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Magnetic resonance imaging (MRI) is increasingly used by the orbital surgeon to aid in the diagnosis, surgical planning, and monitoring of orbital disease. MRI provides superior soft tissue detail compared with computed tomography or ultrasound, and advancing techniques enhance its ability to highlight abnormal orbital pathology. Diffusion-weighted imaging is a specialized technique that uses water molecule diffusion patterns in tissue to generate contrast signals and can help distinguish malignant from benign lesions. Steady-state free precession sequences such as Constructive Interference in Steady-State (CISS) and Fast Imaging Employing Steady-state Acquisition (FIESTA) generate highly detailed, 3-dimensional reconstructed images and are particularly useful in distinguishing structures adjacent to cerebral spinal fluid. Magnetic resonance angiography can be used to characterize vascular lesions within the orbit. New developments in magnetic field strength as well as the use of orbital surface coils achieve increasingly improved imaging resolution.

BACKGROUND: Aplasia cutis congenita is a rare newborn malformation characterized by focal absence of skin. It possesses difficulty in reconstruction surgery for neurosurgeons and plastic surgeons. We report a challenging case of aplasia cutis congenita who received treatment in our center. CLINICAL CASE: A 2-year-old boy, presented to Plastic and Reconstructive Surgery, Hospital USM, with bilateral vertex defect with encephalocele who received a series of surgical interventions since 1 month old. Unfortunately, he returned after 2 years with a chronic nonhealing scalp wound associated with dura defect and cerebral spinal fluid leakage. The wound was debrided and the swab culture result showed no organism growth. Part of the wound bed with dura defect was repaired using a small piece of transplanted fascia lata and Integra was applied. DISCUSSION: There is scarcity in the medical literature on the reconstructive technique of aplasia cutis congenita. In the case we described here, we successfully managed the wound with multiple application of dermal substitute (Integra) dressing with negative pressure wound therapy and split-thickness skin graft. CONCLUSIONS: Management of aplasia cutis congenita with skull defect remains a controversy. Its management varies depends on its pattern and underlying condition. We successfully develop a new simple method in treating scalp accutilizing Integra.

Background Medulloblastoma (MB) is the most common pediatric embryonal tumor. Accurate identification of cerebral spinal fluid (CSF) dissemination is important in prognosis prediction. Both MRI of the central nervous system (CNS) and CSF cytology will appear false positive and negative. Our objective was to investigate the added value of preoperative-enhanced T1-weighted image-based radiomic features to clinical characteristics in predicting preoperative CSF dissemination for children with MB. Materials and methods This retrospective study included 84 children with histopathologically confirmed MB between November 2006 and November 2018 (training cohort, n=60; internal validation cohort, n=24). A set of cases between December 2018 and February 2020 were used for external validation (n=40). The children with normal head and spine magnetic resonance images (MRI) and no subsequent dissemination in 1 year were diagnosed as non-CSF dissemination. The CSF dissemination was manifested as intracranial or intraspinal nodular-enhanced lesions. Clinical features were collected, and conventional MRI features of preoperative head MRI examinations were evaluated. A total of 385 radiomic features were extracted from preoperative-enhanced T1-weighted images. Minimum redundancy, maximum correlation, and least absolute shrinkage and selection operator were performed to select the features with the best performance in predicting preoperative CSF dissemination. A combined clinical-MRI radiomic prediction model was developed using multivariable logistic regression. Receiver operating curve analysis (ROC) was used to validate the predictive performance. Nomogram and decision curve analysis (DCA) were developed to evaluate the clinical utility of the combined model. Results One clinical and nine radiomic features were selected for predicting preoperative CSF dissemination. The combined model incorporating clinical and radiomic features had the best predictive performance in the training cohort with an AUC of 0.89. This was validated in the internal and external cohorts with AUCs of 0.87 and 0.73. The clinical utility of the model was confirmed by a clinical-MRI radiomic nomogram and DCA. Conclusions The combined model incorporating clinical, conventional MRI, and radiomic features could be applied to predict preoperative CSF dissemination for children with MB as a noninvasive biomarker, which could aid in risk evaluation.

The COVID-19 pandemic continues to overwhelm global healthcare systems. While the disease primarily causes pulmonary complications, reports of central nervous system (CNS) involvement have recently emerged ranging from encephalopathy to stroke. This raises a practical dilemma for clinicians as to when to pursue neuroimaging and lumbar tap with cerebrospinal fluid (CSF) analysis in COVID-19 patients with neurological symptoms. We present a case of an encephalopathic patient infected with SARS-CoV-2 with no pulmonary symptoms. We propose a three-tier risk stratification for CNS COVID-19 aiming to help clinicians to decide which patients should undergo CSF analysis. The neurological examination remains an integral component of screening and evaluating patients for COVID-19 considering the range of emerging CNS complications.

Meroanencephaly occurs when there is an incomplete open median calvarial defect. This condition, which is in the spectrum of anencephaly, results in ectopic brain without skin covering and a normal foramen magnum. We present a rare case of a female fetus with meroanencephaly referred to our institution at 24 weeks and imaged with both prenatal ultrasound and MRI, demonstrating an open neural tube defect in the high parietal area and lack of visualization of the supratentorial ventricular system. Postnatal the child survived and went on to require antibiotic therapy and closure of the defect without cerebral spinal fluid diversion but demonstrates severe permanent neurologic deficits.

PURPOSE Our purpose was to assess our proposed new synthetic MRI (synMRI) technique, combined with T2-based water suppression (T2wsup), to reduce cerebral spinal fluid (CSF)-partial volume effects (PVEs). These PVEs are problematic in the T2-weighted fluid-attenuation inversion recovery (FLAIR) images obtained by conventional synMRI techniques. METHODS Our T2wsup was achieved by subtracting additionally acquired long TE spin echo (SE) images of water signals dominant from the originally acquired images after T2 decay correction and a masking on the long TE image using the water volume (Vw) map to preserve tissue SNR, followed by quantitative mapping and then calculation of the synthetic images. A simulation study based on a two-compartment model including tissue and water in a voxel and a volunteer MR study were performed to assess our proposed method. Parameters of long TE and a threshold value in the masking were assessed and optimized experimentally. Quantitative parameter maps of standard and with T2wsup were generated, then wsup-synthetic FLAIR and SE images were calculated using those suitable combinations and compared. RESULTS Our simulation clarified that the CSF-PVE artifacts in the standard synthetic FLAIR increase T2 as the water volume increases in a voxel, and the volunteer MR brain study demonstrated that the hyperintense artifacts on synthetic images were reduced to

BACKGROUND Lumbar puncture (LP) is a frequently performed diagnostic and therapeutic procedure in oncology patients. Transfusing to a minimum preprocedural platelet threshold of 50 × 109 /L is widely upheld without good quality evidence. The objective was to compare the outcomes of LPs performed with platelets above and below this threshold. An increased risk of adverse events in patients with lower platelet counts was not expected. As a corollary, transfusion reaction rates incurred by transfusing to this recommended threshold are also reported. METHODS A total of 2259 LPs performed on 1137 oncology patients (adult, n = 871, and pediatric, n = 266) were retrospectively analyzed between February 2011 and December 2017. The incidence of LP-related complications for groups above and below the minimum platelet threshold was compared. Traumatic tap was defined as 500 or more red blood cells per high-power field in the cerebral spinal fluid. Groups were compared using the 2-Proportion Z-test and Fisher exact test. RESULTS At time of LP, the total number of events with platelets less than 50 × 109 /L and 50 × 109 /L or greater were 110 and 2149, respectively. There were no significant differences in LP-associated complications between patients with platelet counts above or below 50 × 109 /L (P = .29). Patients with a pre-LP platelet count of less than 50 × 109 /L had a higher proportion of traumatic taps (P

