Hereditary spastic paraplegia type 35 in a Turkish girl with fatty acid hydroxylase-associated neurodegeneration.

OBJECTIVES: The fatty acid 2-hydroxylase gene (FA2H) compound heterozygous or homozygous variants that cause spastic paraplegia type 35 (SPG35) (OMIM # 612319) are autosomal recessive HSPs. FA2H gene variants in humans have been shown to be associated with not only SPG35 but also leukodystrophy and neurodegeneration with brain iron accumulation. CASE PRESENTATION: A patient with a spastic gait since age seven was admitted to the paediatric metabolism department. She was born to consanguineous, healthy Turkish parents and had no family history of neurological disease. She had normal developmental milestones and was able to walk at 11 months. At age seven, she developed a progressive gait disorder with increased muscle tone in her lower limbs, bilateral ankle clonus and dysdiadochokinesis. She had frequent falls and deteriorating school performance. Despite physiotherapy, her spastic paraplegia was progressive. Whole exome sequencing (WES) identified a homozygous NM_024306.5:c.460C>T missense variant in the FA2H gene, of which her parents were heterozygous carriers. A brain MRI showed a slight reduction in the cerebellar volume with no iron deposits. CONCLUSIONS: Pathogenic variants of the FA2H gene have been linked to neurodegeneration with iron accumulation in the brain, leukodystrophy and SPG35. When patients developed progressive gait deterioration since early childhood even if not exhibited hypointensity in the basal ganglia detected by neuroimaging, FA2H-related neurodegeneration with brain iron accumulation should be ruled out. FA2H/SPG35 disease is characterised by notable clinical and imaging variability, as well as phenotypic diversity.

Ocular hemodynamics in epileptic children treated with antiepileptic drugs.

PURPOSE: To evaluate the quantitative measurements obtained for vessel density (VD) of the optic nerve head, macula, peripapillary retinal nerve fibre layer (p-RNFL) and total retinal thicknesses (Trt) by optical coherence tomography angiography (OCT-A) and the choroidal vascular structure using an image binarization method in children with epilepsy using three different antiepileptic drugs (AEDs) and to compare these measurements with healthy participants. METHODS: This observational, cross-sectional study included 124 patients divided into 4 groups: Group-1: patients receiving carbamazepine(n = 30), group-2: patients receiving levetiracetam (n = 31), group-3: patients receiving valproic acid (n = 32), and group 4: healthy controls (n = 31).A fully automated microstructural analysis of the VD of the retinal superficial capillary plexus (SCP), deep capillary plexus (DCP), and the choriocapillaris (CC) layers and radial peripapillary capillary, and Trt, p-RNFL thickness were analyzed by using OCT-A. Enhanced depth imaging (EDI)-OCT scans of the macula were obtained and the images were binarized using the ImageJ software. RESULTS: The mean age, gender distribution and the duration of epilepsy were similar in all groups. Evaluation of the p-RNFL thickness and perifoveal Trt between the groups showed a statistically significant difference in all quadrants.The p-RNFL thickness was lower in patients receiving carbamazepine and valproic acid. The lowest values of the luminal area and choroidal vascular index (CVI) were found in patients receiving valproic acid; comparison with matched healthy controls showed statistically significant differences. CONCLUSION: Valproic acid and carbamazepine are associated with thinning of the p-RNFL in epilepsy patients, but the macular and radial peripapillary VD were not affected.However, a reduction of choroidal vascular blood flow was found in epilepsy patients taking valproic acid.

Difficult to think about but easy to treat: scurvy.

OBJECTIVES: Severe vitamin C deficiency, or scurvy, presents as a syndrome of multisystem abnormalities associated with defective collagen synthesis and antioxidative functions. The many clinical features of scurvy lead to frequent misdiagnoses, as they can often point to other diseases, such as vasculitis, venous thrombosis and musculoskeletal disorders. As such, an extensive workup is recommended in cases in which scurvy is suspected. CASE PRESENTATION: A 21-month-old male patient and a 36-month-old female patient presented with difficulty in walking, painful joint movements, irritability, gingival hypertrophy and bleeding. After exhaustive investigations and risky invasive procedures, vitamin C deficiency was diagnosed in both cases, and the symptoms improved dramatically with vitamin C treatment. CONCLUSIONS: The importance of taking a dietary history in pediatric patients is highly recommended. In cases where scurvy is considered, serum ascorbic acid levels should be checked to confirm the diagnosis prior to conducting invasive tests.

Two Patients Diagnosed as Succinate Dehydrogenase Deficiency: Case Report.

