The neuropsychiatry of multiple sclerosis: a review of recent developments

PURPOSE OF REVIEW: The aim of this review is to summarize the current literature on the neuropsychiatry of multiple sclerosis (MS). RECENT FINDINGS: Data from community samples have supported earlier findings from tertiary referral centres of high rates of depression in MS patients. Neuroimaging offers important clues as to the pathogenesis of depression, but psychosocial factors cannot be ignored and emerge as equally important predictors. Cognitive-behavioural therapy is an effective treatment, rivalling standard dosing of sertraline in patients with depression. An allied disorder--pseudobulbar affect--occurs in up to 10% of MS patients and responds well to a combination of dextromethorphan and quinidine. Cognitive dysfunction affects approximately 40% of MS patients. Markers of cerebral atrophy have emerged as more important correlates of impaired cognition than lesion volume. Moreover, functional MRI studies have demonstrated the brain's ability to compensate, in part, for damage. Should the disease burden be too severe, however, compensatory mechanisms fail and cognitive deficits increase accordingly. SUMMARY: Neuropsychiatric abnormalities are common in MS patients. No aspect of mentation is spared. Advances in neuroimaging are increasing our understanding of the pathogenesis of these disorders. Translating these findings into improved methods of treatment for patients presents researchers with pressing challenges.     

多发性硬化与认知功能障碍

多发性硬化(multiple Sclerosis, MS)是中枢神经系统最常见的脱髓鞘疾病,常分为复发-缓解型(RRMS)、原发进展型(PPMS)及继发进展型(SPMS)三种类型.MS不仅可以导致患者躯体残疾,还常常造成不同程度认知功能损害.提高临床医师对MS认知障碍的认识,并及早采取有效的干预措施,可有效改善MS患者的预后.     

Cognitive impairments in multiple sclerosis: a review

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Cognitive impairment (CI) may develop at any time during the course of the disease in the presence or absence of neurological disability. On the basis of comprehensive neuropsychological studies, there is now a consensus among investigators that 45 percent to 65 percent of MS patients suffer from some degree and form of cognitive difficulty. Features of CI include bradyphrenia; impaired attention, concentration and abstract reasoning; reduced manual speed and dexterity; deficits in memory retrieval; and language deficits in both the relapsing-remitting and progressive forms of MS. Impairments in all cognitive domains may result from the diffuse spread of microscopic pathology, although a preferential lobar distribution of plaques can present with a predominant deficit in the corresponding cognitive function. Nevertheless, the severity of CI best correlates with total microscopic and macroscopic disease burden of the brain as defined by recently developed magnetic resonance imaging (MRI) sequences. A disruption of connecting intercortical and subcortical pathways is likely to be the main cause of metabolic and functional abnormalities in neurons. However a direct toxic effect of soluble inflammatory products may also compromise neuronal function and survival. Early treatment of MS with interferons and copaxone can prevent or delay the onset of both neurological and cognitive disabilities by reducing the inflammatory activity and damage in the CNS. Until more powerful neuroprotective agents become available, simple neuropsychological screening and cognitive rehabilitation for memory and language impairments will remain important components in the care of MS patients.     

Cognitive dysfunction in early-onset multiple sclerosis: a reappraisal after 10 years

OBJECTIVE: To reassess, in a cohort of patients with early-onset multiple sclerosis, the long-term evolution of cognitive deficits, their relationship to the disease's clinical progression, and their effects on daily life. DESIGN: Ten years after our baseline assessment, we again compared the cognitive performance of patients and control subjects on a neuropsychological test battery. Clinical and demographic correlates of cognitive impairment and their effects on everyday functioning were determined by multiple linear regression analysis. SETTING: The research clinic of a university department of neurology. PARTICIPANTS: Forty-five inpatients and outpatients with multiple sclerosis and 65 demographically matched healthy controls from the original sample. MAIN OUTCOME MEASURES: Mean scores of both groups on the neuropsychological test battery in initial and 2 follow-up evaluations (about 4 and 10 years, respectively); number of cognitively impaired subjects, defined by the number of subtests failed; regression coefficients measuring the relationship between clinical variables and cognitive outcome and between mental decline and everyday functioning assessed by the Environmental and the Incapacity Status Scales. RESULTS: Previously detected cognitive defects in verbal memory, abstract reasoning, and linguistic processes were confirmed on the third testing, at which time deficits in attention/short-term spatial memory also emerged. Only 20 of 37 patients who were cognitively unimpaired on initial testing remained so by the end of the follow-up, when the proportion of subjects who were cognitively impaired reached 56%. Degree of physical disability, progressive disease course, and increasing age predicted the extent of cognitive decline. Disability level and degree of cognitive impairment were independent predictors of a patient's handicap in the workplace and in social settings. CONCLUSIONS: In the course of a sufficiently long follow-up, cognitive dysfunction is likely to emerge and progress in a sizable proportion of patients. As multiple sclerosis advances, neurological and cognitive involvement tend to converge. Limitations in a patient's work and social activities are correlated with the extent of cognitive decline, independent of degree of physical disability.     

