The interaction of global small vessel disease burden and Alzheimer's disease pathologies do not change the independent association of amyloid-beta with hippocampal volume: A longitudinal study on mild cognitive impairment subjects.

The purpose of this study was to investigate whether the co-existence of global small vessel disease (SVD) burdens and Alzheimer's disease (AD) pathologies change hippocampal volume (HV) and cognitive function of mild cognitive impairment (MCI) subjects. We obtained MRI images, cerebrospinal fluid biomarkers (Aß1-42 and p-tau), and neuropsychological tests of 310 MCI subjects from ADNI. The global SVD score was assessed. We used linear regression and linear mixing effect to analyze the effects of global SVD burdens, AD pathologies, and their interactions (SVD*AD) on baseline and longitudinal HV and cognition respectively. We used simple mediation effect to analyze the influencing pathways. After adjusting for global SVD and SVD*AD, Aß remained independently correlated with baseline and longitudinal HV (std ß = 0.294, p = .007; std ß = 0.292, p < .001), indicating that global SVD did not affect the correlation between Aß and HV. Global SVD score was correlated with longitudinal but not baseline HV (std ß = 0.470, p = .050), suggesting that global SVD may be more representative of long-term permanent impairment. Global SVD, AD pathologies, and SVD*AD were independently correlated with baseline and longitudinal cognitions, in which the association of Aß (B = 0.005, 95% CI: 0.005; 0.024) and p-tau (B = -0.002, 95% CI: -0.004; -0.000) with cognition were mediated by HV, suggesting that HV is more likely to explain the progression caused by AD pathology than SVD. The co-existence of global SVD and AD pathologies did not affect the individual association of Aß on HV; HV played a more important role in the influence of AD pathology on cognition than in SVD.

Large and Small Cerebral Vessel Involvement in Severe COVID-19: Detailed Clinical Workup of a Case Series.

BACKGROUND AND PURPOSE: Case series indicating cerebrovascular disorders in coronavirus disease 2019 (COVID-19) have been published. Comprehensive workups, including clinical characteristics, laboratory, electroencephalography, neuroimaging, and cerebrospinal fluid findings, are needed to understand the mechanisms. METHODS: We evaluated 32 consecutive critically ill patients with COVID-19 treated at a tertiary care center from March 9 to April 3, 2020, for concomitant severe central nervous system involvement. Patients identified underwent computed tomography, magnetic resonance imaging, electroencephalography, cerebrospinal fluid analysis, and autopsy in case of death. RESULTS: Of 32 critically ill patients with COVID-19, 8 (25%) had severe central nervous system involvement. Two presented with lacunar ischemic stroke in the early phase and 6 with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in 3 with additional subarachnoid hemorrhage and in 2 with additional small ischemic lesions. In 3 patients, intracranial vessel wall sequence magnetic resonance imaging was performed for the first time to our knowledge. All showed contrast enhancement of vessel walls in large cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. Reverse transcription-polymerase chain reactions for SARS-CoV-2 in cerebrospinal fluid were all negative. No intrathecal SARS-CoV-2-specific IgG synthesis was detectable. CONCLUSIONS: Different mechanisms of cerebrovascular disorders might be involved in COVID-19. Acute ischemic stroke might occur early. In a later phase, microinfarctions and vessel wall contrast enhancement occur, indicating small and large cerebral vessels involvement. Central nervous system disorders associated with COVID-19 may lead to long-term disabilities. Mechanisms should be urgently investigated to develop neuroprotective strategies.

Cerebrospinal Fluid Biomarkers in Idiopathic Normal Pressure Hydrocephalus versus Alzheimer's Disease and Subcortical Ischemic Vascular Disease: A Systematic Review.

