Radiomic detection of abnormal brain regions in tuberous sclerosis complex.

BACKGROUND: Radiomics refers to the extraction of quantitative information from medical images and is most commonly utilized in oncology to provide ancillary information for solid tumor diagnosis, prognosis, and treatment response. The traditional radiomic pipeline involves segmentation of volumes of interest with comparison to normal brain. In other neurologic disorders, such as epilepsy, lesion delineation may be difficult or impossible due to poor anatomic definition, small size, and multifocal or diffuse distribution. Tuberous sclerosis complex (TSC) is a rare genetic disease in which brain magnetic resonance imaging (MRI) demonstrates multifocal abnormalities with variable imaging and epileptogenic features. PURPOSE: The purpose of this study was to develop a radiomic workflow for identification of abnormal brain regions in TSC, using a whole-brain atlas-based approach with generation of heatmaps based on signal deviation from normal controls. METHODS: This was a retrospective pilot study utilizing high-resolution whole-brain 3D FLAIR MRI datasets from retrospective enrollment of tuberous sclerosis complex (TSC) patients and normal controls. Subjects underwent MRI including high-resolution 3D FLAIR sequences. Preprocessing included skull stripping, coregistration, and intensity normalization. Using the Brainnetome and Harvard-Oxford atlases, brain regions were parcellated into 318 discrete regions. Expert neuroradiologists spatially labeled all tubers in TSC patients using ITK-SNAP. The pyradiomics toolbox was used to extract 88 radiomic features based on IBSI guidelines, comparing tuber-affected and non-tuber-affected parenchyma in TSC patients, as well as normal brain tissue in control patients. For model training and validation, regions with tubers from 20 TSC patients and 30 normal control subjects were randomly divided into two training sets (80%) and two validation sets (20%). Additional model testing was performed on a separate group of 20 healthy controls. LASSO (least absolute shrinkage and selection operator) was used to perform variable selection and regularization to identify regions containing tubers. Relevant radiomic features selected by LASSO were combined to produce a radiomic score ω, defined as the sum of squared differences from average control group values. Region-specific ω scores were converted to heat maps and spatially coregistered with brain MRI to reflect overall radiomic deviation from normal. RESULTS: The proposed radiomic workflow allows for quantification of deviation from normal in 318 regions of the brain with the use of a summative radiomic score ω. This score can be used to generate spatially registered heatmaps to identify brain regions with radiomic abnormalities. The pilot study of TSC showed radiomic scores ω that were statistically different in regions containing tubers from regions without tubers/normal brain (p < 0.0001). Our model exhibits an AUC of 0.81 (95% confidence interval: 0.78-0.84) on the testing set, and the best threshold obtained on the training set, when applied to the testing set, allows us to identify regions with tubers with a specificity of 0.91 and a sensitivity of 0.60. CONCLUSION: We describe a whole-brain atlas-based radiomic approach to identify abnormal brain regions in TSC patients. This approach may be helpful for identifying specific regions of interest based on relatively greater signal deviation, particularly in clinical scenarios with numerous or poorly defined anatomic lesions.

Alexia without agraphia: from infarctions to malignancies.

Alexia without agraphia is a neurological syndrome characterised by an acquired inability to read with a preserved ability to write. It is caused by the combined effect of two lesions: in the splenium of the corpus callosum and in the occipital lobe of the dominant hemisphere. Splenial lesions disconnect the language areas in the temporal and parietal lobes of the dominant hemisphere from the visual areas in the occipital cortex of the contralateral side, while lesions in the dominant occipital lobe cause homonymous hemianopia. We describe two patients with lesions affecting the splenium and dominant occipital lobe, with different causes. Together, these cases highlight the importance of performing a thorough language evaluation in patients presenting with homonymous visual field deficits, as otherwise, clinicians may overlook impairments in writing (agraphia) or reading (alexia).

Anti-CV2 Antibody-Positive Sensorimotor Polyneuropathy Following Bacillus Calmette-Guérin Intravesical Infusion Therapy.

