Showing papers in "Brain in 1988"

Optic ataxia: a specific disruption in visuomotor mechanisms. I. Different aspects of the deficit in reaching for objects.

Abstract: Visually directed arm movements have been studied by film recordings in 10 patients with optic ataxia resulting from unilateral lesions of the parietal region, in 3 cases on the right and in 7 on the left. Half of the patients also underwent visuospatial perceptive tests. The results indicate the following. (1) Optic ataxia is a specific visuomotor disorder, independent of visual space misperception. (2) The proximal and the distal components of the movements are equally affected as shown in reaching and hand orientation tasks. (3) The percentages of spatial and orientation errors quantified, respectively, in these two situations show a different distribution across the different hand-field combinations according to the side of the lesion: whereas the right-damaged patients show a deficit essentially related to a field effect, the left-damaged patients show in addition to the latter an impairment related to a hand effect. These findings suggest that the 2 types of visuomotor mechanisms responsible for the proximal and distal components of visually-directed arm movements are controlled by the parietal cortex and that there should exist a hemisphere asymmetry in the functional organization of these mechanisms. (4) Reconstruction of the lesions drawn from CT scans in 8 of the patients shows a salient and constant involvement of the posterior parietal cortex, always including the intraparietal sulcus and either the superior part of the inferior parietal lobule or more often various parts of the superior parietal lobule. The weak co-occurrence of optic ataxia and hemispatial neglect, and their different lesion sites, indicate a double dissociation between these two symptoms.

‘frontal’ cognitive function in patients with parkinson's disease ‘on’and ‘off’ levodopa

Abstract: A wide range of cognitive impairments can be observed in patients with Parkinson's disease. A close parallel exists between these deficits and those found following damage to prefrontal cortex. Anatomical evidence is reviewed which reveals a complex pattern of neuronal circuits connecting the frontal cortex and basal ganglia. All these circuits are in some way dependent upon dopamine, suggesting that changes in the levels of dopamine stimulation may alter performance on 'frontal' tests. To test this hypothesis, a group of patients with Parkinson's disease were assessed both on and off levodopa treatment, on a range of tests selected from the human and animal experimental literature as being sensitive to disruption of prefrontal cortex. A variable pattern of results was obtained. On one test, a measure of verbal fluency, patients were impaired, compared with normal controls, only when off levodopa. On two measures, associative conditional learning and subject- ordered pointing, patients were impaired only when on levodopa, while on the final measures, the Wisconsin Card Sorting Test, patients were impaired both on and off levodopa. Two mechanisms are discussed to explain these results, one based on the effects of dopamine depletion, and the other based on the adverse effects of dopamine overstimulation. The results suggest that different areas of prefrontal cortex are involved in the tasks employed, and that functional levels of dopamine in separate areas of cortex and caudate may differ crucially in Parkinson's disease.

A comparative study of visuospatial memory and learning in alzheimer-type dementia and parkinson's disease

Abstract: Groups of patients with dementia of Alzheimer type (DAT) and idiopathic Parkinson's disease, together with age and IQ-matched normal controls, were compared on several computerized tests of visuospatial memory and learning. Two different groups of parkinsonian patients were studied: (1) a newly diagnosed group, early in the course of the disease, not receiving medication (NMED PD) and (2) a group later in the course of the disease, receiving medication (MED PD). The DAT and MED PD group were significantly impaired in both spatial and visual pattern recognition memory. The DAT group exhibited a delay-dependent deficit (over 0–16 s) in a delayed matching-to-sample procedure, but were not impaired at simultaneous-matching-to-sample. By contrast, the MED PD group showed delay-independent deficits in the delayed matching-to-sample test and both the MED PD and the NMED PD group were also significantly impaired in simultancous matching. In a form of delayed response test, the subjects were required first to memorize and then to learn the locations of several abstract visual stimuli which varied progressively in number from 1 to 8. The DAT group were severely impaired in this conditional associative learning task. A significant proportion of patients, but none of the controls, in the NMED and MED PD group also failed the test at the levels of 6 or 8 items. There was a significant correlation between the performance on the first trial, memory score in the delayed response task and indices of clinical disability and disease duration in the patients with Parkinson's disease. The results are discussed in terms of the utility of the comparison between DAT and PD in characterizing the nature of the cognitive deficits in these conditions and their relation to those findings from animal neuropsychology which use comparable paradigms.

