Dietary supplementation with partially hydrolyzed guar gum helps improve constipation and gut dysbiosis symptoms and behavioral irritability in children with autism spectrum disorder.

Prebiotic dietary water-soluble fiber obtained from partially hydrolyzed guar gum was added to diets of children with autism spectrum disorders who presented constipation symptoms. Supplementation with partially hydrolyzed guar gum altered gut microbiota and significantly increased the frequency of defecation per week and altered the gut microbiota. In addition, supplementation with partially hydrolyzed guar gum significantly (p<0.05) decreased and tended to decrease (p = 0.07) the concentrations of serum interleukin-1ß and tumor necrosis factor-α, respectively. More importantly, supplementation with partially hydrolyzed guar gum significantly ameliorated behavioral irritability as per the Aberrant Behavior Checklist, Japanese Version. The present study demonstrated that supplementation with partially hydrolyzed guar gum to diets of constipated autism spectrum disorders children helped improve constipation and gut dysbiosis symptoms, which in turn helped attenuate the level of serum inflammation cytokines and behavioral irritability.

X-linked Charcot-Marie-Tooth disease type 5 with recurrent weakness after febrile illness.

X-linked Charcot-Marie-Tooth disease type 5 (CMTX5) is an X-linked disorder characterized by early-onset sensorineural hearing impairment, peripheral neuropathy, and progressive optic atrophy. It is caused by a loss-of-function mutation in the phosphoribosyl pyrophosphate synthetase 1 gene (PRPS1), which encodes isoform I of phosphoribosyl pyrophosphate synthetase (PRS-I). A decreased activity leads to nonsyndromic sensorineural deafness (DFN2), CMTX5, and Arts syndrome depending upon residual PRS-I activity. Clinical and neurophysiological features of pediatric CMTX5 are poorly defined. We report two male siblings with peripheral neuropathy and prelingual sensorineural hearing loss who carried a novel c.319A>G (p.Ile107Val) PRPS1 missense mutation. They exhibited recurrent episodes of transient proximal muscle weakness, showing Gowers' sign and waddling gait after suffering from febrile illness. This transient weakness has not been previously reported in CMTX5. A patient with Arts syndrome was reported to have transient proximal weakness after febrile illness. The transient weakness presenting in both CMTX5 and Arts syndrome suggests an overlap of signs and a continuous spectrum of PRS-I hypoactivity disease. Children presenting with transient neurological signs should be evaluated for peripheral neuropathy and consider genetic analysis for PRPS1.

Immunohistochemical and biochemical evidence for the presence of serotonin-containing neurons and nerve fibers in the octopus arm.

The octopus arm contains a tridimensional array of muscles with a massive sensory-motor system. We herein provide the first evidence for the existence of serotonin (5-HT) in the octopus arm nervous system and investigated its distribution using immunohistochemistry. 5-HT-like immunoreactive (5-HT-lir) nerve cell bodies were exclusively localized in the cellular layer of the axial nerve cord. Those cell bodies emitted 5-HT-lir nerve fibers in the direction of the sucker, the intramuscular nerves cords, the ganglion of the sucker, and the intrinsic musculature. Others 5-HT-lir nerve fibers were observed in various tissues, including the cerebrobrachial tract, the skin, and the blood vessels. 5-HT was detected by high-performance liquid chromatography in various regions of the octopus arm at levels matching the density of 5-HT-lir staining. The absence of 5-HT-lir interconnections between the cerebrobrachial tract and the other components of the axial nerve cord suggests that two types of 5-HT-lir innervation exist in the arm. One type, which originates from the brain, may innervate the periphery through the cerebrobrachial tract. Another type, which originates in the cellular layer of the axial nerve cord, may form an intrinsic network in the arm. In addition, 5-HT-lir fibers likely emitted from the neuropil of the axial nerve cord were found to project into cells showing staining for peripheral choline acetyltransferase, a marker of sensory cells of the sucker. Taken together, these observations suggest that intrinsic 5-HT-lir innervation may participate in the sensory transmission in the octopus arm.

The Role of Nutritional Supplements in the Treatment of ADHD: What the Evidence Says.

