Biomedical subjects

J Noth

Publications and source records attributed to J Noth.

At least 73 records · Page 4Linked to original sources

PubMed1995

Motor function in a patient with bilateral lesions of the globus pallidus.

This study describes the long-term deficits of a patient who, after a toxic encephalopathy, sustained extensive bilateral damage to both segments of the globus pallidus (GP) and the right substantia nigra (SN). There were no signs of lesions of the pyramidal tracts or of other motor structures. The most obvious deficits were an abnormal gait with an exaggerated knee extension and a tendency to fall slowly, especially when pushed backward. In contrast, Romberg's test on an unstable platform was normal, as were long-latency leg reflexes induced by perturbations. Inadequate anticipatory and compensatory postural responses, in particular across the hip and knee joints, and slow movements seemed responsible for the falls. Muscle tone was normal but reflex studies showed signs of abnormal facilitation and inhibition at various levels of the neuraxis. We conclude that the GP and SN lesions caused defective input to premotor cortical and brain stem target zones. Dysfunctioning of these zones leads to improper control of the descending ventromedial motor system responsible for locomotion, postural control, and reflex status. The deficits in upper extremity motor performance included delayed and slow movements, inaccurate amplitudes of ballistic responses, a lack of predictive control, and deficits in bimanual coordination. Sensory feedback, proprioceptive more than visual, played a powerful compensating role in rapid aiming movements. Regional blood flow (studied using 15(O)2) was reduced in multiple frontal cortical regions, among which are the hand areas of the supplementary and premotor cortex. We hypothesize that this reflected impaired functioning of these areas, caused by defective bilateral output from GP and SN, and resulting in the motor deficits of the arm and hand.

Adult↗

PubMed1995

Rapid appearance of beta-amyloid precursor protein immunoreactivity in glial cells following excitotoxic brain injury.

Clinical and experimental data have indicated an up-regulation of amyloid precursor protein (APP) after various types of CNS injury. In the present study the cellular source of lesion-induced APP has been investigated in a neurotoxic CNS model. Quinolinic acid injection into the striatum results in neuronal degeneration, while glial cells survive. APP immunoreactivity was detected in glial cells starting at postoperative day 3 and persisted until day 21, the last time point studied. Double immunocytochemistry identified the majority of APP-immunoreactive cells as glial fibrillary acidic protein-immunoreactive astrocytes. There was no evidence of amyloid fibril deposition during this time. It is concluded that following excitotoxic neuronal degneration APP is mainly produced by reactive astrocytes in the lesioned area.

Amyloid beta-Protein Precursor↗

PubMed1995

Structural changes of anterior horn neurons and their synaptic input caudal to a low thoracic spinal cord hemisection in the adult rat: a light and electron microscopic study.

Structural changes in lumbosacral ventral horn neurons and their synaptic input were studied at 3, 10, 21, 42, and 90 days following low thoracic cord hemisection in adult rats by light microscopic examination of synaptophysin immunoreactivity (SYN-IR) and by electron microscopy. There was an ipsilateral transient decrease in SYN-IR at the somal and proximal dendritic surfaces of anterior horn neurons which extended caudally from the site of injury over a postoperative (p.o.) period of 42 days. Concomitantly, at 21 days p.o., perineuronal SYN-IR started to recover in upper lumbar segments. By 90 days p.o., a normal staining pattern of SYN was noted in upper and mid lumbar segments, but the perineuronal SYN-IR was still slightly below normal levels in low lumbar and sacral segments. Electron microscopy revealed ultrastructural changes coincident with the alterations in SYN-IR. At 3 days p.o., phagocytosis of degenerating axon terminals by activated microglial cells was observed at the somal and proximal dendritic surfaces of ventral horn neurons. These changes were most prominent up to two segments caudal to the lesion. At 10 days p.o., advanced stages of bouton phagocytosis were still detectable in all lumbosacral motor nuclei. Additionally, abnormal axon terminals, with a few dispersed synaptic vesicles and accumulations of large mitochondria, appeared at the scalloped somal surfaces of anterior horn neurons. At 21 days p.o., several large lumbosacral motoneurons had developed chromatolysis-like ultrastructural alterations and motoneuronal cell bodies had become partially covered by astrocytic lamellae. At 42 days p.o., there was a transient appearance of polyribosomes in some M-type boutons. In addition, at 42 and 90 days p.o., a few degenerating motoneurons were detected in all lumbosacral segments, but most displayed normal neuronal cell bodies contacted by numerous intact synapses as well as by astrocytic processes. In contrast to these striking alterations of synaptic input at somal and proximal dendritic surfaces of motoneurons, relatively few degenerating boutons were detected in the neuropil of motor nuclei at all the p.o. times studied. We suggest that the preferential disturbance of the predominantly inhibitory axosomatic synapses on ventral horn neurons may be involved in the mechanisms which influence the well-established increase in motoneuronal excitability after spinal cord injury.

