Reliability and validity of neuropsychological screening and assessment strategies in MS

Neuropsychological impairment is common in MS but routine evaluation is cumbersome. Many proposed avenues to more cost effective evaluation of cognition in MS have appeared in the literature. In this article, we summarize work conducted at our center over the past five years involving two specific evaluation methods, the Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ) designed to screen for neuropsychological impairment in MS and the Minimal Assessment of Cognitive Function in MS (MACFIMS) designed to quantify cognitive function with psychometric testing. Our research shows that these methods are reliable and valid. Data show strong relationships with neuropsychiatric features of the disease, brain imaging and vocational outcomes. Work with new non-conventional brain imaging techniques and finer analysis of reliability during serial testing protocols is underway.     

Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis.

The International Panel on MS Diagnosis presents revised diagnostic criteria for multiple sclerosis (MS). The focus remains on the objective demonstration of dissemination of lesions in both time and space. Magnetic resonance imaging is integrated with dinical and other paraclinical diagnostic methods. The revised criteria facilitate the diagnosis of MS in patients with a variety of presentations, including "monosymptomatic" disease suggestive of MS, disease with a typical relapsing-remitting course, and disease with insidious progression, without clear attacks and remissions. Previously used terms such as "clinically definite" and "probable MS" are no longer recommended. The outcome of a diagnostic evaluation is either MS, "possible MS" (for those at risk for MS, but for whom diagnostic evaluation is equivocal), or "not MS."     

The roles of blink reflex and sympathetic skin response in multiple sclerosis diagnosis

The neurological history and examination are important in multiple sclerosis (MS) diagnosis, but early and accurate diagnosis of MS often requires judicious use of paraclinical information. Electrophysiologic techniques have an important role in demonstrating lesions that are clincally silent but magnetic resonance imaging (MRI) is accepted as the most sensitive paraclincal test for detecting asymptomatic dissemination in space for MS patients. In order to test the sensitivity of electrophysiologic techniques in diagnosing asymptomatic MS lesions, we performed blink reflex (BR) and sympathetic skin response (SSR) studies on 13 female (mean age 39 -/+ 9 years) and 8 male (mean age 35 -/+ 14 years) patients with a diagnosis of definite MS who do not have any clinical symptoms nor signs referable to brainstem or autonomic system dysfunction. Forty three percent of patients on SSR testing and 40% of patients on BR testing demonstrated abnormal results. In countries with unfavorable economic conditions, diagnosis, especially the follow-up evaluation of MS patients, poses a major dilemma. The role of diagnostic techniques in MS diagnosis when MRI is available is an economic problem. Diagnostic evaluation adds to the cost of health expenses. We usually choose to perform MRI only at the initial diagnosis of MS and perform follow-up evaluations during remissions and exacerbations with the aid of electrophysiologic techniques. We stress the importance of electrophysiologic screenings in MS patients because they provide data that cannot be obtained through clinical evaluations only with a little cost.     

Motion Sickness: Current Knowledge and Recent Advance

Motion sickness (MS) is a common physiological response to real or virtual motion. Numerous studies have investigated the neurobiological mechanism and the control measures of MS. This review summarizes the current knowledge about pathogenesis and pathophysiology, prediction, evaluation, and countermeasures of MS. The sensory conflict hypothesis is the most widely accepted theory for MS. Both the hippocampus and vestibular cortex might play a role in forming internal model. The pathophysiology focuses on the visceral afference, thermoregulation and MS‐related neuroendocrine. Single‐nucleotide polymorphisms (SNPs) in some genes and epigenetic modulation might contribute to MS susceptibility and habituation. Questionnaires, heart rate variability (HRV) and electrogastrogram (EGG) are useful for diagnosing and evaluating MS. We also list MS medications to guide clinical practice. Repeated real motion exposure and combined visual‐vestibular interaction training accelerate the progress of habituation. Behavioral and dietary countermeasures, as well as physiotherapy, are also effective in alleviating MS symptoms.     

Pain and MS

Pain is frequently evident in the course of multiple sclerosis (MS) and is estimated to occur in approximately 50% of patients. The incidence of pain has no apparent correlation to disease severity. Moreover, a comprehensive definition of pain has not been established, thus making the evaluation of this chronic, evolving symptom difficult. On the basis of its pathophysiology, pain can occur as a consequence of neurological impairment and disability, somatic pain or because of neurological damage. Although there are few randomized trials for pain in MS, new therapeutic strategies are now available and interest in the symptomatic treatment of MS is growing.     

