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We performed a retrospective analysis of the patients assessed at our memory unit for whom Alzheimer disease (AD) cerebrospinal fluid biomarker results were available. We selected patients diagnosed with mild cognitive impairment due to AD (National Institute on Aging-Alzheimer's Association clinical criteria), confirmed neuropsychological deficit, a Global Deterioration Scale score of 3, and an abnormal profile of cerebrospinal fluid biomarkers. Of the 588 cases reviewed, 110 met the inclusion criteria. During follow-up, 50 cases (45.45%) progressed to dementia due to AD. Baseline levels of total and phosphorylated tau were higher in the group of patients that progressed to dementia than in those remaining with mild cognitive impairment. After adjusting for age, sex, history of hypertension, diabetes, and educational level, a 10% increase in total tau protein values was associated with a 7.60% increase in the risk of progression to dementia (hazard ratio: 2.22; 95% confidence interval, 1.28-3.84]; P = .004). Among patients with mild cognitive impairment due to AD and abnormal cerebrospinal fluid biomarker profiles, progressively higher concentrations of total or phosphorylated tau were associated with increased risk of progression to dementia.

Primary central nervous system lymphoma (PCNSL) is infrequent and often poses diagnostic conundrums due to its protean manifestations. We present the case of a South Asian young man presenting with raised intracranial pressure and a lymphocytic cerebrospinal fluid (CSF) with pronounced hypoglycorrhachia. Progression of the neuro-ophthalmic signs while on early stages of antitubercular treatment led to additional investigations that produced a final diagnosis of primary leptomeningeal lymphoma. Treatment with chemoimmunotherapy (methotrexate, cytarabine, thiotepa and rituximab (MATRix)) achieved full radiological remission followed by successful autologous transplant. This case highlights the difficulties and diagnostic dilemmas when PCNSL presents as a chronic meningeal infiltrative process. While contextually this CSF is most often indicative of central nervous system tuberculosis and justifies empirical treatment initiation alone, it is essential to include differential diagnoses in the investigation work-up, which also carry poor prognosis without timely treatment. High suspicion, multidisciplinary collaboration and appropriate CSF analysis were the key for a correct diagnosis.

Laboratory studies identified changes in the metabolism of halogens in the serum and cerebrospinal fluid (CSF) of patients with Parkinson's disease, which indicates the presence of «accelerated self-halogenation» of CSF and/or an increase in haloperoxidases, specifically serum thyroperoxidase and CSF lactoperoxidase. Furthermore, an excess of some halogenated derivatives, such as advanced oxygenation protein products (AOPP), has been detected in the CSF and serum. «Accelerated self-halogenation» and increased levels of haloperoxidases and AOPP proteins indicate that halogenative stress is present in Parkinson's disease. In addition, 3-iodo-L-tyrosine, a halogenated derivative, shows «parkinsonian» toxicity in experimental models, since it has been observed to induce α-synuclein aggregation and damage to dopaminergic neurons in the mouse brain and intestine. The hypothesis is that patients with Parkinson's disease display halogenative stress related to a haloenzymatic alteration of the synthesis or degradation of oxyacid of halogens and their halogenated derivatives. This halogenative stress would be related to nervous system damage.

BACKGROUND Transsphenoid meningoencephalocele is a congenital anomaly formed by herniation of an ependyma delimited sac through a bony defect into the sphenoid sinus. The sac contains cerebrospinal fluid and neurovascular structures. The prevalence of transsphenoid meningoencephalocele in the adult population is rare. It usually manifests as nasal liquorrhoea. METHODS AND RESULTS This case report presents an adult male who underwent surgery due to suspected pituitary macroadenoma. The surgery was performed endoscopically via the transnasal approach with a surprising finding of true transsphenoid meningoencephalocele. Ectopic solid tissue was found in the sphenoid sinus in which pituitary adenoma was histologically confirmed. CONCLUSION This paper presents a previously unpublished combination of true transsphenoid meningoencephalocele and pituitary adenoma in an adult individual.

Abstract. Because its secretion is changed in cerebrospinal fluid and peripheral blood, the neuronal polypeptide VGF (nonacronymic) has been discussed as a biomarker for neuropsychiatric disorders. We have shown an enhanced VGF expression by T-cells from Alzheimer’s disease (AD) patients. In this study, we investigated the VGF expression by peripheral monocytes in 38 AD patients, 5 patients with vascular dementia (VD), and 20 neuropsychiatrically healthy individuals using flow cytometry. We determined an enhanced number of VGF-expressing monocytes in VD patients compared to AD patients. VGF+CD14+ monocytes were not correlated with age, body mass index, Mini-Mental State Examination (MMSE), or Q albumin. These preliminary data support findings indicating that VGF might play a role as a peripheral biomarker in VD.

Introduction Endoscopic management of frontal sinus cerebrospinal fluid leaks has become the gold standard of treatment, with high success rates and low morbidity. The aim of this study is to review our experience in managing this challenging condition. Objective To review our experience in treating frontal sinus cerebrospinal fluid leaks through an endonasal endoscopic approach. Methods A retrospective evaluation of patients undergoing endoscopic surgery for frontal sinus cerebrospinal fluid leaks was performed. Demographics, defect location and etiology, surgical and reconstructive technique, complications, and postoperative followup were examined. Results Twenty-two patients with a mean age of 40.4 years were treated surgically by the senior author between 2015 and 2019. Cerebrospinal fluid leak was either traumatic (17) or spontaneous (5). Successful first-attempt endoscopic repair was accomplished in all cases. A combined endoscopic-trephination approach was necessary in 5 patients (22.8%). No serious complications were reported, and frontal sinus drainage pathway was patent in all our cases. Revision surgery was necessary in only 2 patients for synechia formation. The mean patient followup was 22.7 months (range: 7 − 41 months). Conclusion Progress in the field of endoscopic surgery has shifted the paradigm, establishing endoscopic repair of frontal sinus leaks as the standard of care. A few remaining limits of this approach could be addressed by combining endoscopy with frontal trephination.

OBJECTIVE Spontaneous CSF leaks into the anterior skull base nasal sinuses are often associated with meningoencephaloceles and occur in patients with idiopathic intracranial hypertension (IIH). Endonasal endoscopic repair has become the primary method of choice for repair. The authors sought to evaluate the success rate of endoscopic closure and to identify predictive factors for CSF leak recurrence. METHODS A consecutive series of endonasally repaired anterior skull base meningoencephaloceles was drawn from a prospectively acquired database. Lumbar punctures were not performed as part of a treatment algorithm. All patients had at least 5 months of follow-up. Chart review and phone calls were used to determine the timing and predictors of recurrence. Demographic information and details of operative technique were correlated with recurrence. Two independent radiologists reviewed all preoperative imaging to identify radiographic markers of IIH, as well as the location and size of the meningoencephalocele. RESULTS From a total of 54 patients there were 5 with recurrences (9.3%), but of the 39 patients in whom a vascularized nasoseptal (n = 31) or turbinate (n = 8) flap was used there were no recurrences (p = 0.0009). The mean time to recurrence was 24.8 months (range 9–38 months). There was a trend to higher BMI in patients whose leak recurred (mean [± SD] 36.6 ± 8.6) compared with those whose leak did not recur (31.8 ± 7.4; p = 0.182). Although the lateral recess of the sphenoid sinus was the most common site of meningoencephalocele, the fovea ethmoidalis was the most common site in recurrent cases (80%; p = 0.013). However, a vascularized flap was used in significantly more patients with sphenoid (78.3%) defects than in patients with fovea ethmoidalis (28.6%) defects (Fisher’s exact test, p = 0.005). Radiographic signs of IIH were equally present in all patients whose leak recurred (75%) compared with patients whose leak did not recur (63.3%); however, an enlarged Meckel cave was present in 100% (2/2) of patients whose leaks recurred compared with 13.3% (4/30) of patients whose leaks did not recur (p = 0.03). The average meningoencephalocele diameter tended to be larger (1.73 ± 1.3 cm) in patients with recurrence compared to those without recurrence (1.2 ± 0.66 cm; p = 0.22). A ventriculoperitoneal shunt was already in place in 3 patients, placed perioperatively in 5, and placed at recurrence in 2, none of whose leaks recurred. CONCLUSIONS Recurrence after endonasal repair of spontaneous CSF leaks from meningoencephaloceles can be dramatically reduced with the use of a vascularized flap. Although failures of endonasal repair tend to occur in patients who have higher BMI, larger brain herniations, and no CSF diversion, the lack of vascularized flap was the single most important risk factor predictive of failure.

