Callosal function in multiple sclerosis: bimanual motor coordination

Evidence of callosal dysfunction in patients with multiple sclerosis (MS) was examined using a test of bimanual coordination. MS patients were slower than non-patients on the Bimanual Coordination Test (BCT) on both unimanual trials (simple motor speed) and bimanual trials (intermanual coordination). Further, when compared to normals, MS patients exhibited a substantially greater difference between bimanual and unimanual response time, suggesting a deficit in interhemispheric motor interactions. A subgroup of MS subjects who showed markedly inefficient callosal transmission had previously been identified on the basis of abnormal evoked potentials (low amplitude cross-callosal evoked potentials). In comparisons of MS subgroups, the deficit in bimanual motor coordination was found only in MS patients with EP evidence of inefficient callosal transmission. These data support the conclusion that deficits in bimanual motor coordination occur in MS and that these deficits are related to callosal dysfunction.     

Cognitive and motor function in people with multiple sclerosis in Stockholm County

The aim of this study was to analyse cognitive and motor function in a population-based sample of people with multiple sclerosis (PwMS), taking into account both disease-related data and sociodemographic factors. Data were collected from 166 PwMS during home visits. Cognitive function was assessed by the Mini-Mental State Examination (MMSE), the Free Recall and Recognition of 12 Random Words Test (FRR12RWT), and the Symbol Digit Modalities Test (SDMT); manual dexterity by the Nine-Hole Peg Test (NHPT); global motor capacity by the Lindmark Motor Capacity Assessment; and walking capacity by a timed 10-metre walk. On cognitive tests, 55% (MMSE), 84% (FRR12RWT), and 45% (SDMT) of PwMS scored within the normal range; 27% of PwMS displayed normal manual dexterity, 9% had a maximal motorcapacity score, and 8% walked at normal speed. Factors associated with normal cognitive function were lower disability and higher education; lower disability and current employment were predictive of capacity to perform the NHPT and to walk 10 metres. In conclusion, cognitive function was normal in approximately half of the PwMS investigated, while a minority displayed normal manual dexterity and normal walking capacity. Thus, both disease severity and sociodemographic factors appear to influence cognitive and motor function in MS.     

Practical problems in the organisation of clinical trials in multiple sclerosis

The problems of organising clinical trials in MS include the general aspects relating to clinical trials in any discipline but extend also to specific problems arising in the assessment of a relapsing remitting condition. These factors relating to the clinical characteristics of the disease, the diagnosis, the selection of patients and the methods of clinical and laboratory assessment are described and discussed. Suggestions are made for the use of internationally accepted diagnostic criteria for MS and a review is made of the other recognised problems in this field.     

Unusual ocular motor findings in multiple sclerosis

In multiple sclerosis (MS), nystagmus or internuclear ophthalmoplegia (INO) are the usual ocular motor dysfunctions. However, in patients with focal brainstem lesions, other rare manifestations may be observed, such as an isolated ocular motor nerve palsy or complex ocular motor disturbances. We report five MS patients with unusual ocular motor disturbances (bilateral third nerve palsy [n = 2], opsoclonus, Horner's syndrome and one-and-a-half syndrome). We discuss possible correlations between clinical disturbances and MRI abnormalities. Patients were seen in two MS centres. They had a confirmed diagnosis of MS and underwent a brain MRI and a complete neuro-ophthalmological work-up. In one case (opsoclonus), ocular motor manifestations were the first manifestation of MS. In the other four cases they occurred 3 months (Horner syndrome), 6 years and 12 years (bilateral third nerve palsy) and 2 years (one-and-a-half syndrome) after the disease onset, respectively. Four out of five patients were still in a relapsing-remitting form of MS. In the opsoclonus case, there was no evidence of a brainstem lesion. A gadolinium-enhanced lesion (2 cases) or a new T2-weighted lesion located in the brainstem correlated with the clinical presentation. All patients completely or partially recovered after corticosteroid infusions. Our study shows some rare or previously undescribed complex ocular motor symptoms in MS.     

