagnosis of 18 (20.69%) patients changed after VEM. The medications of 27 (31%) patients who took AEDs before VEM were discontinued after VEM. During VEM, sleep movement, psychogenic seizures, infantile masturbation, and tic disorder were observed in 19 (41.3%), 17 (36.9%), three (6.5%), and three (6.5%) patients, respectively.Conclusion: In conclusion, VEM is the gold standard diagnostic method used to distinguish between epilepsy and NEPEs. After VEM, the clinical diagnosis of patients can change, and unnecessary drug administration may be prevented. Psychogenic nonepileptic seizures and NEPEs are common in the pediatric population; however, they are often overlooked.

Profiles of indigenous patients with epilepsy in a Brazilian village

IntroductionIdentifying epilepsy in local indigenous populations and describing its epidemiological, etiological, electroencephalographic, and therapeutic aspects can assist public health policies planning toward epilepsy in indigenous communities. MethodsThis descriptive, cross-sectional study investigated epilepsy among indigenous people residing in Jaguapirú Village, Dourados, Mato Grosso do Sul, Brazil. Participants had their clinical histories reviewed and physical examination performed, as well as one or more electroencephalograms (EEG) registered. Other laboratory tests and neuroimaging data available were analyzed and patients with nonepileptic paroxysmal events were additionally identified. ResultsOut of 2,994 respondents, 49 had a confirmed diagnosis of epilepsy (2.37%) and 22 had self-limited epileptic syndromes, a rate that exceeds the global prevalence but is close to other data reported in the Brazilian population. Focal epilepsy, predominantly from temporal lobe origin, was the most prevalent epileptic syndrome (71.4%). Febrile seizures occurred in only 0.4% of respondents, much lower rate than reported in the general population, which can be attributed to the cross-sectional study design. The etiology of epilepsy was undetermined in 82.6% of cases, with the remaining cases attributed to head trauma, hypoxic-ischemic encephalopathy, and brain malformations. A history of delayed neuropsychomotor development was significantly associated with epilepsy. Monotherapy with first-generation antiseizure medications was greatly effective in most epilepsy cases (87.7%). Electroencephalogram helped to define focal epilepsies and diagnose seizures of nonepileptic origin; the latter mostly included cases of psychogenic seizures and, less frequently, syncope. ConclusionDiagnosing epilepsy, its clinical presentation, and therapeutical response profile in traditional communities is essential for the establishment of public health policies in developing countries and may help community involvement for successful treatment.

The operational definition of epileptiform discharges significantly improves diagnostic accuracy and inter-rater agreement of trainees in EEG reading.

To assess whether trainees can learn and implement the operational definition of interictal epileptiform discharges (IEDs) of the International Federation of Clinical Neurophysiology (IFCN), based on six morphological criteria, and whether its implementation improves their diagnostic performance and inter-rater agreement (IRA). Seven trainees evaluated a balanced dataset of 70 EEG samples containing sharp transients (35 from patients with epilepsy and 35 from patients with non-epileptic paroxysmal events). The gold standard was derived from video-EEG recordings of the habitual clinical episodes. The trainees individually reviewed the EEGs, blinded to all other data, in two successive training sessions, three months apart. The second session was preceded by a teaching module about the IFCN criteria, and the trainees implemented them during the second reading session. By implementing the IFCN criteria, trainees significantly improved their specificity (94.29% vs. 77.14%; p=0.01) and overall accuracy (81.43% vs. 64.29%; p=0.01) for identifying IEDs. Sensitivity also improved but did not reach the level of statistical significance (77.14% vs. 60%; p=0.07). IRA improved significantly from fair (k=0.31; 95%CI: 0.22-0.40) to high-moderate (k=0.56; 95%CI:0.46-0.67) beyond-chance agreement. Implementing the IFCN criteria significantly improves the diagnostic performance and IRA of trainees in identifying IEDs. Teaching the IFCN criteria for IEDs will increase specificity in clinical EEG and avoid over-reading, the most common cause of misdiagnosing epilepsy.

