Involuntary Movements in Cobalamin Deficiency.

OBJECTIVE: Neurologic problems are frequently described in infants with nutritional vitamin B12 (cobalamin) deficiency.Major neurologic consequences of infantile cobalamin deficiency include delays or regression in neurodevelopment and the occurrence of involuntary movements METHODS: We reviewed the medical records of infants with cobalamin deficiency and divided infants with involuntary movements into two groups as those, who developed involuntary movements during vitamin B12 supplementation (Group I) and those, who developed involuntary movements prior to supplementation therapy (Group II). RESULTS: We evaluated a total of 32 infants with the diagnosis of cobalamin deficiency. Involuntary movements were observed in 12 out of 32 infants. Group I and Group II consisted of 6 infants each. Of the infants with involuntary movements, five were exclusively breastfed until the time of diagnosis. The majority of infants in Group II had choreoathetoid movements; twitching and myoclonus in the face, tongue, and lips, and tremor in the upper extremities. These involuntary movements disappeared in one to three weeks after clonazepam therapy. In Group I; shaking movements, myoclonus, tremor, and twitching or protrusion were observed in patients' hands, feet, tongue, and lips on the 3rd-5th day of cobalamin supplementation. These involuntary movements disappeared within 5-12 days of clonazepam therapy. CONCLUSION: Recognition of nutritional cobalamin deficiency is important to perform a differential diagnosis of the condition from seizures or other causes of involuntary movements and avoid aggressive therapy and over treatment.

Effect of Chronic Valproic Acid Use on Anterior Cerebral Blood Flow of Children with Idiopathic Generalized Epilepsy.

OBJECTIVE: Cerebral blood flow has been blamed as a factor in the negative effect of antiepileptic drugs on neurocognition. This study aimed to investigate whether valproic acid (VPA), used for the treatment of idiopathic generalized epilepsy (IGE), causes a change in cerebral blood flow in children. METHODS: Included in this study were 33 children who were receiving VPA for IGE and 34 age-matched controls. Doppler and spectral measurements in common carotid artery (CCA), left and right internal CA (ICA) and external CA (ECA), anterior cerebral artery (ACA) and middle cerebral artery (MCA) were performed and the maximum velocity (VM), end-diastolic velocity (EDV), resistive index (RI), pulsatility index (PI) and flow rate (FR) were calculated. RESULTS: The mean age of drug and control groups were 9.33 plus or minus 2.11, and 9.74 plus or minus 2 years, respectively. Follow-up of patients was 17.7 plus or minus 3.2 months. The period of VPA treatment was 17.4 plus or minus 3.4 months. No statistically significant differences were found between control and VPA group for the VM, EDV, RI, PI, and FR values obtained from the bilateral ICA, ACA, and MCA. CONCLUSIONS: The results showed that VPA in therapeutic doses did not affect anterior cerebral blood flow. However according to result, it is still difficult to conclude that neurocognitive deterioration is not observed in patients receiving VPA.

The management of elevated intracranial pressure and sinus vein thrombosis associated with mastoiditis: the experience of eighteen patients.

PURPOSE: Cerebral sinus vein thrombosis (CSVT) associated with acute mastoiditis is a rare complication of acute otitis media. Elevated intracranial pressure (ICP) frequently occurs secondary to CSVT. The study aims to review the 5 years of experience of four medical centres to treat sigmoid sinus thrombosis and elevated intracranial pressure in children. METHODS: Patients with CSVT that developed secondary mastoiditis from 2016 through 2021 were evaluated in four centres from Turkey. Patients diagnosed with a preceding or synchronous mastoiditis and intracranial sinus thrombosis were included in the study. Magnetic resonance imaging (MRI), magnetic resonance venography (MRV), ICP measurements, ophthalmological examinations, thrombophilia studies and treatments for increased ICP have also been recorded. RESULTS: The study group comprises 18 children. Twelve patients were diagnosed with right-sided, six patients with left-sided sinus vein thrombosis. All of the patients had ipsilateral mastoiditis. The most common presenting symptoms were fever, ear pain, headache, visual disorders and vomiting. The most encountered neurologic findings were papilledema, strabismus and sixth cranial nerve palsy. ICP was over 20 cm H2O in eleven patients. Anticoagulant treatment, antibiotics, pressure-lowering lumbar puncture and lumboperitoneal shunt were among the treatment modalities. CONCLUSION: Elevated ICP can damage the brain and optic nerve irreversibly, without treatment. For treating elevation of ICP associated with cerebral sinus thrombosis, pressure-lowering lumbar puncture (LP), acetazolamide therapy, optic nerve sheath fenestration (ONSF) and cerebrospinal fluid (CSF)-shunting procedures are suggested in case of deteriorated vision.

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.

Vanishing white matter disease with different faces.

