Motor Retardation Research Articles

THU218 Congenital Craniopharyngioma - Cases Recruited In The German Kraniopharyngeom Trials And Review Of The Literature

Abstract Disclosure: S. Boekhoff: None. J. Beckhaus: None. B. Bison: None. C. Friedrich: None. H.L. Muller: None. Background: Craniopharyngiomas (CP) are rare malformational tumors. Clinical presentation and outcome of patients with congenital CP (cCP) are not clear and refer mainly to few case reports in the literature. The aim of this study was to analyze clinical presentation and outcome in patients with cCP. Clinical cases: Seven hundred and nine patients diagnosed with adamantinomatous CP were recruited 1999-2021 in HIT-ENDO, KRANIOPHARYNGEOM 2000 / 2007 / Registry 2019 and prospectively observed. In 3 cases, cCP was diagnosed prenatally and in one case at the 2nd day of life. Pre- and perinatal diagnostic findings, postnatal evaluation, therapeutic interventions and outcome in these 4 cases of cCP were analyzed. When compared to cases of cCP reported in the literature, more recent cases like our reported cCP have an overall better prognosis with regard to survival and sequelae. Two of our 4 cCP suffered from hemiparesis and one patient presented with mild motor retardation. In contrast to historical reports (lethal rate of >50%), all patients in our report recruited after 2000 survived. Prenatal routine ultrasound examination was the usual diagnostic procedure leading to diagnosis of cCP. Tumor resection was performed during early postnatal period (range: 11 - 51 days of age). Complete resection of the mostly large sized tumors could be achieved in two of four patients with cCP. Conclusion: Based on improvements of diagnostic and therapeutical methods and techniques, earlier prenatal diagnosis of cCP should lead to intrauterine transfer of cCP patients to a specialized center for postnatal treatment of newborns with sellar masses by a multidisciplinary team to secure an improved prognosis of these patients. Presentation: Thursday, June 15, 2023

Clinical and molecular analysis of Guangxi patients with Kabuki syndrome and KMT2D mutations

Kabuki syndrome (KS) is a multiple congenital anomaly syndrome that is characterized by postnatal growth deficiency, hypotonia, short stature, mild-to-moderate intellectual disability, skeletal abnormalities, persistence of fetal fingertip pads, and distinct facial appearance. It is mainly caused by pathogenic/likely pathogenic variants in the KMT2D or KDM6A genes. Here, we described the clinical features of nine sporadic KS patients with considerable phenotypic heterogeneity. In addition to intellectual disability and short stature, our patients presented with a high prevalence of motor retardation and recurrent otitis media. We recommended that KS should be strongly considered in patients with motor delay, short stature, intellectual disability, language disorder and facial deformities. Nine KMT2D variants, four of which were novel, were identified by whole-exome sequencing. The variants included five nonsense variants, two frameshift variants, one missense variant, and one non-canonical splice site variant. In addition, we reviewed the mutation types of the pathogenic KMT2D variants in the ClinVar database. We also indicated that effective mRNA analysis, using biological materials from patients, is helpful in classifying the pathogenicity of atypical splice site variants. Pedigree segregation analysis may also provide valuable information for pathogenicity classification of novel missense variants. These findings extended the mutation spectrum of KMT2D and provided new insights into the understanding of genotype-phenotype correlations, which are helpful for accurate genetic counseling and treatment optimization.

Psychomotor slowing in schizophrenia is associated with cortical thinning of primary motor cortex: A three cohort structural magnetic resonance imaging study