Cathepsin B (CatB), a lysosomal cysteine protease, is important to brain function and may have dual utility as a peripheral biomarker of moderate-severe traumatic brain injury (TBI). The present study determined levels of pro- and mature (mat) CatB protein as well as cysteine protease activity within the frontal cortex (FC; proximal injury site), hippocampus (HC; distal injury site), and cerebral spinal fluid (CSF) collected 1–7 days after craniotomy and penetrating ballistic-like brain injury (PBBI) in rats. Values were compared with naïve controls. Further, the utility of CatB protein as a translational biomarker was determined in CSF derived from patients with severe TBI. Craniotomy increased matCatB levels in the FC and HC, and led to elevation of HC activity at day 7. PBBI caused an even greater elevation in matCatB within the FC and HC within 3–7 days. After PBBI, cysteine protease activity peaked at 3 days in the FC and was elevated at 1 day and 7 days, but not 3 days, in the HC. In rat CSF, proCatB, matCatB, and cysteine protease activity peaked at 3 days after craniotomy and PBBI. Addition of CA-074, a CatB-specific inhibitor, confirmed that protease activity was due to active matCatB in rat brain tissues and CSF at all time-points. In patients, CatB protein was detectable from 6 h through 10 days after TBI. Notably, CatB levels were significantly higher in CSF collected within 3 days after TBI compared with non-TBI controls. Collectively, this work indicates that CatB and its cysteine protease activity may serve as collective molecular signatures of TBI progression that differentially vary within both proximal and distal brain regions. CatB and its protease activity may have utility as a surrogate, translational biomarker of acute-subacute TBI.

We aimed to investigate the CXCL13 concentration of the serum and cerebral spinal fluid (CSF) in human immunodeficiency virus (HIV)-negative latent syphilis patients with treatment failure and explore the change in CXCL13 after treatment. Sixty-eight latent syphilis patients with treatment failure (failure group), 68 syphilis patients with successful treatment (seroconversion group) and 18 patients with non-inflammatory diseases of the nervous system (control group) were included and serum and CSF were collected. Enzyme-linked immunosorbent assay was employed to detect the CXCL13 in the serum and CSF. Results showed that the serum CXCL13 concentration was comparable among three groups, and the CSF leukocyte count, IgG index and CXCL13 concentration in the failure group were significantly higher than those in the seroconversion group and control group (P < 0.05, P < 0.01). CSF CXCL13 concentration in the failure group was positively related to the CSF leukocyte count (r = 0.3594, P < 0.001). Of the 68 patients in the treatment failure group, neurosyphilis was found in 17 (25.0%). In conclusion, involvement of nervous system is one of the reasons for the treatment failure in patients with latent syphilis. Detection of CSF CXCL13 concentration is helpful for the diagnosis and therapeutic evaluation of HIV-negative latent syphilis patients with treatment failure and neurosyphilis.

Dravet syndrome (DS) is a neurodevelopmental genetic disorder caused by mutations in the SCN1A gene encoding the α subunit of the NaV1.1 voltage-gated sodium channel that controls neuronal action potential firing. The high density of this mutated channel in GABAergic interneurons results in impaired inhibitory neurotransmission and subsequent excessive activation of excitatory neurons. The syndrome is associated with severe childhood epilepsy, autistic behaviors, and sudden unexpected death in epilepsy. Here, we compared the rescue effects of an adeno-associated viral (AAV) vector coding for the multifunctional β1 sodium channel auxiliary subunit (AAV-NaVβ1) with a control vector lacking a transgene. We hypothesized that overexpression of NaVβ1 would facilitate the function of residual voltage-gated channels and improve the DS phenotype in the Scn1a+/- mouse model of DS. AAV-NaVβ1 was injected into the cerebral spinal fluid of neonatal Scn1a+/- mice. In untreated control Scn1a+/- mice, females showed a higher degree of mortality than males. Compared with Scn1a+/- control mice, AAV-NaVβ1-treated Scn1a+/- mice displayed increased survival, an outcome that was more pronounced in females than males. In contrast, behavioral analysis revealed that male, but not female, Scn1a+/- mice displayed motor hyperactivity, and abnormal performance on tests of fear and anxiety and learning and memory. Male Scn1a+/- mice treated with AAV-NaVβ1 showed reduced spontaneous seizures and normalization of motor activity and performance on the elevated plus maze test. These findings demonstrate sex differences in mortality in untreated Scn1a+/- mice, an effect that may be related to a lower level of intrinsic inhibitory tone in female mice, and a normalization of aberrant behaviors in males after central nervous system administration of AAV-NaVβ1. The therapeutic efficacy of AAV-NaVβ1 in a mouse model of DS suggests a potential new long-lasting biological therapeutic avenue for the treatment of this catastrophic epilepsy.

Glutamate is a nonessential amino acid and a putative neurotransmitter. When its consumption exceeds its synthesis, it becomes necessary to monitor its levels. Hence, a low-cost, sensitive and real-time monitoring of glutamate to quantify pain and detect neurodegenerative diseases is imperative to improve pharmacotherapy and early diagnosis for health care. While enzymatic electrochemical sensors are promising to address issues in lab-based detection techniques, non-enzymatic sensors are better due to their higher stability and lower cost. In this review, we aim to discuss the recent advances and remaining challenges of sensing glutamate in biofluids. First, we discuss the metabolic routes of glutamate, followed by its transmission processes to the biofluids. Second, we identify the connection of glutamate to pathologies as a potential biomarker. Third, we emphasize electrochemical sensors instantaneously detect glutamate in biofluids in real-time, quantifying pain and monitoring neurodegenerative diseases. The literature shows the concentration of glutamate in biofluids, such as plasma, cerebral spinal fluid, urine, and saliva are in the range of 5–100 μM, 0.5–2 μM, 8.5 (3.3–18.4) μM mM−1 creatinine, and 0.232 ± 0.177 μM respectively. While these concentration levels are sometimes lower than the detection limit of electrochemical sensors, functionalization of the nanomaterials currently being used such as NiO and Co3O4 with carbon nanotubes or beta-cyclodextrin may improve the sensing performance. Another key challenge in the research is to develop relationships between glutamate and biofluids. Finally, we have to advance electrochemical sensors that are compatible to detect glutamate in physiological conditions for long durations of time.

Cerebrospinal fluid (CSF) leakage is a common complication after neuroendoscopic surgery through a burr hole and can lead to further complications including infection.We describe the use of a dural substitute larger than the burr hole itself, placed over the burr hole and then secured underneath a burr hole cover by microscrews running through the graft itself into the underlying skull.This simple technical modification contributes to achieving a watertight seal to aid in preventing CSF leakage in this setting.Our technical modification of endoscopy through a burr hole may help to prevent postoperative CSF leak and secondary CSF infections.

