Shear Wave Elastography in Patients with Spinal Muscular Atrophy Types 2 and 3.

INTRODUCTION: This study aimed to investigate selective muscle involvement by shear wave elastography (SWE) in patients with spinal muscular atrophy (SMA) types 2 and 3 and to compare SWE values with magnetic resonance imaging (MRI) in demonstrating muscle involvement. METHODS: Seventeen patients with SMA types 2 and3 were included in the study. SWE was used to evaluate stiffness of the upper and lower extremities and paraspinal muscles. Involvement of the paraspinal muscles was evaluated using 1.5-T MRI. RESULTS: Among the upper extremity muscles, SWE values were the highest for the triceps brachii; however, no significant difference was noted (p = 0.23). In post hoc analysis, a significant difference was observed between triceps brachii and biceps brachii (p = 0.003). Patients with a longer disease duration have the highest SWE values for the triceps brachii (r = 0.67, p = 0.003). Among the lower extremity muscles, SWE values for the iliopsoas were significantly higher than the gluteus maximus (p < 0.001). A positive correlation was found between SWE values and MRI scores of paraspinal muscles (r = 0.49, p = 0.045; r = 0.67, p = 0.003). CONCLUSION: This is the first study to report muscle involvement assessed by SWE in patients with SMA types 2 and 3. Our findings are similar to the presence of selective muscle involvement demonstrated in previous studies, and also SWE and MRI values were similar. SWE is an alternative noninvasive practical method that can be used to demonstrate muscle involvement in patients with SMA, to understand the pathogenesis of segmental involvement, and to guide future treatments or to monitor the effectiveness of existing new treatment options.

Seizure treatment with olfactory training: a preliminary trial.

OBJECTIVE: Epilepsy is a chronic condition characterized by recurrent seizures. Despite miscellaneous antiseizure medications, resistance to treatment is still approximately 30%. This resistance brings forward the multidisciplinary approach and complementary treatments. In this study, we aimed to investigate the effect of olfactory training on epileptic seizures with special aromas having antiseizure effects in patients diagnosed with drug-resistant epilepsy. METHODS: A total of 24 patients (14 pediatric and 10 adults) with drug-resistant epilepsy were recruited for the study. Participants were asked to inhale the standardized bottle filled with lavender aroma (Lavandula Angustifolia) twice a day (morning and evening) for 30-45 s (2 cm in front of nose; 10-15 s to right and left nostril and 10-15 s to both nostrils) for 3 months. The type, frequency, duration of seizures, the quality of life (SF-36 and PedsQL 4.0), and olfactory functions (Sniffin' Sticks Test and Pediatric Smell Wheel) were re-assessed. RESULTS: Statistical analysis showed that olfactory training decreased the seizure frequency (p < 0.001) and the seizure duration (p = 0.02). A global 50% seizure reduction was seen among patients. Moreover, olfactory training increased the quality of life (p = 0.003) and improved the olfactory function in both the pediatric and adult groups (p = 0.017, p = 0.05, respectively). There was no adverse reaction and no increase in seizure frequency. SIGNIFICANCE: The observations of the present investigation suggest that olfactory training is a successful complementary therapy with no adverse reaction in patients with drug-resistant epilepsy. Large cohort studies and longer follow-up periods are needed for providing olfactory training as a therapy modality in patients with epilepsy.

Evaluation of eating behaviors in childhood epilepsy with centrotemporal spikes: Case-control study.

BACKGROUND: Psychosocial and behavioral disorders have been reported in childhood epilepsy with centrotemporal spikes (CECTS). We aimed to identify the symptoms of eating disorders in CECTS. METHODS: Patients with CECTS were recruited from the pediatric neurology outpatient clinic between September 2019 and July 2020. The Children's Eating Behaviour Questionnaire (CEBQ) was administered to 39 patients and 31 controls. Patients' scores were compared with those of healthy subjects. RESULTS: There was no significant difference between the CEBQ of patients with CECTS and the control group (p > 0.05). There was no significant difference between the BMI of the patients with CECTS and the control group. In the patient group with CECTS, no significant difference was found in terms of CEBQ according to the antiepileptic drug used and EEG findings (p > 0.05). CONCLUSION: No difference was found in the eating habits of patients with CECTS compared with the healthy control group.

