Brain and Development - Articles in Press

A case of D-lactic acid encephalopathy associated with use of probiotics - Corrected Proof

2009-11-18

Abstract: A five year old girl was admitted to the hospital for evaluation of intermittent ataxia. She had undergone serial resections of the small intestine after birth, resulting in short bowel syndrome. Lactomin was prescribed for watery diarrhea at twice the regular dose 2weeks before the onset of neurologic symptoms. D-lactic acidosis was diagnosed on the basis of a plasma D-lactate level of 5.537mmol/l. Lactomin was discontinued, and she was treated with sodium bicarbonate and oral antibiotics. The probiotics the patient had taken were likely the cause of D-lactic acidosis and should therefore be avoided in patients with short bowel syndrome.

A special report of the 10th AOCCN - Corrected Proof

Dong Wook Kim — 2009-11-16

About 700 delegates from 26 countries came to Daegu, Korea to participate in the 10th Asian & Oceanian Congress of Child Neurology (10th AOCCN) and the 32nd Congress of the Korean Child Neurology Society (32nd CKCNS) from June 10 to 13, 2009 ().

Early development of brain responses to rapidly presented auditory stimulation: A magnetoencephalographic study - Corrected Proof

2009-11-09

Abstract: Background: The processing of rapidly presented stimuli has been shown to be a precursor for the perception of speech in infants, long before they learn to speak. However, the onset and early development of rapid temporal processing (RTP) skills is not yet well understood. The main goal of this study was to assess the development of RTP skills during the prenatal and early postnatal stages of life. Methodology: Tone pairs were presented in two difficulties (long and short) and event-related magnetic fields were recorded using MEG. Pregnant women (22) (gestational ages between 29 and 38weeks’) participated in the fetal study and 15 returned for a neonatal follow-up study between 2 and 38days after delivery or 38 and 44weeks gestational age (GA). Results: In the postnatal follow-up study, a trend towards two peaks with increasing chronological and gestational age was observed in the longer tone pair. However, no such trend was evident in neonatal responses to the short tone pairs or in fetal recordings. Conclusions: Neonates showed a gradual trend to successful processing of the longer tone pair with increasing age. By 22days of chronological age, the infants processed this tone pair successfully, as indicated by two-peak waveforms. Therefore, the first 3weeks of life could be critical for the development of RTP. Significance: This study is a first approach towards the assessment of early RTP development. The results provide promising indications for future studies, which might lead to an early detection of deficits in speech perception and therefore prevent further language impairments.

How do the clinical features of brain tumours in childhood progress before diagnosis? - Corrected Proof

2009-11-05

Abstract: Objectives: To investigate the progression of the clinical features from symptom onset to diagnosis in children with brain tumours. Design: Retrospective case note review. Patients: Sixty children with brain tumours: 27 patients from Nagoya University Hospital diagnosed between February 2004 and April 2008, and 33 patients from Anjo Kosei Hospital diagnosed between April 1995 and December 2008. Results: Various symptoms and signs were observed. The most common initial symptoms or signs were vomiting (24.1%), headache (17.2%), unsteadiness (10.3%), and paresis (10.3%). Sixteen patients were diagnosed based on the initial symptom or sign alone; six, at routine medical check-ups or had perinatal diagnosis; and the remaining 38, based on one or more additional features following the initial symptom. Nine of the 10 patients with headache as the initial symptom subsequently developed either vomiting (in seven) or unsteadiness with cranial nerve palsies (in two). Twelve of the 14 patients with vomiting as the initial symptom subsequently developed headache (in three), unsteadiness (in five), or other manifestations of increased intracranial pressure (in four). The remaining 14 had varied initial symptoms and combinations of symptoms and signs associated with the tumour location. The median pre-diagnosis symptomatic interval was 20.5days. There was no significant difference in the median symptomatic interval between patients with headache or vomiting as the initial symptom and those with any neurological sign. Conclusion: Paediatric brain tumours present with various initial symptoms and signs. Many are diagnosed as additional symptoms or signs develop. The clinical features exhibit several patterns of progression, which are related to the tumour location.

What is the point of specifying Panayiotopoulos syndrome from a practical point of view? - Corrected Proof

Eishi Asano, Tomoyuki Akiyama — 2009-11-02

What is the point of defining a specific epilepsy syndrome in clinical practice? Definition of a specific epilepsy syndrome could be judged redundant, unless it helps in clinical management, prediction of prognosis or understanding of its underlying pathophysiology.

Regional cerebral blood flow changes in early-onset anorexia nervosa before and after weight gain - Corrected Proof

2009-10-30

Abstract: To investigate the changes of regional cerebral blood flow (rCBF) in early-onset anorexia nervosa (AN) before and after weight gain, we examined resting rCBF using single photon emission computed tomography (SPECT) with [123I]iodoamphetamine (123I-IMP). Ten female children with AN (mean age 13.2years old) participated in this study. SPECT examinations were performed in all patients twice at the beginning of treatment and after weight gain. The mean body mass index (BMI) was changed from 13.1 to 16.6 during 4months treatment period. Automatic voxel-based analysis of the images was carried out using statistical parametric mapping (SPM) software. Relatively increased rCBF in the bilateral parietal lobe and limbic lobe including the posterior cingulate cortex (PCC) were observed after weight gain in early-onset AN. There was no significant decrease in the rCBF after weight gain. A significant positive correlation was observed between BMI and rCBF in the right thalamus, right parietal lobe, and right cerebellum. These results suggested that weight gain during the process of recovery from early-onset AN might activate specific brain regions which are possibly relevant to the pathophysiological aspects of the disorder.

The role of EEG in febrile status epilepticus (FSE) - Corrected Proof

D.R. Nordli, S.L. Moshé, S. Shinnar — 2009-10-28

Abstract: Febrile status epilepticus is an important neurological emergency and a risk factor for later development of epilepsy. There are guidelines recommending against the use of EEG in the evaluation of simple febrile seizures but the role in febrile status epilepticus is not well established. This article reviews the literature on the role of EEG in the evaluation of the patient with prolonged febrile seizures, summarizes the findings, and concludes with some simple recommendations based upon the existing knowledge. At least 30–40% of EEGs obtained within one week of febrile status epilepticus will contain abnormalities including focal slowing. In some series focal slowing appears to be associated with development of a spike focus in the same location. Prospective series with large numbers of patients and follow-up are required to ascertain whether such abnormalities are associated with later development of epilepsy.

Influence of premature rupture of membrane on the cerebral blood flow in low-birth-weight infant after the delivery - Corrected Proof

2009-10-28

Abstract: Cerebral white matter injury, usually called periventricular leukomalacia (PVL), is the most common form of injury to preterm infants that is associated with adverse motor and cognitive outcomes. Intrauterine infection may be an important etiological factor in PVL, and premature rupture of the membranes (PROM) can be identified antepartum. In order to investigate the pathophysiology of cerebral white matter injury induced by PROM, the cerebral blood flow (CBF) of the internal carotid artery and the vertebral artery was measured by neck ultrasonography. The CBF was determined in 84 low-birth-weight infants with gestational ages ranging from 24 to 35weeks, including 71 infants without PROM and 13 infants with PROM. The mean blood flow velocity and diameter of each vessel were measured on postnatal days 0–70. The intravascular flow volume was determined by calculating the mean blood flow velocity and the cross-sectional area. The mean blood pressures were recorded, and the ejection fraction was determined. The total cerebral blood flow (CBF) was significantly lower in infants with PROM than in infants without PROM from day 10 to day 70. The ejection fraction was significantly higher in infants with PROM than in infants without PROM on days 0, 5, 10, 21, and 42. There was no difference in the mean blood pressure between infants with PROM and infants without PROM. The results of the present study suggest that PROM may decrease cerebral blood flow after the birth.