Pupillary function in multiple sclerosis

Eighteen MS patients with visual acuity of 20/30 or better and without recent visual complaints, and 14 age- and sex-matched controls were studied by TV pupillography. The response amplitude and the maximum rate of pupillary constriction or dilation of the light, dark, accommodation and ciliospinal reflexes were unchanged. The latency of the pupillary light response (PLR), however, was prolonged and closely related to walking performance (R = 0.76; p less than 0.001). No relationship was established between PLR latency and previous history of optic neuritis or latency of the VEP. It is concluded that MS patients with preserved visual acuity have only discrete autonomic pupillary disturbances and that the PLR delay is related to disease progression.     

The organisation of health care and epidemiology of multiple sclerosis in France

STATE OF THE ART: According to the available previous studies, France is considered a zone of medium to high risk of multiple sclerosis (MS) with an estimated overall prevalence of at least 50/100,000 inhabitants, incidence rates were stable in some areas but increased over time in others and a strong ethnic effect on the incidence, clinical presentation, and course of MS is reported. RESULTS: Based on two health insurance survey the prevalence has been deduced. At January 1, 2003 from the data of agricultural health insurance the prevalence is evaluated at 65.5/100,000 inhabitants (95p.cent CI=62.5-67.5) with a gradient of North East towards South-West. The data from the national health insurance were very near. During the period 2000-2004, recent studies in Auvergne and Brittany demonstrated an annual incidence comprising between 4.2 and 5.1 per 100,000 inhabitants. In Lorraine, in a large population-based study, in December 31, 2004 the prevalence rate was 120/100,000 (95p.cent CI: 119 to 121). During the period 1990-2002, the average age- and sex-adjusted annual incidence rate was 5.5/100,000 (95p.cent CI: 4.4-6.6). In Lorraine, we found that the age-adjusted incidence rate increased during the period 1990-2002. The incidence of MS in women increased, whereas that in men did not change significantly during this period. Similarly, in Norway, North Ireland and Denmark, the incidence among women increased the most. The clinical features of MS were compared in 211 North Africans patients and 2 945 Europeans patients in two French MS centres (Lorraine and Nice) with definite MS according to McDonald's criteria. The course of MS appears more aggressive in North Africans than in Europeans patients. For example, we demonstrated a shorter time to reach the Expanded Disability Status Scale score of 4.0 (p=0.001) or 6.0 (p<0.0001) in North Africans patients. PERSPECTIVES AND CONCLUSIONS: The incidence rates found in these studies were comparable to those reported in several European populations. This undoubtedly places France in the category of regions with a high risk zone of MS. The incidence of MS in women increased; thus, exogenous (or epigenetic) factors vary over time and may affect men and women differently. The course of MS appears more aggressive in North Africans than in Europeans patients.     

Thyroid function in multiple sclerosis

Thyroid function was studied in 112 MS patients and 175 controls on the basis of T3, T4, T.B.G. and T.S.H. radioimmunoassays. In 33 MS patients the T.R.H. stimulation test was employed additionally. The MS patients had significantly increased T4 levels whereas T3 and T.S.H. were found to be significantly lower. No differences were found in the T.R.H.-stimulated T.S.H. response. The changes in thyroid function parameters were similar in different courses of MS and did not correlate with the degree of clinical disability. The results suggest that in MS the T4/T3 conversion might be reduced as seen in acute or chronic diseases.     

Endocrine function in multiple sclerosis

In 31 patients with multiple sclerosis (MS) the endocrine functions of the hypothalamus, the pituitary and several peripheral endocrine glands were assessed with a combined pituitary test; 3/31 patients had an endocrine disease: one primary hypothyroidism, one primary amenorrhea and one primary male hypogonadism. We found no patient with endocrine disease of the hypothalamus, the pituitary or the adrenals. However, the poststimulatory secretion of cortisol, growth hormone or thyroid-stimulating hormone was impaired in 7/31 patients, suggesting a possible preclinical endocrine insufficiency in these patients.     