Bacillus Calmette-Guérin (BCG) intravesical infusion therapy is widely used to control recurrence after transurethral resection of bladder tumors. Herein, we report a case of polyneuropathy with transiently positive onconeural antibodies after BCG bladder infusion therapy. A man in his 70s presented with upper and lower extremity weakness 11 weeks after BCG intravesical infusion therapy, a postoperative therapy for superficial bladder cancer. Nerve conduction studies revealed findings that were consistent with demyelinating sensorimotor polyneuropathy. Anti-CV2 antibody was positive; however, contrast-enhanced computed tomography and positron emission tomography revealed no malignancy. The patient's symptoms improved with immunoglobulin therapy. Contrast-enhanced computed tomography showed no malignancy, and the anti-CV-2 antibody test result was negative six months after discharge. The immune response to BCG bladder infusion therapy may have caused the transient CV2 antibody positivity and polyneuropathy. The possibility of transiently positive onconeural antibodies after BCG intravesical infusion therapy should be considered.

Therapeutic advances in neuroinfectious diseases.

There have been several major advances in therapeutic options for the treatment of neurological infections over the past two decades. These advances encompass both the development of new antimicrobial therapies and the repurposing of existing agents for new indications. In addition, advances in our understanding of the host immune response have allowed for the development of new immunomodulatory strategies in the treatment of neurological infections. This review focuses on the key advances in the treatment of neurological infections, including viral, bacterial, fungal, and prion diseases, with a particular focus on immunomodulatory treatment options. This review also highlights the process by which clinicians can request access to therapeutic agents on a compassionate or emergency basis when they may not be commercially available. While many therapeutic advances have been achieved in the past several years, there remains a pressing need for the continued development of additional therapeutic agents in the treatment of neurological infections.

David G. Sherman Lecture: Improving Stroke Diagnosis and Treatment-A Journey Toward the End of Time.

In the 2024 David G. Sherman Lecture, Steven J. Warach, illustrating with examples from his research, walks through the history of magnetic resonance imaging in acute stroke from the 1990s and early 2000s with the introduction, validation, and application of diffusion-weighted imaging, penumbral imaging (the diffusion-perfusion mismatch), and other imaging markers of the acute stroke pathology into routine clinical practice and stroke trials. The adaptation of diffusion-weighted imaging for clinical scanners in the acute hospital setting began a revolution in ischemic stroke diagnosis as the presence, location, and size of ischemic lesions could now be visualized at the earliest times after stroke onset when computed tomography and conventional magnetic resonance imaging still appeared normal. In combination with perfusion magnetic resonance imaging, diffusion-weighted imaging made imaging of the ischemic penumbra a practical reality for routine clinical use and feasible for integration as a selection tool into clinical trials. It was apparent from the initial use of diffusion-perfusion imaging in acute stroke that many patients had persistence of penumbra as late as 24 hours after stroke onset although the probability of penumbra decreased over time. The therapeutic time window for ischemic stroke selected by clinical and temporal criteria reflected the decreased proportion of patients with the therapeutic target over time rather than the absence of the penumbral target in all patients at later times. This work provided the empirical and conceptual framework for the shift toward selection and evaluation of patients for acute stroke therapies based on direct observation of the target pathology and away from the exclusive dependence on clinical and temporal surrogates to infer the presence of stroke therapeutic targets, a shift that has expanded the indications for acute reperfusion therapies over the last 10 years.

Life After Neonatal Seizures: Characterizing the Longitudinal Parent Experience.

BACKGROUND: Parents of neonates with seizures report persistent symptoms of depression, anxiety, and posttraumatic stress. We aimed to characterize the parent experience of caring for children impacted by neonatal seizures, including longitudinal assessment across childhood. METHODS: This prospective, observational, multicenter study was conducted at Neonatal Seizure Registry (NSR) sites in partnership with the NSR Parent Advisory Panel. Parents completed surveys at discharge; 12, 18, and 24 months; and 3, 4, 5, 7, and 8 years. Surveys included demographic information and open-ended questions targeting parent experience. A conventional content analysis approach was used. RESULTS: A total of 320 caregivers completed at least one open-ended question, with the majority of respondents at discharge (n = 142), 12 months (n = 169), 18 months (n = 208), and 24 months (n = 245). We identified the following three primary themes. (1) Personal Burden of Care: Parents experienced emotional distress, financial strain, physical demands, and fears for their child's unknown outcome; (2) Managing Day-to-Day Life: Parents described difficulties navigating their parenting role, including managing their child's challenging behaviors and understanding their child's needs amid neurodevelopmental impairment; (3) My Joys as a Parent: Parents valued bonding with their child, being a caregiver, and watching their child's personality grow. CONCLUSIONS: Parents of children impacted by neonatal seizures face persistent challenges, which are interwoven with the joys of being a parent. Our findings suggest that future interventions should promote resiliency, address caregivers' psychosocial needs longitudinally, and provide enhanced support for parents caring for children with medical complexity.