Behavioral improvement after transplantation of neural precursors derived from embryonic stem cells into the globally ischemic brain of adolescent rats - Corrected Proof

2009-10-26

Summary: Purpose: We intended to determine whether transplanted neural precursors, derived from mouse embryonic stem (ES) cells, can migrate and differentiate into mature neurons and glial cells in damaged brains and improve functional deficits caused by global cerebral ischemic injury in adolescent rats. Methods: Global ischemia was induced using the four-vessel occlusion method. ES cells that display enhanced expression of yellow fluorescent protein were co-cultured in N2 supplemented media with PA6 cells that had stromal derived inducing activity. Neural precursor cells were directly transplanted bilaterally into hippocampal C3 areas 2weeks after induction of global ischemia. Assessments of the Morris water-maze test at eight weeks and, the Open field activity levels at two, four, six and eight weeks after transplantation were carried out according to standard methods. Results: From neural precursors, we were able to generate neural lineages, including neurons and glial cells in vitro. Eight weeks following transplantation, cellular migration as well as generation of neural cells including neurons, astrocytes, and oligodendrocytes developed from the grafted ES cell-derived neural precursors were observed. Cell-transplanted animals exhibited enhanced functional recovery on sensorimotor and behavioral tests, compared to vehicle-treated control animals. Conclusion: Therefore, transplantation of mouse ES cell-derived neural precursor cells shows promise for improving recovery after global ischemia in adolescent rats.

Dravet syndrome: Early clinical manifestations and cognitive outcome in 37 Italian patients - Corrected Proof

2009-10-26

Abstract: Aims of our study were to describe the early clinical features of Dravet syndrome (SMEI) and the neurological, cognitive and behavioral outcome. The clinical history of 37 patients with clinical diagnosis of SMEI, associated with a point mutation of SCN1A gene in 84% of cases, were reviewed with particular attention to the symptoms of onset. All the patients received at least one formal cognitive and behavior evaluation. Epilepsy started at a mean age of 5.7months; the onset was marked by isolated seizure in 25 infants, and by status epilepticus in 12; the first seizure had been triggered by fever, mostly of low degree in 22 infants; the first EEG was normal in all cases. During the second year of life difficult-to-treat seizures recurred, mostly triggered by fever, hot bath, and intermittent lights and delay in psychomotor development became evident. At the last evaluation, performed at a mean age of 16±6.9years, mental retardation was present in 33 patients, associated with behavior disorders in 21. Our data indicate that the most striking features of SMEI are: the early onset of seizures in a previously healthy child, the long duration of the first seizure, the presence of focal ictal symptoms, and sensitivity to low-grade fever. Diagnosis of SMEI may be proposed by the end of the first year of life, and a definite diagnosis can be established during the second year based on the peculiar seizure-favoring factors, EEG photosensitivity and psychomotor slowing. The temporal correlation between high seizure frequency and cognitive impairment support the role of epilepsy in the clinical outcome, even if a role of channelopathy cannot be ruled out.

Treatment of febrile seizures: Historical perspective, current opinions, and potential future directions - Corrected Proof

Andrew L. Lux — 2009-10-26

Abstract: Although most febrile seizures do no harm and two-thirds of initial cases have no witnessed recurrence, the seizures cause much family anxiety, and are sometimes prolonged. In rare cases they are the first evidence of important epilepsy syndromes or are implicated in the development of epilepsy with mesial temporal sclerosis in later life. There have been trials of prophylactic treatment with antiepileptic drugs including carbamazepine, diazepam, phenobarbital, phenytoin, and sodium valproate. Several strategies have been employed with these drugs, including continuous secondary prophylaxis, intermittent secondary prophylaxis in response to later episodes of fever, and rescue medication early in the course of further seizures. Another treatment strategy has been using one or more antipyretic agents in early response to fever using agents such as acetaminophen and ibuprofen. Over the years, researchers have identified a variety of clinical, genetic, and environmental risk factors for more severe or prolonged febrile seizures and higher risk of recurrence. This review evaluates the rationale for secondary prophylaxis of febrile seizures, the potential effectiveness of such treatment, and whether it can be recommended as a general approach to treating febrile seizures or as an approach to be used in groups identified to be at increased risk.

Genetic susceptibility to febrile seizures: Case-control association studies - Corrected Proof

2009-10-26

Abstract: Objective: A genetic predisposition to febrile seizures (FS) has long been recognized. The inheritance appears to be polygenic in small families or sporadic cases of FS encountered in daily clinical practice. To determine whether candidate genes are responsible for the susceptibility to FS, we have performed genetic association studies in FS patients and controls. Methods: The single-nucleotide polymorphisms (SNPs) of genes involved in immune response (interleukin (IL) 1B), endocannabinoid signaling (CNR1), acid–base balance (SLC4A3, SLC9A1, SLC9A3), gap junction channel (CX43), and GABAA receptor trafficking (PRIP1) were examined in 249 FS patients (186 simple and 63 complex FS) and 225 controls. Results: There were no significant differences in the allele frequencies of the SNPs between controls and all FS, simple FS, and complex FS patients. When the simple FS patients were divided into two groups according to either having (familial) or not having a family history of FS in close relatives (sporadic), there was a significant association between IL1B −511 SNP and sporadic simple FS (p=0.003). Conclusions: These data suggest that cytokine genes may act as enhancers or attenuators of FS susceptibility. Genetic association study may be an effective approach to understanding the molecular basis of FS at least in a subgroup of patients.

Current management of febrile seizures in Japan: An overview - Corrected Proof

Kenji Sugai — 2009-10-23

Abstract: Febrile seizures (FS) require both acute and chronic management. Acute management includes the treatment and differential diagnosis of FS and depend on the presence of seizures and a patient’s level of consciousness upon arrival at hospital: a patient may be discharged after physical examination if there are no seizures and no alteration of consciousness; close observation and laboratory examinations may be indicated in cases when there are no seizures but the patient exhibits altered consciousness; and intravenous diazepam (DZP) is indicated if seizures persist. Central nervous system infections should be ruled out: if the patient has signs of meningeal irritation or increased intracranial pressure, disturbed consciousness for >1h, atypical seizures (partial seizures, seizures for >15min, or recurrent seizures within 24h), cerebrospinal fluid examinations and/or computed tomography/magnetic resonance imaging are warranted. Chronic management includes the prevention of recurrent FS, counseling parents, and vaccination. Japanese guideline for the prevention of recurrent FS defines two types of warning factors (WF) for selecting patients who should be monitored carefully: factors related to the onset of epilepsy (EP factors) and recurrence of FS (FS factors). The EP factors consist of neurological or developmental abnormalities prior to the onset of FS, atypical seizures, and history of epilepsy in parents or siblings. The FS factors include the onset of FS before 1year of age and a history of FS in one or both parents. The guideline recommends no medication for children with two or fewer past episodes of FS without WF; prophylactic DZP for children with prolonged FS exceeding 15min, or two or more episodes of FS with two or more WF; and daily administration of phenobarbital or valproate for children in whom FS occur under 38°C or who have prolonged FS despite prophylactic DZP. To reduce parents’ anxiety, the natural history of FS should be explained. A child can be given all current vaccinations 2–3months after the last episode of FS by his/her family doctor with information provided to the parents as to how to cope with fever and convulsions.