Stroke is the destruction of brain function and structure, and is caused by either cerebrovascular obstruction or rupture. It is a disease associated with high mortality and disability worldwide. Brain edema after stroke is an important factor affecting neurologic function recovery. The glymphatic system is a recently discovered cerebrospinal fluid (CSF) transport system. Through the perivascular space and aquaporin 4 (AQP4) on astrocytes, it promotes the exchange of CSF and interstitial fluid (ISF), clears brain metabolic waste, and maintains the stability of the internal environment within the brain. Excessive accumulation of fluid in the brain tissue causes cerebral edema, but the glymphatic system plays an important role in the process of both intake and removal of fluid within the brain. The changes in the glymphatic system after stroke may be an important contributor to brain edema. Understanding and targeting the molecular mechanisms and the role of the glymphatic system in the formation and regression of brain edema after stroke could promote the exclusion of fluids in the brain tissue and promote the recovery of neurological function in stroke patients. In this review, we will discuss the physiology of the glymphatic system, as well as the related mechanisms and therapeutic targets involved in the formation of brain edema after stroke, which could provide a new direction for research against brain edema after stroke.

Spontaneous cerebrospinal fluid (CSF) rhinorrhea is a rare occurrence. We present a case of spontaneous CSF rhinorrhea in a 57-year-old patient secondary to a sphenoid osseous defect involving the foramen rotundum and maxillary nerve with an associated arachnoid cyst and meningocele compressing the maxillary nerve. The location of the defect made correction amenable to an open skull-based approach. To the best of our knowledge, this is the first reported case of a spontaneous meningocele herniating into the sphenoid osseous defect through the medial aspect of the foramen rotundum. Early detection of these defects, open or endoscopic approaches and definitive treatment by closing the defect can result in excellent outcomes.

OBJECTIVES: The incidence of neonatal herpes simplex virus (nHSV) infections is monitored periodically in the Netherlands, yet management and outcome is unknown. Comprehensive national guidelines are lacking. We aim to describe management and outcome in the last decade to explore current diagnostic and therapeutic challenges. We aim to identify possible variability in management of patients with a suspected nHSV infection. METHODS: We conducted a retrospective case series of management and outcome of nHSV infections at 2 tertiary care center locations in the Netherlands. RESULTS: An nHSV infection was diagnosed in 1% (12 of 1348) of patients in whom polymerase chain reaction for HSV was performed. Of the patients with nHSV infection, 3 of 12 died, and 4 of 9 (44%) survivors suffered neurologic sequelae. Neurologic symptoms at presentation were seen in only 2 of 8 patients with nHSV encephalitis. A cerebral spinal fluid analysis was performed in 3 of 6 patients presenting with skin lesions. Only 3 of 6 patients with neurologic symptoms received suppressive therapy. nHSV infection was diagnosed in 8 of 189 (4%) patients who were empirically treated. CONCLUSIONS: Management of nHSV infection, particularly when presented with skin lesions, is inconsistent. Many infants without a HSV infection are exposed to antiviral medication. There is substantial interhospital variation in diagnostic and therapeutic management of a suspected infection. Comprehensive guidelines need to be developed to standardize management of suspected nHSV infection.

We studied relationships of cerebral spinal fluid (CSF) pulsatile flow at cervical, thoracic, and lumbar levels using phase-contrast cine MRI (PCCMRI) to determine the following: 1) instantaneous and average net flows at cervical, thoracic, and lumbar levels, 2) stochastic correlations of CSF flow with major arterial supplies and major draining veins, and 3) whether adjustments of cord-flow curves—using cord cross-sectional areas, caudal lengths, and caudal volumes—would normalize flow curves from different levels. We scanned 15 healthy volunteers without anesthesia, ages 23–46 yr, using external, retrocardiac-gated, two-dimensional PCCMRI at 3T. Transverse scans of the subarachnoid space, arteries, and veins were acquired and analyzed at cervical, thoracic, and lumbar levels. Instantaneous CSF flow decreased craniocaudally along the full time course of a cardiac cycle. Downward net flow generally increased craniocaudally. During diastole, instantaneous CSF flow decreased proportionally to cross-sectional area, caudal residual length, and caudal residual volume of the cord. The proportionalities were less consistent during systole. CSF, internal carotid artery (ICA), vertebral artery, and lower aorta temporal correlations were highest in systole and decreased craniocaudally. CSF flow temporally correlated better with lower aorta flow than with the ICA at T7 and L2 during systole but not diastole. Inferior vena cava temporal correlation increased craniocaudally. We conclude that whereas instantaneous flow is attenuated cranial caudally, net downward flow, per cardiac cycle, increases caudally, becoming statistically significant at T7 and below the conus medullaris. We can explain the results with the assumption of cord CSF production and peripheral-dominated CSF absorption.

Many previous studies have investigated the use of post-mortem biochemistry to estimate the post-mortem interval (PMI). Vitreous humour (VH) potassium and sodium/chloride levels are well recognized...

OBJECTIVE: To describe the clinical presentation, advanced imaging findings, and short‐ and long‐term outcomes in dogs with intracranial empyema. DESIGN: Retrospective case series. ANIMALS: Client‐owned dogs diagnosed with intracranial empyema. METHODS: Medical records from 2 referral hospitals were searched for dogs diagnosed with intracranial empyema. To be included in this study, dogs had to fulfill 1 or more of the following 3 inclusion criteria: a magnetic resonance imaging (MRI) scan with space occupying accumulation of extra‐axial material suggestive of empyema, a cerebrospinal fluid analysis suggestive of empyema, or direct visualization of purulent material during intracranial surgery. RESULTS: Nine dogs with intracranial empyema were included, with a median age of 3.5 years (range: 4 mo–12.5 y). All presented as emergencies with 7 of the 9 dogs showing neurological abnormalities and 2 of the 9 with retrobulbar swelling and exophthalmos. Six had surgical intervention, 1 was medically managed, and the remaining 2 dogs were euthanized. Typical MRI findings included extra‐axial, T1‐weighted hypo‐ to isointense, T2‐weighted hyperintense material compared to gray matter with varying degrees of contrast enhancement, with 6 of 8 showing evidence of contiguous infection from adjacent structures on MRI. For 7 dogs, ≥1 samples were sent for culture and sensitivity, with Enterococcus (surgical swab), Streptococcus pneumonia (from cerebral spinal fluid), and coagulase positive Staphylococcus (ear swab) being cultured. The median antimicrobial course length was 6 weeks (range: 2–28 wk). All dogs for which treatment was attempted survived to discharge, with a median hospitalization time of 7 days (range: 4–10 d). Four of the 7 are still alive at the time of writing (1 lost to follow‐up; 2 euthanized for other reasons) with all 4 considered neurologically normal with a successful long‐term outcome. CONCLUSION: Although intracranial empyema in dogs is a rare condition, excellent outcomes are possible in those cases treated appropriately.

