Clinical Neurology

Background: Brain microstructural maturation progresses rapidly in the third trimester of gestation and first weeks of life, but typical microstructural development may be influenced by the presence of critical congenital heart disease (CHD). Objective: The aim of this study was to investigate the pattern of white matter (WM) microstructural development in neonates with different types of critical CHD. The secondary aim was to examine whether there is an association between WM microstructural maturity and neonatal ischemic brain injury. Methods: For this prospective, longitudinal cohort study, 74 term born neonates underwent diffusion tensor imaging (DTI) before (N = 56) and after (N = 71) cardiac surgery performed < 30 days of life for transposition of the great arteries (TGA), single ventricle physiology with aortic arch obstruction (SVP-AO), left-(LVOTO) or right ventricle outflow tract obstruction (RVOTO). Microstructural integrity was investigated by fractional anisotropy (FA) and by mean diffusivity (MD) in 16 white matter (WM) structures in three WM regions with correction for postmenstrual age. Ischemic brain injury was defined as moderate-severe white matter injury or stroke. Results: Before cardiac surgery, the posterior parts of the corona radiata and internal capsule showed significantly higher FA and lower MD compared to the anterior parts. Centrally-located WM structures demonstrated higher FA compared to peripherally-located structures. Neonates with TGA had higher FA in projection-, association-and commissural WM before surgery, when compared to other CHD groups. Neonates with LVOTO showed lower preoperative MD in these regions, and neonates with SVP-AO higher MD. Differences in FA/MD between CHD groups were most clear in centrally located WM structures. Between CHD groups, no differences in postoperative FA/MD or in change from pre-to postoperative FA/MD were seen. Neonatal ischemic brain injury was not associated with pre-or postoperative FA/MD. Conclusions: Collectively, these findings revealed brain microstructural WM development to follow the same organized pattern in critical CHD as reported in healthy and preterm neonates, from posterior-to-anterior and central-to-peripheral. Neonates with TGA and LVOTO showed the most mature WM microstructure before surgery and SVP-AO the least mature. Degree of WM microstructural immaturity was not associated with ischemic brain injury.

Evidence for the comparative teratogenic risk of antiepileptic drugs is insufficient, particularly in relation to the dosage used. Therefore, we aimed to compare the occurrence of major congenital malformations following prenatal exposure to the eight most commonly used antiepileptic drugs in monotherapy. We did a longitudinal, prospective cohort study based on the EURAP international registry. We included data from pregnancies in women who were exposed to antiepileptic drug monotherapy at conception, prospectively identified from 42 countries contributing to EURAP. Follow-up data were obtained after each trimester, at birth, and 1 year after birth. The primary objective was to compare the risk of major congenital malformations assessed at 1 year after birth in offspring exposed prenatally to one of eight commonly used antiepileptic drugs (carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, and valproate) and, whenever a dose dependency wa...

Holoprosencephaly (HPE) is a pathology of forebrain development characterized by high phenotypic and locus heterogeneity. Seventeen genes are known so far in HPE but the understanding of its genetic architecture remains to be refined. Here, we investigated the oligogenic nature of HPE resulting from accumulation of variants in different relevant genes. Exome data from 29 patients diagnosed with HPE and 51 relatives from 26 unrelated families were analyzed. Standard variant classification approach was improved with a gene prioritization strategy based on clinical ontologies and gene co-expression networks. Clinical phenotyping and exploration of cross-species similarities were further performed on a family-by-family basis. We identified 232 rare deleterious variants in HPE patients representing 180 genes significantly associated with key pathways of forebrain development including Sonic Hedgehog (SHH) and Primary Cilia. Oligogenic events were observed in 10 families and involved novel HPE genes including recurrently mutated genes (FAT1, NDST1, COL2A1 and SCUBE2) and genes implicated in cilia function. This study reports novel HPE-relevant genes and reveals the existence of oligogenic cases resulting from several mutations in SHH-related genes. It also underlines that integrating clinical phenotyping in genetic studies will improve the identification of causal variants in rare disorders.

Background and PurposezzThe potential association between the severity of autonomic dysfunction and peripheral neuropathy has not been extensively investigated, with the few studies yielding inconsistent results. We evaluated the relationship between autonomic dysfunction and peripheral neuropathy in chronic hemodialysis patients in a cross-sectional study. MethodszzCardiovascular autonomic function was assessed in 42 consecutive patients with chronic renal failure treated by hemodialysis, using a standardized battery of 5 cardiovascular reflex tests. Symptoms of autonomic dysfunction and of peripheral neuropathy were evaluated using the Autonomic Neuropathy Symptom Score (ANSS) and the Neuropathy Symptoms Score. Neurological deficits were assessed using the Neuropathy Disability Score. Conduction velocities along the sensory and motor fibers of the sural and peroneal nerves were measured. Thermal thresholds were documented using a standardized psychophysical technique. ResultszzParasympathetic and sympathetic dysfunction was prevalent in 50% and 28% of cases, respectively. Peripheral neuropathy was identified in 25 cases (60%). The prevalence of peripheral neuropathy did not differ between patients with impaired (55%) and normal (75%) autonomic function (p=0.297; Fisher's exact test). The electrophysiological parameters for peripheral nerve function, neuropathic symptoms, abnormal thermal thresholds, age, gender, and duration of dialysis did not differ significantly between patients with and without autonomic dysfunction. Patients with autonomic dysfunction were more likely to have an abnormal ANSS (p=0.048). The severity of autonomic dysfunction on electrophysiological testing was positively correlated with ANSS (r=0.213, p=0.036). ConclusionszzThe present data indicate that although cardiovascular autonomic dysfunction is prevalent among patients with chronic renal failure, it is not associated with the incidence of peripheral neuropathy.