Multiple sclerosis and birth order

The relation between birth order and risk of multiple sclerosis (MS) was studied among MS patients in Israel. The evaluation was both by case-control study and comparison of expected and observed birth order in Israel-born patients. Results showed an excess of first-born and a low birth order among MS patients. Conversely, in MS patients born abroad but who developed the disease in Israel, MS was connected with an excess of last-born and high birth order. These contradictory results could not be explained by bias of case selection, difference in age, or changes in family size with time, and could indicate that different etiological factors are responsible for MS in distinct populations.     

Magnetic resonance imaging in the assessment of disease activity in multiple sclerosis

Magnetic resonance imaging (MRI) has been shown to be a good method of visualizing the lesions in MS. We have studied several applications of MRI to the evaluation of patients and experimental models. In diagnosis, MRI is the most sensitive test for the demonstration of dissemination of lesions in space. Pathological correlation studies show that MRI reliably measures the extent of chronic demyelination. Experimental studies show that MRI detects acute inflammatory lesions and measures their evolution. MRI also is a reliable measure of the extent of the MS process, serial MRI scans detect evidence of disease activity in MS not always disclosed by clinical evaluation. MRI will have an enormous future impact on the evaluation of patients in clinical studies and in understanding the evolution of pathological processes.     

Multiple sclerosis and affective disorder. Family history, sex, and HLA-DR antigens

To investigate a possible genetic cause underlying the clinical association between multiple sclerosis (MS) and affective disorder, we studied 56 patients with MS for psychiatric and genetic (family history, sex, and HLA-DR) characteristics. The 2:1 ratio of females to males expected for patients with MS was observed in this sample (40:16), but the excess of females occurred entirely among the 31 MS patients with major affective disorder (27 females and four males). Bipolar probands with MS had significantly more relatives with affective disorder or MS than did unipolar probands with MS. The HLA-DR antigen frequencies in patients with MS categorized by type and family history of affective disorder suggest that it may be possible to validate such clustering of patients. We concluded that sex and other genetic factors are related to the affective symptoms in MS and emphasize the importance of psychiatric evaluation of these patients.     

New error type and recall consistency indices for the Brief Visuospatial Memory Test - Revised: performance in healthy adults and multiple sclerosis patients

The Brief Visuospatial Memory Test - Revised (BVMT-R) is a reliable and well-validated test of visual-spatial memory with six equivalent, alternate forms. While the BVMT-R is commonly used in the evaluation of patients with craniocerebral trauma, schizophrenia, and multiple sclerosis (MS), the range of variables is limited. In this study, we developed new BVMT-R error and recall consistency indices. Inter-rater reliability and validity for the new indices were examined in 70 MS patients and 72 healthy volunteers. In addition to poorer general performance, MS patients made more intrusions and qualitative errors, and showed a trend toward poorer BVMT-R recall consistency. Findings suggest these error types and inconsistent learning contribute to poorer recall of visual material in MS.     

Multiple sclerosis: magnetic resonance imaging, evoked responses, and spinal fluid electrophoresis

Magnetic resonance images (MRI), evoked responses (ER), and CSF findings were compared in 39 patients with possible, probable, or definite MS. MRI disclosed multiple lesions (72%) more often than ERs (55%) in the total group of patients. In possible MS, MRI showed multiple lesions in 71%, and ER abnormalities were found in 41%. MRI is the preferred test for patients with suspected MS, but ERs are useful when MRI is normal and in the evaluation of optic nerve or spinal cord lesions.     

Ocular and cervical vestibular evoked myogenic potentials in multiple sclerosis patients

ObjectiveVestibular evoked myogenic potentials (VEMPs) are thought to provide useful information about brainstem functions, as the neural pathways of both ocular and cervical VEMPs pass through the brainstem. The aim of this study was to investigate the clinical value of ocular and cervical VEMP tests in the evaluation of brainstem involvement in multiple sclerosis (MS) patients and to assess their relation with clinical and cranial MRI findings.MethodsOcular and cervical VEMPs were recorded in 62 MS patients and 35 age and sex matched healthy volunteers. The latencies, amplitude asymmetry ratios of both VEMP responses and abnormality ratios (prolonged latencies and absent responses) were compared between the MS patients and the control group and among the groups of MS patients.ResultsoVEMP mean n1 and p1 latencies and cVEMP mean p13 latency were significantly prolonged in MS patients. Although the abnormality ratios of both VEMPs were higher in patients with brainstem clinical or MRI lesions, the correlation was not statistically significant. Both ocular and cervical VEMP latencies were significantly correlated with expanded disability status scale.ConclusionsAlthough there is no significant correlation with clinical or MRI findings, MS patients show high frequency of abnormality in VEMP tests, especially in oVEMP tests.SignificanceVEMP tests may be useful as an adjunct test in the evaluation of brainstem dysfunction in MS patients.     