[Integration and development of acupuncture and neurology: interviewing Professor SUN Shentian, Master of Traditional Chinese Medicine].

The semi-structured interview was adopted to in-depth interview Professor SUN Shentian, a Master of Traditional Chinese Medicine, on the integration and development of acupuncture and neurology. In the interview, we traced the first "ward of acupuncture and neurology" in China, established by Professor SUN Shentian and the origin of his proposal, "transcranial repeated needling stimulation therapy", aiming at advancing the development of acupuncture discipline. Professor SUN Shentian explained that the ward of acupuncture and neurology was established under specific historical conditions, on account of the relationship between acupuncture and nerves and the characteristics of the neurological diseases, as well as the personal practical knowledge and his unique clinical experience. In order to specify the point selection of scalp acupuncture and further expound its mechanism, he innovated "transcranial repeated needling stimulation therapy" that is advantageous at preciser operation, clearer theoretic foundation and better therapeutic effect of scalp acupuncture. Professor SUN Shentian pointed out that the deepening development of acupuncture is firmly based on "inheritance, practice and innovation", and constant exploration practice along with inheriting the experience of predecessors to propel the innovation and development of acupuncture and move towards a new historical stage.

Exploring research participation in Scottish care homes since the COVID-19 pandemic.

Knowledge about research participation in care homes is sparse. To explore research participation in Scottish care homes, including the potential barriers and facilitators, a short survey was distributed to all care homes in Scotland in 2014. The survey was repeated in 2022 as care homes emerged from the effects of the coronavirus disease 2019 (COVID-19) pandemic. This article provides a comparison of the results of the 2022 survey (45 responses) with those of the 2014 survey (130 responses); the surveys were completed by care home staff. The results indicate that there has been a slight increase in the proportion of care homes involved in research in the intervening period but overall, research participation has remained low in this sector. In the 2022 survey, the main factors identified as influencing a resident's decision to participate in research were 'to help others', 'to benefit the resident' and the 'resident's desire to participate'. The main obstacles to research participation by staff and/or residents were workload pressure and lack of time, which had increased significantly since the 2014 survey. The results reinforce the importance of ensuring care home staff feel equipped to participate in research.

Decreased Systemic Monocyte Colony Protein-1 (MCP-1) Levels and Reduced sCD14 Levels in Curcumin-Treated Patients with Moderate Anxiety: A Pilot Study.

Psychosocial stress may alter cortisol and/or affect the normal functioning of the immune system. Curcuminoids can promote beneficial effects in neuropsychiatric diseases. We evaluated whether curcumin supplementation for 15 consecutive days (1800 mg/day) would decrease systemic MCP-1, sCD14, and TNF alpha levels in patients with moderate anxiety (n = 81). A total number of 81 subjects were enrolled in this study, divided into the following groups according to their Hamilton scores: a control group including patients without anxiety who were not taking curcumin (Cont, n = 22) and an anxiety group including patients with moderate anxiety (Anx, n = 22). The curcumin-treated patients experienced moderate anxiety, and they take curcumin for 15 consecutive days (Anx-Cur (after), n = 15, 1800 mg/day). An evaluation of 128 patients was conducted, which allowed for their assignment to the study groups according to their scores on Hamilton scale II. The cortisol levels were quantified in salivary samples through ELISA (ng/mL), and malonaldehyde (MDA) levels were measured in plasma via the TBARS assay as an index of lipoperoxidation. Several systemic proinflammatory cytokines (pg/mL: MCP-1, TNF alpha, IL-1 beta) and mediators were quantified through ELISA (pg/mL), including systemic sCD14 levels as a marker of monocyte activation. A two-way bifactorial ANOVA was conducted to evaluate the contributions of the anxiety factor (Anx) and/or curcumin factor (Cur) in all the tested markers, including interactions between both factors. High systemic MCP-1 and elevated sCD14 levels were observed in patients with moderate anxiety, which were reduced with curcumin supplementation. In addition, curcumin prevented cortisol overexpression and decreased MDA levels as an antioxidant response in these patients. Collectively, curcumin presented anti-chemotactic effects by reducing systemic MCP-1 levels in anxiety. Curcumin decreased systemic MCP-1 as well as sCD14 levels in patients with moderate anxiety.