Cognitive rehabilitation in multiple sclerosis: a review of the literature

Introduction

Cognitive impairment is now well-known in multiple sclerosis (MS). However, few rehabilitation interventions are proposed or really efficient.

Objectives

To present a review of cognitive rehabilitation intervention research conducted in people with multiple sclerosis (MS), regarding different findings about episodic memory, working memory, attention and executive function disorders in MS.

Data sources

A search of Medline (yield 20 papers) and of PsychInfo (yield 1 article), using combinations of the following terms: cognitive rehabilitation, multiple sclerosis, cognitive therapy, neuropsychological rehabilitation, in the title or in the abstract, from 1960 to March 2010, excluding animal studies.

Results

Episodic memory rehabilitation studies appear to be promising. Programs on working memory, attention and executive functions are in the very early phases.

Conclusions

Results are encouraging and allow specific recommendations for future research about: (1) inclusion criteria, often not defined, (2) a specific baseline adapted to the program of rehabilitation, (3) a control measure regarding program efficiency and (4) a role for the psychologist (presence and advice during the program).     

Cognitive dysfunction in patients with relapsing-remitting multiple sclerosis

Cognitive dysfunction is considered one of the clinical markers of multiple sclerosis (MS). However, in the literature there are inconsistent reports on the prevalence of cognitive dysfunction, and separate data for the relapsing-remitting (RR) type of the disease are not always presented. In this study, we submitted 461 RRMS patients to a battery of neuropsychological tests to investigate their impairment in various cognitive domains. As a consequence of the exclusion criteria, the sample is not fully representative of the entire population of RRMS patients. In this selected sample, when only the eight scores of a core battery (Mental Deterioration Battery) were considered (with respective cutoffs), it emerged that 31% of the patients were affected by some degree of cognitive deficit. In particular, 15% had mild, 11.2% moderate and 4.8% had severe impairment. Information processing speed was the most frequently impaired area, followed by memory. When two other tests (SDMT and MCST) were added and cognitive domains were considered, it emerged that 39.3% of the patients were impaired in two or more domains. When four subgroups were obtained by means of cluster analysis and then compared, it emerged that information processing speed and memory deficits differentiated the still cognitively unimpaired from the mildly impaired MS patients. Significant associations were found between cognitive and clinical characteristics. However, due to the large sample size, clinically irrelevant relationships may also have emerged. Even with the limitations imposed by the sample selection and the possible underestimation of the prevalence and severity of cognitive dysfunction, these results seem to provide further evidence that information processing speed deficit may be an early and important marker of cognitive impairment in MS patients.     

RETRACTED ARTICLE: Cognitive deficits in multiple sclerosis: a review of functional MRI studies

Cognitive dysfunction frequently occurs during the course of multiple sclerosis (MS). In patients with MS the severity of cognitive manifestations is not closely related to indices of structural brain damage. Neuroplasticity may contribute to the maintenance of normal performance despite scattered brain lesions. Changes in functional organization of the cerebral cortex have been reported by functional magnetic resonance imaging (fMRI) studies in MS. fMRI studies provide an interesting way of understanding how the brain changes its functional organization in response to MS, and might be useful in the study of the effects of rehabilitative or pharmacological therapy on brain plasticity. The purpose of this review is to examine major fMRI studies focusing on cognitive dysfunction in MS.     

Cognitive dysfunction in multiple sclerosis: natural history and impact on productive living

Studies in which groups of patients with multiple sclerosis (MS) and controls of comparable age and education are compared reveal consistent impairments by the patient groups on test of anterograde explicit memory, controlled attentional processing, information processing speed, and abstract reasoning and problem solving. Vocabulary, naming and visual perception are less often affected. However, the extent of cognitive impairment for individual patients varies from none at all to global dementia. Both physical and cognitive impairment contribute equally to predicting employment status, but some patients with global cognitive impairment can continue to work effectively at mentally demanding professional jobs. Recently developed screening examinations could detect cognitive impairment early and permit interventions when they should be maximally effective. Three key issues in clinical neuropsychology are identified which have not been addressed by traditional neuropsychology. Italian neuropsychology, because of its unique characteristics, could lead in understanding these important questions.     