Introduction: Succinate dehydrogenase deficiency, also known as mitochondrial complex II deficiency, is a rare inborn error of metabolism, accounting for approximately 2% of mitochondrial disease. Mutations in the four genes SDHA, B, C,and D have been reported resulting in diverse clinical presentations. The vast majority of clinically affected individuals reported in the literature harbor genetic variants within the SDHA gene and present with a Leigh syndrome phenotype, clinically defined as a subacute necrotizing encephalopathy. Case Report: Herein, we report the first case of a 7-year-old child who was diagnosed as having succinate dehydrogenase deficiency. The affected child presented at 1 year of age with encephalopathy and developmental regression following viral illnesses. MRI changes supported a clinical diagnosis of Leigh syndrome and c.1328C>Q and c.872A>C SDHA variants were identified as compound heterozygous. Mitochondrial cocktail treatment including L-carnitine, riboflavin, thiamine, biotin, and ubiquinone was started. Mild clinical improvement was observed after treatment. He is now unable to walk and speak. The second patient, a 21-year-old woman, presented with generalized muscle weakness, easy fatigability, and cardiomyopathy. Investigations revealed increased lactate level of 67.4 mg/dL (4.5-19.8) with repeatedly increased plasma alanine levels 1,272 µmol/L (200-579). We administered carnitine, coenzyme, riboflavin, and thiamine for empirical therapy with the suspicion of mitochondrial disease. Clinical exome sequencing revealed compound heterozygous variants NM_004168.4:c.1945_1946del (p.Leu649GlufsTer4) at exon 15 of the SDHA gene and NM_004168.4:c.1909-12_1909-11del at intron 14 of SDHA gene. Discussion and Conclusion: There are several very different presentations including Leigh syndrome, epileptic encephalopathy, and cardiomyopathy. Some cases present following viral illness; this feature is not specific to mitochondrial complex II deficiency and occurs in many other mitochondrial disease presentations. There is no cure for complex II deficiency, though some reported patients showed clinical improvement following riboflavin therapy. Riboflavin is not the only therapeutic intervention that is available to patients with an isolated complex II deficiency and various other compounds have shown promise in the treatment of symptoms, including L-carnitine and ubiquinone. Treatment alternatives such as parabenzoquinone EPI-743 and rapamycin are under study in the treatment of the disease.

Ocular perfusion characteristics of children with newly diagnosed epilepsy.

BACKGROUND: To investigate the vascular changes of the optic nerve head (ONH) and macula by using optical coherence tomography angiography (OCT-A), and also the choroidal vascular structure by using an image binarization tool in children with newly diagnosed epilepsy and to then compare these parameters with healthy subjects. METHODS: Forty-one epilepsy children and 36 healthy controls were included in this prospective and cross-sectional study.The radial peripapillary capillary (RPC) vessel density (VD) and macular foveal,parafoveal,perifoveal of superficial capillary plexus (SCP),deep capillary plexus (DCP) and choriocapillaris (CC) VD, and CC flow area were analyzed.Enhanced depth imaging (EDI) OCT scans of the macula were obtained and the images were binarized using the ImageJ software (National Institutes of Health, Bethesda, MD, USA).The subfoveal choroidal thickness (SFCT),the area of choroidal, luminal, and interstitial and the percentage of luminal area in the choroid (Choroidal vascular index (CVI)) were analyzed.We also evaluated the thickness of the peripapillary retinal nerve fiber layer (RNFL),the macular ganglion cell layer (GCL), and the inner plexiform layer (IPL). RESULTS: There was a significant decrease in the VD of the CC and the CC flow area in children with epilepsy compared to healthy subjects (p<0.05).However, the VD of the RPC, and of the SCP and DCP of the macula were similar between the two groups(p>0.05).The SFCT,choroidal area,luminal area, and CVI were statistically significant lower in children with newly diagnosed epilepsy compared to healthy subjects. CONCLUSION: This study has demonstrated that the choroidal perfusion from the microcirculation is lower in children with newly diagnosed epilepsy.The pathophysiology of epilepsy and neurodegenerative processes may also include this vascular dysfunction as one of the factors.

Re-examining the characteristics of pediatric multiple sclerosis in the era of antibody-associated demyelinating syndromes.