BACKGROUND: The diagnostic workup of idiopathic normal pressure hydrocephalus (iNPH) can be challenging due to an overlap in symptoms and neuroimaging features with other disorders. Despite a growing interest, a cerebrospinal fluid (CSF) biomarker profile in iNPH has not yet been identified. OBJECTIVE: To determine the CSF biomarkers with the greatest evidence for differentiating iNPH from the most common differential diagnoses, Alzheimer's disease (AD) and subcortical ischemic vascular disease (SIVD). METHODS: A systematic literature search was conducted in PubMed to identify relevant articles up to July 2018 using the following MESH-terms: "Cerebrospinal fluid", "diagnos*", "hydrocephalus, normal pressure". Relevant data were extracted to assess the risk of bias in the included studies. RESULTS: Twenty-five studies including 664 patients with iNPH, 502 with AD, 57 with SIVD, 81 with other disorders, and 338 healthy controls (HC) were included. They investigated the diagnostic value of 92 CSF biomarkers. Most evidence existed for amyloid-ß 42 (Aß42), phosphorylated tau (p-tau), and total tau (t-tau) in iNPH versus AD and HC: Aß42 did not differ between iNPH and AD, but was lower than in HC subjects. T-tau and p-tau were lower in iNPH versus AD on a level comparable to HC subjects. There was moderate or limited evidence for 62 and 88 biomarkers, respectively. Several plausible biases characterize the literature including small sample sizes and inconsistent diagnostic criteria. CONCLUSION: T-tau and p-tau may differentiate iNPH from AD and Aß42 from HC. A combination of these biomarkers may improve the diagnostic accuracy in iNPH.

Distinct White Matter Changes Associated with Cerebrospinal Fluid Amyloid-ß1-42 and Hypertension.

BACKGROUND: Alzheimer's disease (AD) pathology and hypertension (HTN) are risk factors for development of white matter (WM) alterations and might be independently associated with these alterations in older adults. OBJECTIVE: To evaluate the independent and synergistic effects of HTN and AD pathology on WM alterations. METHODS: Clinical measures of cerebrovascular disease risk were collected from 62 participants in University of Kentucky Alzheimer's Disease Center studies who also had cerebrospinal fluid (CSF) sampling and MRI brain scans. CSF Aß1-42 levels were measured as a marker of AD, and fluid-attenuated inversion recovery imaging and diffusion tensor imaging were obtained to assess WM macro- and microstructural properties. Linear regression analyses were used to assess the relationships among WM alterations, cerebrovascular disease risk, and AD pathology. Voxelwise analyses were performed to examine spatial patterns of WM alteration associated with each pathology. RESULTS: HTN and CSF Aß1-42 levels were each associated with white matter hyperintensities (WMH). Also, CSF Aß1-42 levels were associated with alterations in normal appearing white matter fractional anisotropy (NAWM-FA), whereas HTN was marginally associated with alterations in NAWM-FA. Linear regression analyses demonstrated significant main effects of HTN and CSF Aß1-42 on WMH volume, but no significant HTN×CSF Aß1-42 interaction. Furthermore, voxelwise analyses showed unique patterns of WM alteration associated with hypertension and CSF Aß1-42. CONCLUSION: Associations of HTN and lower CSF Aß1-42 with WM alteration were statistically and spatially distinct, suggesting independent rather than synergistic effects. Considering such spatial distributions may improve diagnostic accuracy to address each underlying pathology.

Study protocol on Alzheimer's disease and related disorders: focus on clinical and imaging predictive markers in co-existing lesions.