Management of bladder dysfunction in multiple sclerosis patients: the nurse’s point of view

It is estimated that as many as 90% of people with multiple sclerosis (MS) experience some type of urinary disturbance over the course of the disease. The importance of an interdisciplinary approach is crucial in the management of a symptom requiring the involvement of different professionals, with specific expertise in evaluation and treatment. The MS nurse is perhaps the professional most likely to be in a position to initiate the process of identifying urological dysfunction. The evaluation can be started by reviewing symptoms recorded in the patient’s medical records over time. Along with the use of a urinary diary and a check of the patient’s post-void residual at the time of each visit, this can aid the MS nurse in recognising which urinary dysfunction could be affecting the patient. The MS nurse can also have an important role in teaching the patient behaviour strategies that aid in both evaluating and treating urinary dysfunction. Finally, the MS nurse can be the primary instructor of techniques related to intermittent catheterisation procedures. A new topic highlighting the ever-developing role of the MS nurse is in the field of rehabilitation. This article highlights urinary symptoms experienced by people with MS and strategies used for treating them. The role of the MS nurse in managing urinary dysfunction is also discussed.     

Multiple sclerosis tremor and the Stewart-Holmes manoeuvre.

The objective of this study is to define tremor and cerebellar dysfunction and determine whether kinetic and postural tremor correlate with cerebellar dysfunction in patients with multiple sclerosis (MS). Cerebellar symptoms such as dysmetria often interfere with tremor evaluation in MS. The Stewart-Holmes (SH) manoeuvre, which has been recently quantified, may offer a selective evaluation of cerebellar dysfunction in such patients. Thirty-two patients with definite MS and arm tremor were evaluated (simplified Fahn tremor scale for kinetic and postural tremor, finger-to-nose test, clinical SH manoeuvre, quantitative study of the SH manoeuvre). Median severity of kinetic and postural tremor on the most disabled side was, respectively, 2 (range 0-4) and 1.5 (range 0-4). Clinical SH scores were moderately correlated to quantified SH measures (r = 0.36, P < 0.05). Kinetic and postural tremors were strongly correlated (r = 0.73, P < 0.0001) but did not correlate with clinical or quantified SH scores. Patients with bilateral tremor had higher scores for quantified SH, and a trend to higher clinical SH and finger-to-nose scores than patients with unilateral tremor. Although clinically associated, cerebellar dysfunction and tremor may be partly independent symptoms, suggesting they may relate to dysfunction of different neuronal systems. The SH manoeuvre should be part of the evaluation of MS patients considered for surgery of tremor.     

Delay in the diagnosis of multiple sclerosis in Croatia

BackgroundThe National Institute for Health and Clinical Excellence (NICE) guidelines for multiple sclerosis (MS) recommend the time from initial presentation to first neurological evaluation to be no longer than 6 weeks, and a further 6 weeks until any necessary investigations are completed. The aim of this study was to evaluate how many patients with MS are diagnosed within the NICE timelines in two settings specific for Croatia.Patients and methodsAll patients with the final diagnosis of clinically isolated syndrome (CIS) or MS in a 6 months period were retrospectively reviewed. We calculated time from first symptom to first neurological evaluation, time from first symptom to MRI scan, time from first neurological evaluation to MRI scan, time from first neurological evaluation to lumbar puncture (LP), time from first symptom to diagnosis and time from first neurological evaluation to diagnosis. We also calculated the percentage of patients fulfilling the NICE timelines.ResultsThis study showed that only 61.5% of MS patients in Croatia see neurologist within 6 weeks of first symptoms, and 64.1% are diagnosed within next 6 weeks. However, 80% and 100% of patients presented to the emergency room of our hospital (where a visit to a MS clinic can be automatically made) met the NICE guidelines for time from first symptom to first neurological evaluation and time from first neurological evaluation to diagnosis, respectively.ConclusionA specifically designed demyelinating disease diagnostic clinic offers a better service than other existing models in the diagnosis and management of MS patients.     