Autism spectrum disorder and attention-deficit/hyperactivity disorder-related symptoms in benign childhood epilepsy with centrotemporal spikes: A prospective case-control study.

BACKGROUND: Benign childhood epilepsy with centrotemporal spikes (BECTS), one of the most common idiopathic epilepsy syndromes in children, has been associated with neuropsychological problems. PURPOSE: The objective of this study was to investigate the frequency of symptoms related to comorbid neurodevelopmental disorders, the autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in children with typical BECTS, and to identify corresponding risk factors. METHODS: Children and adolescents with typical BECTS aged 6-16 years were included in the study period from January 1, 2017, to December 31, 2017. Children with atypical presentations of BECTS, other neurological disorders, and preexisting neuropsychiatric disorders were excluded. The ASD and ADHD were assessed by the Social Communication Questionnaire (SCQ) and the Turgay Diagnostic and Statistical Manual of Mental Disorders - 4th Edition - Disruptive Behavior Disorders Rating Scale (T-DSM-IV-S), respectively. Patients' scores were compared with those of healthy subjects. Correlation analyses were performed to evaluate the association between the age at seizure onset, the total number of seizures and the SCQ and T-DSM-IV-S scores. RESULTS: Fifty-eight children with BECTS and 60 healthy children participated in the study. The total SCQ score, the SCQ reciprocal social interaction score, and the SCQ communication score significantly differed between children with BECTS and the control group (p = 0.001, p < 0.001, p = 0.001, respectively). The total ADHD score was significantly different between patients and controls (p < 0.001). A significant difference was observed between patients and controls in terms of the T-DSM-IV-S hyperactivity-impulsivity score and the T-DSM-IV-S inattention score (p = 0.012, p < 0.001, respectively). The age at seizure onset was significantly correlated with the total SCQ score (p = 0.03). The Spearman's correlation coefficient was 0.352 for the total SCQ score, indicating a positive association between the age at seizure onset and the total SCQ score. CONCLUSION: Children with typical BECTS may have an increased risk of suffering from symptoms of ASD and ADHD. Children with late onset of seizures may be more likely to develop neuropsychological disturbances regarding ASD and ADHD.

The influence of levetiracetam on psychosocial and behavioral functioning in children: A case-control and follow-up study.

BACKGROUND: Levetiracetam, a widely used antiepileptic drug in children, has been associated with psychosocial and behavioral problems, which are also influenced by epilepsy variables, including duration or seizure frequency. PURPOSE: The objective of this study is to investigate the frequency and timing of treatment-emergent psychosocial and behavioral problems in children receiving levetiracetam, irrespective of seizure variables which are possible confounders. METHODS: A prospective, case-control study with a 3-month follow-up was conducted. Consecutive children aged 6 to 16years with new-onset partial seizures were included in case of starting treatment with either levetiracetam or valproic acid. Psychosocial and behavioral functioning were assessed using a set of standardized questionnaires including Strengths and Difficulties Questionnaire (SDQ) and Children's Depression Inventory (CDI) at baseline, 1 and 3-month follow-up. Patients' baseline scores were compared to healthy subjects. The difference in the follow-up SDQ and CDI scores was evaluated in patients receiving levetiracetam and valproic acid. RESULTS: A total of 101 participants were analyzed; 32 patients in levetiracetam group, 19 patients in valproic acid group and 50 healthy controls. Baseline SDQ and CDI scores were not statistically different between patients and healthy subjects (p>0.05). No statistically significant difference was observed in CDI, total and subscale SDQ scores between patients receiving levetiracetam or valproic acid during the study period (p>0.05). A girl aged 15years receiving levetiracetam had a CDI score of 18 without suicidal ideation at baseline. She developed suicidal ideation and depression, which resolved after switching of levetiracetam to valproic acid, at the 1-month follow-up. No other psychiatric or behavioral side-effects were observed in other patients. CONCLUSION: Psychosocial and behavioral side-effects of levetiracetam treatment are not frequent and they don't emerge in most of children at lower doses. At this dose, and after 3months, using these specific instruments, we did not observe any difference between the valproic acid and levetiracetam treatment groups.

