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Biomedical subjects

A M Halliday

Publications and source records attributed to A M Halliday.

At least 19 recordsLinked to original sources

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.

Adult

Frequent involvement of the optic radiation in patients with acute isolated optic neuritis.

Magnetic resonance imaging revealed asymptomatic lesions in white matter regions corresponding with the optic radiations in 20 of 28 patients (71%) with clinically isolated optic neuritis. In contrast to the findings with symptomatic lesions, there was no relationship between the latency of the visual evoked potential and the presence of these asymptomatic posterior visual pathway lesions.

Acute Disease

Sensory evoked potentials.

Small potentials, evoked by repetitive visual, auditory or somatosensory stimulation in the afferent pathways of the cord, brainstem or cortex, and detected by averaging signals from distant electrodes on the skin of the neck or scalp, can be used to investigate sensory loss or to detect clinically "silent" lesions in multiple sclerosis and other diseases.

Central Nervous System Diseases

Chronic unilateral optic neuropathy: a magnetic resonance study.

We studied the clinical, electrophysiological, and magnetic resonance imaging (MRI) features of 20 patients with chronic unilateral optic neuropathy (CUON): progressive unilateral visual failure lasting a minimum of 6 months. The patients, 10 male and 10 female, ranged in age from 12 to 77 years (mean 44) and had a mean duration of symptoms of 22 months. All had signs of optic nerve dysfunction. Each patient was studied with MRI using a short TI inversion recovery (STIR) sequence to delineate the optic nerve from surrounding orbital tissue. Three distinct groups of patients with CUON were identified using MRI. In the first group (8/20) the optic nerve was compressed by an extrinsic mass, whereas in the second group (5/20) CUON resulted from an intrinsic tumor of the optic nerve or sheath. In both groups STIR sequences compared favorably with computed tomography in identifying mass lesions. MRI was superior in delineating distortion of the optic nerve by mass or tumor extension beyond the orbit. In the third group (7/20) no mass was evident on MRI. However, STIR sequences revealed altered signal (long T1) in clinically symptomatic nerves. In 4 of the patients T2-weighted cerebral MRI disclosed periventricular lesions suggestive of disseminated white matter disease. We conclude that MRI complements clinical and electrophysiological testing in the assessment of CUON.

Adolescent

Recovery after optic neuritis in childhood.

Thirty-nine children who presented with optic neuritis in childhood were reviewed after a follow up period from 3 months to 29 years (mean 8.8 years). At follow-up, 30 out of 39 (77%) of the children had had no further episodes and in three (8%) there was recurrence of optic neuritis alone. Multiple sclerosis had developed in six patients (15%), a much lower frequency than after optic neuritis in adult life. Regardless of the initial degree of visual impairment or neurological outcome, the visual prognosis was excellent. Pattern evoked potentials at follow-up were much more frequently normal (55%) than in adults (10%) after optic neuritis.

Adolescent

Magnetic resonance imaging of the optic nerve in optic neuritis.

Magnetic resonance imaging (MRI) of the optic nerves using the STIR (short inversion time inversion recovery) sequence was performed in 37 adult patients with a recent or past attack of optic neuritis. MRI revealed high-signal regions in 84% of symptomatic and 20% of asymptomatic nerves. The mean longitudinal extent of lesions was 1 cm. Slow or poor visual recovery was associated with more extensive lesions, or lesions within the optic canal. Disk swelling was usually associated with anterior lesions but also occurred with lesions in the canal. Visual evoked potentials were even more sensitive than MRI in detecting lesions and are still the investigation of choice in suspected demyelinating disease involving the optic nerve.

Adult

Magnetic resonance imaging in isolated noncompressive spinal cord syndromes.

