Discover the most talked about and latest scientific content & concepts.

Concept: Subarachnoid space


Prospective studies of infants at risk for autism spectrum disorder have provided important clues about the early behavioural symptoms of autism spectrum disorder. Diagnosis of autism spectrum disorder, however, is not currently made until at least 18 months of age. There is substantially less research on potential brain-based differences in the period between 6 and 12 months of age. Our objective in the current study was to use magnetic resonance imaging to identify any consistently observable brain anomalies in 6-9 month old infants who would later develop autism spectrum disorder. We conducted a prospective infant sibling study with longitudinal magnetic resonance imaging scans at three time points (6-9, 12-15, and 18-24 months of age), in conjunction with intensive behavioural assessments. Fifty-five infants (33 ‘high-risk’ infants having an older sibling with autism spectrum disorder and 22 ‘low-risk’ infants having no relatives with autism spectrum disorder) were imaged at 6-9 months; 43 of these (27 high-risk and 16 low-risk) were imaged at 12-15 months; and 42 (26 high-risk and 16 low-risk) were imaged again at 18-24 months. Infants were classified as meeting criteria for autism spectrum disorder, other developmental delays, or typical development at 24 months or later (mean age at outcome: 32.5 months). Compared with the other two groups, infants who developed autism spectrum disorder (n = 10) had significantly greater extra-axial fluid at 6-9 months, which persisted and remained elevated at 12-15 and 18-24 months. Extra-axial fluid is characterized by excessive cerebrospinal fluid in the subarachnoid space, particularly over the frontal lobes. The amount of extra-axial fluid detected as early as 6 months was predictive of more severe autism spectrum disorder symptoms at the time of outcome. Infants who developed autism spectrum disorder also had significantly larger total cerebral volumes at both 12-15 and 18-24 months of age. This is the first magnetic resonance imaging study to prospectively evaluate brain growth trajectories from infancy in children who develop autism spectrum disorder. The presence of excessive extra-axial fluid detected as early as 6 months and the lack of resolution by 24 months is a hitherto unreported brain anomaly in infants who later develop autism spectrum disorder. This is also the first magnetic resonance imaging evidence of brain enlargement in autism before age 2. These findings raise the potential for the use of structural magnetic resonance imaging to aid in the early detection of children at risk for autism spectrum disorder or other neurodevelopmental disorders.

Concepts: Nuclear magnetic resonance, Subarachnoid space, Meninges, Brain, Autism spectrum, Magnetic resonance imaging, Cerebrospinal fluid, Autism


Object The pathophysiology of occult tethered cord syndrome (OTCS) with no anatomical evidence of a caudally shifted conus and a normal terminal filum is hard to understand. Therefore, the diagnosis of OTCS is often difficult. The authors hypothesized that the posterior displacement of the terminal filum may become prominent in patients with OCTS who are in a prone position if filum inelasticity exists, and they investigated prone-position MRI findings. Methods Fourteen patients with OTCS and 12 control individuals were examined using T2-weighted axial MRI with the patients in a prone position on a flat table. On each axial view, the distance between the posterior and anterior ends of the subarachnoid space (A), the distance between the posterior end of the subarachnoid space and the terminal filum (B), the distance between the posterior end of the subarachnoid space and the dorsal-most nerve among the cauda equina ©, and the distance between the posterior end of the subarachnoid space and the ventral-most nerve (D) were measured. The location ratios of the terminal filum, the dorsal-most nerve, and the ventral-most nerve were calculated by the ratio of A to B (defined as TF = B/A), A to C (defined as DN = C/A), and A to D (defined as VN = D/A), respectively. Patients underwent sectioning of the terminal filum with the aid of a surgical microscope. The low-back pain Japanese Orthopaedic Association score was obtained before surgery and at the final follow-up visit. Results On prone-position axial MRI, the terminal filum was separated from the cauda equina and was shifted caudally to posterior in the subarachnoid space in all patients with OTCS. The locations of the caudal cauda equina shifted to ventral in the subarachnoid space. The TF values in the OTCS group were significantly lower than those in the control group at the L3-4 (p = 0.023), L-4 (p = 0.030), L4-5 (p = 0.002), and L-5 (p < 0.001) levels. In contrast, the DN values in the OTCS group were significantly higher than those of the control group at the L-2 (p = 0.003), L2-3 (p = 0.002), L-3 (p < 0.001), L3-4 (p < 0.001), L-4 (p = 0.007), L4-5 (p = 0.003), and S-1 (p = 0.014) levels, and the VN values in the OTCS group were also significantly higher than those of the control group at the L2-3 (p = 0.022), L-3 (p = 0.027), L3-4 (p = 0.002), L-4 (p = 0.011), L4-5 (p = 0.019), and L5-S1 (p = 0.040) levels. Sections were collected during surgery for histological evaluation, and a decreased elasticity within the terminal filum was suggested. Improvements in the Japanese Orthopaedic Association score were observed at the final follow-up in all patients. Conclusions The authors' new method of using the prone position for MRI shows that the terminal filum is located significantly posterior and the cauda equina is located anterior in patients with OTCS, suggesting a difference in elasticity between the terminal filum and cauda equina.

