Neurobehavioral and Hemodynamic Evaluation of Cognitive Shifting in Children with Autism Spectrum Disorder

The restrictive, stereotyped behavior in autism spectrum disorder (ASD) is considered to be related to deficits in execu- tive function. In particular, cognitive shifting in executive function is deeply related to stereotyped behavior in ASD. Previous investigations have clarified that the lateral prefrontal cortex is involved in cognitive shifting when flexible changes in attention were needed. However, a few studies have revealed a direct association between cognitive shifting tasks and lateral prefrontal cortex activity in children with ASD. We examined cognitive shifting in 7- to 12-year-old children with ASD and typically developing children using the dimensional change card sort task. In addition, using near-infrared spectroscopy, we examined prefrontal brain activity in conjunction with cognitive shifting. The autistic children provided fewer correct answers and slower reaction times in the task than typically developing children. Fur- thermore, the autistic children displayed a decline in right lateral prefrontal cortex activity during the task compared with typically developing children. In addition, a negative correlation was observed between the severity of autism and brain activity during the task. These results suggest that the activity and physiological indices used in this study may be useful for identifying the symptoms of ASD and discriminating ASD from other disabilities.

Assessment of Quality of Life, Family Function and Family Empowerment for Families Who Provide Home Care for a Child with Severe Motor and Intellectual Disabilities in Japan

Background: About 70% of Japanese children with severe motor and intellectual disabilities (SMID) live at home, and the number is increasing. Family members have an enormous burden of daily physical care for these children. A top priority is to understand quality of life (QoL), family function, and family empowerment to effectively support these families. We aimed to assess current living situations of families with a SMID child, and to reveal the relationships between QoL, family function, and family empowerment. Methods: Sixty-five family members from 34 families with a SMID child participated in this study. We assessed 5 parameters using the Japanese versions of the following instruments: World Health Organization Quality of Life 26 (WHOQOL26), Kinder Lebensqualitats Fragebogen (KINDL), Family Assessment Device (FAD), Family Adaptability and Cohesion Evaluation Scale KG-4 (FACESKG-4), and Family Empowerment Scale (FES). Correlation and multiple regression analyses were conducted;QoL score was the objective variable. Results: Participants included 54 parents (34 mothers, 20 fathers) and 11 siblings. The mean age of SMID children was 10.4 ± 5.03 years. Twenty-two children needed multiple types of medical care. The mean age of parents and siblings was 41.5 ± 6.16 years and 15.5 ± 2.35 years, respectively. The mean QoL score (3.28 ± 0.5) was similar to the Japanese average. The mean KINDL score (77.2 ± 12.1) was higher than those of previous studies. The mean FAD score was 1.97 ± 0.32. For FACEKG-4, the score of adaptability was correlated with WHOQOL score (r = 0.459, p < 0.05). The mean score of FES was 113.6 ± 14. As the result of multiple regression analysis, lower family FAD scores ([sb] = ?0.61, p < 0.01) indicated higher family function and greater age of participants (sb = 0.495, p < 0.01) was correlated with higher WHOQOL scores (F = 15.208, p < 0.01). Conclusions: Our results indicated that the individual QoL depended on the age of participants (equals the years of experience caring for a SMID child) and the recognition of family function as a whole. Thus, to improve family members’ QoL, we should focus on individuals and also approach the family as a whole.

Remain Aggressive Behavior in Children with Temporal Lobe Epilepsy after Surgery

Behavioral problems have a high rate in patients with temporal lobe epilepsy but there have been few detailed reports about pediatric patients. We report two children with temporal lobe epilepsy who manifest behavior abnormality remaining after surgery. One child developed complex partial seizures at 10 years and 3 months of age caused by a left temporal ganglioglioma and manifested behavioral problems of lability, aggression, impulsivity and disinhibition. Seizures were relieved after temporal lobe resection at 10 years and 8 months of age but behavioral symptoms had been remained. The second child developed epilepsy at 3 years of age. He manifested similar behavioral problems at 7 years old. Seizures were relieved after temporal lobe resection at 13 years old but behavioral symptoms had been remained. Their courses suggested that aggressive behavior might be associated with not only temporal lesion but also other lesions such as frontal lobe or neural circuitry between both lobes. It is important to inform families of patients that behavioral disorders may not improve after epileptic surgery.