Seizures and Epilepsy in Childhood.

This article highlights basic concepts of seizures and epilepsy in pediatric patients, as well as basic treatment principles for this age group. Epilepsy is the most common neurologic disorder in childhood. Accurate diagnosis is key; in older children, epileptic seizures need to be differentiated from various paroxysmal nonepileptic events, whereas in neonates, the majority of seizures are subclinical (electroencephalographic). Antiseizure medications remain the first-line treatment, but ketogenic diet and epilepsy surgery have also shown positive outcomes and can decrease drug burden. Genetic causes account for approximately 30% of cases, and the recognition of electroclinical syndromes is being replaced by the concept of genetic spectrums. Precision medicine therapies are promising, but wide application in daily practice still has a long way to go. Early access to specialist centers and optimal treatments positively affects prognosis and future neurodevelopment. Although novel findings from all fields of research are being incorporated into everyday clinical practice, a better quality of life for children with seizures and epilepsy and their families is the ultimate priority.

Evaluation of First Seizure and Newly Diagnosed Epilepsy.

This article focuses on the evaluation of children and adults who present with new-onset seizures, with an emphasis on differential diagnosis, classification, evaluation, and management. New-onset seizures are a common presentation in neurologic practice, affecting approximately 8% to 10% of the population. Accurate diagnosis relies on a careful history to exclude nonepileptic paroxysmal events. A new classification system was accepted in 2017 by the International League Against Epilepsy, which evaluates seizure type(s), epilepsy type, epilepsy syndrome, etiology, and comorbidities. Accurate classification informs the choice of investigations, treatment, and prognosis. Guidelines for neuroimaging and laboratory and genetic testing are summarized. Accurate diagnosis and classification of first seizures and new-onset epilepsy are key to choosing optimal therapy to maximize seizure control and minimize comorbidities.

Accurate identification of EEG recordings with interictal epileptiform discharges using a hybrid approach: Artificial intelligence supervised by human experts.

ObjectiveTo evaluate the diagnostic performance of artificial intelligence (AI)–based algorithms for identifying the presence of interictal epileptiform discharges (IEDs) in routine (20‐min) electroencephalography (EEG) recordings.MethodsWe evaluated two approaches: a fully automated one and a hybrid approach, where three human raters applied an operational IED definition to assess the automated detections grouped into clusters by the algorithms. We used three previously developed AI algorithms: Encevis, SpikeNet, and Persyst. The diagnostic gold standard (epilepsy or not) was derived from video‐EEG recordings of patients' habitual clinical episodes. We compared the algorithms with the gold standard at the recording level (epileptic or not). The independent validation data set (not used for training) consisted of 20‐min EEG recordings containing sharp transients (epileptiform or not) from 60 patients: 30 with epilepsy (with a total of 340 IEDs) and 30 with nonepileptic paroxysmal events. We compared sensitivity, specificity, overall accuracy, and the review time‐burden of the fully automated and hybrid approaches, with the conventional visual assessment of the whole recordings, based solely on unrestricted expert opinion.ResultsFor all three AI algorithms, the specificity of the fully automated approach was too low for clinical implementation (16.67%; 63.33%; 3.33%), despite the high sensitivity (96.67%; 66.67%; 100.00%). Using the hybrid approach significantly increased the specificity (93.33%; 96.67%; 96.67%) with good sensitivity (93.33%; 56.67%; 76.67%). The overall accuracy of the hybrid methods (93.33%; 76.67%; 86.67%) was similar to the conventional visual assessment of the whole recordings (83.33%; 95% confidence interval [CI]: 71.48–91.70%; p > .5), yet the time‐burden of review was significantly lower (p < .001).SignificanceThe hybrid approach, where human raters apply the operational IED criteria to automated detections of AI‐based algorithms, has high specificity, good sensitivity, and overall accuracy similar to conventional EEG reading, with a significantly lower time‐burden. The hybrid approach is accurate and suitable for clinical implementation.