Epileptic encephalopathy in children possibly related to immune-mediated pathogenesis - Corrected Proof

Nicola Specchio, Lucia Fusco, Dianela Claps, Federico Vigevano — 2009-10-22

Abstract: Severe epilepsy in the paediatric population negatively influences neurological and cognitive development. Different etiological factors could be responsible of these severe epilepsies, and an early diagnosis could change, in some cases, the neurological and cognitive development. Immune mechanisms have been reported in epilepsy. Epilepsy has been associated with systemic lupus erythematosus, with the presence of anti-phospholipid antibodies (aPL), anti-cardiolipin antibodies, anti-nuclear antibodies, Β2-glycoprotein antibodies, and anti-glutamic acid decarboxylase (anti-GAD) antibodies. CNS inflammation and markers of adaptive immunity have been, also, associated with some epileptic syndromes, such as West syndrome, temporal lobe epilepsy, febrile seizures, tonic–clonic seizures, and tuberous sclerosis. Inflammation and blood–brain barrier (BBB) disruption could be one of the mechanisms responsible for seizure recurrence. Recently clinical entities, characterized by severe epilepsy with a febrile, acute or sub-acute onset, sometimes associated with status epilepticus, followed by drug-resistant, partial epilepsy have been described. Some of these publications also suggested acronyms for the condition described: Acute Encephalitis with Refractory, Repetitive Partial Seizures (AERRPS) reported by Japanese authors, Devastating Epileptic Encephalopathy in School-aged Children (DESC) reported by French authors. Among children with acquired symptomatic severe epilepsy, we identified a group of previously normal children who had developed severe partial epilepsy after an acute/sub-acute illness resembling encephalitis. The etiological factors for those patients seems to remain unknown, and a possible immune-mediating or inflammatory process as pathogenesis of the disease could be hypothesized. More studies need to be addressed to finally define this peculiar epileptic entity.

Febrile seizures – Semiology in humans and animal models: Evidence of focality and heterogeneity - Corrected Proof

Brian G.R. Neville, Diane Gindner — 2009-10-19

Abstract: The relationship between febrile seizures and hippocampal sclerosis has been the subject of longstanding discussion. Animal models for prolonged seizures have shown a clear causal relationship with focal limbic features at low dose and hippocampal damage at high dose. Careful history taking of febrile seizure semiology has shown focal early features often with clear temporal lobe elements. This would suggest that many febrile seizures are secondarily generalised hippocampal seizures. There is evidence of varying levels of epileptogenicity in specific infective causes of febrile seizures. Seizure semiology also suggests that a proportion of such seizures may be non-epileptic reflex asystolic attacks. Seizure semiology in febrile seizures deserves closer scrutiny.

Gamma oscillations in the primary motor cortex studied with MEG - Corrected Proof

2009-10-19

Abstract: In recent years, there has been a growing interest on the role of gamma band (>30Hz) neural oscillations in motor control, although the function of this activity in motor control is unknown clearly. With the goal of discussing the high frequency sources non-invasively and precisely during unilateral index finger movement, we investigated gamma band oscillations in 20 right-handed normal adults with magnetoencephalography (MEG). The results showed that gamma band activity appeared only during finger movement. Nineteen subjects displayed consistently contralateral event-related synchronization (C-ERS) within high gamma band (70–150Hz) in primary motor cortex (M1) of both hemispheres. Interestingly, 15 subjects displayed ipsilateral event-related desynchronization (I-ERD) and C-ERS within broad gamma band (30–150Hz). The locations of the broad gamma band I-ERD and C-ERS revealed hemispherical symmetry in M1. These findings demonstrate that there are consistent high gamma C-ERS and inconsistent low gamma I-ERD during a simple finger movement in the motor cortex. This study provides new evidence for the use of high gamma frequency oscillations as biomarkers in the analyses of functional brain activity and the localization of the motor cortex.

Comparison of the strengths and difficulties questionnaire (SDQ) scores between children with high-functioning autism spectrum disorder (HFASD) and attention-deficit/hyperactivity disorder (AD/HD) - Corrected Proof

2009-10-15

Abstract: The aim of this research was to compare the Strengths and Difficulties Questionnaire (SDQ) scores and subscale scores in children with high-functioning autism spectrum disorder (HFASD) and attention-deficit/hyperactivity disorder (AD/HD), and also to clarify the differences between parent- and teacher-assessed SDQ scores/subscores in HFASD and AD/HD children. These patients’ total difficulties scores were significantly high compared to the community sample. In the parent rating, HFASD children had significantly higher scores in the subscales of emotional symptoms and peer problems. In the teacher rating, AD/HD children showed significantly higher scores in the subscales of hyperactivity/inattention and conduct problems, whereas peer problems were significantly higher in HFASD. The teacher rating showed significantly greater difficulties than the parent rating on the subscale of prosocial behavior in both the AD/HD and HFASD groups. These results suggest that each subscale may reflect behavioral, emotional, and social characteristics of HFASD and AD/HD.

Low-dose levodopa is effective for laryngeal dystonia in xeroderma pigmentosum group A - Corrected Proof

2009-10-12

Abstract: Xeroderma pigmentosum (XP), a genetic disorder in DNA nucleotide excision repair, is characterized by skin hypersensitivity to sunlight and progressive neurological impairment. Laryngeal dystonia and vocal cord paralysis are complications that can arise in older XP group A (XPA) patients. We report three patients with XPA being administered low-dose levodopa (0.3–1.5mg/kg/day) for laryngeal dystonia. Patients were aged from 13 to 18years, exhibited paroxysmal choking and inspiratory stridor, and were diagnosed with laryngeal dystonia. Two XPA patients responded to low-dose levodopa, and paroxysmal choking and involuntary movements resolved, although one of the two patients showed incomplete resolution due to suspected vocal cord paralysis. The other patient was unable to tolerate the medication because of a transient decrease of muscle tone in the extremities. We previously reported a decreased immunostaining of dopaminergic (DA) terminals in the basal ganglia of XPA patients, which may be involved in laryngeal dystonia. Low-dose levodopa has been reported to alleviate DA receptor supersensitivity in tic patients, while laryngeal dystonia occurs in patients with tardive dyskinesia caused by DA receptor supersensitivity. Thus, low-dose levodopa may improve laryngeal dystonia by alleviating DA receptor supersensitivity in XPA patients. We recommend that low-dose levodopa be used for treatment of paroxysmal respiratory disturbances and/or involuntary movements in XPA patients.

Nutritional state, maturational delay on electroencephalogram, and developmental outcome in extremely low birth weight infants - Corrected Proof

2009-10-12

Abstract: The aim of this study is to clarify the relation among developmental outcome, nutritional state during the neonatal period, maturational electroencephalographic changes. Thirteen extremely low birth weight infants who completed 6- or 9-year follow-up were a subject of this study. Undernutrition was defined as enteral feeding below 100mL/kg/day at 3weeks of age. Dysmature patterns were defined as the persistence of EEG patterns 2weeks or more immature for post-conceptional age. IQ was examined at 6 and 9years of age. Body height and weight, and head circumference at 6years of age were stratified by the percentile grades. Full and verbal IQ was significantly lower in infants with undernutrition than those with normal nutrition. Among infants with undernutrition, those with persistent dysmature patterns tended to have lower full and performance IQ than those without persistent dysmature patterns. Head circumference was 50 percentile or larger in all infants with normal nutrition, whereas it was below 50 percentile in six of eight infants with undernutrition. Extremely low birth weight infants with undernutrition had worse neurodevelopmental outcome at 6 or 9years of age than those with normal nutrition. Among infants with undernutrition, developmental outcome was relatively worse in those with persistent dysmature patterns than those without.