BACKGROUND: The discovery of anti-myelin oligodendrocyte glycoprotein (MOG)-IgG and anti-aquaporin 4 (AQP4)-IgG and the observation on certain patients previously diagnosed with multiple sclerosis (MS) actually have an antibody-mediated disease mandated re-evaluation of pediatric MS series. AIM: To describe the characteristics of recent pediatric MS cases by age groups and compare with the cohort established before 2015. METHOD: Data of pediatric MS patients diagnosed between 2015 and 2021 were collected from 44 pediatric neurology centers across Türkiye. Clinical and paraclinical features were compared between patients with disease onset before 12 years (earlier onset) and ≥12 years (later onset) as well as between our current (2015-2021) and previous (<2015) cohorts. RESULTS: A total of 634 children (456 girls) were enrolled, 89 (14%) were of earlier onset. The earlier-onset group had lower female/male ratio, more frequent initial diagnosis of acute disseminated encephalomyelitis (ADEM), more frequent brainstem symptoms, longer interval between the first two attacks, less frequent spinal cord involvement on magnetic resonance imaging (MRI), and lower prevalence of cerebrospinal fluid (CSF)-restricted oligoclonal bands (OCBs). The earlier-onset group was less likely to respond to initial disease-modifying treatments. Compared to our previous cohort, the current series had fewer patients with onset <12 years, initial presentation with ADEM-like features, brainstem or cerebellar symptoms, seizures, and spinal lesions on MRI. The female/male ratio, the frequency of sensorial symptoms, and CSF-restricted OCBs were higher than reported in our previous cohort. CONCLUSION: Pediatric MS starting before 12 years was less common than reported previously, likely due to exclusion of patients with antibody-mediated diseases. The results underline the importance of antibody testing and indicate pediatric MS may be a more homogeneous disorder and more similar to adult-onset MS than previously thought.

Infantile spasms: Knowledge, attitude, and practice of pediatricians in Turkey.

BACKGROUND: Infantile Spasms Syndrome (ISS) encompasses both West syndrome (WS), comprising epileptic spasms, psychomotor stagnation or regression and hypsarrhythmia, and also infants presenting with epileptic spasms who do not fulfill the triad of WS. OBJECTIVE: To investigate the knowledge, attitude, and practice regarding ISS among Turkish pediatricians and pediatric residents. METHODS: A cross-sectional study was conducted among pediatricians and pediatric residents from all regions of Turkey. Knowledge, attitude, and practice (KAP) about ISS were assessed using a questionnaire including 45 questions. RESULTS: Out of 174 participants, 91.4% of respondents thought that ISS was a type of epilepsy. The two most recognized etiologic causes were structural abnormalities (90.8%) and genetic disorders (90.2%). Infantile colic (78.7%) and gastroesophageal reflux (75.9%) were reported to be the most common confusing diagnoses in this study. Almost all the respondents agreed that EEG recordings should be obtained for a patient with suspected ISS. Half of the participants stated that steroids were the first choice for treatment. Nearly all participants agreed on referring a pediatric patient with suspected ISS to a pediatric neurologist. CONCLUSION: Our findings highlight the importance of medical education as awareness is critical for diagnosing ISS. To facilitate rapid diagnosis, it is also important to combine medical education with public action. To ensure a sufficient level of knowledge about epileptic spasms and ISS, a strategy based on the socio-cultural characteristics of each population should be developed.

Mild encephalopathy with reversible extensive white matter lesions in a child with acute adenoviral infection and a literature review.

BACKGROUND: Mild encephalopathy with a reversible splenial lesion (MERS) is a known clinical-radiological description. However, MERS with extensive lesions (MERS type-2) is rarely associated with adenovirus. There are only three published cases of MERS type-2 associated with adenovirus infection. CASE: We present a 10-year-old previously healthy girl who presented with speech difficulty and mild encephalopathy after three days of prodromal illness. The magnetic resonance imaging (MRI) revealed bilateral diffusion restriction in the parietal white matter, splenium and genu of the corpus callosum without mass effect and slight thickening at the splenium of corpus callosum with no contrast enhancement. With empirical and support treatment, her neurological examination was completely normal by the 18th hour. The nasopharyngeal respiratory adenoviral PCR resulted positive. She was discharged with total clinical and radiological resolution on the 10th day of admission. The case was diagnosed with MERS type-2 which is rarely associated with adenoviral infection. CONCLUSION: This report is the first case of adenovirus related MERS type-2 in a Turkish child. Pediatricians, child neurologists, child infection specialists and radiologists should recognize this condition to ensure appropriate diagnosis.

Differences in corpus callosum morphology between healthy adolescents and adolescents with migraine: a case control study

Background/aim: This study objected to compare the measurements of corpus callosum substructures of adolescents with migraine and healthy adolescents. Materials and methods: Materials and methodsIn a case-control design, adolescents aged 12­18 years with the diagnosis of migraine and healthy control group had brain magnetic resonance imaging examination. The CC dimensions including anteroposterior length, truncus, genu and splenium widths of the case and control groups were measured and compared. Results: The sample consisted of 188 adolescents, 109 girls (58.0%), and 79 boys (42.0%). Of these 87 (46.3%) were in the migraine group and 101 (53.7%) were in the healthy control group. The mean genu and splenium width of the migraine group were significantly lower than the control group (p = 0.024 and p = 0.01 respectively). Conclusion: The results of this study firstly demonstrated that CC splenium and genu widths were smaller in adolescents with migraine when compared to healthy adolescents. Our findings may contribute to enlighten migraine pathophysiology.