Psychomotor slowing (PS) is characterized by slowed movements and lower activity levels. PS is frequently observed in schizophrenia (SZ) and distressing because it impairs performance of everyday tasks and social activities. Studying brain topography contributing to PS in SZ can help to understand the underlying neurobiological mechanisms as well as help to develop more effective treatments that specifically target affected brain areas. Here, we conducted structural magnetic resonance imaging (sMRI) of three independent cohorts of right-handed SZ patients (SZ#1: n = 72, SZ#2: n = 37, SZ#3: n = 25) and age, gender and education matched healthy controls (HC) (HC#1: n = 40, HC#2: n = 37, HC#3: n = 38). PS severity in the three SZ cohorts was determined using the Positive and Negative Syndrome Scale (PANSS) item #G7 (motor retardation) and Trail-Making-Test B (TMT-B). FreeSurfer v7.2 was used for automated parcellation and segmentation of cortical and subcortical regions. SZ#1 patients showed reduced cortical thickness in right precentral gyrus (M1; p = 0.04; Benjamini-Hochberg [BH] corr.). In SZ#1, cortical thinning in right M1 was associated with PANSS item #G7 (p = 0.04; BH corr.) and TMT-B performance (p = 0.002; BH corr.). In SZ#1, we found a significant correlation between PANSS item #G7 and TMT-B (p = 0.005, ρ=0.326). In conclusion, PANSS G#7 and TMT-B might have a surrogate value for predicting PS in SZ. Cortical thinning of M1 rather than alterations of subcortical structures may point towards cortical pathomechanism underlying PS in SZ.

Mild Behavioral Impairment in Psychogeriatric Patients: Clinical Features and Psychopathology Severity.

The Mild Behavioral Impairment (MBI) concept was developed to determine whether late-onset persistent neuropsychiatric symptoms (NPSs) may be early manifestations of cognitive decline. Our study aims to investigate the prevalence and differentiating features of MBI with respect to major neurocognitive disorders (MNDs) and primary psychiatric disorders (PPDs). A total of 144 elderly patients who were referred to our psychogeriatric outpatient service were recruited. The severity of mental illness was evaluated by means of the Clinical Global Impression Severity scale, the severity of psychopathology was evaluated by means of the Brief Psychiatric Rating Scale (BPRS), and overall functioning was evaluated by means of the Global Assessment of Functioning scale. The sample included 73 (50.6%) patients with PPDs, 40 (27.8%) patients with MBI, and 31 (21.5%) patients with MNDs. Patients with MNDs reported the greatest severity of mental illness, the highest BPRS Total, Psychosis, Activation, and Negative Symptom scores, and the lowest functioning. Patients with MBI and PPDs had comparable levels of severity of mental illness and overall functioning, but MBI patients reported higher BPRS Total and Negative Symptom scores than PPD patients. Patients with MBI frequently reported specific clinical features, including a higher severity of apathy and motor retardation. These features merit further investigation since they may help the differential diagnosis between MBI and PPDs.

Experience with agomelatine therapy for non-psychotic depression with a single and recurrent course

Therapy of depression is a current problem in psychiatry. Agomelatine is not inferior to other modern drugs in terms of antidepressant efficacy (response and remission rates) and is characterized by the best tolerability.Objective: to evaluate the efficacy and safety of agomelatine in the treatment of nonpsychotic depression with a single and recurrent course.Material and methods. Patients (n=37) with a current depressive episode (DE; F32 according to ICD-10), mean age 41.2±2.07 years, were studied. Clinical psychopathological and psychometric methods were used in the study (Hamilton Hospital Depression Scale – HAMD-17; Spielberger–Khanin Anxiety Self-Assessment Scale, Sheehan Anxiety Scale, Clinical Global Impression Scale – CGI-I). A single DE was diagnosed in 62.2% of patients, and recurrent depressive disorder in 37.8%. Stress-related onset of current DE was found in 56.8% of cases, autochthonous in 43.2%.Results. 94.6% of patients were responders, including 68.6% who went into remission. A statistically significant decrease in scores on the HAMD-17 scale was noted in the remission group from the 7th day of agomelatine therapy (p<0.05), in the responder group – from the 14th day of therapy (p<0.05). According to the Sheehan scale, a statistically significant decrease in scores was noted at the end of the first week of therapy (p<0.05), according to the Spielberger–Khanin scale – in the second week (p<0.05) in all patients. According to the CGI-I scale, the condition at the end of therapy improved in 57.1% of patients, significantly in 42.9%. Clinical predictors of therapeutic response in patients with remission included significantly higher frequency of a single DE (p<0.02), moderate severity of current depression (p<0.02), dizziness among autonomic disorders (p<0.01), a significantly lower representation of the melancholic type of depression (p<0.05), a symptom of a gloomy and pessimistic vision of the future (p<0.05), sleep disturbances (p<0.04), a factor of personal significance in the form of a threat in patients with stress-provoked onset of the current DE (p<0.05).Adverse events occurred in the first week of treatment with agomelatine in 14.3% of cases (nausea – 8.6%, headache and dizziness – 2.9% each), they were mild and did not require discontinuation of the drug. Two patients taking agomelatine at a dose of 50 mg discontinued the study: in one case persisted social phobia, increased fatigue, motor retardation, and persistent modern insomnia; in the other case – a pronounced senestoalgic syndrome with cerebral localization.Conclusion. Agomelatine therapy has been shown to be highly effective and well tolerated in nonpsychotic depression.