Lacosamide treatment of childhood refractory focal epilepsy: the first reported side effect in paediatric patients.

PURPOSE: Lacosamide (LCM) is an effective antiepileptic drug (AED) approved for the treatment of focal epilepsy in both children and adults. The aim of this observational study was to review our centre's experience with LCM and to characterise its efficacy and tolerability as an adjunct therapy in children with refractory focal epilepsy. METHODS: We retrospectively reviewed the medical records of 12 paediatric patients who underwent treatment with LCM from January 2014 to December 2015. We recorded the treatment response at three time points: at 3 and 6 months after LCM therapy and at the final follow-up visit. Children showing seizure reduction ≥ 50% were considered responders. RESULTS: We included 12 patients (five boys), and their mean age was 13.8 years (range: 6.2-17.6 years) at the end of LCM treatment. The average length of follow-up after starting LCM was 23 months (11-37 months). Eight patients (66%) had > 50% reduction in seizures at the 3-month follow-up visit, and seven (58%) had > 50% reduction at the 6-month follow-up visit. Six patients (50%) maintained ≥ 50% reduction in seizures at the final follow-up visit. Two patients (16.6%) were seizure free at the 6-month and final follow-up visits. Common adverse side effects included dizziness, ataxia, nausea, and vomiting. Two patients developed status epilepticus (SE), one each at 3 and 11 days after the first LCM dose; they both discontinued treatment. CONCLUSIONS: Our study points to the efficacy of LCM in a small paediatric group. Furthermore, it was important to report status epilepticus after LCM administration in the paediatric population for the first time.

Exome sequencing reveals homozygous TRIM2 mutation in a patient with early onset CMT and bilateral vocal cord paralysis.

Charcot-Marie-Tooth disease is a heterogeneous group of inherited distal symmetric polyneuropathies associated with mutations in genes encoding components essential for normal functioning of the Schwann cell and axon. TRIM2, encoding a ligase that ubiquitinates the neurofilament light chain, was recently associated with early-onset neuropathy in a single patient. We report a TRIM2 homozygous missense mutation (c.2000A>C; p.D667A) in a patient with peripheral neuropathy and bilateral vocal cord paralysis, allowing for further delineation of the associated phenotypic spectrum.

Association of epilepsy with neuroimaging patterns in children with cerebral palsy.

OBJECTIVES: In this study, we examined whether epilepsy and drug-resistant epilepsy are associated with neuroimaging findings in children with cerebral palsy (CP). METHODS: Magnetic resonance imaging classification system (MRICS) proposed by Surveillance of Cerebral Palsy in Europe (SCPE) was used for classification of different MRI patterns in patients with cerebral palsy. We reviewed the brain MRI scans and medical records of children with CP who were followed-up in our clinic between 2019 and 2023. Patients were divided into three categories: CP without epilepsy, CP with controlled epilepsy and CP with DRE. MRI patterns were grouped as maldevelopments, predominant white matter injury, predominant gray matter injury, miscellaneous (delayed myelination, cerebral atrophy, cerebellar atrophy, brainstem lesions and calcifications, lesions that were not classified under any other group) and normal according to MRICS of the SCPE. RESULTS: There were 325 CP patients. The most common MRI patterns were predominant white matter injury (47.6%) and gray matter injury (23.8%). There was a 1.5-fold reduction in the risk of epilepsy in patients with predominant white matter injury (OR = 1.54, 95% CI 1.23-1.94). In contrast, children in the miscellaneous group had significantly higher risks of epilepsy (p < 0.001), and we were able to determine that miscellaneous findings increased the risk by 1.8 times (OR = 1.77, 95% CI 1.47-2.12). CONCLUSION: In conclusion, more than half of the children with CP had epilepsy, 40.7% of whom had DRE. On MRI, miscellaneous findings may indicate a poor prognosis for epilepsy, while predominant white matter injury may indicate a good outcome. Children with CP, especially those with miscellaneous findings on MRI, should be closely monitored for epilepsy development.