Animals↗

PubMed1995

Occurrence of transcranial Doppler high-intensity transient signals in patients with potential cardiac sources of embolism. A prospective study.

BACKGROUND AND PURPOSE: Cerebral emboli can be recognized by typical "high-intensity transient signals" (HITS) in the transcranial Doppler (TCD) spectral curves. Patients with potential cardiac sources of embolism are at higher risk for stroke. METHODS: We examined the frequency of HITS in the left middle cerebral artery (MCA) with TCD over periods of 30 minutes in 100 patients having potential cardiac sources of embolism, as indicated by transthoracic or transesophageal echocardiography. RESULTS: Thirty-six (36%) of the patients presented with HITS. Sex, age, sufficient anticoagulation level, antiplatelet therapy, neurological symptoms, and a history of thrombosis had no influence on the prevalence and number of HITS. The patients with a single echocardiographic diagnosis were separated into eight echocardiographically defined groups: patients with (1) atrial fibrillation, (2) coronary artery disease plus ejection fraction of more than 30% including at least three wall segments of hypokinesia/akinesia, (3) coronary artery disease with less than 30% ejection fraction, (4) dilated cardiomyopathy, (5) infectious endocarditis, (6) aortic stenosis, (7) mitral stenosis, and (8) patent foramen ovale. A significant difference in HITS occurrence could not be found in any of the defined groups. Only patients with infectious endocarditis showed a tendency for a higher HITS prevalence. CONCLUSIONS: HITS are common phenomena in patients with potential cardiac sources of embolism. The clinical relevance of these HITS remains unclear.

Adolescent↗

PubMed1993

B-50 (GAP-43) in the spinal cord caudal to hemisection: indication for lack of intraspinal sprouting in dorsal root axons.

Sprouting of dorsal root axons has been suggested to occur in the mature cat spinal cord caudal to a hemisection at a low thoracic level sparing the dorsal columns. The lesion interrupts supraspinal descending projections, while leaving ascending collaterals of dorsal root axons intact. This hypothesis was re-evaluated by comparing the light and electron microscopic immunoreactivity of B-50 (GAP-43) on both sides of the postulated target regions for sprouting, the intermediate gray and the dorsal horn. The neural-specific phosphoprotein B-50 is involved in regenerative and developmental axonal outgrowth and synaptic plasticity. The light microscopic distribution pattern and density of B-50 immunostaining, measured by quantitative densitometry, were bilaterally symmetrical in all segments below the hemisection 3.5, 8, 14, 21, and 56 days postoperatively, as they were in the intact animal. Ultrastructurally, growth cone-like profiles were not detectable during putative periods of sprouting in regions of interest. After removal of degenerated axon terminals, vacated postsynaptic places appeared to be covered by astrocytic processes. These results indicate that, under the present experimental conditions, sprouting of primary afferents in adult cats is unlikely to be involved in functional plasticity after removal of descending pathways.

Animals↗

PubMed1993

B-50 (GAP-43) in Onuf's nucleus of the adult cat.