CSF hypotension arises in the context of a leak of CSF which causes negative intracranial pressure. Sacral fractures result from high-energy trauma which are frequently underdiagnosed. A ten-year-old boy presented with hip pain, after a fall. He mobilized both lower limbs, reported no leg pain, irradiation nor lack of sphincter control. The neurological examination was normal. When asked to stand, he began biparietal headache, nausea and vomiting, which improved laying down. CT scan showed an occult intrasacral meningocele; the MRI revealed collections of CSF along the spine, a S3 fracture with potential laceration of the meningocele and opening of a CSF fistula. Our diagnosis was the CSF hypotension, secondary to the fistula opening. The diagnosis was challenging. The child first presented with symptoms of CSF hypotension without evident cause. The discovery of the meningocele led us to hypothesize the opening of a fistula, a rare diagnosis, later confirmed by MRI. info:eu-repo/semantics/publishedVersion

A 52-year-old woman with HIV and recent antiretroviral therapy non-adherence presented with a 5-day history of widespread painful vesicular skin lesions. Direct fluorescent antibody testing of the skin lesions was positive for varicella zoster virus (VZV). On day 3, she developed profound right upper extremity weakness. MRI of the brain and cervical spine was suggestive of VZV myelitis. Lumbar puncture was positive for VZV PCR in the cerebrospinal fluid (CSF) and CSF HIV viral load was detected at 1030 copies/mL, indicating ‘secondary’ HIV CSF escape. She was treated with intravenous acyclovir for 4 weeks and subsequent oral therapy with famciclovir then valacyclovir for 6 weeks. She also received dexamethasone. The patient had an almost full recovery at 6 months. Myelitis is a rare complication of reactivated VZV infection that can have atypical presentation in immunocompromised patients. Such ‘secondary’ HIV CSF escape should be considered in immunosuppressed patients with concomitant central nervous system infection.

The most common cause of spontaneous intracranial hypotension headache is a cerebrospinal fluid (CSF) leakage, but the underlying mechanisms remain unknown. Intracranial hypotension is characterised by diffuse pachymeningeal enhancement on cranial MRI features, low CSF pressure and orthostatic headaches mostly caused by the dural puncture. We report a 31-year-old woman who presented to our services with reports of continuous severe bifrontal headache, which increased on sitting up and resolved on lying down. MRI of the cervical and lumbosacral spine showed signs of CSF leak; hence, patient was diagnosed with spontaneous intracranial hypotension headache. A CT-guided epidural blood patch was done at L4–5 with fibrin glue injected at the site of leak. The patient’s signs and symptoms improved after the procedure.

A 76-year-old man was admitted to the hospital with acute onset of involuntary movements of the left side of his body. His neurological examination revealed he was oriented only to himself, and aforementioned movements of his left arm and leg. CT head demonstrated old infarcts in his right aspect of his pons and basal ganglia. Cerebrospinal fluid analysis was unremarkable. He initially had a normal blood glucose with an elevated anion gap and elevated creatine kinase. Brain MRI showed a small lacunar-type ischaemic infarct within the anteromedial aspect of the right cerebral peduncle, which localised to his haemiballism. To prevent worsening rhabdomyolysis associated with his haemiballism, the primary team initiated both tetrabenazine and diazepam. His movements improved after 1 week of medication therapy. This report discusses a thorough workup for this movement disorder and when to intervene for this distressing condition.

A 13-year-old male asthmatic presented to the general paediatric clinic with papilloedema identified following a check-up with his optician due to blurred vision. His asthma was well controlled on a moderate dose of inhaled corticosteroid and there had been no recent increase or decrease in the dose. A diagnosis of benign intracranial hypertension (BIH) was made based on a raised cerebrospinal fluid opening pressure, papilloedema, a normal neurological examination and normal neuroimaging. The only associated risk factor was his inhaled corticosteroids. He was commenced on acetazolamide and the inhaled corticosteroid dose was reduced, resulting in resolution of his papilloedema. This case serves to highlight that steroid side effects including BIH may occur at moderate doses of inhaled corticosteroids and that inhaled corticosteroid dose should be regularly reviewed and decreased to the lowest dose that maintains asthma control.

Idiopathic intracranial hypertension (IIH) is being diagnosed more often in the UK due to the rise in obesity. In fact, patients who present with bilateral optic disc swelling are habitually put on the papilloedema pathway, often without consideration of other diagnoses. We report the case of a middle-aged woman diagnosed with papilloedema and managed as IIH, until, cerebrospinal fluid (CSF) analysis revealed evidence of lymphocytic meningitis secondary to syphilis. The patient was treated successfully with intravenous antibiotics. Syphilis is the great masquerader and should be a diagnosis to consider in patients who have CSF findings incongruent with their clinical presentation.

We herein report two cases of cerebrospinal fluid (CSF) rhinorrhea associated with lung infiltrates. One patient presented with symptomatic non-resolving pneumonia, while the other was asymptomatic. In both cases, the lung infiltrates completely resolved when CSF leakage had subsided. Pulmonary involvement in CSF rhinorrhea is under-recognized, and despite being the definitive treatment, surgery for CSF rhinorrhea is typically postponed due to the presence of lung infiltrates. However, meningitis is a serious complication due to a delay in surgical management. Physicians should be made aware that CSF rhinorrhea is a potential cause of intractable lung infiltrates.

Diagnosis of LM is limited by low sensitivity of cerebrospinal fluid (CSF) cytopathology. Detecting tumor cells in CSF (CSF-TCs) might be more sensitive. We evaluated if CNSide (CNSide), a novel assay for tumor cell detection in CSF, can detect CSF-TCs better than conventional CSF cytology.We enrolled adults with metastatic breast cancer and clinical suspicion for LM to undergo lumbar puncture (LP) for CSF cytopathology and CNSide. CNSide captured CSF-TCs using a primary 10-antibody mixture, streptavidin-coated microfluidic channel, and biotinylated secondary antibodies. CSF-TCs were assessed for estrogen receptor (ER) expression by fluorescent antibody and HER2 amplification by fluorescent in situ hybridization (FISH). CSF cell-free DNA (cfDNA) was extracted for next-generation sequencing (NGS). Leptomeningeal disease was defined as positive CSF cytology and/or unequivocal MRI findings. We calculated sensitivity and specificity of CSF cytology and CNSide for the diagnosis of LM.Ten patients, median age 51 years (range, 37-64), underwent diagnostic LP with CSF evaluation by cytology and CNSide. CNSide had sensitivity of 100% (95% Confidence Interval [CI], 40%-100%) and specificity of 83% (95% CI, 36%-100%) for LM. Among these patients, concordance of ER and HER2 status between CSF-TCs and metastatic biopsy were 60% and 75%, respectively. NGS of CSF cfDNA identified somatic mutations in three patients, including one with PIK3CA p.H1047L in blood and CSF.CNSide may be a viable platform to detect CSF-TCs, with potential use as a diagnostic tool for LM in patients with metastatic breast cancer. Additional, larger studies are warranted.