Objective: Predictable patterns of atrophy are associated with the clinical subtypes of frontotemporal dementia (FTD): behavioral variant (bvFTD), semantic dementia (SEMD), and progressive nonfluent aphasia (PNFA). Some studies of pathologic subtypes have also suggested specific atrophy patterns; however, results are inconsistent. Our aim was to test the hypothesis that clinical, but not pathologic, classification (FTD with ubiquitin inclusions [FTD-U] and FTD with tau inclusions [FTD-T]) is associated with predictable patterns of regional atrophy. Methods: Magnetic resonance scans of nine FTD-U and six FTD-T patients (histologically confirmed) were compared with 25 controls using voxel-based morphometry (VBM). Analyses were conducted with the patient group classified according to histologic or clinical variant. Additionally, three Alzheimer pathology patients who had the syndrome of SEMD in life (FTD-A) were analyzed. The VBM studies in clinical variants confirmed established patterns of atrophy (SEMD, rostral temporal; bvFTD, mesial frontal; PNFA, left insula). FTD-U and FTD-T VBM results were very similar, showing severe atrophy in the temporal poles, mesial frontal lobe, and insulae. A conjunction analysis confirmed this similarity. Subgroup analysis found that SEMD associated with either FTD-T or FTD-U was associated with similar rostral temporal atrophy; however, FTD-A had a qualitatively different pattern of left hippocampal atrophy. While there is predictable atrophy for clinical variants of frontotemporal dementia (FTD), histologic FTD variants show no noticeable differences. Reports of specific atrophy profiles are likely the result of idiosyncrasies in small groups. Semantic dementia associated with Alzheimer pathology, however, presented a distinct atrophy pattern. Neurology ® 2009;72:1653-1660 GLOSSARY AD ϭ Alzheimer disease; bvFTD ϭ behavioral variant frontotemporal dementia; FTD ϭ frontotemporal dementia; FTD-A ϭ Alzheimer pathology with semantic dementia; FTD-T ϭ frontotemporal dementia with tau inclusions; FTD-U ϭ frontotemporal dementia with ubiquitin inclusions; FTLD ϭ frontotemporal lobar degeneration; MMSE ϭ Mini-Mental State Examination; PNFA ϭ progressive nonfluent aphasia; SEMD ϭ semantic dementia; VBM ϭ voxel-based morphometry. Frontotemporal lobar degeneration (FTLD) is unique among the dementias in that it is heterogeneous in terms of both clinical syndrome and underlying histopathologic signature. Clinically, patients may present with semantic dementia (SEMD), progressive nonfluent aphasia (PNFA), or personality change with neuropsychiatric symptoms referred to as behavioralvariant frontotemporal dementia (bvFTD, or simply FTD). As the name implies, FTLD macroscopically involves degeneration of the frontal and temporal lobes but the histopathology may include cases with tau-positive inclusions (FTD-T), ubiquitin-positive inclusions (FTD-U), or neither (dementia lacking distinctive histology). Identification of biomarkers for these histologic groupings would be desirable for stratification in disease-modifying therapy trials.

Objective: Recent post-mortem studies indicate that 30-40% of patients with clinically diagnosed progressive aphasia (PA) have AD pathology, while the remainder have pathology in the FTD spectrum. This study aimed to compare the clinical features of patients from these two groups. Materials & Methods: A retrospective chart review was conducted on 33 pathologically verified PA patients: n=13 AD and n=20 FTD-spectrum pathology. Demographics, global cognitive function, non-verbal memory, neuropsychiatric symptoms and structural imaging were compared between the two pathology-confirmed groups. Results: Median survival was 6.3 years in the FTD group versus 8.1 years in the AD group, in spite of the fact that onset for AD was on average 2.0 years older than FTD. Features highly specific in predicting FTD-spectrum pathology were age-of-onset before 60 years, preference for sweet food, disinhibition and focal knife-edge frontotemporal atrophy, although sensitivity for each of these was remarkably low (highest sensitivity was 45% for disinhibition). Some clinical features hypothesized to distinguish AD from FTD-spectrum pathology, such as global functional impairment within two years of onset and poor non-verbal memory ability, were not useful in separating the two groups. Conclusions: If present, certain clinical and imaging features can help to identify PA with FTD-spectrum pathology, notably the presence of the neuropsychiatric features seen with behavioural presentations of FTD and knife-edge atrophy on structural imaging. The profile of non-linguistic cognitive deficits does not appear discriminating though prospective studies are needed to evaluate this issue further. might have predictive value for AD pathology, diagnostic sensitivity and specificity for such features are not yet available. Moreover, it is unclear whether all patients with PA can be accommodated within a binary classification of PNFA and LPA. Identification of general clinical predictors of pathology in PA therefore remains relevant. Case ascertainment: PA cases were identified retrospectively from the local Brain Bank database. These were patients who had attended the Cognitive Disorders Clinics at Addenbrooke's Hospital, Cambridge, between 1990-2008 and had consented to post-mortem tissue donation. The research program was approved by the Addenbrooke's Hospital Local Research Ethics Committee. Criteria for PA were (i) an insidious onset, gradually progressive loss of language fluency as the primary presenting syndrome; (ii) effortful, distorted (or dysprosodic) speech output; (iii) phonological errors in conversation and/or repetition; (iv) preservation of single content-word comprehension. The study did not include patients whose loss of fluency appeared to be driven by word-finding pauses alone. All cases had been diagnosed as "PNFA" in life but, because this was a retrospective review, it was not always possible to be certain that cases pre-dating the description of LPA might not have had features more closely aligned to this latter syndrome. In particular, recent conceptualisation of LPA proposes that phonological errors may be part of the syndrome and such errors had always been considered a prominent feature in the local diagnostic formulation of PNFA. [9] As such the term "PA" is used in this study. Finally, in order to avoid biasing the results, less severe symptoms in other cognitive domains, such as memory, were not considered exclusion criteria. A total of 33 patients were identified, including 26 patients reported in an earlier clinicopathological study. Data collection 1/ Demographics and clinical features: Age at first presentation and death, and years of education, were noted. Age of onset was estimated according to the caregivers' reports at the first clinic attendance. Measures of clinical features, including global cognitive function, activities of daily living and neuropsychiatric symptoms, were obtained from the case records. These records had been systematically compiled in a clinical research-focused environment with particular specialist interest in documenting the features of neurodegenerative cognitive and behavioral syndromes. In latter years these records were further supplemented by care-giver rating questionnaires regarding cognition, behaviour and functional abilities (Cambridge Behavioural Inventory, CBI) and neuropsychiatric symptoms (Neuropsychiatric Inventory, NPI). Activities of daily living (ADLs) were assessed with reference to the patients' abilities in bathing, continence, dressing, feeding, going to the toilet and finding their way independently in and around the home. Impaired global cognitive function was defined as impairment in multiple cognitive domains on

Reports on the clinical meaningfulness of outcome measures in spinal muscular atrophy (SMA) are rare. In this two-part study, our aim was to explore patients&#39; and caregivers&#39; views on the clinical relevance of the Hammersmith Functional Motor Scale Expanded- (HFMSE). First, we used focus groups including SMA patients and caregivers to explore their views on the clinical relevance of the individual activities included in the HFMSE. Then we asked caregivers to comment on the clinical relevance of possible changes of HFMSE scores over time. As functional data of individual patients were available, some of the questions were tailored according to their functional level on the HFMSE. Part 1: Sixty-three individuals participated in the focus groups. This included 30 caregivers, 25 patients and 8 professionals who facilitated the discussion. The caregivers provided a comparison to activities of daily living for each of the HFMSE items. Part 2: One hundred and forty-nine caregivers ...

Somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 occur at high frequency in several tumour types. Even though these mutations are confined to distinct hotspots, we show that gliomas are the only tumour type with an exceptionally high percentage of IDH1R132H mutations. Patients harbouring IDH1R132H mutated tumours have lower levels of genome-wide DNA-methylation, and an associated increased gene expression, compared to tumours with other IDH1/2 mutations (“non-R132H IDH1/2 mutations”). This reduced methylation is seen in multiple tumour types and thus appears independent of the site of origin. For 1p/19q non-codeleted glioma (astrocytoma) patients, we show that this difference is clinically relevant: in samples of the randomised phase III CATNON trial, patients harbouring tumours with IDH mutations other than IDH1R132H have a better outcome (hazard ratio 0.41, 95% CI [0.24, 0.71], p = 0.0013). Such non-R132H IDH1/2-mutated tumours also had a significantly lower p...

Ethnic variations have been described in medical conditions, such as hypertension, diabetes, and multiple sclerosis. Whether ethnicity plays a role in Parkinson&#39;s disease (PD), particularly with regard to non-motor symptoms (NMS), remains unclear. Existing literature is diverse, controversial, and inadequately documented. This review aims to analyse and report the currently available literature on NMS, specifically in Asian PD patients. We conducted a literature review using PubMed, searching for articles and currently available publications that reference and assess NMS in PD patients living in Asia using the validated NMS Questionnaire (NMS Quest) and NMS Scale (NMSS). In total, 24 articles were included: 12 using the NMS Quest and 12 using the NMSS. Symptoms of constipation, memory impairment, and nocturia were the most frequently self-reported symptoms (NMS Quest) in selected Asian populations, while symptoms within the domains sleep/fatigue, attention/memory, and mood/apath...

For amyotrophic lateral sclerosis (ALS), achieving and maintaining effective drug levels in the brain is challenging due to the activity of ATP-binding cassette (ABC) transporters which efflux drugs that affect drug exposure and response in the brain. We investigated the expression and cellular distribution of the ABC transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) using immunohistochemistry in spinal cord (SC), motor cortex, and cerebellum from a large cohort of genetically well characterized ALS patients (n = 25) and controls (n = 14). The ALS group included 17 sporadic (sALS) and 8 familial (fALS) patients. Strong P-gp expression was observed in endothelial cells in both control and ALS specimens. Immunohistochemical analysis showed higher P-gp expression in reactive astroglial cells in both gray (ventral horn) and white matter of the SC, as well as in the motor cortex of all ALS patients, as compared with controls. BCRP expression was higher in gli...

The prevalence of dementia is increasing in South Korea. Multidomain interventions may be useful for preventing dementia. Such programs need to be disseminated to elderly Koreans throughout the country. We have developed programs of the SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN), which consists of a facility-based multidomain intervention (FMI) program and a home-based multidomain intervention (HMI) program suitable for elderly Koreans. We aim to determine the feasibility of the SUPERBRAIN programs before a large-scale randomized controlled trial. Methods We will recruit 150 participants among those without dementia aged 60-79 years with at least 1 modifiable dementia risk factor. They will be randomly assigned in a 1:1:1 ratio to the FMI, HMI, and the waiting-list control arm. The 6-month multidomain intervention consists of management of metabolic and vascular risk factors, cognitive training and social activity, physical exercise, nutritional guidance, and motivational enhancement programs. The primary outcomes are adherence and retention rates and changes in the total scale index score of the Repeatable Battery for the Assessment of Neuropsychological Status from baseline to the study end. The main secondary outcomes are disability, depressive symptoms, quality of life, vascular risk factors, physical performance, nutritional assessment, and motivation questionnaire. There will be an exploratory evaluation of neurotrophic, neurodegeneration, and neuroinflammation factors, microbiome, telomere length, electroencephalography, and neuroimaging measures. The results obtained will provide information on the applicability of these multidomain intervention programs to at-risk elderly people.

Background: Satoyoshi syndrome is a multisystemic rare disease of unknown etiology, although an autoimmune basis is presumed. Its main symptoms are: painful muscle spasms, diarrhea, alopecia and skeletal abnormalities. Clinical course without treatment may result in serious disability or death. A review of treatment and its response is still pending. Results: Sixty-four cases of Satoyoshi syndrome were published between 1967 and 2018. 47 cases described the treatment administered. Drugs used can be divided into two main groups of treatment: muscle relaxants/ anticonvulsants, and corticosteroids/immunosuppressants. Dantrolene improved muscle symptoms in 13 out of 15 cases, but not any other symptoms of the disease. Other muscle relaxants or anticonvulsant drugs showed little or no effect. 28 out of 30 cases responded to a regimen that included costicosteroids. Other immunosuppressive drugs including cyclosporine, mycophenolate mofetil, azathioprine, methotrexate, tacrolimus and cyclophosphamide were used to decrease corticosteroid dose or improve efficacy. Immunoglobulin therapy was used in nine patients and four of them obtained a favorable response. Conclusion: Corticosteroids was the most widely treatment employed with the best results in Satoyoshi syndrome. Further studies are needed to determine optimal dose and duration of corticosteroids as well as the role of other immunosuppressants and immunoglobulin therapy. Genetic or autoimmune markers will be useful to guide future therapies.

ObjectiveTo determine predictors of alcohol responsiveness in a large cohort of patients with dystonia.MethodsA total of 2,159 participants with dystonia were prospectively enrolled in the cross-sectional Dystonia Coalition multicenter study. Patients with secondary, combined, or confirmed genetic dystonia (total n = 164) or unknown alcohol responsiveness (n = 737) were excluded. Patients answered a standardized questionnaire and were clinically examined using a standardized video protocol and the Burke-Fahn-Marsden Dystonia Rating Scale. Alcohol responsiveness was determined by patients&#39; self-report.ResultsA total of 1,258 patients with isolated dystonia (mean age: 59.5 ± 12.2 years; 898 women) met the inclusion criteria; 369 patients (29.3%) reported improvement of dystonia after alcohol consumption. Alcohol responsiveness was not related to sex (p = 0.742), age (p = 0.715), or severity of dystonia (p = 0.623). Age at onset was lower in patients who responded to alcohol (p &lt...

Mitochondrial neurogastrointestinal encephalomyopathy is a fatal, recessive disease caused by mutations in the gene encoding thymidine phosphorylase leading to reduced enzymatic activity, toxic nucleoside accumulation and secondary mitochondrial DNA damage. Thymidine phosphorylase replacement has been achieved by allogeneic hematopoietic stem cell transplantation, a procedure hampered by high mortality. Based on the high thymidine phosphorylase expression in the liver, a 25-year-old severely affected patient underwent liver transplantation. Serum levels of toxic nucleosides rapidly normalized. At 400 days of follow-up the patient&#39;s clinical conditions are stable. We propose liver transplantation as a new therapy for mitochondrial neurogastrointestinal encephalomyopathy. This article is protected by copyright. All rights reserved.

Background Neurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe. Methods A survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP). The survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30 min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25 mmHg, 18% 30 mmHg, and 17% 20 mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions. The CENTER-TBI Investigators and Participants and their affiliations are listed at the end of the manuscript in the Appendix.