The nucleus of Onuf in the sacral spinal cord contains motoneurons that innervate the pelvic floor muscles and possess somatic and autonomic characteristics. We show in this study that in the intact adult cat, the immunocytochemical labelling of the nervous tissue-specific growth-associated protein, B-50 (GAP-43), which persists in Onuf's nucleus, differs markedly from that in the remaining 'purely somatic' motor nuclei of the sacral spinal cord. At the light microscopic level, an intense B-50 (GAP-43) immunoreactivity (B-50-IR) in the neuropil of Onuf's nucleus contrasts with a faint staining in the other spinal motor nuclei. Ultrastructurally, B-50-IR is found in Onuf's nucleus within some unmyelinated small diameter nerve fibres and numerous axon terminals on dendritic and somatic surfaces. Conversely, in all other motor nuclei only a few of these structures are stained. No other cellular profiles show B-50-IR in the tissue examined. According to the proposed functions of B-50 (GAP-43), its persistence in mature spinal axon terminals may indicate a latent capability of functional and structural remodeling, as well as an involvement in long-term enhancement in synaptic transmission. If so, these properties would be considerably more pronounced in Onuf's nucleus as compared to purely somatic motor nuclei.

Animals↗

PubMed1993

Comparison of somatosensory evoked potentials with striatal glucose consumption measured by positron emission tomography in the early diagnosis of Huntington's disease.

Both somatosensory evoked potentials (SEP) and striatal glucose consumption (rCMRGlc) measured by positron emission tomography (PET) have been reported to be abnormal early in the course of Huntington's disease (HD). To compare their diagnostic value, SEP and rCMRGlc were measured in a group of 18 first degree off-spring of HD families: 6 had manifest HD with chorea and the remaining 12 individuals were chorea-free subjects at risk for HD. In five patients with manifest disease, both SEP and striatal rCMRGlc were significantly abnormal, defined in SEP as having either a bilaterally absent frontal N30 amplitude or a reduction of the parietal N20/P25 amplitude below 1 microV on at least one side; in PET as exhibiting a reduction of the cerebellar ratio (CR) of both caudate and lentiform rCMRGlc below the 99% confidence limits of these variables determined in 20 normal volunteers. The remaining patient with manifest HD had questionably abnormal SEP and significantly reduced indices of striatal rCMRGlc. The five persons at risk for HD who had normal SEP also had normal striatal rCMRGlc; those three at-risk patients with abnormal SEP also had a reduction of the CR of both caudate and lentiform rCMRGlc. Of the remaining four individuals at risk for HD who had questionably abnormal SEP, three had CR values of striatal rCMRGlc in the normal range and one a reduction of the CR of lentiform rCMRGlc. In at-risk patients, the SEP diagnosis correlated significantly with caudate (r = -0.8; p < 0.002) and lentiform (r = -0.76; p < 0.005) rCMRGlc. These data indicate a parallel deterioration of SEP and striatal rCMRGlc early in the course of HD even before the development of chorea.

Adult↗

PubMed1993

Remote microglial activation in the quinolinic acid model of Huntington's disease.

Intrastriatal injection of quinolinic acid (QA) in the rat leads to several structural and biochemical events which resemble neuropathological changes seen in the striatum of Huntington's disease patients. In the present experiment the accompanying microglial response in striatal projection areas following QA injection was studied immunocytochemically using monoclonal macrophage/microglial markers. After injection of 240 nmol of QA a marked microglial reaction was observed in the entire striatum, whereas injection of the same amount of solvent resulted only in a local microglial reaction around the injection site. Activated microglia were also found in the globus pallidus (GP), the entopeduncular nucleus (EP), the substantia nigra (SN), and the ventroanterior/ventrolateral, the ventromedial, and, in some rats, the reticular thalamic nucleus. The remote microglial reaction started in the first-order projection areas at Day 1 (GP) or Day 3 (EP, SN) and was found in the second-order projection areas (thalamic nuclei) by Day 5. Areas projecting to the striatum such as the amygdala and intralaminar thalamic nuclei remained free of activated microglia. It is concluded that a microglial response in striatal projection areas accompanies excitotoxic striatal injury. Anterograde degeneration of striatal projection neurons can explain the microglial activation in first-order projection areas but other mechanisms such as neuronal hyperexcitation following removal of inhibitory striatal input must be responsible for the rapid transsynaptic microglial activation seen in the thalamus.

Animals↗

PubMed1993

Immunocytochemistry of B-50 (GAP-43) in the spinal cord and in dorsal root ganglia of the adult cat.