Introduction The aim of the study was to analyze the clinical and microbiological characteristics of adult patients with cerebrospinal fluid (CSF) drainage-related ventriculitis. Methods Retrospective study from January 2010 to June 2019 performed in the Complexo Hospitalario Universitario de Vigo (Spain). Cases of CSF drainage-related ventriculitis in patients ≥18-year-old were gathered. Clinical characteristics of patients, type of drainage devices, management and microbiological isolates were analyzed. Results Ninety-one episodes of CSF drainage-related ventriculitis were identified. The most frequent organisms isolated were Gram-positive cocci (65%), mainly Staphylococcus epidermidis (48%). Multidrug-resistant microorganisms were detected in 21 episodes (23%). In multivariate analysis, the independent factors related with multidrug-resistant ventriculitis were the length of hospital stay >14 days (HR 6.7; 95%CI 1.75–25.86, p = 0.006) and previous antimicrobial therapy (HR 5.58; 95%CI 1.44–21.65, p = 0.013). Conclusions Our study shows a large number of drainage-related ventriculitis episodes caused by multidrug-resistant organisms and reinforce the importance of a judicious use of antibiotics.

Background Structural magnetic resonance imaging studies in individuals at clinical high risk for psychosis (CHR) have yielded conflicting results. Methods The aim was to compare intracranial- and structural brain volumes and variability of CHR individuals with those of healthy controls (HCs), and to investigate brain volume differences and variability in CHR subjects with and without transition to psychosis. The PubMed and Embase databases were searched for relevant studies published before June 1st, 2020. Results Thirty-four studies were deemed eligible, which included baseline data of 2111 CHR and 1472 HC participants. Additionally, data was included of 401 CHR subjects who subsequently transitioned to psychosis and 1023 non-transitioned CHR participants. Whole brain and left, right and bilateral hippocampal volume were significantly smaller in CHR subjects compared to HC subjects. Cerebrospinal fluid and lateral ventricle volumes were significantly larger in CHR compared to HC subjects. Variability was not significantly different in CHR compared to HC. CHR individuals with and without subsequent transition to psychosis did not show significant differences in any of the volumetric assessments, nor in variability. Conclusions The current meta-analysis demonstrates reduced whole brain and hippocampal volumes, and increased CSF and lateral ventricle volumes in CHR individuals. However, no significant differences were observed in any of the volumetric assessments between CHR individuals with and without subsequent transition to psychosis. These findings suggest that although structural brain alterations are present before the onset of the disorder, they may not significantly contribute to the identification of CHR individuals at highest risk for the development of psychosis.

Alzheimer’s disease is a neurodegenerative disorder characterized clinically by cognitive decline and pathologically by amyloid deposition and neurofibrillary changes. These neuropathological hallmarks are accompanied by reactive events including microglial activation and astrogliosis. The inflammatory response in Alzheimer’s disease brains is distinguished by a pro-inflammatory signature involving amyloid peptides1, inflammasome signaling2 and disrupted blood brain barrier3. Inflammatory changes are observed also in the cerebrospinal fluid in Alzheimer’s disease4,5. It remains unknown, however, whether the choroid plexus which produces cerebrospinal fluid and guards the brain from peripheral inflammatory insults6,7, contributes to the inflammation and pathogenesis of Alzheimer’s disease. Here we show that the choroid plexus in Alzheimer’s disease exhibits a pro-inflammatory signature with aberrant protein accumulations, which contribute to the age-dependent inflammatory changes observed in the cerebrospinal fluid. Magnetic resonance imaging reveals that the choroid plexus in patients with Alzheimer’s disease displays pathological signal and increased volume, which inversely correlates with cognitive decline. Our findings suggest that the choroid plexus, being unable to efficiently resolve inflammatory insults over the lifetime, eventually ignites and drives the aberrant inflammatory response observed in Alzheimer’s disease. These findings advance our understanding of the pathogenesis and open new vistas in the diagnostics and therapeutics of Alzheimer’s disease.

Anti N-methyl-D-aspartate (NMDA) receptor encephalitis is new entity discovered over a decade. It is a type of autoimmune encephalitis characterized by a sequential onset of neuropsychiatric symptoms especially in the young population. Early diagnosis and treatment lead to better outcome and may prevent permanent neurological deficit or even death. Most patients respond well to first-line treatment and the resection of tumors associated with the disease. Here we present a case, which based on radiological findings, was diagnosed as cerebral venous sinus thrombosis (CVST), and was started on anticoagulation. Failure to respond to treatment and development of new movement abnormalities warranted for further investigations and he was found to have anti-NMDA receptor antibody positive in cerebrospinal fluid. Due to overlapping symptoms of CVST and encephalitis, high incidence of cerebral venous sinus thrombosis in this part of the world, and radiological findings, was initially thought to have CVST which was also confirmed on brain imaging. Lack of consent by the parents for a lumbar puncture delayed the definitive diagnosis. Patient developed movement disorder suggestive of autoimmune encephalitis, and this time after extensive counselling, when the cerebrospinal fluid was send for work up, it showed a positive anti-NMDA receptor antibody. He was promptly started on plasmapheresis after which patient had dramatic improvement both in movement abnormalities and neuropsychiatric symptoms.

Remote intracranial hemorrhage (ICH) is a rare but dreaded complication after spinal surgery. The physiopathology of this phenomenon is closely related to a loss of cerebrospinal fluid (CSF) after an incidental durotomy during spine surgery. The most common remote ICH location is cerebellar, but few articles report intraventricular hemorrhage. Its clinic is associated with cerebral hypotension due to decreased CSF, mainly headache, dysarthria, hemiparesis, an impaired level of awareness and seizures. The diagnosis of remote ICH after a non-cranial surgery can be a challenge to anesthesiologists, this pathology should be suspected face an immediate neurological deterioration after anesthetic awakening. Non-specific symptoms make it difficult to identify the origin of intracranial hemorrhagic from other differential diagnoses. We present a patient with an impaired level of awareness and seizures who suffered a hemorrhage in the right ventricle with cerebral and cerebellar edema in the immediate postoperative period after spinal surgery.

Background The Brain Trauma Foundation (BTF) published evidence-based guidelines with a detailed approach to the management of intracranial hypertension (ICH) in traumatic brain injury (TBI) patients. However, management with cerebrospinal fluid (CSF) drainage in TBI patients remains a controversial topic and is a recent addition to the 4th Edition of the BTF guidelines. External lumbar drainage (ELD) has been proposed for the management of patients with refractory ICH despite aggressive measures. ELD has been described in the literature with possible benefits in outcomes; still, many questions remain unanswered. Methods A systematic search on MEDLINE was conducted for articles that studied lumbar CSF drainage in adult TBI patients with ICH. Results Eleven studies met the inclusion criteria, which included 5 prospective and 6 retrospective studies. Several studies showed that CSF drainage via lumbar drain resulted in significant reduction of ICP compared to before ELD placement and had a low complication rate. However, the data reporting mortality and functional outcomes are varied across studies. Conclusion The literature suggests that ELD may play a role in the management of refractory ICH in TBI patients when first and second-tier measures fail and may be a safe, effective, and minimally invasive method to significantly lower ICP. Additional research and standardized treatment protocols are necessary.

Open and endovascular repairs of the descending thoracic and thoracoabdominal aorta are associated with a substantial risk of spinal cord injury, namely paraplegia. Endovascular repairs seem to have a lower incidence of spinal cord injury, but there have been no randomized trials comparing outcomes of open and endovascular repairs. Paraplegia occurs when collateral blood supply to the anterior spinal artery is impaired. The risk of spinal cord injury can be mitigated with perioperative protocols that include drainage of cerebrospinal fluid, avoidance of hypotension and anemia, intraoperative neurophysiologic monitoring, and advanced surgical techniques. Drainage of cerebrospinal fluid using a spinal drain decreases the risk of spinal cord ischemia by improving spinal cord perfusion pressure. However, cerebrospinal fluid drainage has risks including neuraxial and intracranial bleeding, and these risks need to be carefully weighed against its potential benefit. This review discusses current surgical management of descending thoracic and thoracoabdominal aortic disease, incidence of and risk factors for spinal cord injury, and elements of spinal cord protection protocols that pertain to anesthesiologists, with a focus on cerebrospinal fluid drainage.