Clinical and therapeutic implications of psychiatric comorbidity in high functioning autism/Asperger syndrome: An Italian study

The present study describes the occurrence of psychiatric comorbid disorders in a cohort of 86 high functioning autism (HFA)/Asperger syndrome (AS) patients, examined at Child Neurology and Psychiatry Unit of Tor Vergata University. 38 patients out of 86 (44.2%) presented one or more psychiatric comorbidities, such as mood disorders, Attention Deficit/Hyperactivity Disorder (ADHD), Tourette syndrome (TS), anxiety disorders, including obsessive-compulsive disorder (OCD), and psychotic symptoms. We compared our sample with the evidences from the scientific literature on psychiatric comorbidity in ASD patient, in particular in HFA/AS. In this paper we focus on the high frequency of comorbid psychiatric disorders in HFA/AS patients, such as mood disorders, Attention Deficit/Hyperactivity Disorder (ADHD), Tourette syndrome (TS), anxiety disorders, including obsessive-compulsive disorder (OCD), and psychosis, including schizophrenia. We analyzed rates of all psichiatric comorbidities diagnosed in a sample of HFA/AS subjects and we compared findings from our study with the evidences from the scientific literature on psychiatric comorbidity in ASD patients, in particular HFA/AS. We point out that comorbid psychiatric symptoms can be hardly diagnosed, because they could present atipically in ASDs then in general population. Furthermore, they could be masked by ASD core symptoms.

Challenges to associate early onset epilepsy with COVID-19 autoimmune encephalitis:A case

BACKGROUND Diagnosis of coronavirus disease 2019(COVID-19)-related neurological events in the pediatric population is challenging.Overlapping clinical picture of children with altered neurological state and inborn errors of metabolism,in addition to the frequency of asymptomatic COVID-19 cases,pose the main challenges for diagnosis.Diagnostic approaches to the onset post-COVID 19 subacute encephalopathy are still troublesome as seronegative autoimmune encephalitis(AIE)is reported.CASE SUMMARY A 27-mo-old boy was admitted for stormy refractory seizure of polymorphic semiology and altered mental status followed by various neuropsychiatric features that were suggestive of AIE.Brain magnetic resonance imaging and cerebrospinal fluid analysis were normal.Neither the immunological assessment,including viral serologies,antinuclear antibodies,autoimmune antibodies(NMDA,AMPA,CASPR2,LG11,GABARB,Hu,Yo,Ri,CV2,PNMA2,SOX1,Titin,amphiphysin,Recoverin),nor the metabolic assessment for lactate and pyruvate showed significant anomaly.Both positive history of COVID-19 infection and the findings of characteristic repetitive extreme delta brush played a key role in the diagnosis of COVID-19-related AIE.A remarkable improvement in the state of the child was noted after two pulse doses of intravenous Veinoglobulin and high dose of intravenous Corticosteroid.CONCLUSION Diagnostic biomarkers for AIE might aid effective treatment.

MLC1在调节星形胶质细胞-突触相互作用中的新角色

星形胶质细胞膜蛋白MLC1的功能丧失是伴皮质下囊肿的巨脑性白质脑病(MLC)的主要遗传原因,这一罕见病的特征是脑内离子和水稳态失衡。MLC1蛋白主要分布于大脑中的液体屏障周围,例如在星形胶质细胞接触血管的终足和接触脑膜的突起中。该蛋白是否在其他星形胶质细胞结构域中发挥作用尚不清楚。本研究表明MLC1存在于星形胶质细胞远端突起中,也称为突触周围星形胶质细胞突起(PAP)或星形胶质细胞小叶;在海马CA1区域它们与兴奋性突触密切相互作用。我们发现在Mlc1缺失小鼠中,向兴奋性突触延伸的PAP末端缩短。这一改变会影响谷氨酸能突触传递,导致自发释放事件的速率降低,并在具有挑战性的条件下减慢谷氨酸的再摄取。此外,虽然野生型小鼠中的PAP在恐惧调节过程从突触回缩,但我们发现在Mlc1缺失小鼠中,这种结构可塑性在本已更短的PAP出现障碍。最后,Mlc1缺失小鼠显示情境恐惧记忆减少。总之,本研究揭示了星形胶质细胞蛋白MLC1在调节PAP结构方面的意想不到的作用。MLC1的缺失会改变兴奋性突触传递,阻止恐惧调节诱导的正常PAP重塑,并破坏情境恐惧记忆表达。因此,MLC1是调节星形胶质细胞-突触相互作用的新参与者。

