Showing papers in "Brain in 1989"

The natural history of multiple sclerosis: a geographically based study. I. Clinical course and disability.

Abstract: The outcome of multiple sclerosis (MS), assessed according to the Kurtzke Disability Status Scale (DSS), was reviewed in 1,099 consecutive patients followed in London, Canada, between 1972 and 1984. A geographically based subgroup of 196 patients representing 90% of Middlesex County MS patients as well as a group of 197 patients seen from onset of disease were separately analysed. The clinical course was progressive from onset in 33% of the total population and in 28% of the Middlesex County subgroup. Of those with duration of 6-10 yrs, 30-40% with initially remitting disease developed progressive MS. The cross-sectional distribution of disability was bimodal with peaks at DSS 1 (no disability) and DSS 6 (assistance required for walking). Actuarial analysis showed that the median time to reach DSS 6 from onset of MS was 14.97 +/- 0.31 yrs in the total population and 9.42 +/- 0.44 yrs in the "seen from onset' subgroup. Survival was minimally altered; 87% of patients followed up to 40 yrs were still alive, although ascertainment of cases with this duration of MS was incomplete. Data describing the rate at which disability develops after the onset of a progressive phase of MS are also presented. The implications of these data in planning and interpretation of clinical therapeutic trials are discussed.

Hand and sex differences in the isthmus and genu of the human corpus callosum. A postmortem morphological study

Abstract: The midsagittal area of the corpus callosum was measured in its entirety and in seven subdivisions in a sample of 50 brains consecutively obtained from autopsies of individuals who had neuropsychological testing before death. A 12-item test of hand preference was used as an index of the pattern of interhemispheric functional asymmetry. Callosal size was analysed for two factors: hand preference, classified as consistent-right-hand preference (CRH) versus non consistent-right-hand preference, and sex. The group of nCRH (n = 18) was found to have a larger overall callosal area, with the greatest difference occurring in the posterior body segments, especially the isthmus. The isthmus probably includes interhemispheric fibres from posterior parietal and superior temporal cortex which involves cortical regions related to functional asymmetry. The results of variation in callosal morphology are discussed as part of a possible substrate of functional asymmetry and due to variation in axonal elimination in early brain development. Sex differences were found in several aspects of callosal anatomy. (1) The difference between hand groups in the posterior body occurred in interaction with sex:handedness was a factor in callosal size in males (n = 15), but not in females (n = 35). This result is consistent with the general hypothesis of females having less clear lateralization than males. (2) Females did not have a larger overall callosum or a larger splenium, either in absolute size or size proportional to brain weight. The latter measure was considered since callosal area correlated with cerebrum weight (r = 0.48). In contrast, female of both hand groups were found to have a larger proportional isthmus compared to CRH males. (3) Of all callosal regions, only the genu and a part of the anterior body were found to be larger in absolute size in males than females. (4) Callosal size decreased with chronological age in males, but not in females.

The natural history of multiple sclerosis: a geographically based study. 2. Predictive value of the early clinical course.

Abstract: Controversy exists regarding the predictive value of the early clinical course of multiple sclerosis (MS). Three parameters often considered are the attack rate, the first interattack interval and the rate at which disability develops in the early years of the disease. We have recorded the time to reach successive levels of disability defined by the Kurtzke Disability Status Scale (DSS) in 1,099 MS patients followed at University Hospital, London, Canada between 1972 and 1984. Our population is particularly suitable because of its size, the high degree of ascertainment of cases in the community, and the regular follow-up provided. Life table analysis was used to compare survival in patients stratified according to the above three parameters using DSS 6 as end point. Significant differences were evident in the survival distributions. Despite the extensive interindividual variation in the rate at which disability developed, the early course of MS may be useful in determining the relative risk of rapid progression.

Inclusion body myositis. Observations in 40 patients.

Abstract: Inclusion body myositis (IBM) was suspected on light microscopic grounds in 48 of 170 consecutive patients with inflammatory myopathies. One or more vacuoles containing membranous material, groups of atrophic fibres, and an autoaggressive endomysial inflammatory exudate occurred in 100, 96 and 92% of the muscle specimens. All three of these features were present in 88% of the specimens. Electron microscopy confirmed the presence of filamentous inclusions in 40 of 43 patients. The inclusions are typically near vacuoles and a minimum of three vacuolated fibres must be scrutinized to detect them with confidence. There is no electromyographic pattern that can reliably distinguish IBM from other inflammatory myopathies. The typical clinical features in the patients diagnosed by histological criteria as IBM were: insidious onset after age 50 yrs with painless, proximal lower extremity weakness; slow but relentless progression with selectively severe involvement of quadriceps, iliopsoas, tibialis anterior, biceps and triceps muscles; relatively early depression of the knee reflexes; and a normal or mildly elevated serum creatine kinase level. The male: female ratio was 3:1. Distal weakness occurred in about 50%, but only in 35% was it as great or greater than proximal weakness. Significant associated illnesses include other autoimmune disorders (15%), diabetes mellitus (20%), and diffuse peripheral neuropathy (18%). Prednisone treatment at dose levels frequently effective in polymyositis failed to prevent disease progression in those patients observed for 2 or more years. Our findings support the notion that IBM is a distinct entity in which a set of pathological features is associated with a constellation of clinical findings.

