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• Diffusion in subarachnoid space was more isotropic with aging in young adults. • Other brain regions did not show an age-related decline of diffusion anisotropy. • Diffusion anisotropy in subarachnoid space was highest in the temporal lobe. • Reduced anisotropy may be relevant to reduced glymphatic transport with aging. The glymphatic system theory postulates that brain waste is removed through the cerebrospinal fluid (CSF) flow. According to this theory, CSF in the subarachnoid space (SAS) moves to the perivascular space around the penetrating arteries, flows into parenchyma to mix with interstitial fluid and brain waste, and then moves to the perivenous space to be flushed out of the brain. Despite the controversies about the glymphatic theory, it is clear that SAS plays a key role in waste clearance. For instance, the SAS around the middle cerebral artery is known to be highly involved in glymphatic influx. While diffusion tensor imaging has been used for studying the glymphatic system, there has been limited exploration of age-related changes in diffusion anisotropy within SAS and their regional variations. Given the narrow and heterogeneous morphology of SAS, the fractional anisotropy (FA) in diverse brain regions may be more relevant to glymphatic transport than mean diffusivity (MD). The goal of this study was to investigate FA in SAS to observe age-related changes across different brain regions and to interpret the results based on the glymphatic transport. We segmented SAS in the whole brain of 83 young adults and divided SAS into four cortical lobes. We demonstrated regional variations in FA and MD within SAS and an age-related decline in FA among young adults, indicating that diffusion within SAS becomes more isotropic with aging. These findings raise new questions about the factors influencing diffusion anisotropy within SAS, which are relevant to glymphatic transport. [ABSTRACT FROM AUTHOR]

• The FROUNT inhibitor, Disulfiram, suppressed inflammatory cell infiltration. • Disulfiram suppressed microglia activation after subarachnoid hemorrhage in animals. • Disulfiram suppressed the death after experimental subarachnoid hemorrhage. • Disulfiram prevented the neuronal death after experimental subarachnoid hemorrhage. • Disulfiram prevented the vasospasm after experimental subarachnoid haemorrhage. Subarachnoid hemorrhage due to rupture of intracranial aneurysms has a poor outcome, making this disease being the social problem. Inflammation evoked by the increase in intracranial pressure and the clot in the subarachnoid space after the onset of SAH exacerbates neuronal death and vasospasm, resulting in the poor outcome and severe aftereffects. Here, FROUNT mediates CCR2 and CCR5 signaling as an intracellular molecule binding to these chemoattractant receptors which facilitate the migration of inflammatory cells, such as macrophages, in situ to trigger inflammation there. Animal model of subarachnoid hemorrhage was established in rats through intrathecal injection of autologous blood. The effect of the FROUNT inhibitor, disulfiram, on survival rate, neuronal death in hippocampus or vasospasm was then examined. The intrathecal administration of disulfiram significantly suppressed the infiltration of CD68-positive macrophages and myeloperoxidase-positive neutrophils toward the clot in the cistern in situ. In this condition, disulfiram ameliorated the death of animals after the onset of subarachnoid hemorrhage in rats. In addition, disulfiram suppressed both the two major events after subarachnoid hemorrhage, the neuronal death in hippocampus and vasospasm. The pharmacological inhibition of CCR2 and CCR5 signaling by disulfiram could thus be the therapeutic strategy to improve the outcome of subarachnoid hemorrhage. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the histological and biochemical neuroprotective effects of secukinumab (SEC) on brain damage induced by subarachnoid hemorrhage (SAH) in male Wistar Albino rats. Forty male Wistar Albino rats were randomly divided into 4 groups of equal size: control, SEC, SAH, and SAH + SEC. SAH was induced the SAH and SAH + SEC groups by injecting autologous blood collected from the hearts of the rats into the subarachnoid space via the foramen magnum. SEC was administered intraperitoneally once a week to the SEC and SAH + SEC groups after the surgical procedure. On the 14th day of surgery, the rats were sacrificed and their cerebral tissues were collected for biochemical analysis and histopathological examination. SAH led to changes in oxidative stress parameters by increasing malondialdehyde levels and decreasing superoxide dismutase, glutathione, catalase, and glutathione peroxidase levels. Histopathologically, cerebral tissues in the SAH groups showed alterations such as congestion and cell infiltration. Treatment with SEC significantly reduced malondialdehyde levels and increased superoxide dismutase, glutathione, catalase, and glutathione peroxidase levels. SEC also decreased histopathological alterations in brain tissues. This study revealed that SEC (3 mg/kg) therapeutically influenced oxidative and histopathological changes in blood parameters and brain tissues caused by experimental SAH. SEC helps reduce brain damage in rats with SAH and possesses antioxidant and neuroprotective properties. Further advanced studies are needed to prove its potential benefits for humans. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid (CSF) circulates throughout the ventricles, cranial and spinal subarachnoid spaces, and central spinal cord canal. CSF protects the central nervous system through mechanical cushioning, regulation of intracranial pressure, regulation of metabolic homeostasis, and provision of nutrients. Recently, investigators have characterized the glial-lymphatic (glymphatic) system, the analog of the lymphatic system in the central nervous system, and described a fourth meningeal layer; the subarachnoid lymphatic-like membrane (SLYM)relevant to the CSF. A narrative review was conducted. In this review, we summarize these advances. We describe the development of the original model, controversies, a revised model, and a new conceptual framework. We characterize the biological functions, influence of sleep-wake cycles, and effect of aging with relevance to the glymphatic system. We highlight the role of the glymphatic system in Alzheimer's disease, idiopathic normal pressure hydrocephalus, ischemic stroke, subarachnoid hemorrhage, and traumatic brain injury. Next, we characterize the structure and role of the SLYM. Finally, we explore the relevance of the glymphatic system and SLYM to neurosurgery. This manuscript will inform clinicians and scientists regarding preclinical and translational advances in the understanding of the structure, dynamics, and function of the CSF. [ABSTRACT FROM AUTHOR]

Superficial siderosis (SS) of the central nervous system is a rare disease characterized by deposition of hemosiderin along the leptomeninges due to chronic or recurrent bleeding into the subarachnoid space. The association of unruptured intracranial aneurysm (IA) and cortical SS is quite rare. A systematic literature review to assess possible commonalities and/or differences of previous reported cases was undertaken. We report an additional case from our institution. A 40-year-old woman presented with a history of generalized seizures over the past year. There was no clinical history suggestive of aneurysm rupture. Magnetic resonance imaging revealed 2 aneurysms of the right middle cerebral artery (MCA) bifurcation associated with hemosiderin deposition along the right sylvian fissure and a third aneurysm of the left MCA bifurcation. Magnetic resonance imaging showed wall enhancing thickening of the larger right MCA aneurysm. The patient underwent surgical clipping of all 3 MCA aneurysms in a staged procedure. Histological examination revealed hemosiderin deposits within the aneurysm wall and surrounding gliosis. Our literature review found 24 reported cases of unruptured IA associated with cortical SS. The possible source for leakages could be neovessels visible in IA walls. The case reported illustrates an uncommon presentation of recurrent bleeding from an IA as a source of SS. The presence of an apparently unruptured IA surrounded by cortical SS on imaging studies is of high relevance as this should be considered a sign of aneurysm wall instability and should indicate prompt treatment. [ABSTRACT FROM AUTHOR]

The nervous system is divided topographically into two parts: the central nervous system and the peripheral nervous system. From a functional perspective, however, the two systems are intimately connected and function in an integrated and coordinated manner. The central nervous system comprises the brain and spinal cord, while the peripheral nervous system is made up of the cranial and peripheral nerves and associated neurological structures. This article presents a broad and general overview of the structure and organization of the nervous system emphasizing several important functional features. [ABSTRACT FROM AUTHOR]