Von Recklinghausen neurofibromatosis: a clinical and population study in south-east Wales

Abstract: A population-based study in south-east Wales (population 668,100) identified 135 patients with von Recklinghausen neurofibromatosis (prevalence 20/10(5]. In addition to multiple cafe-au-lait spots and/or dermal neurofibromas, freckling was present in the axilla (67%), groin (44%) or submammary areas (29% of adult females). Although not a criterion for diagnosis, Lisch nodules were almost invariably present in the iris (93% of patients overall; 96% of those aged greater than or equal to 20 yrs). The complications of von Recklinghausen neurofibromatosis in this cohort (n = 135 unless stated) were plexiform neurofibromas (40/125), severe mental retardation (1), epilepsy (6), optic glioma (2), spinal neurofibroma (2), aqueduct stenosis (2), meningioangiomatosis (1), scoliosis requiring surgery (6), pseudoarthrosis (3), delayed puberty (2), visceral and endocrine tumours (6), and congenital glaucoma (1). There were no cases of acoustic neuroma. Considering all living family members aged greater than or equal to 18 yrs, together with their deceased relatives, the frequency of CNS and malignant tumours related to the disease was 4.4-5.2%. Uncomplicated von Recklinghausen neurofibromatosis is disfiguring but not a major cause of morbidity. The management of the disease relates to its complications which can be divided into three categories: those which occur in childhood and cause lifelong morbidity (moderate-severe mental handicap, facial plexiform neurofibromas, orthopaedic), those which can occur at any time but are 'treatable' (benign disorders of the nervous system, visceral and endocrine tumours, renal artery stenosis), and malignant or CNS tumours. The combined frequency for each category based on this survey was 12%, 16% and 4.4-5.2%, respectively.

The Lambert-Eaton myasthenic syndrome. A review of 50 cases

Abstract: The clinical and electrophysiological features of 50 consecutive patients with the Lambert-Eaton myasthenic syndrome (LEMS) have been analysed. Carcinoma was detected (CD group) in 25, of whom 21 had small cell lung cancer (SCLC). SCLC was evident within 2 yrs of onset of LEMS symptoms in 20/21 cases, and at 3.8 yrs in 1/21. In the cases in whom no carcinoma was detected (NCD group), 14/25 had a history of LEMS greater than 5 yrs. The dominant neurological features were similar in the CD and NCD groups, and consisted of proximal lower limb weakness (100%), depressed tendon reflexes (92%) with posttetanic potentiation (78%), autonomic features, especially dryness of the mouth (74%) and mild/moderate ptosis (54%). The compound evoked muscle action potential amplitude in abductor digiti minimi was below the lower limit of control values in 48/50, and the increment following maximum voluntary contraction above the upper limit of control values in 48/50. Single fibre electromyographic abnormalities were found in 29/29 cases. The analysis indicates that a patient presenting with LEMS has a 62% risk of an underlying SCLC, and that this risk declines sharply after 2 yrs, becoming very low at 4 to 5 yrs. It is argued that in SCLC cases antigenic determinants on tumour cells initiate the autoimmune response, often early in the course of the malignancy, but that the association of LEMS with tumours other than SCLC may be fortuitous. In the latter, and in NCD patients, the initiating factor(s) are unknown.

Internal versus external cues and the control of attention in parkinson's disease

Abstract: In recent years, several attempts have been made to characterize the nature of the cognitive deficits shown by patients with Parkinson's disease. It has been suggested variously that they have difficulty in switching cognitive set, in performing effortful (or controlled) as opposed to automatic tasks, or that their impairment is found in tasks which maximize the amount of 'self-directed task specific planning'. It is proposed that this latter distinction may be reformulated in terms of the degree of internal versus external attentional control which is required by the task. An experiment is described which attempted to manipulate this parameter. A version of the Stroop colour-word test was used, in which the words 'red' and 'green' were presented in the complementary coloured 'ink'. Subjects responded either to the colour of the ink in which the word was written or the colour named by the word. The relevant attribute changed at intervals during the course of the experiment. In one condition, the relevant stimulus attribute was cued before each trial. In another condition, subjects had to remember which attribute was currently relevant. Results revealed that patients with Parkinson's disease were impaired mainly on the second version of the task which required internal attentional control. The results are discussed in relation to the models of Working Memory (Baddeley, 1986), and attentional control (Norman and Shallice, 1980). Exploration of these models leads to the formulation of a theory in which the crucial determinant of cognitive impairment in Parkinson's disease is reduced resources in the Supervisory Attentional System. Provided the demands of the task are within the patient's available attentional resources the patient may not show any deficit. If, however, the attentional demands exceed available resources, as in tasks which depend upon internal cues, then deficits will be observed.

Procedural learning and neostriatal dysfunction in man.