Редукция тревоги и депрессии через программы на гарнитуре виртуальной реальности высокой иммерсивности

<p style="text-align: justify;">The work is aimed at considering the influence of modern special training programs in virtual reality (VR) on personality anxiety in adolescence. Materials of empirical research obtained on a sample of students of 2-4 courses of Moscow and Smolensk universities are presented. Respondents aged from 19 to 24 years old participated in the study 1 (N=15) (using the training VR environment with a first-person avatar) and 2 (N=24) (using the training VR program with an anthropomorphic avatar (female) (third-person). To diagnose anxiety we used methods: Spielberger-Hanin Self-Assessment Anxiety Test, A.T. Beck Anxiety Scale. A single-factor experimental design with independent groups was used; dependent variables were different types of anxiety, independent variables were the parameters of subjects' work with the training VR-program of high immersiveness. The results show that the high level training VR environment has a significant effect on anxiety reduction. Both personal and situational anxiety, as well as the general level of anxiety, decreased. In the control samples, either anxiety decreases, but at a much lower level, or no change occurs. Psychosemantic analysis of consciousness indicates changes not only in the conscious plan (connections between connotative meanings), but also in unconscious attitudes about one's anxiety state (manifested in the triad of depression: decreased mood, ideomotor and motor retardation). In general, VR programs with avatars should be considered as effective technologies and means of changing functional personality properties, in particular anxiety.</p>

Development of CRISPR Cas9, spin-off technologies and their application in model construction and potential therapeutic methods of Parkinson's disease.

Parkinson's disease (PD) is one of the most common degenerative diseases. It is most typically characterized by neuronal death following the accumulation of Lewis inclusions in dopaminergic neurons in the substantia nigra region, with clinical symptoms such as motor retardation, autonomic dysfunction, and dystonia spasms. The exact molecular mechanism of its pathogenesis has not been revealed up to now. And there is a lack of effective treatments for PD, which places a burden on patients, families, and society. CRISPR Cas9 is a powerful technology to modify target genomic sequence with rapid development. More and more scientists utilized this technique to perform research associated neurodegenerative disease including PD. However, the complexity involved makes it urgent to organize and summarize the existing findings to facilitate a clearer understanding. In this review, we described the development of CRISPR Cas9 technology and the latest spin-off gene editing systems. Then we focused on the application of CRISPR Cas9 technology in PD research, summarizing the construction of the novel PD-related medical models including cellular models, small animal models, large mammal models. We also discussed new directions and target molecules related to the use of CRISPR Cas9 for PD treatment from the above models. Finally, we proposed the view about the directions for the development and optimization of the CRISPR Cas9 technology system, and its application to PD and gene therapy in the future. All these results provided a valuable reference and enhanced in understanding for studying PD.

Mental disorders during the pandemic of a new coronavirus infection: clinical features

Objective: to study the clinical features of mental disorders during the COVID-19 epidemic in those who turned to psychiatrist for the first time, as well as in patients with already diagnosed mental illness.Material and methods. We examined 100 patients who turned to psychiatrist due to deterioration of their mental state on the background of a pandemic. Of these, 50 were new cases (1st group; 23 women and 27 men, mean age 34 years) and 50 were cases with previously diagnosed mental disorders (2nd group; 25 women and 25 men, mean age 37 years). 80% of patients of the 1st group, 54% of patients of the 2nd group had coronavirus infection. Anxiety and depressive disorders prevailed in the 1st group, endogenous diseases prevailed in the 2nd group: bipolar affective disorder, recurrent depressive disorder, schizophrenia. The study was conducted by the clinical method using a specially designed map; the severity of depression was assessed using the Montgomery-Asberg Depression Rating Scale, and the severity of anxiety was assessed using the Hamilton Anxiety Rating Scale.Results. The clinical picture of primary and recurrent depressive episodes after infection was characterized by the presence of motor and associative retardation, severe apathy, hypersomnia and lack of sleep, fatigue, increased appetite, and complaints of impaired attention and memory. Depression in SARS-CoV-2 survivors was characterized by anxiety, anhedonia, irritability, somatic complaints, and hypochondriacal inclusions. Anxiety symptoms in those who were not ill included severe anxiety, reaching agitation, disturbed sleep with frequent awakenings, irritability, somatic complaints, and hypochondriacal fixation on one’s condition. In recovering patients, anxiety was accompanied by control of somatic functions, cognitive impairments, and fear of retention or even intensification.Conclusion. The results obtained indicate the existing differences between the mental disorders that first appeared and worsened during the pandemic, as well as the differences in the structure of the depressive and anxiety syndrome depending on the presence or absence of coronavirus infection.