Attention-deficit hyperactivity disorder (ADHD) is a common behavioral disorder in children and adolescents and may persist into adulthood. Insufficient nutritional supply of long-chain polyunsaturated fatty acids (LC-PUFAs) and other components including various minerals has been suggested to play a role in the development of ADHD symptoms. This review presents the evidence regarding the role of nutritional PUFA, zinc, iron, and magnesium supplements in the treatment of ADHD with a focus on the critical evaluation of the relevant literature published from 2014 to April 2016. The evaluation of therapeutic nutritional LC-PUFA supplementation in ADHD has shown mixed and inconclusive results and at best marginal beneficial effects. The benefits of PUFAs are much smaller than the effect sizes observed for traditional pharmacological treatments of ADHD. The effectiveness of PUFA supplements in reducing medication dosage has been suggested but needs to be confirmed. Zinc, iron, and magnesium supplementation may reduce ADHD symptoms in children with or at high risk of deficiencies in these minerals. However, convincing evidence in this regard is lacking.

A preliminary investigation on the relationship between gut microbiota and gene expressions in peripheral mononuclear cells of infants with autism spectrum disorders.

Fecal and blood samples of infants with autism spectrum disorders (ASD) and healthy infants were analyzed to investigate the association of altered gut microbiota and ASD development. 16S rRNA gene-based sequencing found that, unlike those of healthy infants, feces of ASD infants had significantly higher and lower abundance of genera Faecalibacterium and Blautia, respectively. Moreover, DNA microarray analysis of peripheral blood mononuclear cells (PBMC) detected more highly than low expressed genes in ASD infants than in healthy infants. Gene Ontology analysis revealed that differentially expressed genes between ASD and healthy infants were involved in interferon (IFN)-γ and type-I IFN signaling pathways. Finally, strong positive correlations between expression of IFN signaling-associated genes in PBMC and fecal abundance of Faecalibacterium were found. Our results strongly suggested that altered gut microbiota in infants resulted from ASD development and was associated with systemic immunity dysregulation, especially chronic inflammation.

Immunohistochemical localization of two types of choline acetyltransferase in neurons and sensory cells of the octopus arm.

Cholinergic structures in the arm of the cephalopod Octopus vulgaris were studied by immunohistochemistry using specific antisera for two types (common and peripheral) of acetylcholine synthetic enzyme choline acetyltransferase (ChAT): antiserum raised against the rat common type ChAT (cChAT), which is cross-reactive with molluscan cChAT, and antiserum raised against the rat peripheral type ChAT (pChAT), which has been used to delineate peripheral cholinergic structures in vertebrates, but not previously in invertebrates. Western blot analysis of octopus extracts revealed a single pChAT-positive band, suggesting that pChAT antiserum is cross-reactive with an octopus counterpart of rat pChAT. In immunohistochemistry, only neuronal structures of the octopus arm were stained by cChAT and pChAT antisera, although the pattern of distribution clearly differed between the two antisera. cChAT-positive varicose nerve fibers were observed in both the cerebrobrachial tract and neuropil of the axial nerve cord, while pChAT-positive varicose fibers were detected only in the neuropil of the axial nerve cord. After epitope retrieval, pChAT-positive neuronal cells and their processes became visible in all ganglia of the arm, including the axial and intramuscular nerve cords, and in ganglia of suckers. Moreover, pChAT-positive structures also became detectable in nerve fibers connecting the different ganglia, in smooth nerve fibers among muscle layers and dermal connective tissues, and in sensory cells of the suckers. These results suggest that the octopus arm has two types of cholinergic nerves: cChAT-positive nerves from brain ganglia and pChAT-positive nerves that are intrinsic to the arm.

Seizure susceptibility due to antihistamines in febrile seizures.

The aim of this study was to determine whether seizure susceptibility due to antihistamines is provoked in patients with febrile seizures. The study population comprised 14 patients with simple febrile seizures and 35 patients with complex febrile seizures. Detailed clinical manifestations were compared between patients with and without administration of antihistamine. The time from fever detection to the seizure onset was significantly shorter in the antihistamine group than that in the nonantihistamine group, and the duration of seizures was significantly longer in the antihistamine group than that in nonantihistamine group. Interleukin-1beta is thought to be associated with causing febrile seizures via its dual role as a pyrogen and convulsant substance. Moreover, interleukin-1beta may activate the turnover of hypothalamic neural histamine. These considerations, along with the present results, suggest that the depletion of hypothalamic neuronal histamine induced by antihistamines may increase neuronal excitability, thereby increasing seizure susceptibility in patients with febrile seizures.

Large congenital melanocytic nevi presenting with lissencephaly with an absent corpus callosum.

