Mutations in LAMB1 cause cobblestone brain malformation without muscular or ocular abnormalities.

Cobblestone brain malformation (COB) is a neuronal migration disorder characterized by protrusions of neurons beyond the first cortical layer at the pial surface of the brain. It is usually seen in association with dystroglycanopathy types of congenital muscular dystrophies (CMDs) and ocular abnormalities termed muscle-eye-brain disease. Here we report homozygous deleterious mutations in LAMB1, encoding laminin subunit beta-1, in two families with autosomal-recessive COB. Affected individuals displayed a constellation of brain malformations including cortical gyral and white-matter signal abnormalities, severe cerebellar dysplasia, brainstem hypoplasia, and occipital encephalocele, but they had less apparent ocular or muscular abnormalities than are typically observed in COB. LAMB1 is localized to the pial basement membrane, suggesting that defective connection between radial glial cells and the pial surface mediated by LAMB1 leads to this malformation.

Effects of ebselen on radiocontrast media-induced hepatotoxicity in rats.

Oxidative stress is accepted as a potential responsible mechanism in the pathogenesis of radiocontrast media (RCM)-induced hepatotoxicity. Therefore, we aimed to investigate the protective effects of ebselen against RCM-induced hepatotoxicity by measuring tissue oxidant/antioxidant parameters and histological changes in rats. Wistar albino rats were randomly separated into four groups consisting of eight rats per group. Normal saline was given to the rats in control group (group 1). RCM was given to the rats in group 2, and both RCM and ebselen were given to the rats in group 3. Only ebselen was given to the rats in group 4. Liver sections of the killed animals were analyzed to measure the levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), as well as histopathological changes. In RCM group, SOD and CAT levels were found increased. In RCM-ebselen group, MDA, SOD and CAT levels were found decreased. In RCM-ebselen group, however, GSH-Px activities of liver tissue increased. All these results indicated that ebselen produced a protective mechanism against RCM-induced hepatotoxicity and took part in oxidative stress.

Bilateral Abducens Paralysis Secondary to Compression of Abducens Nerve Roots by Vertebrobasilar Dolichoectasia.

Vertebrobasilar dolichoectasia is characterized by dilatation, tortuosity, and marked elongation of the vertebral and basilar arteries. Dolichoectatic arteries usually have thin arterial walls secondary to degeneration of the internal elastic lamina, reticular fibre deficiency, and smooth muscle atrophy. This anomaly is relatively uncommon and generally asymptomatic. Clinical manifestations of dolichoectasia result from the compression and displacement of adjacent structures, causing cranial nerve palsy, obstructive hydrocephalus, or ischaemic stroke. The authors present a case in which vertebrobasilar dolichoectasia led to the development of bilateral abducens nerve paralysis in a 9-year-old girl.

Evaluation of auditory brainstem potentials in children with acute Herpes simplex encephalitis.

OBJECTIVE: In this study, auditory brainstem potentials (ABPs) were studied in children with Herpes simplex encephalitis (HSE) to determine the ABP abnormalities in HSE during childhood. We also wished to determine whether or not to use ABP in early diagnosis of HSE. METHOD: The study includes 28 children; eight children with acute HSE, nine with nonspecific encephalitis, and 11 healthy age-matched control subjects. The diagnosis of HSE was confirmed by the demonstration of Herpes simplex virus type 1 in CSF by polymerase chain reaction. Recordings of ABPs were performed by using Nihon Kohden Neuropack 2 device. RESULTS: The study includes eight children (four females and four males) with acute HSE, nine children (five males and four females) with nonspecific encephalitis, and 11 healthy age-matched control subjects (six males and five females). Age ranges of the patients and controls were between six months and 12 years. There was not statistically significant difference between the groups for age and gender (p > .05). There were significant differences in the mean latencies of the wave IV on the right ear and in the mean interpeak latencies (IPLs) of the waves III-V on the right and left ears between the nonspecific encephalitis group and the control group (p < .05). However, there were no statistically significant differences between the HSV and control groups (p > .05). In addition, there was no significant difference between HSV and nonspecific groups (p > .05). CONCLUSIONS: Our findings revealed that there were mild ABP abnormalities in children with nonspecific encephalitis, but no ABP abnormality in patients with HSV encephalitis. However, we think that more extensive and detailed studies should be performed to determine whether or not there were ABP abnormalities in childhood HSV encephalitis.

