Allan G. Kermode

Patterns of disease activity in multiple sclerosis: clinical and magnetic resonance imaging study.

OBJECTIVE--To compare the abnormalities shown by magnetic resonance imaging of the brain in three clinically distinct groups of patients with multiple sclerosis, and to correlate the extent of abnormality with the degree of clinical disability in the three groups. DESIGN--All patients underwent magnetic resonance imaging and full neurological examination, and their disability was scored according to the expanded Kurtzke disability state scale. SETTING--National Hospital for Nervous Diseases (Multiple Sclerosis NMR Research Group). PATIENTS--Three groups of patients with confirmed multiple sclerosis were studied: 12 patients with minimal disability despite a long (greater than 10 years) duration of illness (benign multiple sclerosis), 16 who had developed progressive disability after a relapsing and remitting course (secondary progressive multiple sclerosis), and 13 who had had progressive disability from the onset of the disease (primary progressive multiple sclerosis). MAIN OUTCOME MEASURES--Number and size of lesions in 17 anatomically defined sites; total lesion load, estimated with an arbitrary scoring system weighted for the size of lesions; and disability score. RESULTS--Magnetic resonance imaging showed that all 41 patients had abnormalities. These were extensive in the groups with secondary progressive and benign disease compared with the group with primary progressive disease. The lesions in the patients with secondary progressive disease were larger and more confluent than those in the two other groups (p = 0.007). Most lesions (85%) in the patients with primary progressive disease were under 5 mm in diameter; this percentage was higher than that in the two other groups (p = 0.032). Consequently the patients with primary progressive disease had the lowest mean lesion load (36.7); that in the patients with benign disease was 52.7 and that in the patients with secondary progressive disease 64.6 (p = 0.05). No correlation existed between disability and total lesion load. The distribution of brain lesions and of detectable lesions of the spinal cord, and the frequency of cortical atrophy, were similar in all groups. CONCLUSIONS--No relation was found between the degree of clinical disability and the extent of abnormality shown by magnetic resonance imaging: patients with clinically benign disease often had extensive abnormalities and those with primary progressive disease had surprisingly few lesions. Though magnetic resonance imaging increases knowledge of the disease process in multiple sclerosis and is invaluable in diagnosis, it is not helpful in predicting disability in individual patients.

Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci

To perform a 1‐stage meta‐analysis of genome‐wide association studies (GWAS) of multiple sclerosis (MS) susceptibility and to explore functional consequences of new susceptibility loci.

Heterogeneity of blood‐brain barrier changes in multiple sclerosis An MRI study with gadolinium‐DTPA enhancement

We performed 15 dynamic gadolinium-DTPA (Gd-DTPA)-enhanced MRI studies in 8 patients with relapsing and remitting multiple sclerosis; 7 were follow-up studies. We measured the time course of enhancement in 102 enhancing lesions for up to 384 minutes, with rest breaks. Immediate postcontrast MRIs demonstrated many different patterns of enhancement. We observed both uniformly enhancing and ring enhancing lesions. The enhancing regions were often less extensive than the corresponding high signal on T2-weighted images. Three lesions were seen with Gd-DTPA but not on unenhanced scans; 1 was seen on unenhanced scans 10 days later, suggesting that blood-brain barrier disturbance may precede other MRI signs of MS lesions. Three months later, some high-signal areas on T2-weighted scans had decreased in size to resemble the areas previously outlined by Gd-DTPA. This technique provides useful information about the pathogenesis and behavior of MS lesions.

Seizures due to multiple sclerosis: seven patients with MRI correlations.

The MRI data of seven patients with clinically definite multiple sclerosis who developed epileptic seizures are presented. Six of these cases demonstrated new or enhancing lesions. Cerebral biopsy in one of these lesions confirmed inflammation with myelin breakdown products. Lesions implicated in the causation of seizures involved the cortex or subcortical area. In one patient, a new lesion was associated with EEG abnormalities which resolved as the lesion reduced in size. In three patients epileptic activity was the only clinical manifestation of disease. Large, unresolving lesions tended to be associated with continuing seizures.

Central motor drive and perception of effort during fatigue in multiple sclerosis.

ObjectiveTo determine if task performance and fatiguability during repeated low-level contractions of an intrinsic hand muscle differ in a group of MS subjects compared with a control group, and what central changes accompany the development of fatigue and the period of recovery, whether these measures are related to subjective ratings of fatigue or perception of effort.MethodsForce of index finger abduction, rating of perceived effort, and motor evoked potential amplitude and silent period duration were measured during and after a 20-min. intermittent submaximal (40%) contraction of the first dorsal interosseous muscle in 23 clinically definite MS subjects with mild-moderate symptoms, and 15 controls.ResultsRating of perceived effort increased at a greater rate in the MS group than in control subjects during exercise, and this was associated with larger increases in both MEP amplitude and silent period duration.ConclusionsSubmaximal fatiguing exercise is associated with an enhanced central motor drive and increased perception of effort in MS.SignificanceMS subjects can increase central drive during fatiguing exercise to a greater degree than controls, but this is associated with greater perceived exertion. These factors may underlie the more general complaint of fatigue experienced by people with MS.

