The diagnosis of acute disseminated encephalomyelitis (ADEM) is challenging due to the existence of other medical conditions that mimic its symptoms and the lack of precise biomarkers. Timely diagnosis is essential for commencing an appropriate treatment, which enhances the clinical trajectory and long-term prognosis. The purpose of the present study was to emphasize significant concerns, specifically for neurologists and radiologists, due to the difficulties involved in identifying this disorder. Neurologists must have an extensive understanding of the clinical manifestations and constraints of current diagnostic tests. Furthermore, this understanding is equally essential for radiologists, as it serves as the foundation for precise diagnostic interpretations derived from imaging findings. The intricate nature of neurological disorders frequently necessitates a cooperative effort between neurologists and radiologists to guarantee precise diagnosis and efficient therapy strategizing. The present study discusses a case of a male patient who was diagnosed with ADEM based on clinical, biological and imaging evaluations.

Extracellular vesicles (EVs) are suggested to have a role in the progression of neurodegeneration, and are able to transmit pathological proteins from one cell to another. One of the biofluids from which EVs can be isolated is cerebrospinal fluid (CSF). However, so far, few studies have been performed on small volumes of CSF. Since pooling of patient samples possibly leads to the loss of essential individual patient information, and CSF samples are precious, it is important to have efficient techniques for the isolation of EVs from smaller volumes. In this study, the SmartSEC HT isolation kit from System Biosciences has been evaluated for this purpose. The SmartSEC HT isolation kit was used for isolation of EVs from 500 μL starting volumes of CSF, resulting in two possible EV fractions of 500 μL. Both fractions were characterised and compared to one another using a whole range of characterisation techniques. Results indicated the presence of EVs in both fractions, albeit fraction 1 showed more reproducible results over the different characterisation methods. For example, CMG (CellMask Green membrane stain) fluorescence nanotracking analysis (NTA), ExoView, and the particles/μg ratio demonstrated a clear difference between fraction 1 and 2, where fraction 1 came out as the one where most EVs were eluted with the least contamination. In the other methods, this difference was less noticeable. We successfully performed complementary characterisation tests using only 500 μL of CSF starting volume, and, conclude that fraction 1 consisted of sufficiently pure EVs for further biomarker studies. This means that future EV extractions may be based upon smaller CSF quantities, such as from individual patients. In that way, patient samples do not have to be pooled and individual patient information can be included in forthcoming studies, potentially linking EV content, size and distribution to individualised neurological diagnoses.

First-line pharmacotherapy for peripheral neuropathic pain (NP) of diverse pathophysiology consists of antidepressants and gabapentinoids, but only a minority achieve sufficient analgesia with these drugs. Opioids are considered third-line analgesics in NP due to potential severe and unpredictable adverse effects in long-term use. Also, opioid tolerance and NP may have shared mechanisms, raising further concerns about opioid use in NP. We set out to further elucidate possible shared and separate mechanisms after chronic morphine treatment and oxaliplatin-induced and diabetic polyneuropathies, and to identify potential diagnostic markers and therapeutic targets. We analysed thermal nociceptive behaviour, the transcriptome of dorsal root ganglia (DRG) and the metabolome of cerebrospinal fluid (CSF) in these three conditions, in rats. Several genes were differentially expressed, most following oxaliplatin and least after chronic morphine treatment, compared with saline-treated rats. A few genes were differentially expressed in the DRGs in all three models (e.g. Csf3r and Fkbp5). Some, e.g. Alox15 and Slc12a5, were differentially expressed in both diabetic and oxaliplatin models. Other differentially expressed genes were associated with nociception, inflammation, and glial cells. The CSF metabolome was most significantly affected in the diabetic rats. Interestingly, we saw changes in nicotinamide metabolism, which has been associated with opioid addiction and withdrawal, in the CSF of morphine-tolerant rats. Our results offer new hypotheses for the pathophysiology and treatment of NP and opioid tolerance. In particular, the role of nicotinamide metabolism in opioid addiction deserves further study.