Biallelic loss of human CTNNA2, encoding αN-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration.

Neuronal migration defects, including pachygyria, are among the most severe developmental brain defects in humans. Here, we identify biallelic truncating mutations in CTNNA2, encoding αN-catenin, in patients with a distinct recessive form of pachygyria. CTNNA2 was expressed in human cerebral cortex, and its loss in neurons led to defects in neurite stability and migration. The αN-catenin paralog, αE-catenin, acts as a switch regulating the balance between ß-catenin and Arp2/3 actin filament activities1. Loss of αN-catenin did not affect ß-catenin signaling, but recombinant αN-catenin interacted with purified actin and repressed ARP2/3 actin-branching activity. The actin-binding domain of αN-catenin or ARP2/3 inhibitors rescued the neuronal phenotype associated with CTNNA2 loss, suggesting ARP2/3 de-repression as a potential disease mechanism. Our findings identify CTNNA2 as the first catenin family member with biallelic mutations in humans, causing a new pachygyria syndrome linked to actin regulation, and uncover a key factor involved in ARP2/3 repression in neurons.

Activity of mannitol and hypertonic saline therapy on the oxidant and antioxidant system during the acute term after traumatic brain injury in the rats.

In this study, our objective is to investigate the effects of mannitol and 7.5% hypertonic saline (HS) therapy on the levels of malondialdehyde (MDA), catalase and glutathione peroxidase (GSH-Px) in the early stages of experimental head traumas in rats. Rats included in the study were divided into four groups: Group I Control, Group II Trauma, Group III Mannitol, and Group IV 7.5% Hypertonic Saline. Rats in Group II were subject to head trauma only. Mannitol was injected intraperitoneally to rats in Group III after head trauma and 7.5% HS was injected intraperitoneally to rats in Group IV after head trauma. Rats were sacrificed 4 h after administration of mannitol or 7.5% HS, and the levels of MDA catalase and GSH-Px in brain tissues extracted from rats were determined. MDA levels in the trauma group were significantly increased compared with the control group (p<0.01), whereas there was a reduction in catalase and GSH-Px levels, although these differences were not significant. By contrast, in the mannitol group, MDA, catalase and GSH-Px levels were lower than the levels in the trauma group, and these reductions were statistically significant (p<0.05). The MDA, catalase and GSH-Px levels of the 7.5% HS group were lower than those of the trauma group; however, this reduction was not statistically significant. It was concluded that mannitol and 7.5% HS therapies that are used to reduce intracranial pressure and to increase the use of catalase, an antioxidant enzyme, and GSH-Px, are likely to reduce cellular damage by reducing the formation of MDA, the levels of which are known to be indicative of cellular level oxidant damage.

Brain magnetic resonance imaging findings in children with headache. / Resultados de la resonancia magnética nuclear de cerebro en niños con cefalea.

INTRODUCTION: The aim was to describe the findings on magnetic resonance imaging (MRI) in children with headache. POPULATION AND METHODS: Retrospective review of the medical records of patients who were admitted to our pediatric outpatient neurology clinics with the complaint of headache between January 2013 and December 2014. RESULTS: A total of 478 patients (273 female, 205 male) were admitted with the complaint of headache. The types of headache were migraine in 218 (45.6%), tension-type in 159 (33.3%), secondary in 39 (8.2%) and unspecified headaches in 62 (13%) patients. Brain MRI was performed in 407 (85%) patients and revealed cerebral abnormalities in 128 (31.4%) patients; 5 patients had cerebral abnormalities relevant with headache, including tumors. Amongst the others 123 patients, the most common findings were 42 cases (10%) of nonspecific white matter abnormalities, 17 cases (4%) of enlarged perivascular spaces, 17 cases (4%) of arachnoid cyst, 16 cases (3.9%) of asymmetric ventricles, 12 cases (2.9%) with Chiari type I and cerebellar tonsillar ectopia. Also, 17 (4.1%) patients had extra-cerebral MRI abnormalities including sinusitis, mucosal thickening and retention cysts of sinuses. CONCLUSIONS: In this study, the contribution of brain MRI in the diagnosis and management of the children with headache was still low.

