Neurovisual rehabilitation in multiple sclerosis: Why a close integration of low-vision rehabilitation and neuropsychological rehabilitation may be effective for visual complaints.

OBJECTIVE: The quality of life of people with multiple sclerosis (MS) is often affected by visual complaints. A previous study suggested that visual complaints are not likely to be related to specific visual functions, but by a global decline of cognitive and visual functioning. In this study, we further explore this hypothesis, by investigating the relation between visual functions and global cognitive functioning, aiming to provide recommendations for rehabilitation for visual complaints. DESIGN: Cross-sectional study. SETTING: A rehabilitation centre for partially sighted and blind people and a MS centre at a university hospital. PARTICIPANTS: 102 people with MS. MAIN MEASURE: Correlations between assessments of visual functions (acuity, contrast sensitivity, visual field, smooth pursuit and saccades) and composite scores of a neuropsychological assessment (tests with a visual component and without a visual component). RESULTS: All composite scores correlated with visual acuity, contrast sensitivity and the sensitivity of the monocular field, but not with smooth pursuit and saccades. Similar patterns were found in various subgroups. Results showed that visual functions that related to visual complaints correlated with a diffuse decline of global cognitive functioning and that visual and cognitive functioning may decline concurrently in people with MS. CONCLUSIONS: Visual complaints may occur as a result of a diffuse decline of the integrity of a cerebral network involved in vision and cognition. People with MS with visual complaints may benefit from neurovisual rehabilitation, in which low-vision rehabilitation and neuropsychological rehabilitation are closely intertwined.

The complex relation between visual complaints and decline in visual, visuoperceptual and cognitive functions in people with multiple sclerosis.

People with multiple sclerosis (pwMS) report many different visual complaints, but not all of them are well understood. Decline in visual, visuoperceptual and cognitive functions do occur in pwMS, but it is unclear to what extend those help us understand visual complaints. The purpose of this cross-sectional study was to explore the relation between visual complaints and decline in visual, visuoperceptual and cognitive functions, to optimize care for pwMS. Visual, visuoperceptual and cognitive functions of 68 pwMS with visual complaints and 37 pwMS with no or minimal visual complaints were assessed. The frequency of functional decline was compared between the two groups and correlations were calculated between visual complaints and the assessed functions. Decline in several functions occurred more frequently in pwMS with visual complaints. Visual complaints may be an indication of declined visual or cognitive functioning. However, as most correlations were not significant or weak, we cannot infer that visual complaints are directly related to functions. The relationship may be indirect and more complex. Future research could focus on the overarching cognitive capacity that may contribute to visual complaints. Further research into these and other explanations for visual complaints could help us to provide appropriate care for pwMS.

Recognizing visual complaints in people with multiple sclerosis: Prevalence, nature and associations with key characteristics of MS.

BACKGROUND: Visual disturbances are common in multiple sclerosis (MS), but visual complaints may be underestimated. While these complaints decrease quality of life, they may not be discussed during clinic visits. People with MS (pwMS) may not be referred to appropriate care. We therefore investigated the prevalence, nature and associations of visual complaints of pwMS. METHODS: We performed a cohort study with a comparison group. PwMS (n = 493) and healthy controls (n = 661) filled out the Screening Visual Complaints questionnaire (SVCq). Primary outcomes were the percentage of pwMS and controls that reported the 19 complaints, and total scores of the SVCq. We also compared the scores on the SVCq between different groups of pwMS. RESULTS: In general, the complaints were reported more often by pwMS than by controls. PwMS especially reported experiencing complaints 'often/always', while controls reported the complaints primarily 'sometimes'. PwMS with and without a history of optic neuritis showed similar complaints. PwMS with a longer disease duration and those with SPMS reported more complaints. EDSS score and disease duration only showed a limited association with discomfort of visual complaints. CONCLUSION: The prevalence of visual complaints among pwMS is high and any person with MS may experience a wide array of different visual complaints anywhere along the disease course, regardless of a history of optic neuritis. Using the SVCq may help detect pwMS' visual complaints and may facilitate referrals to appropriate care.

Independent outdoor mobility of persons with multiple sclerosis - A systematic review.