We aimed to investigate the protective effect of remote ischemic preconditioning against spinal cord ischemia and find a clue to its mechanism by measuring glutamate concentrations in the spinal ventral horn.Male Sprague-Dawley rats were divided into 5 groups (n = 6 in each group) as follows: sham; SCI (only spinal cord ischemia); RIPC/SCI (perform remote ischemic preconditioning before spinal cord ischemia); MK-801/RIPC/SCI (administer MK-801, N-methyl-D-aspartate receptor antagonist, before remote ischemic preconditioning); and MK-801/SCI (administer MK-801 without remote ischemic preconditioning). Remote ischemic preconditioning was achieved by brief limb ischemia 80 minutes before spinal cord ischemia. MK-801 (1 mg/kg, intravenous) was administered 60 minutes before remote ischemic preconditioning. The glutamate concentration in the ventral horn was measured by microdialysis for 130 minutes after spinal cord ischemia. Immunofluorescence was also performed to evaluate the expression of N-methyl-D-aspartate receptor 2B subunit in the ventral horn 130 minutes after spinal cord ischemia.The glutamate concentrations in the spinal cord ischemia group were significantly higher than in the sham group at all time points (P .01). Remote ischemic preconditioning attenuated the spinal cord ischemia-induced glutamate increase. When MK-801 was preadministered before remote ischemic preconditioning, glutamate concentration was increased after spinal cord ischemia (P .01). Immunofluorescence showed that remote ischemic preconditioning prevented the increase in the expression of N-methyl-D-aspartate receptor 2B subunit on the surface of motor neurons (P = .047).Our results showed that remote ischemic preconditioning prevented spinal cord ischemia-induced extracellular glutamate increase in ventral horn and suppressed N-methyl-D-aspartate receptor 2B subunit expression.

OBJECTIVE: Do MRI-based metrics of a CSF-dynamics disorder, disproportionately enlarged subarachnoid-space hydrocephalus (DESH), correlate with discordant amyloid biomarkers (low CSF β-amyloid 1–42, normal Aβ-PET scan)? METHODS: Individuals ≥50 years from the Mayo Clinic Study of Aging, with MRI, (11)C-Pittsburgh compound B (Aβ) PET scans, and CSF phosphorylated-tau protein and Aβ42, were categorized into four groups: normal/ abnormal by CSF β-amyloid 1–42 and Aβ amyloid PET. Within groups, we noted MRI patterns of CSF-dynamics disorders; categorization into low-CSF β-amyloid 1–42/normal Aβ-PET scan versus normal-CSF and PET groups; and Aβ-PET accumulation-change rate. RESULTS: 100 participants (21%) in the abnormal-CSF/normal-PET group had highest DESH-pattern scores and lowest CSF-phosphorylated-tau levels. Among normal amyloid-PET individuals, a one-unit DESH-pattern score increase correlated with 30%-greater odds of abnormal amyloid CSF after age and sex adjustment. Mean rate over time of amyloid-PET accumulation in abnormal-CSF/normal-PET individuals approximated individuals with normal amyloid values. Adjusting for phosphorylated-tau, abnormal CSF-amyloid/normal amyloid-PET individuals had higher mean amyloid-PET accumulation rates than normal individuals. CONCLUSIONS: CSF dynamics disorders confound β-amyloid and phosphorylated-tau CSF-biomarker interpretation.

Degenerative cervical myelopathy (DCM) is hallmarked by spinal canal narrowing and related cord compression and myelopathy. CSF pressure dynamics are likely disturbed due to spinal canal stenosis. The study aims to investigate the diagnostic value of continuous intraoperative CSF pressure monitoring during surgical decompression. Prospective single center study (NCT02170155) with enrolment of DCM patients that underwent surgical decompression between December 2019 and May 2021. Data from N=17 patients were analyzed, symptom severity graded with the modified Japanese Orthopedic Score (mJOA). CSF pulsations were continuously monitored with a lumbar intrathecal catheter during surgical decompression. Mean patient age was 62±9 years (range 38-73; 8F), symptoms were mild-moderate in most patients (mean mJOA 14±2, range 10-18). Measurements were well tolerated without safety concerns. In 15/16 (94%) CSF pulsations increased at the time of surgical decompression. In one case, responsiveness could not be evaluated for technical reasons. Unexpected CSF pulsation decrease was related to adverse events (i.e., CSF leakage). Median CSF pulsation amplitudes increased from pre-decompression (0.52 mmHg [IQR 0.71]) to post-decompression (0.72 mmHg [IQR 0.96]) (P=0.001). Mean baseline CSF pressure increased with lower magnitude than pulsations, from 9.5±3.5 to 10.3±3.8 mmHg (P=0.003). Systematic relations of CSF pulsations were confined to surgical decompression, independent of arterial blood pressure (P=0.927) or heart rate (P=0.102). Intraoperative CSF pulsation monitoring was sensitive, timely, and specifically related to surgical decompression while in addition adverse events could be discerned. Further investigation of the clinical value of intraoperative guidance for decompression in complex DCM surgery is promising.

Objectives We report the clinical, radiological, laboratory, and neuropathological findings in support of the first diagnosis of lethal, small-vessel cerebral vasculitis triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a pediatric patient. Patient description A previously healthy, 8-year-old Hispanic female presented with subacute onset left-sided weakness two weeks after a mild febrile illness. SARS-CoV-2 nasopharyngeal swab was positive. Magnetic resonance imaging (MRI) revealed an enhancing right frontal lobe lesion with significant vasogenic edema. Two brain biopsies of the lesion showed perivascular and intraluminal lymphohistiocytic inflammatory infiltrate consistent with vasculitis. Despite extensive treatment with immunomodulatory therapies targeting primary angiitis of the central nervous system, she experienced neurologic decline and died 93 days after presentation. SARS-CoV-2 testing revealed positive serum IgG and positive cerebrospinal fluid IgM. Comprehensive infectious, rheumatologic, hematologic/oncologic, and genetic evaluation did not identify an alternative etiology. Post-mortem brain autopsy remained consistent with vasculitis. Discussion This is the first pediatric presentation to suggest SARS-CoV-2 can lead to a fatal, post-infectious, inflammatory small-vessel cerebral vasculitis. Our case is unique in including supportive cerebrospinal fluid and post-mortem tissue analysis. While most children recover well from neurologic complications of SARS-CoV-2, we emphasize the potential mortality in a child with no risk factors for severe disease.

Purpose: Ceritinib is an orally bioavailable, small-molecule inhibitor of anaplastic lympoma kinase (ALK), insulin-like growth factor 1 receptor (IGFR1), and focal adhesion kinase (FAK), which are highly expressed in glioblastoma and many brain metastases. Preclinical and clinical studies indicate that ceritinib has antitumor activity in central nervous system (CNS) malignancies. This phase 0 trial measured the tumor pharmacokinetics (PK) and pharmacodynamics (PD) of ceritinib in patients with brain metastasis or recurrent glioblastoma. Patients and Methods: Preoperative patients with brain tumors demonstrating high expression of pSTAT5b/pFAK/pIGFR1 were administered ceritinib for 10 days prior to tumor resection. Plasma, tumor, and cerebrospinal fluid (CSF) samples were collected at predefined timepoints following the final dose. Total and unbound drug concentrations were determined using LC-MS/MS. In treated tumor and matched archival tissues, tumor PD was quantified through IHC analysis of pALK, pSTAT5b, pFAK, pIGFR1, and pIRS1. Results: Ten patients (3 brain metastasis, 7 glioblastoma) were enrolled and no dose-limiting toxicities were observed. Ceritinib was highly bound to human plasma protein [median fraction unbound (Fu), 1.4%] and to brain tumor tissue (median Fu, 0.051% and 0.045% in gadolinium-enhancing and -nonenhancing regions respectively). Median unbound concentrations in enhancing and nonenhancing tumor were 0.048 and 0.006 μmol/L, respectively. Median unbound tumor-to-plasma ratios were 2.86 and 0.33 in enhancing and nonenhancing tumor, respectively. No changes in PD biomarkers were observed in the treated tumor samples as compared to matched archival tumor tissue. Conclusions: Ceritinib is highly bound to plasma proteins and tumor tissues. Unbound drug concentrations achieved in brain metastases and patients with recurrent glioblastoma were insufficient for target modulation.