INTRODUCCIÓN: El objetivo fue describir los resultados de la resonancia magnética nuclear (RMN) en niños con cefalea. POBLACIÓN Y MÉTODOS: Revisión retrospectiva de las historias clínicas de los pacientes ingresados a los consultorios externos de neurología pediátrica con síntomas de cefalea entre enero de 2013 y diciembre de 2014. RESULTADOS: Se ingresaron 478 pacientes (273 mujeres, 205 varones) con síntomas de cefalea. Los tipos de cefalea fueron migraña en 218 pacientes (45,6%), cefalea tensional en 159 (33,3%), cefalea secundaria en 39 (8,2%) y cefalea inespecífica en 62 (13%). Se realizó una RMN de cerebro a 407 pacientes (85%); se observaron anomalías cerebrales en 128 pacientes (31,4%); cinco tenían anomalías cerebrales relevantes para cefalea, incluso tumores. Entre los otros 123 pacientes, los hallazgos casuales más frecuentes correspondieron a 42 casos (10%) de anomalías inespecíficas de la sustancia blanca, 17 casos (4%) de espacios perivasculares agrandados, 17 casos (4%) de quiste aracnoideo, 16 casos (3,9%) de ventrículos asimétricos, 12 casos (2,9%) de malformación de Chiari tipo 1 y ectopia amigdalina cerebelosa. Asimismo, 17 pacientes (4,1%) tenían anomalías extracerebrales en la RMN, entre otras, sinusitis, engrosamiento de la mucosa y quistes de retención de los senos paranasales. CONCLUSIONES: A pesar del incremento en la realización de estudios de neuroimagenología, la contribución de la RMN de cerebro al diagnóstico y el tratamiento de los niños con cefalea es aún baja.

Bilateral brachial plexopathy complicating Henoch-Schönlein purpura.

An 11-year-old boy presented with convulsion, fever, rash, abdominal pain, swelling on the eyelids, elbow and wrists, oliguria and hematuria. Based on the abnormal findings the patient was diagnosed with Henoch-Schönlein purpura. On the 3rd day of admission, neurological examination showed ataxic gait, loss of deep tendon reflexes, and decreased (4/5) of muscle strength on all extremities. Additionally, bilateral loss of touch, pain and temperature sensation in a glove, from the elbows to distal region (on C5-T1 level) was diagnosed. Cerebrospinal fluid examination and cranial magnetic resonance imaging (MRI) were normal. The patient was discharged with oral prednisolone on the 7th day of admission. One week after discharging from the hospital, he was re-admitted with vertigo and seizures. He was in coma. MRI of cranial, cervical and cervical plexus were normal. Electromyography showed severe bilateral brachial plexopathy. Prednisolone and intravenous immunglobulin (IVIG) therapy were given without significant improvement. He was discharged from the hospital on the 17th day of admission. On the second month of follow-up, a second cure of IVIG was given because of no clinical improvement. Now, he is on the 4th month of follow-up, unfortunately, no improvement was noted on his muscle strength and sensorial abnormalities on the upper extremities.

Intracranial lipomas--a clinical study.