Impact of COVID-19 on serum melatonin levels and sleep parameters in children

Background/aim: This study aimed to analyze the serum melatonin levels and changes in sleep patterns in pediatric patients with coronavirus disease 2019 (COVID-19). Materials and methods: This study was designed as a descriptive, cross-sectional study. Serum melatonin levels and sleep parameters of children with the diagnosis of COVID-19 who had mild and moderate disease (i.e., COVID-19 group) were compared with those of children admitted with non-COVID-19 nonspecific upper respiratory tract infection (i.e., control group). The sleep disturbance scale for children (SDSC) questionnaire was applied to the participants> primary caregivers to analyze their sleep patterns at present and six months before symptom onset and to investigate the impact of COVID-19 on sleep patterns. Results: The entire study cohort consisted of 106 patients. The COVID-19 group included 80 patients, while the control group consisted of 26 patients. The mean serum melatonin levels were 136.72 pg/mL and 172.63 pg/mL in the COVID-19 and control groups, respectively (p = 0.16). There was no significant difference between the groups in terms of 6 subcategories of the SDSC questionnaire regarding the present time and 6 months before symptom onset. The total SDSC scores were also similar in two different evaluation time points described above (p = 0.99) Conclusions: We conclude that COVID-19 did not impact the sleep parameters of children. Serum melatonin levels of all patients were higher than the reference range; however, they were higher in the non-COVID-19 patient group than the COVID-19 group. Since serum melatonin levels were higher than the reference values in children with COVID-19, and this disease is significantly less morbid in children, melatonin may have protective effects against COVID-19.

Relationship between headache and Internet addiction in children

Background/aim: We aimed to investigate Internet addiction in pediatric patients with migraine- and tension-type headache in this study. Materials and methods: Among our 200 subjects, 103 had migraine-type headache and 97 had tension-type headache. Results: Headache triggered by computer use was more common in the migraine-type headache group. There was no difference between the Internet addiction scale score of the two groups. The Internet addiction scale scores of the patients were found to differ depending on the aim and duration of computer use. Internet addiction was found in six (6%) patients. Internet addiction prevalence was 3.7% and 8.5% in the two groups, respectively. Conclusion: The prevalence of Internet addiction in children with recurrent headache was lower than that found in their peers in Turkey, possibly due to avoidance of computer use as a headache trigger. This finding raises the question of whether migraine- or tension-type headaches actually prevent Internet addiction.

High monocyte level and low lymphocyte to monocyte ratio in autism spectrum disorders.

Objective: This study aims to investigate the level of peripheral blood mononuclear cells and their ratios which may point to the immunological mechanisms involved in the etiopathogenesis of ASD. Method: The complete blood count parameters of the 45 ASD cases were compared with those of healthy controls.Childhood Autism Rating Scale (CARS) was performed to measure the disease severity. Results: The monocytes of ASD group were significantly higher; and the lymphocyte-to-monocyte ratio (LMR) was lower than the controls'. LMR and neutrophil-to-lymphocyte ratio were found to be predictors of ASD. The decrease in LMR (B: -0.744; P=0.035; CI: -1.431 to -0.056) and the increase in age (B: 0.432; P=0.045; CI: 0.011-0.853) were related to high CARS scores in linear regression analyses. Conclusions: The results of this study support the role of altered immune cell counts and ratios in ASD. A high monocyte level and low LMR may have diagnostic values in autism.

Subacute sclerosing panencephalitis in a child with recurrent febrile seizures.

Subacute sclerosing panencephalitis (SSPE) is a devastating disease of the central nervous system (CNS) caused by persistent mutant measles virus infection. The diagnosis of SSPE is based on characteristic clinical and EEG findings and demonstration of elevated antibody titres against measles in cerebrospinal fluid. Subacute sclerosing panencephalitis can have atypical clinical features at the onset. Herein, we report an unusual case of subacute sclerosing panencephalitis in a child with recurrent febrile seizures. The disease progressed with an appearance of myoclonic jerks, periodic high amplitude generalized complexes on EEG, and elevated titers of measles antibodies in cerebrospinal fluid leading to the final diagnosis of subacute sclerosing panencephalitis.