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.

Early diagnostic clues of mucolipidosis type II: Significance of radiological findings.

Mucolipidosis type-II (ML-II) is an ultra-rare disorder caused by deficiency of N-acetylglucosaminyl-1-phosphotransferase enzyme due to biallelic pathogenic variants in GNPTAB gene. There are a few known about the natural history of ML-II. In this study, we presented the natural course of 24 patients diagnosed with ML-II. Mean age at diagnosis was 9.3 ± 5.7 months. All patients had coarse face, developmental delay, and hypotonia. The mean survival time was 3.01 ± 1.4 years. The oldest patient was 6.5 years old. Twelve patients died due to lung infection and respiratory failure. We observed early and significant radiological findings of ML-II were different from typical dysostosis multiplex such as femoral cloaking, rickets-like changes, and talocalcaneal stippling. These are significant findings observed in the fetal or newborn period which is considered to be highly characteristic of ML-II and disappears in the first year. Cloaking, rickets-like changes, and stippling were not observed in patients older than three months of age and this suggests that these findings disappear within the first year. These radiological features can be used as important clues for diagnosis. We detected eight different pathogenic variants in GNPTAB gene, three of them were novel.

Posttraumatic epilepsy in critically ill children with traumatic brain injury.

PURPOSE: The aim of this study was to determine the clinical, laboratory, and radiological factors related with posttraumatic epilepsy (PTE). METHODS: The study is a multicenter descriptive cross-sectional cohort study. Children who followed up for TBI in the pediatric intensive care unit between 2014 and 2021 were included. Demographic data and clinical and radiological parameters were recorded from electronic case forms. All patients who were in the 6-month posttraumatic period were evaluated by a neurologist for PTE. RESULTS: Four hundred seventy-seven patients were included. The median age at the time of trauma was 66 (IQR 27-122) months, and 298 (62.5%) were male. Two hundred eighty (58.7%) patients had multiple traumas. The mortality rate was 11.7%. The mean duration of hospitalization, pediatric intensive care unit hospitalization and mechanical ventilation, Rotterdam score, PRISM III score, and GCS at admission were higher in patients with epilepsy (p < 0.05). The rate of epilepsy was higher in patients with severe TBI, cerebral edema on tomography and clinical findings of increased intracranial pressure, blood transfusion in the intensive care unit, multiple intracranial hemorrhages, and intubated patients (p < 0.05). In logistic regression analysis, the presence of intracranial hemorrhage in more than one compartment of the brain (OR 6.13, 95%CI 3.05-12.33) and the presence of seizures (OR 9.75, 95%CI 4.80-19.83) were independently significant in terms of the development of epilepsy (p < 0.001). CONCLUSIONS: In this multicenter cross-sectional study, intracranial hemorrhages in more than one compartment and clinical seizures during intensive care unit admission were found to be independent risk factors for PTE development in pediatric intensive care unit patients with TBI.

The outcome of 41 Late-Diagnosed Turkish GA-1 Patients: A Candidate for the Turkish NBS.

BACKGROUND: Glutaric aciduria type 1(GA-1) is an inherited cerebral organic aciduria. Untreated patients with GA-1 have a risk of acute encephalopathic crises during the first 6 years of life. In so far as GA-1 desperately does not exist in Turkish newborn screening (NBS) program, most patients in our study were late-diagnosed. METHOD: This study included 41 patients diagnosed with acylcarnitine profile, urinary organic acids, mutation analyses in the symptomatic period. We presented with clinical, neuroradiological, and molecular data of our 41 patients. RESULTS: The mean age at diagnosis was 14.8 ± 13.9 (15 days to 72 months) and, high blood glutaconic acid, glutarylcarnitine and urinary glutaric acid (GA) levels in 41 patients were revealed. Seventeen different mutations in the glutaryl-CoA dehydrogenase gene were identified, five of which were novel. The patients, most of whom were late-diagnosed, had a poor neurological outcome. Treatment strategies made a little improvement in dystonia and the frequency of encephalopathic attacks. CONCLUSION: All GA-1 patients in our study were severely affected since they were late-diagnosed, while others show that GA-1 is a treatable metabolic disorder if it is diagnosed with NBS. This study provides an essential perspective of the severe impact on GA-1 patients unless it is diagnosed with NBS. We immediately advocate GA-1 to be included in the Turkish NBS.

