Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy r...Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as glutathione to address offensive enhanced cytokines, in patients with suspected PANDAS/CANS.展开更多
Immune-mediated mechanisms are involved in the pathogenesis of both cerebral vasculitis and Parkinson’s disease（PD, brainstem-predominant Lewy pathology）, but the presentation of cerebral vasculitis with comorbid L...Immune-mediated mechanisms are involved in the pathogenesis of both cerebral vasculitis and Parkinson’s disease（PD, brainstem-predominant Lewy pathology）, but the presentation of cerebral vasculitis with comorbid Lewy pathology has not yet been reported. Here we present a case of pathologically confirmed vasculitis in a 73-year-old male patient whose postmortem examination revealed Lewy pathology diagnostic of PD. This case study suggests a comorbidity of cerebral vasculitis and Lewy pathology, as well as potential pathogenic interactions between these two disorders with immune-mediated mechanisms.展开更多
In the last decades,a large variety of oxidative phosphorylation (OXPHOS) defects have been reported,expressed as an increasing variety of clinical phenotypes. With the expanding number of genes and proteins involved,...In the last decades,a large variety of oxidative phosphorylation (OXPHOS) defects have been reported,expressed as an increasing variety of clinical phenotypes. With the expanding number of genes and proteins involved,new screening techniques leading to more effective diagnostic routes are in ever-increasing demand. Cultured skin fibroblasts from a cohort of patients with various OXPHOS defects,previously recognized by enzyme activity studies and blue native PAGE,were investigated with an immunocytochemical technique. Cytospins of cultured fibroblasts were air dried,fixed,and stained with antibodies specifically directed against subunits of each OXPHOS complex. Control cells stained homogeneously and strongly. In fibroblasts from five out of seven patients with a severe deficiency of one of the OXPHOS complexes,a homogeneous reduction of cytoimmunore activity of the affected complex was observed. In five out of seven fibroblast strains harboring a mitochondrial tRNA mutation,a mosaic pattern of staining was observed for both complexes I and IV,reflecting the heteroplasmic nature of the defect. The proportion of deficient fibroblasts varied considerably between cell strains from different subjects. The method described offers a convenient and rapid approach to first-line screening of OXPHOS defects. In association with routine assays of enzyme activity,the technique is helpful in orienting molecular investigation further.展开更多
Previous sleep studies of preterm neonates describe the rudimentary expression of sleep state cyclicity after 30 wk postconceptional age (PCA), with stability over multiple cycles only after 36 wk PCA. The research ob...Previous sleep studies of preterm neonates describe the rudimentary expression of sleep state cyclicity after 30 wk postconceptional age (PCA), with stability over multiple cycles only after 36 wk PCA. The research objective for this study was to determine whether sleep state cyclicity was expressed in neonates of 25-30 wk PCA, using two criteria for state identification. Our neonatal sleep consortium includes a total cohort of 359 children who were healthy and medically ill neonates who were recruited from three obstetric-neonatal services and received multiple-hour EEG sleep studies. A subset of the 33 youngest preterm infants were selected to evaluate the first of serial 2-to 3-h EEG-sleep recordings to assess the presence of sleep state cyclicity. One neonatal neurophysiologist visually assigned EEG-sleep characteristics for each record. Rapid eye movement (REM) counts and EEG discontinuity were specifi-cally chosen to assess whether sleep cyclicity was expressed. A combined measure of REM and EEG discontinuity were used in an autocovariance analysis to assess cycling and mean cycle duration. A mean cycle duration of 68 ± 19 min with a range of 37-100 min was determined from the REM-EEG discontinuity state for 24 neonates. The remaining nine infants had absent or poor sleep cyclicity. Sleep state cyclicity is expressed for a majority of neonates between 25 and 30 wk PCA, reflecting an ultradian biologic rhythm during the early perinatal stage of brain development.展开更多
The authors assessed whether magnetoencephalography/magnetic source imaging (MEG/MSI) identified epileptogenic zones in patients with tuberous sclerosis complex (TSC). In six TSC children with focal seizures, ictal vi...The authors assessed whether magnetoencephalography/magnetic source imaging (MEG/MSI) identified epileptogenic zones in patients with tuberous sclerosis complex (TSC). In six TSC children with focal seizures, ictal video-EEG predicted the region of resection with 56%sensitivity, 80%specificity, and 77%accuracy (p = 0.02), whereas interictal MEG/MSI fared better (100%, 94%, and 95%, respectively; p < 0.0001). Interictal MEG/MSI seems to identify epileptogenic zones more accurately in children with TSC and focal intractable epilepsy.展开更多
