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.

Mechanisms underlying muscle fatigue differ between multiple sclerosis patients and controls: a combined electrophysiological and neuroimaging study.

Increased sense of fatigue is an important and conspicuous symptom in multiple sclerosis (MS). Muscle fatigue is associated with increased sense of fatigue in MS (Steens et al., 2011). The aim of this study was to investigate mechanisms that can explain muscle fatigue in MS patients and controls. We assessed changes in cortical activation (BOLD), voluntary activation (twitch interpolation) and muscle force during a sustained maximal voluntary contraction (MVC) in twenty MS patients and twenty healthy controls. In control participants, individual differences in force decline (mean 65% MVC, 8 SD) during the sustained maximal contraction could be accounted for by differences in maximal voluntary force (R(2): 0.49, p = 0.001); stronger participants presented a larger force decline. The small decline in voluntary activation (mean 7.8%, 11.8 SD) did not contribute significantly to the force decline. During the sustained contraction, the force decline was accompanied by an increase in cortical activation in the main motor areas. In MS patients, the differences in the decline in force (mean 67% MVC, 9 SD) were significantly associated (R(2): 0.51, p = 0.001) with a decline in voluntary activation (mean 20.1%, 20.6 SD) and not with maximal force or decline in rest twitch. The corresponding cortical activation in motor areas showed an increase in the first two intervals of the sustained contraction but declined during the last interval. Our data indicate that muscle fatigue during a sustained contraction in MS patients is associated with changes in the voluntary activation that are not sufficiently compensated by increased cortical activation. Control participants, however, show increased cortical activation to compensate for these fatigue-related changes in voluntary activation and the major cause of force decline is therefore to be found in the periphery (muscles).

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.

T2 lesions and rate of progression of disability in multiple sclerosis.

BACKGROUND AND PURPOSE: To assess the predictive value of T2 lesions on the rate of progression of disability in multiple sclerosis (MS). METHODS: We reanalyzed T2 lesion number and load on brain MRI scans, performed before 1997, of 186 MS patients, who were clinically followed. There were 90 patients with progressive MS (35 secondary progressive and 55 primary progressive), and 96 with relapsing remitting MS. The rate of progression of disability was measured by time to sustained progression of disability (defined as an increase in ≥ 1 point when the Expanded Disability Status Scale (EDSS) was 5.5 or less and an increase in EDSS of ≥ 0.5 point when the EDSS was 6.0 or higher), and by the Multiple Sclerosis Severity Score (MSSS). RESULTS: During follow-up (median 15 years, IQR 12-17 years), 94% of the patients with progressive MS and 50% of the patients with relapsing remitting MS had progression of disability. Higher T2 lesion number and load were modestly associated with a higher rate of disease progression on the MSSS and a shorter time to progression of disability in relapsing remitting MS, but not in progressive MS. CONCLUSIONS: Our findings indicate that the amount of T2 lesions has a small predictive value for progression of disability in relapsing remitting MS, but has no influence on the rate of progression in progressive MS.

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.

Effects of fluoxetine on disease activity in relapsing multiple sclerosis: a double-blind, placebo-controlled, exploratory study.

BACKGROUND: Suppressing the antigen-presenting capacity of glial cells could represent a novel way of reducing inflammatory activity in multiple sclerosis (MS). AIMS: To evaluate the effects of fluoxetine on new lesion formation in patients with relapsing MS. METHODS: In a double-blind, placebo-controlled exploratory study, 40 non-depressed patients with relapsing remitting or relapsing secondary progressive MS were randomised to oral fluoxetine 20 mg or placebo daily for 24 weeks. New lesion formation was studied by assessing the cumulative number of gadolinium-enhancing lesions on brain MRI performed on weeks 4, 8, 16 and 24. RESULTS: Nineteen patients in both groups completed the study. The mean (SD) cumulative number of new enhancing lesions during the 24 weeks of treatment was 1.84 (2.9) in the fluoxetine group and 5.16 (8.6) in the placebo group (p = 0.15). The number of scans showing new enhancing lesions was 25% in the fluoxetine group versus 41% in the placebo group (p = 0.04). Restricting the analysis to the past 16 weeks of treatment showed that the cumulative number of new enhancing lesions was 1.21 (2.6) in the fluoxetine group and 3.16 (5.3) in the placebo group (p = 0.05). The number of patients without enhancing lesions was 63% in the fluoxetine group versus 26% in the placebo group (p = 0.02). CONCLUSIONS: This proof-of-concept study shows that fluoxetine tends to reduce the formation of new enhancing lesions in patients with MS. Further studies with this compound are warranted. TRIAL REGISTRATION: Number: ISRCTN65586975.