BACKGROUND: One of the crucial challenges for the future of therapeutic approaches to Alzheimer's disease (AD) is to target the main pathological processes responsible for disability and dependency. However, a progressive cognitive impairment occurring after the age of 70, the main population affected by dementia, is often related to mixed lesions of neurodegenerative and vascular origins. Whereas young patients are mostly affected by pure lesions, ageing favours the occurrence of co-lesions of AD, cerebrovascular disease (CVD) and Lewy body dementia (LBD). Most of clinical studies report on functional and clinical disabilities in patients with presumed pure pathologies. But, the weight of co-morbid processes involved in the transition from an independent functional status to disability in the elderly with co-lesions still remains to be elucidated. Neuropathological examination often performed at late stages cannot answer this question at mild or moderate stages of cognitive disorders. Brain MRI, Single Photon Emission Computed Tomography (SPECT) with DaTscan®, amyloid Positron Emission Tomography (PET) and CerebroSpinal Fluid (CSF) AD biomarkers routinely help in performing the diagnosis of underlying lesions. The combination of these measures seems to be of incremental value for the diagnosis of mixed profiles of AD, CVD and LBD. The aim is to determine the clinical, neuropsychological, neuroradiological and biological features the most predictive of cognitive, behavioral and functional impairment at 2 years in patients with co-existing lesions. METHODS: A multicentre and prospective cohort study with clinical, neuro-imaging and biological markers assessment will recruit 214 patients over 70 years old with a cognitive disorder of AD, cerebrovascular and Lewy body type or with coexisting lesions of two or three of these pathologies and fulfilling the diagnostic criteria for dementia at a mild to moderate stage. Patients will be followed every 6 months (clinical, neuropsychological and imaging examination and collection of cognitive, behavioural and functional impairment) for 24 months. DISCUSSION: This study aims at identifying the best combination of markers (clinical, neuropsychological, MRI, SPECT-DaTscan®, PET and CSF) to predict disability progression in elderly patients presenting coexisting patterns. TRIAL REGISTRATION: NCT02052947 .

An MRI measure of degenerative and cerebrovascular pathology in Alzheimer disease.

OBJECTIVE: To develop, replicate, and validate an MRI-based quantitative measure of both cerebrovascular and neurodegeneration in Alzheimer disease (AD) for clinical and potentially research purposes. METHODS: We used data from a cross-sectional and longitudinal community-based study of Medicare-eligible residents in northern Manhattan followed every 18-24 months (n = 1,175, mean age 78 years). White matter hyperintensities, infarcts, hippocampal volumes, and cortical thicknesses were quantified from MRI and combined to generate an MRI measure associated with episodic memory. The combined MRI measure was replicated and validated using autopsy data, clinical diagnoses, and CSF biomarkers and amyloid PET from the Alzheimer's Disease Neuroimaging Initiative. RESULTS: The quantitative MRI measure was developed in a group of community participants (n = 690) and replicated in a similar second group (n = 485). Compared with healthy controls, the quantitative MRI measure was lower in patients with mild cognitive impairment and lower still in those with clinically diagnosed AD. The quantitative MRI measure correlated with neurofibrillary tangles, neuronal loss, atrophy, and infarcts at postmortem in an autopsy subset and was also associated with PET amyloid imaging and CSF levels of total tau, phosphorylated tau, and ß-amyloid 42. The MRI measure predicted conversion to MCI and clinical AD among healthy controls. CONCLUSION: We developed, replicated, and validated an MRI measure of cerebrovascular and neurodegenerative pathologies that are associated with clinical and neuropathologic diagnosis of AD and related to established biomarkers.

Blood-brain barrier breakdown, neuroinflammation, and cognitive decline in older adults.

INTRODUCTION: Blood-brain barrier (BBB) breakdown is observed in older versus younger adults and in late-onset Alzheimer's disease versus age-matched controls, but its causes and consequences in aging are unclear. We tested the hypothesis that BBB breakdown is associated with cognitive decline and inflammation in nondemented elders. METHODS: Cerebrospinal fluid and serum inflammatory markers were measured using sandwich immunoassays in 120 subjects. Least Absolute Shrinkage and Selection Operator-logistic regression selected cerebrospinal fluid and serum signatures that best classified BBB impairment defined by the cerebrospinal fluid albumin index ≥9. Linear regression examined changes in Clinical Dementia Rating sum of boxes as a function of BBB integrity at baseline. RESULTS: Mean age was 70 years, mean Mini­Mental State Examination was 27, and BBB impairment was recorded in 13.5%. BBB breakdown was associated with cognitive decline (P = .015). Cerebrospinal fluid intercellular adhesion molecule-1, vascular endothelial growth factor, interleukin-8, serum amyloid A, macrophage derived chemokine, and gender generated an area under the curve of 0.95 for BBB impairment, and serum IL-16, VEGF-D, IL-15, and other variables generated an AUC of 0.92 for BBB impairment. DISCUSSION: BBB breakdown is associated with more rapid cognitive decline. Inflammatory mechanisms, including cell adhesion, neutrophil migration, lipid metabolism, and angiogenesis may be implicated.

