Evaluation of the Patients with the Diagnosis of Pontocerebellar Hypoplasia: A Multicenter National Study.

Pontocerebellar hypoplasia (PCH) is a heterogeneous group of neurodegenerative disorders characterized by hypoplasia and degeneration of the cerebellum and pons. We aimed to identify the clinical, laboratory, and imaging findings of the patients with diagnosed PCH with confirmed genetic analysis. We collected available clinical data, laboratory, and imaging findings in our retrospective multicenter national study of 64 patients with PCH in Turkey. The genetic analysis included the whole-exome sequencing (WES), targeted next-generation sequencing (NGS), or single gene analysis. Sixty-four patients with PCH were 28 female (43.8%) and 36 (56.3%) male. The patients revealed homozygous mutation in 89.1%, consanguinity in 79.7%, pregnancy at term in 85.2%, microcephaly in 91.3%, psychomotor retardation in 98.4%, abnormal neurological findings in 100%, seizure in 63.8%, normal biochemistry and metabolic investigations in 92.2%, and dysmorphic findings in 51.2%. The missense mutation was found to be the most common variant type in all patients with PCH. It was detected as CLP1 (n = 17) was the most common PCH related gene. The homozygous missense variant c.419G > A (p.Arg140His) was identified in all patients with CLP1. Moreover, all patients showed the same homozygous missense variant c.919G > T (p.A307S) in TSEN54 group (n = 6). In Turkey, CLP1 was identified as the most common causative gene with the identical variant c.419G > A; p.Arg140His. The current study supports that genotype data on PCH leads to phenotypic variability over a wide phenotypic spectrum.

Optic neuritis in Turkish children and adolescents: A multicenter retrospective study.

BACKGROUND: Various etiologies may underlie optic neuritis, including autoantibody-mediated disorders described in the last decade. We re-examined demographic, clinical, laboratory features and prognostic factors in pediatric patients with autoimmune optic neuritis according to current knowledge. METHODS: Cases of pediatric ON from 27 centers in Türkiye diagnosed between 2009 and 2022 were included for retrospective evaluation. RESULTS: The study included 279 patients, 174 females and 105 males, with a female-to-male ratio of 1.65. The average age at onset was 12.8 ± 3.4 years, and mean follow-up, 2.1 years (range: 1-12.1 years). Patients <10 years old were grouped as "prepubertal" and those ≥10 years old as "others". The diagnoses made at the end of follow-up were multiple sclerosis associated optic neuritis (n = 90, 32.3 %), single isolated optic neuritis (n = 86, 31 %), clinically isolated syndrome (n = 41, 14.7 %), myelin oligodendrocyte glycoprotein antibody associated optic neuritis (n = 22, 7.9 %), and relapsing isolated optic neuritis (n = 18, 6.5 %). Predominant diagnoses were myelin oligodendrocyte glycoprotein antibody associated optic neuritis and acute disseminated encephalomyelitis associated optic neuritis in the prepubertal group and multiple sclerosis associated optic neuritis in the older group. Recurrences were observed in 67 (24 %) patients, including 28 with multiple sclerosis associated optic neuritis, 18 with relapsing isolated optic neuritis, 11 with myelin oligodendrocyte glycoprotein antibody associated optic neuritis, 8 with aquaporin-4 antibody related optic neuritis, and 2 with chronic relapsing inflammatory optic neuropathy. Recurrences were more common among female patients. Findings supporting the diagnosis of multiple sclerosis included age of onset ≥ 10 years (OR=1.24, p = 0.027), the presence of cranial MRI lesions (OR=26.92, p<0.001), and oligoclonal bands (OR=9.7, p = 0.001). Treatment in the acute phase consisted of intravenous pulse methylprednisolone (n = 46, 16.5 %), pulse methylprednisolone with an oral taper (n = 212, 76 %), and combinations of pulse methylprednisolone, plasmapheresis, or intravenous immunoglobulin (n = 21, 7.5 %). Outcome at 12 months was satisfactory, with 247 out of 279 patients (88.5 %) demonstrating complete recovery. Thirty-two patients exhibited incomplete recovery and further combination treatments were applied. Specifically, patients with relapsing isolated optic neuritis and aquaporin-4 antibody related optic neuritis displayed a less favorable prognosis. CONCLUSION: Our results suggest optic neuritis is frequently bilateral in prepubertal and unilateral in peri­ or postpubertal patients. Age of onset 10 or older, presence of oligoclonal bands, and brain MRI findings reliably predict the development of multiple sclerosis. The risk of developing multiple sclerosis increases mostly during the second and third years of follow-up. Relapsing isolated optic neuritis remains a separate group where the pathogenesis and outcome remain unclear. Investigation of predisposing and diagnostic biomarkers and long follow-up could help to define this group.