A case of combined oxidative phosphorylation deficiency 32 caused by MRPS34 gene variation and literature review

Objective: To investigate the clinical features and genetic features of combined oxidative phosphorylation deficiency 32 (COXPD32) caused by MRPS34 gene variation. Methods: The clinical data and genetic test of a child with COXPD32 hospitalized in the Department of Neurology, Children's Hospital, Capital Institute of Pediatrics in March 2021 were extracted and analyzed. A literature search was implemented using Wanfang, China biology medicine disc, China national knowledge infrastructure, ClinVar, human gene mutation database (HGMD) and Pubmed databases with the key words "MRPS34" "MRPS34 gene" and "combined oxidative phosphorylation deficiency 32" (up to February 2023). Clinical and genetic features of COXPD32 were summarized. Results: A boy aged 1 year and 9 months was admitted due to developmental delay. He showed mental and motor retardation, and was below the 3rd percentile for height, weight, and head circumference of children of the same age and gender. He had poor eye contact, esotropia, flat nasal bridge, limbs hypotonia, holding instability and tremors. In addition, Grade Ⅲ/6 systolic murmur were heard at left sternal border. Arterial blood gases suggested that severe metabolic acidosis with lactic acidosis. Brain magnetic resonance imaging (MRI) showed multiple symmetrical abnormal signals in the bilateral thalamus, midbrain, pons and medulla oblongata. Echocardiography showed atrial septal defect. Genetic testing identified the patient as a compound heterozygous variation of MRPS34 gene, c.580C>T (p.Gln194Ter) and c.94C>T (p.Gln32Ter), with c.580C>T being the first report and a diagnosis of COXPD32. His parents carried a heterozygous variant, respectively. The child improved after treatment with energy support, acidosis correction, and "cocktail" therapy (vitaminB1, vitaminB2, vitaminB6, vitaminC and coenzyme Q10). A total of 8 cases with COXPD32 were collected through 2 English literature reviews and this study. Among the 8 patients, 7 cases had onset during infancy and 1 was unknown, all had developmental delay or regression, 7 cases had feeding difficulty or dysphagia, followed by dystonia, lactic acidosis, ocular symptoms, microcephaly, constipation and dysmorphic facies(mild coarsening of facial features, small forehead, anterior hairline extending onto forehead,high and narrow palate, thick gums, short columella, and synophrys), 2 cases died of respiratory and circulatory failure, and 6 were still alive at the time of reporting, with an age range of 2 to 34 years. Blood and (or) cerebrospinal fluid lactate were elevated in all 8 patients. MRI in 7 cases manifested symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia. Urine organic acid test were all normal but 1 patient had alanine elevation. Five patients underwent respiratory chain enzyme activity testing, and all had varying degrees of enzyme activity reduction. Six variants were identified, 6 patients were homozygous variants, with c.322-10G>A was present in 4 patients from 2 families and 2 compound heterozygous variants. Conclusions: The clinical phenotype of COXPD32 is highly heterogenous and the severity of the disease varies from development delay, feeding difficulty, dystonia, high lactic acid, ocular symptoms and reduced mitochondrial respiratory chain enzyme activity in mild cases, which may survive into adulthood, to rapid death due to respiratory and circulatory failure in severe cases. COXPD32 needs to be considered in cases of unexplained acidosis, hyperlactatemia, feeding difficulties, development delay or regression, ocular symptoms, respiratory and circulatory failure, and symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia, and genetic testing can clarify the diagnosis.