Mesenchymal Stem Cell-Derived Exosomes as a Neuroregeneration Treatment for Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is the most prevalent kind of dementia and is a long-term degenerative disease. Pathologically, it is defined by the development of extracellular amyloid-ß plaques and intracellular neurofibrillary tangles made up of hyperphosphorylated tau protein. This causes neuronal death, particularly in the hippocampus and cortex. Mesenchymal stem cell (MSC)-derived exosomes have been identified as possibly therapeutic and have promise for Alzheimer's disease due to their regenerative characteristics. METHODS: A systematic retrieval of information was performed on PubMed. A total of 60 articles were found in a search on mesenchymal stem cells, exosomes, and Alzheimer's disease. A total of 16 ongoing clinical trials were searched and added from clinicaltrials.gov. We added 23 supporting articles to help provide information for certain sections. In total, we included 99 articles in this manuscript: 50 are review articles, 13 are preclinical studies, 16 are clinical studies, 16 are ongoing clinical trials, and 4 are observational studies. Appropriate studies were isolated, and important information from each of them was understood and entered into a database from which the information was used in this article. The clinical trials on mesenchymal stem cell exosomes for Alzheimer's disease were searched on clinicaltrials.gov. RESULTS: Several experimental investigations have shown that MSC-Exo improves cognitive impairment in rats. In this review paper, we summarized existing understanding regarding the molecular and cellular pathways behind MSC-Exo-based cognitive function restoration, with a focus on MSC-Exo's therapeutic potential in the treatment of Alzheimer's disease. CONCLUSION: AD is a significant health issue in our culture and is linked to several important neuropathological characteristics. Exosomes generated from stem cells, such as mesenchymal stem cells (MSCs) or neural stem cells (NSCs), have been examined more and more in a variety of AD models, indicating that they may be viable therapeutic agents for the treatment of diverse disorders. Exosome yields may be increased, and their therapeutic efficacy can be improved using a range of tailored techniques and culture conditions. It is necessary to provide standardized guidelines for exosome manufacture to carry out excellent preclinical and clinical research.

Effect of volatile anaesthetic agents on intracranial pressure, cerebrovascular flow and autoregulation: a protocol for a systematic review and meta-analysis.

INTRODUCTION: The use of volatile anaesthetic agents for the sedation of patients requiring critical care treatment offers several theoretical advantages over intravenous sedation, which may be of benefit in neurocritical care. However, there are concerns that they may increase intracranial pressure. The objective of this systematic review is to assess whether, and if so, to what extent volatile anaesthetic agents affect intracranial pressure, cerebral blood flow (CBF), cerebral oximetry and cerebrovascular autoregulation. If sufficient data exist, subgroup analyses will be conducted in traumatic brain injury and decompressive craniectomy patients. METHODS AND ANALYSIS: A database search of PubMed, Medline (including Medline plus), CINAHL (including CINAHL Plus), Embase databases and the Cochrane Central Controlled Trials Register without time limits will be conducted. The search results will be screened by title and abstract by two independent researchers on a rule-in basis against predetermined criteria-controlled studies in humans of contemporary fluorinated volatile anaesthetic agents against a control, which measures intracranial pressure, CBF, cerebral oximetry or cerebrovascular autoregulation. Articles responsive to screening will then be reviewed in full text by two independent researchers, requiring consensus or a tie-break by a third independent researcher. Reference lists and a non-generative AI tool will be examined for missed articles, with all identified articles being reviewed in full text by two independent researchers. The included articles will be assessed for risk of bias and will have data extracted by two independent researchers. If sufficient data exist, a meta-analysis will be performed; otherwise, a narrative description of outcomes will be performed. ETHICS AND DISSEMINATION: No ethics approval will be sought for this systematic review. This study has no explicit funding. The results of this study will be disseminated in a peer-reviewed journal, in a conference presentation and on PROSPERO. TRIAL REGISTRATION NUMBER: PROSPERO number CRD42023474587.