Clinical and Genetic Spectrum of Myotonia Congenita in Turkish Children.

BACKGROUND: Myotonia congenita is the most common form of nondystrophic myotonia and is caused by Mendelian inherited mutations in the CLCN1 gene encoding the voltage-gated chloride channel of skeletal muscle. OBJECTIVE: The study aimed to describe the clinical and genetic spectrum of Myotonia congenita in a large pediatric cohort. METHODS: Demographic, genetic, and clinical data of the patients aged under 18 years at time of first clinical attendance from 11 centers in different geographical regions of Türkiye were retrospectively investigated. RESULTS: Fifty-four patients (mean age:15.2 years (±5.5), 76% males, with 85% Becker, 15% Thomsen form) from 40 families were included. Consanguineous marriage rate was 67%. 70.5% of patients had a family member with Myotonia congenita. The mean age of disease onset was 5.7 (±4.9) years. Overall 23 different mutations (2/23 were novel) were detected in 52 patients, and large exon deletions were identified in two siblings. Thomsen and Becker forms were observed concomitantly in one family. Carbamazepine (46.3%), mexiletine (27.8%), phenytoin (9.3%) were preferred for treatment. CONCLUSIONS: The clinical and genetic heterogeneity, as well as the limited response to current treatment options, constitutes an ongoing challenge. In our cohort, recessive Myotonia congenita was more frequent and novel mutations will contribute to the literature.

Peripheral facial nerve palsy in children: clinical manifestations, treatment and prognosis.

Background: Sudden onset of unilateral weakness of the upper and lower muscles of one side of the face is defined as peripheral facial nerve palsy. Peripheral facial nerve palsy is often idiopathic and sometimes it could be due to infectious, traumatic, neoplastic, and immune causes. This study aimed to report the clinical manifestation, evaluation, and prognosis in children with peripheral facial nerve palsy. Methods: 57 children under 18 years of age diagnosed with peripheral facial nerve palsy at Çukurova University, Balcali Hospital, between January 2018 and September 2021, were included in the study. Results: The mean age of the children at the time of diagnosis was 9.6 ± 7, 4 years. Thirty-two (56.1%) of the patients were female and 25 (43.9%) were male. A total of 57 patients were diagnosed with peripheral facial nerve palsy and categorized into many groups by etiology: idiopathic Bell's palsy in 27 (47.5%), infectious in 11 (19.2%), traumatic in 6 (10.5%), and others (due to congenital, immune, neoplastic, Melkersson-Rosenthal syndrome, drug toxicity, and iatrogenic causes) in 13 (22.8%). Forty-six of the children achieved full recovery under oral steroids within 1-7 months. Four patients with acute leukemia, myelodysplastic syndrome, Mobius syndrome and trauma did not recover and two patients (schwannoma, trauma) showed partial improvement. Five patients could not come to follow-up control. Conclusion: Peripheral facial nerve palsy is a rare condition in children with different causes. It could be idiopathic, congenital, or due to infectious, traumatic, neoplastic, and immune reasons. So, when a child presents with facial palsy, a complete clinical history and a detailed clinical examination are recommended. Giving attention to the red flag is very important. Peripheral facial nerve palsy in children is considered to have a good prognosis.

Clinical, radiological, and genetic variation in pontocerebellar hypoplasia disorder and our clinical experience.

Pontocerebellar hypoplasia (PCH) constitutes a heterogeneous neurodegenerative/neurodevelopmental disorder of the pons and cerebellum with onset in the prenatal period. Our study aimed to present different clinical and radiological manifestations of our genetically diagnosed PCH patients. METHOD:  Six patients were enrolled in this study from September 2018 to March 2021. All the clinical radiological and genetic investigations were done at Cukurova University Medical School. RESULTS: Five children were diagnosed genetically and categorized under one of the types of PCH (type 10,7,11). Homozygous mutations in CLP1 In PCH type 10, TOE1 in PCH type 7, and TBC1D23 in PCH type 11 were respectively detected. Pateint with PCH type 11 and female patient with PCH type 7 could walk and speak few words. Male patient with PCH type 7 had disorder of sex development. CONCLUSION: According to our study, PCH is a rare neurodegenerative disease, although some types are static as PCH11 male gender and PCH7 female gender. Some clinical features are specific to a definite type. PCH7 express disorders of sex development most apparent in 46 XY. Some ethnic groups could express distinct subtypes. PCH10 is seen in the Turkish population. Radiological imaging is beneficial in pre-diagnosis; all the patients had different pons and cerebellar hypoplasia degrees. Genetic testing like whole exome sequencing -next-generation sequencing is essential in setting the definite diagnosis and determining the type/subtype of PCH.