Neuroprotective effects of morroniside from Cornus officinalis sieb. Et zucc against Parkinson’s disease via inhibiting oxidative stress and ferroptosis

Parkinson’s disease (PD) is the second most common neurodegenera­tive disorder after Alzheimer disease accompanied by the death of dopaminergic neurons and brain nigrostriatal mitochondrial damage in the elderly population. The features of the disease include tremor, rigidity, postural instability, and motor retardation. The pathogenesis of Parkinson’s disease is complex, and abnormal lipid metabolism resulting in ferroptosis due to the excessive accumulation of free radicals from oxidative stress in the substantia nigra of the brain was thought to be one of the factors causing the disease. Morroniside has been reported to have significant neuroprotective effects, although it has not been studied in PD. Therefore, this study focused on determining the neuroprotective effects of morroniside (25, 50, and 100 mg/kg) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg)-induced mice models of PD and explored 1-methyl-4-phenylpyridinium MPP+-induced ferroptosis in PC12 cells. Morroniside restored impaired motor function in the PD mice models while reducing neuronal injury. The activation of nuclear factor erythroid 2-related factor 2/antioxidant response elements (Nrf2/ARE) by morroniside promoted antioxidation, the content of reducing agent glutathione (GSH) increased, and the level of the lipid metabolite malondialdehyde (MDA) decreased. Notably, morroniside inhibited ferroptosis in substantia nigra of the brain and PC12 cells, reduced iron levels, and upregulated the expression of the iron-regulated proteins glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), ferritin heavy chain 1 (FTH-1), and ferroportin (FPN). More importantly, morroniside repaired the mitochondrial damage, restored the mitochondrial respiratory chain, and inhibited the production of reactive oxygen species (ROS). These data indicated that morroniside could activate the Nrf2/ARE signaling pathway to increase the antioxidant capacity, thereby inhibiting abnormal lipid metabolism and protecting dopaminergic neurons from ferroptosis in PD.

Changes in indicators of the autonomic nervous system in acute poisoning with 1,4-butanediol complicated by withdrawal syndrome

Introduction. The article presents an assessment of the functional state of the autonomic nervous system in patients with acute 1,4-butanediol poisoning complicated by withdrawal syndrome using pupillometry. Purpose of the study: to analyze changes in the indicators of the autonomic nervous system in patients with acute 1,4-butanediol poisoning complicated by withdrawal syndrome.
 Material and methods. In the course of the work, a prospective examination of 30 patients with acute 1,4-butanediol poisoning, complicated by withdrawal syndrome, aged 19 to 39 years (median age was 25.3 [20.1; 24.9] years) was carried out. All patients were treated at the Center for the Treatment of 
 St. Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine. Pupullometry was performed using the hardware-software complex KSRZRts-01. Statistical processing of the obtained results was carried out in the program Statistica for Windows (version 10).
 Results. In the course of the study, patients with acute poisoning with 1,4-butanediol develop a neurovegetative variant of AS, manifested by signs of parasympathicotonia, expressed in changes in the bioelectrical activity of the brain in the form of irritation of cortical-subcortical structures with rapid exhaustion and instability of the functional tone of cortical neurons, cognitive impairment, ideation and motor retardation, deviations of pupillometry parameters (decrease in the initial pupil diameter and constriction amplitude, increase in the time of onset of the pupillary reaction).
 limitations. In the study of the effect of 1,4-butanediol on the indicators of the autonomic nervous system in the course of a prospective examination of 30 male patients of the Center for the Treatment of 
 St. Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine with acute poisoning by a toxicant, it was found that there were significant changes in the parameters of this system in the withdrawal period.
 Conclusion. The indicators revealed during the study prove the predominance of the neurovegetative variant of the withdrawal syndrome with a characteristic change in the bioelectrical activity of the brain, cognitive functions and pupillometry parameters.