Visual field and grating acuity development in low-risk preterm infants during the first 2 1/2 years after term.

The effect of early visual experience on visual field size and grating acuity development was studied longitudinally in 36 appropriate for gestational age (AGA) and 26 small for gestational age (SGA) low-risk preterm infants. These were selected out of 194 very low birth weight (VLBW) infants (birthweight less than 1500 g) born in 1985 and 1986. Criteria for inclusion as low-risk were the absence of neurological, respiratory, circulatory and alimentary problems in the neonatal period; no retinopathy of prematurity and no evidence of abnormality on the neonatal cranial ultrasound scans. Binocular field sizes were assessed using kinetic arc perimetry. Binocular grating acuity was tested by means of the prototype version of the acuity card procedure. Results were compared with norms obtained in control fullterms in earlier studies. Infants were tested at 6 weeks, 6, 6, 9 and 12 months of age from the expected term date. Twenty-two of these infants were retested at 2 1/2 years of corrected age. Visual field size and visual acuity estimates of (both AGA and SGA) low-risk, VLBW preterms and control fullterms overlapped at all test ages, except for a slight but significantly faster development of the upper and the lower visual field at 6 weeks corrected age in the preterm group. These results indicate that for clinical purposes visual experience before the expected term date has not only no measurable effect on the normal development of behavioural acuity, but also no accelerating effect on the development of peripheral vision.

[Behavioral determination of visual acuity in 1-to-4-year-old children]. / Gedragsmatige bepaling van de gezichtsscherpte bij kinderen van 1 tot 4 jaar.

Visual acuity was assessed in 210 children aged 1 to 4 years using the Acuity card method. Visual acuity is expressed in minutes of arc, indicating the minimal angle for separate perception of two lines. Binocular visual acuity showed a gradual growth from 1.8 to 0.9 min, arc and monocular visual acuity from 1.7 to 1 min. arc during this age period. Adult values of 0.65 min. arc(binocular) and 0.70 (monocular) were not yet reached at 4 years of age. Age norms for visual acuity in children from 1 to 4 years of age were determined. The success rate for binocular visual acuity assessment was 99.5% at all ages and increased for monocular acuity assessment from 50% in the 1 to 2 year old to 100% in the 4 year olds. Acuity assessment was fast (test time 3.3 and 2.0 minutes for assessment of binocular and monocular acuity respectively). The inter-observer reliability of the binocular assessment in the same child was high.

Serum uric acid, dehydroepiandrosterone sulphate, and apolipoprotein E genotype in benign vs. progressive multiple sclerosis.

The majority of patients with multiple sclerosis (MS) experience gradual progression of disability, either as secondary progressive MS (SPMS) or primary progressive MS (PPMS). A subgroup with relapsing-remitting MS shows a benign course with little or no disease progression and minimal disability decades after the first manifestations, so called benign MS (BMS). In our search to identify factors that are associated with progression of MS, we investigated serum levels of uric acid and dehydroepiandrostenedione sulphate (DHEAS), and apolipoprotein (apo)E genotype in 28 patients with BMS, 33 with SPMS, 21 with PPMS, and 29 healthy individuals. We found no significant changes in uric acid levels and apoE genotype between the four groups. Mean DHEAS levels were lower in MS patients compared with healthy controls (P = 0.049), but there were no significant differences between the clinical subgroups of MS. In patients with SPMS and PPMS there was no correlation between progression rate and serum levels of either uric acid or DHEAS. Our results suggest that serum levels of uric acid and DHEAS, and apoE genotype do not differ between patients with a benign and progressive course of MS.

A randomized crossover study of bee sting therapy for multiple sclerosis.

BACKGROUND: Bee sting therapy is increasingly used to treat patients with multiple sclerosis (MS) in the belief that it can stabilize or ameliorate the disease. However, there are no clinical studies to justify its use. METHODS: In a randomized, crossover study, we assigned 26 patients with relapsing-remitting or relapsing secondary progressive MS to 24 weeks of medically supervised bee sting therapy or 24 weeks of no treatment. Live bees (up to a maximum of 20) were used to administer bee venom three times per week. The primary outcome was the cumulative number of new gadolinium-enhancing lesions on T1-weighted MRI of the brain. Secondary outcomes were lesion load on T2*-weighted MRI, relapse rate, disability (Expanded Disability Status Scale, Multiple Sclerosis Functional Composite, Guy's Neurologic Disability Scale), fatigue (Abbreviated Fatigue Questionnaire, Fatigue Impact Scale), and health-related quality of life (Medical Outcomes Study 36-Item Short Form General Health Survey). RESULTS: During bee sting therapy, there was no significant reduction in the cumulative number of new gadolinium-enhancing lesions. The T2*-weighted lesion load further progressed, and there was no significant reduction in relapse rate. There was no improvement of disability, fatigue, and quality of life. Bee sting therapy was well tolerated, and there were no serious adverse events. CONCLUSIONS: In this trial, treatment with bee venom in patients with relapsing multiple sclerosis did not reduce disease activity, disability, or fatigue and did not improve quality of life.

