Pulse pressure is associated with walking impairment in multiple sclerosis

Persons with multiple sclerosis (MS) have reduced gait performance and this is associated with disability and disease progression. The current study sought to test the hypothesis that higher central (aortic and carotid) and peripheral (brachial) pulse pressure (PP), manifestations of ventricular-vascular uncoupling related to increased arterial stiffness and pressure from wave reflections, would be associated with reduced gait performance in persons with MS. Participants consisted of 33 individuals with MS and 33 age/sex matched controls. Central blood pressure (BP) was assessed via applanation tonometry. Brachial BP was measured using an automated oscillometric cuff. PP was defined as systolic BP--diastolic BP. Gait performance was measured as 6-minute walk (6 MW) distance. Within the sample with MS, the 6 MW distance was significantly associated with brachial (r = -.49, p<.005), aortic (r = -.52, p<.001), and carotid (r = -.57, p<.001) pulse pressure. There was no association between any PP measure and 6 MW distance in controls (p>0.05 for all). In conclusion, PP is a predictor of gait performance in persons with MS. These findings suggest that vascular senescence and altered ventricular-vascular coupling may contribute, in part, to the deterioration of physical function in persons with MS.     

Contractile speed and fatigue of adductor pollicis muscle in multiple sclerosis

The purpose of the study was to investigate differences in contractile speed, force, and fatigability of the adductor pollicis muscle between 12 patients with multiple sclerosis (MS) and 8 sedentary control subjects matched for age and gender. There were no differences between the patients with MS and control subjects with respect to the percentage of maximal muscle force that could be recruited during voluntary effort (95.5 +/- 3.9% and 98.2 +/- 2.0%, respectively, P = 0.10), the stimulation frequency/force and force/velocity relationships, the rates of force development and relaxation, fatigue resistance, and the recovery rate of adductor pollicis muscle. However, previous results from the same group of MS patients showed that quadriceps femoris muscle force and resistance to fatigue were reduced. Therefore, our data support the clinical experience that, in patients with MS, lower limb muscle function is more or earlier affected than upper limb muscle function.     

Relation between EEG and disability scores in multiple sclerosis

A disability-scoring and an EEG-spectral analysis was performed in patients suffering from clinically and biochemically (oligoclonal aspect in cerebro-spinal fluid) proven multiple sclerosis at two stages of their illness, that are before and after a short intensive immuno suppressive therapy. In both stages a relationship is found between the degree of disability and the amount of beta activity in the fronto-central area and the amount of the theta activity in the temporal area. Significant improvement in the clinical state of the patient and a marked increase of the mean alpha frequency in the parietooccipital region could be demonstrated after short intensive immunosuppressive therapy.     

Assessing walking disability in multiple sclerosis

Most patients with multiple sclerosis (MS) eventually experience walking disability. The objective of this review was to evaluate the clinical utility of measures specific for walking in MS. Walking assessments had high reliability and were correlated with related measures, including the 12-item multiple sclerosis walking scale (MSWS-12). Shorter timed walking tests (Timed 25-foot Walk (T25FW), 10-metre Timed Walk, 30-metre Timed Walk) measure overall walking disability and are best suited for clinical settings, whereas longer timed or distance tests (100-metre Timed Walk, 6-minute Walk Test, 2-minute Walk Test) are better for the assessment of walking fatigability, distance limitations and functional capacity. The MSWS-12 measures different, but related, aspects of walking than the objective tests. The T25FW is the best characterised objective measure of walking disability and can be used across a wide range of walking disabilities. Additional work is needed to fully characterise the other objective walking assessments in MS.     

Cortical somatosensory magnetic responses in multiple sclerosis

Somatosenosor evoked magnetic fields (SEFs) to contralateral medium and ulnnar nerve stimulation were analyzed in 10 patients with multiple sclerosis and in 8 healthy controls. SEFs were recorded with a 24-channel SQUID gradiometer over both hemispheres. Seven patients' showed abnormally large-amplitude SEF deflections at 60–80 msec; 5 of them had multiple lesions around lateral ventricles in magnetic resonance imaging. In 2 patients with plaques at the level of 3rd and 4th ventricles and medulla, the 30 msce response were enlarged. The equivalent sources of 20 msec and 30–80 msec responses were in the primary hand sensorimotor cortex both in patients and in control subjects. The results suggest that early and middle-latency SEFs reflect parallel processing of somatosensory input. Recording of middle-latency evoekd responses, electric or magnetic, may give additional information about the somatosensory function in multiple sclerosis.     