A Retrospective Review of 18 Patients With Childhood-Onset Hereditary Spastic Paraplegia, Nine With Novel Variants.

BACKGROUND: Hereditary spastic paraplegias (HSPs) are a group of genetically heterogeneous neurodegenerative disorders. Our objective was to determine the clinical and molecular characteristics of patients with genetically confirmed childhood-onset HSPs and to expand the genetic spectrum for some rare subtypes of HSP. METHODS: We reviewed the charts of subjects with genetically confirmed childhood-onset HSP. The age at the disease onset was defined as the point at which the delayed motor milestones were observed. Delayed motor milestones were defined as being unable to hold the head up by four months, sitting unassisted by nine months, and walking independently by 17 months. If there were no delayed motor milestones, age at disease onset was determined by leg stiffness, frequent falls, or unsteady gait. Genetic testing was performed based on delayed motor milestones, progressive leg spasticity, and gait difficulty. The variant classification was determined based on the American College of Medical Genetics standard guidelines for variant interpretation. Variants of uncertain significance (VUS) were considered disease-associated when clinical findings were consistent with the previously described disease phenotypes for pathogenic variants. In addition, in the absence of another pathogenic, likely pathogenic, or VUS variant that could explain the phenotype of our cases, we concluded that the disease is associated with VUS in the HSP-causing gene. Segregation analysis was also performed on the parents of some patients to demonstrate the inheritance model. RESULTS: There were a total of 18 patients from 17 families. The median age of symptom onset was 18 months (2 to 84 months). The mean delay between symptom onset and genetic diagnosis was 5.8 years (5 months to 17 years). All patients had gait difficulty caused by progressive leg spasticity and weakness. Independent walking was not achieved at 17 months for 67% of patients (n = 12). In our cohort, there were two subjects each with SPG11, SPG46, and SPG 50 followed by single subject each with SPG3A, SPG4, SPG7, SPG8, SPG30, SPG35, SPG43, SPG44, SPG57, SPG62, infantile-onset ascending spastic paralysis (IAHSP), and spastic paraplegia and psychomotor retardation with or without seizures (SPPRS). Eight novel variants in nine patients were described. Two affected siblings had a novel variant in the GBA2 gene (SPG46), and one subject each had a novel variant in WASHC5 (SPG8), SPG11 (SPG11), KIF1A (SPG30), GJC2 (SPG44), ERLIN1 (SPG62), ALS2 (IAHSP), and HACE1 (SPPRS). Among the novel variants, the variant in the SPG11 was pathogenic and the variants in the KIF1A, GJC2, and HACE1 were likely pathogenic. The variants in the GBA2, ALS2, ERLIN1, and WASHC5 were classified as VUS. CONCLUSIONS: There was a significant delay between symptom onset and genetic diagnosis of HSP. An early diagnosis may be possible by examining patients with delayed motor milestones, progressive spasticity, gait difficulties, and neuromuscular weakness in the context of HSP. Eight novel variants in nine patients were described, clinically similar to the previously described disease phenotype associated with pathogenic variants. This study contributes to expanding the genetic spectrum of some rare subtypes of HSP.