Factors affecting epilepsy prognosis in patients with tuberous sclerosis.

PURPOSE: We aimed to determine the characteristics of epileptic seizures that significantly affect the cognitive functions of 83 patients followed with tuberous sclerosis complex (TSC), their resistance to treatment and risk factors causing this resistance. MATERIALS-METHODS: In order to determine the prognosis, the seizure-free/seizure-controlled group and the group with refractory seizures were compared. In addition, risk factors affecting cognitive functions in the patients were determined. RESULTS: There was a statistical significance between the presence of a history of seizures in the neonatal period, the age of onset of seizures being less than 2 years of age, autism, status epilepticus, Lennox-Gastaut syndrome (LGS), presence of infantile spasm, generalization of the electroencephalography (EEG) findings, the number of tubers in cerebral imaging being more than three and refractory seizures (p < 0.05). Statistically significant relationship was found between presence of a history of seizures in the neonatal period, the age of onset of seizures, autism, LGS, presence of infantile spasm, presence of status epilepticus history, history of using more than three antiepileptic drugs, generalization of EEG findings, presence of SEGA in cerebral imaging, number of tubers being more than three and the patient's mental retardation (p < 0.05). CONCLUSION: In logistic regression analysis, the age of the seizure onset being less than 2 years of age, the presence of autism and number of tubers being more than three in cerebral magnetic resonance imaging (MRI) are determined to be the risk factors that most likely to increase the seizures to be more resistant.

A homozygote novel L451W mutation in CECR1 gene causes deficiency of adenosine deaminase 2 in a pediatric patient representing with chronic lymphoproliferation and cytopenia.

Deficiency of Adenosine Deaminase 2 (DADA2) is a monogenic autoinflammatory disorder characterized by livedo reticularis, skin ulcers, subcutaneous rash, aphthous ulcers, and leukocytoclastic vasculitis, neurological signs such as early onset stroke and polyneuropathy. A minority of DADA2 patients suffer from severe cytopenia and lymphoproliferation. Herein, we report an adolescent patient, followed up as having a hematological disorder for many years, eventually diagnosed as having DADA2. In view of the presence of elevated acute phase reactants, hepatosplenomegaly, low IgM level, lymphopenia, anemia, and neutropenia, and a subtle neurological involvement we considered DADA2 diagnosis. The diagnosis was confirmed by identification of a novel L451W mutation in CECR1 gene. The patient has been successfully treated with etanercept, monthly intravenous immunoglobulin replacement, and low-dose methylprednisolone. In conclusion, although the absence of skin and neurological findings, low IgM levels, and persistent lymphopenia should lead the physicians to consider DADA2 in patients with particularly complicated hematological abnormalities.

MEDNIK syndrome with a frame shift causing mutation in AP1S1 gene and literature review of the clinical features.

MEDNIK syndrome is an autosomal recessive rare disease as one of the most recently described copper metabolism disorder characterized by intellectual disability, ichthyosis, hearing loss, peripheral neuropathy, enteropathy and keratodermia. Here in, we reported a case presented with ichthyosis and intellectual disability with MEDNIK syndrome that confirmed by mutation analysis in a Turkish child. She was finally diagnosed with MEDNIK syndrome by clinical findings, which were confirmed by molecular genetic testing. Sequencing of AP1S1 gene showed a homozygous insertion c.364dupG (NM_001283.4), which is predicted to cause a frameshift of the reading frame (p.D122Gfs*18). To our knowledge, this is the first case of MEDNIK syndrome from Turkey. Diagnosis of MEDNIK syndrome is still challenging and we hope that this case will contribute to further understanding.