The distribution of muscular weakness in upper motor neuron lesions affecting the arm.

Abstract: SUMMARY The strength of 12 muscle groups of the arm was measured to determine the distribution of upper motor neuron weakness in man. Three groups of subjects were studied 14 intact volunteers (both sides recorded), 10 patients with unilateral arm paresis (both sides recorded) and 6 patients with severe paralysis of the arm (the ‘intact’ arm only measured). On the side contralateral to the causative lesion the pattern of weakness was not the same in all patients. Shoulder muscles were relatively spared while the wrist and finger flexors were relatively severely affected, the difference being statistically significant. In hemiparetic and hemiplegic patients the strength of muscles ipsilateral to the lesion was reduced compared with normal controls. These observations refine previous clinical descriptions of upper motor neuron weakness and have implications for its pathophysiology.

Obsessive-compulsive and other behavioural changes with bilateral basal ganglia lesions. A neuropsychological, magnetic resonance imaging and positron tomography study.

Abstract: SUMMARY Eight patients are reported who shared the combination of bilateral basal ganglia lesions and a frontal lobe-like syndrome. The main features were inertia and loss of drive, with preservation of intellectual function. Some patients showed stereotyped activities with compulsive and obsessive behaviour which were sometimes highly elaborate in pattern. Extrapyramidal clinical signs were absent or mild. Brain damage, related to anoxic or toxic encephalopathy, was demonstrated by CT scans and MRI. The lesions appeared to be confined to the lentiform nuclei, particularly affecting the pallidum, although there was generalized brain atrophy in 2 cases. Positron emission tomography (PET) in 7 patients revealed hypometabolism of the prefrontal cortex relative to other parts of the brain. The PET studies suggest dysfunction of the prefrontal cortex as a result of damage to the lentiform nuclei These clinical, anatomical and functional observations emphasize the role of the circuits linking the prefrontal associative cortex and some specific areas of the neostriatum, including the pallidum. The existence of distinct nonoverlapping circuits in the motor field or in the associative field can explain the fact that basal ganglia lesions may give rise to a clinical picture that is either purely motor, purely behavioural (as in some of our patients), or both. Similarities existed between some symptoms found in our patients and certain features of major psychiatric illnesses such as severe depression, catatonic schizophrenia, and obsessive-compulsive disorder. This raises the hypothesis that some aspects of these psychiatric disorders could be related to structural and physiological disturbances in the systems linking the frontal associative cortex and the basal ganglia.

X-linked recessive bulbospinal neuronopathy. A clinicopathological study.

Abstract: A clinicopathological study on X-linked recessive bulbospinal neuronopathy was undertaken on 9 cases, with morphological observations on 3 autopsied cases and sural nerve biopsies from 6 patients. Both lower motor and primary sensory neurons were involved. Lower motor neurons were markedly depleted through all spinal segments and in brainstem motor nuclei except for the third, fourth and sixth cranial nerves. Primary sensory neurons were less severely affected. A quantitative study of primary sensory axons at several levels in the peripheral nervous system suggested that a distally accentuated axonopathy was the salient pathological process. Segmental demyelination and remyelination clustered on individual fibres, and g ratios (axon diameter: total fibre diameter) in the sural nerve showed an increased scatter in some cases. Evidence of regeneration was inconspicuous. Unmyelinated fibres were well preserved throughout all the nerves examined. Neurons in the Onufrowicz nuclei, in the intermediolateral columns and in Clarke's columns of the spinal cord were generally well preserved. These observations indicate that a lower motor and primary sensory neuronopathy is a major neurological manifestation in this disease.

Reciprocal inhibition between forearm muscles in patients with writer's cramp and other occupational cramps, symptomatic hemidystonia and hemiparesis due to stroke.

Abstract: Reciprocal inhibition of H reflexes in the forearm flexor muscles was examined in a group of 16 patients with writer's and other occupational cramps. The early disynaptic phase of reciprocal inhibition was normal. However, there was a reduction in the amount of later, presynaptic inhibition, when compared with age-matched normal subjects. Similar findings were seen in 2 patients with symptomatic hemidystonia in whom structural brain lesions were present. However, this reduction in presynaptic inhibition was not specific to patients with dystonia. In a further group of 13 patients with hemiparesis or hemiplegia due to stroke, abnormalities of both early and later phases of reciprocal inhibition were found. The patients with spasticity exhibited less disynaptic inhibition than those with normal tone or flaccid limbs. The changes in the presynaptic phase of reciprocal inhibition did not correlate with the clinical signs of spasticity and increased muscle tone. These results provide objective evidence of a physiological basis for the action or task-specific focal dystonias such as writer's cramp.