Genetic and clinical evaluation of congenital myasthenic syndromes with long-term follow-up: experience of a tertiary center in Turkey.

INTRODUCTION: Congenital myasthenic syndromes (CMS) are a heterogeneous group of genetic disorders affecting the safety factor which required for neuromuscular transmission. Here we reported our experience in children with CMS. METHODS: We retrospectively collected the data of 18 patients with CMS who were examined in our outpatient clinic between January 2021 and January 2022. The diagnosis of CMS was based on the presence of clinical symptoms such as abnormal fatigability and weakness, absence of autoantibodies against acetylcholine receptor and muscle-specific kinase, electromyographic evidence of neuromuscular junction defect, molecular genetic confirmation, and response to treatment. RESULTS: The most common mutations were in the acetylcholine receptor (CHRNE) gene (8/18) and choline acetyltransferase (ChAT) (2/18) gene. Despite targeted gene sequencing and whole exome sequencing (WES) were underwent, we couldn't detect a genetic mutation in three out of patients. The most commonly determined initial finding was eyelid ptosis, followed by fatigable weakness, and respiratory insufficiency. Although the most commonly used drug was pyridostigmine, we have experienced that caution should be exercised as it may worsen some types of CMS. DISCUSSION: We reported in detail the phenotypic features of very rare gene mutations associated with CMS and our experience in the treatment of this disease. Although CMS are rare genetic disorder, the prognosis can be very promising with appropriate treatment in most CMS subtypes.

Triosephosphate Isomerase Deficiency: E105D Mutation in Unrelated Patients and Review of the Literature.

Introduction: Chronic haemolytic anaemia, increased susceptibility to infections, cardiomyopathy, neurodegeneration, and death in early childhood are the clinical findings of triosephosphate isomerase (TPI) deficiency, which is an ultra-rare disorder. The clinical and laboratory findings and the outcomes of 2 patients with TPI deficiency are reported, with a review of cases reported in the literature. Case Presentation: Two unrelated patients with haemolytic anaemia and neurologic findings who were diagnosed as having TPI deficiency are presented. Neonatal onset of initial symptoms was observed in both patients, and the age at diagnosis was around 2 years. The patients had increased susceptibility to infections and respiratory failure, but cardiac symptoms were not remarkable. Screening for inborn errors of metabolism revealed a previously unreported metabolic alteration determined using tandem mass spectrometry in acylcarnitine analysis, causing elevated propionyl carnitine levels in both patients. The patients had p.E105D (c.315G>C) homozygous mutations in the TPI1 gene. Although severely disabled, both patients are alive at the ages of 7 and 9 years. Discussion: For better management, it is important to investigate the genetic aetiology in patients with haemolytic anaemia with or without neurologic symptoms who do not have a definitive diagnosis. The differential diagnosis of elevated propionyl carnitine levels using tandem mass spectrometry screening should also include TPI deficiency.

Evaluation of inflammatory acquired demyelinating syndromes in children: a single-center experience.

To evaluate the clinical and neuroimaging features of pediatric acquired demyelinating syndromes (ADS) in a tertiary pediatric neurology clinic in Turkey. All children diagnosed with any subset of ADS between 2013 and 2018 were included in this retrospective cohort study. Forty-two patients (21 female) with a median follow-up period of 30 months were included. The median age of the patients at disease onset was 11 years (range 1.5-17 years). The most common pediatric ADS categories according to the International pediatric Multiple Sclerosis Study Group consensus classification criteria were acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS), each of which seen in 15 patients, followed by clinically isolated syndrome (CIS) (n = 11) and Neuromyelitis Optica Spectrum Disorder (NMOSD) (n = 1). At the first clinical event, children with ADEM significantly differed from the children affected by MS and CIS in terms of the following parameters: median age at onset (7 vs. 13.5 and 14.5 years; p < 0.001), encephalopathy (93.3 vs 0% and 0%; p < 0.001), and basal ganglia/thalamus lesions (73.3 vs 9.1% and 9.1%; p < 0.001). The frequency of seizure and pleocytosis were higher in ADEM group than MS group (p < 0.05), whereas oligoclonal bands (p < 0.001) and periventricular white matter lesions (p < 0.01) were more frequently observed in MS patients. Rituximab was used with great success in the prevention of relapses in 3 patients: NMOSD (n = 1), MS (n = 1) and ADEM followed by recurrent optic neuritis (n = 1). Our results define the longitudinal disease course of various ADS categories in a single referral center. In addition, this study compares various clinical, laboratory and neuroimaging features between these ADS categories.