Correlation of phasic muscle strength and corticomotoneuron conduction time in multiple sclerosis

Central motor conduction times for the adductor pollicis muscle, the twitch force of that muscle to scalp magnetic motor cortex stimulation, and the maximum force of phasic voluntary contraction of the same muscle were measured in 15 patients with multiple sclerosis. Two tests of manual dexterity of the same hand also were studied: the Purdue pegboard test, and the maximal frequency of a scissors movement of the thumb and index finger. The patients had normal strength or minimal weakness of the intrinsic muscles of the hand on clinical examination. The mean central motor conduction times for the adductor pollicis muscle for the patients were longer than normal, the peak twitch force of the adductor pollicis muscle evoked by cortical stimulation and the maximum force of a phasic voluntary contraction of the adductor pollicis muscle were smaller than normal. There were strong correlations between all these measures. Central motor conduction time in the patients was inversely correlated with voluntary phasic force and the twitch force after cortical stimulation. That is, the longer the central motor conduction time, the weaker the force. Prolonged central motor conduction time is likely to be accompanied by conduction block in corticomotoneuron pathways. The correlation of central motor conduction time with voluntary phasic force and the twitch force most likely reflects the degree of conduction block and temporal dispersion rather than delay in conduction per se. These results indicate that objective assessments of phasic muscle strength may reveal correlations with central motor conduction time that are not evident on conventional clinical examination which assesses tonic muscle contraction strength.(ABSTRACT TRUNCATED AT 250 WORDS)     

The dynamics of finger tremor in multiple sclerosis is affected by whole body position

Multiple sclerosis (MS) is a disease that results in widespread damage to the nervous system. One consequence of this disease is the emergence of enhanced tremor. This study was designed to (1) compare the tremor responses of persons with MS to that of healthy adults and to (2) examine the impact of whole body position (i.e., seated/standing) on tremor. Bilateral postural tremor was recorded using accelerometers attached to each index finger. Results revealed some similarity of tremor between groups in regard to the principal features (e.g., presence of peaks in similar frequency ranges). However, significant differences were observed with tremor for the MS persons being of greater amplitude, more regular (lower ApEn) and more strongly coupled across limbs compared to the elderly. The effects of body position were consistent across all subjects, with tremor increasing significantly from sitting-to-standing. However, the tremor increase for the MS group was greater than the elderly. Overall, the tremor for MS group was negatively affected by both this disease process and the nature of the task being performed. This latter result indicates that tremor does not simply reflect the feed-forward output of the neuromotor system but that it is influenced by the task constraints.     

LHON mutations in Italian patients affected by multiple sclerosis

The occurrence of a multiple sclerosis (MS)-like phenotype in subjects carrying mitochondrial DNA (mtDNA) mutations associated with Leber hereditary optic neuropathy (LHON) has suggested that mitochondrial genes may contribute to susceptibility to MS. With the present study 74 unrelated Italian patients (53 females and 21 males; mean age 37.9, SD 9.9, range 20–59) affected by MS with early and prominent optic nerve involvement and 99 normal control subjects were analysed for the presence of primary (nps 11778,3460,14484) and an alleged secondary one (np 15257) LHON mutations. A single MS patient carrying a virtually homoplasmic LHON mutation at np 11778 was found. Family history revealed a maternal uncle affected by MS, deceased at age of 64 in consequence of a stroke. The patient's mother harboured the same mutation in a homoplasmic way. Primary LHON mutations were not detected in any other MS patient or control. Of the MS patients 5.4% (4 out of 74), and 5.1% (5 out of 99) of the controls carried the 15257 mutation in a homoplasmic state. Present data do not support any contribution of primary LHON mutations to genetically determined susceptibility in MS. There is no evidence that the 15257 mutation has any pathogenetic significance in the Italian population.     

Cortical somatosensory magnetic responses in multiple sclerosis.