CSF biomarkers of neuroinflammation and cerebrovascular dysfunction in early Alzheimer disease.

OBJECTIVE: To measure CSF levels of biomarkers reflecting microglia and astrocytes activation, neuroinflammation, and cerebrovascular changes and study their associations with the core biomarkers of Alzheimer disease (AD) pathology (ß-amyloid [Aß] and tau), structural imaging correlates, and clinical disease progression over time. METHODS: The study included cognitively unimpaired elderly (n = 508), patients with mild cognitive impairment (MCI, n = 256), and patients with AD dementia (n = 57) from the longitudinal Swedish BioFINDER cohort. CSF samples were analyzed for YKL-40, interleukin (IL)-6, IL-7, IL-8, IL-15, IP-10, monocyte chemoattractant protein 1, intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), placental growth factor, and fms-related tyrosine kinase 1 (Flt-1). MRI data were available from 677 study participants. Longitudinal clinical assessments were conducted in control individuals and patients with MCI (mean follow-up 3 years, range 1-6 years). RESULTS: CSF levels of YKL-40, ICAM-1, VCAM-1, IL-15, and Flt-1 were increased during the preclinical, prodromal, and dementia stages of AD. High levels of these biomarkers were associated with increased CSF levels of total tau, with the associations, especially for YKL-40, being stronger in Aß-positive individuals. The results were similar for associations between phosphorylated tau and YKL-40, ICAM-1, and VCAM-1. High levels of the biomarkers were also associated with cortical thinning (primarily in the precuneus and superior parietal regions) and with subsequent cognitive deterioration in patients without dementia as measured with Mini-Mental State Examination (YKL-40) and Clinical Dementia Rating Sum of Boxes (YKL-40, ICAM-1, VCAM-1 and IL-15). Finally, higher levels of CSF YKL-40, ICAM-1, and Flt-1 increased risk of development of AD dementia in patients without dementia. CONCLUSIONS: Neuroinflammation and cerebrovascular dysfunction are early events occurring already at presymptomatic stages of AD and contribute to disease progression.

Are the brain's vascular and Alzheimer pathologies additive or interactive?

PURPOSE OF REVIEW: Alzheimer's disease and cerebrovascular disease (CVD) commonly co-occur. Whether CVD promotes the progression of Alzheimer's disease pathology remains a source of great interest. Recent technological developments have enabled us to examine their inter-relationship using quantifiable, biomarker-based approaches. We provide an overview of advances in understanding the relationship between vascular and Alzheimer's disease pathologies, with particular emphasis on ß-amyloid and tau as measured by positron emission tomography and cerebrospinal fluid (CSF) concentration, and magnetic resonance imaging markers of small vessel disease (SVD). RECENT FINDINGS: The relationship between cerebral ß-amyloid and various markers of SVD has been widely studied, albeit with somewhat mixed results. Significant associations have been elucidated, particularly between ß-amyloid burden and white matter hyperintensities (WMH), as well as lobar cerebral microbleeds (CMB), with additive effects on cognition. There is preliminary evidence for an association between SVD and tau burden in vivo, although compared with ß-amyloid, fewer studies have examined this relationship. SUMMARY: The overlap between Alzheimer's disease and cerebrovascular pathologies is now being increasingly supported by imaging and CSF biomarkers, indicating a synergistic effect of these co-pathologies on cognition. The association of WMH and CMB with Alzheimer's disease pathology does not establish direction of causality, for which long-term longitudinal studies are needed.

Quantification and regulation of the adipokines resistin and progranulin in human cerebrospinal fluid.