Characterization of the molecular dysfunctions occurring in Aicardi-Goutieres syndrome patients with mutations in ADAR1

Aicardi-Goutieres syndrome(AGS)is a systemic inflammatory disorder caused by mutations in any one of the nine different genes,whose deficiency provokes a type I(interferon)IFN response probably central to pathogenesis.^(1) ADAR1,one of the genes mutated in AGS(AGS6),encodes for an enzyme that belongs to the ADAR family(ADAR1,ADAR2,and ADAR3)that catalyzes the conversion of adenosine to inosine within double-stranded RNAs(dsRNAs)(RNA editing A-to-1).

扩散加权成像与常规MR成像在新生儿缺氧缺血中的应用:2年的随访研究

目的 通过对缺血缺氧的新生儿2年后临床预后的评估，明确扩散加权成像（DWI）对于常规MR成像的信息补充价值。材料和方法 46例缺血缺氧新生儿作为本项前瞻性研究对象．年龄在出生后1～45d不等。这项研究经过了当地伦理委员会的认可，告知患儿家属并获得同意。在大脑14个不同的区域测定表观扩散系数（ADC）。

Thoraco-Lumbar Junction Disc Herniation and Tight Filum: A Unique Combination?

Purpose: The incidence of both symptomatic thoraco-lumbar junction disc herniation (TLJDH) and tight filum (TF) may be underestimated. Both conditions have a complex clinical presentation that may involve the distal spinal cord, conus medullaris, and/or cauda equina, including upper and/or lower motor neuron impairment, sensory impairment, urological and sexual dysfunction. The coexistence of both conditions has not been previously reported and may be a diagnostic and therapeutic challenge. Methods: We report three teenage girls, a 24-year-old woman, and two middle-aged women who were diagnosed with both conditions and treated at our institution. Results: Disc herniation level was T11-T12 in 2, T12-L1 in 3, and L1-L2 in one. All patients had a fatty filum (n = 5) and/or a low-lying CM (at or above L1-L2 in 2, at or below L2-L3 in 4), and were treated with filum sectioning first. All patients noted marked improvement of preoperative complaints including back pain (n = 5), leg pain and fatigue (n = 4), urological complaints (n = 4), and toe gait (n = 1). One 16-year-old girl successfully underwent a thoracoscopic microdiscectomy for persisting pain at the thoraco-lumbar junction two years after filum sectioning. Conclusions: Thoraco-lumbar junction disc herniation and tight filum both act on the distal spinal cord close to the transition to the cauda equina. Both conditions may coincide and may even act synergistically, the disc herniation acting as a fulcrum, aggravating the deleterious effect of the tethering force (and vice versa). This might explain why both conditions combined may present at a younger age. We suggest filum sectioning as the primary treatment option in all patients, however, more cases and a longer follow-up are needed to better understand their unique combination and interaction. Nevertheless, when confronted with a symptomatic TLJDH especially in young patients we advise to rule out a coinciding TF by careful consideration of all clinical, radiological, and urological data.

Urinary polyomavirus infections in neurodevelopmental disorders

We have recently reported enhanced frequencies of polyomavirus infection in post-mortem brain tissue of autistic patients compared to controls. To further explore potential contributions to neurodevelopmental disorders by polyomaviruses, we have employed specie-specific TaqMan assays to assess the prevalence and titres of BKV, JCV and SV40 inthe urines of 87 patients with autism spectrum disorder, 84 controls matched by sex and age with the autistic sample, 15 subjects with Down syndrome and 13 fragile X individuals. Prevalence rates of urinary BKV infection were significantly greater in Down syndrome and fragile X patients compared to autistic and control individuals (P < 0.01). In a large majority of patients who showed the presence of urinary genomes, viral titres resulted significantly higher among Down syndrome patients (P < 0.01) compared to controls, autism spectrum disorder and fragile X individuals, who did not significantly differ from each other. Our results are consistent with previous evidence supporting hampered immunological surveillance and/or immune deficits in fragile X and especially in Down syndrome patients.