Movement disorders in MCT8 deficiency/Allan-Herndon-Dudley Syndrome

Background and objectivesMCT8 deficiency is a rare genetic leukoencephalopathy caused by a defect of thyroid hormone transport across cell membranes, particularly through blood brain barrier and into neural cells. It is characterized by a complex neurological presentation, signs of peripheral thyrotoxicosis and cerebral hypothyroidism. Movement disorders (MDs) have been frequently mentioned in this condition, but not systematically studied. MethodsEach patient recruited was video-recorded during a routine outpatient visit according to a predefined protocol. The presence and the type of MDs were evaluated. The type of MD was blindly scored by two child neurologists experts in inherited white matter diseases and in MD. Dystonia was scored according to Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). When more than one MD was present, the predominant one was scored. Results27 patients were included through a multicenter collaboration. In many cases we saw a combination of different MDs. Hypokinesia was present in 25/27 patients and was the predominant MD in 19. It was often associated with hypomimia and global hypotonia. Dystonia was observed in 25/27 patients, however, in a minority of cases (5) it was deemed the predominant MD. In eleven patients, exaggerated startle reactions and/or other paroxysmal non-epileptic events were observed. ConclusionMDs are frequent clinical features of MCT8 deficiency, possibly related to the important role of thyroid hormones in brain development and functioning of normal dopaminergic circuits of the basal ganglia. Dystonia is common, but usually mild to moderate in severity, while hypokinesia was the predominant MD in the majority of patients.

Epilepsy and BRAF Mutations: Phenotypes, Natural History and Genotype-Phenotype Correlations.

Objective: Cardiofaciocutaneous syndrome (CFCS) is a rare developmental disorder caused by upregulated signaling through the RAS-mitogen-activated protein kinase (MAPK) pathway, mostly resulting from de novo activating BRAF mutations. Children with CFCS are prone to epilepsy, which is a major life-threatening complication. The aim of our study was to define the natural history of epilepsy in this syndrome and exploring genotype–phenotype correlations. Methods: We performed an observational study, including 34 patients with molecularly confirmed diagnosis (11 males, mean age: 15.8 years). The mean follow-up period was 9.2 years. For all patients, we performed neurological examination, cognitive assessment when possible, neuroimaging, electrophysiological assessment and systematic assessment of epilepsy features. Correlation analyses were performed, taking into account gender, age of seizure onset, EEG features, degree of cognitive deficits, type of mutation, presence of non-epileptic paroxysmal events and neuroimaging features. Results: Epilepsy was documented in 64% of cases, a higher prevalence compared to previous reports. Patients were classified into three groups based on their electroclinical features, long-term outcome and response to therapy. A genotype–phenotype correlation linking the presence/severity of epilepsy to the nature of the structural/functional consequences of mutations was observed, providing a stratification based on genotype to improve the clinical management of these patients.

A web-based algorithm to rapidly classify seizures for the purpose of drug selection.

To develop and validate a pragmatic algorithm that classifies seizure types, to facilitate therapeutic decision-making. Using a modified Delphi method, five experts developed a pragmatic classification of nine types of epileptic seizures or combinations of seizures that influence choice of medication, and constructed a simple algorithm, freely available on the internet. The algorithm consists of seven questions applicable to patients with seizure onset at the age of 10years or older. Questions to screen for nonepileptic attacks were added. Junior physicians, nurses, and physician assistants applied the algorithm to consecutive patients in a multicenter prospective validation study (ClinicalTrials.gov identifier: NCT03796520). The reference standard was the seizure classification by expert epileptologists, based on all available data, including electroencephalogram (EEG), video-EEG monitoring, and neuroimaging. In addition, physicians working in underserved areas assessed the feasibility of using the web-based algorithm in their clinical setting. A total of 262 patients were assessed, of whom 157had focal, 51had generalized, and 10had unknown onset epileptic seizures, and 44had nonepileptic paroxysmal events. Agreement between the algorithm and the expert classification was 83.2% (95% confidence interval = 78.6%-87.8%), with an agreement coefficient (AC1) of .82 (95% confidence interval = .77-.87), indicating almost perfect agreement. Thirty-two health care professionals from 14 countries evaluated the feasibility of the web-based algorithm in their clinical setting, and found it applicable and useful for their practice (median = 6.5 on 7-point Likert scale). The web-based algorithm provides an accurate classification of seizure types, which can be used for selecting antiseizure medications in adolescents and adults.