SCAF4 variants associated with focal epilepsy accompanied by multisystem disorders

PurposeThe SCAF4 gene encodes serine/arginine-related carboxyl-terminal domain-associated factor 4, which is highly expressed in the brain and potentially affects neurodevelopment. However, the functional significance of SCAF4 variants in human diseases remains unknown. MethodsTrio-based whole-exome sequencing was performed in three individuals with focal epilepsy. Bioinformatics tools were used to assess the pathogenicity of SCAF4 variants. Knockout scaf4a/b zebrafish were created using CRISPR-Cas9 used to validate the phenotype. ResultsSCAF4 variants were identified in three individuals from three unrelated families with focal epilepsy. All patients had focal seizures and focal discharges on EEG recordings, with intellectual disability or motor retardation, skeletal abnormalities, and one had cryptorchidism. However, no recurrence was observed after short-term ASMs treatment. The identified SCAF4 variants included two nonsense variants and one compound heterozygous variant, consisting of a missense and an in-frame variant. A low frequency of SCAF4 variants was observed in gnomAD in this study. Computational modelling has suggested that missense variants lead to functional impairments. In zebrafish, abnormal epileptiform signals, skeletal development, and neurodevelopment have been found in scaf4a/b knockout compared to wild-type zebrafish. ConclusionThese results indicate that SCAF4 is associated with focal epilepsy accompanied by multisystem disorders. Otherwise, the management of patients with SCAF4 variants requires more attention to multisystem involvement.

Genetic analysis of a child with SATB2‑associated syndrome and literature study.

The present study aimed to investigate clinical phenotype and genotype characteristics of a male child with SATB2-associated syndrome (SAS) and analyzed the relationship between these characteristics and the possible underlying genetic mechanism. His clinical phenotype was analyzed. Using a high-throughput sequencing platform, his DNA samples were subjected to medical exome sequencing, screened for suspected variant loci and analyzed for chromosomal copy number variations. The suspected pathogenic loci were verified by Sanger sequencing. He presented with phenotypic anomalies of delayed growth, delayed speech and mental development, facial dysmorphism showing the typical manifestation of SAS and motor retardation symptoms. Gene sequencing result analyses revealed a de novo heterozygous repeat insertion shift mutation in the SATB2 gene (NM_015265.3) c.771dupT (p.Met258Tyrfs*46), resulting in a frameshift mutation from methionine to tyrosine at the amino acid site 258 and a truncated protein with 46 amino acids missing. The parents showed no mutation at this locus. This mutation was identified as the nosogenesis of this syndrome in children. To the best of the authors' knowledge, this is the first report on this mutation. The clinical manifestations and gene variation characteristics of 39 previously reported SAS cases were analyzed together with this case. The findings of the present study suggested severely impaired language development, facial dysmorphism and varying degrees of delayed intellectual development as the characteristic clinical manifestations of SAS.

Neuropsychiatric symptoms in idiopathic brain calcification

INTRODUCTION: Idiopathic basal ganglia calcification (IBGC) is a rare neurological disease characterized by the deposition of calcium in the brain, without calcium metabolism abnormalities. IBGC may be asymptomatic or clinically evident, causing predominantly movement disorders (parkinsonism, chorea, tremor, dystonia, dyskinesia) and a wide range of neuropsychiatric symptoms (dementia, psychosis, mood disorders, anxiety), which are currently poorly defined in literature. The aim of this study is to deepen the knowledge on psychiatric disorders associated with IBGC, providing an accurate description of eleven cases and summarizing information from the review of literature.EVIDENCE ACQUISITION: From our clinical database, we selected patients meeting the diagnostic criteria for IBGC and collected demographic, clinical, genetic, and neuroradiological data. Psychiatric assessment was performed using the 18-item Brief Psychiatric Rating Scale, the Positive and Negative Syndrome Scale, the Hamilton Anxiety Rating Scale and the Hamilton Depression Rating Scale. We also searched the PubMed database for papers dealing with psychiatric features in IBGC, and the related treatments.EVIDENCE SYNTHESIS: Eight of the eleven patients included in the study reported at least one psychiatric symptom during the course of the disease. The assessment through the HDRS21 and HAM-A Scale confirmed the presence of mild depression and anxiety as the main psychiatric disturbs associated with IBGC. Mean total PANSS and BPRS scores were 40.3±12.4 and 27.6±8.6 respectively, with a major involvement in specific items such as depressive mood, anxiety, tension, motor retardation and disorientation. Data from literature confirmed a significant psychiatric involvement in IBGC. Available case reports mainly concern atypical presentations of IBGC with abrupt onset psychotic symptoms. An in-depth analysis of psychiatric features associated with IBGC is lacking.CONCLUSIONS: Neuropsychiatric involvement is frequent in IBGC. A neuropsychiatric evaluation is highly recommended in patients with evidence of brain calcifications. Conversely, IBGC should be considered in patients presenting with psychiatric symptoms, especially if movement disorders and neurocognitive impairment are co-existing features.