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UNASSIGNED: B cell depleting anti-CD20 monoclonal antibodies (aCD20 mAbs) are highly effective in treatment of multiple sclerosis (MS) but fail to halt the formation of meningeal ectopic lymphoid tissue (mELT) in the murine model experimental autoimmune encephalomyelitis (EAE). While mELT can be examined in EAE, it is not accessible in vivo in MS patients. Our key objectives were to compare the immune cells in cerebrospinal fluid (CSF), which is accessible in patients, with those in mELT, and to study the effects of aCD20 mAbs on CSF and mELT in EAE.
UNASSIGNED: Applying single cell RNA sequencing, we compared gene expression profiles in immune cells from (1) CSF with mELT and (2) aCD20 mAbs treated with control treated mice in a spontaneous 2D2xTh EAE model.
UNASSIGNED: The immune cell composition in CSF and mELT was very similar. Gene expression profiles and pathway enrichment analysis revealed no striking differences between the two compartments. aCD20 mAbs led not only to a virtually complete depletion of B cells in the CSF but also to a reduction of naïve CD4+ T cells and marked increase of macrophages. No remarkable differences in regulated genes or pathways were observed.
UNASSIGNED: Our results suggest that immune cells in the CSF may serve as a surrogate for mELT in EAE. Future studies are required to confirm this in MS patients. The observed increase of macrophages in B cell depleted CSF is a novel finding and requires verification in CSF of aCD20 mAbs treated MS patients. Due to unresolved technical challenges, we were unable to study the effects of aCD20 mAbs on mELT. This should be addressed in future studies.

BACKGROUND: Accurate diagnosis of Alzheimer\'s disease (AD) and frontotemporal dementia (FTD) represents a health issue due to the absence of disease traits. We assessed the performance of a SIMOA panel in cerebrospinal fluid (CSF) from 43 AD and 33 FTD patients with 60 matching Control subjects in combination with demographic-clinical characteristics.
METHODS: 136 subjects (AD: n = 43, FTD: n = 33, Controls: n = 60) participated. Single-molecule array (SIMOA), glial fibrillary acidic protein (GFAP), neurofilament light (NfL), TAU, and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) in CSF were analyzed with a multiplex neuro 4plex kit. Receiver operating characteristic (ROC) curve analysis compared area under the curve (AUC), while the principal of the sparse partial least squares discriminant analysis (sPLS-DA) was used with the intent to strengthen the identification of confident disease clusters.
RESULTS: CSF exhibited increased levels of all SIMOA biomarkers in AD compared to Controls (AUCs: 0.71, 0.86, 0.92, and 0.94, respectively). Similar patterns were observed in FTD with NfL, TAU, and UCH-L1 (AUCs: 0.85, 0.72, and 0.91). sPLS-DA revealed two components explaining 19% and 9% of dataset variation.
CONCLUSIONS: CSF data provide high diagnostic accuracy among AD, FTD, and Control discrimination. Subgroups of demographic-clinical characteristics and biomarker concentration highlighted the potential of combining different kinds of data for successful and more efficient cohort clustering.

(1) Background: The recent emphasis on sexual and gender diversity\'s impact on human health underscores the need for tailored diagnostic and therapeutic approaches in neurology. The aim of this article is to conduct a narrative review of the available scientific literature on sex differences in cerebrospinal fluid analysis. (2) Methods: The literature search encompassed PubMed databases, focusing on cerebrospinal fluid analysis and sex differences, considering parameters like cerebrospinal fluid protein content, cell count, albumin quotient (QAlb) and intrathecal IgG synthesis. (3) Results: Nine articles from the past two decades were identified, revealing limited research in this area. Males consistently exhibited higher cerebrospinal fluid protein content and albumin quotient values across various pathologies and age groups. Consequently, males more frequently manifested blood-cerebrospinal fluid barrier dysfunction than females. No significant sex differences were observed in cerebrospinal fluid leukocyte count or intrathecal IgG synthesis. (4) Conclusions: This review highlights the dearth of research on sex differences in cerebrospinal fluid analysis, despite consistent findings of higher protein content and albumin quotient values in males. Revisiting current diagnostic thresholds based on sex is crucial for accurate prognosis and personalised treatment strategies in neurological disorders. Moving towards sex-specific approaches in clinical practice is imperative for advancing personalised medicine.