BACKGROUND: Multiple sclerosis (MS) can manifest itself in many ways, all of which can affect the independent outdoor mobility of persons with MS (pwMS). In most studies, mobility of pwMS is defined by the ability to walk. However, mobility comprises more than walking alone. This systematic review provides an overview of the literature on several types of independent outdoor mobility of pwMS. We aimed to identify which specific factors may influence outdoor mobility and how the lives of pwMS may be affected by a reduced mobility. METHODS: A systematic literature search was performed, using three databases (PubMed, PsychInfo and Web of Science). Studies had to describe a group of pwMS sclerosis and had to concern some type of mobility other than walking. RESULTS: The 57 studies that fulfilled the criteria included in total 10,394 pwMS and in addition, 95,300 pwMS in separate prevalence study. These studies showed that pwMS as a group have a decreased fitness to drive, make use of a wheelchair or mobility scooter more often and have difficulties making use of public transport. Mobility problems especially occur in patients with cognitive problems, secondary progressive MS or high disability scores. CONCLUSIONS: The reduced mobility may prevent pwMS participating in society. However, few studies investigating interventions or rehabilitation options to improve mobility were found in the existing literature, highlighting an until now under recognised unmet need.

[Cerebral vasculitis, a diagnostic labyrinth]. / Cerebrale vasculitis, een diagnostisch doolhof.

- A diagnosis of cerebral vasculitis is frequently considered in patients with new or progressive neurological symptoms for which there is no other explanation.- A clinician considering a diagnosis of cerebral vasculitis should be well aware of alternative diagnoses, since these are generally more common.- Several consecutive examinations are required for diagnosing cerebral vasculitis, because there is no diagnostic procedure that is highly sensitive as well as highly specific.- The added value of the different procedures may depend on the type of blood vessels involved.- Standard MRI examinations are sensitive but not specific.- Special MRI techniques now make it also possible to make images of the vessel wall itself.- Catheter angiography remains important, especially when non-invasive angiographic techniques do not reveal any abnormalities.- Brain biopsy can provide proof of cerebral vasculitis and also serves to exclude mimicking conditions.

Change in disability profile and quality of life in multiple sclerosis patients: a five-year longitudinal study using the Multiple Sclerosis Impact Profile (MSIP).

BACKGROUND: Evidence on the progress of disease severity in multiple sclerosis (MS) is generally limited in scope. OBJECTIVES: To examine the course of a broad spectrum of MS-related disabilities and quality of life (QOL) in relation to disease severity, and responsiveness of the Multiple Sclerosis Impact Profile (MSIP). METHODS: The mortality rate was calculated after checking the national population register for vital status of the initial cohort. We performed a longitudinal study among 245 patients with MS attending the Groningen MS Center in the Netherlands. We assessed these patients in 2004 and 2009 using a postal survey including the MSIP to evaluate disabilities, the World Health Organization Quality of Life-Abbreviation version (WHOQOL-BREF) to evaluate QOL, and the ambulation question of the Expanded Disability Status Scale (EDSS) to evaluate disease severity. Responsiveness of the MSIP was estimated using standardized response mean (SRM). RESULTS: Increase of disability in the MSIP disability domains and loss of QOL were most prevalent and pronounced in patients with EDSS 0 to < 4.5 in 2004. MSIP and QOL scores were remarkably stable in the higher disease severity groups. Mortality rates were highest (24%) in patients with EDSS ≥ 7 to < 10 in 2004. SRM indices for the MSIP ranged between 0.26 and 0.56. CONCLUSIONS: Prominent increases in multiple aspects of disability and loss of QOL occur especially in the early stages in MS. Health care interventions may lead to health and QOL gains, in particular when offered to patients in the first stage of the MS process. Responsiveness was sufficient for nine of the 11 MSIP domains.

Intravascular lymphoma as an unusual cause of multifocal cerebral infarctions discovered on FDG-PET/CT.

Intravascular large B-cell lymphoma (IVLBCL) is a rare and aggressive variant of diffuse large B-cell lymphoma with frequent involvement of the central nervous system. Its atypical presentation often delays the diagnosis and due to its aggressive behaviour, the diagnosis is made post-mortem in half of the cases. We report a case of a 67-year-old male patient presenting with speech difficulties and balance disturbances in whom a magnetic resonance imaging (MRI) scan showed multiple lesions of the white matter, denoted as embolic infarctions. He was treated for a suspected endocarditis with antibiotics, but deteriorated neurologically with persistent fever. A consecutive FDG -PET /CT revealed an increased uptake in the adrenals, of which a biopsy showed IVLB CL. The patient was successfully treated with systemic R-CHOP with intrathecal methotrexate and achieved complete remission after six cycles of chemotherapy. The potential role of FDG-PET/CT is illustrated by this case leading to an exceptional diagnosis of IVLBCL.

A subtype of multiple sclerosis defined by an activated immune defense program.