Abstract: Patients with early stage Parkinson's disease are shown to be selectively impaired in a cognitive task of procedural learning while remaining intact in recall and recognition tests of declarative memory. In contrast, amnestic patients showed the opposite set of deficits, thus demonstrating a double dissociation. Patients with early Huntington's disease were either comparable to the parkinsonian patients or to amnesties. In the advanced Huntington's group, both procedural learning and declarative memory were impaired. It is argued that cognitive procedural learning depends on the establishment of heuristic strategies through the action of a circuit which involves the neostriatum and the prefrontal cortex.

Some proprioceptive influences on the perceptual representation of body shape and orientation

Abstract: Perception of the surface contour of the body is generally thought to depend on topographically organized neural maps of somatosensation in the thalamus and cortex. Recent neurophysiological studies indicate that these maps are potentially modifiable through alterations in their sensory input. We present evidence that the apparent shape and orientation of the body can be changed within seconds by using muscle vibration to generate proprioceptive misinformation about limb position. Depending on the position of the hands or feet in relation to the rest of the body and to the test chamber, it is possible to generate systematic perceptual distortions of the body and changes in the apparent orientation of the body. Some implications of these observations for the maintenance of an accurate body schema, for spatial orientation, and for the encoding of ocular position are described.

Serial gadolinium enhanced magnetic resonance imaging in multiple sclerosis

Abstract: Serial gadolinium-DTPA (Gd-DTPA) enhanced magnetic resonance imaging (MRI) was performed in 9 patients with multiple sclerosis (MS). On the first scan enhancing lesions were seen in 7 patients, all of whom were in acute relapse. Most enhancing lesions were asymptomatic. On the second scan (3 to 5 weeks later), persisting enhancement was seen in only 12/54 lesions which enhanced on the first scan. No lesion showed persisting enhancement on the third scan (after 6 months). Enhancement occurred in all 12 new lesion areas seen on the unenhanced second scan and in 8 of 15 new lesions seen on the third scan. Enhancement was also seen in 4 older lesions which had been nonenhancing on earlier scans. Relaxation time measurements demonstrated a high water content in some nonenhancing lesions, which could be due to a subtle blood-brain barrier disturbance not detected with Gd-DTPA. The results show that blood-brain barrier impairment is a consistent finding in new MS lesions detected with MRI. Gd-DTPA is a useful marker of new and biologically active lesions and should prove of value in monitoring therapeutic trials in MS.

Neck muscle vibration modifies the representation of visual motion and direction in man.

Abstract: The retinal coordinates of an image are normally insufficient to define the direction of an object in body-centred visual space. Gaze direction, specified by information on the position of eye-in-head and on the position of head-on-torso, is also required. While the source of the eye-in-head signal is controversial, it is clear that proprioceptive signals from neck muscles are sufficient to provide head-on-torso information. Observations by Goodwin et al., beginning in 1972, that vibration of limb muscles modifies proprioception from them, and induces illusory motion and false perception of limb position, suggested this study of the effects of neck muscle vibration on the representation of visual space. Verbal reports, supported by objective measures, revealed that vibration of muscles on one side of the neck induces a visual illusion: contralateral displacement of a small visual target viewed in the dark. Pointing movements towards the target are similarly affected, confirming that the representation of directions in visual space is modified by neck muscle vibration. A second vibration-induced illusion was uncovered when apparent displacement ceased. This is an illusion of pure target motion in the same direction as the previously observed displacement. The magnitudes of both the displacement and pure motion illusions were dependent on vibration amplitude and were unrelated to real or apparent movements of eyes or head. Taken together these observations indicate that vibration of neck muscles can modify independently (1) the central representation of the instantaneous direction of gaze and (2) the signal of the velocity with which this direction is changing.

Cholinergic 'blockade' as a model for cholinergic depletion. A comparison of the memory deficits with those of Alzheimer-type dementia and the alcoholic Korsakoff syndrome.

Abstract: The effect of cholinergic ‘blockade’ on human memory performance as a model for the effect of cholinergic depletion in clinical disorders was investigated. A wide range of memory functions was assessed in 70 subjects, using tests which were identical or closely similar to those which have previously been employed in clinical studies of Alzheimer and Korsakoff patients. In addition, a physiological measure of the degree of central cholinergic blockade was included, as well as measures of subjective arousal and objective attention. It was found that cholinergic blockade had no significant effect on the more passive aspects of primary (or ‘working’) memory, namely span tests and a measure of verbal short-term forgetting; in this, it contrasts with the marked deficits seen in Alzheimer-type dementia. On the other hand, cholinergic blockade produced impairment at a visuospatial short-term forgetting test, and at a verbal test in which the distractor task was made more difficult. On tests of secondary memory, cholinergic blockade produced a pattern similar to that seen in the anterograde amnesia of Alzheimer and Korsakoff patients, namely a pronounced impairment in learning verbal and visuospatial material, a ‘normal’ forgetting rate once learning had been accomplished, and relative preservation of the response to priming and of skill learning (procedural memory). Cholinergic blockade, however, did not produce a retrograde amnesia, nor did it affect the recall of temporal context or of long-established semantic knowledge. This pattern of results is compared with that obtained in previous studies of Alzheimer and Korsakoff patients.