Movement disorders associated with glial fibrillary acidic protein (GFAP) autoantibodies have rarely been reported as ataxia or tremors. A 32-year-old man with headache and fever, initially diagnosed with viral meningoencephalitis, showed gradual improvement with empirical treatment. Two weeks after the illness, he suddenly developed orofacial, tongue, and neck dyskinesia accompanied by oculomotor abnormalities, which developed into severe generalized choreoballism. Brain magnetic resonance imaging (fluid-attenuated inversion recovery) showed signal hyperintensities in the bilateral globus pallidus interna. The clinical picture suggested an acute inflammatory trigger of secondary autoimmune encephalitis. The autoimmune antibody test was positive for GFAP, with the strongest reactivity in the cerebrospinal fluid (CSF) before treatment and decreased reactivity in serial CSF examinations during immunotherapy. Dyskinesia gradually improved to the extent that it could be controlled with only oral medications. This patient presented with parainfectious GFAP meningoencephalitis with distinctive clinical features and imaging findings.

The central nervous system (CNS) was previously thought to be the only organ system lacking lymphatic vessels to remove waste products from the interstitial space. Recently, based on the results from animal experiments, the glymphatic system was hypothesized. In this hypothesis, cerebrospinal fluid (CSF) enters the periarterial spaces, enters the interstitial space of the brain parenchyma via aquaporin-4 (AQP4) channels in the astrocyte end feet, and then exits through the perivenous space, thereby clearing waste products. From the perivenous space, the interstitial fluid drains into the subarachnoid space and meningeal lymphatics of the parasagittal dura. It has been reported that the glymphatic system is particularly active during sleep. Impairment of glymphatic system function might be a cause of various neurodegenerative diseases such as Alzheimer's disease, normal pressure hydrocephalus, glaucoma, and others. Meningeal lymphatics regulate immunity in the CNS. Many researchers have attempted to visualize the function and structure of the glymphatic system and meningeal lymphatics in vivo using MR imaging. In this review, we aim to summarize these in vivo MR imaging studies and discuss the significance, current limitations, and future directions. We also discuss the significance of the perivenous cyst formation along the superior sagittal sinus, which is recently discovered in the downstream of the glymphatic system.

Enteroviruses (EVs) are common causes of viral encephalitis in children. To better understand the epidemiological and pathological characteristics of EV encephalitis, we enrolled suspected encephalitis patients younger than 15 years old in Hangzhou, China, from October, 2016 to September, 2019 for cerebrospinal fluid (CSF) collection and analyses. A total of 7735 CSF samples were collected, among which 330 (4.27%) were positive for the EV genome. The positivity rate was significantly higher in boys than girls (χ2 = 5.68, P = 0.02). The monthly case numbers peaked from June to August (80.30%). Among the different age groups, the 0-2 months age group showed the highest number of cases (28.48% of all cases). The 6-7 years (10.82%) and 9-10 years (9.29%) age groups showed the highest EV-positivity rates among suspected encephalitis cases. Sixty-two EV-positive and 53 control CSF samples were collected for Bio-Plex Pro human cytokine assays that simultaneously tested 48 cytokines. Principle component analyses showed significant separation between EV-positive and control samples, but insignificant separation between children and newborns. The levels of 28 cytokines and chemokines were significantly elevated in EV-positive group including many pro-inflammatory and a few anti-inflammatory cytokines, as well as chemokines belonging to the CC and CXC subfamilies. Only one cytokine, SCGF-β, showed a decrease in the EV-positive group. Thus, this study revealed age, sex and seasonal preferences for EV encephalitis incidences in children and identified many cytokines dysregulated during EV encephalitis. This article is protected by copyright. All rights reserved.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia have a strong clinical, genetic, and pathological connection but association of ALS with Alzheimer’s disease (AD) is seldom reported. We report a series of 5 cases of AD associated with ALS. Our patients presented with cognitive deterioration with episodic memory impairment meeting criteria for AD. ALS occurred subsequently in all cases and its phenotype was not homogenous. Amyloid process was confirmed in four cases with cerebrospinal fluid biomarkers. One case underwent postmortem exam, demonstrating hallmarks lesions of both diseases. This series highlights that ALS-AD phenotype could be a specific underexplored entity.

Key Points The NGS-MRD assay detected clonotypic DNA in 100% of CSF samples from patients who had lymphoma with parenchymal CNS involvement.Clonotypic DNA in CSF was present in 36% of newly diagnosed aggressive lymphomas and was associated with a 29% risk of CNS recurrence., Visual Abstract, The diagnosis of parenchymal central nervous system (CNS) invasion and prediction of risk for future CNS recurrence are major challenges in the management of aggressive lymphomas, and accurate biomarkers are needed to supplement clinical risk predictors. For this purpose, we studied the results of a next-generation sequencing (NGS)–based assay that detects tumor-derived DNA for clonotypic immunoglobulin gene rearrangements in the cerebrospinal fluid (CSF) of patients with lymphomas. Used as a diagnostic tool, the NGS-minimal residual disease (NGS-MRD) assay detected clonotypic DNA in 100% of CSF samples from 13 patients with known CNS involvement. They included 7 patients with parenchymal brain disease only, whose CSF tested negative by standard cytology and flow cytometry, and 6 historical DNA aliquots collected from patients at a median of 39 months before accession, which had failed to show clonal rearrangements using standard polymerase chain reaction. For risk prognostication, we prospectively collected CSF from 22 patients with newly diagnosed B-cell lymphomas at high clinical risk of CNS recurrence, of whom 8 (36%) had detectable clonotypic DNA in the CSF. Despite intrathecal prophylaxis, a positive assay of CSF was associated with a 29% cumulative risk of CNS recurrence within 12 months of diagnosis, in contrast with a 0% risk among patients with negative CSF (P = .045). These observations suggest that detection of clonotypic DNA can aid in the diagnosis of suspected parenchymal brain recurrence in aggressive lymphoma. Furthermore, the NGS-MRD assay may enhance clinical risk assessment for CNS recurrence among patients with newly diagnosed lymphomas and help select those who may benefit most from novel approaches to CNS-directed prophylaxis.

Aim: There is a critical need to validate biofluid-based biomarkers as diagnostic and drug development tools for traumatic brain injury (TBI). As part of the TBI Endpoints Development Initiative, we identified four potentially predictive and pharmacodynamic biomarkers for TBI: astroglial markers GFAP and S100B and the neuronal markers UCH-L1 and Tau. Materials & methods: Several commonly used platforms for these four biomarkers were identified and compared on analytic performance and ability to detect gold standard recombinant protein antigens and to pool control versus TBI cerebrospinal fluid (CSF). Results: For each marker, only some assay formats could differentiate TBI CSF from the control CSF. Also, different assays for the same biomarker reported divergent biomarker values for the same biosamples. Conclusion: Due to the variability of TBI marker assay in performance and reported values, standardization strategies are recommended when comparing reported biomarker levels across assay platforms.

To our knowledge, this is the first case report of a transudative pleural effusion with positive Cryptococcal antigen and culture. We describe a 32-year-old male with end-stage liver disease (ESLD) who presented to an outside hospital with dyspnea and a large pleural effusion. An initial pleural fluid analysis was positive for Cryptococcal Ag. However, the infection was eventually found to be widespread as he had positive Cryptococcal Ag and cultures in his pleural fluid, serum, and cerebrospinal fluid (CSF). His antimicrobial regiment was escalated from fluconazole to amphotericin B and flucytosine. His medical condition deteriorated, and the patient passed away. Due to its rarity and range of clinical severity, diagnosis of disseminated Cryptococcosis can be delayed. We present this case to bring awareness of this diagnosis as a differential in immunocompromised patients regardless of a transudative pleural effusion.