Evaluation of immunization status in patients with cerebral palsy: a multicenter CP-VACC study.

Children with chronic neurological diseases, including cerebral palsy (CP), are especially susceptible to vaccine-preventable infections and face an increased risk of severe respiratory infections and decompensation of their disease. This study aims to examine age-appropriate immunization status and related factors in the CP population of our country. This cross-sectional prospective multicentered survey study included 18 pediatric neurology clinics around Turkey, wherein outpatient children with CP were included in the study. Data on patient and CP characteristics, concomitant disorders, vaccination status included in the National Immunization Program (NIP), administration, and influenza vaccine recommendation were collected at a single visit. A total of 1194 patients were enrolled. Regarding immunization records, the most frequently administrated and schedule completed vaccines were BCG (90.8%), hepatitis B (88.9%), and oral poliovirus vaccine (88.5%). MMR was administered to 77.3%, and DTaP-IPV-HiB was administered to 60.5% of patients. For the pneumococcal vaccines, 54.1% of children received PCV in the scope of the NIP, and 15.2% of children were not fully vaccinated for their age. The influenza vaccine was administered only to 3.4% of the patients at any time and was never recommended to 1122 parents (93.9%). In the patients with severe (grades 4 and 5) motor dysfunction, the frequency of incomplete/none vaccination of hepatitis B, BCG, DTaP-IPV-HiB, OPV, and MMR was statistically more common than mild to moderate (grades 1-3) motor dysfunction (p = 0.003, p < 0.001, p < 0.001, p < 0.00, and p < 0.001, respectively). Physicians' influenza vaccine recommendation was higher in the severe motor dysfunction group, and the difference was statistically significant (p = 0.029).Conclusion: Children with CP had lower immunization rates and incomplete immunization programs. Clinicians must ensure children with CP receive the same preventative health measures as healthy children, including vaccines. What is Known: • Health authorities have defined chronic neurological diseases as high-risk conditions for influenza and pneumococcal infections, and they recommend vaccines against these infections. • Children with CP have a high risk of incomplete and delayed immunization, a significant concern given to their increased healthcare needs and vulnerability to infectious diseases. What is New: • Influenza vaccination was recommended for patients hospitalized due to pneumonia at a higher rate, and patients were administered influenza vaccine more commonly. • Children with CP who had higher levels of motor dysfunction (levels 4 and 5) were more likely to be overdue immunizations.

Evaluation of ultrasonographic optic nerve sheath diameter and central retinal artery Doppler indices by point-of-care ultrasound in pediatric patients with increased intracranial pressure.

BACKGROUND: Measurement of the optic nerve sheath diameter (ONSD) with point-of-care ultrasound (POCUS) is a non-invasive and radiation-free technique that can be used to assess increased intracranial pressure (ICP). Ophthalmic artery and central retinal artery Doppler indices can be used like transcranial Doppler to evaluate increased ICP. This study aims to examine the diagnostic value of ONSD measurements and central retinal artery Doppler indices in the evaluation of pediatric patients with increased ICP. METHODS: This was a prospective, case-controlled single center study. The study group was comprised of a total of 38 pediatric patients with increased ICP and the control group included 19 healthy children. Ophthalmic ultrasound was performed and ONSD and central retinal artery Doppler indices were measured. RESULTS: The mean age of the study group was 80.84 ± 65.12 months. The mean ONSD was 5.9 ± 0.8 (3.6-8.1) mm in the study group and the mean resistive index (RI) was 0.71 ± 0.08 (min:0,55-max:1) and was significantly greater than the control group (p < 0.001 and p < 0.001, respectively). In terms of predicting increased ICP, the ONSD measurement was the strongest parameter, with its area under the curve: 0.767 (95 percent confidence interval: 0.68-0.85). In the study group, the cut-off value for ONSD was 5.8 mm (66 percent sensitivity, 100 percent specificity) and the cut-off value for RI was 0.68 (63 percent sensitivity, 83 percent specificity). CONCLUSIONS: Point-of-care ultrasound is a noninvasive and important tool in pediatric intensive care units. Our study is significant as one of the few pediatric studies where central retinal artery Doppler indices are evaluated in addition to OSND, in patients with increased ICP.