Risk factors affecting prognosis in infantile spasm.

AIM: To assess risk factors that affect epilepsy prognosis and neurodevelopmental outcome and response to treatment in patients diagnosed with infantile spasm. METHODS: In this study, demographics, treatment modalities, etiologies, risk factors affecting neurodevelopmental outcome and epilepsy prognosis were assessed retrospectively at the end of a minimum 24-months follow-up of 104 patients diagnosed with infantile spasm from May 2012 to October 2015. RESULTS: Neonatal seizure during neonatal period, abnormal head circumference, young age at the time of presentation and early gestational age, symptomatic etiology, abnormal initial examination and abnormal development test at the time of diagnosis, consanguinity, the medical center where treatment was started in the second center or beyond and magnetic resonance imaging finding were found to be statistically significant for poor prognosis in terms of neurodevelopment (p < 0.05). Abnormal initial examination and abnormal development test both at the time of diagnosis and at the end of follow-up, consanguineous parents, young age at the time of presentation, symptomatic etiology, a family history of mental retardation and epilepsy were found to be statistically significant for poor prognosis in terms of epilepsy. Administration of adrenocorticotropic hormone (ACTH) for seizure control was statistically significant compared to other antiepileptic drugs (p < 0.05). CONCLUSION: Infantile spasm is an age-related epileptic encephalopathy, and it was observed that it is still catastrophic, and that the most important factor affecting prognosis of epilepsy is etiology, age at the time of presentation and the medical center where treatment was started in the second center or beyond.

Tyrosinemia type 1 and irreversible neurologic crisis after one month discontinuation of nitisone.

Tyrosinemia type I is an autosomal recessively inherited metabolic disease of tyrosine metabolism due to the deficiency of fumarylacetoacetate hydrolase. Clinical manifestations include hepatic failure, cirrhosis, hepatocellular carcinoma, renal fanconi syndrome, and neurologic crisis. With the introduction of 2-(2-nitro-4-trifluoro-methylbenzyol)-1,3 cyclohexanedione treatment the prognosis improved with reduced rate of complications. "Neurologic crisis" of tyrosinemia type I is a rare complication seen after discontinuation of treatment characterized with anorexia, vomiting, and hyponatremia in the initial phase continuing with paresthesia and paralysis of the extremities and the diaphragm. Here, we report a tyrosinemia type I patient who admitted to the hospital with nonspecific symptoms such as vomiting, anorexia, weakness, and restlessness only after one month discontinuation of nitisone and diagnosed as neurological crisis.

Neurofibromatosis type 1 and cardiac manifestations.

OBJECTIVE: Cardiac manifestations of neurofibromatosis type 1 (NF1) may include hypertension, congenital heart disease, and hypertrophic cardiomyopathy. The aim of this study was to evaluate cardiac abnormalities in patients with NF1. METHODS: Sixty-five NF1 patients (mean age: 9±4.48 years) were retrospectively studied. Standard electrocardiography and echocardiography were performed in all patients. RESULTS: Cardiac abnormalities were found in 11 of the 65 patients (15.3%). Five patients had mitral valve regurgitation, 2 patients had secundum atrial septal defect, 1 patient had pulmonary valvular stenosis, 1 patient had ventricular septal defect, 1 patient had tricuspid valve regurgitation, and 1 patient had aortic valve regurgitation. CONCLUSION: Cardiac abnormalities have potential long-term hemodynamic consequences that justify an early diagnosis. Thus, for any patient with NF1, a cardiologic assessment is mandatory at the time of diagnosis and with regular follow-up intervals.

Hashimoto's encephalopathy: four cases and review of literature.

