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.

Ketogenic diet experience at Ondokuz Mayis University.

BACKGROUND AND OBJECTIVES: The ketogenic diet (KD) is a special diet that is rich in fat, and poor in protein and carbohydrates. KD is the first-line treatment for some metabolic disorders, and is also used in resistant epilepsy, autism, cancer, Parkinson, Alzheimer's diseases, and stroke. The KD team consists of a doctor (child neurologist), nurse, and dietician. After diet adjustment, family training, metabolic tests, consultations, material supply, the initial and follow-up stages are performed by this team. METHOD: Retrospective data analyses of patients followed at ketogenic diet outpatient clinic were made. RESULTS: Fourteen patients (6F, 8M) continued their KD treatment, and nine (4F, 5M) of them stopped the treatment. KD treatment duration for those who continued KD was between 1 and 24 months (mean 7.1, median 4), and KD duration of those who left was between 0.5 and 12 months (mean 5, median 5). Three patients became seizure-free, seven patients had ≥ 50% reduction in their seizures, and four patients had no change in seizure. Anti-epileptic drugs could be reduced in five patients. Improvement in perception and social behaviour of the children was expressed by the families. Although one of the patients was seizure-free and the others had 75% decrease in seizures, they left KD due to frequent infection and family desire. The other seven patients who left KD had no changes in their seizures, but four of them continued KD in less than 2 months, and two of them only for 15 days. Weight loss, family problems, infection, and financial concerns were the reasons for them leaving. CONCLUSION: Today, although the approach is changing, KD still comes to mind for the most resistant, troubled patients. Stopping the patients' seizures, opening their perceptions, and reducing the medications are satisfactory results. We wanted to share our small group of patients and their results in the hope of expanding the ketogenic diet.

Neuroinfluenza: evaluation of seasonal influenza associated severe neurological complications in children (a multicenter study).

PURPOSE: Although influenza primarily affects the respiratory system, in some cases, it can cause severe neurological complications. Younger children are especially at risk. Pediatric literature is limited on the diagnosis, treatment, and prognosis of influenza-related neurological complications. The aim of the study was to evaluate children who suffered severe neurological manifestation as a result of seasonal influenza infection. METHODS: The medical records of 14 patients from six hospitals in different regions of the country were evaluated. All of the children had a severe neurological manifestations related to laboratory-confirmed influenza infection. RESULTS: Median age of the patients was 59 months (6 months-15.5 years) and nine (64.3%) were male. Only 4 (28.6%) of the 14 patients had a comorbid disease. Two patients were admitted to hospital with influenza-related late complications, and the remainder had acute complication. The most frequent complaints at admission were fever, altered mental status, vomiting, and seizure, respectively. Cerebrospinal fluid (CSF) analysis was performed in 11 cases, and pleocytosis was found in only two cases. Neuroradiological imaging was performed in 13 patients. The most frequent affected regions of nervous system were as follows: cerebellum, brainstem, thalamus, basal ganglions, periventricular white matter, and spinal cords. Nine (64.3%) patients suffered epileptic seizures. Two patients had focal seizure, and the rest had generalized seizures. Two patients developed status epilepticus. Most frequent diagnoses of patients were encephalopathy (n = 4), encephalitis (n = 3), and meningitis (n = 3), respectively. The rate of recovery without sequelae from was found to be 50%. At discharge, three (21.4%) patients had mild symptoms, another three (21.4%) had severe neurological sequelae. One (7.1%) patient died. The clinical findings were more severe and outcome was worse in patients <5 years old than patients >5 years old and in patients with comorbid disease than previously healthy group. CONCLUSION: Seasonal influenza infection may cause severe neurological complications, especially in children. Healthy children are also at risk such as patients with comorbid conditions. All children who are admitted with neurological findings, especially during the influenza season, should be evaluated for influenza-related neurological complications even if their respiratory complaints are mild or nonexistent.

Hyperekplexia: A Single-Center Experience.