Delay in the execution of voluntary movement by electrical or magnetic brain stimulation in intact man: evidence for the storage of motor programs in the brain

Abstract: Experiments were undertaken to study the effect on voluntary movement of an electrical or magnetic stimulus delivered to the brain through the scalp. Subjects were trained to flex or extend their wrist rapidly in response to an auditory tone. A single brain stimulus (electrical or magnetic) delivered after the tone and before the usual time of onset of the voluntary reaction could delay the execution of the movement for up to 150 ms, without affecting the pattern of the agonist and antagonist EMG bursts. The delay increased with increasing stimulus intensity and with stimuli which were applied nearer to the usual time of onset of the voluntary reaction. A stimulus given after the onset of the first voluntary agonist EMG burst only delayed the onset of the first antagonist and later EMG bursts. Movement was not delayed when similar experiments were performed with supramaximal stimulation of the median nerve instead of the brain stimulus. The delay following a cortical shock was not due to spinal motoneurons being inaccessible to descending input during the delay period since a second brain stimulus, given in the middle of the delay period, was capable of producing a direct muscle response. Neither could the delay be explained by the brain stimulus altering the time of the subject's intention to respond since a stimulus delivered to one hemisphere before an attempted simultaneous bilateral wrist movement produced a far greater delay of the contralateral than the ipsilateral movement. We suggest that the brain stimulus delayed movement by inhibiting a group of strategically placed neurons in the brain (probably in the motor cortex) which made them unresponsive for a brief period to the command signals they receive which initiate the motor program of agonist and antagonist muscle activity. The results have implications for the issues of the storage of motor programs, internal monitoring of central movement commands and the site of organization of the antagonist EMG burst.

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

Abstract: 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.).

The bereitschaftspotential is abnormal in parkinson's disease

Abstract: The average Bereitschaftspotential (BP) preceding a rapid, self-paced voluntary extension movement of the index finger was recorded from 6 scalp locations in 14 patients with Parkinson's disease who had been withdrawn from their normal drug therapy for at least 12 h before testing. The amplitude of the potential was measured at the peak negativity (Nl) and 650 ms prior to this (NSI), and compared with that recorded in a group of 12 age-matched control subjects. The Nl amplitude was the same as in the normals, but the NS1 component was smaller in the patients, especially in midline leads As a result, the rise in the BP between the peak NS1 and Nl component (termed NS2) was larger in the patient group. The NS1 component of the BP is thought to reflect preparatory activity in the supplementary motor area (SMA) of cortex. Since the basal ganglia provide a major source of afferent input to SMA, the reduction in NS1 in the patients probably results from inadequate basal ganglia activation of SMA. The larger NS2 component may reflect extra activity in other brain areas to compensate for the reduced SMA activity.

Severe nonfluency in aphasia. Role of the medial subcallosal fasciculus and other white matter pathways in recovery of spontaneous speech.

Abstract: The relationship between location and extent of lesion on CT scan and limitation in spontaneous speech was examined. The severity of spontaneous speech ranged from cases with no speech or only verbal stereotypies (first major group) to those with reduced, hesitant, poorly articulated, agrammatic speech (nonfluent Broca's aphasia, second major group). CT scan analysis revealed no single neuroanatomical area that contained an extensive lesion which could be used to discriminate the most severe cases from the least severe. The two groups were separable, however, on the basis of the CT scan when the extent of the lesion in two subcortical white matter areas were combined: (1) the most medial and rostral portion of the subcallosal fasciculus plus (2) the periventricular white matter near the body of the lateral ventricle, deep to the lower motor/sensory cortex area for the mouth. The most rostral portion of the medial subcallosal fasciculus, located in the lateral angle of the frontal horn (extremely deep to Broca's area), contains projections from the cingulate gyrus (area 24) and the supplementary motor area, to the caudate nucleus. We suggest that one explanation for the more severe limitation in spontaneous speech in the first group is the extensive white matter lesion in these two subcortical pathways had interrupted a large number of connections for (1) initiation and preparation of speech movements, and limbic aspects of speech (lesions in the medial subcallosal fasciculus), and (2) motor execution and sensory feedback for spontaneous speech (lesions in periventricular white matter deep to the motor/sensory cortex area for the mouth). Extensive lesion in only one of these two white matter pathway areas, alone was not sufficient to produce long-lasting severe limitation in spontaneous speech and could not be used to discriminate the two groups on the basis of the CT scans. The patients with less severe limitation in spontaneous speech (nonfluent Broca's aphasia) had less extensive lesion within these two white matter areas combined, and had interrupted a smaller number of these subcortical connections. The sites of the lesions in subcortical white matter in CT scans in Broca's original case who could only produce a verbal stereotypy are similar to those in our first group with the most severe limitation in spontaneous speech. The presence or absence of hemiplegia was not related to severity or recovery of spontaneous speech. Careful examination of lesion extent in these two areas of subcortical white matter on CT scanning appears to be relevant in predicting potential for recovery of spontaneous speech in some stroke patients.

The origins of utilization behaviour

Abstract: Utilization behaviour has previously been described clinically by Lhermitte (1983). An experimental investigation is reported of utilization behaviour in a patient with a localized inferior medial bifrontal lesion. The patient picked up and used irrelevant objects not only when placed directly in front of him—the procedure developed by Lhermitte—but also when he had been instructed to carry out other tasks and his attention had not been directed to the objects. The behaviour occurred most frequently in the brief intervals between tasks, and more often when auditory-verbal rather than visuomotor tasks were being performed. The results are interpreted within an information-processing model of frontal lobe function. A differentiation is made between two forms of utilization behaviour—an ‘incidental’ form, as exhibited by the patient, and an ‘induced’ form where it occurs only when Lhermitte's procedure is adopted.