The frequency with which patients presenting with acute or chronic noncompressive cord syndromes subsequently develop multiple sclerosis is uncertain. Magnetic resonance imaging (MRI) was performed on 121 patients with such syndromes to determine the frequency of asymptomatic brain lesions and to assess the sensitivity of MRI in detecting the local cord lesion. MRI findings were compared with those from visual, brainstem, and somatosensory evoked potentials (VEPs, BAEPs, SEPs), and cerebrospinal fluid electrophoresis. Lesions were seen in the appropriate cord region in 47 of 73 patients (64%) with a cervical syndrome, and in 7 of 25 patients (28%) with a thoracic or lumbar syndrome. MRI demonstrated more cervical lesions than did SEPs, but fewer thoracic or lumbar lesions. Cord swelling was seen in 6 patients and atrophy in 10. Of those with acute syndromes, abnormalities were seen with brain MRI in 18 of 32 patients (56%), with VEPs in 2 of 30 patients (7%), and with BAEPs in 2 of 24 patients (8%). In patients with chronic syndromes, abnormalities were seen with brain MRI in 73 of 89 patients (82%), with VEPs in 22 of 80 patients (28%), and with BAEPs in 12 of 62 patients (19%). Brain MRI was thus more sensitive than evoked potentials were in establishing multiplicity of lesions. However, in acute syndromes, it was not possible to diagnose multiple sclerosis from a single abnormal brain scan in chronic syndromes, a diagnosis of clinically probable multiple sclerosis could be made from one scan, provided there was no better explanation for the abnormalities: the added presence of oligoclonal bands allows a diagnosis of laboratory-supported, definite multiple sclerosis as was the case in 28 patients in this series.

Adolescent

Retinal venous sheathing in optic neuritis. Its significance for the pathogenesis of multiple sclerosis.

A systematic study of the frequency of retinal vascular abnormalities and cells in the media has been made in 50 patients presenting with acute optic neuritis. Abnormalities were found in 14 (fluorescein leakage in 10, perivenous sheathing in 6, cells in the vitreous in 6 and in the anterior chamber in 4; in 2 the cells in the media were seen without vascular changes). After a mean follow up of 3.5 years multiple sclerosis (MS) had developed in 8/14 patients with vascular abnormalities and/or evidence of inflammation and in 5/32 without; the difference is significant (P less than 0.02). The occurrence of perivenular abnormalities in a region free of myelin and oligodendrocytes provides evidence that the vascular changes in MS can occur independently of contiguous demyelination, and may be the primary event in the formation of a new lesion.

Adolescent

The role of NMR imaging in the assessment of multiple sclerosis and isolated neurological lesions. A quantitative study.

The form and distribution of MRI abnormalities in 114 patients with clinically definite multiple sclerosis (MS) have been compared with observations on 53 apparently healthy individuals, 129 patients with isolated focal neurological lesions with which MS often presents (51 patients with optic neuritis, 44 with isolated brainstem lesions and 34 with isolated spinal cord syndromes) and 105 patients with disorders which may be confused clinically or radiologically with MS. The latter comprised 55 patients with cerebral vascular disease (including 7 cases of dementia with diffuse white matter disease), 24 with degenerative ataxic disorders, 8 with cerebellar tonsillar ectopia, 7 with sarcoidosis and 11 with a variety of other disorders. Periventricular abnormalities were found in all but 2 patients with MS and discrete white matter lesions in all but 12. Characteristically the periventricular changes in MS were irregular in outline. Periventricular abnormalities which were often milder and of smooth outline were seen in 37/55 patients with cerebral vascular disease, 9/24 with cerebellar degeneration, 5/7 with sarcoidosis and in 2/3 apparently healthy individuals over the age of 60. The appearances in the 7 cases of dementia resembled those with advanced MS. Cerebellar and/or brainstem atrophy characteristic of the cerebellar degenerations, in the absence of white matter abnormalities, was helpful in making the distinction from MS. Congenital anomalies and tumours in the region of the brainstem and foramen magnum were readily shown. More than half the patients with symptoms attributable to isolated focal neurological lesions had additional lesions at presentation. MS cannot be diagnosed in these cases at presentation, but repeat scans after 5 to 20 months in 25 patients with optic neuritis and 10 with clinically isolated brainstem lesions have shown new lesions in 7 (20%). The patients with new lesions fulfil the criteria for clinically probable MS (Poser et al., 1983). Measurements of T1 and T2 in vivo permitted the distinction of acute from chronic brainstem lesions. There were quantitative differences in T1 and T2 between the normal appearing white matter in MS and normal brain. Studies of postmortem brains provided convincing evidence that the MRI abnormalities in MS correspond with plaques. Evidence is adduced to support the view that an important source of the abnormal NMR signals in acute lesions is oedema, and in chronic lesions is gliosis; demyelination per se is unlikely to make an important contribution.

