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Biomedical subjects

I M Donaldson

Publications and source records attributed to I M Donaldson.

At least 37 records · Page 2Linked to original sources

Evidence for corrective effects of afferent signals from the extraocular muscles on single units in the pigeon vestibulo-oculomotor system.

The role of extraocular muscle (EOM) afferent feedback signals in the control of eye movement is still controversial. We recorded from 106 single units in the vestibular nuclei, oculomotor nuclei and reticular formation of 80 decerebrate, paralysed pigeons. EOM afferents were stimulated by passive eye movement (PEM) during vestibular stimulation by sinusoidal oscillation in the horizontal plane. We found that EOM afferent signals profoundly modified the vestibular responses of 91 (86%) of the single units recorded. As well as using PEM to simulate eye movements similar to saccades, we moved the eye in a manner which mimicked the slow phase of the vestibulo-ocular reflex (artificial VOR, AVOR). We have found evidence that, as well as providing signals closely related to the parameters of eye movement, PEM alters the vestibular responses of cells during AVOR in a manner which suggests that EOM afferent signals may play a corrective role in the moment-to-moment control of eye movement in the vestibulo-ocular reflex.

Animals↗

Inclusion body myositis presenting solely as dysphagia.

Two patients presenting with dysphagia due to cricopharyngeal muscle dysfunction developed limb weakness 2 to 3 years later. Cricopharyngeal and limb muscle biopsies demonstrated changes typical of inclusion body myositis (IBM). Both patients improved following cricopharyngeal myotomy. IBM should be considered in patients presenting with dysphagia.

Biopsy↗

Trial of Sinemet CR4 in patients with Parkinson's disease.

OBJECTS: to compare the efficacy of Sinemet CR4 (CR4), a slow release levodopa preparation, with that of standard Sinemet in patients with Parkinson's disease and motor fluctuations. METHODS: forty-five patients with Parkinson's disease of mild to moderate severity and motor fluctuations were entered into the 12 month trial. After a four week baseline period of optimal therapy, standard Sinemet was completely substituted by CR4 over 12 weeks, and clinical status monitored regularly over another 36 weeks. Evaluation was based on standard rating scales and patient's and physician's opinion ratings. RESULTS: forty-two patients completed the study. The mean optimum total daily dosage of Sinemet CR4 was 702 mg, significantly greater than the mean optimum daily dose of standard Sinemet--496 mg (p less than 0.01). Median number of doses per day was less, being 3 and 4 respectively (p less than 0.01). There was reduction in tremor (p less than 0.01) and rigidity (p less than 0.05) with Sinemet CR4 therapy compared with standard Sinemet, but no difference in disability scores, bradykinesia, gait, or postural instability. Twenty-five patients rated the change to Sinemet CR4 from standard Sinemet as "more helpful", 15 "about the same", and two "less helpful". There were no serious or unexpected adverse effects. CONCLUSIONS: it was concluded that Sinemet CR4 was at least as effective as standard Sinemet, and it seemed particularly helpful in those patients with wearing-off who require frequent doses of standard Sinemet throughout the day.

Aged↗

Impairment of high-contrast visual acuity in Parkinson's disease.

Several studies have shown that the visual system is affected in Parkinson's disease (PD) with reduced contrast sensitivity, low-contrast acuity, and flicker sensitivity, as well as altered electroretinograms (ERGs) and pattern visual evoked potentials (VEPs). Apparently, however, no study has yet specifically determined whether visual acuity to high-contrast stimuli is impaired in PD. Visual acuity was measured in a group of 16 patients with PD, both on and off drugs (for 24 h), and 16 age- and sex-matched normal control subjects. Acuity was impaired in the PD group both on standard Snellen chart and on a screen in a computerized test of visual resolution. The degree of impairment was 24 and 25%, respectively, in the two tests. The PD patients had marginally better acuity on both tests while receiving drugs, but the differences were not significant. The difference between the two groups was consistent with impaired resolution and could not be accounted for by any perceptual dysfunction that may also have been present in the PD group. Conversely, however, impaired acuity may be implicated in studies that have reported mild deficits of visuospatial/visuoperceptual function in PD. Reduced acuity appears to be a subtle sequela of dopaminergic deficiency in the visual system.

Adult↗

Afferent signals from the extraocular muscles of the pigeon modify the electromyogram of these muscles during the vestibulo-ocular reflex.