OBJECTIVE: This study aimed to investigate the localization of the lipoma, as well as associated intracranial and extracranial lesions in 14 patients immediately following hospital admission. The pathological findings from the neurological examinations of these patients are also investigated. METHODS: Fourteen patients who were admitted to our clinic with a variety of symptoms and diagnosed with intracranial lipoma were included in the study. Problems presented upon admission, neurological findings, and other existing system abnormalities were evaluated. Localization of the lipomas and accompanying pathologies were determined by using computerised tomography and magnetic resonance imaging. RESULTS: The most frequent reasons for admission of patients with intracranial lipomas were: headache 7 (50%), trauma 3 (21.5%), epilepsy 3 (21.5%) and one with symptoms due to the local mass effect of tumor (7%). Although the pericallosal region is accepted as the region where lipomas commonly occur, this study found the most frequent occurrence in the quadrigeminal cistern. Intracranial lipoma calcification was only evident in 1 of the 14 patients. In addition, contrary to the expectations, intracranial and extracranial lesions accompanying lipomas were rare. All patients received systematic treatment. CONCLUSION: This study showed that intracranial lipomas are more frequent in the quadrigeminal region of the brain; most are asymptomatic, generally caught incidentally; and accompanying intracranial and extracranial pathologies are less common than expected.

Acute amitriptyline intoxication: an analysis of 44 children.

The tricyclic antidepressant agents, particularly amitriptyline and dothiepin, are recognized for their potentially lethal cardiovascular and neurological effects in poisoned patients. In this article, the clinical and laboratory findings of 44 children with amitriptyline intoxication are reviewed. Our purpose was to investigate amitriptyline intoxication in childhood. Of 44 patients, 21 (47.7%) were boys, 23 (52.3%) were girls, and the ages ranged from 12 months to 14 years (mean +/- SD; 4.09 +/- 2.9 years). All children except one who took an overdose of amitriptyline to decrease his pain accidentally ingested an overdose of amitriptyline. The amount of amitriptyline ingested was between 2 mg/kg and 97.5 mg/kg (mean +/- SD; 13.6 +/- 17.7 mg/kg per dose) (the drug dosage was not known in 13 children). The most commonly observed clinical and laboratory findings were lethargy, tachycardia, convulsion, hyperglycemia and leukocytosis. In all patients except for two children who died the abnormal clinical and laboratory findings returned to normal within a few days after admission and they were discharged from the hospital in good health within the fourth day of admission. One of the children ingested 97.5 mg/kg amitriptyline and probably died due to status epilepticus and another child who died ingested 36 mg/ kg amitriptyline and died due to cardiopulmonary arrest. In conclusion, our findings showed that initial symptoms and signs of acute amitriptyline intoxication appeared severe, but they disappeared with only supportive care required in most children except for cases that ingested high doses of drug within a few days. In contrast to adults, we infrequently noted respiratory insufficiency, arrhythmia and hypotension in children with acute amitriptyline intoxication.

Early-Onset Mild Type Leukoencephalopathy Caused by a Homozygous EARS2 Mutation.

Childhood leukoencephalopathies are a broad class of diseases, which are extremely rare. The treatment and classification of these disorders are both challenging. Nearly half of children presenting with a leukoencephalopathy remain without a specific diagnosis. Leukoencephalopathy with thalamus and brain stem involvement and high lactate (LTBL) is a newly described childhood leukoencephalopathy caused by mutations in the gene encoding a mitochondrial aminoacyl-tRNA synthetase specific for glutamate, EARS2 Magnetic resonance images show a characteristic leukoencephalopathy with thalamic and brain stem involvement. Here, we report a different clinical course of LTBL supported by typical MRI features in a Turkish patient who presented with a history of failure to walk. The EARS2 gene mutation analysis identified a c.322C>T transition, predicting a p.R108W change. This is the first reported early-onset mild type LTBL caused by a homozygous EARS2 mutation case in the literature.

Predictors of recurrence in Sydenham's chorea: Clinical observation from a single center.