The coexistence of bradykinesia and chorea in Huntington's disease and its implications for theories of basal ganglia control of movement.

Abstract: Investigation of motor function in a group of 17 patients with Huntington's disease reveals that, in addition to the chorea that many patients exhibit, defects in voluntary motor performance also are evident. Fast simple wrist flexion movements to 15° or 60° were slower, and individual movements showed greater variability than seen in normal subjects. This bradykinesia was most pronounced in those patients who were akinetic and rigid, but also was seen in those with chorea alone; bradykinesia was independent of the drug treatment that the patients were receiving (and was therefore not due to drug-induced parkinsonism). The electromyographic activity of the agonist muscles during such simple but slow movement differed from that seen in Parkinson's disease. The performance of complex movements revealed further deficits. Some patients were unable to combine two movements in a simultaneous or sequential movement task of squeezing the hand and flexing the elbow. Those who could perform these complex movements exhibited slowing of the velocity of the movement and prolongation of the interval between movements. These abnormalities were present in patients with chorea who were not taking neuroleptic drugs. It is argued that they represent an abnormality of motor programming of complex movements, over and above the defect in executing simple movements. The long latency stretch reflexes in wrist flexor muscles and flexor pollicis longus were reduced or absent, but this did not correlate with changes in motor performance, or with the reduced size of the early components of cortical sensory evoked potentials. Bradykinesia is thus shown to be an integral component of the motor disorder of Huntington's disease, in addition to the chorea. The coexistence of bradykinesia and chorea in this illness is compatible with current theories of the role of the basal ganglia in the control of movement.

Recording of movement-related potentials from scalp and cortex in man.

Abstract: Movement-related cortical potentials (MRPs) were recorded from scalp electrodes in 8 normal volunteers and from chronically implanted subdural electrodes in 7 patients who were being evaluated for surgical treatment of epilepsy. From subdural electrodes, a clearly defined, extremely localized slow negative potential preceding the voluntary movement of the middle finger (Bereitschaftspotential, BP) was recorded in the contralateral and ipsilateral hand sensorimotor areas. The negative slope (NS') began approximately 250 to 400 ms before EMG onset and was recorded exclusively from the contralateral hand sensorimotor area. Both BP and NS' were maximum in the hand motor area. Although a negative slope was recorded also from the supplementary motor area, whether that particular slope corresponded to BP or NS', or both, could not be determined. Three kinds of progressively steeper negative potentials starting around the onset of the EMG were identified: (1) the 'hand motor potentials' which were seen in the contralateral hand motor area and started immediately before EMG onset and peaked 130 +/- 32 ms after EMG onset; (2) the 'hand somatosensory potentials' seen in the contralateral hand somatosensory area which started simultaneously or immediately after the EMG onset; and (3) the 'vicinity potentials' seen in the immediate surroundings of the contralateral hand area and which started after the EMG onset. The 'hand motor potentials' had the highest amplitude. From these findings, we concluded that bilateral hand sensorimotor areas and the supplementary motor area participate in the 'preparation' of movements, but that mainly the contralateral cortex generates the discharges necessary to produce the actual movement.

CHANGES IN PRESYNAPTIC INHIBITION OF Ia FIBRES IN MAN WHILE STANDING

Abstract: Presynaptic inhibition of homonymous Ia afferent terminals to soleus, quadriceps and tibialis anterior motoneurons and of heteronymous Ia fibres from quadriceps to soleus was compared in the same subjects when standing without support and during a control situation (sitting or standing with back support). Changes in presynaptic inhibition of Ia fibres were indirectly deduced from alterations in the amount of monosynaptic Ia facilitation elicited in motoneurons by a constant conditioning stimulation. Facilitation was measured during the first 0.5 ms when the monosynaptic Ia excitatory postsynaptic potential (EPSP) was not yet contaminated by polysynaptic effects evoked by the conditioning stimulation. Two indirect methods were used to provide an estimate of the size of the conditioning Ia EPSP: (1) the resulting H reflex facilitation; and (2) the peak of increased firing probability elicited in voluntarily activated motoneurons by stimulation of homonymous and heteronymous Ia fibres (poststimulus time histogram PSTH method). Only those PSTH experiments in which the 'spontaneous' firing rate of the motor unit was identical in the different positions, thus ensuring an identical net synaptic drive to the motoneuron, were considered. Under these conditions it is assumed that changes in the size of the peak of facilitation elicited by the monosynaptic Ia volley are likely to be caused by changes in presynaptic inhibition of Ia fibres. It is argued that the substantial changes in monosynaptic Ia excitation observed when standing without support probably reflect changes in presynaptic inhibition of Ia fibres. Under this interpretation, presynaptic inhibition of Ia fibres to soleus motoneurons is increased while standing without support, whereas presynaptic inhibition of homonymous Ia fibres to quadriceps motoneurons is decreased. There is no evidence for a change in presynaptic inhibition of Ia fibres to tibialis anterior motoneurons. The resulting alterations in the gain of the monosynaptic reflex of these muscles are discussed in relation to the possible role of the monosynaptic stretch reflex in human gait.