There is no general agreement on whether afferent signals from the extraocular muscles play any part in oculomotor control. However, we have previously shown that they modify the responses of cells in the oculomotor control system during the vestibulo-ocular reflex (VOR). If, as we suspect, these signals have an important role in the control of the VOR from moment-to-moment, we should be able to demonstrate similar, functionally significant, modifications at the output of the reflex. We have recorded the electromyographic activity of several extraocular muscles of the right eye during the VOR and while imposing movements on the left eye. We describe how the activity of the muscles, reflected in the electromyogram, is modified in specific ways depending on the parameters of the imposed eye movements. The effects of the extraocular afferent signals on the eye-muscle responses to vestibular drive during the slow phase of the VOR appear to be corrective. Thus the present results provide strong evidence that afferent signals from the extraocular muscles are concerned in the control of the reflex from moment-to-moment, and suggest that the wider question of their role in oculomotor control merits further consideration.

Afferent Pathways↗

Afferent signals from pigeon extraocular muscles modify the vestibular responses of units in the abducens nucleus.

Although the extraocular muscles contain stretch receptors it is generally believed that their afferents exert no influence on the control of eye movement. However, we have shown previously that these afferent signals reach various brainstem centres concerned with eye movement, notably the vestibular nuclei, and that the decerebrate pigeon is a favourable preparation in which to study their effects. If the extraocular muscle afferents do influence oculomotor control from moment-to-moment they should exert a demonstrable effect on the oculomotor nuclei. We now present evidence that extraocular muscle afferent signals do, indeed, alter the responses of units in an oculomotor nucleus (the abducens, VI nerve nucleus, which supplies the lateral rectus muscle) to horizontal, vestibular stimulation induced by sinusoidal oscillation of the bird. Such stimuli evoke a vestibulo-ocular reflex in the intact bird. The extraocular stretch receptors were activated by passive eye movement within the pigeon's saccadic range; such movements modified the vestibular responses of all 19 units studied which were all, histologically, in the abducens nucleus. The magnitude of the effects, purely inhibitory in 15 units, depended both on the amplitude and the velocity of the eye movement and most units showed selectivity for particular combinations of plane (e.g. horizontal versus vertical) and direction (e.g. rostral versus caudal) of eye movement. The results show that an afferent signal from the extraocular muscles influences vestibularly driven activity in the abducens nucleus to which it carries information related to amplitude, velocity, plane and direction of eye movement in the saccadic range. They thus strongly support the view that extraocular afferent signals are involved in the control of eye movement.

Abducens Nerve↗

The anatomical substrate for cat extraocular muscle proprioception.

The localization of cell bodies and of the central terminal projections of extraocular muscle afferent neurons was examined in adult cats using transport of horseradish peroxidase. The results confirm that primary afferent cell somata subserving extraocular muscle proprioception are located within the medial portion of the ipsilateral trigeminal ganglion. Occasional labeling of cell bodies in the mesencephalic nucleus of the trigeminal nerve occurred only in association with evidence of spread of tracer beyond the eye muscles. These results, taken together with work of others, make it unlikely that the trigeminal mesencephalic nucleus participates significantly in eye muscle proprioception. The central projections of extraocular muscle afferent neurons were found consistently in a restricted area in the ventral portion of the pars interpolaris of the spinal trigeminal nucleus. This corresponds exactly with their site of termination in the monkey [Porter (1986) J. comp. Neurol. 247, 133-143]. Terminal labeling was restricted to this area in cases in which there was no evidence of spread of the tracer beyond the extraocular muscles. In contrast to previous findings in the monkey, the cat did not exhibit a second muscle afferent representation in the cuneate nucleus. Though it is known that extraocular muscle afferent signals interact with both retinal and vestibular signals, and thus probably are involved in both visual processing and oculomotor control, the details of their roles in these processes are not yet clear.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

Eaton-Lambert myasthenic syndrome: two cases with typical and atypical features.

Eaton-Lambert myasthenic syndrome is a rare disorder of neuromuscular transmission. We are unaware of previous New Zealand reports and present two patients. Characteristic abnormalities in compound muscle action potential amplitude following repetitive nerve stimulation and on single fibre electromyography were present. Both patients also showed mild patchy abnormalities in peripheral nerve conduction. The clinical picture resembled Guillain-Barre syndrome in one patient who developed severe generalised weakness and respiratory failure. In both patients the neurological presentation lead to the recognition of a previously asymptomatic small cell lung carcinoma.