Epilepsies are very ancient diseases and the most widespread neurological diseases in the world. They are common conditions that constitute a heterogeneous group from an etiological perspective. The annual incidence of epilepsy is estimated at around 50 new cases per 100,000 inhabitants per year in industrialized countries, while in developing countries, this figure is higher, ranging from 100 to 190 new cases per 100,000 inhabitants per year. We conducted a cross-sectional analytical prospective study with stratified probabilistic sampling to select the subjects who participated. A total of 72 families were collected and subjected to statistical analyses. The patients living with epilepsy were aged 40 years or younger and had a family history of epilepsy. We found that the prevalence of familial epilepsy in Lubumbashi is 11.23% of cases and the mean age of patients with epilepsy and a family history of epilepsy is 15.24 ± 11.03 years, with a median of 14 years, a 1st quartile of 7 years and a 3rd quartile of 20 years. The sex ratio is 1.32 in favor of men and generalized tonic-clonic seizures represent 70.83% of cases, followed by absence seizures at 8.33%. The frequency of other seizures fluctuates between 1.39% and 4.17% of cases.

Epilepsies are very ancient diseases and the most widespread neurological diseases in the world. They are common conditions that constitute a heterogeneous group from an etiological perspective and, to this day, represent a source of tension between magical and scientific concepts, between superstitious beliefs and rational explanations. Most cases are multifactorial pathologies whose determinism involves environmental and genetic factors, which depend on the epilepsy group considered. The lack of genetic data on this disease in Lubumbashi prompted us to conduct a study on the clinical and genetic aspects of familial epilepsy in Lubumbashi. This study included patients aged 40 years or less who were diagnosed with epilepsy and had a family history of the disease. We performed a stratified probabilistic sampling, which allowed us to collect 72 families. In the first phase, these families were subjected to a cross-sectional analytical study, which led us to find a prevalence of 11.23% for familial epilepsy in Lubumbashi, with a mean patient age of 15.24 years ± 11.03 years and a sex ratio of 1.32 favoring the male sex. Generalized seizures were present in 70.83% of cases and absence seizures in 8.33%. The EEG showed paroxysmal grapho-elements in 35.75% and was normal in 27.78%. Epilepsy was transmitted in an autosomal dominant manner in 41.67% and in a recessive manner in 33.33% and no cases of consanguinity were noted. Five families were subjected to a second phase, a matched case-control study with whole-exome sequencing, which allowed us to highlight genetic variants/mutations. The sequencing data from our study indicated that genetic variants with good phenotype-genetic concordance according to ACMD criteria in cases of idiopathic epilepsy with generalized tonic-clonic seizures are: ATP2B1, SCN3A. The genetic mutations in cases of absence seizures are: CACNA1, NPRL2.

SummaryMedial temporal lobe of epilepsy (MTLE) is considered as local/regional epilepsy. However, as was discussed in Part I of this review (To provide contemporary review of MTLE in relation to the declarative memory system and the newly recognized hippocampo-frontal memory consolidation during slow wave sleep.A review of the available literature on experimental and clinical data and also the authors own studies in MTLE patients.New experimental and clinical neurophysiological data have shown that MTLE is closely linked to the hippocampal memory system. It is likely that hippocampal spiking is the epileptic variations of the normal sharp wave ripple events mediating the encoding and consolidation of memory engrams by a hippocampo-frontal dialogue during slow wave sleep.The source of memory impairment in MTLE patients is not merely the cell loss and synaptic transformation of the hippocampal structure, but the every night interference with memory consolidation due to interictal spik...

Progress in understanding and management of vascular cognitive impairment (VCI) has been hampered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Consensus Study (VICCCS) to agree on principles (VICCCS-1) and protocols (VICCCS-2) for diagnosis of VCI. We present VICCCS-2. We used VICCCS-1 principles and published diagnostic guidelines as points of reference for an online Delphi survey aimed at achieving consensus on clinical diagnosis of VCI. Six survey rounds comprising 65-79 participants agreed guidelines for diagnosis of VICCCS-revised mild and major forms of VCI and endorsed the National Institute of Neurological Disorders-Canadian Stroke Network neuropsychological assessment protocols and recommendations for imaging. The VICCCS-2 suggests standardized use of the National Institute of Neurological ...

The risk of stroke associated with carotid artery restenosis after stenting or endarterectomy is unclear. We aimed to compare the long-term risk of restenosis after these treatments and to investigate if restenosis causes stroke in a secondary analysis of the International Carotid Stenting Study (ICSS). ICSS is a parallel-group randomised trial at 50 tertiary care centres in Europe, Australia, New Zealand, and Canada. Patients aged 40 years or older with symptomatic carotid stenosis measuring 50% or more were randomly assigned either stenting or endarterectomy in a 1:1 ratio. Randomisation was computer-generated and done centrally, with allocation by telephone or fax, stratified by centre, and with minimisation for sex, age, side of stenosis, and occlusion of the contralateral carotid artery. Patients were followed up both clinically and with carotid duplex ultrasound at baseline, 30 days after treatment, 6 months after randomisation, then annually for up to 10 years. We included pa...

Prior research has suggested that individuals with Autism Spectrum Disorders (ASD) demonstrate heterogeneity in cognitive efficacy, challenged executive resources but efficient visual processing. These contrasts lead to opposing predictions about visuospatial working memory competency in both ASD and the broader autism phenotype (BAP); compromised by constrained executive processes, but potentially scaffolded by effective visual representation. It is surprising therefore, that there is a paucity of visual working memory (VWM) research in both the ASD and BAP populations, which have focused upon the visual features of the to‐be‐remembered stimulus. We assessed whether individual differences in VWM were associated with autistic‐like traits (ALTs) in the BAP. About 76 children carried out the Visual Just Noticeable Difference task, designed to measure high fidelity feature representation within VWM. ALTs were measured with the Children&#39;s Empathy Quotient and Systemizing Quotient. A...

Real-life social processing abilities of adults with autism spectrum disorders (ASD) can be hard to capture in lab-based experimental tasks. A novel measure of social cognition, the &quot;Strange Stories Film task&#39; (SSFt), was designed to overcome limitations of available measures in the field. Brief films were made based on the scenarios from the Strange Stories task (Happé) and designed to capture the subtle social-cognitive difficulties observed in ASD adults. Twenty neurotypical adults were recruited to pilot the new measure. A final test set was produced and administered to a group of 20 adults with ASD and 20 matched controls, alongside established social cognition tasks and questionnaire measures of empathy, alexithymia and ASD traits. The SSFt was more effective than existing measures at differentiating the ASD group from the control group. In the ASD group, the SSFt was associated with the Strange Stories task. The SSFt is a potentially useful tool to identify social co...