Bupivacaine (BUP) is an anesthetic commonly used in clinical practice that when used for spinal anesthesia, might exert neurotoxic effects. Thioredoxin-interacting protein (TXNIP) is a member of the α-arrestin protein superfamily that binds covalently to thioredoxin (TRX) to inhibit its function, leading to increased oxidative stress and activation of apoptosis. The role of TXNIP in BUP-induced oxidative stress and apoptosis remains to be elucidated. In this context, the present study aimed to explore the effects of TXNIP knockdown on BUP-induced oxidative stress and apoptosis in the spinal cord of rats and in PC12 cells through the transfection of adeno-associated virus-TXNIP short hairpin RNA (AAV-TXNIP shRNA) and siRNA-TXNIP, respectively. In vivo, a rat model of spinal neurotoxicity was established by intrathecally injecting rats with BUP. The BUP + TXNIP shRNA and the BUP + Control shRNA groups of rats were injected with an AAV carrying the TXNIP shRNA and the Control shRNA, respectively, into the subarachnoid space four weeks prior to BUP treatment. The Basso, Beattie & Bresnahan (BBB) locomotor rating score, % MPE of TFL, H&E staining, and Nissl staining analyses were conducted. In vitro, 0.8 mM BUP was determined by CCK-8 assay to establish a cytotoxicity model in PC12 cells. Transfection with siRNA-TXNIP was carried out to suppress TXNIP expression prior to exposing PC12 cells to BUP. The results revealed that BUP effectively induced neurological behavioral dysfunction and neuronal damage and death in the spinal cord of the rats. Similarly, BUP triggered cytotoxicity and apoptosis in PC12 cells. In addition, treated with BUP both in vitro and in vivo exhibited upregulated TXNIP expression and increased oxidative stress and apoptosis. Interestingly, TXNIP knockdown in the spinal cord of rats through transfection of AAV-TXNIP shRNA exerted a protective effect against BUP-induced spinal neurotoxicity by ameliorating behavioral and histological outcomes and promoting the survival of spinal cord neurons. Similarly, transfection with siRNA-TXNIP mitigated BUP-induced cytotoxicity in PC12 cells. In addition, TXNIP knockdown mitigated the upregulation of ROS, MDA, Bax, and cleaved caspase-3 and restored the downregulation of GSH, SOD, CAT, GPX4, and Bcl2 induced upon BUP exposure. These findings suggested that TXNIP knockdown protected against BUP-induced spinal neurotoxicity by suppressing oxidative stress and apoptosis. In summary, TXNIP could be a central signaling hub that positively regulates oxidative stress and apoptosis during neuronal damage, which renders TXNIP a promising target for treatment strategies against BUP-induced spinal neurotoxicity. [Display omitted] Here are 3 highlights of our research: • A significant increase in TXNIP expression was observed in bupivacaine-induced neurotoxicity both in vitro and in vivo. • Bupivacaine exposure activates TXNIP which positively regulates oxidative stress and apoptosis in vitro and in vivo. • Knocking down TXNIP protects against bupivacaine-induced neurotoxicity by inhibiting oxidative stress and apoptosis. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify preoperative magnetic resonance imaging (MRI) findings that can predict the shunt responsiveness in idiopathic normal-pressure hydrocephalus (iNPH) patients and to investigate postoperative outcome and complications. A total of 192 patients with iNPH who underwent shunt at our hospital between 2000 and 2021 were included to investigate complications. Of these, after exclusion, 127 (1-month postoperative follow-up) and 77 (1-year postoperative follow-up) patients were evaluated. The preoperative MRI features (the presence of tightness of the high-convexity subarachnoid space, Sylvian fissure enlargement, Evans' index, and callosal angle) of the shunt-response and nonresponse groups were compared, and a systematic review was conducted to evaluate whether preoperative MRI findings could predict shunt response. Postoperative complications within one month after surgery were observed in 6.8% (13/192), and the most common complication was hemorrhage. Changes in corpus callosum were observed in 4.2% (8/192). The shunt-response rates were 83.5% (106/127) in the 1-month follow-up group and 70.1% (54/77) in 1-year follow-up group. In the logistic regression analysis, only Evans' index measuring >0.4 had a significant negative relationship with shunt response at 1-month follow-up; however, no significant relationship was observed at 1-year follow-up. According to our systematic review, it is still controversial whether preoperative MRI findings could predict shunt response. Evans' index measure of >0.4 had a significant relationship with the shunt response in the 1-month follow-up group. In systematic reviews, there is ongoing debate about whether preoperative MRI findings can accurately predict responses to shunt surgery. Postoperative corpus callosal change was observed in 4.2% of iNPH patients. • No preoperative magnetic resonance imaging (MRI) finding was associated with shunt response in idiopathic normal-pressure hydrocephalus (iNPH) patients. • It is still unclear whether preoperative MRI findings can predict shunt response. • Postshunt corpus callosal hyperintensity was observed in 4.2% of iNPH patients. [ABSTRACT FROM AUTHOR]

Patients with leptomeningeal carcinomatosis (LMC) experience a poor prognosis and rapid progression, and cerebrospinal fluid drainage (CSFD) is used to manage intracranial hypertension and hydrocephalus in LMC patients. This study aims to describe a novel discovery of preoperative radiological features in patients who underwent CSFD for LMC. A retrospective review was conducted during the past 5 years of LMC patients with intracranial hypertension and hydrocephalus who underwent CSFD. We evaluated the patients' preoperative radiological features, clinical characteristics, and survival times. A total of 36 patients were included. Of the 36 patients, 34 underwent ventriculoperitoneal shunting, and 2 patients underwent only external ventricular drainage due to rapid progression. The median preoperative Karnofsky performance scale score was 40.0 (interquartile range [IQR], 20.0–40.0). The median survival time after surgery was 5 months (IQR, 0.00–10.43 months). Of the 36 patients, 24 (66.7%) had supratentorial cerebral edema before surgery, including 14 patients (38.9%) with features of disproportionately enlarged subarachnoid space hydrocephalus (DESH). Four patients (11.1%) exhibited cerebellar swelling and had a median survival time of 0.27 month (IQR, 0.00–0.56 month). Nine patients (25%) have enhancement lesions on the cerebellum. The survival curve analysis shows that patients with features of cerebellar enhancement have shorter survival times than other patients. Patients with DESH features have longer survival times compared with those with global cerebral edema. Patients with radiological features of cerebellar enhancement have shorter postoperative survival than other patients; however, those with supratentorial cerebral edema, especially features of DESH, could benefit from CSFD. Patients with cerebellar swelling should avoid undergoing CSFD. [ABSTRACT FROM AUTHOR]

Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. SAH disrupts the blood‒brain barrier, leading to the release of iron ions from blood within the subarachnoid space, subsequently inducing neuronal ferroptosis. A recently discovered protein, known as ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10 by introducing the neuron-targeting peptide Tet1 onto the surface of liposomal CoQ10. Our objective was to determine whether this formulation could activate the FSP1 system and subsequently inhibit neuronal ferroptosis. Our findings revealed that neuron-targeted liposomal CoQ10 effectively localized to neurons at the lesion site after SAH. Furthermore, it facilitated the upregulation of FSP1, reduced the accumulation of malondialdehyde and reactive oxygen species, inhibited neuronal ferroptosis, and exerted neuroprotective effects both in vitro and in vivo. Our study provides evidence that supplementation with CoQ10 can effectively activate the FSP1 system. Additionally, we developed a neuron-targeted liposomal CoQ10 formulation that can be selectively delivered to neurons at the site of SAH. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH. Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. Ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10. We find that it effectively localized to neurons at the lesion site after SAH and activated the FSP1/CoQ10 system. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH and other central nervous system diseases characterized by disruption of the blood-brain barrier. [Display omitted] [ABSTRACT FROM AUTHOR]

In comparison to other stroke types, subarachnoid hemorrhage (SAH) is characterized by an early age of onset and often results in poor prognosis. The inadequate blood flow at the site of the lesion leads to localized oxygen deprivation, increased level of hypoxia-inducible factor-1α (HIF-1α), and triggers inflammatory responses and oxidative stress, ultimately causing hypoxic brain damage. Despite the potential benefits of oxygen (O 2) administration, there is currently a lack of efficient focal site O 2 delivery following SAH. Conventional clinical O 2 supply methods, such as transnasal oxygenation and hyperbaric oxygen therapy, do not show the ideal therapeutic effect in severe SAH patients. The perfluorocarbon oxygen carrier (PFOC) demonstrates efficacy in transporting O 2 and responding to elevated levels of CO 2 at the lesion site. Through cellular experiments, we determined that PFOC oxygenation serves as an effective therapeutic approach in inhibiting hypoxia. Furthermore, our animal experiments showed that PFOC oxygenation outperforms O 2 breathing, leading to microglia phenotypic switching and the suppression of inflammatory response via the inhibition of HIF-1α. Therefore, as a new type of O 2 therapy after SAH, PFOC oxygenation can effectively reduce hypoxic brain injury and improve neurological function. Subarachnoid hemorrhage primarily arises from the rupture of intracranial aneurysms. The rupture of an aneurysm results in a substantial influx of blood into the subarachnoid space, exerting arterial pressure and accumulating within the cerebral sulcus cerebral pool, thereby forming a hematoma that compresses the brain tissue. Consequently, this compression leads to localized tissue hypoxia, which subsequently triggers excitatory neuroinflammation and oxidative stress. Considering these circumstances, we propose a novel approach utilizing perfluorocarbons following subarachnoid hemorrhage, enhancing oxygenation at the site of the lesion in comparison to conventional O 2 breathing. Perfluorocarbon oxygen carrier oxygenation has been found to have a downregulating effect on HIF-1α, leading to a decrease in the population of M1-type microglia and an increase in the population of M2-type microglia. Additionally, this oxygenation process inhibits inflammatory responses and oxidative stress following subarachnoid hemorrhage, ultimately resulting in an improvement in neurological function. [Display omitted] • HIF-1α mediates hypoxic brain injury after SAH. • We developed a method of supplying oxygen that can be administered intravenously. • Perfluorocarbon oxygen carrier ameliorates hypoxic brain injury by inhibiting HIF-1α. [ABSTRACT FROM AUTHOR]

Long thought to be immune privileged, the central nervous system is far from being devoid of local immunity. Subarachnoid hemorrhage (SAH) and traumatic brain injury represent 2 distinct central nervous system injury situations which, while both exposed to external ventricular drains, present different incidences of ventriculostomy-related infection (VRI). We sought to compare VRI incidence and initial cerebrospinal fluid (CSF) inflammatory profiles in these 2 clinical situations. From 2015 to 2020, 227 patients treated for SAH (193) or traumatic brain injury (34) with an external ventricular drain were prospectively included. CSF samples were sent daily for microbiological examination, cell count, and biochemical analysis. VRI was defined as a positive CSF culture associated with CSF profile modifications and clinical signs. Ventriculostomy-related colonization was defined as positive catheter culture at removal. Positive events were defined as VRI and/or ventriculostomy-related colonization. Eleven patients suffered from VRI, with an incidence of 3.6 VRI per 1000 catheter-days. All VRIs occurred among SAH patients without a significant difference. Median duration of drainage was 12 (7–18) days, there were no significant differences for known VRI risk factors. Positive events were significantly higher in SAH patients (20.7% vs. 2.9%, P = 0.013). Inflammatory CSF markers and serum white blood cells were higher in SAH patients. Local inflammatory markers were markedly higher in SAH than in traumatic brain injury. However, positive events were more frequent in SAH. Furthermore, SAH may be a risk factor for VRI. Hypothesis that a primary injury to the subarachnoid space could impair central nervous system immune functions should be explored. [ABSTRACT FROM AUTHOR]