Depression in multiple sclerosis: a review

Several studies have reported high rates of depression in multiple sclerosis (MS) with a lifetime prevalence of ～50% and an annual prevalence of 20% not uncommon. Concern about the potential of new drug treatments to exacerbate or precipitate depression in MS has led to increased interest in the relation between MS and depression. This review on MS and depression identifies the following key issues: How common is depression in people with MS? Is depression in MS associated with lesions in specific regions of the central nervous system? Is there an increased risk of suicide in MS? Is there a higher than expected incidence of anxiety disorders in MS? Are fatigue and depressed mood related in MS? Is there a relation between depression and cognitive impairment in MS? Which psychosocial variables affect the development of depression in MS? Does treatment with interferon increase the risk of depression? How effective are treatments for MS patients with depression? Each of these issues is briefly reviewed with critical commentary, and some priorities for future research are suggested.     

Cognitive impairments in relapsing-remitting multiple sclerosis: a meta-analysis

There is debate in the literature regarding the magnitude, nature, and influence of cognitive impairment in individuals with relapsing-remitting multiple sclerosis (RRMS). Therefore, we conducted a meta-analysis that quantified the overall magnitude of cognitive impairment in individuals with RRMS and identified the domains of cognition and clinical/demographic variables that were moderators of the overall effect. We included 57 studies with 3891 participants that yielded a total of 755 effect sizes. Overall, there was a moderate decline in cognitive functioning in individuals with RRMS compared with healthy controls. Larger effects were observed in cognitive domains of motor functioning, mood status and memory and learning. Regarding demographic and clinical variables, age and gender were moderators of cognitive impairment in all cognitive domains, whereas neurological disability and disease duration primarily moderated performance on tasks assessing memory and learning.     

Mortality in multiple sclerosis: a review

This work was undertaken to evaluate studies on mortality caused by multiple sclerosis (MS), to evaluate if useful inferences can be drawn from survival studies that can be applied to clinical practice. A literature search was carried out to find epidemiological studies on MS prognosis, survival, mortality and causes of death relevant to our aim. The World Health Organization (WHO) reports on worldwide cause-specific mortality were also considered. Studies were evaluated according to the duration of the follow-up study, the year of publication and the methodology used. We evaluated MS survival from a methodological point of view and considered if time trends could be drawn from study results. We conclude that mortality is only slightly higher in MS patients when compared with that in the general population. Mortality is higher particularly for older patients and those with longer disease duration.     

Autonomic dysfunction in multiple sclerosis and other updates on recent autonomic research

Clinical Autonomic Research -     

Cognitive dysfunction and multiple sclerosis: developing a rationale for considering the efficacy of exercise training

Cognitive impairment is a prevalent, disabling, and poorly managed consequence of multiple sclerosis (MS). This underscores the importance of considering alternative approaches, such as exercise training, for managing cognitive impairment in persons with MS. The consideration of exercise training is warranted based on evidence summarized in literature reviews and meta-analyses that (1) aerobic fitness, physical activity, and exercise training are associated with better cognitive function in older adults; and (2) exercise training has comparable effects on mobility and quality of life outcomes in older adults and persons with MS. To date, research examining aerobic fitness, physical activity, and exercise training effects on cognition in MS is nascent and mostly includes cross-sectional designs that provide preliminary evidence for a well-designed randomized controlled trial (RCT). We believe that a future RCT should adopt research methodologies and practices from gerontology when examining exercise training and cognition in MS. This will maximize the potential for successfully generating a body of knowledge on exercise training and cognition with the potential for impacting the lives of persons with MS.     

Cognitive dysfunction in different stages in multiple sclerosis – presentation of 3 cases

Journal of Neurology - Although multiple sclerosis (MS) is a physically disabling disease, many patients also suffer from cognitive dysfunction in all stages of the disease. Recent studies have...     

Cognitive screening in multiple sclerosis

Cognitive screening tests in multiple sclerosis (MS) are time- and cost-saving test instruments. In the case of a positive test result (alert function) a comprehensive cognitive test procedure should be administered. This paper explains what cognitive screening in MS means and presents several screening instruments used in MS with their statistical test characteristics, e. g. sensitivity and specificity.     

Cognitive disorders in multiple sclerosis

Forty to sixty percent of patients with multiple sclerosis (MS) have cognitive dysfunction. The frequency of cognitive disturbances according to the clinical form is not completely understood and the natural history of these disorders has not been extensively studied. Cognitive deficits can be detected in early stages of the disease. Their frequency increases from clinically isolated syndromes, to relapsing-remitting and secondary progressive MS. Cognitive abnormalities are frequently observed also in primary progressive MS. The most frequently impaired functions are information processing speed, attention and memory. Dementia is uncommon but may disclose the disease. Diffuse cerebral injury, assessed by magnetic resonance imaging, contributes to cognitive dysfunction in MS, probably by interrupting connecting fibers between neuronal networks involved in these cognitive functions. Compensatory mechanisms may occur at early stages but they are limited by extension of brain injury.