Background Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. Methods The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 95% uncertainty intervals (UIs) were generated for all final estimates as the 2•5th and 97•5th percentiles values of 500 draws. Uncertainty was propagated at each step of the estimation process. Counts and age-standardised rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations, from 1990 to 2021. Here we report data for 2010 to 2021 to highlight trends in disease burden over the past decade and through the first 2 years of the COVID-19 pandemic.

Background Cancers represent a challenging public health threat in Asia. This study examines the temporal patterns of incidence, mortality, disability and risk factors of 29 cancers in Asia in the last three decades. Methods The age, sex and year-wise estimates of incidence, mortality, and disability-adjusted life years (DALYs) of 29 cancers for 49 Asian countries from 1990 through 2019 were generated as a part of the Global Burden of Disease, Injuries and Risk Factors 2019 study. Besides incidence, mortality and DALYs, we also examined the cancer burden measured in terms of DALYs and deaths attributable to risk factors, which had evidence of causation with different cancers. The development status of countries was measured using the socio-demographic index. Decomposition analysis was performed to gauge the change in cancer incidence between 1990 and 2019 due to population growth, aging and age-specific incidence rates. Findings All cancers combined claimed an estimated 5.6 million [95% uncertainty interval, 5.1-6.0 million] lives in Asia with 9.4 million [8.6-10.2 million] incident cases and 144.7 million [132.7-156.5 million] DALYs in 2019. The agestandardized incidence rate (ASIR) of all cancers combined in Asia was 197.6/100,000 [181.0-214.4] in 2019, varying from 99.2/100,000 [76.1-126.0] in Bangladesh to 330.5/100,000 [298.5-365.8] in Cyprus. The age-standardized mortality rate (ASMR) was 120.6/100,000 [110.1-130.7] in 2019, varying 4-folds across countries from 71.0/100,000 [59.9-83.5] in Kuwait to 284.2/100,000 [229.2-352.3] in Mongolia. The age-standardized DALYs rate was 2970.

Magnetic resonance imaging (MRI) and electromyography (EMG) are complimentary investigations in diagnosis of lumbosacral radiculopathy (LSR). With changing pattern of S1 electrodiagnosis by H-reflex study measures, electrophysiological studies were conducted to establish most common electrophysiological predictors of LSR in MRI diagnosed L5S1 neural foramina compression subjects. Fifty subjects, with definite L5S1 neural foramina compression underwent electrophysiological evaluation and the data was analyzed using established electrodiagnostic criteria. Reduced H/M ratio in combination with absent H response was evident in 74 nerves. H-reflex study was abnormal in 88% subjects. Study concluded that, H/M ratio if used with other H-reflex study variables may be most common predictor of LSR.

We describe a case of 25-year-old-female with no significant medical history who presented with aphasia and right-sided hemiparesis & right upper motor neuron facial palsy. On examination she had feeble pulse, blood pressure difference in both arm, bruit heard over artery. Imaging studies revealed left middle cerebral artery infarct and carotid Doppler showed circumferential wall thickening suggestive of narrowing and near total occlusion. The diagnosis of Takayasu's arteritis was made and the patient was started on steroids with good clinical response.

The authors described their experience with 9 patients with PD, 18 with ET, and 3 with both. The clinical efficacy was monitored using a rating scale (Clinical Rating Scale for Tremor), the scores of which improved significantly at both 1 and 6 months following the treatment. The authors reported the adverse events, which included those that were transient and related to the sonication (headache, vertigo, nausea, and vomiting) and more long-term effects (ataxia and numbness). Of note, more than one-third of the patients experienced headache, although there is no comment on the severity. Also, almost half experienced vertigo, although only 10% experienced nausea. Of concern, 2 patients vomited around the time of the sonication. There is no mention of claustrophobia or positional discomfort, both of which we have seen at our center. Apart from local anesthetic administration for placement of the stereotactic frame, there is no mention of any other analgesia, sedation, or antiemetic. In a series reported by Elias et al., 1 there was a 60% incidence of head pain during sonication, and a 33% incidence of nausea with a 20% incidence of vomiting. In our experience with more than 50 patients with ET, we have seen the following. 1) Pain. The headache experienced can be severe enough to limit the power used. This can necessitate intravenous analgesia or risk aborting the procedure. 2) Nausea and vomiting. The vertigo is a relatively consistent experience for ET patients and may contribute to the nausea. Vomiting while secured to the MRI table and helmet poses a safety threat to the patient. 3) Claustrophobia is usually mild, but we observed severe symptoms requiring moderate to heavy sedation to complete the procedure. 4) Positional discomfort is a relatively common experience for these lengthy procedures (3-4 hours) and is effectively managed with sedation. Therefore, we contend that the comment in the authors' conclusions that there is no need for anesthesia is premature. While general anesthesia may not be required, we believe that the presence of personnel able to provide intravenous sedation and analgesia is essential for the safety of the patients and a more comfortable experience throughout the procedure.

Purpose: The aim of the case is to present the significance of a thorough analysis of the cases of patients with newly developed memory disorders accompanied by epileptic seizures. Case description: We present a case of a 61-year-old male patient who was admitted to the hospital due to unexplained memory disorders and seizures. Further examination showed the presence of anti-LGI1 (leucine-rich glioma-inactivated 1) antibodies. Computed tomography of the abdominal cavity revealed a mass located between the stomach and the spleen. Histopathological examination identified the mass as a gastrointestinal tumour (GIST). After the surgical removal of the tumour the symptoms were significantly reduced. The early diagnosis and treatment of the tumour contributed to favourable neurological and oncological outcomes for the patient. Comment: Paraneoplastic neurological syndrome is a clinical condition in which the functioning of the nervous system is impaired, not resulting from local tumour growth or metastases. The currently recognized underlaying mechanism of this condition is an autoimmune reaction occurring in the patient's body. In response to the presence of tumour, the antibodies called onconeural antibodies are produced, which are then directed against antigens present on the nervous system cells. To the best of our knowledge this is the first and so far only anti-LGI1-antibody autoimmune encephalitis as a neurological paraneoplastic syndrome associated with GIST.

El presente artículo complementa la tesis del Neuroabsurdismo introducida en el paper "El Órgano Fantástico" (Forlán et al., 2024), redefiniendo la mente como un Radar (Modelo de Procesamiento Predictivo). Aquí, buscamos establecer la validación neurofisiológica del protocolo de Incongruencia Controlada. Sostenemos que el reset bayesiano forzado por el Neuroabsurdismo se manifiesta como una restauración de la coherencia y complejidad funcional. Esta restauración se evidencia en tres niveles:
El aumento de la sincronización intercerebral (Feldman et al., 2022), reestableciendo la base neurofisiológica de la interacción social.
La modulación del Exponente de Hurst (H) en las ondas cerebrales gamma y beta (Maureira Cid et al., 2023), indicando un tránsito hacia un estado de Caos Óptimo para la atención e inhibición.
La amplificación de la percepción multimodal (ej. la detección de estímulos trigeminales compensatorios en anosmia), lo que constituye la activación plena del Radar de Bienestar.
El Neuroabsurdismo se propone, por tanto, como un método de Neuroplasticidad Aplicada para aumentar la complejidad dinámica del cerebro, restaurando el vínculo primario de seguridad y exploración con el entorno.