Multimodal biofeedback for Parkinson’s disease motor and nonmotor symptoms

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor retardation, myotonia, quiescent tremor, and postural gait abnormality, as well as nonmotor symptoms such as anxiety and depression. Biofeedback improves motor and nonmotor functions of patients by regulating abnormal electroencephalogram (EEG), electrocardiogram (ECG), photoplethysmography (PPG), electromyography (EMG), respiration (RSP), or other physiological signals. Given that multimodal signals are closely related to PD states, the clinical effect of multimodal biofeedback on patients with PD is worth exploring. Twenty-one patients with PD in Beijing Rehabilitation Hospital were enrolled and divided into three groups: multimodal (EEG, ECG, PPG, and RSP feedback signal), EEG (EEG feedback signal), and sham (random feedback signal), and they received biofeedback training five times in two weeks. The combined clinical scale and multimodal signal analysis results revealed that the EEG group significantly improved motor symptoms and increased Berg balance scale scores by regulating β band activity; the multimodal group significantly improved nonmotor symptoms and reduced Hamilton rating scale for depression scores by improving θ band activity. Our preliminary results revealed that multimodal biofeedback can improve the clinical symptoms of PD, but the regulation effect on motor symptoms is weaker than that of EEG biofeedback.

A novel pathogenic variant of CEP164 in an infant with Senior-Loken syndrome.

A novel pathogenic variant of CEP164 in an infant with Senior-Loken syndrome.

Delusions and Hallucinations Are Associated With Greater Severity of Delirium.

The 3 core domains of delirium (cognitive, higher level thinking, circadian) do not include the less common noncore psychotic symptoms. However, psychosis might inform about perturbations of neural circuitry, outcomes, or suggest tailored clinical management. We assessed relationships between psychosis and other characteristics of delirium in patients without dementia or antipsychotics treatment. Cross-sectional analysis of 366 adults with delirium per the Delirium Rating Scale Revised-98, whose items distinguish hallucinations and delusions from other types of misperceptions and abnormal thought content, assessed during the preceding 24 hours to capture symptom severity fluctuation. The relationship of psychosis with other delirium characteristics was assessed using bivariate comparisons and analysis of variance as appropriate for groups with no psychosis and any psychosis (hallucinations and/or delusions), and subgroups with only hallucinations, only delusions, or both. A discriminant logistic model assessed variables associated with presence of any psychotic features versus none. Delirium with any psychotic features occurred in 44.5% (163 of 366). Of the 366, 119 (32.5%) had only hallucinations (Hall), 14 (3.8%) had only delusions (Del), and 30 (8.2%) had both (Both). In the psychotic group (n= 163), 73.0% were Hall, 8.6% Del, and 18.4% Both. All psychotic patient groupings had significantly greater delirium severity on the Delirium Rating Scale Revised-98. Delusions and hallucinations were discordant for occurring together. The discriminant model found increased odds of having psychosis as 3 symptom severities increased (visuospatial ability, thought process, and sleep-wake cycle) where these each represented a delirium core domain. The noncore symptom of lability of affect had high odds ratio for psychosis, while motor retardation reduced odds of psychosis in this model. Consistent with prior reports, psychosis occurred in less than half of delirious patients with delusions being infrequent, and anassociation with affective lability was found. Given thatprevious functional magnetic resonance imaging research found a correlation between neural network dysconnectivity with greater severity of delirium, psychotic symptoms might be a clinical marker for greater underlying cerebral cortical neural circuitry dysfunction.