[Palliative care in children with severe neurological diseases]. / Cuidados paliativos en niños con enfermedades neurológicas graves.

Pediatric palliative care focuses on improving the quality-of-life in children with severe illnesses and their families, addressing relief of pain and other physical symptoms, as well as emotional, social and spiritual support. Its approach is comprehensive and multidisciplinary. Severe neurological diseases are life-limiting and threatening, significantly affecting the well-being of the child. The families of these children face significant stress and need support to make complex decisions about them. This includes advance care planning, setting therapeutic goals, and end-of-life decisions. Early intervention can improve quality-of-life, reduce unnecessary hospitalizations, and provide emotional support for the family. Coordination between different health services is essential to ensure patient-centered care. Education and training of health professionals in this field are essential to improve the care of these children.

Los cuidados paliativos pediátricos se centran en mejorar la calidad de vida de niños con enfermedades graves y sus familias, abordando el alivio del dolor y otros síntomas físicos, así como brindar apoyo emocional, social y espiritual. Su enfoque es integral y multidisciplinario. Las enfermedades neurológicas graves pueden limitar y amenazar la vida, y afectan significativamente el bienestar del niño. Las familias de estos niños enfrentan un estrés significativo y necesitan apoyo para tomar decisiones complejas sobre el cuidado de su hijo. Esto incluye planificar anticipadamente la atención, establecer objetivos terapéuticos y, eventualmente, decisiones sobre el final de la vida. La intervención temprana puede mejorar la calidad de vida, reducir hospitalizaciones innecesarias y proporcionar un apoyo emocional crucial para la familia. La coordinación entre los diferentes servicios de salud es esencial para asegurar una atención centrada en el paciente. La formación de los profesionales de la salud en este campo es fundamental para mejorar la calidad de atención de estos niños.

Anything is better than nothing': exploring attitudes towards novel therapies in leukodystrophy clinical trials.

BACKGROUND/AIM: Leukodystrophies comprise a group of genetic white matter disorders that lead to progressive motor and cognitive impairment. Recent development of novel therapies has led to an increase in clinical trials for leukodystrophies. To enable recruitment of individuals with a leukodystrophy into clinical trials, clinical trial acceptability should be ascertained. We sought therefore, to identify the motivations for and barriers to clinical trial participation in addition to clinical trial features that may be of concern to individuals with a leukodystrophy and/or their carers. METHODS: Adults with a leukodystrophy and parents/carers of individuals with a leukodystrophy were recruited through the Australian Leukodystrophy Registry and through online advertisements. Qualitative semi-structured interviews were used to explore participants views on what clinical trials involve, the perceived risks and benefits of clinical trials, their desire to participate in clinical trials and their personal experience with leukodystrophy. Thematic analysis of data was performed with co-coding of interview transcripts. RESULTS: 5 interviews were held with parents of children with leukodystrophy, 4 with parents of adults with leukodystrophy and 3 with adults diagnosed with leukodystrophy. Motivations for clinical trial enrolment include access to potentially lifesaving novel treatments and improved prognostic outcomes. Participants were concerned about adverse clinical trial outcomes, including side effects and exacerbation of illness. Despite this, majority of participants were willing to try anything in clinical trials, demonstrating a high tolerance for first in human trials and trials utilising invasive treatment options. CONCLUSIONS: Interviewees communicated a strong desire to participate in interventional clinical trials involving novel therapies. To support enrolment into future leukodystrophy clinical trials we suggest the provision of transparent information regarding clinical trial treatments, consideration of alternative trial control measures, and inclusion of treating clinicians in the trial recruitment process. Clinicians play an integral role in initiating transparent conversations regarding trial risks and adverse outcomes.

Bile acid modulation by gut microbiota: a bridge to understanding cognitive health.

The gut microbiota plays an important role in regulating the body's physiological system, and more recently its impact on bile acid metabolism and cognitive function has been investigated by many studies. In addition to their conventional function in fat digestion and absorption, bile acids are now considered crucial signaling molecules that control several metabolic processes and immunological responses. For this purpose, the authors conducted comprehensive research using relevant terms in an attempt to understand more about the gut microbiota and its impact on bile acid metabolism and cognitive health. The gut-brain axis refers to the network of routes through which gut bacteria communicate with the brain. Through its capacity to bio-transform primary bile acids into secondary bile acids, the gut microbiota plays a significant role in bile acid metabolism. Bile acids function as signaling molecules and act on the brain through nuclear and membrane-bound receptors, influencing neurotransmitter production, neuroinflammation, and neuroplasticity to modify this communication. Any dysregulation in this axis can result in cognitive dysfunction. The link between gut microbiota, bile acids, and cognitive health cannot be ignored. It is imperative to explore this link further by conducting large-scale trials to improve the cognitive health of patients with multiple comorbidities, especially those involving the gastrointestinal tract and nervous system.