Optic Nerve Sheath Diameter and Retinal Artery Resistive Index Measurements with Bedside Ophthalmic Ultrasound in Pediatric Patients with Pseudotumor Cerebri Syndrome.

Pseudotumor cerebri syndrome (PTCS) is characterized by raised intracranial pressure (ICP) with no neuroradiological abnormalities. Ocular ultrasound has been in use to measure optic nerve sheath diameter (ONSD), and retinal artery Doppler indices have been used for indirect assessment of ICP by pediatric intensivists. Here, we aimed to evaluate the correlation of the lumbar puncture (LP) opening pressure with the ultrasonographic ONSD and retinal resistive index (RRI) measures in patients with PTCS. And we wanted to find an answer to the following question: Can ultrasonographic ONSD measures serve as a follow-up tool in patients with PTCS? A prospective, single-center, case-control study was performed by pediatric intensive care and pediatric neurology departments. A total of 7 patients with PTCS were evaluated as patient group and 15 healthy children were evaluated as control group. The mean age of patient group was 138.8 ± 43.7 months. The mean right ONSD was 6.7 ± 0.5 mm and the mean left ONSD was 6.7 ± 0.6 mm. The mean right RRI value was 0.73 ± 0.03 and the mean left RRI was 0.73 ± 0.09. For the patient group, ONSD and RRI values of both eyes were statistically significant higher values than for the control group. The mean LP opening pressure was 56.57 ± 16.36 cmH 2 O. We detected strong, positive, and statistically significant correlations between the LP opening pressure and ONSD baseline measures for both the right eye ( r = 0.882, p = 0.009) and the left eye ( r = 0.649, p = 0.004). There was no correlation between opening pressure in LP and RRI measurements. We detected a statistically significant decrease in the right ONSD and left ONSD values and visual analog scale scores at the third-month follow-up. Our study results demonstrate that ultrasonographic ONSD measurements can be used as a noninvasive tool for assessment of the ICP at first admission and can be used as a follow-up tool in PTSC patients.

Levetiracetam Treatment-Associated Acute Rhabdomyolysis in an Adolescent.

Etiology of rhabdomyolysis includes hereditary muscle enzyme deficiencies, trauma, viral infections, excessive exercise, hypothyroidism, and medications such as colchicine, lithium, and statins. Several studies have reported that various antiepileptic drugs may induce rhabdomyolysis. Levetiracetam is one of the antiepileptic drugs implicated in the etiology of rhabdomyolysis. Herein, we present a case of rhabdomyolysis in an adolescent treated with levetiracetam. We wanted to draw attention to the increasing trend of levetiracetam-associated rhabdomyolysis frequency in pediatric patients.

Two novel missense mutations in nonketotic hyperglycinemia.

Nonketotic hyperglycinemia (OMIM no. 605899) is an autosomal recessively inherited glycine encephalopathy, caused by a deficiency in the mitochondrial glycine cleavage system. Here we report 2 neonates who were admitted to the hospital with complaints of respiratory failure and myoclonic seizures with an elevated cerebrospinal fluid/plasma glycine ratio and diagnosed as nonketotic hyperglycinemia. We report these cases as 2 novel homozygous mutations; a missense mutation c.593A>T (p.D198 V) in the glycine decarboxylase gene and a splicing mutation c.339G>A (Q113Q) in the aminomethyltransferase gene were detected. We would like to emphasize the genetic difference of our region in inherited metabolic diseases once again.

Factors affecting epilepsy development and epilepsy prognosis in cerebral palsy.

A study was conducted between November 2006 and October 2009 to determine the factors predicting the presence and prognosis of epilepsy in patients with cerebral palsy. We enrolled 2 groups of patients: 42 with cerebral palsy in group 1 and 56 patients with cerebral palsy and epilepsy in group 2. The subjects in group 2 were considered to have good epilepsy prognosis if they were free of seizures for the previous year; otherwise they were considered to have poor epilepsy prognosis. In group 2, neonatal epilepsy, family history of epilepsy, and moderate to severe mental retardation were significantly higher than in group 1 (P < 0.05). In univariate analysis, neonatal seizures, epileptic activity as measured by electroencephalography, and polytherapy were found to be predictors of poor epilepsy prognosis. Additionally, the need for long-term medication to control seizures unfavorably affects prognosis. In logistic regression analysis, neonatal seizure and interictal epileptic activity in electroencephalography were found to be independent predictors of poor epilepsy outcome. In addition, logistic regression analysis revealed that increasing age reduces the success of epilepsy treatment. Neonatal seizures, family history of epilepsy, and mental retardation were found to be important and independent predictors of development of epilepsy in patients with cerebral palsy.