White matter changes in dementia of Alzheimer's type. Biochemical and neuropathological correlates.

Abstract: A correlative neuropathological-biochemical study was undertaken in order to characterize the selective incomplete white matter infarctions (SIWI) frequently found in dementia of Alzheimer's type. The brain tissue analysed represented white matter with incomplete infarction, complete infarcts and with histologically normal tissue, in cases with dementia, mainly of Alzheimer and multi-infarct type, in nondemented subjects with cerebral infarcts and in age-matched control cases. The biochemical results verify the existence of the white matter changes and agree on their regional distribution as they appear in the morphological analyses. The increasing severity of SIWI as assessed histologically was reflected in a proportional reduction of several biochemically quantified white matter components. The histological difference between incomplete and complete infarction was also expressed biochemically. Incomplete white matter infarction with and without associated complete infarcts were biochemically similar. The aetiological significance of the loss of different white matter components is discussed. The biochemical data support the concept of SIWI as being an independent white matter disorder of cerebrovascular, hypoperfusional/hypoxic origin.

Remote memory function in Alzheimer's disease and Parkinson's disease.

Abstract: Remote memory for public and personal events was evaluated in Alzheimer's disease (AD) and Parkinson's disease (PD), using a series of recall and recognition tests. Information related to content and date of past events was assessed separately. In recall of the content of personal and public events, both groups showed a gradient of deficit in which remote events were affected less than recent ones; the magnitude and temporal extent of the retrograde loss was related to severity of dementia. By contrast, gradient effects were not evident in the recall of date and were less marked in the recognition of content or date. In public and personal events tests, patients with PD showed a relative impairment in dating capacity, compared with their memory for the content of events, which was independent of dementia. These results suggest that dementia affects the recall of distant events less than recall of recent ones. Furthermore, the selective gradient effects in recall of content suggest that memory for date is served by cognitive processes independent of memory for event content. In PD, dating capacity is a sensitive measure of remote memory function that may be disrupted independently of dementia.

Orienting of visual attention in progressive supranuclear palsy.

Abstract: Orienting of visual attention was studied in 8 patients with progressive supranuclear palsy (PSP) and 8 parkinsonian control subjects. While maintaining fixation on the centre of a visual display, subjects made simple reaction time (RT) key press responses on detecting visual targets which appeared above, below, to the left or right, equidistant from fixation. On each trial the target was preceded by a preparatory cue, either a peripheral luminance change or a central arrow, to summon attention to one of the four locations. The orienting of attention was measured as a facilitation in detection RT at the cued location. For the parkinsonian controls, this facilitation was equal for horizontal and vertical directions, whereas for both types of cues, PSP patients were slower moving attention in the vertical than in the horizontal plane. Midbrain retinotectal pathways are important not only for controlling eye movements, but also for orienting attention.

The epidemiology of multiple sclerosis in three australian cities: perth, newcastle and hobart

Abstract: An epidemiological survey of multiple sclerosis (MS) in three Australian cities, Perth, Newcastle and Hobart, was undertaken with its prevalence day being the national census day on June 30, 1981, exactly twenty years after a previous survey of the same cities. The relationship between increasing prevalence and increasing south latitude found in the 1961 survey was confirmed in this present study. Prevalence rates had increased significantly over the twenty years between the studies. Over the same time period incidence rates had also increased in Newcastle and Hobart but had remained essentially stable in Perth although these changes were not significant. The rise in prevalence was due to a combination of factors of differing importance in each city. These factors included better case ascertainment, increased recognition of the less severely disabled patient, increased survival time and differential immigration of a population at a higher risk of developing MS than the indigenous population. Finally, analysis of MS prevalence rates amongst migrant populations in Perth and Hobart suggested that either the risk of acquisition of MS may extend over a wider age range than is generally accepted or that environmental factors prevalent in the former city have modified disease expression there.

Kufs' disease: a critical reappraisal.