We examined the role of protein tyrosine phosphatase receptor sigma (PTPRS) in the context of Alzheimer\'s disease and synaptic integrity. Publicly available datasets (BRAINEAC, ROSMAP, ADC1) and a cohort of asymptomatic but \"at risk\" individuals (PREVENT-AD) were used to explore the relationship between PTPRS and various Alzheimer\'s disease biomarkers. We identified that PTPRS rs10415488 variant C shows features of neuroprotection against early Tau pathology and synaptic degeneration in Alzheimer\'s disease. This single nucleotide polymorphism correlated with higher PTPRS transcript abundance and lower p(181)Tau and GAP-43 levels in the CSF. In the brain, PTPRS protein abundance was significantly correlated with the quantity of two markers of synaptic integrity: SNAP25 and SYT-1. We also found the presence of sexual dimorphism for PTPRS, with higher CSF concentrations in males than females. Male carriers for variant C were found to have a 10-month delay in the onset of AD. We thus conclude that PTPRS acts as a neuroprotective receptor in Alzheimer\'s disease. Its protective effect is most important in males, in whom it postpones the age of onset of the disease.

UNASSIGNED: Tabes dorsalis is a late manifestation of neurosyphilis, characterized by progressive ataxia, lightning pains, loss of proprioception, and urinary incontinence. The absence of a definitive diagnostic standard and the non-specific clinical manifestations have led to a significant rate of misdiagnoses.
UNASSIGNED: Hospitalized patients with tabes dorsalis at Peking Union Medical College Hospital between January 2010 and December 2023 were reviewed.
UNASSIGNED: A total of 13 patients were included, with 10 males and 3 females. The median age was 50 years (range, 34-64). The most frequent initial symptoms were limb numbness (30.8%) and lightning pains (30.8%). Eleven patients (84.6%) received misdiagnoses prior to the final diagnosis. The most frequently observed physical sign was positive Romberg\'s sign (84.6%). Notably, Argyll Robertson pupil was presented in 7 subjects (53.8%). Serological tests revealed positive rapid plasma regain (RPR) and Treponema pallidum particle agglutination (TPPA) for all patients. All CSF samples were TPPA-reactive. Intramedullary hyperintensity on T2-weighted imaging of spinal MRI was found in 5 patients (38.5%). All patients received anti-syphilitic treatment, with effective treatment recorded in five cases.
UNASSIGNED: This study underscores the importance of neurological symptoms and signs in diagnosing tabes dorsalis. Individuals with progressive ataxia and positive Romberg\'s sign should be closely monitored for potential neurosyphilis. Integrating clinical features, laboratory tests, and neuroimaging could reduce misdiagnosis and expedite the initiation of anti-syphilitic therapy.

Spontaneous intracranial hypotension (SIH) is a rare neurological syndrome. We report the case of a 47-year-old woman with acute, severe orthostatic headache after surgery, chemotherapy, and radiotherapy for breast cancer. The brain and spine magnetic resonance imaging showed signs of intracranial hypotension. We describe the results of a non-targeted epidural blood patch with 10 mL of the patient\'s blood administered after unsuccessful conservative treatment. After the procedure, the patient reported gradual headache relief. This effect persisted over one year. The case shows that a single non-targeted low-volume epidural blood patch can be an effective treatment option for a patient with SIH when conservative treatment fails.