The incidence of meningoencephalitis in developing countries is high and its diagnosis being inadequate as it is mainly based on conventional methods with a limited diagnostic capacity for bacterial, fungal and viral detection. This results in prescription of a cocktail of antibiotics, antifungal, or anti-viral drugs, since the causative agent is often unknown. There is therefore need for timely and appropriate diagnosis to guide treatment. This study aims at evaluating the utility of molecular diagnostic over conventional methods in detection of etiologic agents of central nervous system infections in Rwanda. Using a cross sectional design, 845 hospitalized patients suspected to have meningoencephalitis were enrolled from 8 study sites across the country. Four sterile tubes of Cerebral Spinal Fluid (CSF) specimens were collected from each patient. Two tubes were analyzed on site for bacteriology, fungal, biochemistry and cytology while the other two were transported to the National Reference Laboratory (NRL) for culture and Real-Time Multiplex Polymerase Chain Reaction (PCR) assays. Data entry and analysis was done using Epi Info7, Excel; SPSS and STATA16. In the study, no viruses were detected using the conventional methods while a range of viruses, 152/845 (18%) were detected using real time multiplex PCR. In addition, 185/845 (22%) samples were detected as positive for different types of bacteria using the PCR compared with the 59/845(7%) that were positive using conventional methods. There was however no difference in the detection capacity of fungal agents between the two methods with a detection level of 6% (49). This study has shown increased capacity for detection of bacterial and viral causative agents of Central Nervous System (CNS) infections using RT multiplex PCR compared with conventional methods. This result facilitated the development of a novel algorithm for both conventional and molecular diagnostic methods for CNS infections. Key words: Meningoencephalitis, RT- Multiplex PCR, conventional methods, causative agents, diagnostic capacity, cerebral spinal fluid.

ObjectiveThe purpose of this study was to verify that hypothalamus-pituitary dysfunction is one of the risk factors for postoperative central nervous system infections (PCNSIs).MethodWe performed a retrospective analysis of all patients with sellar region lesions who underwent surgery between January 2016 and November 2019 at Peking Union Medical College Hospital. In total, 44 age− and sex-matched controls were enrolled. Univariate and multivariate analyses were performed to identify risk factors for PCNSIs.ResultWe enrolled 88 patients, 44 of whom had PCNSIs. Surgical approach (TCS) (P+ levels(ConclusionTCS, intraoperative CSF leakage, postoperative DI and postoperative adrenal insufficiency are risk factors for PCNSIs in patients with sellar region tumors.

Quantification of proton magnetic resonance spectroscopy (1 H-MRS) data is commonly performed by referencing the ratio of the signal from one metabolite, or metabolite group, to that of another, or to the water signal. Both approaches have drawbacks: ratios of two metabolites can be difficult to interpret because study effects may be driven by either metabolite, and water-referenced data must be corrected for partial volume and relaxation effects in the water signal. Here, we introduce combined reference (CRef) analysis, which compensates for both limitations. In this approach, metabolites are referenced to the combined signal of several reference metabolites or metabolite groups. The approach does not require the corrections necessary for water scaling and produces results that are less sensitive to the variation of any single reference signal, thereby aiding the interpretation of results. We demonstrate CRef analysis using 202 1 H-MRS acquisitions from the brains of 140 infants, scanned at approximately 1 and 3 months of age. We show that the combined signal of seven reference metabolites or metabolite groups is highly correlated with the water signal, corrected for partial volume and relaxation effects associated with cerebral spinal fluid. We also show that the combined reference signal is equally or more uniform across subjects than the reference signals from single metabolites or metabolite groups. We use CRef analysis to quantify metabolite concentration changes during the first several months of life in typically developing infants.

Amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, leads to the loss of motor neurons. There are currently no effective therapies to treat this disease as the molecular mechanisms of motor neuron degeneration are largely unknown. The diagnosis of ALS, or motor neuron disease, is not a simple process that can be carried out with one doctor visit or a single simple test. This has created a major problem for patients with ALS and their physicians since they are often not diagnosed until about a year into the disease. In order to combat this issue, new techniques of detecting the clinical and pathological changes of the disease are critical. These techniques are currently being studied and developed which can revolutionize the diagnosis of ALS. Once this technology is established, it may have application to monitor the progression of the disease. RNA-Seq is a powerful tool that has potential to identify RNA as small molecules in patients' biological samples (Plasma, Cerebral Spinal Fluid) which can be used to inform the system changes in patients with ALS. In this review, we will explore and discuss our current work on RNA-Seq and its development of biomarkers to diagnose and assess the rate of progression in the disease.

Background Post-Infectious Neurological Syndromes (PINS) are heterogeneous neurological disorders with post or para-infectious onset. PINS diagnosis is complex, mainly related to the absence of any recognized guidelines and a univocal definition. Aim of the study To elaborate a diagnostic guide for PINS. Materials and methods We retrospectively analysed patients younger than 14 years old admitted to Bambino Gesù Children’s Hospital in Rome for PINS from December 2005 to March 2018. Scientific literature using PubMed as research platform was analysed: the key words “Post-Infectious Neurological Syndromes” were used. Results A polysymptomatic presentation occurred in a percentage of 88% of the children. Motor signs and visual disturbances the most observed symptoms/signs were the most detached, followed by fever, speech disturbances, sleepiness, headache and bradipsychism. Blood investigations are compatible with inflammation, as a prodromal illnesses was documented in most cases. Normal cerebral spinal fluid (CSF) characteristics has been found in the majority of the study population. Magnetic resonance imaging (MRI) was positive for demyelinating lesions. Antibiotics, acyclovir and steroids have been given as treatment. Discussion We suggest diagnostic criteria for diagnosis of PINS, considering the following parameters: neurological symptoms, timing of disease onset, blood and CSF laboratory tests, MRI imaging. Conclusions We propose criteria to guide clinician to diagnose PINS as definitive, probable or possible. Further studies are required to validate diagnostic criteria.

The glymphatic system is a relatively new concept that has been associated with regulation of cerebrospinal fluid (CSF), as well as brain waste clearance. Novel techniques to study glymphatic dysfunction have in turn prompted new concepts pertaining to brain physiology and have reviewed interest in understanding the underlying elements of neurological disease. This review incorporates a radiologic and human imaging perspective that focuses on contemporary understanding of the regulation of CSF flow, expanding the putative clinical relevance of this system and the relationships between CSF flow and glymphatic function. MR imaging studies, especially those that employ intrathecal gadolinium contrast, have identified potentially new pathways that may regulate CSF production, absorption, and clearance. These studies particularly emphasize putative mechanisms for brain waste clearance. Glymphatic flow around cranial nerves and within the subarachnoid region may be under-investigated, and could be related to various pathophysiologic processes in neurodegeneration. We emphasize several clinical exemplars of CSF clearance that point to the interaction between the epidural space, perivascular spaces, and the neurovascular unit. Given insufficient understanding of these interactions, further studies should focus on techniques addressing glymphatic functionality and potentially linking this system to neurological disease.