Concepts: Cerebrospinal fluid, Subarachnoid space, Meninges, Nuclear magnetic resonance, Anatomy, Cauda equina, Magnetic resonance imaging, Spinal cord


Cerebral vasospasm (CV) and the resulting delayed cerebral ischemia (DCI) significantly contribute to poor outcomes following aneurysmal subarachnoid hemorrhage (aSAH). Free hemoglobin (Hb) within the subarachnoid space has been implicated in the pathogenesis of CV. Haptoglobin (Hp) binds free pro-oxidant Hb, thereby modulating its harmful effects. Humans can be of three Hp phenotypes: Hp1-1, Hp2-1, or Hp2-2. In several disease states, the Hp2-2 protein has been associated with reduced ability to protect against toxic free Hb. We hypothesized that individuals with the Hp2-2 phenotype would have more CV, DCI, mortality, and worse functional outcomes after aSAH. In a sample of 74 aSAH patients, Hp2-2 phenotype was significantly associated with increased focal moderate (P = 0.014) and severe (P = 0.008) CV and more global CV (P = 0.014) after controlling for covariates. Strong trends toward increased mortality (P = 0.079) and worse functional outcomes were seen for the Hp2-2 patients with modified Rankin scale at 6 wk (P = 0.076) and at 1 y (P = 0.051) and with Glasgow Outcome Scale Extended at discharge (P = 0.091) and at 1 y (P = 0.055). In conclusion, Hp2-2 phenotype is an independent risk factor for the development of both focal and global CV and also predicts poor functional outcomes and mortality after aSAH. Hp phenotyping may serve as a clinically useful tool in the critical care management of aSAH patients by allowing for early prediction of those patients who require increased vigilance due to their inherent genetic risk for the development of CV and resulting DCI and poor outcomes.

Concepts: Cerebrospinal fluid, Vasospasm, Subarachnoid space, Wilhelm Johannsen, Phenotype, Modified Rankin Scale, Gene, Subarachnoid hemorrhage


We previously reported that infants who developed autism spectrum disorder (ASD) had increased cerebrospinal fluid (CSF) in the subarachnoid space (i.e., extra-axial CSF) from 6 to 24 months of age. We attempted to confirm and extend this finding in a larger independent sample.

Concepts: Subarachnoid space, Autism, Autism spectrum, Cerebrospinal fluid


During and after missions on the International Space Station, some astronauts experience ophthalmic changes, including choroidal folds, optic disc edema, cotton-wool spots, globe flattening, and refraction changes. Astronauts with ophthalmic issues had significantly higher plasma concentrations of metabolites that are associated with the 1-carbon metabolic pathway than those without ophthalmic issues. We hypothesized that genetic differences might explain the metabolite differences. Indeed, genetics and B vitamin status were significant predictors of ophthalmic issues. We now have developed a hypothesis regarding the mechanisms that link 1-carbon pathway genetics and the condition that we suggest calling, “astronaut ophthalmic syndrome.” We maintain that this condition is genetically predisposed and is associated with endothelial dysfunction that is induced by oxidative stress. Subsequent edema can hinder cerebrospinal fluid efflux and can lead to locally increased pressures in the subarachnoid space within the orbit, which impinges on the optic nerve and/or eye in affected individuals. Confirming this hypothesis will help characterize the genetics of 1-carbon pathway metabolism, homocysteine, oxidative stress, endothelial dysfunction, and cardiovascular and potentially other diseases.-Zwart, S. R., Gibson, C. R., Gregory, J. F., Mader, T. H., Stover, P. J., Zeisel, S. H., Smith, S. M. Astronaut ophthalmic syndrome.