OBJECTIVE: Sydenham's chorea is the most common cause of acquired chorea in children and is the major manifestation for acute rheumatic fever. Despite being known as a benign, self-limiting condition, recurrences and persistence of symptoms can be seen. In this study, we aimed to evaluate retrospectively the clinical and laboratory features of patients with Sydenham's chorea and the rate and the course of recurrences, and to assess the risk of recurrences. METHODS: The study was a retrospective study conducted in a tertiary hospital. Patients with Sydenham's chorea who were admitted to our outpatient clinics between January 2013 and June 2015 were included. Both newly diagnosed and follow-up patients were enrolled during this period. We retrospectively reviewed the medical charts of the patients. RESULTS: There were 90 patients with female predominance. The mean age of onset was 11±2.4years. Complete remission was maintained in 77 patients (85.6%) at 1-6months and 4 patients had symptoms at more than 12months. Patients were followed for 6months to 9years. The recurrence rate was 16%. When we compared recurrent patients with the non-recurrent group, complete remission in 6months, the presence of persistent chorea, and regular use of prophylaxis were significantly different between the 2 groups. CONCLUSIONS: Sydenham's chorea is still an important health problem and has high morbidity in patients with recurrent and persistent chorea. The irregular usage of antibiotic prophylaxis, failure to achieve remission within 6months, and prolongation of symptoms for more than 1year are risk factors for recurrence of chorea.

Auditory brainstem potentials in children with protein energy malnutrition.

OBJECTIVE: In this study, auditory brainstem potentials (ABPs) were studied in children with protein energy malnutrition (PEM) to determine the effects of PEM on the developing brain in children. METHODS: A total of 31 children, aged 3-36 months with moderate/severe PEM and 25 healthy children, aged 3-48 months were included in the study. Nutritional status of the children was assessed by the Gomez classification. Recordings of ABPs were performed by using Nihon Kohden Neuropack 2 device. RESULTS: Of 31 children, 22 (71%) had severe malnutrition, 9 (29%) had moderate malnutrition. Additionally, 8 (26%) and 9 (29%) children had iron deficiency anemia and hypoalbuminemi, respectively. There were significant differences in the mean latencies of the waves I-V on the right and left ears and in the mean interpeak latencies (IPLs) of the waves III-V and I-V on the right ear between the study and control groups (P<0.05). The mean IPLs of I-V on the left side were found to be longer in the moderate PEM group than those of severe PEM group (P<0.05). There was not any difference between the groups of PEM with low serum albumin and PEM with normal serum albumin. While the mean IPLs of I-III on the right side were found longer in the cases of PEM without iron deficiency anemia, the mean latency of wave I on the left side, and the mean IPLs of III-V on the right side were longer in the children with PEM plus iron deficiency anemia (P<0.05). CONCLUSIONS: Our findings showed that children with moderate/severe PEM had ABPs abnormalities in different degrees, which reflect defects in myelination of auditory brainstem pathways in children with moderate/severe PEM. However, we found contradictory results between abnormalities in ABPs and degree of malnutrition and iron deficiency anemia. We think that more extensive studies should be performed to determine whether or not there was a relationship between these parameters.

Evaluation of Lymphocyte Subgroups in Children With Down Syndrome.

In this study, lymphocyte subgroups including blood CD3, CD4, CD8, CD4/CD8, CD19, and CD16.56 values were analyzed in children with Down syndrome (DS). The study includes 85 children with DS, followed at Department of Pediatrics, Faculty of Medicine, Yüzüncü Yil University and 64 healthy age-matched control participants. Blood CD3, CD4, CD8, CD4/CD8, CD19, and CD16.56 values were examined in both the groups. Significantly decreased blood CD3, CD4, and CD19 values were found in the study group (P < .05) when compared with the control group. In conclusion, we would like to emphasize that blood CD3, CD4, and CD19 levels were found to be decreased in children with DS. Based on these finding, we think that these decreased lymphocyte subgroups might be responsible for increased susceptibility to infections in children with DS.

Oxidative Status in Epileptic Children Using Carbamazepine.