Idiopatic normal pressure hydrocephalus (iNPH) is a progressive neurologic syndrome featured by the triad of gait disturbance, mental deterioration and urinary incontinence, associated with ventriculomegaly and normal cerebrospinal fluid (CSF) pressure. The clinical presentation may be atypical or incomplete, or mimicked by other diseases, so conventional neuroradiologic imaging plays an important role in defining this pathology. iNPH pathophysiologic mechanisms have not yet been fully elucidated, although several studies have demonstrated the involvement of the glymphatic system, a highly organized fluid transport system, the malfunction of which is involved in the pathogenesis of several disorders including normotensive hydrocephalus. Recent studies have shown how crucial in the diagnosis of this pathology is the definition of morphologic biomarkers, such as ventricular enlargement disproportionate to cerebral atrophy and associated ballooning of frontal horns; periventricular hyperintensities; and corpus callosum thinning and elevation, with callosal angle <90 degrees. Another interesting feature that is becoming a well-recognized factor to look for and useful for the diagnosis of iNPH is disproportionately enlarged subarachnoid space hydrocephalus, which includes enlarged ventricles, tight high-convexity and medial surface subarachnoid spaces, and expanded Sylvian fissures. A correct choice of MRI sequences is important for a proper characterization identification of others diseases that may underlie this pathology. Magnetic resonance imaging allows us to evaluate CSF flow, enabling us to define qualitative and quantitative parameters necessary for the purpose of accurate iNPH diagnosis. iNPH can represent a real diagnostic challenge; a proper correlation among clinical features, traditional MRI, and CSF dynamics analysis can lead to a correct diagnosis. [ABSTRACT FROM AUTHOR]

Giant pituitary adenomas (>4 cm, GPAs) have presented great challenges to surgeons because the residual tumor in the subarachnoid space can cause hemorrhage or vessel injury following apoplexy. This study aimed to investigate the factors limiting surgical success in endoscopic skull base surgery (ESS) for GPAs. ESS was performed on 67 consecutive patients with GPAs from 2010 to 2020. We retrospectively analyzed the clinical and radiologic features and surgical outcomes. Correlations between the tumor characteristics and extent of resection were statistically presented with odds ratios (ORs). Preoperative visual and hormonal impairments were present in 59 (88.1%) and 55 patients (82.1%), respectively. Gross total resection (GTR) was achieved in 58.2% of patients, and the tumor remained on the lateral side of the subarachnoid space or the cavernous sinus when complete resection failed. The tumor volume, maximal diameter, multilobulated shape, cavernous sinus invasion, posterior fossa extension, and extent of suprasellar lateral extension of tumors were significantly correlated with incomplete resection. In tumors with subarachnoid lateral extension, greater distances from the medial wall of the proximal cavernous internal carotid artery to the most lateral tumor significantly increased the risk of incomplete resection for the suprasellar lateral portion of the tumor, with an OR of 1.21. Considerable surgical planning in ESS for GPAs is crucial for complete resection and patient safety. We elucidated that lateral extension of tumors in the subarachnoid space hindered the surgical success of the suprasellar portion of the tumor. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid (CSF) dynamics has dramatically changed in this century. In the latest concept of CSF dynamics, CSF is thought to be produced mainly from interstitial fluid excreted from the brain parenchyma and is absorbed in the meningeal lymphatics. Moreover, CSF does not always flow from the ventricles to the subarachnoid space unidirectionally through the foramina of Magendie and Luschka. In an environment of increased intracranial CSF in idiopathic normal pressure hydrocephalus, CSF freely moves through the inferior choroidal point of the choroidal fissure, which interfaces between the inferior horn of the lateral ventricles and the ambient cistern and through the velum interpositum between the third ventricle and the quadrigeminal cistern. The structure of the hippocampus adjacent to the inferior part of the choroidal fissure may be important in preventing the accumulation of waste products in the hippocampus. A recent imaging technology for CSF dynamics, such as four-dimensional flow and intravoxel incoherent motion magnetic resonance imaging, can visualize and quantify the pulsatile complex CSF motion in clinical usage. We present the current concepts of CSF dynamics with advanced magnetic resonance imaging techniques, which will be helpful in the management and understanding of the pathogenesis of chronic hydrocephalus in adults. [ABSTRACT FROM AUTHOR]

Classical leptomeningeal disease (cLMD) has historically been considered a global phenomenon impacting the entire craniospinal axis, but isolated parenchymal metastases sometimes display focal leptomeningeal extension into the surrounding leptomeninges without diffuse LMD elsewhere. Descriptions of this phenomenon are lacking, and the optimal management of such patients remains unclear. We hypothesized that, in order to spare such patients the deleterious outcomes of whole brain radiation (WBRT), patients with focal LMD (fLMD) could be successfully managed with stereotactic radiation (SRS/SRT) without excess development of adverse sequelae such marginal recurrences or subsequent cLMD. We identified 796 patients with 2,354 newly-diagnosed brain metastases (BrM) secondary to a solid tumor primary without cLMD at diagnosis managed at a tertiary cancer center between 2007-2022. Each metastasis was assessed for fLMD, which was defined as isolated focal leptomeningeal extension of an intact brain metastasis or single, isolated focal leptomeningeal enhancement without cytologic or radiographic evidence of cLMD (enhancement of cranial nerves or multifocal involvement of subarachnoid spaces including the cerebellar folia and supratentorial sulci). Multivariable Fine and Gray's models were constructed for the primary outcomes of local recurrence and development of cLMD. Among 796 patients, 138 (17.3%) displayed evidence of fLMD, corresponding to 185 of 2,354 (7.9%) BrM. Patients with versus without fLMD were not more likely to display distant intracranial failures post-initial treatment (56.8% vs. 58.3% at 1 year, respectively, p=0.78) or local recurrence (4.4% vs. 8.2% at 1 year, respectively, p=0.14), including in lesions managed with SRS/SRT (1-year local recurrence: 4.4% vs. 4.9%, respectively; p=0.63). On a per-patient level, the presence of fLMD was not a significant predictor of development of cLMD (1-year rate: 5.2% vs 5.2%, HR: 0.99 [0.52-1.89], p=0.97). We describe a novel pattern of LMD that has not been well-characterized in prior literature; fLMD appears to be a distinct oncologic entity whose pattern of intracranial failure resembles that of parenchymal BrM. Nationally, it may be that patients with fLMD are managed as having cLMD with routine use of WBRT. Our study suggests that despite the presence of enhancing disease in the leptomeningeal space, stereotactic approaches may be viable in this population given the lack of detectable excess risk of local recurrence or development of cLMD. [ABSTRACT FROM AUTHOR]

The presence of tightened sulci in the high-convexities (THC) is a key morphological feature for the diagnosis of idiopathic normal pressure hydrocephalus (iNPH), but the exact localization of THC has yet to be defined. The purpose of this study was to define THC and compare its volume, percentage, and index between iNPH patients and healthy controls. According to the THC definition, the high-convexity part of the subarachnoid space was segmented and measured the volume and percentage from the 3D T1-weighted and T2-weighted magnetic resonance images in 43 patients with iNPH and 138 healthy controls. THC was defined as a decrease in the high-convexity part of the subarachnoid space located above the body of the lateral ventricles, with anterior end on the coronal plane perpendicular to the anterior commissure–posterior commissure (AC–PC) line passing through the front edge of the genu of corpus callosum, the posterior end in the bilateral posterior parts of the callosomarginal sulci, and the lateral end at 3 cm from the midline on the coronal plane perpendicular to the AC–PC line passing through the midpoint between AC and PC. Compared to the volume and volume percentage, the high-convexity part of the subarachnoid space volume per ventricular volume ratio < 0.6 was the most detectable index of THC on both 3D T1-weighted and T2-weighted magnetic resonance images. To improve the diagnostic accuracy of iNPH, the definition of THC was clarified, and high-convexity part of the subarachnoid space volume per ventricular volume ratio <0.6 proposed as the best index for THC detection in this study. [Display omitted] [ABSTRACT FROM AUTHOR]

Spontaneous third ventriculostomy (STV) is a rare occurrence in cases of obstructive hydrocephalus where the walls of the third ventricle rupture, communicating the ventricular system, and the subarachnoid space leading to arrest of active hydrocephalus. We aim to review our series of STVs while reviewing previous reports. A retrospective review of cases undergoing cine phase-contrast magnetic resonance imaging (PC-MRI) from 2015 to 2022 of any age with imaging evidence of arrested obstructive hydrocephalus was performed. Patients in which aqueductal stenosis was radiologically evident and the presence of third ventriculostomy through which cerebrospinal fluid flow was detectable were included. Patients who previously underwent endoscopic third ventriculostomy were excluded. Data on patient demographics, presentation, and imaging details of STV and aqueductal stenosis were collected. We searched the PubMed database using the following keyword combination: ((("spontaneous ventriculostomy") OR ("spontaneous third ventriculostomy")) OR ("spontaneous ventriculocisternostomy")) including English reports of STV published between 2010 and 2022. Fourteen cases were included (7 adults, 7 pediatrics), all with history of hydrocephalus. STV occurred in the floor of the third ventricle in 57.1% of the cases, at the lamina terminalis in 35.7%, and at both sites in 1 case. Eleven publications reporting 38 cases of STV were identified from 2009 to date. Minimum follow-up period was 10 months and maximum follow-up is 77 months. In cases of chronic obstructive hydrocephalus, neurosurgeons should be minded with the possibility of the presence of an STV on cine phase-contrast magnetic resonance imaging leading to arrested hydrocephalus. The delayed flow at the aqueduct of Sylvius might not be the only determinant of the necessity of cerebrospinal fluid diversion and the presence of an STV should be factored into the neurosurgeon's decision considering the patient's clinical picture. [ABSTRACT FROM AUTHOR]