Chronic hyperalgesia and skin warming caused by sensitized c nociceptors

Abstract: A patient suffering from an acquired painful syndrome, due to injury to primary somatic afferent units, was studied. Clinical features included chronic spontaneous burning pain in one hand, abnormal painful response to nonnoxious cutaneous stimuli, and deviation of temperature and dystrophic changes in symptomatic skin. Diagnostic stellate ganglion blocks did not improve spontaneous or stimulus-induced pains, and observation of sympathetic efferent neural activity and vasomotor effector responses revealed no abnormality, failing to support an autonomic contribution to the pathogenesis of the pains. A quantitative psychophysical assessment documented exaggerated magnitude of pain in response to noxious stimuli in symptomatic skin, together with abnormal painful quality and prolongation of sensation induced by nonnoxious tactile or warm stimuli. Such mechanical and thermal hyperalgesia persisted during A fibre blocks, suggesting transmission by primary afferents with unmyelinated C fibres and implying sensitization of C polymodal nociceptors. Direct microneurographic recordings of single, identified C polymodal nociceptors from symptomatic skin confirmed the presence of units with pathologically enhanced receptor responses: lowered threshold and very prolonged afterdischarges. While bypassing skin receptors, strongly intraneural microstimulation in fascicles supplying symptomatic or control skin evoked equivalent magnitudes and temporal profiles of pain from both sides. Thus secondary CNS dysfunction need not be postulated to explain the painful syndrome. Skin grafted onto the affected region partially recovered tactile and thermal sensation (but not pain) without expressing the painful syndrome. This supports the overall conclusion that in this patient A fibres are not involved as primary carriers of input decoded as pain. Sensitization of C polymodal nociceptors is consistent with the features of hyperalgesia in this patient: pain evoked by nonnoxious stimuli, exaggerated pain magnitude, and abnormally prolonged aftersensation of pain. This is the first documentation of chronic sensitization of human C polymodal nociceptors as a symptom of disease. In the context of sensitized C nociceptors and in the absence of sympathetic vasoconstrictor deficit, the abnormally elevated temperature in symptomatic skin is interpreted as due to antidromic vasodilatation triggered by neurosecretion from hyperactive nociceptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Anticipation in myotonic dystrophy: fact or fiction?

Abstract: In 1918 Fleischer reported that after transmission from one generation to the next, myotonic dystrophy has an earlier onset and is more severe. The hypothesis put forward by Penrose in 1948 that 'anticipation' is caused by bias of index case selection was based on theoretical arguments only and has not been supported by clinical observations. This hypothesis was tested in a clinical and genetic study of 14 families with myotonic dystrophy. Excluding index patients, an earlier onset in the child was found in 98% of 61 parent-child pairs. A greater mean difference in age of onset was found with transmission via the father than via the mother. The comparison of the severity of the disease between parents and children was difficult because of the variation in symptoms but, in general, the disease was more severe in the child than in the parent. The penetrance of the abnormal gene was nearly complete in the 14 families combined, leaving little room for the observation of 'complementary' parent-child pairs in the future. Also in retrospect no complementary parent-child pairs were found in the first generations. Fertility was severely reduced only in the very early onset patient group and this selective infertility cannot be responsible for the total amount of anticipation observed. It is therefore concluded that anticipation may be inherent in the transmission of myotonic dystrophy. This has important consequences for genetic counselling.

Local brain haemodynamics and oxygen metabolism in cerebrovascular disease. Positron emission tomography.

Abstract: Using position emission tomography (PET) and equilibrium imaging with oxygen-15 labelled gases, the cerebral blood flow (CBF), blood volume (CBV), oxygen extraction fraction (OEF) and oxygen consumption rate (CMRO2) were measured in multiple regions of interest over the cerebral cortex of 5 control subjects, 4 patients with strictly unilateral longstanding carotid artery occlusion, 1 patient with middle cerebral artery embolic stroke in the acute stage, and 4 patients with subcortical stroke and no cervical arterial disease. In each control subject, the regional CBV was linearly and positively correlated with both CBF and CMRO2, while the local mean transit time (t = CBV/CBF) was uniformly distributed, reflecting the local adaptation of both the vascular tone and the capillary density to the metabolic demand at constant cerebral perfusion pressure that characterizes the normal brain. In patients with subcortical stroke, cortical blood volume was reduced in proportion to the matched reduction in CBF and CMRO2, suggesting that the metabolic depression resulting from cortical deafferentation increases the resting tone of pial vessels. Unilateral carotid occlusion induced larger CBV and t, and steeper slopes of the CBV-CBF relationship, particularly on the occluded but also on the patent side. The assessment of the local cerebral perfusion pressure (CPP) as judged by the ratio CBF/CBV in 3 patients with focally raised OEF and preserved or reduced CMRO2, allowed the demonstration in multiple cerebral regions of single patients of two well-known physiological phenomena: the autoregulation of CBF, followed by the rise of the OEF as local CPP falls further. In addition, the depression of CMRO2 in the ischaemic cortex was associated with a trend for CBV to return towards normal values, compared with the maximally elevated CBV found in oligaemic but metabolically normal areas. This suggests that a process of metabolic vasoconstriction may participate, among other factors, in the vascular collapse that occurs, and would serve to regenerate some haemodynamic reserve, at very low CPP levels.