青少年学习困难者非典型EEG相关指数:I.视觉辨别相关指数

Objective: To find out whether 14 16 year old pupils with visual perception disabilities have atypical EEG activation patterns during visual discrimination . Methods: EEG correlation indices (EEGCIs), based on the waveform characteristi cs of two EEG signals, were used as measures of slow joint activation of cortica l regions during visual discrimination in pupils with visual perception disabili ties. Results: During visual discrimination low EEGCIs were seen between the lef t temporal and both parieto occipital EEG channels in pupils with visual percep tion disabilities and in pupils with a poor occupational outcome. The pupils wit h low performance intelligence and those with difficulties in the visual discrim ination task had low EEGCIs within the left hemisphere. The left hemispheric dom inance of the findings is suggested to reflect the psychophysiology of the task since visual discrimination demands attention to details (local processing) and is thus supposed to be more strongly represented in the left hemisphere. Conclus ions: During visual discrimination, low EEGCIs were seen in the posterior and le ft hemispheric regions of pupils with disabilities in visual perception and visu al discrimination and with a poor occupational outcome. Significance: Low EEGCIs in posterior and left hemispheric regions during visual discrimination can to s ome extent be seen as neurophysiological markers for visual perception disabilit ies and a poor occupational outcome and imply an increased need for adjustment o f the educational curriculum and a need for occupational guidance.

青少年学习困难者非典型EEG相关指数:II.阅读相关指数

Objective: To find out whether 14 16 year old reading and writing impaired pu pils have atypical EEG activation patterns during reading. Methods: EEG correlat ion indices (EEGCIs), based on the waveform characteristics of twoEEG signals, w ere used as measurers of slow joint activation of cortical regions during readin g in pupils with reading and writing impairment. Results: Reading was associated with high EEGCIs within the right hemisphere in reading and writing impaired pu pils. The finding is analogous to the results of an earlier study [Byring, Elec t roencephalogr. Clin. Neurophysiol. 63 (1986) 1] in boys with spelling disabilit i es. The activation in the right hemisphere might represent a compensation for a left hemisphere dysfunction in pupils with reading and writing impairment during reading, as suggested by a number of functional neuroimaging studies. T his interpretation was corroborated by high EEGCIs especially in those impaired pupils who had a good occupational outcome. Conclusions: EEGCIs during reading a re high within the right hemisphere in pupils with reading and writing impairmen t. Significance: High EEGCIs within the right hemisphere during reading might be considered neurophysiological markers for reading and writing impairment.

动力敏感性对比磁共振成像对缺血性卒中患者异常脑血流量的检测

Background and Purpose - The determination of cerebral blood flow heterogeneity (FH) by dynamic susceptibility contrast (DSC) magnetic resonance imaging has recently been proposed as a tool to predict final infarct size in acute stroke. In this study, we describe the evolution of FH during the first week as well as its correlation to the patients’ clinical status. Methods - Ten patients with ischemic stroke were studied with DSC MRI and diffusion- weighted imaging in hyperacute ( < 6 hours) phase, at 24 hours, and 1 week after symptom onset. In addition to intravoxel FH, cerebral blood volume (CBV), cerebral blood flow (CBF), and contrast agent mean transit time (MTT)- were determined from DSC MRI. All patients were evaluated neurologically with National Institute of Health Stroke Scale concurrently with the imaging sessions. Results - All patients showed infarct growth, judged by diffusion- weighted imaging, during the week with simultaneous decrease in the sizes of FH, CBV, CBF, and MTT abnormalities. The FH abnormality was shown to be larger than CBV and CBF abnormalities at the hyperacute phase and 24 hours, but smaller than MTT abnormality in all 3 imaging sessions. The sizes of hyperacute FH, CBV, CBF, and MTT abnormalities correlated well with infarct size at 24 hours and at 1 week. Additionally, FH was the only perfusion parameter that correlated with the clinical score. Conclusions - FH predicts infarct size equally well with the other perfusion parameters but is superior in correlation with the clinical score. FH can easily be incorporated to hyperacute stroke imaging without additional efforts.