Background: Saccades are essential for optimal visual function. Chiari type I I malformation (CII) is a congenital anomaly of the cerebellum and brainstem, as sociated with spina bifida. Objective: To investigate the ...Background: Saccades are essential for optimal visual function. Chiari type I I malformation (CII) is a congenital anomaly of the cerebellum and brainstem, as sociated with spina bifida. Objective: To investigate the effects of CII on sacc ades and correlate saccadic parameters with brain MRI measurements. Methods: Sac cades were recorded in 21 participants with CII, aged 8 to 19, using an infrared eye tracker. Thirty- nine typically developing children served as controls. Pa rticipants made saccades to horizontal and vertical target steps. Nineteen parti cipants with CII had MRI. Regression analyses were used to investigate the effec ts of spinal lesion level, number of shunt revisions, presence of nystagmus, and midsagittal MRI measurements on saccades. Results: Saccadic amplitude gains, as ymptotic peak velocities, and latencies did not differ between the control and C II groups (p > 0.01). No significant differences were found between saccadic gai ns, asymptotic peak velocities or latencies, and spinal lesion level, number of shunt revisions, presence of nystagmus, or MRI measurements. Conclusions: Saccad es were normal in most participants with Chiari Ⅱ malformation (CII). Neural c oding of saccades is robust and is typically not affected by the anatomic deform ity of CII.展开更多
To the Editor:Currently,there is no standardized treatment protocol for the pediatric anti-N-methyl-D-aspartate receptor(NMDAR).There are two surveys by Kahn et al[1]and Bartolini et al[2]that aimed at determining the...To the Editor:Currently,there is no standardized treatment protocol for the pediatric anti-N-methyl-D-aspartate receptor(NMDAR).There are two surveys by Kahn et al[1]and Bartolini et al[2]that aimed at determining the treatment strategies that are used for pediatric NMDAR encephalitis in other parts of the world rather than China.Bartolini et al[2]performed a worldwide survey involving 199 participants:61 adult neurologists,86 pediatric neurologists,and 52 pediatric rheumatologists.Their survey investigated the differences in anti-NMDAR encephalitis treatment strategies,according to medical specialty,years in practice,and geographical location.[2]The survey of Kahn et al[1]involved 151 pediatric neurologists and focused on identifying the indications for the initiation of immunotherapy,type of the used immunotherapy,length of the first-line immunotherapy,time for the initiation of the second-line immunotherapy,and the preferable options for the second-line immunotherapy.Additionally,they investigated the indications and time for adding a disease-modifying therapy,and how long should patients continue with the immunotherapy once returned to their neurologic baseline.[1]Both surveys did not sufficiently focus on identifying the utility of the modified Rankin Scale(mRS),dosages and duration of the treatments(including the duration of oral prednisone),the utility of Cluster of Differentiation 19 positive(CD19+)B cells in adjusting the dosages of rituximab,the necessity of long-term immunosuppressive treatment(for relapse prevention),and the indications for stopping the immunotherapy.展开更多
Autonomic nervous system dysfunction has been described with focal and generalized epileptic seizures;occurring during their ictal,interictal,or postictal states.International League Against Epilepsy Seizure Classific...Autonomic nervous system dysfunction has been described with focal and generalized epileptic seizures;occurring during their ictal,interictal,or postictal states.International League Against Epilepsy Seizure Classification Manual defines autonomic seizures as a distinct alteration of autonomic nervous system function involving cardiovascular,pupillary,gastrointestinal,sudomotor,vasomotor,and thermoregulatory functions.Autonomic seizures represent a great challenge for neonatologists and neurophysiologists;and distinguishing between ictal and non-ictal autonomic changes in neonates is rarely straightforward,especially in the premature ones.To avoid overdiagnosis and overtreatment,International League Against Epilepsy and the American Clinical Neurophysiology Society currently require electrographic correlation for any seizure diagnosis,including preterm neonates.There is very little scientific evidence about the pathophysiology of autonomic seizures.The data reporting on their incidence,clinical features,and diagnostic pathway is also insufficient.In this paper,we hypothesize that in the developing brain of preterm neonates,seizures involving deeper autonomic networks and subcortical structures might not propagate sufficiently to the cortex,and therefore the association of the seizures with specific ictal electrographic changes on surface electroencephalogram might be lacking.We propose considering autonomic seizures in the differential diagnosis of unexplained autonomic changes in neonates,especially preterm neonates,even in the absence of clear initial electrographic correlation.Unexplained autonomic changes could therefore be thought of as a“seizure alarm”in this population.展开更多