Clustered subclinical seizures in a patient with acute encephalopathy with biphasic seizures and late reduced diffusion - Corrected Proof

2009-10-12

Abstract: Using single-channel amplitude-integrated electroencephalography (aEEG), we monitored clustered seizures in a 12-month-old boy suffering from acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). He was admitted to our hospital after losing consciousness and experiencing repeated seizures in association with fever. Although the patient’s state of consciousness improved the next day, it declined on the fifth day of illness, and clinical seizures were observed. Diffusion-weighted images revealed abnormal high intensities in the frontal area bilaterally. On the same day, aEEG monitoring revealed an unexpected cluster of subclinical seizures. Attending pediatricians, nurses, and other caregivers did not recognize the presence of these frequent subclinical seizures. The efficacy of antiepileptic drugs could also be objectively assessed from aEEG findings. aEEG is useful for continuous monitoring in children with acute encephalopathy, may disclose subclinical seizures, and can contribute to an objective evaluation of the efficacy of antiepileptic drugs.

Effects of stress of postnatal development on corticosterone, serotonin and behavioral changes - Corrected Proof

2009-10-09

Abstract: Stressful events early in life are associated with later psychiatric disorders. We focused on developmental stage and evaluated changes in the corticosterone and serotonergic systems as well as in later anxiety-related behavioral tests. Stressed male Wistar rats were divided into two groups: stressed from postnatal day 11 (PND 11) to 15 and stressed from PND 16 to 20. The rats were exposed to an elevated open platform. Stress increased corticosterone in both experimental groups. In the hypothalamus, amygdala and hippocampus, 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) increased in the rats stressed from PND 11 to 15, and decreased in the rats stressed from PND 16 to 20. In a later behavioral test, rats stressed from PND 11 to 15 traveled shorter distances and tended to spend less time in the center than control rats following restraint stress. There were no significant changes in 5-HT and 5-HIAA in hypothalamus, amygdala and hippocampus after restraint stress in adults. These findings indicate that stress reactions and later effects are different depending on the developmental stage during which the rats were stressed. Stress during the PND 11–15 period may enhance later anxiety-related behaviors without altering 5-HT and 5-HIAA content.

Positive association between benign familial infantile convulsions and LGI4 - Corrected Proof

Atsushi Ishii, Bo Zhang, Sunao Kaneko, Shinichi Hirose — 2009-10-08

Abstract: Purpose: LGI4 is located in 19q13.11, where the locus of benign familial infantile convulsions (BFIC) has been mapped. LGI4 belongs to a family of proteins with the epilepsy-associated repeat (EAR) domain and is associated with various epilepsies. We investigated whether LGI4 is a candidate gene for BFIC. Methods: Fifteen patients with BFIC were examined for mutations and/or polymorphisms of LGI4 by using a direct sequencing method. Results: Several frequent polymorphisms were identified. The genotype frequency distribution of c.1722G/A polymorphism was significantly different between patients with BFIC and control subjects (p<0.05). Logistic regression analysis showed that the G allele of c.1722G/A polymorphism had significant recessive effects on the increased relative risk for BFIC (p<0.05). There was no association between c.1722G/A polymorphism and benign familial neonatal convulsion, an epilepsy phenotype similar to BFIC but genetically distinguished from BFIC. Discussion: The positive genotypic association between BFIC and c.1722G/A polymorphism suggests that LGI4 might contribute to the susceptibility to BFIC.

Characteristics of the synchronous occipital and frontopolar spike phenomenon in Panayiotopoulos syndrome - Corrected Proof

Harumi Yoshinaga, Katsuhiro Kobayashi, Yoko Ohtsuka — 2009-10-08

Abstract: Purpose: The synchronous appearance of an occipital and frontopolar spike (the Fp-O spike) is characteristic of Panayiotopoulos syndrome (PS). This phenomenon is also seen in various other types of epilepsy, particularly those that occur in childhood. Using dipole analysis and sequential mapping, we investigated the characteristics of the Fp-O spike observed in seven patients with PS and six patients with symptomatic localization-related epilepsy in childhood (SLE). Methods: We analyzed both one averaged spike and 20 manually selected successive individual Fp-O spikes for each patient through sequential topographical mapping with steps of 10ms from 40ms before to 40ms after the negative maximum peak of each spike. For dipole analysis, a period of 40ms before the maximum negative peak of the averaged spike in each patient was examined using equivalent current dipole localization software. Results: Sequential mapping revealed that occipital negative peaks preceded frontal negative peaks in all of the PS patients, as well as in two of the six SLE patients. The four remaining SLE patients did not exhibit preceding occipital peaks. In all of the patients with PS, representative dipole locations were in the posterior area, whereas in SLE patients they were scattered over more anterior areas. The estimated sources of the Fp-O and O spikes appeared to have the same position and orientation in the two PS patients. Conclusion: We conclude that Fp-O spikes in PS occur as the result of a rapid spread of epileptic activity from the posterior areas to the anterior areas of the brain. Fp-O spikes in PS patients show a uniform topographical pattern and dipole location, whereas those in other patients show more heterogeneity in these features. These findings support the homogeneity of PS and thus its designation as a syndrome.

Prolonged left homonymous hemianopsia associated with migraine-like attacks in a child with Sturge–Weber syndrome - Corrected Proof

Shuichi Shimakawa, Ryohei Miyamoto, Takuya Tanabe, Hiroshi Tamai — 2009-10-05

Abstract: We report a patient with Sturge–Weber Syndrome (SWS) who developed migraine-like headaches followed by cerebral infarction. SWS without facial nevus was diagnosed based on calcification detected by CT and pial angioma detected by enhanced MRI. His migraine-like headaches were preceded by left homonymous hemianopsia, which persisted for more than 60min. Although homonymous hemianopsia disappeared with cessation of the headache until 13years of age, from age 14years onward, this homonymous hemianopsia persisted after the headaches ended. Moreover, reduced cerebral blood flow was seen in the right occipital area on SPECT. At first, his left homonymous hemianopsia persisted for several months after the headache disappeared, but it had recovered completely. However, the durations of episodes of left homonymous hemianopsia, which persisted after headache disappearance, gradually became longer. At last one year after his first admission, the visual defect had become permanent. SWS is well known to be associated with migraine attacks and hemianopsia. However, the course of our present patient, i.e. recurrent homonymous hemianopsia, associated with migraine-like headaches becoming permanent, is rare. The pathophysiological mechanism underlying this clinical course is uncertain. The efficacy of valproate and propranolol as preventive therapy has been inadequate, to date.