Loss of memory for people following temporal lobe damage.

Abstract: A 40-yr-old woman, K.S., is reported, who shows a severe loss of memory for people following a history of epilepsy and right anterior temporal lobectomy. Despite this memory problem, K.S. is not clinically amnesic, has a Memory Quotient of 122 on the Wechsler Memory Scale in line with her IQ of 119, and performs well on conventional tests of recognition and recall. She does not have a generalized semantic memory deficit for living things, but her deficit extends beyond people to include famous animals, buildings and product names. Autobiographical memory is good, except where memory for people is concerned. The nature of the memory store that is impaired in K.S. is discussed, as are the implications of her case for theories of the organization of long-term memory.

The effects of voluntary contraction on the H reflex of human limb muscles.

Abstract: The effects of a voluntary contraction on the H reflexes of various muscles were quantified to determine whether the reflex responses were sufficiently reproducible to be used in diagnostic studies. During a voluntary contraction, H reflexes could be recorded reliably from tibialis anterior and abductor pollicis brevis, but accurate identification of the onset of the H wave from the on-going background EMG required duplicate averages of multiple responses. During a contraction the H reflex could be obtained at lower stimulus intensities in the forearm flexor muscles than when relaxed, and a more clear separation of the H wave from the M wave was possible. The background contraction abolished the attenuation of reflex amplitude with increasing stimulus repetition rates, such that repetition rates of up to 4 Hz could be used without significant loss of reflex amplitude. There were only small and usually insignificant differences in the latency of the H reflex or its variability when elicited with the forearm muscles relaxed and when flexor carpi radialis was contracting steadily. The reflex latencies of abductor pollicis brevis, tibialis anterior and soleus were compared with F wave latencies for these muscles. The minimal F wave latencies were shorter than the H reflex latencies for abductor pollicis brevis (mean 2.2 ms) and tibialis anterior (mean 1.0 ms) but not for soleus. Comparison of the spread of F wave latencies (F max-F min) suggests that, for soleus, F waves are recorded only from the faster conducting motor units in the pool, presumably those less readily recruited in the H reflex. It was calculated that the distribution of motor conduction velocities responsible for the F waves of abductor pollicis brevis was 8.8 m.s-1. This value underestimates the likely distribution of motor conduction velocities for the thenar muscle by as much as 50%, consistent with the view that F waves rarely occur in slowly conducting motor units, the units of lowest threshold in reflex studies. It is concluded that, for many motoneuron pools, the H reflex and the F wave appear preferentially in different motoneurons, low and high threshold, respectively, and that reflex studies can provide information not available from somatosensory evoked potentials or F wave studies.

Abnormal ocular movements in Parkinson's disease. Evidence for involvement of dopaminergic systems.

Abstract: Quantitated automated electro-oculographic data from 45 parkinsonian patients were compared with those from 30 normal control subjects. Patients were selected with idiopathic Parkinson's disease without other associated neurological disease or dementia; 20 had never received antiparkinsonian drugs and in 25 such treatment had been stopped for at least 2 days. Saccade latency, amplitude and peak velocity, smooth pursuit peak velocity, optokinetic nystagmus (OKN) maximal and mean velocities and vestibulo-ocular reflex (VOR) suppression by vision or imagination were significantly altered in patients, whereas VOR gain in darkness was normal. Alterations of saccade latency and smooth pursuit peak velocity were more severe in the more advanced stages of the disease and saccade latency directed towards the symptomatic side was slightly delayed in hemiparkinsonian patients. Saccade amplitude improved 90 min after a single oral dose of L-DOPA. These results suggest a possible dopaminergic control of some ocular movements.

Myoclonus epilepsy and ragged-red fibres (merrf)1. a clinical, pathological, biochemical, magnetic resonance spectrographic and positron emission tomographic study

Abstract: Thirteen patients, including 6 from one family, with the syndrome of myoclonus epilepsy and ragged-red fibres (MERRF) were studied. There was considerable heterogeneity in the age of onset, severity and associated clinical features. Postmortem studies in 3 patients from the one family showed a particular system degeneration. In addition, the youngest and most severely affected family member showed the pathological changes of Leigh's syndrome. Cortical dysfunction is a prominent clinical feature in MERRF, but postmortem examination failed to reveal cortical abnormalities. Positron emission tomographic studies, however, showed decreased cortical metabolic rates for glucose and oxygen utilization, with normal cortical blood flow and cerebral pH. Analyses of kinetic rate constants for uptake and phosphorylation of the glucose analogue, fluorodeoxyglucose showed decreased hexokinase-mediated phosphorylation: normal K1 and k2 values but reduced k3. Phosphorus magnetic resonance spectroscopy studies suggested a normal cerebral intracellular pH. Biochemical studies on muscle homogenates in 6 patients showed partial deficiencies of the activities of certain mitochondrial enzymes in 4 cases, whereas in 2 patients no abnormality was found. Our data, combined with previous reports, show that MERRF is biochemically and genetically heterogeneous. Our experience, and analysis of the literature, suggests that many cases previously described as the Ramsay Hunt syndrome, as well as other hitherto unclassified system degenerations associated with myoclonus epilepsy, are examples of MERRF. These data permit the formulation of a hypothesis to explain the clinical, biochemical and genetic heterogeneity of MERRF, and its overlap with Leigh's syndrome. We suggest that different biochemical defects of the mitochondrial respiratory chain may cause similar cerebral metabolic effects, as measured by positron emission tomography, resulting in similar phenotypes. Reduced activity of one enzyme, however, may result in different phenotypes, depending on the severity of the defect and its tissue distribution. Moreover, the phenotypic expression of certain biochemical defects may be influenced by randomly occurring factors such as fever, which may increase metabolic demand and result in more deleterious cellular metabolic effects.