Adolescent

Colour and brightness coding in the central nervous system: theoretical aspects and visual evoked potentials to homogeneous red and green stimuli.

We designed visual evoked potentials experiments to study the differential aspects of colour and brightness coding in man. The substitution of equally bright red and green stimuli for a background yellow was investigated and compared with different luminance increments and decrements of red and green. A dominant N87 component was found for a colour change from yellow to brighter red colours, which was less pronounced for green and absent for yellow luminance changes. It is also absent for pure red luminance increments and green luminance changes, but reappears with red luminance decrements or red-offset. The data are discussed within the framework of a new concept of how the visual system fuses red-green information and black-white border information. Retinal X-cells can transmit colour and high spatial frequency achromatic information simultaneously by encoding only the presence of edges (a.c.) for the black-white stimuli and the presence of both edges (a.c.) and uniform areas of colour (d.c.) for red-green stimuli. Phylogenetically this kind of information transmission enables colour vision to be implemented in a retina such as the cat's by adding only a second class of cones. Barlow's economy principle will be violated for colour in the periphery, but restored early in the striate cortex where there is an early decoding of the combined chromatic and achromatic information by the concentric double opponent cells. The N87 behaviour correlates with the proposed discharge of peripheral X-type cells, but not with the discharge of cortical double opponent concentric or simple cells, which no longer respond to homogeneous colour stimuli. It is suggested that N87 may be generated by geniculate afferents in the dendritic arborization of cortical cells, reflecting the behaviour of peripheral units, and thus the violation of the economy principle, rather than the next step in cortical processing. The early cortical restoration of the economy principle is supported by the absence of any further dissociated behaviour for colour and brightness in later components.

Adult

Simulation of 'stationary' SAP and SEP phenomena by 2-dimensional potential field modelling.

In order to model the distribution of potentials in the hand due to antidromic SAP propagation and in the body due to afferent conduction of the median nerve volley, 2-dimensional matrices of the appropriate shape were constructed, each containing a 'generator' consisting of up to 3 'source' and 3 'sink' points. The value of the field potential at other sites was calculated using a finite difference method. It was shown that the potential gradient is virtually zero in matrix zones which are separated from the region containing the generator by a constriction in the boundary of the conductor. Points on the far side of the constriction remain virtually equipotential, at a level determined by the potential at the junction. This is naturally influenced by the proximity of the generator, so that as the generator approaches the constriction a potential difference will develop between points on the far side, irrespective of their distance from the junction, and other remote parts of the matrix. In the context of human SAPs and SEPs, such factors may be of paramount importance in the generation of so-called 'stationary' or 'far-field' potentials. With additional postulates concerning the manner in which the SAP is attenuated by the termination of axons as it propagates through the hand, and the course taken by the median nerve volley between the arm and neck, it was possible to model the majority of stationary SAP phenomena described by Kimura et al. (1984), and also the distribution and latency of the P9 SEP component following median nerve stimulation.

Action Potentials

Evolving ideas on the neurophysiology of myoclonus.

Early observations, made between 1935 and 1947, on the EEG discharges associated with myoclonic jerking are reviewed, together with the contemporary findings on the stimulus-sensitive myoclonus produced in cats under chloralose anesthesia. The accumulating evidence on the relative roles of cortex, brainstem, and cerebellum in producing this type of myoclonus is briefly summarized. The significance of large SEPs and their presence and absence in various clinical types of myoclonus is considered. Three distinctions are drawn with regard to the clinical features of myoclonic jerking: between action myoclonus and myoclonus at rest; between focal and generalized jerking; and between the lightning-like, irregular, stimulus-sensitive jerks of myoclonic epilepsy and the rhythmical, stimulus-insensitive jerking of segmental myoclonus. Some findings bearing on the possible mechanisms of the abnormal discharges responsible at cell membrane level are mentioned.

Adult

Hemisphere contributions to the composition of the pattern-evoked potential waveform.

