The effect of prolonged spaceflight on cerebrospinal fluid and perivascular spaces of astronauts and cosmonauts.

Long-duration spaceflight induces changes to the brain and cerebrospinal fluid compartments and visual acuity problems known as spaceflight-associated neuro-ocular syndrome (SANS). The clinical relevance of these changes and whether they equally affect crews of different space agencies remain unknown. We used MRI to analyze the alterations occurring in the perivascular spaces (PVS) in NASA and European Space Agency astronauts and Roscosmos cosmonauts after a 6-mo spaceflight on the International Space Station (ISS). We found increased volume of basal ganglia PVS and white matter PVS (WM-PVS) after spaceflight, which was more prominent in the NASA crew than the Roscosmos crew. Moreover, both crews demonstrated a similar degree of lateral ventricle enlargement and decreased subarachnoid space at the vertex, which was correlated with WM-PVS enlargement. As all crews experienced the same environment aboard the ISS, the differences in WM-PVS enlargement may have been due to, among other factors, differences in the use of countermeasures and high-resistive exercise regimes, which can influence brain fluid redistribution. Moreover, NASA astronauts who developed SANS had greater pre- and postflight WM-PVS volumes than those unaffected. These results provide evidence for a potential link between WM-PVS fluid and SANS.

Clinical manifestations and spinal cord magnetic resonance imaging findings in Chinese neuromyelitis optica patients.

Neuromyelitis optica (NMO) is a disease distinct from multiple sclerosis in terms of clinical and magnetic resonance imaging (MRI) manifestations. Antibody to aquaporin-4 (AQP4) has been identified as a specific biomarker and part of the diagnostic criteria for NMO. Although it is relatively common in Asia, a comprehensive clinical and imaging evaluation of NMO has not been reported in Chinese patients. Here, we reviewed data from 57 Chinese cases. The patients had an obvious female preponderance (female/male = 8.5:1), and transverse myelitis (82.5%) and optic neuritis (56.1%) were the most common manifestations. In MRI, longitudinally extensive transverse myelitis (6.9 ± 2.3 segments) dominated the spinal cord lesions, which were mainly (69.7%) distributed in cervical and thoracic cord. However, the length of the lesions was not correlated with onset age, paralysis severity, relapse rate, or duration. Among 29 patients who underwent AQP4 antibody assay, 17 (58.6%) were positive. There was no difference between seropositive and seronegative patients in terms of female preponderance, onset age, relapse rate, and Expanded Disability Status Scale score. However, seropositive patients had significantly more damaged segments (8.3 ± 3.5) than did seronegative patients (4.5 ± 1.6) (p < 0.001). The data revealed the clinical and MRI characteristics and AQP4 antibody status of NMO in Chinese patients and the correlations between them, which may have important implications for the diagnosis of the disease.

Cerebrospinal fluid congestion in the perioptic space.

Recent attention has been paid to the -cerebrospinal fluid (CSF) dynamics between the intracranial subarachnoid space (SAS) and the SAS around the optic nerve (ON-SAS). We experienced three patients who had an expanded ON-SAS associated with mass lesions extending into the optic canal, and studied their MRI findings after decompressive surgery. In all three patients, decompressive surgery of the optic canal resulted not only in the disappearance of the expanded ON-SAS, but also in improvement of the visual function. The present study may indicate that normalization of the ON-SAS can be considered to be the achievement of "effective" decompression. Therefore, we suggest that, in patients with an expanded ON-SAS associated with mass lesions, the state of the ON-SAS should be evaluated by pre- and postoperative MRI, in addition to the degree of tumor resection.

Large and giant vestibular schwannomas: does cisterna magna hyperproteinorrhachia influence visual status?