Effect of Prophylactic Vitamin D Supplementation on Postoperative Pain and Sedation in Children with Mental Motor Retarded Who Undergoing Dental Treatment Introduction

The frequency of vitamin D deficiency is higher in children with mental motor retardation(MMR). We aimed to investigate the effect of vitamin D supplementation on postoperative pain in children with MMR who underwent dental treatment under general anesthesia. 
 Materials-Methods: Dental treatment was planned for a total of 62 patients with MMR, aged 7-17 years. Participants were divided into two groups. Children were prescribed vitamin D (600 IU of vitamin D per day) or Saline. Serum vitamin D levels were measured. Participants continued to intake oral vitamin D 600 IU (Group D) or 2ml saline (Group C) throughout 12 weeks. All participants were observed postoperative 1st hour, and Non-communicating Children's Pain Checklist–Postoperative Version (NCCPC-PV), Ramsay sedation scores, length of stay in post-anesthesia care unit, and analgesic requirements were recorded.
 Results: The study was completed with fifty children (35 in Group D, 15 in Group C). Serum vitamin D levels were higher in Group D than Group C at 12 weeks(p=0.007). Vitamin D deficiency was found at 13 patients (37.1%) and 6 (40%), and vitamin D sufficiency was found 18 (51.4%) and 7 (46.7%) in Groups D and C, respectively at first admission. There was statistically significant difference between groups in NCCPC-PV score at 15th, 30th and 60th minutes in PACU(p

Clinical and genetic characteristics of 9 rare cases with coexistence of dual genetic diagnoses

Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively. Results: Among the 9 children, 6 were boys and 3 were girls. The age of last visit or follow-up was 5.0 (2.7,6.8) years. The main clinical manifestations included motor retardation, mental retardation, multiple malformations, and skeletal deformity. Cases 1-4 were all all boys, showed myopathic gait, poor running and jumping, and significantly increased level of serum creatine kinase. Disease-causing variations in Duchenne muscular dystrophy (DMD) gene were confirmed by genetic testing. The 4 children were diagnosed with DMD or Becker muscular dystrophy combined with a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, and cerebral cavernous malformations type 3, respectively. Cases 5-9 were clinically and genetically diagnosed as COL9A1 gene-related multiple epiphyseal dysplasia type 6 combined with NF1 gene-related neurofibromatosis type 1, COL6A3 gene-related Bethlem myopathy with WNT1 gene-related osteogenesis imperfecta type XV, Turner syndrome (45, X0/46, XX chimera) with TH gene-related Segawa syndrome, Chromosome 22q11.2 microduplication syndrome with DYNC1H1 gene-related autosomal dominant lower extremity-predominant spinal muscular atrophy-1, and ANKRD11 gene-related KBG syndrome combined with IRF2BPL gene-related neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy. DMD was the most common, and there were 6 autosomal dominant diseases caused by de novo heterozygous pathogenic variations. Conclusions: Pediatric patients with coexistence of double genetic diagnoses show complex phenotypes. When the clinical manifestations and progression are not fully consistent with the diagnosed rare genetic disease, a second rare genetic disease should be considered, and autosomal dominant diseases caused by de novo heterozygous pathogenic variation should be paid attention to. Trio-based whole-exome sequencing combining a variety of molecular genetic tests would be helpful for precise diagnosis.

Neurological Complications in MIS-C: Case Report

COVID-19 has seriously affected children and the whole world. Pediatric multi-system inflammatory syndrome (MIS-C), a new syndrome that has not been known before, has been described. Although MIS-C may progress with different clinical manifestations in children, neurological involvement is reported relatively rarely. A 12-year-old girl with cerebral palsy and motor mental retardation was admitted to the emergency department with complaints of cough, fever, mouth sores and malnutrition. As a result of the evaluation, the patient was hospitalized to investigate the etiology of the fever and empirical antibiotic treatment was started, and she developed a rash on the 3rd day and tonic-clonic convulsions on the 5th day. The patient was hospitalized in the pediatric intensive care unit (PICU), and COVID-19 IgG and IgM were positive. Cerebral imaging of the patient was reported as normal. The patient with fever, rash, convulsions lasting longer than five days, and compatible laboratory results were diagnosed with MIS-C. Intravenous immunoglobulin (IVIG) and methylprednisolone treatments were started, and the patient was discharged on the 14th day of hospitalization, whose condition improved. This case is presented as an example of the rare neurological involvement of MIS-C. Detailed clinical investigation and neurological examination are required to exclude neurological sequelae of COVID-19 during the pandemic. The development of general guidelines that can combine them would be instructive.