Hashimoto's encephalopathy is a rare clinically heterogenous condition consisting of encephalopathy, seizures and variable neurological and psychiatric manifestations, accompanied by high titres of serum antithyroid antibodies. We described the clinical and laboratory findings of four children (aged 8-17 years) with Hashimoto's encephalopathy. The clinical features of three patients at presentation included refractory epilepsy, and confusion, and one patient presented with behavioral and cognitive changes. During their presentation, two of them were in euthyroid, and the others were in hypothyroid status. All patients manifested increased antithyroid antibodies. Two patients improved with steroid treatment. The others responded to plasmapheresis instead of corticosteroid treatment. Physicians' awareness of this complication is of great importance because most patients respond dramatically to the treatment.

A Retrospective Cohort Study of Traumatic Brain Injury in Children: A Single-Institution Experience and Determinants of Neurologic Outcome.

Introduction: Traumatic brain injury (TBI) has become a significant cause of death and morbidity in childhood since the elucidation of infectious causes within the last century. Mortality rates in this population decreased over time due to developments in technology and effective treatment modalities. Aim of the study: This retrospective cohort study aimed to describe the volume, severity and mechanism of all hospital-admitted pediatric TBI patients at a university hospital over a 5-year period. Material and Methods: This was a single-center, retrospective cohort study including 90 pediatric patients with TBI admitted to a tertiary care PICU. The patients' demographic data, injury mechanisms, disease and trauma severity scores, initiation of enteral nutrition and outcome measures such as hospital stay, PICU stay, duration of mechanical ventilation, mortality, and Glasgow Outcome Scale (GOS) were also recorded. Late enteral nutrition was defined as initiation of enteral feeding after 48 hours of hospitalization. Results: Of the 90 patients included in the cohort, 60% had mild TBI, 21.1% had moderate TBI and 18.9% had severe TBI. Their mean age was 69 months (3-210 months). TBI was isolated in 34 (37.8%) patients and observed as a part of multisystemic trauma in 56 (62.2%). The most commonly involved site in multisystemic injury was the thorax (33.3%). The length of hospitalization in the late enteral nutrition group was significantly higher than that in the early nutrition group, while the PICU stay was not significantly different between the two groups. The multiple logistic regression analysis found a significant relationship between GOS-3rd month and PIM3 score, the presence of diffuse axonal injury and the need for CPR in the first 24 h of hospitalization. Conclusion: Although our study showed that delayed enteral nutrition did not affect neurologic outcome, it may lead to prolonged hospitalization and increased hospital costs. High PIM3 scores and diffuse axonal injury are both associated with worse neurologic outcomes.

Fatal encephalitis associated with novel influenza A (H1N1) virus infection in a child.

A 4-year-old girl presented with fever, coughing, and vomiting; followed by unconsciousness. Magnetic resonance imaging showed hyperintense changes in the thalami bilaterally, brain stem, cerebellum, and subcortical cortex. Novel influenza A (H1N1) virus was identified by polymerase chain reaction in patient's nasopharyngeal swab specimen. We reported a rare case of clinically severe, novel influenza A-associated encephalitis. Novel influenza A should be considered in the differential diagnosis in patients with seizures and mental status changes, especially during an influenza outbreak.

Hypohidrosis and hyperthermia during topiramate treatment in children.

Topiramate is one of the newer generation antiepileptic drugs with a beneficial clinical effect on various seizure types. In this study, we present the clinical findings of hypohidrosis and hyperthermia with topiramate in pediatric patients. The data were collected retrospectively on 173 patients diagnosed as epilepsy on topiramate treatment, and hypohidrosis-related symptoms induced by topiramate were found in 22 patients. Their mean age was 64.45 +/- 56.63 months. The mean duration of topiramate treatment was 7.09 +/- 2.46 months, and the mean dose was 5.37 +/- 1.75 mg/kg/day. All of the patients complained of hypohidrosis and hyperthermia. Six (27.2%) of them had facial flushing, 4 (18.1%) had heat sensation and only 1 (4.5%) had lethargy. Hypohidrosis-related symptoms resolved after discontinuation of the medication. In conclusion, children treated with topiramate should be cautioned regarding these potential adverse effects and advised to avoid its use during the hot summer season.