Preterm birth as a determinant of neurodevelopment and cognition in children (PRENCOG): protocol for an exposure-based cohort study in the UK.

INTRODUCTION: Preterm birth (PTB) is strongly associated with encephalopathy of prematurity (EoP) and neurocognitive impairment. The biological axes linking PTB with atypical brain development are uncertain. We aim to elucidate the roles of neuroendocrine stress activation and immune dysregulation in linking PTB with EoP. METHODS AND ANALYSIS: PRENCOG (PREterm birth as a determinant of Neurodevelopment and COGnition in children: mechanisms and causal evidence) is an exposure-based cohort study at the University of Edinburgh. Three hundred mother-infant dyads comprising 200 preterm births (gestational age, GA <32 weeks, exposed) and 100 term births (GA >37 weeks, non-exposed), will be recruited between January 2023 and December 2027. We will collect parental and infant medical, demographic, socioeconomic characteristics and biological data which include placental tissue, umbilical cord blood, maternal and infant hair, infant saliva, infant dried blood spots, faecal material, and structural and diffusion MRI. Infant biosamples will be collected between birth and 44 weeks GA.EoP will be characterised by MRI using morphometric similarity networks (MSNs), hierarchical complexity (HC) and magnetisation transfer saturation imaging (MTsat). We will conduct: first, multivariable regressions and statistical association assessments to test how PTB-associated risk factors (PTB-RFs) relate to MSNs, HC and or MTsat; second, structural equation modelling to investigate neuroendocrine stress activation and immune dysregulation as mediators of PTB-RFs on features of EoP. PTB-RF selection will be informed by the variables that predict real-world educational outcomes, ascertained by linking the UK National Neonatal Research Database with the National Pupil Database. ETHICS AND DISSEMINATION: A favourable ethical opinion has been given by the South East Scotland Research Ethics Committee 02 (23/SS/0067) and NHS Lothian Research and Development (2023/0150). Results will be reported to the Medical Research Council, in scientific media, via stakeholder partners and on a website in accessible language (https://www.ed.ac.uk/centre-reproductive-health/prencog).

Postural Stability in Children with Cerebral Palsy.

Background: A lack of postural control is one of the key problems in children with cerebral palsy (CP). The goals of the present study were to assess static postural stability in children with mild CP using a force platform compared to that of typically developing peers and to identify differences in static stability between children with hemiplegic and diplegic CP. Methods: This study included 45 children with hemiplegic CP and 45 children with well-functioning diplegic CP (Gross Motor Function Classification System; GMFCS scores between I and II) who were patients of local paediatric rehabilitation centres. The testing procedure included two interrelated parts: (1) the analysis of the body weight distribution and (2) the posturometric test (the centre of pressure; CoP measurements) using the force platform. Results: The results of the present study show that children with CP, compared to their TD peers, demonstrated significantly higher values for all of the analysed indexes of postural stability. The obtained results indicate differences in disorders of static postural stability between children with hemiplegic and diplegic CP. Compared to their TD peers, children with hemiplegic CP showed greater body weight asymmetry between the affected and unaffected sides of the body and greater CoP sway in the medial-lateral direction. In contrast, children with diplegic CP exhibited greater CoP displacements in the anterior-posterior direction. Conclusions: The findings of the present study show that (1) children with CP have increased static postural instability compared to their TD peers and (2) children with diplegic CP exhibit weaker mediolateral stability in standing, whereas children with hemiplegic CP show reduced anterior-posterior stability.

Comprehensive analysis of the cerebrospinal fluid and serum metabolome in neurological diseases.