BACKGROUND: Adipokines bearing the potential to cross the blood-brain barrier (BBB) are promising candidates for the endocrine regulation of central nervous processes and of a postulated fat-brain axis. Resistin and progranulin concentrations in paired serum and cerebrospinal fluid (CSF) samples of patients undergoing neurological evaluation and spinal puncture were investigated. MATERIALS AND METHODS: Samples of n = 270 consecutive patients with various neurological diseases were collected without prior selection. Adipokine serum and CSF concentrations were measured by enzyme-linked immunosorbent assay and serum and CSF routine parameters by standard procedures. Anthropometric data, medication and patient history were available. RESULTS: Serum levels of resistin and progranulin were positively correlated among each other, with respective CSF levels, low-density lipoprotein cholesterol levels and markers of systemic inflammation. CSF resistin concentrations were generally low. Progranulin CSF concentrations and CSF/serum progranulin ratio were significantly higher in patients with infectious diseases, with disturbed BBB function and with elevated CSF cell count and presence of oligoclonal bands. Both adipokines are able to cross the BBB depending on a differing patency that increases with increasing grade of barrier dysfunction. Whereas resistin represents a systemic marker of inflammation, CSF progranulin levels strongly depend on the underlying disease and dysfunction of blood-CSF barrier. CONCLUSIONS: Resistin and progranulin represent novel and putative regulators of the fat-brain axis by their ability to cross the BBB under physiological and pathophysiological conditions. The presented data provide insight into the characteristics of BBB function regarding progranulin and resistin and the basis for future establishment of normal values for CSF concentrations and CSF/serum ratios.

[Reversible cerebral vasoconstriction syndrome. Challenge for diagnostics and intensive care therapy]. / Reversibles zerebrales Vasokonstriktionssyndrom. Herausforderung für Diagnostik und Intensivtherapie.

Reversible cerebral vasoconstriction syndrome (RCVS) is a disease of unclear incidence frequently affecting middle aged women and is usually associated with use of adrenergic or serotoninergic substances. The exclusion of relevant differential diagnoses, such as aneurysmal subarachnoid hemorrhage, primary cerebral angiitis, posterior reversible encephalopathy syndrome and carotid artery dissection is critical in terms of time and significance. Thunderclap headache as well as multiple and multilocular vasospasms with direct or indirect angiography without substantial findings in cerebrospinal fluid diagnostics are typical symptoms. The necessity for intensive care treatment is often justified by initial acute impairment of vital functions and possible development of cerebral or extracerebral complications. Because the exact pathophysiology remains unknown, a specific therapy does not exist. This poses significant challenges in intensive care medicine, which are illustrated on the basis of the case study presented.

Cytokine profiles and the role of cellular prion protein in patients with vascular dementia and vascular encephalopathy.

Understanding inflammatory mechanisms in vascular dementia (VD) is pivotal for achieving better insights into changes in brain metabolism. We performed cytokine profiling and measured levels of the cellular prion protein (PrP(C)) in serum and cerebrospinal fluid (CSF) samples from patients with VD and with vascular encephalopathy (VE). Significant changes were observed for interleukin (IL)-1ß, IL-4, IL-5, tumor necrosis factor alpha, interferon gamma, granulocyte-colony stimulating factor, monocyte chemotactic protein 1, and macrophage inflammatory protein 1 beta in serum and for IL-6 and granulocyte macrophage colony-stimulating factor in CSF of VD and VE patients, suggesting that most of immune markers depend on vascular lesions, while only IL-6 was related to dementia. In VD patients, the severity of dementia as defined by the Mini-Mental Status Test or Cambridge Cognitive Examination battery test was significantly correlated with the levels of IL-8 (CSF) and macrophage inflammatory protein 1 beta (serum and CSF). Additionally, in CSF of VD patients, our data revealed a correlation between immune and neurodegenerative marker proteins. Both indicate an association of neuroinflammation and cognitive decline. Levels of PrP(C) were regulated differentially in VD and VE patients compared with Alzheimer's disease patients and controls. Moreover, we observed a significant negative correlation between cytokine levels and PrP(C) in VD patients in CSF and serum, as well as a correlation between PrP(C) expression with levels of neurodegenerative marker proteins in CSF (in VD and VE patients). Our data suggest that immunological modifiers play a role in VD and VE patients and provide evidence for an association of PrP(C) with immune and neurodegenerative markers.