BACKGROUND: Hyperekplexia is a rare neurogenetic disorder that is classically characterized by an exaggerated startle response to sudden unexpected stimuli. This study aimed to determine clinical and genetic characteristics of our patients with hyperekplexia. METHODS: The age of onset and diagnosis, familial and perinatal history, clinical course, complications, metabolic screening tests, magnetic resonance imaging (MRI), medications, neuropsychometric evaluations, and gene mutations of patients diagnosed with hyperekplexia were reviewed retrospectively. RESULTS: All hyperekplexia patients had displayed neonatal excessive startle response and muscle stiffness, which we accepted as the major form of the disorder. Sixteen patients had mutations in genes associated with hyperekplexia. The ages at clinical diagnosis and genetic confirmation ranged from newborn to 16 years old and from 2.5 to 19 years, respectively. Nine patients (56.25%) were initially misdiagnosed with epilepsy. Seven patients (43.75%) carried a diagnosis of intellectual disability, defined here as a total IQ <80. Delayed gross motor development was detected in 4 patients (25%), and speech delay was reported in 3 (18.75%). Mutations in GLRA1 (NM_000171.4) and SLC6A5 (NM_004211.5) were identified in 13 (81.25%) and 3 patients (18.75%), respectively. Fifteen of the 16 patients (93.75%) showed autosomal recessive inheritance. Only 1 patient (6.25%) showed autosomal dominant inheritance. CONCLUSION: Although hyperekplexia is a potentially treatable disease, it can be complicated by delayed speech and/or motor acquisition and also by intellectual disability. This study shows that hyperekplexia is not always a benign condition and that all patients diagnosed with hyperekplexia should be evaluated for neuropsychiatric status and provided with genetic testing.

The relationship between migraine and right-to-left shunt in children.

UNLABELLED: Migraine is the most common headache in childhood, and there are some reports that suggest the relationship between migraine and right-to-left shunt. The aim of this study was to evaluate the frequency of right-to-left shunt in children with migraine with aura and compare it with children with migraine without aura, and in healthy children. In a cross-sectional case-control study, we assessed 20 children with migraine with aura, 20 migraine without aura and 20 healthy age, and gender-matched control group. We determined the frequency of right-to-left shunt by transcranial doppler with contrast and transthoracic echocardiography without contrast. The dopplers and echocardiograms were performed blindly by the same examiners during headache-free periods. The presence of right-to-left shunt was found in 13/20 patients with migraine with aura compared with five of 20 migraine without aura and four of 20 control subjects. The frequency of right-to-left shunt in migraine with aura was statistically different from the other two groups (P < 0.005). There was no association between right-to-left shunt and frequency of attacks, duration and intensity of attacks, uni/bilateral occurence, familial occurrence, gender and age of patients. CONCLUSION: our findings suggest possible association of migraine with aura and right-to-left shunt. It seems that right-to-left shunt does not influence the clinical features of migraine.

Single gene, two diseases, and multiple clinical presentations: Biotin-thiamine-responsive basal ganglia disease.

AIM: To present seven new genetically confirmed cases of biotin-thiamin-responsive basal ganglia disease (BTBGD) with different clinical and brain magnetic resonance imaging (MRI) characteristics. MATERIAL AND METHODS: Genetic variants, clinical presentations, brain MRI findings, treatment response, and prognosis of seven selected patients with BTBGD, diagnosed with SLC19A3 mutations were described. RESULTS: Among seven patients diagnosed with BTBGD, two had early infantile form, four had classic childhood form, and one was asymptomatic. Four different homozygous variants were found in the SLC19A3. Two patients with early infantile form presented with encephalopathy, dystonia, and refractory seizure in the neonatal period and have different variants. Their MRI findings were similar and pathognomonic for the early infantile form. Three siblings had same variants: one presented seizure and encephalopathy at the age of 4 months, one presented seizure at 14 years, and another was asymptomatic at 20 years. Only one of them had normal MRI findings, and the others MRI findings were similar and suggestive of the classic form. Other two siblings; one of them presented with developmental delay, seizure, and dystonia at 18 months and the other presented with subacute encephalopathy and ataxia at 20 months. Their MRI findings were also similar and suggestive of the classic form. CONCLUSION: BTBGD may present with dissimilar clinical characteristics or remain asymptomatic for a long time period even in a family or patients with same variants. Brain MRI patterns may be important for the early diagnosis of BTBGD that would save children's lives.