Given the heterogeneous nature of multiple sclerosis (MS), we applied DNA microarray technology to determine whether variability is reflected in peripheral blood (PB) cells. In this study, we studied whole-blood gene expression profiles of 29 patients with relapsing-remitting MS (RRMS) and 25 age- and sex-matched healthy controls. We used microarrays with a complexity of 43K cDNAs. The data were analyzed using sophisticated pathway-level analysis in order to provide insight into the deregulated peripheral immune response programs in MS. We found a remarkable elevated expression of a spectrum of genes known to be involved in immune defense in the PB of MS patients compared to healthy individuals. Cluster analysis revealed that the increased expression of these genes was characteristic for approximately half of the patients. In addition, the gene signature in this group of patients was comparable with a virus response program. We conclude that the transcriptional signature of the PB cells reflects the heterogeneity of MS and defines a sub-population of RRMS patients, who exhibit an activated immune defense program that resembles a virus response program, which is supportive for a link between viruses and MS.

Autoantibodies against alpha B-crystallin, a candidate autoantigen in multiple sclerosis, are part of a normal human immune repertoire.

Human T-cell responses to the stress protein alpha B-crystallin in multiple sclerosis (MS)-affected brain samples are dominant when compared to other myelin antigens. The establishment of the apparent autoimmune repertoire against this antigen has been suggested to involve cross-priming during viral infection. Yet, another possibility would be that determinant spreading during ocular inflammation could generate a response to alpha B-crystallin, since it is also a major component of the eye. In this study, we compared serum IgG, IgA and IgM repertoires against a range of eye lens-derived ocular antigens using sera from healthy control subjects and MS patients with or without uveitis. This comparison revealed that among ocular antigens, alpha B-crystallin is the dominant target antigen for serum autoantibodies in both MS patients and healthy controls. Uveitis generally did not affect the antibody reactivity profile. These data provide further support for the notion that a normal adult human immune system is selectively reactive to alpha B-crystallin and they indicate that this responsiveness is unlikely to result from determinant spreading following ocular inflammation.

Seasonal variation in immune measurements and MRI markers of disease activity in MS.

BACKGROUND: The exact mechanisms by which T cells contribute to MS progression are not known. Recently, the results of cross-sectional studies suggested seasonal variation of both interferon (IFN)-gamma production and the number of active MRI lesions in MS. OBJECTIVE: To investigate whether seasonal fluctuations of IFN-gamma and active MRI lesions could be confirmed and whether any correlations could be detected. METHODS: Data were analyzed from a group of 28 MS patients in whom detailed longitudinal monitoring of both immune function and MRI measurements had taken place. RESULTS: Significant seasonal variation was observed in T-cell activation as measured by the ability of T cells to secrete the pro-inflammatory cytokines tumor necrosis factor-alpha and IFN-gamma. Maximum values were found in samples obtained during autumn. Even though clear fluctuations were observed, no significant seasonal variation could be detected in the number of active MRI lesions. Fluctuations of in vitro IFN-gamma secretion correlated weakly with changes in active MRI lesions. CONCLUSIONS: The finding of seasonal variation of immune function in serially MRI-monitored MS patients suggests an environmental role in T-cell activation.

TNFalpha production by CD4(+) T cells predicts long-term increase in lesion load on MRI in MS.

Reliable laboratory prognostic factors for MS are still lacking. The predictive value of markers of T-cell activation for long-term disease progression was investigated. Flow cytometry measurements were correlated to changes in Expanded Disability Status Scale and MR T2 lesion load over 36 months in 14 patients with secondary progressive MS. A correlation was found between the percentage of tumor necrosis factor-alpha-producing CD4(+) T cells at baseline and the change in T2 lesion load during 3-year follow-up (r = 0.79, adjusted r(2) = 0.59, p = 0.001).

Ischemic transverse myelopathy after endovascular repair of a thoracic aortic aneurysm.

PURPOSE: To report a dramatic complication after endovascular repair of a descending thoracic aortic aneurysm (TAA) and to present a classification system and possible methods to avoid spinal cord ischemia. CASE REPORT: A 48-year-old man with a descending TAA between T5 and T9 was treated with endovascular stent-grafts. Fourteen hours after the operation, the patient developed partial transverse myelopathy at level T10. During emergency conversion to open surgery and implantation of a conventional tube graft, 3 intercostal arteries that had been covered by the stent-graft were revascularized. Postoperatively, the neurological deficit improved, and the patient was able to walk again. Methods to predict and possibly prevent the induction of spinal cord ischemia after endovascular repair of TAA are suggested. CONCLUSIONS: Endovascular repair of TAA may induce spinal cord ischemia; pre- and intraoperative assessment of involved intercostal arteries should be performed.