PURPOSE: The goal of this study was to better understand vanishing white matter (VWM) disease, which is one of the most common hereditary white matter disorders, and its relationship to radiologic features, genetic analyses, and clinical findings. METHODS: We performed a study on 11 patients to describe the clinical and neuroimaging features of VWM. Patients were grouped into "infantile," "early childhood," and "juvenile" based on their onset age. EIF2B1-5 genes encoding five subunits of eukaryotic translation initiation factor 2B (eIF2B) were analyzed in all patients with clinically suspected VWM disease. RESULTS: In brain magnetic resonance imaging (MRI), all patients showed white matter abnormalities with various degrees. The initial clinical presentation in five of patients was ataxia, with severe refractory epilepsy in three patients. In children with infantile-onset VWM, a rapid deterioration of motor function was detected, and the frequency of epilepsy was higher. Two patients showed manifestations of end-stage VWM disease, and one of them had chronic subdural hematoma. One of our patients and his father were diagnosed with Brugada syndrome. Sequencing of the exons and exon-intron boundaries of the EIF2B1-5 genes revealed mutations in the genes EIF2B5 (5 cases), EIF2B3 (3 cases), and EIF2B4 (2 cases). We also found a novel mutation in one patient: c.323_325delGAA in the EIF2B1 gene. CONCLUSIONS: In this study, in addition to classical clinical and radiological findings, we wanted to emphasize that we may be confronted with refractory epilepsy (early infancy), cardiac problems, and intracranial complications that may occur in advanced stages.

Are diagnostic magnetic resonance patterns life-saving in children with biotin-thiamine-responsive basal ganglia disease?

BACKGROUND: Biotin-thiamine responsive basal ganglia disease (BTBGD) is an autosomal recessive disorder caused by mutations in the SLC19A3 gene and characterized by recurrent sub-acute episodes of encephalopathy that typically starts in early childhood. This study describes characteristic clinical and magnetic resonance imaging (MRI) findings of six cases of BTBGD diagnosed with newly identified mutations and genetically confirmed, with very early and different presentations compared to cases in the previous literature. METHODS: Six patients referred from different centers with similar clinical findings were diagnosed with BTBGD with newly identified mutations in the SLC19A3 gene. Two novel mutations in the SLC19A3 gene were identified in two patients at whole exome sequencing analysis. The clinical characteristics, responses to treatment, and electroencephalography (EEG) and MRI findings of these patients were examined. The other four patients presented with similar clinical and cranial MRI findings. These patients were therefore started on high-dose biotin and thiamine therapy, and mutation analysis concerning the SLC19A3 gene was performed. Responses to treatment, clinical courses, EEG findings and follow-up MRI were recorded for all these patients. RESULTS: Age at onset of symptoms ranged from 1 to 3 months. The first symptoms were generally persistent crying and restlessness. Seizures occurred in five of the six patients. Cranial magnetic resonance imaging revealed involvement in the basal ganglia, brain stem, and the parietal and frontal regions in general. The first two patients were siblings, and both exhibited a novel mutation of the SLC19A3 gene. The third and fourth patients were also siblings and also exhibited a similar novel mutation of the SLC19A3 gene. The fifth and sixth patients were not related, and a newly identified mutation was detected in both these subjects. Three novel mutations were thus detected in six patients. CONCLUSION: BTBGD is a progressive disease that can lead to severe disability and death. Early diagnosis of treatable diseases such as BTBGD is important in order to prevent long-term complications and disability.

Evaluation ofserum free carnitine/acylcarnitine levels and left ventricular systolic functions in children with idiopathic epilepsy receiving valproic acid.

OBJECTIVES: In the study, the effect of valproic acid on serum free/acylcarnitine levels and left ventricular systolic function in pediatric patients with idiopathic epilepsy receiving valproic acid was investigated. PATIENTS AND METHODS: Patients receiving valproic acid treatment for six months between January 2012 and December 2012 were evaluated. Blood samples were obtained from the participants twice (pretreatment and the sixth month of treatment) and serum-free and acylcarnitine levels (from C2 to C18:1-OH) were measured using tandem mass spectrometry. Cardiac functions (ejection fraction, shortening fraction, cardiac output, left ventricular systolic and diastolic diameters, left atrial diameter, aortic diameter, cardiac output, and myocardial performance index) were evaluated by echocardiography simultaneously. RESULTS: A total of fourty patients, 23 female (57.5%) and 17 male (42.5%), with the diagnosis of idiopathic epilepsy and receiving valproic acid monotherapy were studied. Comparison of serum-free and acylcarnitine levels measured pretreatment and sixth month of treatment revealed a decrease in average C0 and C5:1 (respectively p < 0.001, p = 0.013) and an increase in C2, C3, C5-OH, C8:1 and C4-DC levels (respectively p < 0.001, p < 0.001, p = 0.019, p = 0.013, p < 0.001). Other serum acylcarnitine levels did not change significantly (p > 0.05). No difference was observed in concurrent echocardiographic measurements of left ventricular systolic function (p > 0.05). CONCLUSION: The study demonstrated that valproic acid treatment results in low levels of free carnitine and changes in some acylcarnitine subgroups but has no influence on left ventricular systolic function.