BACKGROUND: Hyperproteinorrhachia associated with vestibular schwannomas (VSs) may influence visual status independent of the effect caused by raised intracranial pressure. The role of cisterna magna CSF protein levels (CMCP) in determining visual outcome in patients with large to giant vestibular schwannomas (VSs) was prospectively investigated. METHODS: The mean CMCP levels in VSs and control group; and, levels in VSs with or without visual deterioration were compared. Spearman's rank correlation coefficient tested for relationships between CMCP level with symptom duration and tumour volume (Kawamoto's method). Vision was regarded as normal when visual acuity was >6/18; and, deteriorated when it was between 6/18 and PL negative in the worse eye. Papilloedema (n = 26)/secondary optic atrophy (n = 6) and hydrocephalus (based on Evan's ratio, mild to moderate: n = 22; none: n = 18) were also recorded. The analysis of factors predicting diminished vision was done using logistic regression analysis (p < 0.05 significant). FINDINGS: There was a significant difference (p < 0.001) in mean CMCP levels between VS (456.3 SD 213.6 mg/dl) and control groups (96.3 SD 74.3 mg/dl). The mean CMCP levels in the VS group were also markedly higher than the ventricular mean protein levels. The CMCP levels in patients with visual diminution (<6/18 to PL negative; n = 23) was 561.4 SD 186.9 mg/dl and those without visual loss (n = 17) was 314.2 SD 160.8 mg/dl (p < 0.001). Their grade of visual diminution had a positive correlation with mean CMCP levels (p < 0.001). There was a negative correlation between total duration of symptoms and CMCP levels (p < 0.015). Logistic regression analysis using five independent factors (symptom duration, papilloedema/secondary optic atrophy, tumour volume, hydrocephalus and mean CMCP level) revealed that only CMCP level had a significant association with visual diminution. CONCLUSION: Elevated cisternal CSF proteins may play an important role in determining visual outcome in large to giant VSs. Ventricular CSF analysis is often unable confirm the presence of VS-associated cisternal hyperproteinorrhachia. High CMCP levels may influence decision-making while instituting a permanent CSF diversion for postoperative hydrocephalus or recalcitrant pseudomeningocoele.

A prominent elevation of glial fibrillary acidic protein in the cerebrospinal fluid during relapse in neuromyelitis optica.

Neuromyelitis optica (NMO) is a neurologic disease characterized by severe optic neuritis, longitudinally extended, transverse myelitis and serum aquaporin-4 (AQP4) antibody. Our recent neuropathological study revealed the extensive loss of AQP4 and glial fibrillary acidic protein (GFAP), an astrocyte-specific protein, in NMO lesions, but not in MS lesions, suggesting that severe astrocytic damage or dysfunction may be related to the pathogenesis of NMO. Here we report a patient of NMO, in which the cerebrospinal fluid (CSF) levels of GFAP were measured both during relapse of myelitis and after high-dose intravenous methylprednisolone (HIMP). The patient was a 34-year old woman with two previous episodes of optic neuritis. She developed myelitis longitudinally extending from C3 to T12 with contrast enhancement, and was AQP4 antibody-positive. In the acute phase, the GFAP level in the cerebrospinal fluid (CSF) was prominently elevated (18,966.7 ng/ml) as compared with controls (0.6 +/- 0.33 ng/ml). However, following HIMP, the clinical and MRI findings improved, and the CSF-GFAP level was near-normal (2.1 ng/ml). The CSF of myelin basic protein was also elevated in relapse (1,016.0 pg/ml), and became lower but still remained high (158.7 pg/ml) after HIMP compared with controls (3.36 +/- 3.83 pg/ml). The prominent elevation of the CSF-GFAP level in relapse of NMO, followed by its sharp decline after therapy, suggests severe astrocytic damage with a temporal profile distinct from that of the demyelinating process in NMO. CSF-GFAP may be useful as a biomarker of NMO.

Impaired cerebrospinal fluid pressure.

Abnormalities of cerebrospinal fluid (CSF) pressure are relatively common and may lead to a variety of symptoms, with headache usually being the most prominent one. The clinical presentation of alterations in CSF pressure may vary significantly and show a striking similitude to several primary headache syndromes. While an increase in CSF pressure may be of primary or secondary origin, a pathologic decrease of CSF pressure is usually the result of a meningeal rupture with a resulting leakage of CSF. The pathophysiologic mechanisms of idiopathic intracranial hypertension (IIH) remain largely unknown. However recent evidence indicates that an abnormality in CSF outflow and absorption is likely to play a significant role. Treatment usually consists of a combination of weight loss and a pharmacologic approach using carbonic anhydrase inhibitors. Recent results of the first randomized, double-blind, placebo-controlled trial (RCT) with acetazolamide proved its efficacy in reducing headache and visual disturbances. Clinical evidence suggests efficacy for topiramate and furosemide but no RCT has been conducted to date to confirm these results. In contrast to IIH, spontaneous intracranial hypotension frequently remits spontaneously without specific treatment. If necessary, treatment options range from conservative methods to epidural blood or fibrin sealant patches and surgical interventions.