The distribution of the neural-specific growth associated protein B-50 (GAP-43), which persists in the mature spinal cord and dorsal root ganglia, has been studied by light and electron microscopic immunohistochemistry in the cat. Throughout the spinal cord, B-50 immunoreactivity was seen confined to the neuropil, whereas neuronal cell bodies were unreactive. The most conspicuous immunostaining was observed in the dorsal horn, where it gradually decreased from superficial laminae (I-II) toward more ventral laminae (III-V), and in the central portion of the intermediate gray (mainly lamina X). In these regions, the labelling was localized within unmyelinated, small diameter nerve fibres and axon terminals. In the rest of the intermediate zone (laminae VI-VIII), B-50 immunoreactivity was virtually absent. The intermediolateral nucleus in the thoracic and cranial lumbar cord showed a circumscribed intense B-50 immunoreactivity brought about by the labelling of many axon terminals on preganglionic sympathetic neurons. In motor nuclei of the ventral horn (lamina IX), low levels of B-50 immunoreactivity were present in a few axon terminals on dendritic and somal profiles of motoneurons. In dorsal root ganglia, B-50 immunoreactivity was mainly localized in the cell bodies of small and medium-sized sensory neurons. The selective distribution of persisting B-50 immunoreactivity in the mature cat throughout sensory, motor, and autonomic areas of the spinal cord and in dorsal root ganglia suggests that B-50-positive systems retain in adult life the capacity for structural and functional plasticity.

Animals↗

PubMed1993

Absence of frontal somatosensory evoked potentials in Huntington's disease.

A fast route for transmission of deep and cutaneous afferent information to the frontal cortex is well established in non-human primates. Whether the incoming cortical information gives rise to early frontal somatosensory evoked potentials (SEPs) in humans is still a matter of contention. We attempted to solve this question by investigating the topography of SEP generators evoked by median nerve stimulation in 30 healthy subjects and in 30 patients suffering from Huntington's disease, who are known to have reduced SEP amplitudes. Using an earlobe reference, SEPs were recorded with an array of either five surface electrodes over the contralateral parietal cortex or 32 electrodes distributed over the whole scalp. In normal subjects analysis of frontal potentials revealed an early positive (P22) and negative (N30) component which could not be explained by generators located in the parietal cortex. Apart from the reduction of parietal components (N20, P25) frontal P22 and N30 were diminished or absent in Huntington's disease patients. Frontal potentials were even reduced in those patients who had parietal SEP amplitudes within the range of normal subjects. These frontal changes are similar to those reported in other basal ganglia disorders. Basal ganglia dysfunction might therefore be associated with changes of frontal SEP components.

Adult↗

PubMed1993

Changes in the short- and long-latency stretch reflex components of the triceps surae muscle during ischaemia in man.

1. In order to establish the afferent source responsible for the M1 and M2 stretch reflex components of the voluntarily activated human triceps surae muscle, mechanical reflex testing was applied before and during ischaemic blockade of the lower limb. This procedure is known to affect large, fast conducting afferent fibres earliest, specifically Ia afferents arising from muscle spindle afferents. 2. It was found that both the M1 and M2 components were eliminated at the same time, at a point when the P40 peak in the somatosensory evoked potential, produced from stimulation of fast conducting peripheral afferents, was also abolished. This evidence indicates that both reflex components are mediated by information carried by muscle spindle Ia afferents. 3. The M1 component was selectively increased in the early stages of ischaemia. The M2 response did not increase during this period, but showed a tendency to reduce in amplitude. This effect may arise as the result of increased recruitment of motor units in the M1 component reducing the number of units available for activation in the M2 response. 4. These results do not support the view that the M2 reflex component of the triceps surae muscle is mediated by secondary afferent information, but indicate, rather, that both the M1 and M2 components are mediated by Ia afferent information acting on spinal pathways.

Adult↗

PubMed1992

Abnormalities of somatosensory evoked potentials in the quinolinic acid model of Huntington's disease: evidence that basal ganglia modulate sensory cortical input.