Secondary spinal arachnoid cysts have rarely been reported but present significant challenges for management. These cysts could be anteriorly located with long rostral–caudal extensions and many are related to arachnoiditis, leading to difficult-to-treat disorders. Thus far, due to the scarcity of reports, the features of the disease and the optimal therapeutic strategies remain unclear. To investigate clinical features and the optimal treatment modalities of secondary spinal arachnoid cysts compared with primary spinal arachnoid cysts. Systematic review. Systematic review identified 103 secondary cases from 80 studies and reports. Condition of symptom relief and duration of treatment response were analyzed. An electronic literature search of the PubMed database was conducted for studies on secondary spinal arachnoid cysts between 1990 and 2022. Non-English publications, nonhuman studies, reports of a primary cyst, studies not including case details, and studies of nonsymptomatic cases were excluded. This systematic review included 103 secondary cases. The most commonly reported etiologies were iatrogenic factors, trauma, and subarachnoid hemorrhage, accounting for 88 intradural extramedullary, 11 extradural, one intradural/extradural, one interdural, and one intramedullary spinal arachnoid cyst after a median duration of 30, 12, and 9 months, respectively. Extradural cysts were more prone to occur at dorsal locations and affect thoracic segments (mean cyst length: 3.4 segments). Intradural cysts showed a relatively higher ventral/dorsal ratio (1:1.09, 1.75:1, and 3.50:1 for cysts occurring from iatrogenic factors, trauma, and subarachnoid hemorrhage, respectively) and thoracic distribution, with a mean cyst length of 4.3 segments (5.1 for ventral and 3.5 for dorsal cysts). For intradural cysts, recurrence risk was lower after surgical resection than after fenestration/marsupialization (12-month recurrence risk: 21.43% vs 50.72%, log-rank test: p=.0248, Gehan–Breslow–Wilcoxon test: p=.0126). In cases treated with shunting, one recurrence (1/8 cases) was noted after external shunting and two recurrences (2/5 cases) after internal shunting at a median follow up of 12 months. Secondary spinal arachnoid cysts, particularly intradural cysts, are rarer and more challenging to treat than primary spinal cysts. Although fenestration/marsupialization is the commonly adopted treatment, the recurrence rate is high. For unresectable cysts, shunting procedures, particularly shunting into a body cavity (eg, pleural or peritoneal cavity) away from the subarachnoid space, could be a therapeutic alternative besides fenestration/marupialization, yet its efficacy requires confirmation by more data. [ABSTRACT FROM AUTHOR]

Vertebrobasilar dolichoectasia, a rare vascular anomaly, rarely presents with hydrocephalus. The traditional treatment for hydrocephalus is a ventriculoperitoneal shunt. Conventional endoscopic third ventriculostomy can avoid shunt-related complications but is considered risky due to the presence of the dolichoectatic vessel. A subfrontal extra-axial fenestration of the lamina terminalis can circumvent this anatomic constraint and establish cerebrospinal fluid communication between the third ventricle and subarachnoid space. We performed an extra-axial endoscopic third ventriculostomy to manage hydrocephalus due to vertebrobasilar dolichoectasia in a 26-year-old male. The clinical description, surgical technique, outcome, and rationale are described. The patient had symptomatic improvement in his headaches and vision. There was also improvement in the postoperative ventricular indices: Evans index—19% reduction, frontal occipital horn ratio—14.1% reduction, and third ventricle index—39.5% reduction. A cine-phase magnetic resonance image showed cerebrospinal fluid flow void through the lamina terminalis fenestration, suggesting patency. Extra-axial endoscopic third ventriculostomy may be a suitable treatment alternative to circumvent anatomic constraints produced by vertebrobasilar dolichoectasia in performing conventional endoscopic third ventriculostomy. [ABSTRACT FROM AUTHOR]

Determination of optic nerve sheath diameter (ONSD) with transbulbar sonography has become an easily accessible and time-effective tool in the assessment of increased intracranial pressure. The aim of our study was to evaluate the usefulness of transbulbar sonography in the initial diagnosis and in follow-up examinations of children and adolescents with the diagnosis of pseudotumor cerebri syndrome (PTCS). We retrospectively reviewed imaging results of 24 patients aged 0.75–17 years with PTCS. Serial transbulbar sonography examinations were performed between 2011 and 2021. Sonographic evaluation included the ONSD, papilledema and subarachnoid space. 240 sonographic measurements taken at 108 time points in 17 patients met the inclusion criteria. All patients underwent serial lumbar punctures and routine fundoscopy in close relation to transbulbar sonography. We found that ONSD values remained high in all patients. The longest follow-up period was dated 2498 days (6.84 years) after initial diagnosis. Papilledema resolved in close correlation to fundoscopy normalization. In 16/17 patients the subarachnoid space remained cystic in appearance. These findings were independent of clinical symptoms and lumbar puncture opening pressure. We conclude that transbulbar sonography is a useful diagnostic tool in the initial diagnostic workup of children with PTCS. On follow-up however ONSD values and the cystic transformation of the subarachnoid space remained pathologic in the majority of cases while papilledema resolved parallel to fundoscopy findings. Serial measurements of ONSD are therefore of limited value in the follow-up of patients with PTCS and cannot be considered a reliable tool in subsequent therapeutic decisions. • Transbulbar sonography is useful for diagnosis of pediatric pseudotumor cerebri. • On follow-up optic nerve sheath diameter and subarachnoid space remain enlarged. • Sonographic papillary changes normalize parallel to fundoscopy findings. • Serial ONSD measurements are of limited value. • ONSD measures in follow-up are not a reliable tool for subsequent therapy decisions. [ABSTRACT FROM AUTHOR]

• Rich foci are caseating brain tuberculous (TB) granulomas surrounding the immigrated TB bacilli. • Rich foci are hypothesized as an underlying pathological mechanism of TB meningitis. • The hypothesis is based on necropsy studies and has rarely been depicted in vivo. • Ruptured foci discharge their contents into the neighboring subarachnoid space. • Discharged contents trigger a T cell response, leading to inflammatory meningitis. [ABSTRACT FROM AUTHOR]

• This hypothesis offers a new explanation of ventriculomegaly suggesting that arachnoid membranes may have a valve or fluid diode function. • The brain mechanically pumps CSF around the subarachnoid space using these valves. • Ventriculomegaly in communicating hydrocephalus may be due to an impairment of the brain CSF pump. • Arachnoid membranes may act like Tesla valves. Hydrocephalus can be obstructive or communicating. In cases of communicating hydrocephalus, patients will typically have enlarged brain ventricles. It has long been thought that the reason for this is obstruction to the outflow of cerebrospinal fluid from the subarachnoid space, which also results in raised intracranial pressure (ICP). However, there are several clinical and anatomic observations that are not well explained by this idea. These are for example, the conditions of Normal pressure hydrocephalus (NPH) which has normal ICP but ventriculomegaly, and idiopathic intracranial hypertension (IIH) which has raised ICP but normal sized ventricles. This hypothesis states that the mechanism for raised ICP and large ventricles seen in communicating hydrocephalus (ventriculomegaly) are different and seeks to explain the cause of ventriculomegaly using illustrative examples. It also suggests explanations for why ventriculomegaly occurs in NPH, infectious or carcinomatous meningitis, but is absent in IIH, or dural venous sinus thrombosis. Based on operative neurosurgical observations it states that the arachnoid membranes in the basal cisterns serve as part of a directional CSF flow mechanism consisting of fluid diodes, or "Tesla valves" of arachnoid membrane, containing CSF that is propelled by brain pulsations from the point of exit from the 4th ventricle to its points of absorption. This hypothesis suggests explanations for the physiologic appearance of a near uniform subarachnoid space, as well as the occurrence of the syndrome of the trephined and external hydrocephalus seen following a decompressive craniectomy. Also suggested are avenues of further research testing with MRI phase contrast CSF flow studies, classification of anatomic and peri -operative observations and rationale for creation of novel experiments to test the hypothesis, and aid diagnosis and treatment of a number of cranial CSF disorders. [ABSTRACT FROM AUTHOR]

Microsurgical techniques are increasingly being recommended for the treatment of symptomatic Tarlov cysts (TCs) due to improved long-term outcomes compared to those of other strategies. However, these techniques are associated with a high risk of cyst recurrence and cerebrospinal fluid (CSF) leakage, resulting in the surgical strategy of TCs remaining controversial. We hypothesize that incomplete closure of the ostium between the cyst and the subarachnoid space is the probable cause of surgical failure. Accordingly, we present a novel method of cyst separation and ostium closure that aims to block the ostium more firmly and reliably. Thirty-five consecutive patients (21 females) underwent the modified ostium obstruction surgery due to symptomatic TCs. We collected and compared their outcomes at the final follow-up to evaluate the surgical effect. Thirty-five patients had 74 TCs (S2 level, 48.7%; mean diameter, 2.0 ± 1.0 cm); ostia nerve root fibers were found in all TCs. The mean follow-up duration was 37.8 (range, 13.5–76.8) months. At the final follow-up, 33 patients experienced complete or substantial resolution of the preoperative symptoms. The symptom with the highest improvement rate was radicular pain. Both the modified evaluation criteria for the efficacy of lumbar function criterion and Japanese Orthopedic Association score 29 showed an overall improvement rate of 94.3%. Two patients experienced surgery-related neurological dysfunction. No cyst recurrence or CSF leakage was observed. Magnetic resonance imaging showed that all cysts disappeared or significantly reduced postoperatively. The microscopic fenestration of cysts and modified ostium obstruction described herein is a safe and effective strategy for management of patients with symptomatic TCs and is associated with a low incidence of cyst recurrence and CSF leakage since it achieves complete closure of cyst ostium. [ABSTRACT FROM AUTHOR]