Heat and mechanical hyperalgesia induced by capsaicin. Cross modality threshold modulation in human C nociceptors.

Abstract: Quantitative thermal and mechanical algometry was studied in 4 human subjects exposed to various concentrations of capsaicin administered topically to the skin of the palm or forearm Treated skin patches were assessed for changes in heat pain threshold and in mechanical pain threshold at various controlled temperatures The results showed that: (1) in addition to heat hyperalgesia, capsaicin consistently induces overt mechanical hyperalgesia; (2) thermal and mechanical hyperalgesias are linearly dependent on the log of capsaicin dose, (3) mechanical hyperalgesia is increased by increasing skin temperature; (4) mechanical hyperalgesia is abolished by cooling the skin to a point about 10° C below the threshold for heat pain, a temperature that does not impair touch or sharp pain sensation. These sensory effects of capsaicin are mediated by C fibres, since dissociated A fibre block established by compression-ischaemia does not abolish either spontaneous pain or mechanical hyperalgesia. In addition, abolition of mechanical hyperalgesia by cooling persists during A fibre block Cooling thus appears to act directly, presumably decreasing hyperexcitability of the C nociceptor. Hyperalgesia is also transiently depressed for at least 30 min during the postischaemic period, well beyond the duration of paraesthesiae or overt hyperaemia. Sensory changes identical to those induced experimentally by capsaicin have been observed in patients with a particular variety of neuropathic pain (ABC syndrome) and have been termed polymodal hyperalgesia and cross modality threshold modulation (Ochoa, 1986, Ochoa et al , 1987) Based on these overall observations, it is postulated here that the sensory abnormalities induced by capsaicin and those observed in this particular variety of patients relate to primary hyperalgesia and share a common mechanism in that the excitable receptor membrane of polymodal C nociceptors behaves as if it ‘misreads’ temperature.

The role of cerebellar structures in the execution of serial movements.

Abstract: Thirteen patients with bilateral cerebellar disease and 12 patients with unilateral cerebellar disease were instructed to execute movement sequences in response to a simple reaction signal. Each to-be-executed sequence consisted either of a single, two, or three keypress components. Evidence for cerebellar involvement in the execution of programmed responses was sought in the pattern of response onset times and interkeypress times. Patients with mild bilateral cerebellar dysfunction or mild unilateral dysfunction, and neurologically unimpaired subjects showed increases in response onset time as sequence length increased from L = 1 to L = 3. In contrast to this, there were negligible or no effects of sequence length on response onset time in patients with moderate bilateral cerebellar dysfunction and in patients with moderate unilateral cerebellar dysfunction who responded with the hand ipsilateral to the lesion. Furthermore, cerebellar dysfunction was associated with significantly slower interkeypress reaction times. These results support the hypothesis that the translation of a programmed sequence of responses into action involves cerebellar structures which schedule a sequence of ordered responses before onset of movement.

Sensorimotor disturbances in patients with lesions of the parietal cortex

Abstract: Somatosensory and motor disturbances of hand function were examined in 9 patients with parietal lobe lesions. A quantitative score was used for the elaboration of sensorimotor profiles displaying the relative degree of functional impairment. In patients with anterior parietal lobe lesions somaesthesis was clearly more disturbed than motor function. Simple aspects of somaesthesis (surface sensibility, two-point discrimination, position sense) were disturbed to about the same degree as complex somatosensory (tactile recognition) tasks. On the other hand, patients with lesions of the posterior parietal lobe showed preferential impairment of complex somatosensory and motor functions (exploratory and manipulative finger movements). In 4 patients, analysis of motor behaviour by means of an optoelectronic system showed that reaching, formation of hand aperture and target acquisition were less disturbed than manipulative behaviour. Finger movement trajectories during dynamic digital palpation of objects were grossly deranged in the patients with posterior parietal damage. The temporal characteristics of the finger movements during active touch were completely destroyed. This leads to a breakdown of the finely tuned digital scanning process required for the sequential sampling of mechanoreceptive information. Remarkably, these patients could produce the exploratory finger movements imitatively. The motor disability of the parietal hand does not lie in the loss of the kinetic memory to perform these movements, but in the loss of their evocation by appropriate sensory stimuli. This deficit is not due to a lack of somatosensory information because that may be relatively well preserved. It is concluded that the motor disturbance in posterior parietal lobe disease lies essentially in the conception and execution of the spatiotemporal movement patterns necessary to bring those receptors into action which would normally provide the information about tactile objects. This illustrates the intricate mutual dependence of the spatiotemporal organization of receptor activation by movement and of the formation of movement trajectories on the basis of adequate sensory processing.