Acute encephalopathy of Bacillus cereus mimicking Reye syndrome - Corrected Proof

2009-10-05

Abstract: We present an 11-year-old boy diagnosed as having acute encephalopathy and liver failure with the underlying condition of a metabolic dysfunction. He developed convulsions and severe consciousness disturbance following gastroenteritis after the ingestion of some fried rice. He showed excessive elevation of transaminases, non-ketotic hypoglycemia and hyperammonemia, which were presumed to reflect a metabolic dysfunction of the mitochondrial beta-oxidation, and he exhibited severe brain edema throughout the 5th hospital day. He was subjected to mild hypothermia therapy for encephalopathy, and treated with high-dose methylprednisolone, cyclosporine and continuous hemodiafiltration for liver failure, systemic organ damage and hyperammonemia. The patient recovered with the sequela of just mild intelligence impairment. In this case, Bacillus cereus, producing emetic toxin cereulide, was detected in a gastric fluid specimen, a stool specimen and the fried rice. It was suggested that the cereulide had toxicity to mitochondria and induced a dysfunction of the beta-oxidation process. The patient was considered as having an acute encephalopathy mimicking Reye syndrome due to food poisoning caused by cereulide produced by B. cereus.

Structural basis of neuronal ceroid lipofuscinosis 1 - Corrected Proof

2009-09-30

Abstract: To elucidate the basis of neuronal ceroid lipofuscinosis 1 (CLN1) from the viewpoint of enzyme structure, we constructed structural models of mutant palmitoyl protein thioesterase 1 (PPT1) proteins using molecular modeling software, jackal and TINKER. We classified the amino acid substitutions responsible for CLN1 and divided them into two groups, groups 1 and 2, based on the biochemical phenotype. Then, we examined the structural changes in the PPT1 protein for each group by calculating the solvent-accessible surface area (ASA) and the number of atoms affected. Our results revealed that the structural changes in group 1, which exhibits a complete deficiency of PPT1 activity, were generally large and located in the core region of the enzyme molecule. In group 2 exhibiting residual PPT1 activity, the structural changes in PPT1 were smaller and localized near the surface of the enzyme molecule. Coloring of affected atoms based on the distances between those in the wild type and mutants revealed the characteristic structural changes in the PPT1 protein geographically and semi-quantitatively. Structural investigation provides us with a deeper insight into the basis of CLN1.

Positron emission tomography with glucose hypermetabolism of a hypothalamic hamartoma in infantile spasms associated with Pallister–Hall syndrome - Corrected Proof

Hiroyuki Wakamoto, Akemi Sumi, Takahiro Motoki, Hiromitsu Ohmori — 2009-09-30

Abstract: Although hypothalamic hamartomas (HHs) have been shown to be intrinsically epileptogenic and to participate in the generation of gelastic seizures, no evidence has been reported regarding its contribution to the pathogenesis of infantile spasms. We describe a male infant with Pallister–Hall syndrome who had a large HH presenting with infantile spasms without hypsarrhythmia. [18F]fluoro-deoxyglucose positron emission tomography scan performed during the period of epileptic spasms demonstrated glucose hypermetabolism of the HH, which resolved after cessation of the spasms with adrenocorticotropin hormone treatment. No concurrent increased metabolic activity in the lenticular nuclei or brainstem was observed in the ictal or interictal states. The present case suggests that HHs may be involved in the pathogenesis of infantile spasms, possibly with propagation of epileptic discharges from the hamartoma to the descending spinal pathway.

Functional deficiencies of sulfite oxidase: Differential diagnoses in neonates presenting with intractable seizures and cystic encephalomalacia - Corrected Proof

2009-09-30

Abstract: Sulfite oxidase is a mitochondrial enzyme encoded by the SUOX gene and essential for the detoxification of sulfite which results mainly from the catabolism of sulfur-containing amino acids. Decreased activity of this enzyme can either be due to mutations in the SUOX gene or secondary to defects in the synthesis of its cofactor, the molybdenum cofactor. Defects in the synthesis of the molybdenum cofactor are caused by mutations in one of the genes MOCS1, MOCS2, MOCS3 and GEPH and result in combined deficiencies of the enzymes sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase. Although present in many ethnic groups, isolated sulfite oxidase deficiency and molybdenum cofactor deficiency are rare inborn errors of metabolism, which makes awareness of key clinical and laboratory features of affected individuals crucial for early diagnosis. We report clinical, radiologic, biochemical and genetic data on a Brazilian and on a Turkish child with sulfite oxidase deficiency due to the isolated defect and impaired synthesis of the molybdenum cofactor, respectively. Both patients presented with early onset seizures and neurological deterioration. They showed no sulfite oxidase activity in fibroblasts and were homozygous for the mutations c.1136A>G in the SUOX gene and c.667insCGA in the MOCS1 gene, respectively. Widely available routine laboratory tests such as assessment of total homocysteine and uric acid are indicated in children with a clinical presentation resembling that of hypoxic ischemic encephalopathy and may help in obtaining a tentative diagnosis locally, which requires confirmation by specialized laboratories.

Thiamine-deficient encephalopathy due to excessive intake of isotonic drink or overstrict diet therapy in Japanese children - Corrected Proof

2009-09-28

Abstract: Aim: To report on two children with encephalopathy caused by dietary thiamine deficiency due to newly developing nutritional problems in contemporary Japan. Subjects: A 1-year-old boy who had consumed 1l of isotonic drinks per day for 4months after an episode of diarrhea, and presented with ocular movement disorder, dystonia, and unconsciousness. The other subject was an 11-month-old boy who suffered from vomiting and somnolence; he and his mother had atopic dermatitis, and he had been on a low-allergen diet that strictly restricted intake of eggs, dairy products, meat, and fish since his early infancy. Results: Both patients showed decreased blood thiamine levels and magnetic resonance imaging revealed striatal and thalamic lesions. Thiamine administration yielded prompt improvement of symptoms, but cavitiform lesions in the bilateral putamen persisted in the first patient, accompanied by residual generalized dystonia. Marked elevation of blood/cerebrospinal lactate levels and severe hyponatremia were present in this patient. Conclusion: Thiamine-deficient encephalopathy in Japanese children due to excessive intake of sports drink or overstrict diet therapy for atopic dermatitis has been increasingly reported during the last decade, but is still not broadly recognized. These children may visit hospitals due to persistent vomiting as a symptom of thiamine deficiency, but glucose infusion without thiamine supplementation can aggravate their condition. Knowledge of these facts in medical and public settings is necessary to correct the erroneous impression that nutritional options given to ill children are necessarily beneficial for health, and promote awareness that they can be harmful when consumed in excess.

Central nervous system and muscle involvement in an adolescent patient with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency - Corrected Proof

2009-09-28

Abstract: We report an adolescent case of late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD) characterized by intermittent nausea and depressive state as early symptoms. At the age of 12years and 11months, the patient experienced intermittent nausea and vomiting, and depressive state. She was on medication for depression for 5months but it was ineffective. Brain magnetic resonance imaging showed disseminated high-intensity areas in the periventricular white matter and in the splenium of the corpus callosum on T2-weighted images and fluid-attenuated inversion-recovery images. Progressive muscle weakness occurred and blood creatine kinase level was found to be elevated. The muscle biopsy revealed lipid storage myopathy. Urine organic acid analysis and mutation analysis of the ETFDH gene confirmed the diagnosis of MADD. With oral supplements of riboflavin and l-carnitine, in addition to a high-calorie and reduced-fat diet, her clinical symptoms improved dramatically. Early diagnosis is important because riboflavin treatment has been effective in a significant number of patients with MADD.

