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Concept: Subarachnoid space

201

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

49

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

28

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

26

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

13

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: Autism, Cerebrospinal fluid, Autism spectrum, Subarachnoid space

4

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

2

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 ( clinicaltrials.gov ).

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

1

Visual impairment intracranial pressure (VIIP) syndrome is considered an unexplained major risk for future long-duration spaceflight. NASA recently redefined this syndrome as Spaceflight-Associated Neuro-ocular Syndrome (SANS). Evidence thus reviewed supports that chronic, mildly elevated intracranial pressure (ICP) in space (as opposed to more variable ICP with posture and activity on Earth) is largely accounted for by loss of hydrostatic pressures and altered hemodynamics in the intracranial circulation and the cerebrospinal fluid system. In space, an elevated pressure gradient across the lamina cribrosa, caused by a chronic but mildly elevated ICP, likely elicits adaptations of multiple structures and fluid systems in the eye which manifest themselves as the VIIP syndrome. A chronic mismatch between ICP and intraocular pressure (IOP) in space may acclimate the optic nerve head, lamina cribrosa, and optic nerve subarachnoid space to a condition that is maladaptive to Earth, all contributing to the pathogenesis of space VIIP syndrome. Relevant findings help to evaluate whether artificial gravity is an appropriate countermeasure to prevent this seemingly adverse effect of long-duration spaceflight.

Concepts: Fluid dynamics, Intracranial pressure, Eye, Cerebrospinal fluid, Subarachnoid space

0

Accumulating evidence supports that cerebrospinal fluid (CSF) in the subarachnoid space (SAS) could reenter the brain parenchyma via the glymphatic influx. The present study was designed to characterize the detailed pathway of subarachnoid CSF influx by using a novel CSF tracer.

Concepts: Central nervous system, Time, Spinal cord, Brain, Subarachnoid hemorrhage, Cerebrospinal fluid, Meninges, Subarachnoid space

0

Spirocerca lupi is a nematode infecting dogs mostly in tropical and subtropical areas. Although its typical target is the esophageal wall, aberrant migration is not uncommon, including migration of unknown incidence into the spinal cord. While successful treatment of intraspinal S. lupi (ISSL) infection depends on early diagnosis, tools for definitive ante-mortem diagnosis are unavailable. We therefore aimed at characterizing clinical signs and clinical pathology findings of ISSL in dogs. For that, we analyzed medical records of dogs hospitalized in 2005-2016 presenting with neurological signs consistent with ISSL, which were diagnosed definitively post-mortem. Retrieved information included signalment, medical history, chief complaint, physical and neurological evaluation, neuroanatomical localization at presentation, clinical pathology, imaging findings, treatment, outcome and post-mortem findings. Ten midsize to large breed dogs were included, 7 of which had received prophylactic treatment. In all 10 dogs, onset was acute and neurological deterioration until presentation (2 h-6 d) was fast. Neurological examination localized the lesions within the spinal cord and paresis or paralysis was asymmetric in all dogs. Spinal pain was documented in 9/10 dogs. Cerebrospinal fluid (CSF) analysis was abnormal in all dogs and was characterized by pleocytosis in 8/10, whereas cytology revealed the presence of eosinophils in all dogs. Advanced imaging excluded spinal cord compression in all dogs tested. Post-mortem examination detected spinal cord migration tract in all cases. Nematodes were found in the spinal cord parenchyma (8/10) or adjacent to it (2/10) in all dogs. A larva was found in the subarachnoid space of one dog and an adult nematode in the thoracic intervertebral artery of another. Esophageal nodules were found in 5/10 dogs. These findings suggest that the combination of sudden onset of acute asymmetric paresis accompanied by pain, presence of eosinophils in the CSF and lack of compressive lesion may serve as sufficient evidence for tentative diagnosis of ISSL in endemic areas.

Concepts: Spinal cord, Pathology, Anatomical pathology, Cerebrospinal fluid, Physical examination, Dog, Meninges, Subarachnoid space