BACKGROUND: Comprehensive characterization of the metabolome in cerebrospinal fluid (CSF) and serum by Nuclear Magnetic Resonance (NMR) spectroscopy may identify biomarkers and contribute to the understanding of the pathophysiology of neurological diseases. METHODS: Metabolites were determined by NMR spectroscopy in stored CSF/serum samples of 20 patients with Parkinson's disease, 25 patients with other neuro-degenerative diseases, 22 patients with cerebral ischemia, 48 patients with multiple sclerosis, and 58 control patients with normal CSF findings. The data set was analysed using descriptive and multivariate statistics, as well as machine learning models. RESULTS: CSF glucose and lactic acid measured by NMR spectroscopy and routine clinical chemistry showed a strong correlation between both methods (glucose, R2 = 0.87, n = 173; lactic acid, R2 = 0.74, n = 173). NMR spectroscopy detected a total of 99 metabolites; 51 in both, CSF and serum, 16 in CSF only, and 32 in serum only. CSF concentrations of some metabolites increased with age and/or decreasing blood-brain-barrier function. Metabolite detection rates were overall similar among the different disease groups. However, in two-group comparisons, absolute metabolite levels in CSF and serum discriminated between multiple sclerosis and neurodegenerative diseases (area under the curve (AUC) = 0.96), multiple sclerosis and Parkinson's disease (AUC = 0.89), and Parkinson's disease and control patients (AUC = 0.91), as demonstrated by random forest statistical models. Orthogonal partial least square discriminant analysis using absolute metabolite levels in CSF and serum furthermore permitted separation of Parkinson's disease and neurodegenerative diseases. CSF propionic acid levels were about fourfold lower in Parkinson's disease as compared to neurodegenerative diseases. CONCLUSIONS: These findings outline the landscape of the CSF and serum metabolome in different categories of neurological diseases and identify age and blood-brain-barrier function as relevant co-factors for CSF levels of certain metabolites. Metabolome profiles as determined by NMR spectroscopy may potentially aid in differentiating groups of patients with different neurological diseases, including clinically meaningful differentiations, such as Parkinson's disease from other neurodegenerative diseases.

Clinical Features, Hemorrhage Risk and Epilepsy Outcomes of Familial Cerebral Cavernous Malformation: a 20-year Observational Pragmatic Single-Center Study: Clinical Outcomes of Familial CCM: a 20-year Observational Study.

INTRODUCTION: Familial Cerebral Cavernous Malformations (fCCMs) are rare, hereditary conditions characterized by multiple central nervous system lesions. Despite their rarity, CCMs can cause significant clinical challenges when symptomatic, manifesting as seizure and symptomatic hemorrhage (CASH). Guidelines suggest neurosurgical intervention for symptomatic or previously symptomatic lesions, while conservative management is recommended for new-onset epilepsy. However, the natural history and optimal management remain unclear, necessitating further research. OBJECTIVE: This study aims to provide a comprehensive analysis of the clinical features, hemorrhage risk, and epilepsy outcomes in fCCM patients over an extended follow-up period, offering a more precise estimate of CASH and epilepsy rates in this population. METHODS: This retrospective longitudinal cohort study included fCCM patients enrolled from 2001 to May 2024. Data collected included demographic information, new neurological symptoms, symptomatic hemorrhages, seizures, and modified Rankin Scale (mRS) scores. Incidence rates of first symptomatic events and Kaplan-Meier survival curves were calculated, with logistic and Cox-proportional hazard regression models used to evaluate outcomes. RESULTS: A total of 47 patients were included in this study, with a mean age at diagnosis of 37.51 years. At diagnosis, 68% were symptomatic, with 30% having CASH and 36% experiencing seizures without CASH. During a median follow-up of 126.0 months (interquartile range, 110.5 months), 17% had a new CASH event, 20% had seizures without CASH, and 60% remained asymptomatic. The bleeding rate was 1.02% per patient-year, with new focal neurological symptoms at 2.045 per 1000 patient-years and new CASH at 10.225 per 1000 patient-years. Most patients maintained minimal or no disability (mRS 0 or 1). Presenting with epilepsy at baseline significantly increased the odds of future seizures (OR 18.13, p = 0.001). CONCLUSION: This study highlights the complex presentation and progression of fCCMs, emphasizing the necessity for long-term monitoring. Baseline epilepsy is a significant predictor of future seizures, underscoring the need for individualized management strategies. Future research with larger cohorts and standardized criteria is essential to refine the understanding and management of fCCMs.