Peter Rudge

Quantitative brain MRI lesion load predicts the course of clinically isolated syndromes suggestive of multiple sclerosis

We performed semiautomated quantitative measurement of brain magnetic resonance imaging (MRI) abnormalities seen at presentation and at 5-year follow-up in 84 patients presenting with an acute clinically isolated syndrome of the optic nerves, brainstem, or spinal cord suggestive of multiple sclerosis (MS). At follow-up, 34 (40%) had developed clinically definite and four (5%) clinically probable MS. Patients who developed MS during follow-up had a higher lesion load at presentation than those who did not. There was a strong correlation of the MRI lesion load at presentation with both the increase in lesion load over the next 5 years and disability at follow-up. Increasing initial lesion load correlated with a decreasing time to development of MS clinically (r = −0.328, p <0.05). At follow-up, disability and brain lesion load were strongly correlated in patients who had developed MS. These results establish that MRI at presentation with clinically isolated syndromes suggestive of MS is useful in predicting the subsequent clinical course and the development of new MRI lesions. This suggests that quantitative brain MRI will be helpful in selecting patients with early clinical MS for treatment trials and for subsequent monitoring of their response to treatment.

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.

MR brain scanning in patients with vasculitis: differentiation from multiple sclerosis.

SummaryWe performed MR (magnetic resonance) brain imaging on 24 patients with a systemic vasculitis. MRI proved to be a sensitive method for detecting brain lesions (clinically silent or manifest) in these patients. The most frequent abnormalities were periventricular lesions seen in 12 cases. Such changes are not specific for vascular disease, and are often seen in multiple sclerosis. However, additional changes were commonly seen which suggested the correct diagnosis.

AUDITORY EVOKED RESPONSES IN MULTIPLE SCLEROSIS

The early components of the auditory evoked responses (waves I-V) have been studied in 30 patients with multiple sclerosis. There were abnormalities in 22 patients. All patients with an internuclear ophthalmoplegia and half those with no detectable brainstem abnormality had abnormal responses, although none was clinically deaf.

Magnetic resonance imaging in clinically isolated lesions of the brain stem.

Twenty-seven patients with an isolated brain stem syndrome, thought to be due to demyelination, were examined by magnetic resonance imaging (MRI). A brain stem lesion was identified in 25, and clinically silent lesions outside the brain stem were demonstrated in 20. MRI was more sensitive than evoked potentials in detecting brain stem and other lesions. The scan findings were compared with those in 23 patients with multiple sclerosis, who had chronic brain stem dysfunction, with particular reference to the distribution of abnormalities and the MRI characteristics of the lesions. The relaxation times, T1 and T2, of the lesions were measured by MRI. These values were seen to fall in serial studies of acute lesions, but remained unchanged in the chronic lesions. MRI may therefore allow the age of lesions to be assessed.

Down beating nystagmus: Magnetic resonance imaging and neuro-otological findings

Twenty-four patients with down beating nystagmus (DBN) underwent magnetic resonance imaging (MRI) of the head. MRI provided diagnostic images in Arnold-Chiari malformation (6 cases), cerebellar atrophy (6 cases), 1 case with a prepontine-medullary epidermoid tumour and was helpful in the diagnosis of 2 patients with multiple sclerosis and 1 with a ponto-cerebellar infarct. Multiple cerebral hemisphere lesions were found in 6 patients (5 of them over 60 years of age) in whom no diagnosis was made. All cases of DBN, plus 3 additional patients with Arnold-Chiari malformation and other types of nystagmus, were neuro-otologically assessed. Sensitivity of the nystagmus to head tilt with respect to the gravity vector had no localizing value. Impaired horizontal vestibulo-ocular reflex suppression occurred more frequently in those patients with abnormal posterior fossa MRI. Pure torsional nystagmus, and DBN with a strong torsional component, in patients with Arnold-Chiari malformation was associated with syringomyelia. Magnetic resonance is the imaging method of choice for investigating patients with DBN.