Somatosensory evoked magnetic fields (SEFs) to contralateral median and ulnar nerve stimulation were analyzed in 10 patients with multiple sclerosis and in 8 healthy controls. SEFs were recorded with a 24-channel SQUID gradiometer over both hemispheres. Seven patients showed abnormally large-amplitude SEF deflections at 60-80 msec; 5 of them had multiple lesions around lateral ventricles in magnetic resonance imaging. In 2 patients with plaques at the level of 3rd and 4th ventricles and medulla, the 30 msec responses were enlarged. The equivalent sources of 20 msec and 30-80 msec responses were in the primary hand sensorimotor cortex both in patients and in control subjects. The results suggest that early and middle-latency SEFs reflect parallel processing of somatosensory input. Recording of middle-latency evoked responses, electric or magnetic, may give additional information about the somatosensory function in multiple sclerosis.     

Mitochondrial DNA variants in Bulgarian patients affected by multiple sclerosis

The occurrence of multiple sclerosis (MS) in subjects clustering to a particular mitochondrial DNA (mtDNA) haplogroup/haplotype or carrying mtDNA mutations associated with Leber's hereditary optic neuropathy (LHON) has suggested that mitochondrial genome may contribute to susceptibility to MS. In the present study, 58 unrelated Bulgarian patients with relapsing remitting form of MS and 104 randomly selected healthy individuals were analysed for the presence of 14 mtDNA polymorphisms determining major European haplogroups as well as three (4216, 14 798, 13 708) secondary LHON mutations. Restriction enzyme analysis used to screen patients and controls for the common haplogroup-associated polymorphisms showed that each of these changes was present in MS patients at a similar frequency to control subjects. However, 21 of the 58 patients (36.2%) were positive for T4 216C mutation, while only 11.3% of the controls carried this secondary LHON base change ( P  < 0.01; OR = 4.38). Our finding indicated that 4216C base substitution could be considered as a predisposing marker for MS and supported the hypothesis that particular mtDNA variants could contribute to genetic susceptibility of MS, and merits further investigation.     

Relation between objective and subjective measures of bladder dysfunction in multiple sclerosis

The authors studied 297 patients with multiple sclerosis (MS), correlating urinary symptoms (bowel/bladder Functional System [FS] score of the Expanded Disability Status Scale [EDSS] and bladder dysfunction score of the Guy's Neurological Disability Scale [GNDS[) vs objective measurement of bladder dysfunction (postmicturition residual volume). EDSS and GNDS were of no value for predicting the presence of a clinically relevant postvoiding volume. Therefore, the authors recommend ultrasound scanning of residual volume in every patient with MS, even in the absence of subjective urinary symptoms.     

Visual and somatosensory evoked cortical potentials in multiple sclerosis.

The diagnostic value of the pattern reversal evoked cortical potential (VEP) and the somatosensory evoked cortical potential (SEP) has been compared in 50 patients with established or suspected multiple sclerosis. A prolonged latency of VEP was found in 96% of definite cases of multiple sclerosis, 58% of probable cases, and 20% of possible cases. A prolonged latency of SEP by stimulation of median or peroneal nerves or both was found in 86% of definite cases of multiple sclerosis, 83% of probable cases, and 50% of possibe cases. When combining the results of all three tests the diagnostic yield increased to 100%, 92%, and 50%, respectively.     

Asymptomatic visual loss in multiple sclerosis

Visual disturbances are common in multiple sclerosis (MS) and often a result of acute demyelinating optic neuropathy. Careful examination of MS patients, who have never suffered optic neuritis, may also reveal asymptomatic visual loss. This type of silent disease activity was investigated by computerised resolution perimetry, which has the potential to reflect the percentage of functional retino-cortical neural channels. The time of onset and the evolution of asymptomatic visual loss was investigated. One approach was to retrospectively select patients who never had suffered acute optic neuritis from a closely monitored MS population and re-examine them again. Sixteen patients were identified and vision was evaluated during a period of 5.5–9 years of follow-up and compared with that in 14 healthy controls. The mean channel percentage of the MS group was 89 ± 19 % (SD) on entry into the study, compared with 110 ± 15 % (SD) of controls (p < 0.003). At termination of the study the mean percentage was essentially unchanged both in MS patients (87 ± 21 %, SD) and controls (110 ± 19 %, SD). The second approach was to test a group of 7 patients with MS or strongly suspected MS, with the same method, in close connection with their first clinical exacerbation. All cases lacked visual symptoms and none had previously had acute visual loss. Again, virtually all performed subnormally in the vision tests, and to the same degree as in the first group of patients. Results were compared with those obtained from 25 MS patients who had experienced one or more attacks of optic neuritis. Compared with controls the loss of functional retino-cortical neural channels was 20 % in patients without a previous history of optic neuritis and 30 % in patients who previously had experienced optic neuritis. We conclude that asymptomatic visual loss seems to be a universal feature of MS and has a substantial impact on the visual pathways, that it is present already at the time of clinical onset of the disease, and that any progression thereafter is slow enough to elude detection during several years of follow-up. Received: 28 June 2000, Received in revised form: 7 March 2001, Accepted: 23 April 2001     

Olfactory loss in multiple sclerosis.