Semiological and psychiatric characteristics of children with psychogenic nonepileptic seizures: Gender-related differences.

PURPOSE: To compare semiological characteristics, precipitating stress factors and psychiatric diagnoses of girls and boys with psychogenic nonepileptic seizures (PNESs). METHODS: We retrospectively reviewed medical records of children diagnosed with PNES and who also underwent psychiatric evaluation. Sixty-two children (44 girls, 18 boys), aged 11-18 years (mean age 14.19 ± 1.96 years) were included. Diagnosis of PNES was established by any of the following: (1) observation of the seizure by a neurologist and routine EEG, (2) evaluation of amateur video records of the typical seizure and routine EEG, or (3) video-EEG monitoring. Psychiatric examinations of patients were performed using the Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version (KSADS-PL). RESULTS: Tremor was the most prevalent ictal motor sign in both girls and boys. Atonic falls and longer episodes were significantly more frequent in girls than boys. Tonic-clonic-like movements of the extremities were significantly more prevalent in boys than girls. No gender-specific differences were observed in the rates of semiological types. Academic underachievement was the most prevalent precipitating stressor for boys, and was significantly more prevalent in boys than girls. The rate of major depression was significantly higher in girls than boys. The most prominent diagnosis in boys was attention deficit/hyperactivity disorder, and this was significantly more prevalent than in girls. CONCLUSION: PNES in males of juvenile age may be a distinct entity from that in girls with different semiological and psychogenic correlates. Consideration of these gender-related differences may be beneficial for the early recognition and treatment of PNES.

Evaluation of Nerve Conduction Studies in Obese Children With Insulin Resistance or Impaired Glucose Tolerance.

The aim of the study was to investigate nerve conduction studies in terms of neuropathic characteristics in obese patients who were in prediabetes stage and also to determine the abnormal findings. The study included 69 obese adolescent patients between April 2009 and December 2010. All patients and control group underwent motor (median, ulnar, tibial, and peroneal) and sensory (median, ulnar, sural, and medial plantar) nerve conduction studies and sympathetic skin response test. Sensory response amplitude of the medial plantar nerve was significantly lower in the patients with impaired glucose tolerance and insulin resistance. To our knowledge, the present study is the first study demonstrating the development of sensory and autonomic neuropathy due to metabolic complications of obesity in adolescent children even in the period without development of diabetes mellitus. We recommend that routine electrophysiological examinations be performed, using medial plantar nerve conduction studies and sympathetic skin response test.

Charles Bonnet syndrome after herpes simplex encephalitis.

Visual impairment associated with Charles Bonnet syndrome is rarely reported in childhood. We describe a child who presented with visual hallucinations and postinfectious bilateral retrobulbar optic neuritis. The patient had undergone acyclovir therapy for 3 weeks because of herpes encephalitis. Four days after therapy was completed, he experienced visual impairment in both eyes. He manifested a bilateral decrease in visual acuity, with normal funduscopic findings. The patient experienced visual hallucinations for about 1 week, and then experienced total loss of vision. During his hallucinations, the patient did not exhibit behavioral changes or cognitive impairment. The visual hallucinations included unfamiliar children hiding under his bed, and he spoke to someone whom he did not know. Magnetic resonance imaging indicated bilateral optic nerve hyperintensity on T(2)-weighted and contrast-enhanced images. The patient received corticosteroid therapy for his retrobulbar optic neuritis, and his vision returned to normal after 1 month. Although rare, visual impairment can be associated with complex visual hallucinations indicative of Charles Bonnet syndrome.

Pyridoxine and pyridostigmine treatment in vincristine-induced neuropathy.

Vincristine is a commonly used antineoplastic drug and frequently causes neurotoxicity. Here the authors report a 4-year-old boy with acute lymphoblastic leukemia in whom vincristine-induced peripheral and cranial neuropathy developed during remission induction therapy. The patient seemed to benefit from pyridoxine and pyridostigmine therapy greatly and this therapy is recommended in patients with severe vincristine-induced neuropathy.

Severe hypothyroidism caused by hepatic hemangioendothelioma in an infant of a diabetic mother.

Hemangioendotheliomas can express type 3 iodothyronine deiodinase and cause severe hypothyroidism. The risk of congenital malformations such as vertebral and cardiac abnormalities in infants of diabetic mothers is higher than in babies of healthy women. Here we report an infant of a diabetic mother with hypothyroidism caused by liver hemangioendothelioma. Consumptive hypothyroidism should be an indicator to search for a vascular tumor in infants. Supranormal doses of L-thyroxine might be required for normalization of thyroid function until the tumor involutes or is resected.