Purpose of review Subarachnoid neurocysticercosis (SUBNCC) is caused by a morphologically unique proliferative form of Taenia solium involving the subarachnoid spaces. Prolonged therapy based upon the pathophysiology of SUBNCC and long-term follow-up have shed light on the course of disease and led to highly improved outcomes. Recent findings SUBNCC has a prolonged incubation period of between 10 and 25 years characterized by cyst proliferation and growth and invasion of contiguous spaces leading to mass effect (Stage 1). With induction of the host-immune responses, cysts degenerate leading to a predominately inflammatory arachnoiditis (Stage 2) causing hydrocephalus, infarcts, and other inflammatory based neurological manifestations. Inactive disease (Stage 3) may occur naturally but mostly is a result of successful treatment, which generally requires prolonged intensive anthelminthic and antiinflammatory treatments. Cerebral spinal fluid cestode antigen or cestode DNA falling to nondetectable levels predicts effective treatment. Prolonged treatment with extended follow-up has resulted in moderate disability and no mortality. Repeated short intensive 8-14-day courses of treatment are also used, but long-term outcomes and safety using this strategy are not reported. Summary SUBNCC gives rise to a chronic arachnoiditis. Its unique ability to proliferate and induce inflammatory responses requires long-term anthelmintic and antiinflammatory medications.

Acute RNA viral encephalomyelitis is a serious complication of numerous virus infections. Antibodies in the cerebral spinal fluid (CSF) are correlated to better outcomes, and there is substantive evidence of antibody secreting cells (ASCs) entering the central nervous system (CNS) and contributing to resolution of infection. Here, we review the RNA viruses known to cause acute viral encephalomyelitis with mechanisms of control that require antibody or ASCs. We compile the cytokines, chemokines, and surface receptors associated with ASC recruitment to the CNS after infection and compare known antibody-mediated mechanisms as well as potential noncytolytic mechanisms for virus control. These non-canonical functions of antibodies may be employed in the CNS to protect precious non-renewable neurons. Understanding the immune-specialized zone of the CNS is essential for the development of effective treatments for acute encephalomyelitis caused by RNA viruses.

Hydrocephalus is a common neurosurgical pathology associated with high patient morbidity and systemwide healthcare costs. A significant portion of these costs are related to the failure of ventricular shunting systems. Despite decades of research and technological development, the rate of shunt failure and revision has not significantly improved. The Reflow™ Ventricular System (Anuncia, Inc., Lowell, MA) is a recent technological development with the potential to prolong the shunt lifespan. This system introduces a noninvasive means of flushing a shunt proximally with a controlled, repeatable pulse of cerebral spinal fluid (CSF) and of creating a new ventricular opening for occluded shunts. In this multicenter case series, we present the early clinical experiences with this device and discuss its potential.

Listeria rhombencephalitis (L. rhombencephalitis) is an uncommon form of central nervous system infection caused by Listeria monocytogenes (LM). It often occurs to immunocompetent individuals. Here, we described the case of a 45-year-old female patient without medical histories, who presented for high-grade fever, headache, and focal neurological manifestations. She was initially empirically diagnosed with acute disseminated encephalomyelitis (ADEM) because of clinical symptoms, acute clinical course, and neuroimaging. However, the biochemical analysis of cerebral spinal fluid (CSF) questioned the diagnosis of ADEM. The final diagnosis of L. rhombencephalitis was based on CSF culture for LM. Thus, L. rhombencephalitis should be preferentially and empirically considered for a patient with significantly elevated lactic acid and moderately increased red cells in CSF at early time, accompanied with rapidly progressive neurological dysfunctions involved in the brain stem.

The interfacial condition between the human brain and the skull is complex and has been difficult to emulate in a surrogate system. Surrogate head models have typically been built using a homogenous viscoelastic material to represent the brain, but the effect of different interfacial conditions between the brain and the skull on pressure transduction into the brain during blast has not been studied. In the present work, three interfacial conditions were generated in physical surrogate human head models. The first surrogate consisted of a gel brain separated from the skull by a layer of saline solution similar in thickness to the cerebrospinal fluid (CSF) layer in the human head: the fluid interface head model. The second surrogate head had the entire cranial cavity filled with the gel: the fixed interface head model. The third surrogate head contained a space-filling gel brain wrapped in a thin plastic film: the stick-slip interface head model. The human head surrogates were evaluated in a series of frontal blast tests to characterize the effect of the skull-brain interfacial conditions on overpressure propagation into the gel brains. The fixed and the stick-slip interface head models showed nearly equal peak brain overpressures. In contrast, the fluid interface head model had much higher in-brain peak overpressures than the other two models, thus representing the largest transmission of forces into the gel brain. Given that the elevated peak overpressures occurred only in the fluid interface head model, the presence of the saline layer is likely responsible for this increase. This phenomenon is hypothesized to be attributed to the incompressibility of the saline and/or the impedance differences between the materials. The fixed interface head model showed pronounced high frequency energy content relative to the other two models, implying that the fluid and the stick-slip conditions provided better dampening. The cumulative impulse energy entering the three brain models were similar, suggesting that the interface conditions do not affect the total energy transmission over the positive phase duration of a blast event. This study shows that the fidelity of the surrogate human head models would improve with a CSF-emulating liquid layer.

One challenge in conducting DNA methylation-based epigenome-wide association studies (EWAS) is the appropriate cleaning and quality-checking of the methylation values to minimize biases and experimental artifacts, while simultaneously retaining potential biological signals. These issues are compounded in studies that include multiple tissue types, and/or tissues for which reference data are unavailable to assist in adjusting for cell-type mixture, for example cerebral spinal fluid (CSF). For our study that evaluated blood and CSF taken from aneurysmal subarachnoid hemorrhage (aSAH) patients, we developed a protocol to clean and quality-check genome-wide methylation levels and compared the methylomic profiles of the two tissues to determine whether blood is a suitable surrogate for CSF. CSF samples were collected from 279 aSAH patients longitudinally during the first 14 days of hospitalization, and a subset of 88 of these patients also provided blood samples within the first two days. Quality control (QC) procedures included identification and exclusion of poor performing samples and low-quality probes, functional normalization, and correction for cell-type heterogeneity via surrogate variable analysis (SVA). Significant differences in rates of poor sample performance was observed between blood (1.1% failing QC) and CSF (9.12% failing QC; p = 0.003). Functional normalization increased the concordance of methylation values among technical replicates in both CSF and blood. Likewise, SVA improved the asymptotic behavior of the test of association in a simulated EWAS under the null hypothesis. To determine the suitability of blood as a surrogate for CSF, we calculated the correlation of adjusted methylation values between blood and CSF globally and by genomic regions. Overall, mean correlation (r < 0.26) was low, suggesting that blood is not a suitable surrogate for global methylation in CSF. However, differences in the magnitude of the correlation were observed by genomic region (CpG island, shore, shelf, open sea; p < 0.001 for all) and orientation with respect to nearby genes (3’ UTR, transcription start site, exon, body, 5’ UTR; p < 0.01 for all). In conclusion, the correlation analysis and QC pipelines indicated that DNA extracted from blood was not, overall, a suitable surrogate for DNA extracted from CSF in aSAH methylomic studies.

Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder characterized by motor and vocal tics. There are several hypotheses as to the cause of the disease. One of which suggests that the immune system is involved in the pathophysiology of GTS. Here, we present a 40-year-old female patient with a typical history and clinical presentation of GTS with tics and psychiatric comorbidities, in whom positive oligoclonal bands (OCBs) type 2 in cerebral spinal fluid (CSF) were detected in an earlier study. At that time point, all other investigations were unremarkable (including neurological examination and cMRI), but 2 years later, she presented with further neurological symptoms including tetraparesis mostly affecting the left limbs, distal hypesthesia and paresthesia, and dyspnea. Since further examinations (including EMG, MRI, CSF, virological, and bacteriological tests, as well as autoimmune-encephalitis antibodies) revealed normal results, based on clinical presentation, the diagnosis of Guillain-Barre-like immune-mediated neuropathy was made and treatment with intravenous immunoglobulins (IVIg) (30 g/day for 5 days) was initiated resulting in complete remission of immune-mediated neuropathy. Based on the "immune hypothesis" of GTS, we were interested in whether in this patient positive CSF OCBs might serve as a biomarker for treatment response of tics and additional GTS-related psychiatric symptoms to IVIg, and therefore assessed tics, premonitory urges, and psychiatric comorbidities before and several times after the IVIg treatment. However, even though immune-mediated neuropathy resolved after treatment, tics, premonitory urges, and comorbidities remained unchanged. Thus, this case study suggests that treatment with IVIg is not effective in the treatment of GTS-even in a patient with intrathecal antibody synthesis as expressed by CSF isolated OCBs.

This seems to be the time to gain new knowledge about the meningeal lymphatic system and a deeper understanding of its anatomy and physiology. Although it is known that the meningeal lymphatics present in the layers of the brain, limited information is available about the role of this system in brain function. Here, for the first time we clearly demonstrate that the meningeal lymphatic pathway is involved in brain clearing from the blood after intracranial hemorrhage associated with hypoxia and forms a connective bridge between interstitial, cerebral spinal fluid and peripheral lymphatics. We also show that the development of methods to stimulate meningeal lymph flow after hemorrhagic evidence in the brain might be a neuroprotective strategy for effective recovery of the brain after a cerebrovascular catastrophe.

Dural substitutes are commonly utilized to repair dural defects incurred during routine neurosurgical procedures. The present study aims to examine whether the resorption rate of a novel non-biologic, fully-resorbable nanofabricated dura substitute is suitable for effective repair of large dural defects.Small or large dural defects were created bilaterally in a canine duraplasty model and then repaired with the nanofabricated dura substitute. Animals were monitored post-operatively for signs of cerebral spinal fluid (CSF) leak and neurological abnormalities. Repair sites were explanted 4 or 13 weeks after surgery and evaluated by histopathology to assess neoduralization, implant resorption, and local inflammation.The nanofabricated dura substitute was observed to prevent CSF leakage and infection. Histopathology confirmed that the gradual resorption of the graft was balanced by increasing neoduralization over time and revealed comparable neoduralization and vascularization between small and large defects both 4 and 13 weeks after surgery. By week 13 all defects were healed with complete neoduralization across the implant site.The nanofabricated dura substitute demonstrated an optimal time course of resorption suited for repair of both large and small dural defects. The present study demonstrates the ability of the nanofabricated dura substitute to regenerate pristine dura in variable size defects. Keywords: Animal model, Nanofabricated dura substitute, Histology

Closed brain injuries are a common danger in contact sports and motorized vehicular collisions. Mild closed brain injuries, such as concussions, are not easily visualized by computed imaging or scans. Having a comprehensive head/brain model and using fluid-structure interaction (FSI) simulations enable us to see the exact movement of the cerebrospinal fluid (CSF) under such conditions and to identify the areas of brain most affected.The presented work is based on the first FSI model capable of simulating the interaction between the CSF flow and brain.FSI analysis combining smoothed-particle hydrodynamics and high-order finite-element method is used.The interaction between the CSF and brain under rapid acceleration and deceleration is demonstrated. The cushioning effect of the fluid and its effect on brain are shown.The capability to locate areas (down to the exact gyri and sulci) of the brain the most affected under given loading conditions, and therefore assess the possible damage to the brain and consequently predict the symptoms, is shown.

Background Context During placement of C2 pedicle and pars screws, intraoperative fluoroscopy is used so that neurovascular complications can be avoided, and screws can be placed in the proper position. However, this method is time consuming and increases radiation exposure. Furthermore, it does not guarantee a completely safe and accurate screw placement. Purpose The objective of this study was to evaluate the safety of the C2 pedicle and pars screw placement without fluoroscopic or other guidance methods. Study Design This is a retrospective comparative study. Patient Sample One hundred ninety-eight patients who underwent placement of C2 pedicle or pars screws without any intraoperative radiographic guidance were included in the study. Outcome Measures Medical records and postoperative computed tomography (CT) scans were evaluated. Materials and Methods Clinical data were reviewed for intraoperative and postoperative complications. The accuracy of screw placement was evaluated with postop CT scans using a previously published cortical-breach grading system (described by the location and the percentage of the screw diameter over the cortical edge [0=none, Grade I≤25% of the screw diameter, Grade II=26%–50%, Grade III=51%–75%, and Grade IV=76%–100%]). Results A total of 148 pedicle screws and 219 pars screws were inserted by two experienced surgeons. There were no cases of cerebral spinal fluid leakage and no neurovascular complications during screw placement. Postoperative CT scans were available for 76 patients, which included 52 pedicle screws and 87 pars screws. For cases with C2 pedicle screws, there were 12 breaches (23%); these included 10 screws with a Grade I breach (19%), 1 screw with a Grade II breach (2%), and 1 screw with a Grade IV breach (2%). Lateral breaches occurred in seven screws (13%), inferior breaches occurred in three screws (6%), and superior breaches occurred in two screws (4%). For cases with C2 pars screws, there were 10 breaches (11%); these included 6 screws with a Grade I breach (7%), 2 screws with a Grade II breach (2%), and 2 screws with a Grade IV breach (2%). Medial breaches were found in four (5%), lateral breaches in two (2%), inferior breaches in two (2%), and superior breaches in two (2%). Two of the cases with superior breaches (one for pedicle and one for pars) experienced occipital neuralgia months after surgery. There was no statistically significant difference in the incidence of overall and high-grade breaches between the groups (p=.07 and 1.0, respectively). Conclusions Although even in experienced hands up to 23% of C2 pedicle screws and 11% of C2 pars screws placed using a freehand technique without guidance may be malpositioned, a clear majority of malpositioned screws demonstrated a low-grade breach, and only 2 of 198 patients (1%) experienced complications related to screw placement.

Introduction Brachytherapy is a major adjuvant modality for neoplasms, but few have trialed its use for spinal tumors. This study examines perioperative and oncologic outcomes of patients with malignant spinal tumors who underwent resection with intraoperative phosphorous-32 (P32) brachytherapy. Methods Consecutive adult patients who underwent P32 brachytherapy during malignant spinal tumor resection were retrospectively identified from 2014 to 2015. Complications, tumor recurrence, and survival were reviewed. A comprehensive review of the literature was performed. Results A total of 8 patients were included. Average age was 54.3 years, and 25.0% were males. Tumor types included metastatic leiomyosarcoma, chordoma, multifocal recurrent ependymomas, breast metastasis, malignant meningioma, and myxofibrosarcoma. One-half of patients underwent en bloc tumor resection. P32 plaques were applied to 2 sites per patient for mean 13.1 minutes per site with a goal penetration of 10 Gy to 1-mm depth. Perioperative complications occurred in 3 patients (37.5%), including a persistent cerebral spinal fluid leak, deep infection requiring reoperation, and sacral insufficiency fracture. At a mean 25.6 months follow-up, local recurrence rate was 25.0%, and overall survival was 75.0%. Mean time to recurrence was 14.4 months. Survival at 6, 12, 18, and 24 months was 100.0%, 100.0%, 85.7%, and 71.4%, respectively. Conclusions The use of P32 is safe and feasible. P32 intraoperative brachytherapy does not seem to increase the rate of complications. The sample size of this series is small with heterogeneity in tumor type, but recurrence and survival outcomes seem promising compared with previous reports. Further clinical trials are needed.