Abnormalities of nonvisually-guided eye movements in Parkinson's disease.

Abstract: Rapid eye movements (saccades) were examined in 7 patients with idiopathic Parkinson's disease (PD) and a matched group of normal control subjects. The effect of instructional and stimulus conditions used to elicit saccades was examined using 3 experimental paradigms. Eye movements directly elicited by a novel peripheral target were unimpaired in patients with PD as compared with control subjects. Saccades to a remembered target location, however, were dysmetric in the PD group and showed a characteristic multistepping pattern. The PD impairment was not caused by a loss of information on target location since their final eye position was close to the target at all eccentricities. Peak velocity, duration, and latency did not distinguish between PD patients and controls. These results support the view that for saccades which are not directly elicited by a visual target there is a neural pathway that can be distinguished from structures involved in the generation of visually elicited (or 'reflexive') saccades. The finding that in PD saccades to a remembered target are selectively impaired suggests that structures in the basal ganglia play a crucial role in this alternative pathway.

Prosopagnosia in a right hemispherectomized patient.

Abstract: The first reported case of prosopagnosia in a right hemispherectomized woman, B.M., whose intellectual and cognitive functions were otherwise normal or only slightly impaired, is presented. She was totally unable to identify, and to experience a sense of familiarity with, faces of persons she knew, but she could evoke semantic information about them and retrieve their names from visual contextual cues. She was unaware that she was lacking face-recognition skills and that faces alone could be used to access the identity of individuals. The functional nature of her deficit was investigated through sensory, perceptual, memory, and learning tasks to determine the level at which her prosopagnosic disturbance occurred. She was defective at resolving low spatial-frequency information, but this was insufficient to explain the selectivity of her impairment. She was able to carry out cognitive operations specific to faces as long as facial identity did not have to be ascertained, and she performed as well as control subjects at deriving information about the gender, age, and emotion of faces. She was impaired at matching different views of the same faces, and multidimensional scaling analysis of dissimilarity judgements between faces indicated an inability to combine the component features into a configurational facial representation that would uniquely define each face. In contrast to recently reported cases of prosopagnosia, B.M. showed no sign of covert recognition of known faces in a learning task, and there was no indication that she could, even for a few seconds, store a faithful facial representation. The occurrence of prosopagnosia in this hemispherectomized patient confirms that this deficit can emerge without damage to the left hemisphere, and her unawareness of her deficit, which had remained unnoticed for several years, raises the possibility that other hemispherectomized patients may be prosopagnosic. The pattern of cognitive impairments displayed by B.M. indicates a perceptual basis to her disturbance and is discussed in relation to other cases of prosopagnosia.

The role of complement in the pathogenesis of experimental allergic encephalomyelitis

Abstract: The role of complement in the pathogenesis of demyelination and inflammation has been investigated in a synergistic model of acute experimental allergic encephalomyelitis (EAE) in the Lewis rat. Depletion of serum complement with cobra venom factor (CVF) suppressed the clinical expression of acute inflammatory EAE induced either by immunization with 50 micrograms guinea pig basic protein (MBP) in Freund's complete adjuvant, or by the passive transfer of 10(7), but not 5 X 10(7) MBP activated spleen cells. Despite the suppression of clinical disease in actively induced EAE, treatment with CFF only had a significant effect on the severity of CNS inflammation in early disease (12 days postimmunization) when the number of inflammatory foci was reduced by 35%. Three days later this difference had resolved and no significant difference could be detected in the severity of CNS inflammation, although control animals exhibited severe disease, the CVF treated group being clinically normal. Demyelination in these models is initiated by systemic injection of the antimyelin oligodendrocyte glycoprotein (MOG) monoclonal antibody, 8-18C5, which in vitro lyses oligodendrocytes in a dose, Fc and complement-dependent manner and in vivo induces extensive CNS demyelination in rats with EAE. Treatment with CVF reduced the ability of this antibody to initiate demyelination in vivo and furthermore, its F(ab)2' fragment had no effect on the clinical course of EAE and was unable to initiate demyelination in normal animals. Complement-dependent mechanisms are therefore involved both in the clinical expression of acute inflammatory lesions and in the pathogenesis of antibody-mediated demyelination in EAE.

Evidence for preserved reading in ‘pure alexia’

Abstract: We describe 4 patients who developed pure alexia after infarctions of the left cerebral hemisphere. All subjects employed a letter-by-letter strategy (with varying degrees of success) to explicitly identify visually presented words. Although all 4 subjects explicitly denied that they could identify briefly presented words, they all performed significantly better than chance on lexical decision and forced-choice semantic categorization tasks with briefly presented words which they could not explicitly identify. Three subjects regained the ability to explicitly identify briefly presented words; these subjects were more accurate with nouns than functors and words of high as compared with low imageability. Additionally, these subjects were impaired in the processing of suffixes. These data are not accommodated by the 'disconnection' account of pure alexia but are more consistent with the hypothesis that reading in these patients is mediated by the right hemisphere.