Benign Enlargement of the Subarachnoid Spaces in Infancy (BESSI) is a common finding during workup for progressive macrocephaly. BESSI has been associated with slightly higher prevalence of subdural (SD) spaces and a risk for developing subdural hematoma. This study utilizes fast brain magnetic resonance imaging (MRI) to investigate the prevalence of visible SD spaces in BESSI. A retrospective review was performed for all pediatric patients who underwent brain MRI for macrocephaly. Patients with a diagnosis of BESSI were included in the study. A total of 109 patients met the inclusion criteria. Patient demographics were collected, and images were reviewed for size of subarachnoid, visible SD spaces, and ventricle size. Descriptive and inferential statistics were performed. The average age was 8 ± 4.6 months, 64 (59%) were male, and 55 patients had no previous medical history (50%). Sixty-seven percent of all patients were identified to have visible SD spaces. Eleven patients had confirmed SD hematomas; 1 patient was deemed to have abusive head trauma. Visible SD spaces were associated with younger age (6.9 months). Thirty-one patients with visible SD spaces had follow-up MRI, with complete resolution by 33 months. BESSI is a self-limiting pathology that has been associated with visible SD spaces and potential risk for SD hemorrhages. We report a high prevalence of visible SD spaces within BESSI through utilization of fast brain MRI. These spaces may contribute to the higher rate of incidental subdural hematoma in this population. [ABSTRACT FROM AUTHOR]

Nontraumatic subarachnoid hemorrhage (SAH) refers to high pressure extravasation of blood into the subarachnoid space that typically occurs spontaneously from rupture of cerebral aneurysm. The purpose of this study was to identify postoperative complications requiring increased surveillance in obese, diabetic, and hypertensive patients. Patients who underwent surgical treatment for nontraumatic SAH were queried in the American College of Surgeons National Surgical Quality Improvement Program database from the years 2012–2018. Cases were identified using International Classification of Diseases codes and then classified independently by 3 dichotomous diagnoses: obesity, diabetes, and hypertension. Among 1002 patients meeting inclusion criteria, 311 (31%) were obese (body mass index >30), 86 (9%) had diabetes treated with insulin or noninsulin agents, and 409 (41%) required medication for hypertension. There was a statistically significant association between diabetes and postoperative pneumonia (odds ratio [OR] = 1.694; 95% confidence interval [CI] = 0.995–2.883; P = 0.050), prolonged ventilator dependence (OR = 1.700; 95% CI = 1.087–2.661; P = 0.019), and death (OR = 1.846; 95% CI = 1.071–3.179; P = 0.025). Medication-dependent hypertension was statistically associated with incidence of stroke/cerebrovascular accident (OR = 1.763; 95% CI = 1.056–2.943; P = 0.023). Obesity was not associated with adverse outcomes in this population. In patients undergoing surgical management of SAH, hypertensive and diabetic patients had poorer outcomes, including prolonged ventilator dependence, pneumonia, stroke/cerebrovascular accident, and death. Surprisingly, preexisting obesity was not associated with poor outcomes. In fact, overweight body mass index, class I obesity, and class II obesity had decreased need for transfusion in the 30-day postoperative period. [ABSTRACT FROM AUTHOR]

The perioptic space comprises the subarachnoid space [SAS] of the optic nerve communicating with the SAS of the central nervous system. Pressure variations in the SAS of the central nervous system can be transmitted to the optic papilla through the perioptic space. Variations in the diameter of the perioptic space serve as an important indicator for select intracranial pathologies in the pediatric population. Though the perioptic space can be evaluated using various imaging modalities, MRI is considered highly effective due to its superior soft tissue resolution. With advancement in MR imaging techniques, high-resolution images of the orbits can provide improved visualization of the perioptic space. It is imperative for the pediatric radiologist to routinely assess the perioptic space on brain and orbit MR imaging, as it can prompt exploration for additional features associated with select intracranial pathologies, thus improving diagnostic accuracy. This article reviews basic anatomy of the perioptic space, current understanding of the CSF dynamics between the perioptic space and central nervous system SAS, various imaging modalities utilized in the assessment of the perioptic space, MRI sequences and the optimal parameters of specific sequences, normal appearance of the perioptic space on MR imaging, and various common pediatric pathologies which cause alteration in the perioptic space. • The perioptic space comprises the subarachnoid space (SAS) of the optic nerve communicating with the SAS of the Central Nervous System [CNS]. The pressure variation in the SAS can be transmitted to the perioptic space. • Variations in the diameter of the perioptic space serve as an important indicator of intracranial pathologies. It is imperative for the radiologist to assess the perioptic space in every brain and orbit MRI. • The article reviews the current understanding of the cerebrospinal fluid (CSF) dynamics between the perioptic space and CNS SAS, various imaging modalities utilized in the assessment of the perioptic space, and various pathologies that cause alteration in the perioptic space. • The distention of the perioptic space can be objectively determined by US, CT, or MRI in two different ways: 1. Based on the CSF thickness. 2. Based on the ONS diameter. • Most important MRI sequences in the imaging of perioptic space include high-resolution STIR or fat-suppressed T2W in coronal and axial planes and 3-D Steady State Fast Precession [SSFP] techniques. • We discuss a few common causes of intracranial hypertension and intracranial hypotension in the pediatric population, including Idiopathic Intracranial Hypertension [IIH], CSF Ventricular shunt malfunction, spontaneous and iatrogenic CSF leak. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid (CSF)-venous fistula presents a pathologic connection between spinal subarachnoid space and adjacent epidural vein or veins. It is one of the 3 main causes of spontaneous intracranial hypotension along with dural defects and meningeal diverticulum. We performed a systematic review of the literature and analyzed individual participants' data focusing on clinical outcomes after different treatment modalities of CSF-venous fistula. Systematic review was conducted according to PRISMA recommendations. Literature search was performed in PubMed and Web of Science databases with following key phrases: "CSF-venous fistula", "Spontaneous intracranial hypotension". Overall, 97 articles were found during the initial search; 15 were included for the final analysis, with a total number of 137 patients. Epidural blood patch (EBP) was performed as a first-line treatment in 37.1% of patients in individual data group, often not combined with fibrin glue (61.5%). Either partial (69.2%) or no resolution (30.8%) of symptoms was achieved after EBP injection. Nerve root ligation was the most common method of exclusion of CSF-venous fistula. Complete resolution of symptoms was achieved in 69.0% of patients, in 21.4% it was partial and in 9.5% no regress was found. Endovascular treatment was described only in 1 study. Surgical ligation of fistula is a treatment of choice. In approximately 70% of patients complete long-term resolution of symptoms is achieved after surgery. Endovascular treatment and fibrin glue injections are prospective and evolving options, which require further investigation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hippocampal preservation helped better performance on memory tests in HBOT groups. • HBOT associated with shunt increases the expression of the antioxidant enzyme SOD1. • Joint therapies preserve total and replicating cells in GM and the neuronal viability. • HBOT associated with derivation reduced apoptosis via Caspase-3 in the cortex. • Better myelin preservation in periventricular white matter in HBOT groups. Hydrocephalus is characterized by the accumulation of CSF within the cerebral ventricles and the subarachnoid space. Ventricular volume can progressively increase and generate serious damage to the nervous system, with cerebral hypoxia/ischemia as one of the most important factors involved. Hyperbaric oxygen therapy (HBOT) improves oxygen supply to tissues, which can reduce the progression of lesions secondary to ventricular enlargement. We evaluated whether HBOT associated with CSF diversion can promote neuroprotective effects to structures damaged by ventriculomegaly and understand its role. Seven-day-old male Wistar Hannover rats submitted to hydrocephalus by intracisternal injection of 15% kaolin were used. The animals were divided into six groups, with ten animals in each: control, control associated with hyperbaric therapy, hydrocephalic without treatment, hydrocephalic treated with hyperbaric oxygen therapy, hydrocephalic treated with CSF deviation, and hydrocephalic treated with hyperbaric oxygen therapy associated with CSF deviation. To assess the response to treatment, behavioral tests were performed such as modified Morris water maze and object recognition, evaluation by transcranial ultrasonography, histology by Hematoxylin–Eosin and Luxol Fast Blue, immunohistochemistry for GFAP, Ki-67, Caspase-3, COX-2, NeuN and SOD1, and biochemical ELISA assay for GFAP and MBP. The results show that the association of treatments exerts neuroprotective effects such as neurobehavioral improvement, preservation of periventricular structures, antioxidant effect, and reduction of damage resulting from ischemia and the neuroinflammatory process. We conclude that HBOT has the potential to be used as an adjuvant treatment to CSF deviation surgery in experimental hydrocephalus. [ABSTRACT FROM AUTHOR]

Central nervous system infection after neurosurgical procedures is a severe complication with high morbidity rates and sometimes mortality. Our experimental study aimed to investigate the biochemical and histopathologic effects of vancomycin on neural tissues when applied to the cisterna magna. Wistar albino rats were randomly divided into 4 groups: Control (Group 1) and different vancomycin dose groups (Groups 2, 3, and 4). In Group 1, 0.1 mL cerebrospinal fluid was drained from the cisterna magna and 0.1 mL 0.9% NaCI (normal saline) was administered into the subarachnoid space. In the study groups, 0.1 mL cerebrospinal fluid was drained from the cisterna magna and 0.1 mg/200g rat per day (Group 2), 0.2 mg/200g rat per day (Group 3), and 0.4 mg/200g rat per day (Group 4) vancomycin were administered into the subarachnoid space for 7 days. All rats were sacrificed on the eighth day. Serum superoxide dismutase and catalase levels were measured. Histopathologic and immunohistochemical analyses were conducted. The findings showed that the administration of 0.2 and 0.4 mg/kg doses had significant differences in superoxide dismutase and catalase activity compared with the controls (P < 0.05). These vancomycin doses also induced the apoptotic process, and the enzyme activity results correlated with immunohistochemical results. Dose-related neurotoxicity of intrathecal vancomycin was shown at the cellular level. The importance of dose regulation of intrathecal vancomycin has come into view. To our knowledge, this is the first study in the literature that has investigated the neurotoxic effects of vancomycin. [ABSTRACT FROM AUTHOR]