The ketogenic diet(KD)is a high-fat,low-carbohydrate diet,in which fat is used as the primary energy source through the production of ketone bodies(KBs)in place of glucose.The KD was formally introduced in 1921 to mim...The ketogenic diet(KD)is a high-fat,low-carbohydrate diet,in which fat is used as the primary energy source through the production of ketone bodies(KBs)in place of glucose.The KD was formally introduced in 1921 to mimic the biochemical changes associated with fasting and gained recognition as a potent treatment for pediatric epilepsy in the mid-1990s.The clinical and basic scientific knowledge that supports the anti-seizure efficacy,safety,and feasibility of using the KD in patients with epilepsy is huge.Additionally,the International Ketogenic Diet Study Group’s consensus guidelines provide practical information in 2009 and 2018.The KD is a broad-spectrum therapy for drug resistant epilepsy and is gaining attention as a potential therapy for other neurological disorders.This article will review recent aspects on the use of the KD,including its mechanisms of action,KD alternatives,expanding its use across different age groups and regions,its use as a treatment for other neurologic disorders,and future research subjects.展开更多
Cerebral palsy(CP)is a global,complex and lifelong health issue with a relatively high disease burden in low-resource countries.The benefits of a national disease registry in general and a national CP registry in part...Cerebral palsy(CP)is a global,complex and lifelong health issue with a relatively high disease burden in low-resource countries.The benefits of a national disease registry in general and a national CP registry in particular are twofold,namely the public health and the clinical disease-related benefits.A national CP quality registry has the potential to inform health planning and spending at national,regional and continental levels.In turn,this can help allocate and manage the relevant material and human resources in a more predictable and efficient manner.展开更多
Adevelopmentally normal,15-year-old boy presented with complaint of gait abnormalities since 8 years of age.The child complained of difficulty in climbing stairs and running.He could not climb stairs without the suppo...Adevelopmentally normal,15-year-old boy presented with complaint of gait abnormalities since 8 years of age.The child complained of difficulty in climbing stairs and running.He could not climb stairs without the support of railing.There was no problem with rising from sitting or lying down position.展开更多
Background:Transcriptomic and proteomic profiling of human brain tissue is hindered by the availability of fresh samples from living patients.Postmortem samples usually represent the advanced disease stage of the pati...Background:Transcriptomic and proteomic profiling of human brain tissue is hindered by the availability of fresh samples from living patients.Postmortem samples usually represent the advanced disease stage of the patient.Fur-thermore,the postmortem interval can affect the transcriptomic and proteomic profiles.Therefore,fresh brain tissue samples from living patients represent a valuable resource of metabolically intact tissue.Implantation of deep brain stimulation(DBS)electrodes into the human brain is a neurosurgical treatment for,e.g.,movement disorders.Here,we describe an improved approach to collecting brain tissues from surgical instruments used in implantation of DBS device for transcriptomics and proteomics analyses.Methods:Samples were extracted from guide tubes and recording electrodes used in routine DBS implantation procedure to treat patients with Parkinson’s disease,genetic dystonia and tremor.RNA sequencing was performed in tissues extracted from the recording microelectrodes and liquid chromatography-mass spectrometry(LC-MS)per-formed in tissues from guide tubes.To assess the performance of the current approach,the obtained datasets were compared with previously published datasets representing brain tissues.Results:Altogether,32,034 RNA transcripts representing the unique Ensembl gene identifiers were detected from eight samples representing both hemispheres of four patients.By using LC-MS,we identified 734 unique proteins from 31 samples collected from 14 patients.The datasets are available in the BioStudies database(accession number S-BSST667).Our results indicate that surgical instruments used in DBS installation retain brain material sufficient for protein and gene expression studies.Comparison with previously published datasets obtained with similar approach proved the robustness and reproducibility of the protocol.Conclusions:The instruments used during routine DBS surgery are a useful source for obtaining fresh brain tis-sues from living patients.This approach overcomes the issues that arise from using postmortem tissues,such as the effect of postmortem interval on transcriptomic and proteomic landscape of the brain,and can be used for studying molecular aspects of DBS-treatable diseases.展开更多
文摘Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as glutathione to address offensive enhanced cytokines, in patients with suspected PANDAS/CANS.