The brain is highly enriched in lipids. A growing body of research has shown that brain lipid content and composition change in various neurological disorders. In addition to brain tissues, lipid changes have been detected in cerebrospinal fluid and blood in animal models of various central nervous system diseases and patients. Altered lipid metabolism has also been observed to contribute to the development and progression of sevoflurane-induced neurotoxicity. Analyses of lipid profiles have provided significant insights into the underlying mechanisms of central nervous system diseases. Assessing changes in lipid profiles in the cerebrospinal fluid and blood may provide additional information on the status of the brain in clinical settings. This mini-review summarizes the recent updates on lipids in diverse neurological conditions and discusses the application of lipid analysis to neurotoxicity assessment studies.

Delivery of adeno-associated viral vectors (AAVs) to cerebrospinal fluid (CSF) has emerged as a promising approach to achieve widespread transduction of the central nervous system (CNS) and peripheral nervous system (PNS), with direct applicability to the treatment of a wide range of neurological diseases, particularly lysosomal storage diseases. Although studies in small animal models have provided proof of concept and experiments in large animals demonstrated feasibility in bigger brains, there is not much information on long-term safety or durability of the effect. Here, we report a 7-year study in healthy beagle dogs after intra-CSF delivery of a single, clinically relevant dose (2 × 1013 vg/dog) of AAV9 vectors carrying the canine sulfamidase, the enzyme deficient in mucopolysaccharidosis type IIIA. Periodic monitoring of CSF and blood, clinical and neurological evaluations, and magnetic resonance and ultrasound imaging of target organs demonstrated no toxicity related to treatment. AAV9-mediated gene transfer resulted in detection of sulfamidase activity in CSF throughout the study. Analysis at tissue level showed widespread sulfamidase expression and activity in the absence of histological findings in any region of encephalon, spinal cord, or dorsal root ganglia. Altogether, these results provide proof of durability of expression and long-term safety for intra-CSF delivery of AAV-based gene transfer vectors encoding therapeutic proteins to the CNS., Graphical abstract, Seven-year follow-up of dogs after intra-CSF administration of AAV9-sulfamidase vectors results in detection of sulfamidase activity in CSF and widespread transgene expression in CNS, PNS, and liver, in the absence of any adverse events. Proof of durability and safety of this gene therapy support its clinical translation to treat CNS diseases.

Background Cerebrospinal fluid (CSF) rhinorrhea results from abnormal communications between the subarachnoid and sinonasal spaces. Accurate preoperative diagnosis and localization are vital for positive clinical outcomes. However, the diagnosis and localization of CSF rhinorrhea remain suboptimal due to a lack of accurate understanding of test characteristics. Objective This systematic review aims to assess the diagnostic accuracy of various tests and imaging modalities for diagnosing and localizing CSF rhinorrhea. Methods A systematic review of the MEDLINE and EMBASE databases was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results Our search identified 4039 articles—53 cohort studies and 24 case series describing 1622 patients were included. The studies were heterogeneous and had a wide range of sensitivities and specificities. Many specificities were incalculable due to a lack of true negative and false positive results, thus precluding a meta-analysis. Median sensitivities and specificities were calculated for cohort studies of the following investigations: high-resolution computed tomography (HRCT) 0.93/0.50 (sensitivity/specificity), magnetic resonance cisternography (MRC) 0.94/0.77, computed tomography cisternography (CTC) 0.95/1.00, radionuclide cisternography (RNC) 0.90/0.50, and contrast-enhanced magnetic resonance cisternography (CEMRC) 0.99/1.00, endoscopy 0.58/1.00, topical intranasal fluorescein (TIF) 1.00/incalculable, intrathecal fluorescein (ITF) 0.96/1.00. Case series were reviewed separately. Etiology and site-specific data were also analyzed. Conclusion MR cisternography is more accurate than high-resolution CT at diagnosing and localizing CSF rhinorrhea. CT cisternography, contrast-enhanced MR cisternography, and radionuclide cisternography have good diagnostic characteristics but are invasive. Intrathecal fluorescein shows promising data but has not been widely adopted for purely diagnostic use. Office endoscopy has limited data but does not sufficiently diagnose CSF rhinorrhea independently. These findings confirm with current guidelines and evidence.

Background The ability of antituberculosis drugs to cross the blood–brain barrier and reach the central nervous system is critical to their effectiveness in treating tuberculosis meningitis (TBM). We sought to fill a critical knowledge gap by providing data on the ability of new and repurposed antituberculosis drugs to penetrate into the cerebrospinal fluid (CSF). Methods We conducted a clinical pharmacology study among patients treated for TBM in Tbilisi, Georgia, from January 2019 until January 2020. Serial serum and CSF samples were collected while patients were hospitalized. CSF was collected from routine lumbar punctures with the timing of the lumbar puncture alternating between 2 and 6 hours to capture early and late CSF penetration. Results A total of 17 patients treated for TBM (8 with confirmed disease) were included; all received linezolid, with a subset receiving cycloserine (5), clofazimine (5), delamanid (4), and bedaquiline (2). All CSF measurements of bedaquiline (12), clofazimine (24), and delamanid (19) were below the limit of detection. The median CSF concentrations of cycloserine at 2 and 6 hours were 15.90 and 15.10 µg/mL with adjusted CSF/serum ratios of 0.52 and 0.66. CSF concentrations of linezolid were 0.90 and 3.14 µg/mL at 2 and 6 hours, with adjusted CSF/serum ratios of 0.25 and 0.59, respectively. CSF serum linezolid concentrations were not affected by rifampin coadministration. Conclusions Based on moderate to high CSF penetration, linezolid and cycloserine may be effective drugs for TBM treatment, whereas the utility of bedaquiline, delamanid, and clofazimine is uncertain given their low CSF penetration.

In the present study, via using the mixed ligand synthesis approach, two coordination polymers (CPs) based on Cu(II) and Co(II) ions as nodes, namely, [Cu3(L1)2(1,2,4-BTC)2(H2O)4]n (1) and [Co3(L2)(1,2,4-BTC)2(H2O)4]n (2) (L1 is 3,6-bis(imidazol-1-yl)pyridazine, L2 is 3,6-bis(benzimidazol-1-yl)pyridazine and 1,2,4-H3BTC is benzene-1,2,4-tricarboxylic acid), were synthesized by reaction of the 1,2,4-H3BTC ligand and relevant metal salts with the aid of various nitrogen-donor co-ligands. Their application values on the cerebral ischemia were evaluated and the specific mechanism was studied simultaneously. At first, the enzyme linked immunosorbent assay (ELISA) was carried out to assess the inflammatory cytokines content released into cerebrospinal fluid. Besides, the neuro-apoptosis induced by cerebral ischemia was tested through the Annexin V-FITC Apoptosis Detection Kit.

Background: Bacterial meningitis is a severe infection of the central nervous system with varied clinical presentations. It is associated with substantial mortality and morbidity. Objectives: The objective of this study was to assess the clinical profile, including the clinical features, laboratory and radiological parameters, clinical course, treatment, response to treatment, complications, and outcome of children at discharge. Methods: A prospective observational study was conducted among 52 inpatient children of acute bacterial meningitis aged one month to 14 years over a period of six months. The patients were enrolled during admission and followed up daily till discharge. Socio-demographic, clinical, and diagnostic details and outcomes were recorded and analysed using statistical package for social sciences version 20. Results: The median age of the patients was two years with male to female ratio of 2:1. Fever (45, 87%), vomiting (37, 71%), seizure (33, 64%) and headache (22, 46%) were the most common symptoms. The cerebrospinal fluid culture was positive in three (6%) cases. Complications were seen in 20 (39%) patients including four (7.7%) deaths. Patients with prolonged fever, malnutrition, loss of consciousness, ear discharge, presence of meningeal signs, abnormal pupil, high cerebrospinal fluid protein, positive cerebrospinal fluid, and blood culture, low blood pH, and hyperlactataemia were significantly associated with complications (p

Knowledge about the dynamic metabolism and function of cerebrospinal fluid (CSF) physiology has rapidly progressed in recent decades. It has traditionally been suggested that CSF is produced by the choroid plexus and drains to the arachnoid villi. However, recent findings have revealed that the brain parenchyma produces a large portion of CSF and drains through the perivascular glymphatic system and meningeal lymphatic vessels into the blood. The primary function of CSF is not limited to maintaining physiological CNS homeostasis but also participates in clearing waste products resulting from neurodegenerative diseases and acute brain injury. Aneurysmal subarachnoid hemorrhage (SAH), a disastrous subtype of acute brain injury, is associated with high mortality and morbidity. Post-SAH complications contribute to the poor outcomes associated with SAH. Recently, abnormal CSF flow was suggested to play an essential role in the post-SAH pathophysiological changes, such as increased intracerebral pressure, brain edema formation, hydrocephalus, and delayed blood clearance. An in-depth understanding of CSF dynamics in post-SAH events would shed light on potential development of SAH treatment options. This review summarizes and updates the latest physiological characteristics of CSF dynamics and discusses potential pathophysiological changes and therapeutic targets after SAH.