Vascular function and multiple sclerosis

Multiple sclerosis (MS) is a debilitating disease with an assumed autoimmune etiology which may lead to elevated oxidative stress, vascular dysfunction, and subsequent predisposition to cardiovascular disease. Therefore, the primary aim of this study was to evaluate vascular function and the potential role of oxidative stress in patients diagnosed with MS compared to healthy controls (C). Fourteen patients with relapsing–remitting MS (47 ± 3 years) and 13 age- and activity-matched controls (44 ± 5 years) underwent brachial artery flow-mediated dilation (FMD) and reactive hyperemia testing using ultrasound Doppler. Venous blood was analyzed for C-reactive protein (CRP), lipid hydroperoxides (LH), the ferric reducing ability of plasma (FRAP), superoxide dismutase (SOD), and catalase activity. CRP [1.8 ± 0.5 mg/L (MS), 1.0 ± 0.5 mg/L (C)] and LH [1.2 ± 0.2 μmol/L (MS), 1.1 ± 0.1 μmol/L (C)] were not different between MS patients and controls. FMD [8.0 ± 1.2% (MS) and 9.2 ± 1.6% (C)] and reactive hyperemia [380 ± 61 mL (MS) and 402 ± 69 mL (C)] were also not different between groups. Vascular function, as assessed by both FMD and reactive hyperemia, was not impaired in patients with MS compared to controls. Further, there was no evidence of elevated systemic inflammation or oxidative stress in these patients, who were currently all in remission. These findings suggest that impaired vascular function, elevated inflammation and oxidative stress are not an obligatory accompaniment to MS.     

F responses and central motor conduction in multiple sclerosis

Two electrophysiological investigations were used to study 18 patients with multiple sclerosis--F wave characteristics including amplitude, persistence and frequency, which can provide a measure of motoneurone excitability, and magnetic stimulation of the cortex, which enables measurement of conduction along central motor pathways. There was an increase in the mean amplitude and persistence of the F response in patients with abnormal central motor conduction (CMC), although no correlation between the degree of abnormality of CMC and increase in F response amplitude was found. Increase in mean amplitude and persistence of the F response were also found in patients with normal CMC but clinical evidence of a UMN disorder (spasticity and/or weakness); there was no correlation, however, between any single F response characteristic and any particular clinical sign. CMC appears to be the preferred test for detecting subclinical motor lesions in MS: of the patient sides with normal clinical examination, 36% showed abnormal CMC, whereas 23% showed abnormal F responses.     

Pulmonary function and dysfunction in multiple sclerosis

Pulmonary function was studied in 25 patients with clinically definite multiple sclerosis with a range of motor impairment. Forced vital capacity (FVC), maximal voluntary ventilation (MVV), and maximal expiratory pressure (MEP) were normal in the ambulatory patients (mean greater than or equal to 80% predicted) but reduced in bedridden patients (mean, 38.5%, 31.6%, and 36.3% predicted; FCV, MVV, and MEP, respectively) and wheelchair-bound patients with upper extremity involvement (mean, 69.4%, 50.4%, and 62.6% predicted; FVC, MVV, and MEP, respectively). Forced vital capacity, MVV, and MEP correlated with Kurtzke Expanded Disability Status scores (tau = -0.72, -0.70, and -0.65) and expiratory muscle weakness occurred most frequently. These findings demonstrate that marked expiratory weakness develops in severely paraparetic patients with multiple sclerosis and the weakness increases as the upper extremities become increasingly involved.     

Stimulation of motor tracts in multiple sclerosis.

Percutaneous electrical stimulation of the motor cortex was used to evaluate corticospinal conduction to upper-limb motoneurons in 29 patients with multiple sclerosis. Central motor conduction abnormalities were correlated with clinical signs and somatosensory evoked potentials. Muscle responses to cortical stimulation were altered in 20 patients. The most common abnormality was increased central motor conduction time; in two cases the responses to cortical stimulation were absent. Abnormalities were also present in patients with no clinical evidence of corticomotoneuron deficit. Alterations of muscle responses and of somatosensory evoked potentials were usually correlated, but may appear independently. Both testing methods are useful in the study of patients with multiple sclerosis.     