文摘Immune-mediated mechanisms are involved in the pathogenesis of both cerebral vasculitis and Parkinson’s disease（PD, brainstem-predominant Lewy pathology）, but the presentation of cerebral vasculitis with comorbid Lewy pathology has not yet been reported. Here we present a case of pathologically confirmed vasculitis in a 73-year-old male patient whose postmortem examination revealed Lewy pathology diagnostic of PD. This case study suggests a comorbidity of cerebral vasculitis and Lewy pathology, as well as potential pathogenic interactions between these two disorders with immune-mediated mechanisms.
文摘In the last decades,a large variety of oxidative phosphorylation (OXPHOS) defects have been reported,expressed as an increasing variety of clinical phenotypes. With the expanding number of genes and proteins involved,new screening techniques leading to more effective diagnostic routes are in ever-increasing demand. Cultured skin fibroblasts from a cohort of patients with various OXPHOS defects,previously recognized by enzyme activity studies and blue native PAGE,were investigated with an immunocytochemical technique. Cytospins of cultured fibroblasts were air dried,fixed,and stained with antibodies specifically directed against subunits of each OXPHOS complex. Control cells stained homogeneously and strongly. In fibroblasts from five out of seven patients with a severe deficiency of one of the OXPHOS complexes,a homogeneous reduction of cytoimmunore activity of the affected complex was observed. In five out of seven fibroblast strains harboring a mitochondrial tRNA mutation,a mosaic pattern of staining was observed for both complexes I and IV,reflecting the heteroplasmic nature of the defect. The proportion of deficient fibroblasts varied considerably between cell strains from different subjects. The method described offers a convenient and rapid approach to first-line screening of OXPHOS defects. In association with routine assays of enzyme activity,the technique is helpful in orienting molecular investigation further.
文摘Previous sleep studies of preterm neonates describe the rudimentary expression of sleep state cyclicity after 30 wk postconceptional age (PCA), with stability over multiple cycles only after 36 wk PCA. The research objective for this study was to determine whether sleep state cyclicity was expressed in neonates of 25-30 wk PCA, using two criteria for state identification. Our neonatal sleep consortium includes a total cohort of 359 children who were healthy and medically ill neonates who were recruited from three obstetric-neonatal services and received multiple-hour EEG sleep studies. A subset of the 33 youngest preterm infants were selected to evaluate the first of serial 2-to 3-h EEG-sleep recordings to assess the presence of sleep state cyclicity. One neonatal neurophysiologist visually assigned EEG-sleep characteristics for each record. Rapid eye movement (REM) counts and EEG discontinuity were specifi-cally chosen to assess whether sleep cyclicity was expressed. A combined measure of REM and EEG discontinuity were used in an autocovariance analysis to assess cycling and mean cycle duration. A mean cycle duration of 68 ± 19 min with a range of 37-100 min was determined from the REM-EEG discontinuity state for 24 neonates. The remaining nine infants had absent or poor sleep cyclicity. Sleep state cyclicity is expressed for a majority of neonates between 25 and 30 wk PCA, reflecting an ultradian biologic rhythm during the early perinatal stage of brain development.