Neurodegenerative disorders with high iron in the basal ganglia encompass an expanding collection of single gene disorders collectively known as neurodegeneration with brain iron accumulation. These disorders can largely be distinguished from one another by their associated clinical and neuroimaging features. The aim of this study was to define the phenotype that is associated with mutations in WDR45, a new causative gene for neurodegeneration with brain iron accumulation located on the X chromosome. The study subjects consisted of WDR45 mutation-positive individuals identified after screening a large international cohort of patients with idiopathic neurodegeneration with brain iron accumulation. Their records were reviewed, including longitudinal clinical, laboratory and imaging data. Twenty-three mutation-positive subjects were identified (20 females). The natural history of their disease was remarkably uniform: global developmental delay in childhood and further regression in early adulthood with progressive dystonia, parkinsonism and dementia. Common early comorbidities included seizures, spasticity and disordered sleep. The symptoms of parkinsonism improved with L-DOPA; however, nearly all patients experienced early motor fluctuations that quickly progressed to disabling dyskinesias, warranting discontinuation of L-DOPA. Brain magnetic resonance imaging showed iron in the substantia nigra and globus pallidus, with a 'halo' of T 1 hyperintense signal in the substantia nigra. All patients harboured de novo mutations in WDR45, encoding a beta-propeller protein postulated to play a role in autophagy. Beta-propeller protein-associated neurodegeneration, the only X-linked disorder of neurodegeneration with brain iron accumulation, is associated with de novo mutations in WDR45 and is recognizable by a unique combination of clinical, natural history and neuroimaging features.

As the global elderly population is projected to reach approximately 46.4% by 2070, with nations like South Korea rapidly transitioning into super-aged societies, research into age-related cognitive decline and resilience has grown increasingly critical. The concept of "Superagers," individuals aged 65 and older who maintain cognitive abilities comparable to those decades younger, offers a promising framework for investigating cognitive reserve and resilience against neurodegeneration. Lee, et al., conducted a pioneering study aimed at identifying the biological underpinnings of Superager status using both traditional statistical analyses and advanced machine learning techniques. While conventional methods detected significant differences in only four biomarkers, machine learning-based feature selection expanded the biomarker panel to 15, indicating a more complex biological profile underlying exceptional cognitive aging. Importantly, the study employed Shapley Additive Explanations (SHAP) to enhance model interpretability, demonstrating how specific blood-based biomarkers contribute to cognitive performance. These findings underscore the potential of using routine blood tests to not only assess cognitive function but also to predict and classify Superager status in healthy elderly populations. The study offers clinically significant insights and establishes a foundation for future explorations into the biological mechanisms that support cognitive resilience in aging populations.

Background: Brain Metastasis (BM) is associated with poor prognosis. It affects the Quality of Life (QOL) and causes significant morbidity. BMs are the most common intracranial neoplasm, with a total number that outnumber primary neoplasms by a ratio of 10:1. In the present study, we aim to analyze the clinicodemographic profile and treatment outcomes of brain metastasis. Also, try to identify factors associated with survival in patients with brain metastasis. Methods: A retrospective, single-institutional study of 151 patients with brain metastases was conducted from January 2018 to May 2019. Medical records were reviewed to collect demographic and clinical information. The aim was to analyze the demographic and clinical profiles of patients with brain metastasis. Additionally, it analyzes patient factors, tumor characteristics and treatment plans that may impact overall survival in patients with brain metastases. Results: The median age for diagnosis of brain metastasis was 50 years. 82 patients were male. The common primary metastasizing to the brain was lung carcinoma (61%), followed by breast carcinoma (16%). 58% had adenocarcinoma histology and 14% of patients had infiltrating ductal carcinoma. (54%) showed multiple metastases, which is more common than a single metastasis (39%). 7% of patients showed two sites of metastases. 60% of patients have Supratentorial lesions. 29% of patients showed both supra and infratentorial lesions. Among them, the frontal lobe was the most commonly involved site. Out of 151 patients, 90 patients showed frontal lobe metastasis. Parietal and cerebellar metastasis is the next common site for metastasis 60% of patients are diagnosed upfront for brain metastasis. 3% of patients developed brain metastasis after five years of primary diagnosis. The most commonly used dose prescription for Whole Brain Radiation (WBRT) is 30Gy/10 fractions or 20Gy/5 fractions. 54% patients treated with 30Gy/10fx dose prescription. Median survival for patients with brain metastasis was eight months (ranging from 1 month to 32 months). Younger age (40-50 years), breast primary with a single metastasis and developed brain metastasis after 1-2 years of primary diagnosis were associated with better survival. Conclusion: The study highlights that in patients with brain metastasis, the overall prognosis remains poor; however, younger patients (40-50 years) and those with a single brain lesion demonstrate relatively better survival outcomes. Other factors, such as gender, WBRT dose and site of lesion, did not significantly affect survival.

Reports on the clinical meaningfulness of outcome measures in spinal muscular atrophy (SMA) are rare. In this two-part study, our aim was to explore patients&#39; and caregivers&#39; views on the clinical relevance of the Hammersmith Functional Motor Scale Expanded- (HFMSE). First, we used focus groups including SMA patients and caregivers to explore their views on the clinical relevance of the individual activities included in the HFMSE. Then we asked caregivers to comment on the clinical relevance of possible changes of HFMSE scores over time. As functional data of individual patients were available, some of the questions were tailored according to their functional level on the HFMSE. Part 1: Sixty-three individuals participated in the focus groups. This included 30 caregivers, 25 patients and 8 professionals who facilitated the discussion. The caregivers provided a comparison to activities of daily living for each of the HFMSE items. Part 2: One hundred and forty-nine caregivers ...

Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level. We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer&#39;s disease and other dementias, Parkinson&#...

There is evidence for a beneficial effect of aerobic exercise on cognition, but underlying mechanisms are unclear. In this study, we test the hypothesis that aerobic exercise increases cerebral blood flow (CBF) in patients with vascular cognitive impairment (VCI). This study is a multicenter single-blind randomized controlled trial among 80 patients with VCI. Most important inclusion criteria are a diagnosis of VCI with Mini-Mental State Examination 22 and Clinical Dementia Rating 0.5. Participants are randomized into an aerobic exercise group or a control group. The aerobic exercise program aims to improve cardiorespiratory fitness and takes 14 weeks, with a frequency of three times a week. Participants are provided with a bicycle ergometer at home. The control group receives two information meetings. Primary outcome measure is change in CBF. We expect this study to provide insight into the potential mechanism by which aerobic exercise improves hemodynamic status.