BACKGROUND: There is an increasing attention towards the relationship between oxidative stress and epilepsy. The effect of antiepileptic drugs on oxidant status is of major interest. Antiepileptic drugs can increase levels of free radicals, which consequently might lead to seizures. Carbamazepine (CBZ) is an antiepileptic drug commonly used in childhood and adolescence. OBJECTIVES: Therefore we aimed to investigate the effects of CBZ on total antioxidant status, total oxidant stress, and oxidative stress index. PATIENTS AND METHODS: The study included 40 epileptic patients and 31 healthy children between 4 and 12 years of age. Serum CBZ level, total antioxidant capacity and total oxidant status were measured. Oxidative stress index was also calculated both in controls and patients. RESULTS: In the epileptic group, decreased levels of total antioxidant capacity, increased total oxidative stress and oxidative stress index levels were found. Positive correlation between plasma CBZ levels and total oxidant status was observed. CONCLUSIONS: Antioxidant action could not be playing any role in antiepileptic effect of CBZ. Furthermore, increased oxidative stress induced by CBZ could be the cause of CBZ-induced seizures. Therefore combining CBZ with antioxidants could be beneficial.

[The impact of different antiepileptic drugs on the sedation of children during magnetic resonance imaging]. / Impacto de diferentes medicamentos antiepilépticos na sedação de crianças durante a ressonância magnética.

BACKGROUND AND OBJECTIVES: The induction and inhibition of cytochrome P450 isoenzymes by antiepileptic drugs lead to changes in the clearance of anesthetic drugs eliminated via hepatic metabolism. We investigated the duration of the sedation and additional anesthetic needs during magnetic resonance imaging in epileptic children receiving antiepileptic drugs that cause either enzyme induction or inhibition. METHODS: In American Society of Anesthesiology I-II, 120 children aged 3-10 years were included. Group 1: children using antiepileptic drugs that cause cytochrome P450 enzyme induction; Group 2: those using antiepileptic drugs that cause inhibition; and Group 3: those that did not use antiepileptic drugs. Sedation was induced with the use of 0.05 mg kg(-1) midazolam and 1 mg kg(-1) propofol. An additional 0.05 mg kg(-1) of midazolam and rescue propofol (0.5 mg kg(-1)) were administered and repeated to maintain sedation. The duration of sedation and the additional sedation needed were compared. RESULTS: The duration of the initial dose was significantly shorter in Group I compared with groups II and III (p = 0.001, p = 0.003, respectively). It was significantly longer in Group II compared with groups I and III (p = 0.001, p = 0.029, respectively). The additional midazolam needed for adequate sedation was increased in Group I when compared with groups II and III (p = 0.010, p = 0.001, respectively). In addition, the rescue propofol dose was significantly higher only in Group I when compared with Group III (p = 0.002). CONCLUSION: In epileptic children, the response variability to the initial sedative agents during the magnetic resonance imaging procedure resulting from the inhibition or induction of the cytochrome P450 isoenzymes by the antiepileptic drugs mandated the titration of anesthetic agents.

Magnetic resonance imaging findings of the abducens nerves in type 1 Duane's retraction syndrome.

PURPOSE: To investigate nervus abducens and extraocular mucles in patients with Type 1 Duane's retraction syndrome using high-definition magnetic resonance imaging. METHODS: The study included 10 patients with Type I Duane's retraction syndrome who underwent magnetic resonance imaging (MRI) of the brain and orbits. RESULTS: Overall, 10 cases were included in the study. There were seven women and three men. The mean age was 5.2 years (1-15 years). MRI of the abducens nerve was performed in all cases. Of the cases, the left eye was involved in eight cases, whereas the right eye was involved in two cases. There was no bilateral eye involvement. Among the 10 patients clinically diagnosed as Type 1 Duane's retraction syndrome, the abducens nerve could not be visualized in eight cases, whereas the nerve was hypoplastic in one case and bilateral abducens nerves were present in one case by MRI. The extraocular muscles were normal in all cases on T2 weighted coronal MRI of the orbits. CONCLUSION: Absence of abducens nerve and normal extraocular muscles was detected in patients with Type 1 Duane's retraction syndrome at the affected side.