English

BACKGROUND Breath holding spells (BHS) are common, non-epileptic paroxysmal events that occur in children below 6 years, whose diagnosis is made many times clinically. Exact aetiology is not known, but iron deficiency was one among many proposed aetiological factors. Very few studies were published till date to determine role and effect of iron supplementation in children with breath holding spells. Hence the present study was taken up to assess the presence of iron deficiency and the effect of iron supplementation in children with breath holding spells. METHODS This prospective interventional study was performed from May 2012 to April 2017. 125 children below six years of age brought with the complaint of breath holding spells were screened for presence of anaemia and other systemic illnesses. Ten children were excluded with other organic causes and only 85 children were found to have anaemia and were supplemented with 6 mg/kg/day of ferrous sulphate for 3 months and followed up for a total period of 6 months. Response to iron supplementation was assessed in these children by measuring total number of attacks of BHS before starting iron supplementation, after supplementation of iron for three months and also at the end of follow-up period. The results were analysed by using Microsoft Office Excel. RESULTS 76.52 % (85/115) of patients had anaemia and were supplemented with 6 mg/kg/day of ferrous sulphate for 3 months. The remaining 27 cases had normal Hb % &amp; red blood cells (RBC) indices and were not included. Response to iron therapy was assessed in anaemic children with breath holding spells and we found complete response in 78.41 %, partial response in 15.91 % and no response in 5.7 %. CONCLUSIONS This study proved the role of iron therapy in anaemic children with breath holding spells. KEYWORDS Breath Holding Spells (BHS), Iron Deficiency, Anaemia, Haemoglobin

Non-Epileptic Paroxysmal Events: Clinical features and diagnostic differences with epileptic seizures. A Single Tertiary Centre Study

BackgroundNon-Epileptic Paroxysmal Events (NEPE) are common clinical manifestations in pediatric age presenting with dysfunction of motor and behavioral activity mimicking features of epileptic seizures. ObjectiveTo present and analyze number and clinical characteristic of a group of children/adolescents presenting with various types of NEPE; to compare clinical data of this group of NEPE affected children/adolescents with a group of children/adolescents affected by Epileptic Seizures (ES). MethodsThe retrospective study was conducted at the Pediatric Clinic of University of Catania, Catania, Italy, in a period ranging from January 2005 and January 2018. Two groups of children/adolescents, aged from 1 month to 15 years, were selected: 312 affected by NEPE and 192 by ES. Number and percentage of the single type of NEPE were reported. Then, demographic characteristics, clinical manifestations, duration of the events, time of diagnosis, and age of onset of each type of NEPE and ES affected children/adolescents were analyzed and compared. Results of statistical analysis of the data were carried out between ES and some type of NEPEs including Sandifer syndrome, breath-holding spells, paroxysmal tremors, vertigo, and syncope. ResultsAmong the group of NEPE, vertigo, type of paroxysmal event clinically not classifiable, syncope, and Sandifer syndrome were the most common events; In the comparative analyzed samples, variability between NEPE and ES was found in the duration of the paroxysmal events, in number of episodes, in lag-time between the onset of symptoms and the diagnosis, and in age of onset. Analyzing clinical data of ES with some type of NEPE, statistical significant results were obtained in vertigo as regards the duration and average duration event, in paroxysmal tremors as number of events, in Sandifer syndrome as lag-time of diagnosis, and finally in all the types of NEPE as regards the age of onset, and loss of consciousness. ConclusionsAnalyzing the clinical features of each type of NEPE differences with ES are found. However, globally considered diagnostic differences between NEPE and ES remain difficult, questionable, and unrealizable without the support of correct parental report, direct clinical observations, and video-EEG monitoring.