Abstract: A review of 118 cases published as Kufs' disease revealed only 50 cases, including 2 patients described herein, that fulfilled our criteria for this diagnosis. Of the other 68 cases, 16 had inadequate data for analysis, 21 had evidence of a storage disease other than Kufs' disease, 10 did not have clear evidence of any neuronal storage, and 21 had atypical clinical features considered outside the spectrum of Kufs' disease. The 50 cases accepted as Kufs' disease comprised two clinical phenotypes; progressive myoclonus epilepsy (Type A) and dementia with motor disturbances (Type B). Marked photosensitivity was a striking feature of some Type A cases, and facial dyskinesias were common amongst Type B patients. Onset was typically at around the age of 30 years. A few cases began in adolescence; these differ from the protracted juvenile form of neuronal ceroid-lipofuscinosis by the absence of visual failure. Demonstration of fingerprint profiles or granular osmiophilic deposits by electron microscopy is mandatory for definitive diagnosis. Urinary sediment dolichol levels were markedly elevated in our 2 cases. This biochemical finding confirms the relationship of Kufs' disease to the early forms of neuronal ceroid-lipofuscinosis and is consistent with our hypothesis that these diseases are due to defects in the intracellular processing of lysosomal and related membranes.

Control of isometric finger force in patients with cerebellar disease.

Abstract: Control of isometric forces during grasping or handling of objects is an essential feature of all skilled manual performances. Previous studies of hand function in cerebellar patients were restricted to movements; force control was only investigated under isotonic conditions in combination with movements. Control of isometric forces during voluntary contraction of finger muscles was investigated in 31 patients with chronic cerebellar disease and in 20 normal controls. Eight patients with Friedreich's ataxia were considered to be typical for a disease affecting the afferents to the cerebellum; 4 patients with anterior lobe atrophy, which affects leg movements to a greater extent than finger movements, were compared with 3 patients with hemisphere lesions; 16 patients suffered from diffuse cerebellar atrophy. Using a recently developed microcomputer system for the continuous measurement of finger force, control of isometric force was studied in several tasks within the same subjects. The tasks included the maintenance of constant force output at different force levels with and without visual feedback, fast repetitive force changes, tracking of a sinusoidal target presented visually, and measurement of maximum grip force. The amount of voluntary contraction in terms of muscular power was normal in all patients; in all other tasks clear deficits were observed. The extent of the disturbances was highly variable between patients even within the same clinical subgroup. The detailed analysis of force traces revealed a great variety in types of disturbance. The frequently observed slowing of the speed in repetitive force changes can be attributed to different components in different patients and not only to difficulties at turning points as might be predicted from comparable movement studies. In addition, performance deficits across different tasks were not uniform, indicating dissociation of impairment. Deficits in maintaining force, which may be interpreted as dysmetria or due to tremor, do not necessarily imply an abnormality in diadochokinesis, as measured in fast repetitive force changes, nor does the converse apply.

The neuropathology of the acquired immune deficiency syndrome (aids)a review

Abstract: The nervous system has been involved in the majority (at least 75%), of cases of acquired immune deficiency syndrome (AIDS) examined postmortem, but the pathogenetic mechanisms involved are not well understood. The predominant pathological process is opportunistic infection secondary to the decrease of T-helper (T4) cells and includes toxoplasmosis, encephalitis due to cytomegalovirus and progressive multifocal leucoencephalopathy. On the other hand, mycoses (mainly cryptococcosis) are relatively uncommon. Primary lymphomas are three times more common than secondary lymphoma spreading from other sites. Cerebral involvement by Kaposi sarcoma is metastatic. probably from primary foci in the lungs. Lesions due to the direct involvement of the nervous system by the human immune deficiency virus (HIV) include subacute encephalitis and vacuolar myelopathy. The former is reported with increasing frequency and is localized predominantly to the white matter in which multinucleated giant cells can be found. These are considered typical of AIDS and have been shown to contain HIV particles in their cytoplasm. AIDS lesions due to infectious agents do not always conform to the typical pattern of the uncomplicated disease and not uncommonly there is evidence of more than one infectious agent in the same area. Peripheral nervous system lesions in I-IIV infections, responsible for a variety of clinical symptoms, usually appear, in biopsy material, as nonspecific inflammatory in type. CMV inclusions and lymphomatous infiltrations of peripheral nerve have been reported in autopsy cases.