Blind, deaf and mute after a status epilepticus caused by hyperpyrexia from shigellosis--a case report with a four-year follow-up.

A nearly four-year-old boy awoke blind, deaf and mute from a coma of five days duration after a status epilepticus caused by hyperpyrexia from shigellosis. The authors give a detailed report of the recovery. Visual and auditory functions recovered within six months after the onset but expressive language difficulties remained. Following a discussion of the underlying mechanisms producing the cerebral damage, the hypothesis of a type of "disconnection syndrome" is put forward to explain the persisting language deficit.

Visual acuity and visual field development after cryocoagulation in infants with retinopathy of prematurity.

Visual development was studied in 10 very-low-birth-weight infants (less than 1500 g) with retinopathy of prematurity (ROP) stage 3+ who had been treated with cryocoagulation in both eyes. Binocular visual acuity (acuity cards method) and binocular visual fields (kinetic perimetry) were assessed repeatedly in the first year of life. At 12 months corrected age, visual acuity was normal in seven and impaired in three infants, who appeared to be severely myopic. Normal visual fields were found in eight infants at this age. The results indicate that cryotherapy in cases of ROP stage 3+ does not interfere with visual acuity development. The effect on visual field development needs further investigation.

Strabismus in very low birth weight and/or very preterm children: discrepancy between age of onset and start of treatment.

Very low birth weight (VLBW; less than 1500 g) and/or very preterm children are at risk for strabismus. However, the age of onset of strabismus is still unknown. The present study reports on the frequency of strabismus in 450 5-year-old children born with a birth weight of less than 1500 g and/or with a gestational age below 32 weeks. The age at which strabismus was initially diagnosed was determined retrospectively. At 5 years of age 65 of the at-risk children (14.4%) presented with strabismus. Fifteen of them (3%) had at that age not been referred to or treated by an ophthalmologist. At 3 years of age only 28 strabismic children were being treated; 7 at-risk children (2%) had been treated for strabismus before the end of the 1st year. These results were compared to those from a second study in which eye alignment was longitudinally examined in 194 VLBW children from 6 weeks until 12 months of (corrected) age and additionally in 65 of these children at the age of 2.5 years. At a first glance, the frequency of strabismus in the longitudinal study seemed rather stable during the first 2.5 years of life, with values varying between 14% and 18%. However, only a small percentage of misalignments which were noted at 6 weeks of age persisted until 2.5 years. On the other hand, if children had a misalignment at 9 months, strabismus was still present when they were reexamined at 1 and at 2.5 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Visual functions in relation with neonatal cerebral ultrasound, neurology and cognitive development in very-low-birthweight children.

In order to determine the relationship between visual functions and neonatal cerebral ultrasound, neurological examinations and cognitive development, a prospective longitudinal study was conducted in 69 high-risk very-low-birthweight children. Visual development was studied at 1 and 2.6 years of corrected age by assessment of visual acuity, binocular visual fields, optokinetic nystagmus and strabismus. Visual impairments were found in 33% at age 1 and in 28% at age 2.6. Visual impairments were related to intraparenchymal damage, as detected by neonatal cerebral ultrasound, as well as to abnormal neurological examinations and lower mean developmental indices. A stepwise multiple regression analysis with neonatal cerebral ultrasound as the dependent variable and visual functions at ages 1 and 2.6 and neurological examinations at ages 1 and 2 as independent variables, however, demonstrated that standardized neurological examinations were better markers of neonatal cerebral damage than visual functions. In cognitive development at ages 1 and 2, the neurological examination at age 1 was the most important variable. In cognitive development at age 3.6, visual functions at age 2.6 were more important. Early visual impairments might thus influence later cognitive development. The effectiveness of appropriate early intervention strategies to stimulate visual and cognitive development in infants with less severe visual impairments should be subject to further study.