An epileptic case with mosaic ring chromosome 6 and 6q terminal deletion.

Ring chromosomes are rare chromosome disorders that arise usually de novo. Children with ring chromosome 6 have a wide range of intellectual functioning and congenital anomalies. We report an epileptic case of a 10-year-old boy to be mild psychomotor retardation and dysmorphic traits including microcephaly, brachycephaly, flat occiput, large and apparently low set ears, and bilateral syndactyly between his second and third fingers with mosaic ring chromosome 6 and 6q terminal deletion. Peripheral chromosome and fluorescent in situ hybridisation (FISH) analysis of the patient showed mos46,XY,r(6)(p24;q26),del(6)(q27) [30]/46,XY,del(6)(q27) [20] de novo. We presented the patient in the light of literature because the mosaic ring 6 and 6q terminal deletion was different caryotypically from other mosaic ring 6 patients.

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.

Cerebral thrombosis associated with heterozygous factor V Leiden mutation and high lipoprotein(a) level in a girl with factor XIII deficiency.

A 5-year-old girl in whom the diagnosis of inherited factor XIII deficiency was established at the age of 1 day presented with cryptic tonsillitis along with drowsiness and an abrupt occurrence of getting left interior cross eyed. While an intracranial hemorrhage was expected, cerebral imaging studies surprisingly revealed multiple sino venous thrombosis. In prothrombotic screening studies she and her father were both found to be heterozygous for factor V Leiden mutation along with having elevated levels of lipoprotein(a). Low-molecular-weight heparin was started. Ventriculoperitoneal shunt was applied because of persistence of increased intracranial pressure. Thrombosis disappeared and blood flow was normalized by the end of 2 months and the patient was discharged on coumadin therapy as being well. We would like to report this unusual case and to discuss the possible effects of two major genetic prothrombotic risk factors on inherited bleeding tendency or vice versa.

Cerebral vasculitis in a child with Henoch-Schönlein purpura and familial Mediterranean fever.

In this case report, a 10-year-old girl with Henoch-Schönlein purpura (HSP) with severe central nervous system involvement and also having familial Mediterranean fever (FMF) is presented.

Intravenous immunoglobulin for Guillain-Barré syndrome: how effective?

Guillain-Barré syndrome is an acute inflammatory demyelinating neuropathy characterized by progressive symmetric polyradiculoneuritis, predominantly manifested by weakness and areflexia. In this article, we report our findings in 25 children treated with intravenous immunoglobulin and compare them with the remaining 30 children who received supportive care only. Only supportive care was given to 30 children who were not able to receive intravenous gammaglobulin because of shortcomings in intravenous gammaglobulin availability owing to a poor import during those years. Twenty-five patients were treated with intravenous gammaglobulin; they received intravenous gammaglobulin 0.4 g/kg/day for 5 consecutive days. Seventeen of the intravenous gammaglobulin group had received intravenous gammaglobulin within 10 days after the first symptoms, and eight of them had received intravenous gammaglobulin after the first 10 days. The average time elapsed for the symptoms to reach the maximum level was 6.9 (range 4-12) days in patients receiving intravenous gammaglobulin in the first 10 days, and it was significantly shorter than the time elapsed for the supportive care group (6.9 versus 8.8 days, respectively) (P < .05). Admission to the hospital after the first symptom, disability grade, time to improve in disability grade, the period of hospitalization, and mortality were not different in the intravenous gammaglobulin and supportive care groups (P > .05). Our suggestion for intravenous gammaglobulin treatment in Guillain-Barré syndrome is that if the patient has risk factors for respiratory insufficiency, then the treatment should be started. We more confidently carry out the follow-up of these patients after the results of this study. In conclusion, although it has been reported that intravenous gammaglobulin facilitates improvement in the disease and the decrease in mortality in children with Guillain-Barré syndrome, it has been mentioned in some studies that the intravenous gammaglobulin treatment was not better than supportive care, as in our study. However, further studies are essential to determine when intravenous gammaglobulin should be given to patients having which clinical and laboratory findings.