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe subtype of stroke occurring at a relatively young age with a significant socioeconomic impact. Treatment of aSAH includes early aneurysm exclusion, intensive care management, and prevention of complications. Once the aneurysm rupture occurs, blood spreading within the subarachnoid space triggers several molecular pathways causing early brain injury and delayed cerebral ischemia. Pathophysiologic mechanisms underlying brain injury after aSAH are not entirely characterized, reflecting the difficulties in identifying effective therapeutic targets for patients with aSAH. Although the improvements of the last decades in perioperative management, early diagnosis, aneurysm exclusion techniques, and medical treatments have increased survival, vasospasm and delayed cerebral infarction are associated with high mortality and morbidity. Clinical practice can rely on a few specific therapeutic agents, such as nimodipine, a calcium-channel blocker proved to reduce severe neurologic deficits in these patients. Therefore, new pharmacologic approaches are needed to improve the outcome of this life-threatening condition, as well as a tailored rehabilitation plan to maintain the quality of life in aSAH survivors. Several clinical trials are investigating the efficacy and safety of emerging drugs, such as magnesium, clazosentan, cilostazol, interleukin 1 receptor antagonists, deferoxamine, erythropoietin, and nicardipine, and continuous lumbar drainage in the setting of aSAH. This narrative review focuses on the most promising therapeutic interventions after aSAH. [ABSTRACT FROM AUTHOR]

Congenital arachnoid cysts in the middle fossa accounts for 50% of all intracranial arachnoid cysts. Several management options have been described; however, no single technique has been universally adopted. We describe a series of pediatric patients with middle cranial fossa arachnoid cyst that were treated through an innovative minimally invasive endoscopic technique, along with their clinical aspects and surgical outcomes. Data from 65 patients operated between 2012 and 2018 were retrospectively analyzed. Follow-up ranged from 12 to 96 months. Clinical presentation and surgical outcomes were collected. Endoscopic cystocisternostomy was performed in all patients using a mini endoscope. There were 41 male and 24 female patients, with a mean age of 5.3 years at the time of treatment. Except for 4 patients, all presented with 1 or more symptoms, and the most frequent were intracranial hypertension signs. All patients were treated with the same surgical technique, with an efficacy of 81.5%. Using a mini endoscope allow us to perform multiple fenestrations along the arachnoid and deeply inspect the basal cisterns, achieving a much wider communication between the cyst and subarachnoid space with a high success rate and minimal invasiveness. [ABSTRACT FROM AUTHOR]

Background: Acute subdural hematoma (ASDH) and chronic subdural hematoma (CSDH) in infants have been regarded as highly specific for abuse. Other causes of CSDH have not been investigated in a large population.Purpose: The purpose of this study was to investigate to what extent external hydrocephalus is present in infants with ASDH and CSDH undergoing evaluation for abuse.Material and Methods: Eighty-five infants suspected of being abused, with ASDH (n = 16) or CSDH (n = 69), were reviewed regarding age, risk factor profiles, craniocortical width (CCW), sinocortical width (SCW), frontal interhemispheric width (IHW), subarachnoid space width (SSW), and head circumference (HC). In infants with unilateral subdural hematoma (SDH), correlations between contralateral SSW and ipsilateral CCW and SDH width were investigated.Results: Infants with CSDH had significantly lower mortality, were more often premature and male, and had significantly higher CCW, SCW, IHW, and SSW than infants with ASDH (P < 0.05). Ipsilateral CCW (R = 0.92, P < 0.001) and SDH width (R = 0.81, P < 0.01) correlated with contralateral SSW. Increased HC was more prevalent in infants with CSDH (71%) than in infants with ASDH (14%) (P < 0.01). Forty-two infants, all with CSDH, had at least one of CCW, SCW, or IHW ≥95th percentile. Twenty infants, all with CSDH, had CCW, SCW, and IHW >5 mm, in addition to increased HC.Conclusion: A substantial proportion of infants with CSDH who had been suspected of being abused had findings suggesting external hydrocephalus. [ABSTRACT FROM AUTHOR]

Spinal anaesthesia involves the injection of local anaesthetic solution into the intrathecal space. It is a widely practised anaesthetic technique that can provide surgical anaesthesia for procedures below the umbilicus. Due to the proximity of the central nervous system, safe practice is of paramount importance and requires a good understanding of relevant anatomy, physiology and pharmacology. Complications are rare but need to be recognized and managed rapidly and appropriately. [ABSTRACT FROM AUTHOR]

• Serum annexin A1 levels are decreased substantially after aneurysmal subarachnoid hemorrhage. • Serum annexin A1 levels are closely correlated with severity of aneurysmal subarachnoid hemorrhage. • Serum annexin A1 appears as an independent predictor for a 6-month poor outcome after aneurysmal subarachnoid hemorrhage. • Serum annexin A1 levels efficiently predict a 6-month poor outcome after aneurysmal subarachnoid hemorrhage. Annexin A1 might be neuroprotective and serum annexin A1 concentrations were markedly declined after severe traumatic brain injury. We determine dthe ability of serum annexin A1 to assess severity and predict prognosis after aneurysmal subarachnoid hemorrhage (aSAH). We included 157 aSAH patients and 157 healthy subjects. Serum annexin A1 measurements were measured. A poor outcome was designated as Glasgow outcome scale score of 1–3. Multivariate logistic regression analysis was applied to identify predictors of a poor 6-month outcome. Serum annexin A1 concentrations were significantly lower in patients than in controls. Annexin A1 concentrations were strongly correlated with the World Federation of Neurological Surgeons scale (WFNS) score, Hunt-Hess score, Glasgow coma scale score and modified Fisher score. A total of 59 patients (37.6%) experienced a poor outcome. Serum annexin A1, WFNS score and modified Fisher score emerged as the 3 independent predictors for a poor outcome after aSAH. Under ROC curve analysis, serum annexin A1 had a fair accuracy to predict a poor outcome, AUC of serum annexin A1 concentration was equivalent to those of WFNS score and modified Fisher score and AUC of combination of the 3 factors significantly exceeded that of each one alone. Annexin A1 may be involved in the occurrence and progression of secondary brain injury after aSAH. Detection of serum annexin A1 may have certain ability for assessment of severity and prediction of long-term prognosis following aSAH. [ABSTRACT FROM AUTHOR]

The nervous system is divided topographically into two parts: the central nervous system and the peripheral nervous system. From a functional perspective, however, the two systems are intimately connected and function in an integrated and coordinated manner. The central nervous system comprises the brain and spinal cord, while the peripheral nervous system is made up of the cranial and peripheral nerves and associated neurological structures. This article presents a broad and general overview of the structure and organization of the nervous system emphasizing several important functional features. [ABSTRACT FROM AUTHOR]

Surgical treatment of idiopathic normal pressure hydrocephalus (iNPH) by ventriculoperitoneal (VP) or lumboperitoneal (LP) shunting can achieve long-term recovery of activities of daily living; however, in a subset of patients, maintenance of independence lasted for <6 months. This study examined positive preoperative predictive factors of short-term outcome for shunted iNPH patients. Over a 9-year period, consecutive patients from multiple centers diagnosed with probable iNPH underwent either VP or LP shunt surgery. Preoperative variables of age, symptom duration, iNPH severity, tap test response, and magnetic resonance imaging findings of disproportionately enlarged subarachnoid space hydrocephalus (DESH) or incomplete DESH were retrospectively evaluated in relation to 1-year postoperative outcome. Outcome for 154 shunt patients (12 VP, 142 LP) as measured by postoperative disability modified Rankin Scale (mRS) and iNPH−gait disturbance (GD) was the same regardless of age. Symptom duration was inversely correlated with both iNPH severity (P < 0.0001) and postoperative improvement at 1 year (P = 0.0015). Severity also correlated inversely with postoperative improvement at 1 year (P < 0.0001). Age was not significantly correlated with the degree of postoperative improvement (mRS: P = 0.487; iNPH grading scale [GD]: P = 0.725). Outcome at 1 year (mRS, gait domain, and activities of daily living significantly improved in patients with a good response to the tap test (P < 0.0001) Preoperative DESH correlated with improvement in mRS and GD (P < 0.0001). Mild preoperative iNPH severity, shorter preoperative symptom duration, good tap test response, and complete DESH were associated with good short-term postoperative outcome at 1 year. These positive factors may be useful for prediction of short-term surgical outcome in iNPH patients. [ABSTRACT FROM AUTHOR]

For aSAH patients with external ventricular drainage (EVD) because of hydrocephalus, the consensus on application of CSF drainage from the lumbar cistern is mixed owing to concerns about its safety and questionable effectiveness. This study evaluated the additional effectiveness of CSF drainage from the lumbar cistern in aSAH patients with EVD. This was a retrospective and observational study of adult patients with aSAH who were admitted to the intensive care unit at the Wuhan Union Hospital between June 2018 and June 2019. Three aSAH patients with EVD and serial lumbar punctures (LPs) were selected for comparison of CSF components. Four more aSAH patients who underwent divergent CSF drainage were selected to profile the additional effectiveness of lumbar cistern drainage in aSAH patients with EVD. Cases 1–3 with EVD and serial LPs showed dramatically higher red blood cell (RBC) and leukocyte counts with steeper changing curve in the lumbar cistern CSF than in the ventricle CSF. Case 5 had EVD alone and showed a slower clearing rate of blood clot in subarachnoid space compared with case 1. Case 4, with serial LPs alone, showed a steep changing curve of both RBC and leukocyte counts in the lumbar cistern CSF. Cases 6 and 7, with EVD and follow-up LPs, showed dramatically higher RBC and leukocyte counts in the lumbar cistern CSF than in the ventricle CSF after almost 2 weeks of EVD. For aSAH patients with EVD, serial LPs can accelerate clearance of toxic products from the subarachnoid space. [ABSTRACT FROM AUTHOR]