Empty sella syndrome as complication of benign intracranial hypertension.

An empty sella was demonstrated on air study in five patients with the benign intracranial hypertension (BIH) syndrome. All patients had a protracted course and very high cerebrospinal fluid pressure; two required a shunt procedure. No patient had any endocrine symptoms or visual field defects but an air study was done to exclude a mass lesion in the sella region. Among the last 50 patients seen with the BIH syndrome, there were five cases of an associated empty sella (10%). In these cases, the empty sella is a probable consequence of the long-standing intracranial hypertension associated with a congenital deficiency of the diaphragma sellae.

Association between visual parameters and neuroimaging features of idiopathic intracranial hypertension.

BACKGROUND/AIMS: Papilledema refers to optic disc swelling resulting from high intracranial pressure (ICP). The precise mechanism by which papilledema occurs remains uncertain. Although orbital neuroimaging features associated with papilledema are well-described, it is unclear whether these findings correlate with visual function. Idiopathic Intracranial Hypertension (IIH) is a condition in which the intracranial pressure is elevated with no obvious cause, causing papilledema and visual loss. The utility of papilledema and IIH neuroimaging findings as a surrogate marker for visual loss, or a predictor of visual loss, is understudied. This retrospective cross-sectional review aims to correlate parameters of visual function with orbital magnetic resonance imaging (MRI) findings. METHODS: Patients meeting criteria for IIH who had received orbital imaging within 4 weeks of examination were included. Visual parameters of papilledema grade, visual field mean deviation, and visual acuity were correlated with neuroimaging features, including optic nerve thickness, and optic nerve sheath thickness, among others. All MRI scans were reviewed by a neuroradiologist blinded to clinical status. Spearman rank correlations and t-tests were generated with SAS (v9.2). RESULTS: Thirty five patients were included. No significant relationships were found between the main visual parameters of papilledema grade and visual field mean deviation, and MRI findings. CONCLUSIONS: We found no significant correlation between visual parameters and imaging features of papilledema. This might indicate that MRI features may provide insight into the structural changes that occur in papilledema, but may not be helpful when making clinical management decisions for patients with IIH in particular, and papilledema in general.

CSF biomarkers in posterior cortical atrophy.

OBJECTIVE: To describe CSF biomarker profiles in posterior cortical atrophy (PCA), which induces high-order visual deficits often associated with Alzheimer disease (AD) pathology, and relate these findings to clinical and neuropsychological assessment. METHODS: This prospective observational study included 22 patients with PCA who underwent CSF biomarker analysis of total tau (t-tau), phosphorylated tau on amino acid 181 (p-tau181), and amyloid ß (Aß(42)). At group level, the CSF profiles of patients with PCA were compared to those of patients with typical AD and patients with other dementia (OD). Individually, the clinical presentation of patients with PCA was correlated to their CSF profile to assess the predictability of clinical features for diagnosis of underlying AD pathology. RESULTS: At group level, the PCA biomarker profile was not different from that of the AD group, but very different from that of the OD group (p < 0.001). More than 90% of patients with PCA had CSF profiles consistent with AD. All patients with PCA with either isolated higher-order visual deficit (n = 8) or visual deficit associated with memory impairment (n = 11) had CSF profiles consistent with AD. Only one of the 3 patients with PCA with asymmetric motor signs fulfilled biological CSF criteria for AD. CONCLUSIONS: PCA syndrome is usually associated with CSF biomarkers suggestive of AD, as shown by previous neuropathologic studies. This does not apply in case of motor signs suggesting associated corticobasal syndrome. CSF biomarkers help to discriminate AD from non-AD processes associated with this condition.