Alzheimer biomarkers and clinical Alzheimer disease were not associated with increased cerebrovascular disease in a memory clinic population.

OBJECTIVE: Preclinical and post-mortem studies suggest that Alzheimer disease (AD) causes cerebrovascular dysfunction, and therefore may enhance susceptibility to cerebrovascular disease (CVD). The objective of this study was to investigate this association in a memory clinic population. METHODS: The AD biomarkers CSF amyloid ß42, amyloid ß40 and APOE-ε4 status have all been linked to increased CVD risk in AD, and therefore the first aim of this study was to analyze the association between these biomarkers and CVD. In 92 memory clinic patients the cross-sectional association between AD biomarkersand the severity of CVD was investigated with linear regression analysis. Additionally, we studied whether AD biomarkers modified the relation between vascular risk factors and CVD. CVD was assessed on MRI through a visual rating scale.Analyses were adjusted for age. The second aim of this study was to investigate the association between clinical AD and CVD, where 'clinical AD' was defined as follows: impairment in episodic memory, hippocampal atrophy and an aberrant concentration of cerebrospinal fluid (CSF) biomarkers. 47 of the 92 patients had AD. RESULTS: No association between CSF amyloid ß42, amyloid ß40 or APOE-ε4 status and CVD severity was found, nor did these AD biomarkers modify the relation between vascular risk factors and CVD. Clinical AD was not associated with CVD severity (p=0.83). Patients with more vascular risk factors had more CVD, but this relationship was not convincingly modified by AD (p=0.06). CONCLUSIONS: In this memory clinic population, CVD in patients with AD was related to vascular risk factors and age, comparable to patients without AD. Therefore, in our study, the preclinical and post-mortem evidence that AD would predispose to CVD could not be translated clinically. Further work, including replication of this work in a different and larger sample, is warranted.

Levels of HVA, 5-HIAA, and MHPG in the CSF of vascular parkinsonism compared to Parkinson's disease and controls.

The neurochemical abnormalities underlying vascular parkinsonism (VP) have not been well characterised. A better understanding may help to optimize pharmacological interventions. Since VP patients generally have a poorer response to l-Dopa than Parkinson's disease (PD) patients, we investigated whether levels of relevant CSF neurotransmitter metabolites may be differentially altered in VP and PD and assessed the potential of neurotransmitter metabolites as biomarkers. We compared CSF levels of homovanillic acid (HVA), 5-hydroxyindolacetic acid, and 3-methoxy-4-hydroxyphenylethyleneglycol, in 16 VP patients, 57 PD patients and 60 non-neurological controls. We found that levels of HVA were reduced in PD compared with both VP and controls but did not differ significantly between VP and controls indicating that dopamine deficiency was less pronounced in VP.

Dissociable effects of Alzheimer disease and white matter hyperintensities on brain metabolism.

IMPORTANCE: Cerebrovascular disease and Alzheimer disease (AD) frequently co-occur and seem to act through different pathways in producing dementia. OBJECTIVE: To examine cerebrovascular disease and AD markers in relation to brain glucose metabolism in patients with mild cognitive impairment. DESIGN AND SETTING: Cohort study among the Alzheimer Disease Neuroimaging Initiative clinical sites in the United States and Canada. PARTICIPANTS: Two hundred three patients having amnestic mild cognitive impairment (74 of whom converted to AD) with serial imaging during a 3-year follow-up period. MAIN OUTCOMES AND MEASURES: Quantified white matter hyperintensities (WMHs) represented cerebrovascular disease, and cerebrospinal fluid ß-amyloid represented AD pathology. Brain glucose metabolism in temporoparietal and frontal brain regions was measured using positron emission tomography with fluorodeoxyglucose F18. RESULTS: In converters, greater WMHs were associated with decreased frontal metabolism (-0.048; 95% CI, -0.067 to -0.029) but not temporoparietal metabolism (0.010; 95% CI, -0.010 to 0.030). Greater cerebrospinal fluid ß-amyloid (per 10-pg/mL increase) was associated with increased temporoparietal metabolism (0.005; 95% CI, 0.000-0.010) but not frontal metabolism (0.002; 95% CI, -0.004 to 0.007) in the same patients. In nonconverters, similar relationships were observed except for a positive association of greater WMHs with increased temporoparietal metabolism (0.051; 95% CI, 0.027-0.076). CONCLUSIONS AND RELEVANCE: The dissociation of WMHs and cerebrospinal fluid ß-amyloid in relation to regional glucose metabolism suggests that these pathologic conditions operate through different and independent pathways in AD that reflect dysfunction in different brain systems. The positive association of greater WMHs with temporoparietal metabolism suggests that these pathologic processes do not co-occur in nonconverters.