THE STABILITY OF THE AUDITORY EVOKED POTENTIALS IN NORMAL MAN AND PATIENTS WITH MULTIPLE SCLEROSIS

Sequential records of the early and middle components of the auditory evoked potential in response to a click stimulus have been obtained over a period of 2.5 years in normal subjects and in patients with multiple sclerosis. The latencies of all the components were highly consistent in the control subjects and in the patients who were clinically stable throughout the period of study. In constrast, in some of the patients who had clinical relapses during the study there was variation in the latency and amplitude of some of the components. The significance of this variation is discussed and the poor correlation between the sites of the new lesions as determined clinically and the auditory evoked potential variability is emphasised.

The use of the auditory evoked potential in the diagnosis of multiple sclerosis.

Auditory evoked potentials, both early and middle components, were recorded from 227 patients with a variety of conditions including multiple sclerosis, brain stem vascular disease, intracranial tumours and Arnold-Chiari malformation. Abnormalities were found in a substantial proportion of patients with definite multiple sclerosis and a smaller proportion of those in the less definite clinical categories of this condition. There was a high correlation between clinical evidence of brain stem involvement and an abnormal auditory evoked potential in multiple sclerosis. Abnormalities were also found in a few patients presenting with an isolated episode of central nervous system dysfunction involving the brain stem. The auditory evoked potential was abnormal in other patients with known diagnoses including half of those with Arnold-Chiari malformation. Tumours involving the brain stem caused abnormalities of the brain stem evoked potentials in some cases and more frequently distortion of the middle components. The specificity of these auditory evoked potential abnormalities to multiple slcerosis is discussed.

The site of brainstem lesions causing semicircular canal paresis: an MRI study.

Ten patients with canal paresis of central origin and ten patients with peripheral canal paresis were studied using MRI of the brainstem to identify lesions within the central vestibular pathways. In the central group, the magnitude of the canal paresis was generally lower than in the peripheral group and removal of fixation had little effect on the nystagmic response. In the peripheral group, removal of fixation enhanced the nystagmus and lessened the discrepancy between the two ears. Statistical processing of the MRI showed that in the central group significant spatially coincident lesions occurred within the medial vestibular nucleus, lateral vestibular nucleus and proximal portion of the vestibular fascicle.

BILATERAL LOSS OF VESTIBULAR FUNCTION

The clinical findings in 53 patients with bilateral vestibular failure (BVF) seen in a neurological hospital are reported. Bilateral acoustic neuromas were excluded. Seven patients (13%) had progressive cerebellar degeneration; these patients had no hearing complaints but showed gait ataxia, abnormal eye movements and cerebellar atrophy on neuro-imaging. Referral in these patients was primarily for eye movement assessment, and BVF was usually unsuspected. Neuropathies were present in 5 patients (9%), usually with normal central (brainstem-cerebellar) ocular motor function and variable patterns of hearing loss. The single largest group was idiopathic BVF (11 patients, 21%), patients presenting with vertiginous episodes, progressive unsteadiness or brief paroxysms of oscillopsia; auditory function, eye movements, neurological examination and imaging were usually normal. Nine patients (17%) suffered ototoxicity, mostly due to gentamicin; hearing was normal or mildly impaired. In 6 patients (11%) BVF was post-meningitic, with concomitant auditory loss. Autoimmune disease was found in 5 patients (9%); other organs were involved by the disease, and hearing was impaired but eye movements were spared. Miscellaneous neurological, otological or neoplastic diseases accounted for the remaining 10 patients. This study suggests that i) in patients with cerebellar degenerations, BVF may be underdiagnosed as the unsteadiness may be attributed only to the cerebellar disorder, ii) some patients with idiopathic BVF present with only minor visual or vestibular symptoms, and iii) detailed immunological screenings should be undertaken more often, in view of the significant proportion of patients with autoimmune and idiopathic BVF.