Early infantile epileptic encephalopathy with unusual favourable outcome - Corrected Proof

María Rosario Cazorla, Alfonso Verdú, Carmen Montes, Fernando Ayuga — 2009-09-22

Abstract: The authors report the case of an infant suffered from early infantile epileptic encephalopathy with suppression–burst, or Ohtahara syndrome, a severe form of epilepsy in early childhood. The patient was treated with vigabatrin causing a favourable response. This unusual outcome may be related with the normality of neuroimaging and metabolic studies, as happens with idiopathic West syndrome cases.

Bilateral brachial plexus palsy and right Horner syndrome due to congenital cervicothoracal syringomyelia - Corrected Proof

2009-09-18

Abstract: Syringomyelia (SM) is a disorder in which a cyst forms within the spinal cord. This cyst, called a syrinx, expands and elongates over time, destroying the center of the cord. Horner syndrome is an infrequent illness caused by a lesion of the cervical sympathetic nerve fiber. Its clinical features are facial anhidrosis, ptosis, miosis, and hypochromia iridis of the affected side. A full-term male newborn infant was admitted with weakness in bilateral upper extremities and narrowing of the palpebral fissure on the right side. Ophthalmologic examination revealed a smaller right pupil. Muscle power in bilateral upper limbs was 1/5. Chest X-ray and cranial magnetic resonance imaging were normal. Magnetic resonance imaging of the cervicothoracic spine showed SM at C4-T2 level. Electromyographic examination revealed bilateral brachial plexus palsy. The diagnosis was of brachial plexus palsy and congenital Horner syndrome due to congenital cervicothoracic SM. According to our best knowledge, this association has not been reported in the literature.

The syndrome of perisylvian polymicrogyria with congenital arthrogryposis - Corrected Proof

2009-09-14

Abstract: Background: Bilateral perisylvian polymicrogyria (BPP) is a well-recognized malformation of cortical development commonly associated with epilepsy, cognitive impairment, and oromotor apraxia. Reports have suggested the association of BPP with arthrogryposis multiplex congenita. We sought to investigate the clinical, electrophysiological, and neuroradiological features of this combined syndrome to determine if there are unique features that distinguish BPP with arthrogryposis from BPP alone. Methods: Cases of BPP with congenital arthrogryposis were identified from a large research database of individuals with polymicrogyria. Clinical features (including oromotor function, seizures, and joint contractures), MR brain imaging, and results of neuromuscular testing were reviewed. Results: Ten cases of BPP with congenital arthrogryposis were identified. Most cases had some degree of oromotor apraxia. Only a few had seizures, but a majority of cases were still young children. Electrophysiological studies provided evidence for lower motor neuron or peripheral nervous system involvement. On brain imaging, bilateral polymicrogyria (PMG) centered along the Sylvian fissures was seen, with variable extension frontally or parietally; no other cortical malformations were present. We did not identify obvious neuroimaging features that distinguish this syndrome from that of BPP without arthrogryposis. Conclusions: The clinical and neuroimaging features of the syndrome of BPP with congenital arthrogryposis appear similar to those seen in cases of isolated BPP without joint contractures, but electrophysiological studies often demonstrate coexistent lower motor neuron or peripheral nervous system pathology. These findings suggest that BPP with arthrogryposis may have a genetic etiology with effects at two levels of the neuraxis.

Voxel-based analysis of white matter during adolescence and young adulthood - Corrected Proof

Mingguo Qiu, Qiyu Li, Guangjiu Liu, Bing Xie, Jiang Wang — 2009-09-09

Abstract: Purpose: To evaluate differences in age-related brain white matter by voxel-based analysis of healthy adolescents and young adults. Materials and methods: Echo-planar diffusion-tensor magnetic resonance (MR) imaging was performed in healthy subjects of 3 groups (aged 11–13, 16–18 and 23–25, respectively). Linear correlative analyses were applied to determining age-related fractional anisotropy (FA) and mean diffusivity (MD), and t-test was performed to compare FA and mean diffusion maps between different age groups. Results: Significant positive correlation of FA with age was found in the internal capsule, the external capsule, the frontal white matter, and the body and genu of the corpus callosum. Compared with the 11–13 age group, FA in the 16–18 age group increased in the internal capsule, the frontal white matter, the body and the splenium of the corpus callosum. Compared to the 16–18 age group, FA in the 23–25 age group increased in the frontal white matter, the posterior limb of internal capsule, and the genu of the corpus callosum. Statistically significant negative correlation of the mean diffusion with age was found in the frontal and parietal white matter. Compared with the 11–13 age group, MD in the 16–18 age group decreased in the prefrontal and the temporo-parietal white matter. Compared with the 16–18 age group, MD in the 23–25 age group decreased in the frontal white matter. Conclusion: Diffusion-tensor MR imaging results indicate that white matter maturation assessed at different ages involves increases in FA and decreases in mean diffusion of the white matter during adolescence and young adulthood. FA and mean diffusion may reflect different physiologic processes in healthy adolescents and young adults. Taken together, these data show that maturation of white matter is an important part of brain maturation during adolescence and young adulthood.

A case of hypertensive encephalopathy with extensive spinal lesions on MRI - Corrected Proof

Masako Nagato, Yasuo Takahashi, Mieko Yoshioka, Mitsuhiko Nambu — 2009-09-07

Abstract: A 14-year-old female had repeated vomiting, headache, abdominal pain, visual field deficit and lethargy at the onset of hypertensive encephalopathy. Cerebrospinal fluid (CSF) test revealed a high level of IgG and protein. MRI demonstrated no supratentorial cerebral lesions but hyperintense lesions were observed from the lower pons to the Th8 level of spinal cord and cerebellar cortex on T2 weighted and FLAIR images without contrast enhancement. The two antihypertensive drugs stabilized to control her blood pressure and improved her clinical symptoms. Reexamination of MRI and cerebrospinal fluid test also revealed clear improvement of the above abnormalities. The abnormal findings on abdominal CT and renography led us to suspect renal infarction. Abdominal angiography demonstrated multifocal stenoses of renal interlobar arteries, which were supposed to supply the renal infarcted regions. These suggested that the renal infarctions due to fibromuscular dysplasia caused systemic hypertension. There have been only two reports that demonstrated spinal cord lesions in reversible posterior leukoencephalopathy syndrome (RPLES). We report extensive spinal lesions on MRI and a high level of IgG in CSF at the subacute phase in a young female with RPLES associated with hypertensive (brainstem) encephalopathy.

Non-convulsive status epilepticus and audiogenic seizures complicating a patient with asymmetrical epileptic spasms - Corrected Proof

2009-09-07

Abstract: A female infant suffered from epilepsy since the neonatal period, which evolved into West syndrome at the age of 2months. Spasms in series and hypsarrhythmia disappeared after treatment with high-dose phenobarbital; however, single spasms persisted with right-sided predominance, and polyspike activity in the left parieto-temporal areas preceded or coincided with these spasms. Magnetic resonance imaging revealed a small calcification in the right occipital area, and positron emission tomography showed hypometabolism over the right hemisphere. Widespread epileptic discharges gradually increased on electroencephalography (EEG) during sleep thereafter. The patient presented with daytime unresponsiveness at 1year and 6months, when diffuse, irregular spike and wave activity characterized the waking EEG. Spasms or brief tonic seizures with right-sided predominance were provoked by auditory stimuli during this period, particularly by her mother’s voice, with ictal EEG of right posterior predominant fast activity and subsequent desynchronization. The administration of clobazam resulted in the marked improvement of EEG findings and transient disappearance of spasms. Presumably, certain patients with asymmetrical epileptic spasms may be regarded as a unique type of localization-related epilepsy, and can show an unusual course of evolution in comparison to other cases of epilepsy that evolve after West syndrome.