Preliminary validation of the Turkish version of the pain catastrophizing scale for children and parents (PCS-C and PCS-P) in primary childhood headache.

OBJECTIVES: The aims of this study were to translate the pain catastrophizing scale for children and parents (PCS-C and PCS-P) into Turkish (TurPCS-C and TurPCS-P) and evaluate the psychometric properties in children with primary headache. METHODS: Exploratory factor analysis was used to test the construct validity. Reliability was measured using item-total score correlation, internal consistency (Cronbach α coefficient), Cronbach α if the item was deleted, and test-retest correlation. Concurrent validity and convergent validity of the scales were correlated with other scales (Revised Children's Anxiety and Depression Scale [RCADS], RCADS Parent RCADS-P, Quality of Life Scale for Children [PedsQL], and PedsQL-Parents [PedsQL-P]) and some related features (pain intensity, mobile phone usage time, and headache duration). RESULTS: Of the 80 children participating in the study, 55 (68.8%) were girls and 25 (31.2%) were boys. It was determined that the original three-factor structure was not supported for TurPCS-C and TurPCS-P. Cronbach α value was 0.871 for TurPCS-C consisting of 12 items, and Cronbach α value was 0.890 for TurPCS-P consisting of 12 items. As the PedsQL score increased, there was a negative correlation (p<0.05, r=-0.575) in all three areas of TurPCS-C, and there was a positive correlation (p<0.05) among the scores from the RCADS scale and TurPCS-C. Similarly, there was a negative correlation with PedsQL-P and TurPCS-P and positive correlation with RCADS-P and TurPCS-P (p<0.05 for each). CONCLUSION: TurPCS-C and TurPCS-P are an evaluation instrument with sufficient validity and reliability, and it can be reliably used to examine pediatric patients with primary headache.

Progressive Multifocal Leukoencephalopathy in Children with Primary and Secondary Immune Deficiency.

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system that is caused by John Cunningham virus (JCV). It occurs almost exclusively in immunosuppressed individuals, for example, patients with AIDS and hematological and lymphoreticular malignancies. In this article, we present a review of the literature and 2 case reports with PML. The first report examines a 15-year-old male (who presented with dedicator of cytokinesis 8 deficiency) who was diagnosed as having PML based on characteristic magnetic resonance imaging (MRI) lesions and a positive PCR for JCV in cerebrospinal fluid. He was transferred for bone marrow transplantation after stabilization with therapy of maraviroc and cidofovir. The second report examines a 6-year-old male who presented with encephalitis and was also diagnosed with AIDS. He was diagnosed with PML and started treatment with cidofovir. His clinical status and MRI findings deteriorated rapidly. In immunosuppressive patients who developed encephalopathy, JCV ought to be considered.

Homozygous SQSTM1 nonsense variant identified in a patient with brainstem involvement.

In recent years, with advances in molecular genetics, many new mutations with various ataxic syndromes have been identified. Recently, homozygous sequestosome 1 (SQSTM1) gene variant with a progressive childhood-onset cerebellar ataxia, dystonia and gaze palsy was described. Here we describe a patient with progressive cerebellar ataxia and gaze palsy, as well as myoclonus, cognitive impairment and growth retardation with a homozygous SQSTM1 variant NM_003900.5:c.55G > T (p.Glu19*). Our case had brainstem lesions on brain magnetic resonance imaging that have not been previously reported. This novel finding expands the SQSTM1 gene-associated neuroradiologic spectrum. Homozygous SQSTM1 variant should be considered in the differential diagnosis in patients presenting with cerebellar findings, gaze palsy, and cognitive impairment to facilitate early diagnosis and genetic counseling.