文摘The authors assessed whether magnetoencephalography/magnetic source imaging (MEG/MSI) identified epileptogenic zones in patients with tuberous sclerosis complex (TSC). In six TSC children with focal seizures, ictal video-EEG predicted the region of resection with 56%sensitivity, 80%specificity, and 77%accuracy (p = 0.02), whereas interictal MEG/MSI fared better (100%, 94%, and 95%, respectively; p < 0.0001). Interictal MEG/MSI seems to identify epileptogenic zones more accurately in children with TSC and focal intractable epilepsy.
文摘Background: Saccades are essential for optimal visual function. Chiari type I I malformation (CII) is a congenital anomaly of the cerebellum and brainstem, as sociated with spina bifida. Objective: To investigate the effects of CII on sacc ades and correlate saccadic parameters with brain MRI measurements. Methods: Sac cades were recorded in 21 participants with CII, aged 8 to 19, using an infrared eye tracker. Thirty- nine typically developing children served as controls. Pa rticipants made saccades to horizontal and vertical target steps. Nineteen parti cipants with CII had MRI. Regression analyses were used to investigate the effec ts of spinal lesion level, number of shunt revisions, presence of nystagmus, and midsagittal MRI measurements on saccades. Results: Saccadic amplitude gains, as ymptotic peak velocities, and latencies did not differ between the control and C II groups (p > 0.01). No significant differences were found between saccadic gai ns, asymptotic peak velocities or latencies, and spinal lesion level, number of shunt revisions, presence of nystagmus, or MRI measurements. Conclusions: Saccad es were normal in most participants with Chiari Ⅱ malformation (CII). Neural c oding of saccades is robust and is typically not affected by the anatomic deform ity of CII.
文摘To the Editor:Currently,there is no standardized treatment protocol for the pediatric anti-N-methyl-D-aspartate receptor(NMDAR).There are two surveys by Kahn et al[1]and Bartolini et al[2]that aimed at determining the treatment strategies that are used for pediatric NMDAR encephalitis in other parts of the world rather than China.Bartolini et al[2]performed a worldwide survey involving 199 participants:61 adult neurologists,86 pediatric neurologists,and 52 pediatric rheumatologists.Their survey investigated the differences in anti-NMDAR encephalitis treatment strategies,according to medical specialty,years in practice,and geographical location.[2]The survey of Kahn et al[1]involved 151 pediatric neurologists and focused on identifying the indications for the initiation of immunotherapy,type of the used immunotherapy,length of the first-line immunotherapy,time for the initiation of the second-line immunotherapy,and the preferable options for the second-line immunotherapy.Additionally,they investigated the indications and time for adding a disease-modifying therapy,and how long should patients continue with the immunotherapy once returned to their neurologic baseline.[1]Both surveys did not sufficiently focus on identifying the utility of the modified Rankin Scale(mRS),dosages and duration of the treatments(including the duration of oral prednisone),the utility of Cluster of Differentiation 19 positive(CD19+)B cells in adjusting the dosages of rituximab,the necessity of long-term immunosuppressive treatment(for relapse prevention),and the indications for stopping the immunotherapy.
文摘Autonomic nervous system dysfunction has been described with focal and generalized epileptic seizures;occurring during their ictal,interictal,or postictal states.International League Against Epilepsy Seizure Classification Manual defines autonomic seizures as a distinct alteration of autonomic nervous system function involving cardiovascular,pupillary,gastrointestinal,sudomotor,vasomotor,and thermoregulatory functions.Autonomic seizures represent a great challenge for neonatologists and neurophysiologists;and distinguishing between ictal and non-ictal autonomic changes in neonates is rarely straightforward,especially in the premature ones.To avoid overdiagnosis and overtreatment,International League Against Epilepsy and the American Clinical Neurophysiology Society currently require electrographic correlation for any seizure diagnosis,including preterm neonates.There is very little scientific evidence about the pathophysiology of autonomic seizures.The data reporting on their incidence,clinical features,and diagnostic pathway is also insufficient.In this paper,we hypothesize that in the developing brain of preterm neonates,seizures involving deeper autonomic networks and subcortical structures might not propagate sufficiently to the cortex,and therefore the association of the seizures with specific ictal electrographic changes on surface electroencephalogram might be lacking.We propose considering autonomic seizures in the differential diagnosis of unexplained autonomic changes in neonates,especially preterm neonates,even in the absence of clear initial electrographic correlation.Unexplained autonomic changes could therefore be thought of as a“seizure alarm”in this population.