Concepts: Subarachnoid space, Scientific method, Genetics, International Space Station, Oxidative phosphorylation, Mir, Cerebrospinal fluid, Metabolism


Object Cerebral artery vasospasm is a major cause of death and disability in patients recovering from subarachnoid hemorrhage (SAH). Although the exact cause of vasospasm is unknown, one body of research suggests that clearing blood products by CSF drainage is associated with a lower frequency and severity of vasospasm. There are multiple approaches to facilitating CSF drainage, but there is inadequate evidence to determine the best practice. The purpose of this study was to explore whether continuous or intermittent CSF drainage was superior for reducing vasospasm. Methods The authors performed a randomized clinical trial. Within 72 hours of admission for SAH, patients with an external ventricular drain (EVD) were randomized to undergo continuous CSF drainage with intermittent intracranial pressure (ICP) monitoring (open-EVD group) or continuous ICP monitoring with intermittent CSF drainage (monitor-ICP group). Results After 60 patients completed the study, an interim analysis was performed. The complication rate of 52.9% for the open-EVD group was significantly higher than the 23.1% complication rate for the monitor-ICP group (OR 3.75, 95% CI 1.21-11.66, p = 0.022). These results were reported to the Data Safety and Monitoring Board and enrollment was terminated. The odds ratio of vasospasm for the open-EVD versus monitor-ICP group was not significant (OR 0.44, 95% CI 0.13-1.45, p = 0.177). Conclusions Continuous CSF drainage with intermittent ICP monitoring is associated with a higher rate of complications than continuous ICP monitoring with intermittent CSF drainage, but there is no difference between the two types of monitoring in vasospasm. Clinical trial registration no.: NCT01169454 ( ).

Concepts: Epidemiology, Lumbar puncture, Hydrocephalus, Subarachnoid space, Clinical trial, Intracranial pressure, Subarachnoid hemorrhage, Cerebrospinal fluid


OBJECTIVE The pathogenesis of syringomyelia associated with Chiari malformation type I (CM-I) is unclear. Theories of pathogenesis suggest the cerebellar tonsils may obstruct CSF flow or alter pressure gradients, or their motion might act as a piston to increase CSF pressure in the spinal subarachnoid space. This study was performed to measure cerebellar tonsillar and hindbrain motion in CM-I and assess the potential contributions to syrinx formation. METHODS Sixty-four CM-I patients and 25 controls were retrospectively selected from a clinical database, and all subjects had undergone cardiac-gated cine balanced fast-field echo MRI. There were a total of 36 preoperative CM-I scans, which consisted of 15 patients with and 21 patients without syringomyelia. Nineteen patients underwent paired pre- and postoperative imaging. Anteroposterior (AP) and superoinferior (SI) movements of the tip of the cerebellar tonsils, obex, fastigium of the fourth ventricle, pontomedullary junction, and cervicomedullary junction were measured. The distance between the fastigium and tip of the tonsils was used to calculate tonsillar tissue strain (Δi/i0). RESULTS CM-I patients had significantly greater cerebellar tonsillar motion in both the AP and SI directions than controls (AP +0.34 mm [+136%], p < 0.001; SI +0.49 mm [+163%], p < 0.001). This motion decreased after posterior fossa decompression (AP -0.20 mm [-33%], p = 0.001; SI -0.29 mm [-36%]; p < 0.001), but remained elevated above control levels (AP +56%, p = 0.021; SI +67%, p = 0.015). Similar trends were seen for all other tracked landmarks. There were no significant differences in the magnitude or timing of motion throughout the hindbrain between CM-I patients with and without syringomyelia. Increased tonsillar tissue strain correlated with Valsalva headaches (p = 0.03). CONCLUSIONS Cerebellar tonsillar motion may be a potential marker of CM-I and may have use in tailoring surgical procedures. The lack of association with syringomyelia suggests that tonsillar motion alone is not the driver of syrinx formation. Tonsillar tissue strain may play a part in the pathophysiology of Valsalva headaches.