• The motion of Cerebrospinal Fluid and the dispersion of a solute in the spinal canal are studied. • The Eulerian velocity is modelled by an asymptotic formulation as a purely oscillatory motion and a steady-streaming flow. • The long-time transport of a solute is analytically modelled by means of a two-time-scale asymptotic description. • Direct numerical simulations of the problem are performed to validate the analytical model, with an excellent agreement. • In a human anatomy, the time-averaged flow exhibits recirculating regions that hinder the transport of drugs in the canal. The motion of the cerebrospinal fluid in the spinal subarachnoid space, a slender annular canal surrounding the spinal cord, exhibits an oscillatory velocity component driven by the pressure oscillations induced by the cardiac and respiratory cycles. A time-averaged transport equation has been recently proposed for describing solute transport along the canal, circumventing the need to compute the concentration fluctuations resulting from this fast oscillatory motion. The accuracy and limitations of this time-averaged description are tested here by means of comparisons with results of direct numerical simulations spanning hundreds of oscillation cycles, as needed to generate significant dispersion of the solute. The comparisons between the numerical results and the predictions of the analytical model include velocity fields and quantifications of transient solute-dispersion events for selected values of the flow parameters and two different idealized, canonical geometries of the spinal canal. The comparisons clearly demonstrate the accuracy of the time-averaged description of the analytical model, which is seen to provide a good fidelity at a fraction of the computational cost involved in the direct numerical simulations. The variations of canal eccentricity along the spinal canal are found to play an important role in the dynamics of the solute transport, leading to the emergence of closed recirculating Lagrangian vortices that may hinder solute dispersion along the canal, as revealed by both direct numerical simulations and time-averaged results. [ABSTRACT FROM AUTHOR]

Patients diagnosed with low-pressure hydrocephalus typically present with enlarged ventricles and unusually low intracranial pressure, often measuring below 5 cmH 2 O or even below atmospheric pressure. This atypical presentation often leads to low recognition and diagnostic rates. The development of low-pressure hydrocephalus is believed to be associated with a decrease in the viscoelasticity of brain tissue or separation between the ventricular and subarachnoid spaces. Risk factors for low-pressure hydrocephalus include subarachnoid hemorrhage, aqueduct stenosis, prior cranial radiotherapy， ventricular shunting, and cerebrospinal fluid leaks. For potential low-pressure hydrocephalus, diagnostic criteria include neurological symptoms related to hydrocephalus, an Evans index >0.3 on imaging, ICP ≤ 5 cm H 2 O, symptom improvement with negative pressure drainage, and exclusion of ventriculomegaly caused by neurodegenerative diseases. The pathogenesis and pathophysiological features of low-pressure hydrocephalus differ significantly from other types of hydrocephalus, making it challenging to restore normal ventricular morphology through conventional drainage methods. The primary treatment options for low-pressure hydrocephalus involve negative pressure drainage and third ventriculostomy. With appropriate treatment, most patients can regain their previous neurological function. However, in most cases, permanent shunt surgery is still necessary. Low-pressure hydrocephalus is a rare condition with a high rate of underdiagnosis and mortality. Early identification and appropriate intervention are crucial in reducing complications and improving prognosis. • In this review, we discussed the underlying mecnanism contributing to the development of LPH • We shed light on the distinctive pathophysiological features of LPH that differentiate it from other types of hydrocephalus • We outlined the primary treatments for LPH, including negative pressure drainage and third ventriculostomy. [ABSTRACT FROM AUTHOR]

The cochlear aqueduct (CA) connects between the perilymphatic space of the cochlea and the subarachnoid space in the posterior cranial fossa. The study aimed to examine 1) whether cavitation of the CA occurs on the subarachnoid side or the cochlear side and 2) the growth and/or degeneration of the CA and its concomitant vein. We examined paraffin-embedded histological sections from human fetuses: 15 midterm fetuses (crown-rump length or CRL, 39–115 mm) and 12 near-term fetuses (CRL, 225–328 mm). A linear mesenchymal condensation, i.e., a likely candidate of the CA anlage, was observed without the accompanying vein at 9–10 weeks. The vein appeared until 15 weeks, but it was sometimes distant from the CA. At 10–12 weeks, the subarachnoid space (or the epidural space) near the glossopharyngeal nerve rapidly protruded into the CA anlage and reached the scala tympani, in which cavitation was gradually on-going but without epithelial lining. However, CA cavitation did not to occur in the anlage. At the opening to the scala, the epithelial-like lining of the CA lost its meningeal structure. At near-term, the CA was often narrowed and obliterated. The CA develops from meningeal tissues when the cavitation of the scala begins. The latter cavitation seemed to reduce tissue stiffness leading, to meningeal protrusion. The so-called anlage of CA might be a phylogenetic remnant of the glossopharyngeal nerve branch. A course of cochlear veins appears to be determined by a rule different from the CA development. [ABSTRACT FROM AUTHOR]

Cerebral vasospasm in patients after aneurysmal subarachnoid hemorrhage (aSAH) continues to be a major source of morbidity despite significant clinical and basic science research. The removal of blood and its degradation products from the subarachnoid space through prophylactic lumbar drainage (LD) is a favorable option. However, several studies have delivered conflicting conclusions on its efficacy after aSAH. Systematic searches of Medline, Embase, and Cochrane Central Register of Controlled Trials were performed. The primary outcome was a good functional outcome (modified Rankin scale score, 0–2). Secondary outcomes included symptomatic vasospasm, secondary cerebral infarction, and mortality. A total of 14 studies reporting on 2473 patients with aSAH were included in the meta-analysis. Compared with the non-LD group, no significant differences were found in the rates of good functional outcomes in the LD group at discharge to 1 month (risk ratio [RR], 1.28; 95% confidence interval [CI], 0.64–2.58) or at 6 months (RR, 1.12; 95% CI, 0.97–1.41). These findings were consistent in the subgroup analyses of only randomized controlled trials or observational studies. LD was associated with lower rates of symptomatic vasospasm (RR, 0.61; 95% CI, 0.48–0.77), secondary cerebral infarction (RR, 0.59; 95% CI, 0.45–0.79), and mortality at discharge to 1 month (RR, 0.58; 95% CI, 0.41–0.82). The effect on mortality diminished at 6 months (RR, 0.70; 95% CI, 0.34–1.45). However, when analyzing only randomized controlled trials, the benefit of LD on lower rates of mortality continued even at 6 months (RR, 0.75; 95% CI, 0.58–0.99). For aSAH patients, the use of LD is associated with benefits in the rates of vasospasm, secondary cerebral infarctions, and mortality, without an increased risk of adverse events. [ABSTRACT FROM AUTHOR]

Arachnoid cysts are benign cerebrospinal fluid collection within a duplication of arachnoid membrane and, when found in the retrocerebellar site, they may be associated with tonsils herniation. This rare situation of coexisting retrocerebellar arachnoid cyst (AC) and Chiari malformation type 1 (CM-1) have been previously reported in few cases (10 patients) with syringomyelia and hydrocephalus described to be the most relevant issues. The aim of this paper is to describe 3 pediatric cases of this condition with a systematic review of the literature, underlining the importance of surgical management tailored to the pathogenic mechanism. A restrospective analysis of patients treated for coexisting CM-1 and ACs at the authors' institution has been carried out. A case of a 10-month-old baby with coexisting AC and CM-1 with tri-ventricular hydrocephalus treated with endoscopic third ventriculostomy, a case of a 1-year-old child with a huge retrocerebellar AC and CM-1 treated with a cysto-peritoneal shunt, and a case of a 15-year-old child with retrocerebellar AC causing symptomatic CM-1 treated with C0-C2 decompression, AC fenestration and duraplasty are described. A long-term follow-up is reported. Surgical management of coexisting ACs and CM-1 should not aim at the complete resolution of the cyst or of tonsil herniation, especially when pediatric patients are treated. Rather, the purpose of the neurosurgeon should be to understand the underlying pathogenic mechanism, and then restoring both the cerebrospinal fluid flow in the posterior fossa and the dynamic equilibrium between ventricles, cyst, and subarachnoid space. [ABSTRACT FROM AUTHOR]

A 62-year-old man presented a diffuse and predominantly cisternal acute nonaneurysmal subarachnoid hemorrhage associated with hydrocephalus. An external ventricular drain was placed, followed by clinical deterioration after its removal. At this point, a heavily T2-weighted high-resolution sequence of a brain magnetic resonance imaging showed acute hydrocephalus recrudescence and multiple arachnoid adhesions in the supravermian and interpeduncular cisterns, creating a loculated/cystic appearance. The diagnosis of intracranial arachnoiditis was made. Intracranial arachnoiditis results from meningeal inflammation. Fibrosis and adhesions at the subarachnoid spaces may follow, restricting cerebrospinal fluid circulation, particularly at the cranial base. Hydrocephalus probably resulted from the combination of subarachnoid hemorrhage and extensive scaring at the basal cisterns, precluding transdural and transvenous cerebrospinal fluid efflux. Heavily T2-weighted high-resolution magnetic resonance imaging sequences allow an exquisite depiction of arachnoiditis, displaying obstructive cisternal membranes, and contribute to better etiologic assessment and management of hydrocephalus. [ABSTRACT FROM AUTHOR]

• Ventricular to lumbar protein gradients in CSF fit a Gaussian error function. • CSF protein concentrations modulate molecular current through the barrier. • Normal and pathological protein dynamics share the diffusion-CSF flow model. • Reference range in Reibergrams apply for ventricular, cisternal and lumbar CSF. • Detection of intrathecal Ig synthesis does not depend on CSF extraction volume. Concentrations of blood-derived proteins increase non-linearly between ventricular and lumbar CSF, which could not be satisfactorily explained by known barrier models. Protein data analysis with OriginLab. Interpretations with Quotient diagrams by CSF/ Statistics software. 1. Nonlinearly increasing protein concentrations between ventricular and lumbar CSF are fitting to a Gaussian error function, the differential of the nonlinear concentration distribution function between blood and CSF. Increasing CSF protein concentrations (changing steady state), either due to barrier dysfunctions with reduced CSF flow rate or due to normal steady influx along the rostro-caudal flow path, increase the local gradient at the diffusion flow interface and thus the molecular current through the barrier. 2. With a time- and space-related derivation, the hyperbolic relation between two molecules in CSF (e.g., QIgG: QAlb in quotient diagrams) is independent of the position in subarachnoid space: The reference line, Qlim, in quotient diagrams allows detection of intrathecal synthesis in ventricular, cisternal and lumbar CSF. Detection of intrathecal synthesis is not influenced by CSF extraction volume, only the barrier function, QAlb, is volume sensitive. Common biophysics for barrier dysfunction and normal protein gradients provide additional evidence for the diffusion-flow interface model for barrier functions. [ABSTRACT FROM AUTHOR]