Introducción. La encefalitis viral aguda se define como un proceso inflamatorio asociado a disfunción neurológica con desenlace fatal o daño grave permanente. En México no se han hecho estudios de identificación directa de los agentes etiológicos causales de la encefalitis viral aguda.Objetivo. Identificar mediante PCR en tiempo real los principales agentes virales causantes de encefalitis viral aguda en México.Materiales y métodos. Se obtuvo el líquido cefalorraquídeo de pacientes con sospecha de encefalitis viral que ingresaron al servicio de urgencias del Hospital Civil Fray Antonio Alcalde. Se extrajeron ácidos nucleicos para identificar los patógenos mediante PCR y PCR con transcripción inversa en tiempo real.Resultados. Se captaron un total de 66 pacientes entre el 2011 y el 2014. En 16 de los casos (24 %) se identificó el agente viral y se encontró que el principal agente causal fue el enterovirus, con ocho casos (50 %), seguido del virus del herpes simple (HSV: 37 %), con seis casos, y el citomegalovirus (CMV: 12,5 %), con dos casos. El promedio de edad fue de 25 años (0-70 años). Los casos positivos predominaron en los varones (63,3 %) y se estableció un predominio estacional en otoño (37,5 %).La mayoría de los pacientes presentó fiebre (48,4 %) o cefalea (36,3 %) y, en menor proporción, convulsiones, confusión y debilidad muscular (30,3 %) seguidas de desorientación (28,75 %) y apatía (25,7 %). En dos de los casos se observó el signo de Kerning (3 %) y en otros dos, el signo de Brudzinski (3 %).Conclusiones. La PCR en líquido cefalorraquídeo es una técnica de diagnóstico adecuada para la identificación de virus causales de encefalitis viral, lo cual permite prescribir los medicamentos específicos.

The redox balance of coenzyme Q10 in human plasma is a good marker of oxidative stress because the reduced form of coenzyme Q10 (ubiquinol-10) is very sensitive to oxidation and is quantitatively converted to its oxidized form (ubiquinone-10). Here we describe an HPLC method for simultaneous detection of ubiquinol-10 and ubiquinone-10 in human cerebral spinal fluid to meet a recent demand for measuring local oxidative stress. Since the levels of coenzyme Q10 in human cerebral spinal fluid are less than 1/500 of those in human plasma, cerebral spinal fluid extracted with 2-propanol requires concentration for electrochemical detection. Using human plasma diluted 500-fold with physiological saline as a pseudo-cerebral spinal fluid, we found that addition of tert-butylhydroquinone was effective in preventing the oxidation of ubiquinol-10. The optimized tert-butylhydroquinone concentration in the extraction solvent was 20 µM. The addition of 20 µM ascorbic acid or co-addition of tert-butylhydroquinone and ascorbic acid (20 µM each) were also effective in preventing the oxidation of ubiquinol-10, but ascorbic acid alone gave poor reproducibility. Good within day reproducibility was observed, and day-to-day analytical variance was excellent.

No abstract available Keywords: lysosomal storage disease; mononuclear cell cytoplasmic inclusions; mucopolysaccharidosis type I.

Purpose A gravitational valve (GV) may be used to treat hydrocephalus, offering possible advantages that include avoidance of over drainage and long-term complications. Because a GV is made from metal, there are potential safety and other problems related to the use of MRI. The objective of this investigation was to evaluate MRI-related issues (i.e., magnetic field interactions, heating, and artifacts) for a newly developed, metallic GV. Methods Tests were performed on the GV (GAV 2.0) using well-accepted techniques to assess magnetic field interactions (translational attraction and torque, 3-Tesla), MRI-related heating (1.5-T/64-MH and 3-T/128-MHz, whole body averaged SAR, 2.7-W/kg and 2.9-W/kg, respectively), artifacts (3-Tesla; gradient echo and T1-weighted, spin echo sequences), and possible functional changes related to exposures to different MRI conditions (exposing six samples each to eight different pulse sequences at 1.5-T/64-MHz and 3-T/128-MHz). Results Magnetic field interactions were not substantial (deflection angle 2°, no torque) and heating was minor (highest temperature rise, ≥ 1.9 °C, highest background temperature rise, ≥ 1.7 °C). Artifacts on the gradient echo pulse sequence extended approximately 10 mm from the size and shape of the GV. The different exposures to 1.5-T/64-MHz and 3-T/128-MHz conditions did not alter or damage the operational aspects of the GV samples. Conclusions The findings demonstrated that MRI can be safely used in patients with this GV and, thus, this metallic implant is deemed acceptable or “MR Conditional” (i.e., using current labeling terminology), according to the conditions used in this study.

Leptomeningeal metastasis is an uncommon and typically late complication of cancer with a poor prognosis and limited treatment options. Diagnosis is often challenging, with nonspecific presenting symptoms ranging from headache and confusion to focal neurologic deficits, such as cranial nerve palsies. Standard diagnostic evaluation involves a neurologic examination, magnetic resonance imaging of the brain and spine with gadolinium, and cytologic evaluation of the cerebral spinal fluid. Therapy entails a multimodal approach focused on palliation with surgery, radiation, and/or chemotherapy, which may be administered systemically or directly into the cerebral spinal fluid. Limited trial data exist to guide treatment, and current regimens are based primarily on expert opinion. Although newer targeted and immunotherapeutic agents are under investigation and have shown promise, an improved understanding of the biology of leptomeningeal metastasis and treatment resistance as well as additional randomized controlled studies are needed to guide the optimal treatment of this devastating disease. Cancer 2018;124:21-35. © 2017 American Cancer Society.

Arachnoid cysts (ACs) are intra-arachnoid fluid collections and may be classified as primary or secondary in nature. Neonatal hypoglycemia (NH) is a common, life-threatening metabolic disorder in infants. We present the case of a term infant who suffered severe NH within 72 hours after birth and subsequently developed an acquired Sylvian AC.A child of 13 months of age, with history of severe NH within 72 hours after birth, was admitted after two generalized seizures. Magnetic resonance imaging (MRI) of the brain showed dimensional increase of a left Sylvian AC, not present on imaging on day one of life but revealed with a second MRI at 16 days of age. The timeline of events suggests some kind of correlation between the newborn's metabolic disorder, appearance of the AC, and its progressive expansion. We speculate that NH's organic consequences, i.e., cortical and white matter atrophy might have favored some kind of cerebral spinal fluid (CSF) dynamic alteration and AC development in our patient. Further structured studies are needed to confirm our hypothesis and reveal NH as a risk factor in the pathogenesis of ACs.