The objectives of the present study were to test odor identification ability in patients with multiple sclerosis (MS) and to examine possible correlations between smell identification test scores and various clinical variables. We performed a case-control study comparing the Cross Cultural Smell Identification Test scores of 40 patients with definite multiple sclerosis with those obtained in 40 age-, sex- and smoking-habit-matched healthy controls. The neurological impairment, the disability, the cognitive performances and the psychological functioning were also assessed. Patients with multiple sclerosis scored significantly poorer than controls on the Cross-Cultural Smell Identification Test (P<0.001). Olfactory function was borderline normal in four (10%) and abnormal in five (12.5%) MS patients, whereas it was normal in all controls (P<0.02). Significant correlations between the smell identification score and symptoms of anxiety (r=-0.43, P=0.006), depression (r=-0.42, P=0. 008) and severity of neurological impairment (r=-0.32, P=0.05) were found. Only two (5%) patients with multiple sclerosis reported having episodes of smell loss, suggesting a low level of awareness of this problem. Although smell changes are rarely reported, olfactory function is impaired in a considerable number of patients with MS. The observed association between decreased odor identification ability and symptoms of anxiety and depression in our patients suggests that mood and anxiety disorders have to be considered in assessing olfaction in MS patients. Clearly, smell disturbances deserve greater attention from health professionals and caregivers dealing with such patients.     

Pudendal nerve somatosensory evoked potentials in probable multiple sclerosis

Bladder dysfunctions are often observed in patients with multiple sclerosis (MS). In order to evaluate their sensitivity in detecting abnormalities in bladder central control pathways, pudendal nerve somatosensory evoked potentials (pSEPs) were recorded in 16 patients with clinically probable MS: six were affected by retention or urge incontinence, and ten were asymptomatic. Conventional visual, auditory and somatosensory evoked potentials were also recorded, and all of the patients underwent a urodynamic examination. Prolonged latency or the absence of pSEP cortical responses was found in eight of the ten asymptomatic patients, and in all of the symptomatic cases (87.5%). The urodynamic evaluation revealed abnormalities in 12 patients (75%). Our findings seem to indicate an early and frequent involvement of bladder control pathways in MS patients, as well as a high rate of subclinical disorders.This work was supported by grants from MURST, Italy     

Attention and processing speed performance in multiple sclerosis is mostly related to thalamic volume

Cognitive impairment (CI), mainly involving attention and processing speed (A-PS), is a common and disabling symptom in multiple sclerosis (MS). Symbol Digit Modalities Test (SDMT) is one of the more sensitive and reliable tests to assess A-PS deficits in MS. Structural MRI correlates of A-PS in MS still need to be clarified. This study aimed to investigate, in a large group of MS patients, the relationship between regional gray matter (GM) atrophy and SDMT performance. 125 relapsing remitting MS patients and 52 healthy controls (HC) underwent a 3 T–MRI protocol including high-resolution 3D–T1 imaging. All subjects underwent a neurological evaluation and SDMT. A Voxel Based Morphometry analysis was performed to assess: 1) correlations between regional GM volume and SDMT performance in MS patients; 2) regional differences in GM volume between MS patients and HC. Thalamic, putamen and cerebellar volumes were also calculated using FIRST tool from the FMRIB Software Library. A linear regression analysis was performed to assess the contribution of each one of these structures to A-PS performance. A significant negative correlation was found between regional GM volume and SDMT score at the level of the thalamus, cerebellum, putamen, and occipital cortex in MS patients. Thalamus, cerebellum and putamen also showed significant GM atrophy in MS patients compared to HC. Thalamic atrophy is also an independent and additional contributor to A-PS deficits in MS patients. These findings support the role of thalamus as the most relevant GM structure subtending A-PS performance in MS, as measured by SDMT.