Differentiation of typical absence seizures in epileptic syndromes. A video EEG study of 224 seizures in 20 patients.

Abstract: This is a comparative video-electroencephalographic (EEG) study of typical absence seizures in 4 epileptic syndromes. In 20 patients, 224 absences were recorded and analysed. Significant clinical and EEG differences were found in the seizure patterns of childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy with absences (JMEA) and myoclonic absence epilepsy (MAE). Clinically, CAE demonstrated more severe impairment of consciousness than JAE while, in JMEA, ictal manifestations were frequently mild and difficult to detect. In the latter, the adolescent patient usually continued his activity, was able to perform even mathematical calculations and often his speech was not disturbed. In children with JMEA, impairment of consciousness was more apparent and sometimes severe. Automatisms occurred in all 4 epileptic syndromes and were proportional to the severity of the demonstrated impairment of consciousness, being rare in JMEA but frequent in CAE and JAE. Expressive speech and overbreathing usually persisted for 1-2 s after the onset of the EEG ictal discharge in CAE. It was less disturbed in JAE where in some absence seizures, interrupted speech and overbreathing were restored during the ictus. A characteristic clinical manifestation of CAE was opening of the eyes in all absence seizures within 1.8 +/- 0.6 s (max. 2.5 s) from the onset of the EEG paroxysms. This early eye-opening behaviour was not observed in JMEA. In MAE, rhythmical myoclonic jerks at 3 Hz make the diagnosis unmistakable. Myoclonic jerks were extremely rare in the absences of JMEA, although all patients had independent myoclonic jerks on awakening. The ictal EEG discharge was longer in JAE (mean 16.3 +/- 7.1 s) than in CAE (12.4 +/- 2.1 s) or JMEA (6.6 +/- 4.2 s). The opening phase of the EEG paroxysms did not show significant differences in CAE, JAE and JMEA but significant changes were found in their initial and terminal ictal phases. In JMEA, the spike-multiple spike-slow wave complexes were not rhythmic and frequently demonstrated variable spike-slow wave relationships. Ictal discharge fragmentations and spike-wave discharges looking like compressed capital Ws were often seen and are characteristic of JMEA. seen and are characteristic of JMEA. Absence seizures demonstrated a more severe impairment of expressive rather than receptive speech, irrespective of differences between syndromes. Evoked as well as spontaneous automatisms occurred in the same patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Visuospatial processes of line bisection and the mechanisms underlying unilateral spatial neglect

Abstract: Patients with unilateral spatial neglect fail to report or respond to stimuli contralateral to the lesion which usually involves the right parietal lobe. When asked to mark the centre of a horizontal line, these patients place the mark to the right of the true midpoint. It has been considered that they neglect the left part of the line and bisect the perceived line segment. We investigated the eye-fixation patterns of hemianopic patients with or without unilateral spatial neglect during the bisection of lines, using an eye camera. Hemianopic patients without unilateral spatial neglect saw the whole lines, searching to the endpoint on the hemianopic side, and bisected it correctly. In contrast, left hemianopics with unilateral spatial neglect never searched to the left hemianopic side. Once they fixated a certain point on the right part of the line, they persisted with this point and marked the subjective midpoint there. Taking left homonymous hemianopia into account, the subjective midpoint appeared to be marked, not at the centre of the line segment perceived in the seeing right visual field, but at the leftmost point of it. However, they could appreciate the deviation of the subjective midpoint in the right visual field when forced to fixate the left endpoint of the line. These findings suggest that the left hemisphere has the ability to estimate the midpoint of the line through the right visual field and that visuospatial disorder in the line bisection test is attributable to the pathological change in the right hemisphere. The results are interpreted to mean that left hemianopic patients with unilateral spatial neglect see a totalized image of a line extending equally to either side of the point where they are going to mark the subjective midpoint. We considered that the right hemisphere completes the line, using the visual input relating to the right part of the line perceived by the left hemisphere.

Cytomegalovirus in the nervous system of patients with the acquired immune deficiency syndrome

Abstract: Clinicopathological features of infection of the nervous system by cytomegalovirus (CMV) in 31 patients with the acquired immune deficiency syndrome (AIDS) are reviewed. Neuropathology was variable, ranging from rare isolated CMV inclusions in brain without associated inflammation or necrosis, to severe necrotizing ependymitis and meningoencephalitis. In 1 patient, CMV had produced a necrotizing meningoradiculitis which presented clinically as ascending paralysis. In the brains and spinal cords of 6 patients, evidence of human immunodeficiency virus (HIV) infection of neural parenchyma was seen in close proximity to CMV infection. Both viruses individually or together were associated with low grade (microglial nodule) encephalitis. In retrospect, the diagnosis of CMV had been a difficult one to make clinically in neurologically impaired patients with AIDS. The results suggest that CMV may also localize in the nervous system without significant clinical sequelae. Imaging studies and analysis of cerebrospinal fluid revealed abnormalities in many patients, but none of them (short of culture of CMV itself in two cases) appeared to be specific to this neurological complication of the immunodeficiency.