Temporal ordering and short-term memory deficits in parkinson's disease

Abstract: Previous studies of remote memory function have indicated a dissociability between memory for the content and date of past events and suggested selective deficits of dating capacity in Parkinson's disease (PD). The present study examined the hypothesis that poor dating in PD is linked to a specific deficit in temporal contextual memory which also affects new learning. Patients with PD and patients with Alzheimer's disease (AD) were compared in their ability to perform tasks of content recognition and recency discrimination of words presented sequentially. Compared with AD patients, PD patients were disproportionately impaired in recency discrimination relative to content recognition. When performance was analysed as a function of retention interval, AD patients showed impairment in both tasks at all intervals. PD patients, by contrast, showed deficits in content recognition at the short stimulus-test intervals only, possibly reflecting the clinical phenomenon of bradyphrenia. These results suggest that recency discrimination deficits and impaired short-term memory processing are specific cognitive deficits in PD that may be linked to subcortical deafferentation of the frontal lobes.

Chorea and myoclonus in the monkey induced by gamma-aminobutyric acid antagonism in the lentiform complex: the site of drug action and a hypothesis for the neural mechanisms of chorea

Abstract: Experiments are described in which the gamma-aminobutyric acid (GABA) antagonist bicuculline was injected into the lentiform complex of conscious monkeys. Injections into either the lateral segment of the globus pallidus, or the medial part of the putamen, gave rise to chorea of the contralateral limbs and/or orofacial region. Control injections of vehicle alone were without effect. Injections of bicuculline into the lateral part of the putamen gave rise to contralateral myoclonus. The chorea produced by lateral pallidal or medial putaminal injections was virtually indistinguishable from the dyskinesia (chorea/ballism) which has been shown, in previous studies, to be induced by injection of GABA antagonists into the subthalamic nucleus. It is proposed that the primary site of action of the GABA antagonist in producing chorea, in the present studies, was the lateral segment of the globus pallidus. The mode of action is suggested to be interruption of GABAergic transmission from the striatum to the lateral pallidal segment. Since this also occurs in Huntington's disease, it is proposed that experimental chorea induced by this method in the monkey may be a useful model of the dyskinesia seen in Huntington's disease in man. Loss of influence of inhibitory striatopallidal fibres would lead to abnormally increased activity of lateral pallidal neurons. These in turn project to the subthalamic nucleus, upon which they have an inhibitory action. Dyskinesia is thus produced by physiological inhibition of the subthalamic nucleus, whose destruction, both in man and the monkey, is known to produce ballism. It is proposed that ballism and chorea share common neural mechanisms, both involving the loss of influence of the subthalamic nucleus on the medial segment of the globus pallidus.

Myoclonus in a patient with spinal cord transection. Possible involvement of the spinal stepping generator.

Abstract: A patient with clinically complete cervical spinal cord transection developed rhythmic myoclonic movements of the trunk and lower limbs, demonstrating that, in man, such movements can be generated within the spinal cord itself when deprived of supraspinal control. Electromyographic (EMG) recordings used to define the features of the myoclonus, which had a frequency of 0.3-0.6 Hz, was bilaterally symmetric, and involved extensor muscles. The EMG bursts always appeared in phase in all muscles involved. Peripheral stimulation of flexor reflex afferents (FRA) could induce, slow or interrupt the rhythmic activity. When FRA stimulation induced a flexion reflex, it occurred between extensor EMG bursts and induced alternating flexion-extension activity which could be sustained for several cycles. Soleus and quadriceps monosynaptic reflexes were depressed during the silent period of the rhythmic activity. Several arguments, mainly the great sensitivity of the myoclonus to flexor reflex afferent stimulation, suggest that the myoclonus observed in this patient was due to partial release of a spinal stepping generator.

Scalp-recorded P300 activity in patients following unilateral temporal lobectomy.

Abstract: The bilateral distribution and overall amplitude of the P300 component of the event-related brain potential (ERP) was studied in epileptic patients in whom the amygdala, hippocampal, and anterior temporal lobe areas of the brain had been resected unilaterally. Previous reports have suggested that a neural generator of the P300 elicited in the commonly used target detection (‘Oddball’) paradigm lies in these medial temporal areas. In an Oddball paradigm, there was no evidence of any left-right hemisphere asymmetry in the scalp distribution of the P300 that varied as a function of the side of surgery in either the left or right temporal lobectomy patients. Moreover, there were no statistically significant differences in overall P300 amplitude or latency between the patients and controls. These data do not support the hypothesis that the primary generator of the scalp-recorded P300 in the Oddball paradigm lies in the hippocampus and amygdala.

Slowly progressive aphasia in three patients. The problem of accompanying neuropsychological deficit.

Abstract: Three patients are described presenting with a slowly progressive aphasic disorder associated with degenerative cortical disease. The symptoms began in the presenium and the length of illness was 4 to 5 years. The language disorder corresponded in all patients to a severe form of amnesic aphasia but a moderate to marked semantic breakdown was also found. Formal language examination was complemented by extensive neuropsychological testing. This revealed a severe deficit in language-dependent cognitive tasks. The patients were given a follow-up language and neuropsychological examination. In addition to the deterioration of language functions, a significant decline was observed in nonverbal intelligence tasks even though their level of performance still remained within the normal range. Follow-up with standardized intelligence tests might detect a trend towards generalized dementia in similar cases. This would mean that these patients should be considered as presenting with slowly progressive aphasia preceding generalized dementia.