Aged↗

Directionally-specific effects of afferent signals from the extraocular muscles upon responses in the pigeon brainstem to horizontal vestibular stimulation.

The responses of single units in the brainstem of the decerebrate, paralysed, pigeon were studied. Natural vestibular stimulation was provided by horizontal, sinusoidal, oscillation of the bird and extraocular muscle afferents of the ipsilateral eye were activated by passive eye-movement. Unit responses to vestibular and/or orbital stimuli were examined in sets of peristimulus time histograms interleaved in time. Of 352 units in the brainstem, in the region of the vestibular nuclei, which were exposed to the effects of both vestibular stimuli and passive eye-movement, 40 (11%) responded only to the latter; the other 312 units (89%) responded to vestibular stimulation at 0.4 Hz (amplitude +/- 8 degrees). Of these 312 units, 129 (41%) were affected only by vestibular stimuli; in the other 183 units (59%) passive eye-movement produced clear modification of the vestibular responses by adding excitation or inhibition, or both. There were phasic modifications in most units; in 77 there were longer-lasting changes in the vestibular responses, often following a phasic response. In 124 units whose responses were subjected to statistical analysis, the vestibular responses of 42 (34%) were modified only by horizontal eye-movement and eight (6%) were affected only by vertical movement. A further 18% showed larger effects from horizontal than from vertical eye-movement; in 2% vertical eye-movement was preferred. Further examination of the specificity of the effects of eye-movement in planes between the vertical and horizontal was possible in 29 units which showed various degrees of "tuning" of the effect. In some units there was additional specificity for eye-movement in (a) particular directions (towards the beak rather than towards the tail, for example); (b) in particular arcs of the orbit (centre-to-temporal rather than nasal-to-centre, for example). Note that all these effects were upon the responses of the units to horizontal vestibular stimulation. Thus, the modifications of the vestibular responses depended upon specific characteristics of the passive eye-movement. The exact recording sites of 29 units were determined histologically; some were in the medial vestibular nucleus but many were in the adjacent reticular formation. The principal interest of the results is that they provide more detailed information than was available previously on the specificity of the effects of afferent signals from the extraocular muscles upon the vestibular responses of units in regions of the brainstem known to be involved in oculomotor control. The decerebrate pigeon proves to be a particularly good preparation in which to study these effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Methylprednisolone in multiple sclerosis exacerbation: changes in CSF parameters.

Twenty-six patients with multiple sclerosis (MS) received a total of 45 courses of intravenous methylprednisolone daily for seven days, for acute neurological deterioration. Changes in CSF parameters and clinical status following methylprednisolone were determined and first and repeat courses were compared. There were significant reductions in CSF IgG, CSF albumin, serum IgG and serum albumin levels and CSF IgG synthesis rate in the first and repeat treatment groups. CSF IgG index fell significantly with initial methylprednisolone treatment but not with subsequent courses. Oligoclonal bands disappeared in three patients. Definite clinical improvement followed 30 methylprednisolone courses, possible improvement followed six and no change followed seven. Clinical response was not predicted by pre-treatment CSF IgG synthesis status and did not correlate with its degree of reduction.

Adult↗

Effects of afferent signals from the extraocular muscles upon units in the cerebellum, vestibular nuclear complex and oculomotor nucleus of the trout.