A neonatal case of provisional neurocutaneous melanosis presenting with lissencephaly is reported. Several congenital nevi were observed on the trunk and extremities of the infant, including a giant congenital hairy nevus over the skull. Brain magnetic resonance imaging revealed a marked ventricular dilatation with pachygyria and an absent corpus callosum; however, an injection of gadolinium did not demonstrate any enhanced lesions. Histopathological investigations by a brain biopsy showed a disorganized and anomalous embryonic cerebral architecture, suggesting lissencephaly. The detailed mechanism of this combined pathology is difficult to explain; however, a developmental disturbance was suggested to be present in both the neural crest cells and the neuroepithelial cells, resulting in the development of neurocutaneous melanosis accompanied with lissencephaly.

Delayed myelination at the onset of cryptogenic West syndrome.

To evaluate the prognostic value of delayed myelination at the onset of cryptogenic West syndrome, the relationship between the seizure or developmental outcome and myelination was examined. Cranial magnetic resonance imaging studies were performed in nine cryptogenic cases. Infantile spasms were controlled in all patients, but three cases showed a mild developmental delay at 2 years after onset. Delayed myelination was observed in three cases (33.3%) on T(1)-weighted images and in two cases (22.2%) on T(2)-weighted images. In the present study, neither the seizure outcome nor developmental status was positively correlated with the existence of delayed myelination at the onset of cryptogenic West syndrome.

Pediatric primary leptomeningeal lymphoma treated without cranial radiotherapy.

We report a case of primary leptomenigeal lymphoma (PLML) in an 11-year-old boy presenting with headache, vomiting, and diplopia. The patient was treated on an advanced non-Hodgkin lymphoma protocol with systemic/intrathecal chemotherapy without cranial radiotherapy. He remains in complete remission 33 months after treatment.

Enhanced capacity of epilepsy in brain malformation produced during early development.

This study investigates the clinical features of epilepsy in 20 patients with brain malformation. Epileptic seizures were recognized in 15 patients, 12 of whom had their first seizure by 1 year of age. Partial seizure was the initial seizure type in 10 patients. Epileptic seizures were controlled in only four patients. Patients with holoprosencephaly and lissencephaly had seizure onset by 3 months of age, resulting in the most severe neurologic outcome. Only two patients with porencephaly had epileptic seizures, and in one of those patients the seizures were well controlled. A wide variety of clinical features of epilepsy in patients with brain malformation was found. More immature anomalous brain lesions may be associated with an enhanced capacity of epilepsy and resultant refractory seizures.

Experimental cortical dysplasia following ibotenate administration in hamsters: pathogenesis of microgyria and associated gray matter heterotopia.

The study presented here investigated the pathogenetic relationship among different types of neuronal migration disorders occurring simultaneously in the brain using an experimental model induced by ibotenate in hamsters. In the cerebral cortex, abnormal neuronal arrangement was induced 1 day after ibotenate injection. This brain lesion resulted in microgyria in the rostral portion, focal subcortical heterotopia in the mid-portion, and focal subependymal heterotopia in the caudal portion in the same specimen. Vimentin-immunoreactive radial glial fibers were lacking in the area of disorganized neuronal arrangement, but were detected around the microgyria and the intermediate zone surrounding focal subcortical heterotopia. The focal subependymal heterotopia did not include radial glial elements. Glial fibrillary acidic protein (GFAP)-positive glial reaction was weak in these cortical lesions. We suggest that the occurrence of each type of migration disorder depends on the depth of the cortical lesion, that is, the production of microgyria, focal subcortical heterotopia and focal subependymal heterotopia are closely related to the lesions including the cortical plate, subplate and ventricular zone, respectively.

Peters' anomaly with bilateral perisylvian polymicrogyria and abdominal calcification.

We report a neonatal case of Peters' anomaly with bilateral perisylvian polymicrogyria and abdominal calcification. The male infant was born after a normal labor. Bilateral central corneal opacities with iridocorneal strands indicated Peters' anomaly. The X-ray and abdominal computed tomography demonstrated multiple calcifications beneath the diaphragma around the liver and the spleen. TORCH serology was negative. Intracranial calcification was not detected. Brain magnetic resonance imaging demonstrated bilateral perisylvian polymicrogyria. Abdominal calcification was suspected to be related to vascular disruption. Bilateral perisylvian polymicrogyria has been thought to result from ischemic events such as intrauterine hypotension or vascular occlusions. Based on these considerations, we conclude that a vascular disruption sequence may an important pathogenetic mechanism of Peters' anomaly.