Concepts: Associated Press, Subarachnoid hemorrhage, Central nervous system, Cerebellum, Subarachnoid space, Syringomyelia, Cerebrospinal fluid, Arnold-Chiari malformation


Fluoroscopically guided, contrast-enhanced epidural steroid injections (ESIs) are frequently performed for radicular symptoms. Interventionalists performing these procedures should have a thorough and detailed understanding of spinal anatomy to safely and effectively deliver the desired injectate to the targeted site. Being able to differentiate epidural from nonepidural contrast flow is vital as is recognizing flow to undesired locations. This article summarizes the characteristics that distinguish between ideal epidural flow patterns and nonideal subarachnoid, intradural, and other suboptimal contrast flow patterns. Recognizing these patterns is essential for safe and successful ESIs and to prevent avoidable complications.

Concepts: Integrated Project, Performing arts, Subarachnoid space, Epidural, Performance, Pattern, Flow to HDL


Type I Chiari malformation (CMI) is a neurological condition in which the cerebellar tonsils descend into the cervical spinal subarachnoid space resulting in cervico-medullary compression. Early case-control investigations have indicated cognitive deficits in the areas of attention, memory, processing speed, and visuospatial function. The present study further examined cognitive and emotional processing deficits associated with CMI using a dual-task paradigm. Nineteen CMI patients were recruited during pre-surgical consultation and 19 matched control participants identified emotional expressions in separate single and asynchronous dual-task designs. To extend earlier behavioral studies of cognitive effects in CMI, we recorded event-related potentials (ERPs) in the dual-task design. Though response times were slower for CMI patients across the two tasks, behavioral and ERP analyses indicated that patients did not differ from matched controls in the ability to allocate attentional resources between the two tasks. P1 ERP component analyses provided no indication of an emotional arousal deficit in our CMI sample while P3 ERP component analyses suggested a CMI-related deficit in emotional regulation. P3 analysis also yielded evidence for a frontalization of neurophysiological activity in CMI patients. Pain and related depression and anxiety factors accounted for CMI deficits in single-task, but not dual-task, response times. Results are consistent with a dysfunctional fronto-parietal attentional network resulting from either the indirect effects of chronic pain or the direct effects of CMI pathophysiology stemming from cervico-medullary compression.

Concepts: Electrophysiology, Subarachnoid space, Emotion, Electroencephalography, Neurophysiology, Arnold-Chiari malformation, Psychology, Neuroscience


Abnormal cerebrospinal fluid (CSF) pulsatility has been implicated in patients suffering from various diseases, including multiple sclerosis and hypertension. CSF pulsatility results in subarachnoid space (SAS) width changes, which can be measured with near-infrared transillumination backscattering sounding (NIR-T/BSS). The aim of this study was to combine NIR-T/BSS and wavelet analysis methods to characterise the dynamics of the SAS width within a wide range of frequencies from 0.005 to 2 Hz, with low frequencies studied in detail for the first time. From recordings in the resting state, we also demonstrate the relationships between SAS width in both hemispheres of the brain, and investigate how the SAS width dynamics is related to the blood pressure (BP). These investigations also revealed influences of age and SAS correlation on the dynamics of SAS width and its similarity with the BP. Combination of NIR-T/BSS and time-frequency analysis may open up new frontiers in the understanding and diagnosis of various neurodegenerative and ageing related diseases to improve diagnostic procedures and patient prognosis.

Concepts: Medical terms, Spinal cord, Multiple sclerosis, Subarachnoid space, Brain, Diagnosis, Meninges, Cerebrospinal fluid