The responses of single units in the cerebellum, the vestibular nuclear complex and adjacent regions of the brainstem and in the oculomotor nucleus were studied in decerebrate, paralysed rainbow trout (Salmo gairdneri). Natural vestibular stimulation was provided by horizontal, sinusoidal oscillation of the fish and extraocular muscle afferents of the eye ipsilateral to the recording were activated either by passive eye-movement or by electrical stimulation of the trochlear (IV) nerve in the orbit. Unit responses to vestibular and/or orbital stimuli were examined in peristimulus-time histograms interleaved in time. In the cerebellum and brainstem, of 124 units exposed to both types of stimulus, 26 (21%) responded only to vestibular input, 26 (21%) were affected only by the orbital signal and 23 (18%) received both signals. The remaining 49 units (39%) responded to mechanical stimulation of the head or body or to vibration; they were labelled "polymodal" and discarded. The recording sites of 56 units were verified by histology; 30 were in the cerebellum and 26 in the brainstem. Input from the eye muscles had excitatory or inhibitory effects upon the vestibular responses. The effects of the orbital signal were usually phasic but rare tonic responses also occurred. About half (15 of 34) of the units which responded to passive eye-movement showed statistically significant differences in the magnitude of their responses to horizontal and to vertical eye-movement. More units preferred horizontal movement (11) than preferred vertical passive eye-movement (four). Note that the plane of vestibular stimulation was always horizontal. In the region of the oculomotor nucleus, of 19 units, five (26%) gave vestibular responses only and three (16%) were affected only by the orbital signal; three units (16%) with polymodal responses were discarded. Of the eight units carrying both signals, histological confirmation that the recording site lay in the column of cells forming the oculomotor/trochlear nuclei was obtained in four. The responses and interactions were similar to those found in the brainstem. The results present two principal points of interest. 1. They reinforce the accumulating body of evidence that, in species with widely different oculomotor and visual behaviour, signals from extraocular muscle proprioceptors reach the vestibulo-ocular system; this, in turn, suggests that these signals may play some rather fundamental role in the oculomotor system.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Impairment and recovery of ipsilateral sensory-motor function following unilateral cerebral infarction.

After unilateral cerebral hemisphere stroke, resulting in contralateral arm symptoms but largely sparing higher cerebral function, ipsilateral arm function is generally considered to be unaffected. In this study, 8 subjects with acute unilateral cerebral infarction (confirmed by CT scan) and primarily motor deficits underwent 11 computerized and 6 clinical assessments between 11 days and 12 months poststroke, and were compared with 12 normal subjects. Computerized tests comprised 3 pursuit tracking tasks (preview-random, step and a combination of these), designed to measure different aspects of integrated sensory-motor (S-M) function, and 12 tasks aimed at breaking tracking into various sensory, perceptual and motor components (joint movement sense, visual resolution, object perception, static and dynamic visuospatial perception, range of movement, grip and arm strength, reaction time, speed, static and dynamic steadiness). The asymptomatic arm was impaired on all but one of the computerized tests throughout the 12-month period, although to a lesser degree than the symptomatic arm. Grip strength was marginally impaired initially. Incomplete neurological recovery was seen in the asymptomatic arm for all functions except strength, speed and steadiness, possibly indicating their resistance to improvement. Clinical assessment detected no asymptomatic arm impairment and only a mild transient deficit of higher mental function. Our data suggest that (1) all cerebral hemisphere areas involved in S-M functions can exert some degree of bilateral motor control; (2) ipsilateral influence is never greater than contralateral influence, and is usually considerably less; and (3) the proportion of ipsilateral to contralateral control is closely related to the degree of continuous sensory feedback required by the particular task. The mechanism and degree of ipsilateral dysfunction can be explained by a 3-tier cerebral model of S-M integration comprising a lower level of functions with high contralateral specificity (somatosensory and motor), a middle level of non-limb-specific partially lateralized functions (ideomotor praxis and visuospatial perception) and an upper level of global mental activities (intellect, alertness, etc.).

Adult↗

Spontaneous resolution of cervical spinal epidural haematoma.

A patient with a spontaneous cervical spinal epidural haematoma is described. Surgical decompression is generally regarded as mandatory. There was complete clinical and radiological resolution with non-operative treatment. This is the fifth recorded case of spontaneous resolution of spinal epidural haematoma. In selected patients with incomplete and non-progressing deficit, conservative management may be possible.

Female↗

Multiple sclerosis: problems in the evaluation of intrathecal IgG synthesis.

We report two patients with multiple sclerosis which illustrate problems in the interpretation of the cerebrospinal fluid (CSF) protein studies used to confirm diagnosis. In one case a polyclonal increase in IgG synthesis, secondary to an aseptic meningitis, masked oligoclonal banding, which was confirmed on subsequent examination. In the second case, despite a normal quantitative intrathecal IgG synthesis rate, oligoclonal banding in the CSF confirmed abnormal intrathecal synthesis of IgG. These cases show the value of combining a quantitative index of intrathecal IgG synthesis with examination for oligoclonal banding and illustrate their interpretation.

Adult↗