Hereditary spastic paraplegia and axonal motor neuropathy caused by a novel SPG3A de novo mutation - Corrected Proof

2009-09-07

Abstract: Mutations in the SPG3A gene (atlastin protein) cause approximately 10% of autosomal-dominant hereditary spastic paraplegia. Most patients with an SPG3A mutation present with a pure phenotype and early-onset disease, although complicated forms with peripheral neuropathy are also reported. We report a new heterozygous S398F mutation in exon 12 of the SPG3A gene causing a very early-onset spastic paraplegia in association with motor axonal neuropathy in a 4-year-old girl resembling diplegic cerebral palsy.

Cognitive evolution of a girl submitted to right hemispherotomy when five years old - Corrected Proof

Piernanda Vigliano, Giorgia Margary, Irene Bagnasco, Laura Jarre — 2009-08-28

Abstract: Since the age of three years the patient suffered from early drug-resistant partial epilepsy with electric status during slow sleep, owing to a micropolygyric malformation of the right fronto-temporo-parietal lobes. The hemispherotomy (when five years of age) was followed by immediate and persistent disappearance of the seizures and withdrawal of the treatment. The transfer of right hemispheric functions to the left hemisphere occurred very early; the child’s development was examined in relation to the restoration of these functions and the age at surgery. The early surgical intervention and the plasticity of the brain – along with an intensive cognitive rehabilitation – seem to be important in determining the favorable global cognitive outcome. Visuo-spatial abilities and multi-modal integration of these functions with memory, attention and language have been the most critical domains and are recently in progress. The rapidity of processing complex tasks is particularly lacking. This seems to be the expression of the defective development of the Central Executive System.

Hypomyelination, hypogonadotropic hypogonadism, hypodontia – First Polish patient - Corrected Proof

2009-08-25

Abstract: The term 4H was suggested for the rare, novel entity with hypomyelination, hypogonadotropic hypogonadism and hypodontia. A combination of clinical findings with ataxia and endocrinological abnormalities, brain MRI and dentition history are crucial for the diagnosis. We present the first Polish patient with this disease with repeated brain MRI, MRI of the pituitary gland and orthopantomogram.

Recurrent acute cerebellar ataxia associated with anti-cardiolipin antibodies - Corrected Proof

Nobutsune Ishikawa, Masao Kobayashi — 2009-08-25

Abstract: Various autoantibodies are detected in patients with acute cerebellar ataxia (ACA). Although an autoimmune process may contribute to the mechanism of ACA, its pathophysiology is not completely understood. We report a girl with recurrent ACA and anti-cardiolipin antibodies. Her cerebral blood flow imaging showed hypoperfusion in the cerebellum, which improved when the anti-cardiolipin antibodies disappeared. Our case suggests that vasculopathy or non-vascular neurotoxicity in the cerebellum caused by antiphospholipid antibodies leads to acute cerebellar ataxia.

Rapid oscillatory activity in delta brushes of premature and term neonatal EEG - Corrected Proof

2009-08-17

Abstract: We compared frequency and power of neonatal EEG delta brush rapid oscillatory activity (ROA) using multiple band frequency analysis (MBFA) in three groups; pre-term (PT, post-conceptional age 33–35.6weeks, n=5); full-term (FT, 39.4–40.6weeks, n=5) and pre-term or full-term with phenobarbital exposure (PB, n=5). Mean number of delta brushes analyzed was 29.4 (range 26–47) in PT, 20.8 (14–33) in FT and 20 (7–37) in PB. Mean frequency±standard deviation (s.d.) was 16.9±2.1Hz (range 15–20Hz) in PT, 17.3±1.9Hz (15–20Hz) in FT and 16.1±1.6Hz (14–19Hz) in PB. Mean power±s.d. was 22.9±6.2μV2 (range 16–39μV2) in PT, 11.9±4.1μV2 (7–19μV2) in FT and 17.1±6.2μV2 (9–26μV2) in PB. Power was significantly higher in PT than FT (p<0.005). Power after merging PB into respective PT (PT′, n=8) and FT (FT′, n=7) groups, remained significantly higher in PT′ (mean±s.d. 21.8±7.4μV2) than FT′ (11.4±3.6μV2) (p<0.05). We characterise ROA in delta brushes in maturing neonates using MBFA, which may provide additional information for assessing future seizure recurrence and epilepsy risk.

Magnetic resonance imaging at first episode in pediatric multiple sclerosis retrospective evaluation according to KIDMUS and lesion dissemination in space criteria - Corrected Proof

2009-08-17

Abstract: Background: Several diagnostic imaging criteria are being described and examined in pediatric multiple sclerosis (MS). Compared to adults, children are more likely to experience acute or relapsing demyelinating episodes of various etiologies which show similar clinical and magnetic resonance imaging (MRI) findings. Aim: To investigate the fulfillment of MRI diagnostic criteria at initial episode in pediatric MS. Methods: We reviewed our series of children and adolescents with the final diagnosis of clinically definite MS and applied the McDonald dissemination in space (DIS) and KIDMUS criteria to their initial MRI scans. Results: Thirty patients (17 girls, 13 boys), most with brainstem dysfunction and polysymptomatic presentation, were included in the study. Twenty-five (83.3%) patients fulfilled both McDonald and KIDMUS criteria. Patients who did not meet any McDonald DIS criteria did not meet KIDMUS criteria either. Only one patient met the McDonald criteria but not the KIDMUS criteria because of the absence of lesions perpendicular to corpus callosum. Conclusions: Our results show 5/30 (16.6%) of MS patients may not present the diagnostic MRI features initially. The variable sensitivity observed for the current MRI criteria in different series can be due to referral biases, differences between populations and length of follow-up, and the definition of MS patients by two attacks only.

The axonal damage marker tau protein in the cerebrospinal fluid is increased in patients with acute encephalopathy with biphasic seizures and late reduced diffusion - Corrected Proof

2009-08-13

Abstract: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a recently clinicoradiologically-established encephalopathy syndrome. In the present study, we examined the levels of cerebrospinal fluid (CSF) tau protein, a marker of axonal damage, in 11 patients with AESD. CSF tau levels were normal on day 1 and increased from day 3 of the disease between the initial and the secondary seizures. Magnetic resonance imaging (MRI) reveals reduced diffusion in the subcortical white matter during days 3–7. Two patients showed elevated tau protein prior to the diffusion abnormality of subcortical white matter on MRI. Levels of CSF neuron specific enolase (NSE), a neuronal marker, were elevated in only two out of seven patients with AESD, and CSF tau levels were also increased in these patients. Our results indicated that tau protein is a more sensitive marker than NSE and axonal damage causes the conspicuous MRI findings in AESD patients. A therapeutic strategy for axonal protection should be developed to prevent severe neurological impairment of AESD patients.