Intrastriatal injection of quinolinic acid (QA) in rats provides an animal model that mimics some of the neuropathological and neurochemical alterations observed in the striatum of patients with Huntington's disease (HD). One of the very early neurophysiological signs in HD is a diminution of amplitude of early somatosensory evoked potentials (SEPs) recorded over the parietal cortex. The present study investigated whether the QA model exhibits similar neurophysiological abnormalities. Two weeks after unilateral intrastriatal injection of QA (240 nmol) or of the solvent, early SEPs were recorded with chronically implanted electrodes from the somatosensory cortex or from the ventrobasal nucleus of the thalamus of lightly pentobarbital-anesthetized rats, in response to single-shock electrical stimulation of the contralateral forepaw. Whereas intrastriatal injection of solvent did not influence SEPs, the striatal QA lesion significantly reduced the amplitude of early cortical SEPs by about 40% without affecting the latency. SEPs recorded from the ventrobasal nucleus were unchanged after QA lesion. Histological examination and glial fibrillary acid protein staining after intrastriatal injection of QA revealed no evidence for damage in the somatosensory system. It is concluded that (1) the QA animal model of HD mimics some of the SEP abnormalities of patients, and (2) a striatal lesion modulates somatosensory transmission to the cortex in rats.

Animals↗

PubMed1992

Contralateral early blink reflex in patients with facial nerve palsy: indication for synaptic reorganization in the facial nucleus during regeneration.

Fifty patients with Bell's palsy and 30 patients with etiologically different symptomatic peripheral facial nerve palsy were studied by means of electrically evoked blink reflexes 1-23 days after onset of paresis. Their results were compared with a normal control group of 30 healthy subjects. In a significant number of patients (64% in Bell's palsy and 53% in symptomatic facial nerve palsy) a contralateral early blink reflex response (R1) could be elicited upon stimulation of the normal side as compared to 13% in the control group. It is suggested that this result may be explained by synaptic reorganization of the facial nucleus leading to functional unmasking of pre-existing crossed trigemino-facial reflex pathways during regeneration. This view is in line with previous experimental data in animals on the time course of structural changes in the facial nucleus after lesioning of the ipsilateral facial nerve.

Adolescent↗

PubMed1992

Motor responses evoked by magnetic brain stimulation in Huntington's disease.

In 34 patients with manifest Huntington's disease (HD), and in 21 first-degree offspring without clinical signs or symptoms, the sizes, central motor latencies (CMLs) and variation in latencies of EMG responses (MEPs) following transcranial magnetic brain stimulation were studied in muscles of the upper and lower extremities. In subgroups of patients and their offspring median and tibial nerve somatosensory evoked potentials (SEPs) and electrically elicited long-loop reflexes (LLRs) in hand muscles were also investigated. Increased MEP thresholds were observed in 10% of the HD offspring, while CML, latency variability and MEP amplitudes always lay within normal range. In contrast, SEPs were abnormal in 33%. In HD patients MEPs were found to be abnormal in up to 72% of patients when all available response parameters were taken into consideration. MEP abnormalities correlated with the duration of motor symptoms and the severity of choreic motor activity. When both MEPs and SEPs were evaluated, abnormalities could be detected in 91% of all HD patients. We suggest that abnormal MEPs might reflect an altered excitability of the cortico-spinal system as a consequence of basal ganglia dysfunction, rather than a structural damage of the investigated descending pathways. To localize the pathological mechanism responsible for altered LLRs, a "loop analysis" was performed by recording LLRs, MEPs and SEPs in the same patients. Alterations of LLRs correlated best with abnormal SEPs and might therefore be explained by reduced somatosensory input to the motor cortex.

Adolescent↗

PubMed1991

Trends in the pathophysiology and pharmacotherapy of spasticity.

Spasticity develops after supraspinal or spinal lesions of descending motor systems, with obligate involvement of the corticospinal tract. Spasticity is characterized by an increase in muscle tone, which, in contrast to many other types of enhanced muscle tone, shows a marked velocity-dependent increase when the muscle is passively stretched. The pathophysiological mechanisms underlying this spastic muscle tone remain obscure. Three major causes are currently considered possible: (1) changes in the excitability of spinal interneurones; (2) receptor hypersensitivity; (3) formation of new synapses by sprouting. The latter mechanism could account for the long time course over which spastic muscle tone develops in hemiplegic or paraplegic patients, but there is no experimental evidence for this hypothesis. The electromyographic (EMG) gait analysis of patients with spasticity has thrown doubt on the common belief that the velocity-dependent increase in spastic muscle tone is evoked by stretch reflex activity and has led to the idea that spastic muscle tone resides in the muscle fibres themselves. While such a mechanism may contribute to the slowness of active movements in spastic patients, recent experiments on patients with spastic arm paresis have confirmed the classical view that the spastic muscle tone is related to the EMG activity evoked in the passively stretched muscle. This pathological EMG activity is seen during the entire range of the dynamic phase of the stretch, during which a normal muscle exhibits only an early, phasic burst at the highest stretch velocities employed. For the pharmacological treatment of spasticity, substances with different central or peripheral actions are available. Their assumed receptor actions are described, together with their main indications and side-effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Electromyography↗

PubMed1991

Language functions in progressive supranuclear palsy.