文摘The ketogenic diet(KD)is a high-fat,low-carbohydrate diet,in which fat is used as the primary energy source through the production of ketone bodies(KBs)in place of glucose.The KD was formally introduced in 1921 to mimic the biochemical changes associated with fasting and gained recognition as a potent treatment for pediatric epilepsy in the mid-1990s.The clinical and basic scientific knowledge that supports the anti-seizure efficacy,safety,and feasibility of using the KD in patients with epilepsy is huge.Additionally,the International Ketogenic Diet Study Group’s consensus guidelines provide practical information in 2009 and 2018.The KD is a broad-spectrum therapy for drug resistant epilepsy and is gaining attention as a potential therapy for other neurological disorders.This article will review recent aspects on the use of the KD,including its mechanisms of action,KD alternatives,expanding its use across different age groups and regions,its use as a treatment for other neurologic disorders,and future research subjects.
文摘Cerebral palsy(CP)is a global,complex and lifelong health issue with a relatively high disease burden in low-resource countries.The benefits of a national disease registry in general and a national CP registry in particular are twofold,namely the public health and the clinical disease-related benefits.A national CP quality registry has the potential to inform health planning and spending at national,regional and continental levels.In turn,this can help allocate and manage the relevant material and human resources in a more predictable and efficient manner.
文摘Adevelopmentally normal,15-year-old boy presented with complaint of gait abnormalities since 8 years of age.The child complained of difficulty in climbing stairs and running.He could not climb stairs without the support of railing.There was no problem with rising from sitting or lying down position.
基金the Academy of Finland(Decision Numbers#311934 R.H.[profiling programme]and#331436 J.U.),Pediatric Research Foundation,Finland(J.U.and R.H.),Biocenter Oulu(J.U.and R.H.),Biocenter Finland,Special State Grants for Health Research,Oulu University Hospital,Finland(J.U.)the Terttu Foundation,Oulu University Hospital,Finland(J.K.).
文摘Background:Transcriptomic and proteomic profiling of human brain tissue is hindered by the availability of fresh samples from living patients.Postmortem samples usually represent the advanced disease stage of the patient.Fur-thermore,the postmortem interval can affect the transcriptomic and proteomic profiles.Therefore,fresh brain tissue samples from living patients represent a valuable resource of metabolically intact tissue.Implantation of deep brain stimulation(DBS)electrodes into the human brain is a neurosurgical treatment for,e.g.,movement disorders.Here,we describe an improved approach to collecting brain tissues from surgical instruments used in implantation of DBS device for transcriptomics and proteomics analyses.Methods:Samples were extracted from guide tubes and recording electrodes used in routine DBS implantation procedure to treat patients with Parkinson’s disease,genetic dystonia and tremor.RNA sequencing was performed in tissues extracted from the recording microelectrodes and liquid chromatography-mass spectrometry(LC-MS)per-formed in tissues from guide tubes.To assess the performance of the current approach,the obtained datasets were compared with previously published datasets representing brain tissues.Results:Altogether,32,034 RNA transcripts representing the unique Ensembl gene identifiers were detected from eight samples representing both hemispheres of four patients.By using LC-MS,we identified 734 unique proteins from 31 samples collected from 14 patients.The datasets are available in the BioStudies database(accession number S-BSST667).Our results indicate that surgical instruments used in DBS installation retain brain material sufficient for protein and gene expression studies.Comparison with previously published datasets obtained with similar approach proved the robustness and reproducibility of the protocol.Conclusions:The instruments used during routine DBS surgery are a useful source for obtaining fresh brain tis-sues from living patients.This approach overcomes the issues that arise from using postmortem tissues,such as the effect of postmortem interval on transcriptomic and proteomic landscape of the brain,and can be used for studying molecular aspects of DBS-treatable diseases.