CE and microchip CE (ME) are powerful tools for the analysis of a number of different analytes and have been applied to a variety of clinical fields and human samples. This review will present an overview of the most recent applications of these techniques to different areas of clinical medicine during the period of 2014 to mid-2017. CE and ME have been applied to clinical chemistry, drug detection and monitoring, hematology, infectious diseases, oncology, endocrinology, neonatology, nephrology, and genetic screening. Samples examined range from serum, plasma, and urine to lest utilized materials such as tears, cerebral spinal fluid, sweat, saliva, condensed breath, single cells, and biopsy tissue. Examples of clinical applications will be given along with the various detection systems employed.

Headache is one of the most frequent symptoms leading to visits at the emergency department. Here, we aim at presenting a pragmatic algorithm for headache patients at the emergency department. The basic principle is taking a detailed history of the current headache with a focus on dynamics, phenotype and trigger factors as well as a possible preexisting headache. "Red flags" should be interrogated specifically. Hypotheses of the etiology of the headache should be generated in combination with the clinical examination (vital signs, neurological exam, otorhinolaryngological and ophthalmological exams) and should be tested appropriately with imaging, laboratory, cerebral spinal fluid studies and ultrasound. Secondary headache have to be treated with a causal approach, if necessary also symptomatically. When a secondary headache can be excluded, we recommend aiming for a primary headache diagnosis with subsequent specific therapy. When a headache patient can be discharged, we recommend scheduling a follow-up appointment to understand the development of a secondary headache and its cause. In case of a primary headache, optimizing prophylaxis and acute therapy is important to prevent future emergency department visits.

In the history of medicine, one means to progress is when we make the decision that our assumptions and definitions of disease are no longer consistent with the scientific evidence, and no longer serve our health care needs. The arc of scientific progress is now requiring a change in how we diagnose Alzheimer's disease. Both the National Institute on Aging—Alzheimer's Association (NIA-AA) 2011 workgroup and the International Work Group (IWG) have proposed guidelines that use detectable measures of biological changes in the brain, commonly known as biological markers, or biomarkers, as part of the diagnosis. This Special Report examines how the development and validation of Alzheimer's disease biomarkers—including those detectable in the blood or cerebral spinal fluid, or through neuroimaging—is a top research priority. This has the potential to markedly change how we diagnose Alzheimer's disease and, as a result, how we count the number of people with this disease. As research advances a biomarker-based method for diagnosis and treatment at the earliest stages of Alzheimer's disease, we envision a future in which Alzheimer's disease is placed in the same category as other chronic diseases, such as cardiovascular disease or diabetes, which can be readily identified with biomarkers and treated before irrevocable disability occurs.

Advances in medicine mean there are more women with complex medical histories giving birth. This may include women with conditions such as hydrocephalus requiring a cerebrospinal fluid shunt. Midwives should understand the principles of care for such women and work with the multidisciplinary team to provide indiviulaised care throughout the pregnancy and intrapartum period.

MRI has been a rather important imaging technique in clinical diagnosis in recent years. In particular, brain parenchyma classification and segmentation of normal and pathological tissue is the first step of addressing a wide range of clinical problems. Extenics-based methods are applied in this study for MRI brain tissue classification. Initially, the standard deviation target generation process is employed to select the center point of the extenics-based correlation function without supervision. Then particle swarm optimization is used to modify the extenics-based correlation function. In subsequence, the modified extenics-based correlation function is employed to perform classification using individual images to present the gray matter, white matter and cerebral spinal fluid in the brain. Therefore the proposed method reduce the burden of physicians from huge amounts of multi-spectral information in MR images to make diagnostic work more efficient and more accurate.

The high and increasing incidence of Alzheimer Disease (AD) worldwide is a major global concern. Classical diagnosis is carried out in the dementia phase, often in the moderate stages when treatment efficacy is limited. Nowadays, early diagnosis, even in pre-dementia stages, is possible in selected cases within an appropriate clinical setting, employing cerebral spinal fluid (CSF) sample analysis and neuroimaging procedures. In spite of the accurate diagnosis achieved by novel CSF biomarkers or positron emission tomography beta-amyloid tracers, these tests are invasive and expensive. Therefore, important work is being carried out to discover reliable biomarkers in peripheral biofluids (blood, plasma, urine) to be incorporated in clinical routine for early AD diagnosis. Although the nature of AD pathogenesis is complex, it is known that oxidative stress plays a key role, for which biomarkers are easily determined in peripheral biofluids. This review summarizes recent research on oxidative stress biomarkers in mild cognitive impairment due to AD. Among them, a promising research line is the study of the relationship between lipid peroxidation biomarkers and early AD clinical features. Results show a pronounced imbalance between scientific production and clinical reality due to the lack of clinical validation. We conclude that an important field in oxidative stress biomarkers could be developed with the aim to help clinicians in early disease diagnosis, effective treatment initiation and reliable disease monitoring.

Infection by the rat lungworm Angiostrongylus cantonensis represents the most common cause of infectious eosinophilic meningitis in humans, causing central nervous system (CNS) angiostrongyliasis. Most of CNS angiostrongyliasis cases were described in Asia, Pacific Basin, Australia, and some limited parts of Africa and America. CNS angiostrongyliasis has been reported in the Caribbean but never in the Lesser Antilles. The primary objectives of this study were to depict the first case of CNS angiostrongyliasis in the Lesser Antilles and investigate the environmental presence of A. cantonensis in Guadeloupe, Lesser Antilles. In December 2013, a suspected case of CNS angiostrongyliasis in an 8-month-old infant in Guadeloupe was investigated by real-time polymerase chain reaction (PCR) testing on cerebral spinal fluid (CSF). The environmental investigation was performed by collecting Achatina fulica molluscs from different parts of Guadeloupe and testing the occurrence of A. cantonensis by real-time PCR. CSF from the suspected case of angiostrongyliasis was positive for A. cantonensis by real-time PCR. Among 34 collected snails for environmental investigation, 32.4% were positive for A. cantonensis. In conclusion, we report the first laboratory-confirmed case of CNS-angiostrongyliasis in the Lesser Antilles. We identified the presence and high prevalence of A. cantonensis in A. fulica in Guadeloupe. These results highlight the need to increase awareness of this disease and implement public health programs in the region to prevent human cases of angiostrongyliasis and improve management of eosinophilic meningitis patients.

Objective Postdural puncture headache (PDPH) is an uncommon sequel of lumbar puncture in children. When conservative treatment with bed rest, hydration, and caffeine are ineffective, epidural blood patches are recommended and are generally effective. The purpose of this report was to highlight that when lumbar epidural blood patches fail to eliminate PDPH, diagnostic evaluation should be performed and alternative treatment sought. Case Report An unusual case is described of an 11-year-old boy with PDPH, which was successfully managed with a ventral (anterior) epidural blood patch and epidural saline infusion after headache and other symptoms failed to resolve after conservative treatment and conventionally performed blood patches. Conclusions Ineffectiveness of conservative measures and epidural blood patches performed posteriorly to resolve PDPH should lead the physician both to question the diagnosis of PDPH by pursuing radiographic confirmation of a cerebral spinal fluid leak and, furthermore, identification of its location to best direct further therapy.