The transverse distribution of scalp-recorded potentials evoked by pattern reversal stimulation was studied in 50 healthy subjects. In most individuals the full-field responses were symmetrical over the occipital scalp, but important variations in distribution, symmetry and waveform were recorded in some cases. Asymmetrical responses were similar for each eye (i.e., they were "uncrossed" or homonymous asymmetries). Full-field peak latencies and amplitudes in the lateral channels were more variable than those at midline electrodes. Half-field responses were markedly asymmetric with well-lateralised components widespread over occipital-parietal scalp. In contrast to the full-field responses, component values measured near the midline were less consistent than those from lateral channels due to waveform distortions in this area ("transitional zone"). Upper field stimulation is particularly likely to produce such midline waveform distortions. Activity recorded from the scalp contralateral to the half-field stimulated shows more inter-individual and inter-hemispheric variation than that recorded from ipsilateral electrodes. Variants in the full-field waveform can be accounted for by relative differences in amplitude and distribution of the ipsilateral and contralateral components from each half field. The algebraic sum of these half-field components does not differ significantly from the components of the separately recorded full-field response. Furthermore, responses from the surviving half-field in patients after total hemispherectomy contain all the ipsilateral and contralateral half-field components seen in healthy subjects.

Dominance, Cerebral

The effect of experimental 'scotomata' on the ipsilateral and contralateral responses to pattern-reversal in one half-field.

The averaged cortical responses to a reversing checkerboard pattern presented monocularly in either left or right visual half-fields have been recorded from the occipital scalp using a transverse chain of widely spaced electrodes referred to a common mid-frontal electrode. The half-field responses showed a consistent asymmetry, the dominant feature of which was a positive wave (P100) that was widespread on the ipsilateral scalp and maximally recorded from the midline and ipsilateral electrodes. This formed part of the triphasic negative-positive-negative complex, the other two components being an N75 and an N145. On the contralateral scalp it was generally possible to record a triphasic complex of opposite polarity, but this was usually of smaller amplitude and its components (P75, N105, P135) showed greater variation in latency and morphology than the ipsilateral components. With progressive occlusion of the pattern stimulus from the central regions of the visual half-field, the ipsilateral positive wave (P100) was increasingly attenuated, while components of the contralateral complex were relatively unaffected, or, in some cases, enhanced. By contrast, reducing the radius of the stimulated area had relatively little effect on the ipsilateral P100, while the contralaterally recorded response was attenuated. These differential effects on the half-field response components are discussed in relation to the anatomy of the central and paracentral cortical representation of the visual field. The implications for the interpretation of evoked potential recordings in patients with field defects are considered.

Adolescent

EEG immediately after unilateral ECT.

EEG was continuously recorded in 15 patients for a period extending from just before to 1/2 hour after unilateral ECT. Fourier analysis was performed on the EEG following 15 right-sided treatments and five left-sided treatments. During the induced seizure, epileptic slow-wave activity had significantly greater power on the treated side. Immediately after the seizure, there was significantly more delta activity and less alpha and beta activity on the treated side. This asymmetry, though becoming less marked, was usually still present at the end of the recording period. Analysis of other variables associated with the treatment showed that there was a significant correlation between the time to eye-opening after ECT and both the duration of the seizure and the amount of anaesthetic administered. The similarity between these induced unilateral seizures and unilateral seizures occurring spontaneously in some epileptics is discussed.

Adolescent

Neurological asymmetries immediately after unilateral ECT.

Twenty-nine right handed patients were examined neurologically before and immediately after each of 62 unilateral ECTs to the dominant and non-dominant hemispheres. Most convulsions were followed by signs of transitory neurological dysfunction referable to the treated hemisphere. These signs included deep tendon reflex asymmetry, hemiparesis, tactile and visual inattention, and homonymous hemianopia. After treatment to the right hemisphere some patients had left visuospatial neglect, while all patients who had dominant hemisphere ECT were transiently dysphasic. All neurological abnormalities tested resolved within 20 minutes of treatment.

Aphasia

New developments in the clinical application of evoked potentials.

The introduction of the pattern-evoked response and of far field recording of the auditory and somatosensory short latency responses has provided to major advances in the clinical application of evoked potentials. The sensitivity of the pattern response in the detection of minimal lesions of the visual pathways is now well established, and makes the test of particular value in the diagnosis of demyelinating disease and in the early detection of compressive lesions. The short latency auditory and somatosensory responses also show a high incidence of abnormalities in demyelinating disease. The technique will not compete directly with such well established methods as audiometry and perimetry, but it can provide valuable additional information, not accessible to these methods, particularly where the lesions are clinically silent or inconspicuous.

Auditory Cortex