The role of macrophages and eicosanoids in the pathogenesis of experimental allergic neuritis. Serial clinical, electrophysiological, biochemical and morphological observations.

Abstract: Experimental allergic neuritis (EAN) can be prevented or ameliorated by global blockade of macrophages. How these cells damage peripheral nervous tissue in this autoimmune demyelinating polyneuropathy is not fully understood. Since macrophages exert a number of their inflammatory actions by the release of arachidonic acid-derived eicosanoids, we investigated the possible role of these mediators in the pathogenesis of EAN. Lewis rats with myelin-induced EAN were treated before and after onset of clinical signs. Administration of corticosteroids or of the cyclo-oxygenase inhibitors indomethacin and BW755c before the onset of neurological signs suppressed the disease, as judged by clinical assessment, serial electrophysiological testing and histological examination, while initiation of drug treatment on day 13 postimmunization still markedly attenuated the course of EAN. The selective lipoxygenase blocker nafazatrom had only a slight effect. Determination of the production by macrophages ex vivo of eicosanoids corroborated the predicted site of action of the pharmacological compounds applied. We infer that macrophage-derived proinflammatory arachidonic acid metabolites significantly contribute to functional and tissue damage in EAN. Our results may be relevant to future pharmacological treatment of the acute Guillain-Barre syndrome.

Ocular motor deficits in Parkinson's disease. III. Coordination of eye and head movements.

Abstract: Eye-head coordination was measured in patients with Parkinson's disease as they made horizontal gaze shifts in response to predictable and unpredictable target steps and to targets moving smoothly with either constant or sinusoidally varying velocity. Patients preferred not to move their heads for both large and small amplitude gaze shifts. Both eye and head movement reaction times were prolonged. Saccades were hypometric and, frequently, slow. Head movements were also slow, hypometric, and varied in amplitude for target shifts of a given amplitude. Compensatory eye movements (CEMs) that normally stabilize gaze direction during head movement varied in gain from zero to greater than unity, and often drove the eyes off target. CEM abnormalities occurred most commonly in patients with abnormal vestibulo-ocular reflex (VOR) gain in darkness. We attribute these abnormalities of programming combined eye-head saccades to dysfunction of striatonigralcollicular circuits. Smooth gaze pursuit gain, the ratio of gaze velocity to target velocity, was lowered in patients while tracking sinusoidal targets at 0.3, 0.5 and 1.0 Hz. Some patients could track these targets with the head fixed but not with the head free. We attribute this to abnormal suppression of the vestibuloocular reflex. The results indicate that Parkinson's disease impairs motor programming of coordinated eye-head gaze saccades and disrupts normal interaction between head movement and the VOR.

Neuronal activity in human lateral temporal cortex related to short-term verbal memory, naming and reading

Abstract: Extracellular microelectrode recordings were obtained from lateral temporal cortex that was subsequently resected in patients undergoing craniotomies under local anaesthesia for treatment of medically intractable epilepsy. During these recordings patients performed visually presented measures of overt and silent naming and word reading, short-term verbal memory and a control task requiring matching of angles. These measures were designed so that the same visual stimuli elicited language, short-term memory or spatial responses. Statistically significant changes within and between these various measures were identified. Technically satisfactory recordings were obtained from 17 populations reflecting activity predominantly from 1 neuron, in 13 patients. Two populations demonstrated no significant changes in any measured functions. Only 1 population showed changes suggesting a relation to visual perception. Four populations in or adjacent to the superior temporal gyrus altered activity with overt speech. Four other populations in the anterior temporal lobe altered activity during silent, but not overt speech. Some relation to language or memory was established for 13 of the 17 populations: 1 altered activity during reading alone, 6 during memory alone, and 6 to both. Most of the recording sites showing these language and memory changes were not essential for those functions based on surface electrical stimulation mapping. Thus the area of temporal lobe that participates in language and memory, as indicated by changes in neuronal activity, is substantially larger than the areas essential for those functions as determined by stimulation mapping. Within that participatory area, changes related to language were most often an increase in activity sustained throughout the task, a pattern suggestive of mechanisms of selective attention. Changes related to memory most often included a sustained increase in activity at the time of entry of information into memory, and again at retrieval, with decreased activity during the time the memory was stored. A few neuronal populations demonstrated relative inhibition of activity during the memory task, compared with control measures.