Background and ObjectivesTo report the clinical, biological, and imaging features and clinical course of a French cohort of patients with glial fibrillary acidic protein (GFAP) autoantibodies.MethodsWe retrospectively included all patients who tested positive for GFAP antibodies in the CSF by immunohistochemistry and confirmed by cell-based assay using cells expressing human GFAPα since 2017 from 2 French referral centers.ResultsWe identified 46 patients with GFAP antibodies. Median age at onset was 43 years, and 65% were men. Infectious prodromal symptoms were found in 82%. Other autoimmune diseases were found in 22% of patients, and coexisting neural autoantibodies in 11%. Tumors were present in 24%, and T-cell dysfunction in 23%. The most frequent presentation was subacute meningoencephalitis (85%), with cerebellar dysfunction in 57% of cases. Other clinical presentations included myelitis (30%) and visual (35%) and peripheral nervous system involvement (24%). MRI showed perivascular radial enhancement in 32%, periventricular T2 hyperintensity in 41%, brainstem involvement in 31%, leptomeningeal enhancement in 26%, and reversible splenial lesions in 4 cases. A total of 33 of 40 patients had a monophasic course, associated with a good outcome at last follow-up (Rankin Score ≤2: 89%), despite a severe clinical presentation. Adult and pediatric features are similar. Thirty-two patients were treated with immunotherapy. A total of 11/22 patients showed negative conversion of GFAP antibodies.DiscussionGFAP autoimmunity is mainly associated with acute/subacute meningoencephalomyelitis with prodromal symptoms, for which tumors and T-cell dysfunction are frequent triggers. The majority of patients followed a monophasic course with a good outcome.

Meningomyelocele, one of the neural tube defect (NTD) variants, is a condition in which meninges and neural tissue protrudes through a defect in vertebral arch and forms a cyst-like sac with an incidence of 0.5–11/1000 live births. Hydrocephalus is a major problem for majority of patients with meningomyelocele due to the abnormal accumulation of cerebrospinal fluid (CSF) in the ventricles of the brain. Meticulous preoperative evaluation with planning of the anesthetic technique, especially in regard to managing the airway, plays a crucial role in successful surgical management of these cases. Here, we report a case of lumbosacral meningomyelocele with hydrocephalus underwent a multimodal treatment approach for providing a comprehensive plan of care.

Background. The study aimed to investigate the aspects of glycosyl determinants alteration in human with multiple sclerosis that have not been studied before. Materials and ­methods. Glycosylation of antibodies in cerebrospinal fluid (CSF) have been studied and compared with serum antibodies with the determination of their nature. The detection of multiple sclerosis (MS) specific autoantibodies can serve as a reliable biomarker for this disease. Eighteen samples of serum of healthy donors (HD) and 20 samples of serum of patients with MS were analysed, 12 of which were samples of CSF of patients with MS. Results. An analysis of the immune complexes of IgM molecules bound to IgG molecules revealed a significant difference in their content between the serum of HD and the serum of patients with MS who had slightly higher levels of IgG-IgM immune complexes. Lectin enzyme-linked immunosorbent analysis has shown that the level of exposure of sialic residues detected with SNA lectin was significantly higher in patients with MS compared to healthy donors. There was also an increase in the level of exposure of fucose residues to both serum and CSF immunoglobulins in MS patients compared to healthy donors. The level of their exposure to CSF immunoglobulins was significantly higher than a level in serum immunoglobulins. Conclusions. The level of exposure of fucosyl and sialyl residues to the serum and CSF in MS patients significantly differs. In all cases, the number of immunoglobulin molecules detected was the same. Thus, it was shown that in the tested samples of sera and CSF of the patients with MS, the exposure of terminal sialic acids and bark fucosyl residues significantly altered, which was not associated with changes in the number of N-glycans themselves or the appearance of additional glycosylation sites on immunoglobulins molecules., Целью работы было исследование аспектов изменений гликозильных детерминант человека при рассеянном склерозе (РС), которые ранее не исследовались. Было проведено исследование гликозилирования антител в цереброспинальной жидкости (ЦСЖ), сравнение с антителами сыворотки крови и определение их природы. А также выявление специфического для рассеянного склероза класса аутоантител, что может служить надежным биомаркером этого заболевания. Материалы и методы. Проанализированы 18 образцов сыворотки крови здоровых доноров (ЗД) и 20 образцов сыворотки крови больных РС, из них 12 образцов ЦСЖ больных РС. Результаты. Анализ иммунных комплексов молекул IgM, связанных с молекулами IgG, показал значительную разницу в их содержании между сывороткой ЗД и сывороткой пациентов с РС, у которых наблюдалось достоверно более высокое содержание иммунных комплексов IgG–IgM. Лектин-иммуноферментный анализ исследуемых сывороток показал, что уровень экспонирования сиаловых остатков, обнаруженных с лектином SNA, является достоверно более высоким в сыворотках больных РС по сравнению со здоровыми донорами. Также был отмечен рост уровня экспонирования остатков фукозы на иммуноглобулинах как сыворотки, так и ЦСЖ у больных РС по сравнению со здоровыми донорами. При этом уровень их экспонирования на иммуноглобулинах ЦСЖ был достоверно выше такового в иммуноглобулинах сыворотки. Выводы. Уровень экспонирования фукозильных и сиаловых остатков в сыворотке и ЦСЖ у больных РС достоверно различается. Количество детектированных молекул иммуноглобулинов во всех случаях было одинаковым. Таким образом было показано, что в исследуемых образцах сывороток и ЦСЖ больных РС происходят значительные изменения экспонирования терминальных сиаловых кислот и коревых фукозильных остатков, которые не связаны с изменением количества самих N-гликанов или появлением дополнительных сайтов гликозилирования на молекулах иммуноглобулинов., Метою роботи було дослідження аспектів змін глікозильних детермінант людини при розсіяному склерозі (РС), які раніше не досліджували. Було проведено дослідження глікозилювання антитіл у цереброспінальній рідині (ЦСР), порівняння з антитілами сироватки крові та визначення їх природи. А також виявлення специфічного для розсіяного склерозу класу автоантитіл, що може слугувати надійним біомаркером цього захворювання. Матеріали та методи. Проаналізовано 18 зразків сироватки крові здорових донорів (ЗД) та 20 зразків сироватки крові хворих на РС, із них 12 зразків ЦСР хворих на РС. Результати. Аналіз імунних комплексів молекул IgM, зв’язаних із молекулами IgG, показав значну різницю у їх вмісті між сироваткою ЗД та сироваткою пацієнтів із РС, у яких спостерігався вірогідно вищий вміст імунних комплексів IgG–IgM. Лектин-імуноферментний аналіз досліджуваних сироваток показав, що рівень експонування сіалових залишків, виявлений з лектином SNA, є вірогідно вищим у сироватках хворих на РС порівняно зі здоровими донорами. Також було відзначено зростання рівня експонування залишків фукози на імуноглобулінах як сироватки, так і ЦСР у хворих на РС порівняно зі здоровими донорами. При цьому рівень їх експонування на імуноглобулінах ЦСР був вірогідно вищим за такий в імуноглобулінах сироватки. Висновки. Рівень експонування фукозильних і сіалових залишків у сироватці та ЦСР у хворих на РС вірогідно різниться. Кількість детектованих молекул імуноглобулінів у всіх випадках була однаковою. У такий спосіб було показано, що в досліджуваних зразках сироваток та ЦСР хворих на РС відбуваються значні зміни експонування термінальних сіалових кислот і корових фукозильних залишків, які не пов’язані із зміною кількості самих N-гліканів чи появою додаткових сайтів глікозилювання на молекулах імуноглобулінів.