[Meningovascular neurosyphilis as the cause of ischemic cerebrovascular disease in a young man]. / Meningovascularis neurosyphilis miatti fiatalkori ischaemiás cerebrovascularis betegség.

Authors report a case of a 35-year-old male with right-sided mild paresis, incontinence, dysexecutive syndrome, short-term memory loss and behavioral changes. Bilateral cerebral infarcts in the region of the caudate nuclei and the adjacent white matter were proved by brain MRI and multiple stenoses of the branches of Willis-circle were confirmed by MR angiography. Elevated protein level and pleocytosis were found in the cerebrospinal fluid with intrathecal IgG synthesis. Serum rapid plasma reagin, Treponema pallidum Particle Agglutination test, Treponema pallidum ELISA, liquor Venereal Disease Research Laboratory tests were positive. Meningovascular neurosyphilis was diagnosed. 24M U/day intravenous penicillin-G treatment was given for 14 days. The patient has vascular dementia due to the bilateral strategic infarcts disconnecting the prefrontal circuits; his symptoms are similar to general paresis. Laboratory and radiologic improvement was observed. Still, the patient have severe residual cognitive decline.

Cerebrospinal fluid flow dynamics in patients with multiple sclerosis: a phase contrast magnetic resonance study.

Cerebrospinal fluid (CSF) flow dynamics, which supposedly have a strong relationship with chronic cerebrospinal venous insufficiency (CCSVI), might be expected to be affected in multiple sclerosis (MS) patients. In this study, CSF flow at the level of the cerebral aqueduct was evaluated quantitatively by phase contrast magnetic resonance imaging (PC-MRI) to determine whether CSF flow dynamics are affected in MS patients. We studied 40 MS patients and 40 healthy controls using PC-MRI. We found significantly higher caudocranial (p=0.010) and craniocaudal CSF flow volumes (p=0.015) and stroke volume (p=0.010) in the MS patients compared with the controls. These findings may support the venous occlusion theory, but may also be explained by atrophy-dependent ventricular dilatation independent of the venous theory in MS patients.

Reversible cerebral vasoconstriction syndrome.

BACKGROUND: Reversible cerebral vasoconstriction syndrome is characterized by thunderclap headache associated with multifocal vasoconstriction of cerebral arteries in patients without aneurysmal subarachnoid hemorrhage (SAH). The vasoconstriction reverts within three months. We report a 44-year-old man who had a thunderclap headache during sexual intercourse. A similar episode occurred at rest 36 hours later. The patient had already experienced a thunderclap headache 10 years earlier, during coitus. There were no abnormalities on examination. His brain computed tomography scan was normal and cerebrospinal fluid analysis showed no xanthochromia, 15 WBC/mm³ and 10 RBC/mm³. Lumbar puncture was repeated two days later (WBC = 3/mm³ and RBC = 43/mm³). An initial digital cerebral angiography showed a diffuse segmental intracerebral vasospasm. A new angiography after 15 days was normal. He remains headache-free after twenty six months. In conclusion, patients who have thunderclap headache with normal brain CT and cerebrospinal fluid without xantochromia should be investigated for this syndrome.

[Intracranial pressure. Intracranial pressure monitoring].

Based on the data on the current literature, the authors present the basic physiological and pathophysiological aspects of measurement of intracranial pressure and discuss indications for its monitoring and clinical value.