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.

Neurological complications of pandemic influenza (H1N1) in children.

The aim of this study was to determine the clinical characteristics of children demonstrating neurological complications with pandemic influenza (H1N1). We reviewed the medical and laboratory records of all children who were hospitalized with neurological symptoms and who had proven influenza virus infection by reverse transcriptase-polymerase chain reaction on nasal and throat swabs. Eight children aged between 10 months and 7 years had neurological complications due to pandemic influenza (H1N1) and five of them were female. Four of them were previously healthy; there was chronic renal failure (CRF) in one and neurologic disease in three patients. Seven of them had seizure and altered consciousness. Seven of them were followed in pediatric intensive care units. We performed lumbar puncture in four patients and their cerebrospinal fluid examinations showed pleocytosis in one and no cell in three specimens. Neuroimaging was performed in four patients and three of them had abnormalities. We diagnosed aseptic meningitis in one, acute disseminated encephalomyelitis (ADEM) in one, acute necrotizing encephalopathy (ANE) in one, meningoencephalitis in one, and status epilepticus in four patients. All patients were treated with oseltamivir and antiepileptic drugs. One patient with CRF died; four previously healthy patients recovered fully, and three patients who had neurologic disorder returned to their previous neurological status. In conclusion, during pandemic influenza (H1N1) infection, neurological complications may be seen in addition to the respiratory infection. The type of neurological involvement may be variable such as triggering seizure, aseptic meningitis, encephalitis, ADEM, and ANE. Neurological complications frequently recover fully especially in previously healthy children, but sometimes a severe clinical course occurs.

Guillain-Barré syndrome in children.

Guillain-Barré syndrome (GBS) is one of the reasons of acute polyneuropathy causing severe morbidity and mortality. Forty-six patients with GBS were included in our study. Clinical, laboratory, electrophysiological and prognostic features of the patients were evaluated retrospectively. Patients were divided into two groups. Group A consisted of children who attained a full recovery within 2 months from onset of the disease; group B consisted of children who experienced complete or partial recovery beyond 2 months from onset of the disease. Acute inflammatory demyelinating polyradiculoneuropathy was found in 56.5% of patients and axonal form in 43.5% patients. Antecedent events were found in 28 (60.9%) patients. Five patients (10.8%) needed mechanical ventilation and one patient (2.1%) died. Poor outcome was related with clinic stage and electrophysiological subtypes (axonal form). In our study, poor prognostic factors were related with clinic stage and electrophysiological subtypes (axonal form).

Evaluation of sixteen children with pseudotumor cerebri.

Pseudotumor cerebri (PTC) is a clinical condition characterized by signs and symptoms of increased intracranial pressure, such as headache and papilledema. A total of 16 patients diagnosed with PTC [12 (75%) female; 4 (25%) male] were included in the study. The age of onset of symptoms was 123.4 +/- 34.3 months (range: 60-168 months). Obesity was found in four (25%) of them. Two patients had venous sinus thrombosis, two had corticosteroid withdrawal, and one had posttraumatic PTC. The most common symptom was headache, recorded in 93.8% of the patients. All patients were treated medically. Two patients in our group also required a lumboperitoneal shunt. In conclusion, PTC in children is rare. Both papilledema and sixth nerve palsy resolved rapidly with treatment. However, children can sustain loss of visual field and visual acuity despite treatment.

Albendazole-induced dystonic reaction: a case report.

Drug-induced dystonic reactions are a common presentation to the emergency department and typically occur with drugs like chlorpromazine, haloperidol and metoclopramide. There are no reports in the literature of dystonic reaction caused by albendazole. We report a case of albendazole-induced acute dystonic reaction whose symptoms completely resolved after the discontinuation of the drug. Even though dystonia side effects of albendazole are rare, it can induce an alarming dystonia in some sensitive children. The mechanism of dystonia is unclear.