Multi-spin echo acquisition cine imaging (MUSACI) is a method used for cerebrospinal fluid (CSF) dynamics imaging based on the proton phase dispersion and flow void using 3D multi-spin echo imaging. In a previous study, the refocusing flip angle of MUSACI was set at a constant 80°. We conducted the present study to investigate the preservation the CSF signal intensity even in a long echo train and improve the ability to visualize CSF movement by modifying the refocusing flip angle in MUSACI. The MUSACI images were acquired in 10 healthy volunteers (7 men and 3 women; age range 24–44 years; mean age 29.4 ± 6.2 years) with a 3.0 Tesla MR scanner. Five refocusing flip angle sets were applied: constant 30°, constant 50°, constant 80°, pseudo-steady state (PSS) 50°–70°–100° (PSS 50°), and PSS 80°–100°–130° (PSS 80°). In all sequences, the in-plane spatial resolution was 0.58 × 0.58 mm2, and the CSF movement for one heartbeat was drawn at 80-msec intervals. The signal intensity (SI) of CSF in the lateral ventricle, the foramen of Monro, the third ventricle, the fourth ventricle, and the pons was measured on MUSACI. Pearson's correlation coefficient was calculated between the CSF SI and effective echo time (TE; TE eff) in the lateral ventricle. Both antegrade and retrograde CSF movements on the midsagittal MUSACI images and the retrograde CSF movement in the foramen of Monro was observed in all sequences with the constant flip angles. A strong reverse correlation between the CSF SI in the lateral ventricle and TE eff values was observed with constant 30° (r = −0.96, p < 0.01), constant 50° (r = −0.97, p < 0.01) and constant 80° (r = −0.88, p < 0.01). A weak positive correlation was observed with PSS 50° (r = 0.28, p = 0.43), and a moderate reverse correlation was observed at PSS 80° (r = −0.60, p = 0.07). The SI values of the foramen of Monro, the third ventricle, and the fourth ventricle were significantly lower than that of the lateral ventricle, and those values were higher than that of the pons in both the constant 80° sequence and the PSS 50° sequence. PSS 50° could be the optimal flip angle scheme for MUSACI, because the SI changes due to CSF movement and the SI preservation due to a long echo train were large due to the use of the refocusing flip angle method. • High-resolution (0.58 × 0.58 mm2) 3D CSF dynamic imaging could be obtained by MUSACI. • CSF movement is more detectable using a lower refocusing flip angle in MUSACI. • Variable refocusing flip angle preserves the CSF signal due to a long echo train. • Anterograde and retrograde CSF movement in one cardiac cycle is visualized in MUSACI. [ABSTRACT FROM AUTHOR]

Stem cell transplantation is a potential treatment for intractable spinal cord injury (SCI), and allogeneic human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising candidate because of the advantages of immune privilege, paracrine effect, immunomodulatory function, convenient collection procedure and little ethical concern, and there is an urgent need to develop a safe and effective protocol regarding their clinical application. A prospective, single-center, single-arm study in which subjects received four subarachnoid transplantations of hUC-MSCs (1 × 106 cells/kg) monthly and were seen in follow-up four times (1, 3, 6 and 12 months after final administration) was conducted. At each scheduled time point, safety and efficacy indicators were collected and analyzed accordingly. Adverse events (AEs) were used as a safety indicator. American Spinal Injury Association (ASIA) and SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) total scores at the fourth follow-up were determined as primary efficacy outcomes, whereas these two indicators at the remaining time points as well as scores of pinprick, light touch, motor and sphincter, muscle spasticity and spasm, autonomic system, bladder and bowel functions, residual urine volume (RUV) and magnetic resonance imaging (MRI) were secondary efficacy outcomes. Subgroup analysis of primary efficacy indicators was also performed. Safety and efficacy assessments were performed on 102 and 41 subjects, respectively. Mild AEs involving fever (14.1%), headache (4.2%), transient increase in muscle tension (1.6%) and dizziness (1.3%) were observed following hUC-MSC transplantation and resolved thoroughly after conservative treatments. There was no serious AE. ASIA and IANR-SCIFRS total scores revealed statistical increases when compared with the baselines at different time points during the study, mainly reflected in the improvement of pinprick, light touch, motor and sphincter scores. Moreover, subjects showed a continuous and remarkable decrease in muscle spasticity. Regarding muscle spasm, autonomic system, bladder and bowel functions, RUV and MRI, data/imaging at final follow-up showed significant improvements compared with those at first collection. Subgroup analysis found that hUC-MSC transplantation improved neurological functions regardless of injury characteristics, including level, severity and chronicity. The authors' present protocol demonstrates that intrathecal administration of' allogeneic hUC-MSCs at a dose of 106 cells/kg once a month for 4 months is safe and effective and leads to significant improvement in neurological dysfunction and recovery of quality of life. Graphical abstract of repeated subarachnoid administrations of hUC-MSCs in treating SCI. Following inclusion assessment, appropriate SCI subjects whose chronicity are no less than two months receive baseline evaluation. In this non blinded study, all participants receive a maximum of four times of administration at the interval of one calendar month each time. At each time point of stem cell transplantation and post-administration follow-up, regular follow-ups for both safety and efficacy outcomes are performed for a maximum of eight times, which is expected at the first, second, third, and fourth transplantation, as well as one, three, six and 12 months after the final hUC-MSCs transplantation Image, graphical abstract [ABSTRACT FROM AUTHOR]

Administration of substances directly into the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord is one approach that can circumvent the blood-brain barrier to enable drug delivery to the central nervous system (CNS). However, molecules that have been administered by intrathecal injection, which includes intraventricular, intracisternal, or lumbar locations, encounter new barriers within the subarachnoid space. These barriers include relatively high rates of turnover as CSF clears and potentially inadequate delivery to tissue or cellular targets. Nanomedicine could offer a solution. In contrast to the fate of freely administered drugs, nanomedicine systems can navigate the subarachnoid space to sustain delivery of therapeutic molecules, genes, and imaging agents within the CNS. Some evidence suggests that certain nanomedicine agents can reach the parenchyma following intrathecal administration. Here, we will address the preclinical and clinical use of intrathecal nanomedicine, including nanoparticles, microparticles, dendrimers, micelles, liposomes, polyplexes, and other colloidalal materials that function to alter the distribution of molecules in tissue. Our review forms a foundational understanding of drug delivery to the CSF that can be built upon to better engineer nanomedicine for intrathecal treatment of disease. Unlabelled Image [ABSTRACT FROM AUTHOR]

Spinal extradural arachnoid cyst is an uncommon cause of spinal cord compression. It results from a small dural defect that leads to cerebrospinal fluid (CSF) accumulation in the cyst and subarachnoid space, and the cyst can compress the spinal cord and nerve roots. Surgery is the treatment of choice in symptomatic patients, and most cases have an immediately satisfying outcome after surgery. A 10-year-old Thai boy presented with progressive weakness in both legs. Magnetic resonance imaging (MRI) demonstrated a giant cystic lesion 23 cm in length from T1-L2 level. To our knowledge, this is the longest arachnoid cyst that has been reported in children. The operation included unilateral paraspinal muscle dissection with spinous process translation techniques, T1-L4 laminectomy, total cyst excision, and dural defect repair at the T4 level. The symptoms were fully resolved within 2 months after surgery. However, thoracic kyphosis was slightly increased, but the patient still has a normal sagittal profile. Spinal arachnoid cyst is rare, especially in children. Early diagnosis and treatment are essential for improving the chance of full recovery, and for avoiding complication and irreparable defect. Total cyst removal with dural repair remains the best treatment alternative; however, potential complications, especially spinal malalignment after extensive laminectomy, must be considered. Postoperative MRI showed normal CSF flow and no spinal cord compression. The muscle-sparing technique with multiple-level laminectomy without spinal fusion that we used in this case provided a satisfying outcome. [ABSTRACT FROM AUTHOR]

Nonmissile penetrating injuries to the craniocervical junction caused by a glass fragment are rare, and a standard management strategy has not been established. A 75-year-old Japanese man was brought into our emergency department after receiving a left retroauricular stab wound by broken glass fragments. After spinal immobilization, a computed tomography (CT) scan revealed glass fragments penetrating at the right craniocervical junction to the interatlantooccipital subarachnoid space. CT angiography showed that both vertebral arteries were not injured. Magnetic resonance imaging demonstrated that the glass fragments did not penetrate the cervical cord or medulla oblongata. These glass fragments were removed via a midline incision from the external occipital protuberance to the C7 and with laminectomy without suboccipital craniectomy. Five of the glass fragments were found and removed in total. The dural defect was patched with a free fascia autograft. His postoperative course was uneventful. Postoperative CT angiography showed that both vertebral arteries were intact and the glass fragments had been removed completely. CT graphical diagnosis is useful for the management of penetrating craniocervical junction trauma, and it should be considered in the evaluation of patients who have suffered craniocervical penetrating injury even in the absence of major wounds or bleeding. Spinal immobilization of patients with craniocervical penetrating injuries is crucial to avoid not only secondary neurologic damage but also secondary critical vascular damage. Incomplete or inadequate assessment of craniocervical stab wounds results in unexpected hazards that are preventable. [ABSTRACT FROM AUTHOR]