Depression and quality of life in multiple sclerosis

OBJECTIVES: Health related quality of life (QoL) has gained increasing influence as a relevant evaluation criterion in multiple sclerosis. The high prevalence of psychiatric comorbidity in MS is, however, hardly ever considered in studies concerning QoL. MATERIALS AND METHODS: In 60 patients of a MS outpatient clinic, symptoms of anxiety (Zung Anxiety Scale) and depression (Zung Depression Scale), as well as the health-related quality of life were rated and set into relation to the EDSS and to the duration of illness, respectively. RESULTS: There was a highly significant correlation between depression as well as anxiety and the self-assessed quality of life. Depression was the by far strongest predictor for reduced QoL. CONCLUSION: Clinical studies, which seek to register the increasingly important evaluation criterion of health-related quality of life in MS, should consider the prevalence of depressive disorders and the decisive effect of depression on the self-assessed quality of life of affected patients.     

Picturing multiple sclerosis: conventional and diffusion tensor imaging

Magnetic resonance imaging (MRI) has provided an unparalleled window into understanding multiple sclerosis (MS). Through recognition of relatively specific characteristics of MS, MRI has become an integral part of patient initial evaluation and long-term management. MRI has now been integrated into the formal diagnostic criteria, whereby new lesions can fulfill either dissemination in space or dissemination in time criteria. Long-term MS therapies significantly reduce the development of new lesions as measured by MRI, and clinical trial methodology now routinely uses MRI as the primary outcome in Phase I/II MS trials. Despite the advantages provided by MRI, conventional imaging indicates only the presence of injury to the central nervous system, providing little information on either the severity of injury or its later recovery. Several advanced imaging methodologies such as diffusion tensor imaging (DTI) provide a greater dynamic range for evaluating tissue integrity. DTI has provided useful insights into the pathogenesis of MS, both within lesions as well as within the white matter which appears normal on conventional imaging. Evidence from animal models suggests that DTI may differentiate axonal injury from demyelination and therefore may be useful in the evaluation of neuroprotective therapies.     

Differences in mesenchymal stem cell cytokine profiles between MS patients and healthy donors: implication for assessment of disease activity and treatment

MSCs have been proposed as possible treatment in MS: In this study MSCs obtained from 10 MS patients and 6 healthy donors (HD) were compared in terms of phenotypical and functional characteristics. We show that MSCs isolated from MS and HD differ significantly for IP10 production. Therefore, although MSCs isolated from MS patients exhibit the same properties of HD MSCs in terms of proliferation, phenotype, in vitro differentiation, TLR expression, immunosuppressive ability, inhibition of DC differentiation and activation, the use of autologous MSCs in cell therapy of autoimmune diseases should be submitted to attentive evaluation and treatment.     

Diagnosis and treatment of multiple sclerosis

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system that usually has onset between 20 and 40 years of age. The causes of MS are unknown, but it probably evolves among genetically susceptible individuals as an infrequent response to environmental factors. The diagnosis is based on careful evaluation of the disease history, clinical examination as well as paraclinical examination, aiming to document disseminated disease in both time and space. No cure is available, but corticosteroids can be used for relapses, various symptomatic treatments exist, and several long-term, disease-modifying therapies are available. This article reviews the diagnosis and treatment of MS, focusing on treatment of relapses and disease-modifying therapies.     

Polymorphonuclear neutral protease activity in multiple sclerosis and other diseases

Polymorphonuclear neutral protease activity (PMN-NPA) was examined in 87 patients with definite multiple sclerosis (MS) (48 active, 39 inactive), 49 patients with other neurological diseases (OND), 24 patients with immune-mediated non-neurological diseases (INND), and 32 normal subjects. PMN-NPA was found to be significantly increased in active MS compared with inactive MS and compared with each of the control groups. No differences were found between the group of normal subjects and the groups of patients with OND, INND, or inactive MS. Levels of PMN-NPA were significantly higher in the OND group than in inactive MS group. The differences for INND versus normal controls, neurological controls, and patients with inactive MS were not significant. No significant differences have been detected between active and inactive INND. These results suggest that PMN-NPA may be useful in the diagnosis and evaluation of MS.     

Muscle atrophy associated with multiple sclerosis: a benign condition or the onset of amyotrophic lateral sclerosis?

When muscular atrophy develops in multiple sclerosis (MS) patients, its etiology may vary from benign to serious. We describe an individual with a 24-year history of MS who developed amyotrophic lateral sclerosis (ALS). The literature is reviewed with particular attention to the clinical and electrophysiologic characteristics of patients with MS and muscular atrophy and to those rare patients with concurrent MS and ALS. Circumstances warranting a heightened suspicion for concurrent ALS are discussed and careful evaluation of similar patients is encouraged.