Clinically isolated syndrome and multiple sclerosis in children: a single center study.

BACKGROUND AND OBJECTIVES: This study was conducted to determine the differences in clinical and radiological features at the first demyelinating event in children with clinically isolated syndrome (CIS) and multiple sclerosis (MS). METHODS: This was a single center retrospective cohort study of the children with CIS followed-up at Istanbul University Faculty of Medicine, Department of Pediatric Neurology, between 2010 and 2018. Children with CIS who were assessed at 3, 6, 12 and 24 months following their first identified demyelinating event were included. Demographic data, mode of presentation and the presence of the oligoclonal band in the cerebrospinal fluid (CSF) were abstracted from the medical records. Magnetic resonance imaging of the brain and spinal cord was analyzed for the location, number, size and gadolinium enhancement of the lesions. RESULTS: A total of 51 patients` data was assessed, 38 patients at a mean age of 12.3 years were enrolled in the study. Twenty-seven children (71%) evolved into clinically definite MS after a mean follow-up of 11 months. Older age at first demyelinating event and the presence of the oligoclonal band in CSF were tended to be more common in patients with MS than patients with CIS (p < 0.05). The increased number of T2-hyperintense lesion and the presence of the lesion in periventricular, infratentorial and corpus callosum were associated with a tendency for development of MS (p < 0.05). CONCLUSION: Older age at first demyelinating event, the presence of the oligoclonal band in CSF, the number and localization of T2-hyperintense lesion were associated with a tendency for development of MS.

Efficacy of Stiripentol and the Clinical Outcome in Dravet Syndrome.

Dravet syndrome is a rare and progressive epileptic encephalopathy of infancy. Stiripentol reduces the seizure frequency in patients with Dravet syndrome. We evaluated the clinical characteristics of patients with Dravet syndrome and their response to stiripentol. We retrospectively collected the data of 21 patients (11 females; mean age, 8.2 years, range: 5.4-15 years) with Dravet syndrome who were treated with stiripentol in our outpatient clinic between June 2016 and June 2017. Patients with seizure reduction ≥50% were considered responders. Most of our patients had severe (47%) or moderate (33%) cognitive disabilities, although 14% had mild cognitive disability. There was a significant difference in both status epilepticus and age between the groups with normal/mild versus severe/moderate neurocognitive prognoses. Of the patients, 85.7% were using stiripentol. The mean duration of stiripentol use was 41.2 months (range: 24-64 months). In 12 patients (57%), the seizure frequency decreased by more than 50%, and 2 of them were seizure-free. Status epilepticus was not recorded after stiripentol treatment in 8 of 11 patients with status epilepticus. Despite the small sample size, our results suggest that stiripentol has a favorable efficacy. In addition, considering the absence of status epilepticus after treatment and the negative effects of status epilepticus on cognitive development, early treatment should be initiated in SD patients, for whom disease control is difficult.

Efficacy of rufinamide in childhood refractory epilepsy.