Meningitis is a public health concern. It is caused by several etiologic agents that vary by age group and geographical area. This study aims to highlight the etiological and predictive factors of acute meningitis in hospitalized febrile patients in Mansoura Fever Hospital, Egypt. This study includes cases admitted with suspected meningitis. The study is conducted in the period between April 2019 and March 2020. Lumbar puncture, CSF examination and blood culture and sensitivity were done. Brain Magnetic Resonance Imaging (MRI) was performed before lumbar puncture in some patients. Detailed analysis of epidemiologic characteristics, clinical data, laboratory findings, the causative organisms and predictors of patients with Bacterial Meningitis (BM) were studied. This study included 110 patients had BM with CSF leukocytosis > 100 cells/mm3. Out of 110 CSF samples, 95 cases (86.4%) pathogens were detected by direct Gram-stained smear. Gram positive cocci were the commonest microorganism isolated. 66.4% of patients had blood culture growth of the same organism as the CSF culture. Reagent strip CSF examinations showed a positive correlation compared with laboratory tests. BM had 22.7% mortality rate. Predictive factors of poor outcomes include CSF/serum glucose ratio >0.6, CSF protein >80 mg/dl and Tonsillitis. Prognostic factors that are associated with poor outcome include old age, late presentation, delayed antibiotics treatment, neurologic complications and Glasgo Coma Scale (GCS). BM remains a leading cause of morbidity and mortality,so early diagnosis and treatment decrease both. Predictors of poor outcome of BM are CSF/serum glucose ratio >0.6, CSF protein >80 mg/dl and Tonsillitis. Key words: Bacterial meningitis, lumbar puncture, cerebrospinal fluid (CSF) analysis.

BACKGROUND AND PURPOSE The aim of this study was to identify the long-term radiological changes, autoantibody specificities, and clinical course in a patient with kelch-like protein 11 (KLHL11)-associated paraneoplastic neurological syndrome (PNS). METHODS Serial brain magnetic resonance images were retrospectively assessed. To test for KLHL11 autoantibodies, longitudinal cerebrospinal fluid (CSF) and serum samples were screened by Phage-display ImmunoPrecipitation and Sequencing (PhIP-Seq). Immunohistochemistry was also performed to assess for the presence of KLHL11 in the patient's seminoma tissue. RESULTS A 42-year-old man presented with progressive ataxia and sensorineural hearing loss. Metastatic seminoma was detected 11 months after the onset of the neurological symptoms. Although immunotherapy was partially effective, his cerebellar ataxia gradually worsened over the next 8 years. Brain magnetic resonance imaging revealed progressive brainstem and cerebellar atrophy with a "hot-cross-bun sign", and low-signal intensity on susceptibility-weighted imaging (SWI) in the substantia nigra, red nucleus and dentate nuclei. PhIP-Seq enriched for KLHL11-derived peptides in all samples. Immunohistochemical staining of mouse brain with the patient CSF showed co-localization with a KLHL11 commercial antibody in the medulla and dentate nucleus. Immunohistochemical analysis of seminoma tissue showed anti-KLHL11 antibody-positive particles in cytoplasm. CONCLUSIONS This study suggests that KLHL11-PNS should be included in the differential diagnosis for patients with brainstem and cerebellar atrophy and signal changes not only on T2-FLAIR but also on SWI, which might otherwise be interpreted as secondary to a neurodegenerative disease such as multiple system atrophy.

Older adults with lower education are at greater risk for dementia. It is unclear which brain changes lead to these outcomes. Longitudinal imaging-based measures of brain structure and function were examined in adult individuals (baseline age, 45–86 years; two to five visits per participant over 1–9 years). College degree completion differentiates individual-based and neighborhood-based measures of socioeconomic status and disadvantage. Older adults (~65 years and over) without a college degree exhibit a pattern of declining large-scale functional brain network organization (resting-state system segregation) that is less evident in their college-educated peers. Declining brain system segregation predicts impending changes in dementia severity, measured up to 10 years past the last scan date. The prognostic value of brain network change is independent of Alzheimer’s disease (AD)-related genetic risk (APOE status), the presence of AD-associated pathology (cerebrospinal fluid phosphorylated tau, cortical amyloid) and cortical thinning. These results demonstrate that the trajectory of an individual’s brain network organization varies in relation to their educational attainment and, more broadly, is a unique indicator of individual brain health during older age. A brain-imaging study in humans demonstrates that older age brain network decline varies in relation to an individual’s education and predicts future dementia severity beyond other markers of Alzheimer’s disease-related genetic risk and pathology.

Traumatic brain injury (TBI) is a major neurological disorder without FDA-approved therapies. In this study, we have examined the concept that TBI might trigger global brain proteolysis in the acute post-injury phase. Thus, we conducted a systemic proteolytic peptidomics analysis using acute cerebrospinal fluid (CSF) samples from TBI patients and normal control samples. We employed ultrafiltration-based low molecular weight (LMW

The main causes for cerebrospinal fluid (CSF) leaks are known to be traumatic, iatrogenic, neoplastic, a meningoencephalocele, congenital bone defects, and spontaneous. Off-label intrathecal administration of fluorescein is widely used to localize a CSF leak. Complications are rare and low dose administration is described to be safe. In this case report, we present a case of a patient, who showed a CSF leak due to an encephalocele. Low dose fluorescein was applied intrathecally via lumbar catheter, the CSF leaks could be identified, and multilayered closure was performed. Postoperatively, the patient presented with motor and sensory deficits in the lower limbs which regressed only partially within 2 months. A possible explanation may be an increased local concentration of fluorescein, possibly on the basis of a preexisting lumbar spinal canal stenosis. To our knowledge, this is the first case in which a dose as low as 20 mg of fluorescein (2% saline mixture) led to persisting paraplegia. Therefore, the potential benefits and risks of the intrathecal fluorescein use in the detection of a CSF leak have to be discussed comprehensively prior to surgery.

Background. The prevalence of rheumatoid arthritis (RA) among the world’s population is about 1 %, and among certain populations of people it reaches 5–7 %. The risk factors for the development and high rates of RA progression include high concentrations of quartz (silicon (Si) dioxide) in the inhaled air, the toxic effect of which is considered as one of the most powerful pathogenetic factors of this disease. The purpose of the work was to evaluate the clinical and pathogenetic significance of silicon microelementosis in RA. Materials and methods. Eighty-three patients with RA were examined (22 % were males and 78 % — females aged from 22 to 75 (mean of 45) years). The duration of the disease from the first signs of its manifestation was 9 years. Systemic form of the disease was diagnosed in 19 % of cases, RA seropositive for rheumatoid factor was detected in 68 %, for cyclic citrullinated peptide antibodies — in 80 % of individuals. The content of Si in the blood serum and in 19 patients — in cerebrospinal fluid was determined using an atomic absorption spectrometer SolAAr-Mk2-MOZe with an electrographite atomizer (Great Bri­tain). Using a computer tensiometer PAT2-Sinterface (Germany), the parameters of the surface tension of blood serum and synovial fluid were investigated with a surface life time of 0.01 sec and tending to infinity, and their ratio was calculated. Results. RA is accompanied by the absence of probable changes in the level of silicon. Si microelementosis is associated with the clinical, radiographic and sonographic signs of the disease course, the degree of activity and severity of arthritis, and silicon imbalance is involved in the pathogenesis of the articular syndrome, damage to the ske­letal muscle, the peripheral nervous system, wherein, Si indicators in blood may have prognostic significance.