Lower extremity motor evoked potentials in multiple sclerosis

Transcranial magnetic stimulation was performed on 25 patients with definite multiple sclerosis. Motor evoked potentials were recorded from the anterior tibial muscle. Central motor conduction time was calculated using the equation (F + M-1)/2 by stimulation of the common peroneal nerve. Motor evoked potentials were capable of detecting subclinical pyramidal tract lesions in multiple sclerosis. In patients with multiple sclerosis, the incidence of abnormality of motor and somatosensory evoked potentials was similar. Central motor conduction time was correlated with overall and pyramidal tract subscores on the Kurtzke Disability Status Scale and the Scripps Neurological Rating Scale. Central motor conduction time abnormalities correlated best with the presence of a Babinski's sign but also correlated significantly with weakness and hyperreflexia.     

Corticomotor threshold is reduced in early sporadic amyotrophic lateral sclerosis

The pathogenesis of idiopathic amyotrophic lateral sclerosis (ALS) remains unknown, but accumulating evidence suggests a neu roexcitotoxic mechanism may have some credence. Glutamate-induced hyperexcitability of cortical or spinal motoneurons may be expected to manifest itself as a reduced threshold for activation of these structures. We have measured corticomotor threshold to the first dorsal interosseous (FDI) muscles of 48 patients with sporadic ALS using magnetic brain stimulation and have correlated the findings with physical signs of upper and/or lower motor neuron degeneration. We find that if FDI in patients with ALS shows no weakness, wasting, or signs of an upper motor neuron lesion, mean corticomotor threshold is significantly lower than in 102 healthy control FDI muscles (P = 0.02). In contrast, FDI muscles showing signs of lower motor neuron degeneration only or mixed upper and lower motor neuron signs are associated with a raised corticomotor threshold (P = 0.008, P < 0.001, respectively). We conclude that early in ALS, at a time when hand muscle function is normal, corticomotor threshold is reduced and suggest that this may be a manifestation of abnormal excitability of cortical or spinal motoneurons to neurotransmitters, whose action will ultimately lead to cell death. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20: 1137–1141, 1997     

Pupillary function in early multiple sclerosis

Autonomic pupillary function was assessed with pupillometry in 95 mildly or moderately disabled patients with multiple sclerosis (MS) and 81 healthy subjects. The parasympathetic pupillary function was measured as initial diameter (mm), time to minimum diameter (seconds), reflex amplitude (mm), relative reflex amplitude (%), and maximal constriction velocity (mm/seconds). To reflect the sympathetic pupillary function maximal redilatation velocity (mm/seconds), and time of 75% of redilatation (seconds) were measured. Of MS patients 85-99% were within the reference values of healthy subjects. In MS patients the effect of age was observed in the initial diameter, reflex amplitude, and time of 75% redilatation. There were no such age related effects in healthy subjects. In age adjusted analysis the initial diameter and time of 75% redilatation differed significantly from healthy controls. Autonomic pupillary functions were not associated with fatigue, visual defect, or bladder disturbance, as measured by Fatigue Severity Scale, Kurtzke's Functional System Scales, Expanded Disability Status Scale, or the Multiple Sclerosis Functional Composite. Our results suggest that both parasympathetic and sympathetic pupillary functions are disturbed already early in the course of MS. However, the disturbance is not severe at this stage of the disease. The dysfunction is age-dependent and thus possibly related to the dimished remyelination capacity of the central nervous system.     

Cardiovascular autonomic function in multiple sclerosis

In this study blood pressure (BP) and heart rate (HR) responses to standing and HR responses to deep breathing were assessed in 34 patients with clinically definite multiple sclerosis (MS) and 63 healthy subjects. Normal ranges, which were clearly age related for both HR responses, were obtained. The BP response to standing was abnormal in 13% of the MS patients, these patients demonstrating significant postural hypotension. The HR response to standing was abnormal in 28% of the MS patients, with a normal initial increase in heart rate and a significantly reduced reflex bradycardia. On deep breathing 36% of MS patients showed abnormal HR changes. The resting HR did not differ between both groups. Abnormalities of one or more tests were found in 53% of the MS patients. No relationship was found between abnormal cardiovascular autonomic responses and the symptoms, duration, severity and progression of the disease. Based on clinical and magnetic resonance imaging findings no indications were found for localisation of the autonomic disturbances in the brainstem. It is suggested that at least a part of the cardiovascular autonomic lesions in MS is located outside the brainstem, i.e. in supramedullary reflex pathways or in the spinal cord.