To screen for cognitive and behavioural impairment in people with amyotrophic lateral sclerosis (ALS) and controls with neuromuscular disease and to correlate these with clinical features. 108 people with ALS and 60 controls with other neuromuscular diseases were recruited and assessed with the Addenbrooke&#39;s cognitive examination-III (ACE-III), the frontal assessment battery (FAB), and the executive function component of the Edinburgh cognitive and behavioural ALS screen (ECAS). The Amyotrophic lateral sclerosis-Frontotemporal dementia questionnaire (ALS-FTD-Q) and the Motor Neuron Disease Behavioural instrument (MiND-B) were administered to the caregivers of people with ALS. The prevalence of abnormalities was determined and correlated with clinical features and survival. In 37 people with ALS, serial studies were performed. The frequencies of cognitive impairment based on the ACE-III and FAB were 30.0% and 14.0%, in ALS and 11.7% and 3.3% in controls, respectively. Age and yea...

Mamba (Dendroaspis species) snakebites are critical medical emergencies across sub-Saharan Africa. Envenomings can result in rapid onset of complex neurotoxic symptoms, often leading to high rates of mortality without timely intervention with antivenom. The ancestral state of mambas is the green coloured, forest dwelling type, with the tan/gray coloured, savannah dwelling D. polylepis (Black Mamba) representing a derived state both ecologically and morphologically. However, it has not been tested whether these changes are paralleled by changes in venom biochemistry or if there are differential molecular evolutionary patterns. To fill these knowledge gaps, this study evaluated the neurotoxic effects of all Dendroaspis species venoms using the chick biventer cervicis nerve-muscle preparation, assessed the neutralizing efficacy of three antivenoms commercially available in Africa, and reconstructed the molecular evolutionary history of the toxin types to ascertain if some were unique to particular species. All Dendroaspis venoms demonstrated potent flaccid-paralysis due to postsynaptic neurotoxicity. The only exception was D. angusticeps venom, which conversely exhibited spastic-paralysis due to presynaptic/synaptic neurotoxicity characterised by potentiation of acetylcholine pre-synaptic release and sustained synaptic activity of this neurotransmitter. Antivenom ef-ficacy varied significantly. All three antivenoms neutralized to some degree the flac-cid-paralysis postsynaptic effects for all species, with D. viridis venom being the best neutralized, with this pattern extending to all the antivenoms. However, neutralisation of flaccid-paralysis postsynaptic effects unmasked spastic-paralysis presynaptic/synaptic neurotoxicity within non-angusticeps venoms. Spastic-paralysis presynaptic effects were poorly neutralized for all species by all antivenoms, consistent with prior clinical reports of poor neutralisation of spastic-paralytic effects. Geographic variation in D. polylepis venom was evident for the relative neutralisation of both spastic-paralysis presynap-tic/synaptic and flaccid-paralysis postsynaptic/synaptic neurotoxic pathophysiological effects, with differential neutralization capabilities between the Kenyan and South African populations studied. Molecular phylogenetic analyses confirmed spastic paralysis and flaccid paralysis toxins to be a trait that emerged in the Dendroaspis last common ancestor, with all species sharing all toxin types. Therefore, differences in venoms pathophysio-logical actions between species are due to differential expression of toxin isoforms, rather than the evolution of species-specific novel toxins. Our findings highlight the synergistic nature of flaccid-paralysis postsynaptic and spastic-paralysis presynaptic/synaptic toxins, while contributing significant clinical and evolutionary knowledge of Dendroaspis venoms. These data are crucial for the continued development of more effective thera-peutic interventions to improve clinical outcomes, and the design of evidence-based design of clinical management strategies for the envenomed patient.

Progress in understanding and management of vascular cognitive impairment (VCI) has been hampered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Consensus Study (VICCCS) to agree on principles (VICCCS-1) and protocols (VICCCS-2) for diagnosis of VCI. We present VICCCS-2. We used VICCCS-1 principles and published diagnostic guidelines as points of reference for an online Delphi survey aimed at achieving consensus on clinical diagnosis of VCI. Six survey rounds comprising 65-79 participants agreed guidelines for diagnosis of VICCCS-revised mild and major forms of VCI and endorsed the National Institute of Neurological Disorders-Canadian Stroke Network neuropsychological assessment protocols and recommendations for imaging. The VICCCS-2 suggests standardized use of the National Institute of Neurological ...

Numerous diagnostic criteria have tried to tackle the variability in clinical manifestations and problematic diagnosis of vascular cognitive impairment (VCI) but none have been universally accepted. These criteria have not been readily comparable, impacting on clinical diagnosis rates and in turn prevalence estimates, research, and treatment. The Vascular Impairment of Cognition Classification Consensus Study (VICCCS) involved participants (81% academic researchers) from 27 countries in an online Delphi consensus study. Participants reviewed previously proposed concepts to develop new guidelines. VICCCS had a mean of 122 (98-153) respondents across the study and a 67% threshold to represent consensus. VICCCS redefined VCI including classification of mild and major forms of VCI and subtypes. It proposes new standardized VCI-associated terminology and future research priorities to address gaps in current knowledge. VICCCS now proposed a consensus-based updated conceptualization of VCI...

Para comprender mejor la dimensión real de esta enfermedad más frecuente durante la infancia con un predominio de más del bastante curiosa, desconocida, se menciona como ejemplo la 50% antes de los 7 años. Es más común en familiares de primer película Mejor Imposible con Jack Nicholson y el programa grado que lo padecen y se da con mayor porcentaje en hombres televisivo de dibujos animados South Park relacionado con el que en mujeres con una razón de 4-5:1. También esta enfermedad síndrome de Tourette. se observa más en la raza blanca. El síndrome de Tourette es un desorden neurológico nombrado Con mucha frecuencia, los niños con este síndrome tienen en honor al neurólogo francés Giles de la Tourette. Durante el afectaciones conductuales, académicas y emocionales, junto con año de 1885, investigó y describió los casos de 9 niños que el trastorno obsesivo compulsivo y el trastorno de hiperactividad padecían crónicamente de tics, sonidos incontrolables e mencionado anteriormente. No se sabe con exactitud la causa incomprensibles, trastornos de hiperactividad con déficit de especifica de esta enfermedad; aunque es probable que se atención, trastornos obsesivo-compulsivos y otros problemas de relacione con factores genéticos, neurobiológicos, psicológicos y comportamiento. A pesar de que éste neurólogo lo definió como ambientales. Lo que si se conoce es que afecta el metabolismo de una causa hereditaria, fue hasta más de un siglo después que se transmisores cerebrales de tipo dopaminérgicos, identificaron las influencias de causas psicógenas como parte de serotoninérgicos y noradrenérgicos. A través de los estudios de

This study evaluated the effect of a multidisciplinary treatment program for children with obesity (OB) on motor competence, executive functioning (EF), and brain structure. Nineteen children with OB (7–11 years), who attended a multidisciplinary treatment program consisting of diet restriction, cognitive behavioral therapy, and physical activity, were compared with an age‐matched control group of 24 children with a healthy weight (HW), who did not follow any treatment. For both groups, anthropometric measurements and tests of motor competence and EF were administered twice, with 5 months between pretest and posttest. Additionally, children’s brain structure was assessed by performing a magnetic resonance imaging (MRI) scan at the pretest and posttest, which included a T1 anatomical scan, diffusion MRI scan, and magnetization transfer imaging scan. Compared to HW controls, children with OB lost a considerable amount of their body mass (p ≤ .001) and significantly improved their bala...