Polysomnographic features in infants with early diagnosis of congenital hypothyroidism - Corrected Proof

2009-08-10

Abstract: Thyroid hormones play a major role in the maturation process of the brain. Currently, congenital hypothyroidism is detected by mass screening. The impact of this early hormonal deficiency on the organization of the sleep pattern is not known. In this study, the polysomnographic features in children diagnosed with congenital hypothyroidism were analyzed. Children were detected by mass population screening and the hormonal replacement therapy starts immediately. Children’s age ranged between 1.5 and 18months of age. The duration of hormonal treatment before sleep recordings varied between 8days and 17months. Children were polysomnographically recorded in the morning, for at least 2h, obtaining more than one sleep cycle. Results showed a high prevalence of females (5/1) in the group studied. A high proportion of infants (43%) displayed central apnea in different degrees (mild, moderate and severe) as well as hypopnea (83%), mainly in subjects around 4 and 8months of age. The proportion of infants displaying central apnea decreases as age increases. In addition, indeterminate (light) sleep increase and quiet (slow wave) sleep decrease significantly regardless of age and treatment. The percentage of REM sleep correlated positively with the age of the child at the beginning of the treatment, and negatively with their age at the time of the study. These data indicate that congenital hypothyroidism facilitates the presence of central sleep apnea. The decrease of these respiratory alterations correlates with the increase of the hormonal replacement therapy. It seems that sleep respiratory alterations in congenital hypothyroidism are linked to brain maturation processes in which thyroid hormones play a major role.

Screening of the LIX1 gene in Japanese and Malaysian patients with SMA and/or SMA-like disorder - Corrected Proof

2009-08-07

Abstract: Background: The majority of spinal muscular atrophy (SMA) patients showed homozygous deletion or other mutations of SMN1. However, the genetic etiology of a significant number of SMA patients has not been clarified. Recently, mutation in the gene underlying cat SMA, limb expression 1 (LIX1), has been reported. Similarity in clinical and pathological features of cat and human SMA may give an insight into possible similarity of the genetic etiology. Patients and methods: In this study, we screened for a mutation in LIX1 using direct DNA sequencing in our SMA and/or SMA-like patients who retained SMN1. A total of 33 patients were enrolled in this study, of which 22 were Japanese and 11 were Malaysians. All these patients possessed at least two copies of SMN1. Results: We did not identify any pathogenic mutations in the coding regions or splice sites of LIX1 in the patients. In addition, we described a polymorphism within LIX1 intron 3, c.387+107A>T. We found that A-allele is significantly more frequent in SMA patients compared to normal individuals. Conclusion: Molecular genetic analysis of our SMA and/or SMA-like patients suggests that LIX1 is not associated with the development of their disorders. However, the number of patients analyzed in this study was very limited, and a larger study with bigger sample size is needed to confirm this result.

Pontine hypoplasia in 5p-syndrome: A key MRI finding for a diagnosis - Corrected Proof

Takeshi Ninchoji, Jun-ichi Takanashi — 2009-08-03

Abstract: A 5-year-old female case of 5p-syndrome exhibited pontine hypoplasia on magnetic resonance imaging. A high-pitched cry characteristic of 5p-syndrome disappeared after 2years. 5p-syndrome should be considered as a differential diagnosis for brainstem, especially pontine, hypoplasia. Older patients with brainstem hypoplasia should be asked about a history of a high-pitched cry in infancy so as not to miss this syndrome.

Parieto-occipital encephalomalacia in neonatal hyperammonemia with ornithine transcarbamylase deficiency: A case report - Corrected Proof

2009-07-29

Abstract: Urea cycle disorders are congenital metabolic disorders that often cause episodic hyperammonemia. Neuroimaging in episodic hyperammonemia demonstrates several patterns of brain injuries, including focal lesions in the lentiform nucleus, insula, cingulate gyrus, and perirolandic fissure, as well as diffuse cerebral edema. In cases with neonatal onset of hyperammonemia, similar lesions have also been reported. We herein report a boy with severe neonatal hyperammonemia caused by ornithine transcarbamylase deficiency. He presented with parieto-occipital encephalomalacia, which resembles severe neonatal hypoglycemia on magnetic resonance imaging. This radiological finding may indicate parieto-occipital vulnerability not only to hypoglycemia but also to hyperammonemia.

Hemifacial seizures due to ganglioglioma of cerebellum - Corrected Proof

2009-07-23

Abstract: We present a male infant with hemifacial seizures refractory to antiepileptic medication. Hemifacial spasms around the left eye were frequent during wakefulness and sleep since birth. He also had mild psychomotor retardation. Magnetic resonance imaging (MRI) revealed a large tumor in the left middle cerebellar peduncle. Ictal single photon emission computed tomography (SPECT) and ictal 18F-fluorodeoxyglucose [18F-FDG] positron emission tomography (PET) revealed hyperperfusion and hyper glucose metabolism at the tumor. Total removal of the tumor resulted in complete disappearance of hemifacial seizures and improved psychomotor development, indicating that the cerebellar tumor caused hemifacial seizures. A histopathological study confirmed that the tumor was a ganglioglioma. This case and the literature on similar cases indicated that this was a new epileptic syndrome originating in the cerebellum. Early diagnosis and early complete removal of the epileptogenic lesion should be recommended for this syndrome.

Neurodevelopment in the offspring of Japanese systemic lupus erythematosus patients - Corrected Proof

2009-07-21

Abstract: Objective: To evaluate pregnancy outcome of systemic lupus erythematosus (SLE) and the neuropsychological outcomes in offspring of SLE mothers. Study design: Pregnancy outcomes of SLE patients from 1989 to 2006 were determined and the neuropsychological development of the children born to SLE patients was examined suited for their age; Bayley Scales of Infant Development up to four years and Kauffmann Assessment Battery for Children from four years onwards. Results: Of the 233 deliveries, 58 (24.7%) were preterm, 72 (30.9%) were low-birth-weight, and 46 (19.7%) were IUGR. Twenty-six children enrolled in this study had normal intelligence. The mean MDI and PDI were 95.8±10.1 and 94.6±14.1, respectively. The mean scores for the Sequential Processing scale, Simultaneous Processing scale, and Mental Processing composite were 103.1±13.3, 104.2±10.2, and 104.2±12.2, respectively. In the children with anti-Ro/SS-A antibody-positive mothers, mean gestational age and birth weight were significantly lower (p<0.05), as a result, the mean score of Sequential Processing and Mental Processing were significantly lower than that of negative mothers. The presence of maternal antiphospholipid antibody was not related to gestational age, birth weight and any score on the intelligence tests, except for the rate of IUGR. Conclusion: The rates of preterm delivery and IUGR were frequent in the SLE patients and careful monitoring and management of the disease during pregnancy are still necessary. We should examine the neurodevelopment of the children born from mothers with anti-Ro/SS-A antibody prospectively.

Diffuse subcortical band heterotopia, periodic limb movements during sleep and a novel “de novo” mutation in the DCX gene - Corrected Proof

2009-07-21

Abstract: Mutations of the DCX gene (Xp22.3) cause X-linked lissencephaly in males and double cortex syndrome (DCS) or subcortical band heterotopia (SBH) in females. SBH is characterized by bilateral bands of grey matter interposed in the white matter between the cortex and the lateral ventricles. The main clinical manifestation in patients with SBH is epilepsy, which may be partial or generalized and is intractable in approximately 65% of the patients. An association of periodic limb movements (PLMs) and SBH has not been documented previously. We describe a 2-year-old girl affected by SBH with epilepsy and periodic limb movements (PLMs), in whom a novel “de novo” missense substitution, Met1Val (M1V), was identified in the DCX gene. Physiopathological links between PLMs and SBH are discussed.