Yildiz EP, Hizli Z, Bektas G, Ulak-Özkan M, Tatli B, Aydinli N, Çaliskan M, Özmen M. Efficacy of rufinamide in childhood refractory epilepsy. Turk J Pediatr 2018; 60: 238-243. Rufinamide has been used as a new antiepileptic drug in the treatment of drug-resistant epilepsy, in recent years. The objective of this study was to evaluate the reliability of rufinamide and its impact on seizure frequency in patients diagnosed with drug-resistant epilepsy, where seizures could not be controlled with `classical` antiepileptic drugs. We retrospectively reviewed the data of epileptic patients who were followed up between January 2004 and December 2014 in the Pediatric Neurology Department. Patients who were diagnosed with `drug resistant epilepsy` and treated with rufinamide were evaluated. Decrease in seizure frequency and drug side effects were assessed as parameters. A total of 38 patients (14 girls, 24 boys) with a mean age of 8.5 (range, 3.5-17) years were included in the study. The mean follow-up duration was 25.5 (23-29.5) months, while the mean maximal dose of rufinamide was 32.5 (28-42) mg/kg/day. Response to treatment was assessed by the reduction in frequency of seizures. The decrease was < 50% (essentially unresponsive to treatment) in 20 patients and 50­99% in 8 patients. Ten patients (26.3%) remained seizure-free. The response rate for tonic seizures was 50%. In drop/attacks seizures, this ratio was found as 73%, which was quite high. Patients with myoclonic and tonic-clonic seizures did not significantly benefit from rufinamide. The rate of patients with Lennox-Gestaut syndrome (LGS) who responded very well (reduction in seizure frequency > 50%) was 55.5%. In the LGS group, patients with drop/attacks showed the best response to treatment. Rufinamide was not effective in two patients diagnosed with Dravet syndrome. Rufinamide can be safely used in pediatric patients who use multiple antiepileptic drugs and are unresponsive to the treatment. It was seen to be effective especially in patients diagnosed with LGS and drop/attacks types of seizures.

Predictive factors of drug-resistant epilepsy in children presenting under 2 years of age: experience of a tertiary center in Turkey.

Population-based studies report that children with epilepsy have relatively better prognosis than those with an onset at infancy, though studies about this period are limited. We aimed to evaluate the etiology in infant epilepsy less than 2 years of age and foreseeable risk factors for anti-epileptic drug resistance. We evaluated the patients who were presented to the division of pediatric neurology in our university hospital with seizures when they were between 1 and 24 months of age and diagnosed as epilepsy. Two hundred and twenty-nine patients (110 male and 119 female) who were diagnosed between the ages of 1-24 months were included in the study. The etiologies were structural (n = 55;24%), genetic (n = 29;12.7%), metabolic (n = 27;11.7%), and infectious (n = 8;3.5%), and it was unknown in 110 patients (48%). One-hundred and forty (61%) patients met the criteria for drug-resistant epilepsy (DRE). Multivariate logistic regression analysis showed that developmental delay at onset (OR 3.9, 95% CI 1.22, 12.47, p = 0.021), multifocal epileptiform discharges (OR 2.8, 95% CI 1.1, 7.44, p = 0.031), and history of status epilepticus (OR 32.9, 95% CI 3.8, 285.35, p = 0.001) were strong predictive factors for DRE. The epilepsy in children under 2 years of age is highly resistant to the anti-epileptic drugs, which could be related to the history of status epilepticus, developmental delay at onset, and multifocal epileptiform discharges.

Spinal muscular atrophy with progressive myoclonic epilepsy linked to mutations in ASAH1.

Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME), a rare disorder caused by mutation in the ASAH1 gene, is characterized by progressive muscle weakness and intractable epilepsy. The literature about SMA-PME is very rare and most of the time limited to case reports. Mutation in the ASAH1 gene is also found in another rare syndrome which is Farber disease. We report a case of a 13.5-year-old girl with SMA-PME associated with ASAH1 gene mutation. She presented with progressive muscle weakness, tremor, seizure, and cognitive impairment. Clinical features and electrophysiological investigations revealed a motor neuron disease and generalized epilepsy. The marked difference in disease manifestations may explain why Farber and SMA-PME diseases were not suspected of being allelic conditions. SMA-PME cases with ASAH1 mutation could be treated using therapeutic studies regarding Farber disease. In patients with undefined PME or lower motor neuron disease cases, ASAH1 mutation scans should be studied.