Pseudotumor cerebri complicating measles: a case report and literature review.

A previously healthy 8-year-old girl patient was referred with the complaints of severe headache associated with nausea and vomiting. Three weeks prior to her admission, she had measles manifested with fever and typical skin eruptions. Fundoscopic examination revealed bilateral swollen optic discs with tortuous blood vessels. Other physical examinations were unremarkable, except for photophobia. Lumbar puncture demonstrated a cerebrospinal fluid opening pressure of 30 cm H(2)O, no cells, normal levels of glucose and protein. Serum measles immunoglobulin M level was elevated (183 AU). Our further investigations revealed that the patient had pseudotumor cerebri (PTC) following measles infection.

Increased intracranial pressure due to chronic active Epstein-Barr virus infection.

Central nervous system involvement in Epstein-Barr virus infection usually presents as meningitis, encephalitis, or encephalomyelitis, mostly in the acute form of the disease. In chronic active infection, the clinical situation may also resemble acute infection as well findings of chronic inflammation such as calcification. This report presents an 8-year-old female with chronic active Epstein-Barr virus infection and encephalitis complicated by increased intracranial pressure who was managed with repeated lumbar punctures and medical treatment including anti-edema and antiviral therapies.

Detection of gastroesophageal reflux in children with cerebral palsy using combined multichannel intraluminal impedance-ph procedure.

Gastroesophageal reflux (GER) is a very common condition in children with neurological impairment and this can influence nutritional and respiratory outcomes. The aim of this study was to investigate the presence of GER in children with cerebral palsy (CP) using multiple intraluminal impedance (MII)-pH monitoring. The use of combined MII-pH allows for the detection of both acid and non-acid reflux episodes. A total of 29 CP patients with symptoms suggesting GER, aged 2 to 10 years old, underwent 24-hour combined MII-pH monitoring. There were a total of 3899 reflux episodes, of which 29% were acid, 60% were weakly acid and 11% were alkaline. The number of non-acid reflux episodes was statistically significantly greater (p < 0.01). These findings confirm that GER disease is seen frequently in children with cerebral palsy and most of the reflux episodes are not acidic. Non-acid reflux can also influence the morbidity in patients with cerebral palsy. It can be concluded that 70% of the reflux episodes would not have been recognized by pH measurement alone.

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.

Severe myopathy caused by the new pandemic influenza A (H1N1) in a child.

Myopathy is a rare complication of influenza infections. Here, we report on an eight-year-old girl with severe myopathy due to new pandemic influenza A (H1N1). She presented with severe myopathy following generalized tonic-clonic seizure and recovered completely within a few days.

The influence of valproic acid treatment on hair and serum zinc levels and serum biotinidase activity.

Some of the side effects that develop during long-term valproic acid (VPA) treatment are similar to symptoms of zinc and partial biotinidase deficiencies. This situation suggests an association between these side effects and biotinidase and/or zinc deficiencies. In 32 pediatric patients (22 females, 10 males) receiving VPA treatment, hair and serum zinc levels and serum biotinidase activity (BA) were measured prior to and in the 3rd and 6th months of treatment. Also, serum VPA levels were measured in the 3rd and 6th months of treatment. The mean serum and hair zinc levels were found to be reduced in the 3rd and 6th months of treatment as compared with the pre-treatment values, while the mean serum BA was lower than the pre-treatment values in the 3rd month of treatment, but returned to initial values in the 6th month of treatment. In the 3rd and 6th months of treatment, patients complaining about hair loss had lower hair and serum zinc levels and serum BA but greater mean serum VPA than those who did not. However, the differences between parameters were not statistically significant. Our findings suggest that hair loss in patients can be attributed to zinc and BA depletion within the first 3 months, and to zinc depletion only by the 6th month.