肿瘤中hamartin和tuberin的不同分布以及核糖体S6激酶的磷酸化增加

In a tuberous sclerosis patient with a mutation in the TSC1 tumor suppressor g ene, no second hit mutation was found in a resected cortical tuber. Tuber giant cells showed predominantly nuclear hamartin, cytosolic tuberin, and hyperphosph orylation of S6. Differential accumulation of hamartin and tuberin in separate c ellular compartments of giant cells may prevent formation of the hamartin tuber in complex, resulting in increased S6 phosphorylation. These data provide an alt ernative mechanism for tuberogenesis.

Diagnosis and fine localization of deletion region in Wolf- Hirschhorn syndrome patients

Background Wolf-Hirschhorn syndrome （WHS） results from the fine map the chromosome deletion regions of Chinese ch developmental delay/mental retardation （DD/MR） patients. partial deletion of 4p. This study aimed to identify and Idren with Wolf-Hirschhorn syndrome among the Methods We analyzed the relationship of phenotype and genotype. Inclusion criteria were： moderate to severe DD/MR, no definite perinatal brain injury, and no trauma, toxication, hypoxia, infection of central nervous system; routine karyotyping was normal, no evidence of typical inherited metabolic disorder or specific neurodegenerative disorders from cranial neuro-imaging and blood/urinary metabolic diseases screening; no mutation of FMR1 in male patients, no typical clinical manifestation of Rett syndrome in female patients. Multiplex ligation-dependent probe amplification （MLPA） and Affymetrix genome-wide human SNP array 6.0 assays were applied to accurately define the exact size of subtelomeric aberration region of four WHS patients. Results All four WHS patients presented with severe DD, hypotonia and microcephaly, failure to thrive, 3/4 patients with typical facial features and seizures, 2/4 patients with congenital heart defects and cleft lip/palate, 1/4 patients with other malformations. The length of the deletions ranged from 3.3 Mb to 9.8 Mb. Two of four patients had ＂classic＂ WHS, 1/4 patients had ＂mild＂-to-＂classic＂ WHS, and 1/4 patients had ＂mild＂ WHS. Conclusions WHS patients in China appear to be consistent with those previously reported. The prevalence of signs and symptoms, distribution of cases between ＂mild＂ and ＂classic＂ WHS, and the correlation between length of deletion and severity of disease of these patients were all similar to those of the patients from other populations.

Changes of glucocorticoid receptor mRNA expression in basolateral amygdale-kindled rats

Background Glucocorticoid receptor （GR） is believed to be a major factor in brain maturation and in modulation of a series of brain activity. Hippocampal neurons are abundant in glucocorticoid receptor, and there is significant change in GR expression under certain pathological state. Epilepsy is a special pathological state of the central nervous system. This study aimed to explore the role of GR in epilepsy by observing the change and functions of GR in hippocampus with a basolateral amygdale-electrical kindled rat epilepsy model. Methods Firstly, we established the basolateral amygdale-electrical kindled rat epilepsy model. Then GR mRNA expression in the hippocampus was assayed by semi-quantitative reverse transcription-PCR in this experiment. In addition, the processes of epileptic seizures were observed and electroencephalograms were recorded. One-way analysis of variance （ANOVA） was employed for comparing means of multiple groups, followed Fisher＇s least significant difference （LSD） for paired comparison. Results The rats were successfully kindled after an average of （13.50＋3.99） times electrical stimulation, in which it was showed that GR mRNA expression reduced obviously as compared with the control group and the sham groups （P 〈0.001）. The down-regulation of GR mRNA expression was abated or reversed by some anti-epilepsy drugs （P 〈0.001 compared with the epilepsy group）, accompanied by attenuation of seizures and improvement of electroencephalograms. Conclusions Down-regulation of hippocampal GR mRNA expression may be related to the kindling. Anti-epilepsy drugs exposure can retard this change.