Language functions were studied in 6 patients with clinically diagnosed progressive supranuclear palsy who conformed to the characteristic pattern of 'subcortical dementia'. Dysarthria, reading difficulties and disturbances of handwriting were present in all patients. Some patients showed additional deficits including visual dyslexia, constructional dysgraphia and an increased rate of self-corrections and misnamings in object confrontation naming. In most instances, the naming errors referred to an object visually similar to the target object, suggesting that visual misperception is the major cause of the naming disorder. It is concluded that a variety of language impairments may develop secondary to other neurological and neuropsychological changes in progressive supranuclear palsy.

Aged↗

PubMed1991

Different mechanisms underlie the long-latency stretch reflex response of active human muscle at different joints.

1. Stretch of voluntarily activated human muscle results in a reflex response consisting of short-latency (M1) and delayed long-latency (M2) components. The mechanism of the M2 response remains the subject of controversy. The present study tested the universality of the hypothesis that the M2 response results from the transmission of low-threshold muscle afferent input travelling over a long-loop supraspinal pathway. Muscle reflex responses resulting from imposed stretch were obtained from the first dorsal interosseus (FDI), biceps brachii (BB), triceps brachii (TB) and triceps surae (TS) muscles. 2. Patients suffering from Huntington's disease (HD) show a selective loss of FDI-M2 responses, with sparing of the M1. This has been attributed to disruption of supraspinal pathways as a part of the disease pathology. Accordingly, HD has been used in the present study as a model to test the universality of the long-loop hypothesis: if this is so, then HD patients with an absent FDI M2 should also fail to show an M2 response in other muscles. 3. It is shown that a group of HD patients in whom the FDI-M2 response was absent or residual developed clear M2 responses in the TB, BB and TS muscles following stretch sufficient to invariably evoke this component in normal subjects. 4. It is thus concluded that longer-latency stretch reflex components are not invariably mediated over long-loop supraspinal pathways, but that this mode of control is dominant only in muscles, such as those of the hand, whose function depends largely on direct cortical control.

Adult↗

PubMed1991

Evidence that low-threshold muscle afferents evoke long-latency stretch reflexes in human hand muscles.

1. The aim of the present study was to identify the type of spinal afferents involved in the generation of the long-latency response in intrinsic human hand muscles. Position-controlled extensions were imposed on the index finger or on the wrist of healthy subjects who were exerting a steady voluntary flexion force at the relevant joint. Averaged surface electromyographic (EMG) responses of the first dorsal interosseus muscle (FDI) or of the wrist flexors were evaluated with respect to latency and size. 2. Small transient angular displacements of the index finger (1 degree, as measured at the metacarpophalangeal joint), which are supposed to excite primary rather than secondary afferents, evoked two clearly discernible EMG responses with mean latencies of 32.3 ms (M1 response) and 54.7 ms (M2 response), respectively. The size of the M2 response exceeded the size of the M1 response by 60%. In the wrist flexors, transient stretch (1 degree) gave rise to a large M1 response (latency 22.8 ms) and a small, inconstent M2 response. 3. Small-amplitude vibration of the index finger elicited EMG responses in the FDI that were qualitatively and quantitatively similar to those seen in response to small transient stretches of the index finger. This was also true for fast ramp-and-hold stretches (stretch velocity 400 degrees/s, amplitude 5 degrees), whereas slow ramp-and-hold stretches (125 degrees/s, 5 degrees) elicited predominantly M2 responses. 4. In the FDI, the mechanical threshold of the M1 and M2 response to the transient angular displacement was approximately 0.15 degrees, with a tendency for the M2 response to appear at a lower threshold.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