SummaryObjectiveThe aim of this study is to determine whether the use of 7 tesla (T) MRI in clinical practice leads to higher detection rates of focal cortical dysplasias in possible candidates for epilepsy surgery.MethodsIn our center patients are referred for 7 T MRI if lesional focal epilepsy is suspected, but no abnormalities are detected at one or more previous, sufficient‐quality lower‐field MRI scans, acquired with a dedicated epilepsy protocol, or when concealed pathology is suspected in combination with MR‐visible mesiotemporal sclerosis—dual pathology. We assessed 40 epilepsy patients who underwent 7 T MRI for presurgical evaluation and whose scans (both 7 T and lower field) were discussed during multidisciplinary epilepsy surgery meetings that included a dedicated epilepsy neuroradiologist. We compared the conclusions of the multidisciplinary visual assessments of 7 T and lower‐field MRI scans.ResultsIn our series of 40 patients, multidisciplinary evaluation of 7 T MRI id...

The tau tangle ligand (18)F-AV-1451 ((18)F-T807) binds to neuromelanin in the midbrain, and may therefore be a measure of the pigmented dopaminergic neuronal count in the substantia nigra. Parkinson&#39;s disease is characterized by progressive loss of dopaminergic neurons. Extrapolation of post-mortem data predicts that a ∼30% decline of nigral dopamine neurons is necessary to cause motor symptoms in Parkinson&#39;s disease. Putamen dopamine terminal loss at disease onset most likely exceeds that of the nigral cell bodies and has been estimated to be of the order of 50-70%. We investigated the utility of (18)F-AV-1451 positron emission tomography to visualize the concentration of nigral neuromelanin in Parkinson&#39;s disease and correlated the findings to dopamine transporter density, measured by (123)I-FP-CIT single photon emission computed tomography. A total of 17 patients with idiopathic Parkinson&#39;s disease and 16 age- and sex-matched control subjects had (18)F-AV-1451 pos...

Object The wide application of deep brain stimulation in the management of movement as well as other degenerative neurological and psychiatric disorders has renewed the interest in using deep brain stimulation in the management of medically intractable epilepsy. Various stimulation targets have been used with significantly varying results in aborting seizure activity. Electrical cerebellar stimulation (CS) has been used for more than 50 years in the management of epilepsy, with conflicting results. In the current study, the authors review the pertinent literature to outline the role of CS in the management of medically refractory epilepsy. Methods The PubMed medical database was systematically searched for the following terms: “cerebellar,” “epilepsy,” “stimulation,” and “treatment,” and all their combinations. Case reports were excluded from this study. Results The pertinent articles were categorized into 2 large groups: animal experimental and human clinical studies. Particular em...

The European Restless Legs Syndrome (RLS) Study Group performed the first multi-center, long-term study systematically evaluating RLS augmentation under levodopa treatment. This prospective, open-label 6-month study was conducted in six European countries and included 65 patients (85% treatment naive) with idiopathic RLS. Levodopa was flexibly up-titrated to a maximum dose of 600 mg/day. Presence of augmentation was diagnosed independently by two international experts using established criteria. In addition to the augmentation severity rating scale (ASRS), changes in RLS severity (International RLS severity rating scale (IRLS), clinical global Wayne A. Hening: Deceased.

Background: Disruptive behavior is common in Alzheimer disease (AD). There are conflicting reports regarding its ability to predict cognitive decline, functional decline, institutionalization, and mortality. Objective: To examine whether the presence of disruptive behavior has predictive value for important outcomes in AD. Design: Using the Columbia University Scale for Psychopathology in Alzheimer Disease (administered every 6 months, for a total of 3438 visit-assessments and an average of 6.9 per patient), the presence of disruptive behavior (wandering, verbal outbursts, physical threats/violence, agitation/restlessness, and sundowning) was extracted and examined as a timedependent predictor in Cox models. The models controlled for the recruitment cohort, recruitment center, informant status, sex, age, education, a comorbidity index, baseline cognitive and functional performance, and neuroleptic use. Setting: Five university-based AD centers in the United States and Europe (Predictors Study). Participants: Four hundred ninety-seven patients with early-stage AD (mean Folstein Mini-Mental State Examination score, 20 of 30 at entry) who were recruited and who underwent semiannual follow-up for as long as 14 (mean, 4.4) years. Main Outcome Measures: Cognitive (Columbia Mini-Mental State Examination score, Յ 20 of 57 [approximate Folstein Mini-Mental State Examination score, Յ10 of 30]) and functional (Blessed Dementia Rating Scale score, parts I and II, Ն 10) ratings, institutionalization equivalent index, and death. Results: At least 1 disruptive behavioral symptom was noted in 48% of patients at baseline and in 83% at any evaluation. Their presence was associated with increased risks of cognitive decline (hazard ratio 1.45 [95% confidence interval (CI), 1.03-2.03]), functional decline (1.66 [95% CI, 1.17-2.36]), and institutionalization (1.47 [95% CI, 1.10-1.97]). Sundowning was associated with faster cognitive decline, wandering with faster functional decline and institutionalization, and agitation/restlessness with faster cognitive and functional decline. There was no association between disruptive behavior and mortality (hazard ratio, 0.94 [95% CI, 0.71-1.25]). Disruptive behavior is very common in AD and predicts cognitive decline, functional decline, and institutionalization but not mortality.

A precise definition of a brain state has proven elusive. Here, we introduce the novel local-global concept of intrinsic ignition characterizing the dynamical complexity of different brain states. Naturally occurring intrinsic ignition events reflect the capability of a given brain area to propagate neuronal activity to other regions, giving rise to different levels of integration. The ignitory capability of brain regions is computed by the elicited level of integration for each intrinsic ignition event in each brain region, averaged over all events. This intrinsic ignition method is shown to clearly distinguish human neuroimaging data of two fundamental brain states (wakefulness and deep sleep). Importantly, whole-brain computational modelling of this data shows that at the optimal working point is found where there is maximal variability of the intrinsic ignition across brain regions. Thus, combining whole brain models with intrinsic ignition can provide novel insights into underl...