Symptomatic retrochiasmal lesions in multiple sclerosis: Clinical features, visual evoked potentials, and magnetic resonance imaging

We have studied 18 patients with relapsing-remitting multiple sclerosis (MS) who had symptomatic visual field defects due to retrochiasmal lesions. In 17, the lesion responsible was identified by magnetic resonance imaging (MRI), computed x-ray tomography (CT), or both. The lesion responsible involved the posterior optic radiations in eight cases, the optic tract and lateral geniculate nucleus in six, and the posterior limb of the internal capsule in three. The prognosis for recovery of the field defect was good; complete recovery occurred in 14 patients, and only two showed no recovery at all. The striking characteristic of the lesions was that most were unusually large; indeed, many were detectable on CT as well as MRI. Half-field asymmetries of either amplitude or latency of the visual evoked potentials (VEPs), consistent with a postchiasmal lesion, were present in only five out of 13 patients acutely. In only three of these did the abnormality persist at follow-up. We conclude that only large postchiasmal lesions are likely to cause symptomatic homonymous field defects in MS, usually characterized by rapid recovery. Hemifield VEPs have a low sensitivity for the detection of postchiasmal as compared with prechiasmal abnormalities.

Involvement of the central nervous system in chronic inflammatory demyelinating polyneuropathy: a clinical, electrophysiological and magnetic resonance imaging study.

In a consecutive series of 30 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) minor clinical evidence of CNS involvement was found in five. Cranial magnetic resonance imaging (MRI) was performed in 28 and revealed abnormalities consistent with demyelination in nine patients aged less than 50 years and abnormalities in five aged 50 years or over. Measurements of central motor conduction time (CMCT) were obtained in 18 and showed unilateral or bilateral abnormalities in six. It is concluded that subclinical evidence of central nervous system (CNS) involvement is common, at least in patients with CIDP in the United Kingdom, but that clinically evident signs of CNS disease are infrequent. The association of a multiple sclerosis-like syndrome with CIDP is rare.

Destructive lesions in demyelinating disease.

Three cases are presented in which clinical and radiological features suggested the diagnosis of glioma but surgical biopsy revealed a demyelinating process, with tissue destruction and cyst formation in two. One patient had clinically definite multiple sclerosis. Two had probable acute disseminated encephalomyelitis. Treatment with high dose steroids is appropriate when there is clinical or investigative evidence to suggest the presence of demyelinating disease, before deciding on biopsy.

Hypothalamic lesions in multiple sclerosis

Objectives To determine the frequency of hypothalamic lesions in patients with multiple sclerosis (MS) using conventional MRI (cMRI) protocols. Methods Brain cMRI (1.5 Tesla) scans of 105 Caucasian patients with classical MS (50 with stable and 55 with more active disease) and 12 patients with longitudinal extensive myelopathy (LEM) were reviewed retrospectively. NMO-IgG antibody was assayed in patients with hypothalamic lesions. Results Hypothalamic lesions were found in 13.3% of MS patients and in none of the LEM patients. A higher frequency of hypothalamic lesions was found in patients with active MS (18.2%) than in the stable group (8.0%), but this did not reach statistical significance (p=0.13). Patients with hypothalamic lesions also had more lesions in other cerebral structures. None of the LEM patients had hypothalamic lesions. No patients with hypothalamic lesions were positive for NMO-IgG. Conclusions Hypothalamic lesions in MS are more frequent than previously reported and are not associated with NMO-IgG antibody.

Enhanced corticomotor excitability with dynamic fatiguing exercise of the lower limb in multiple sclerosis

ObjectiveTo determine if task performance and fatigability during rapid repetitive exercise of the lower limb differ in a group of MS subjects compared to a control group, and what central changes accompany the development of fatigue and the period of recovery.MethodsTranscranial magnetic stimulation (TMS) was used to compare motor evoked potential (MEP) responses between 10 clinically definite MS subjects (7F, 33– 64 years of age; EDSS ≤ 4; MRC grade ≥ 4/5) and 13 control subjects during and after 5 bouts of a 15-second maximum rate foot-tapping task performed at 1 minute intervals.ResultsMaximum voluntary contraction (MVC) force of ankle dorsiflexion was lower (15 %) in the MS group compared to controls; however there were no differences in the rate of foot tapping. The rate of foot tapping decreased during each bout of exercise to a comparable degree in both groups, but there was no overall deterioration in performance across the 5 repeat bouts in either group. MS subjects showed a greater decline in strength than controls after exercise (20.7 ± 7.7 % vs. 6 ± 3.6 %; p < 0.05). MEP amplitude increased significantly for the exercised limb in both groups, but the increase was greater in MS subjects (65.9 ± 27 % vs. 31 ± 19.6 %; MS vs. control; p < 0.05). MEP amplitude also increased for the non-exercised limb in controls (40.6 ± 15.6 %, p < 0.01) but not in MS subjects.ConclusionsMild to moderately affected MS subjects can perform a fatiguing exercise requiring a high level of central motor control but this is associated with a greater strength loss and increase in corticomotor excitability compared to unaffected individuals.SignificanceCentral adaptive processes are likely to have a significant role in maintaining task performance in MS.