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Biomedical subjects

C Crone

Publications and source records attributed to C Crone.

At least 19 recordsLinked to original sources
PubMed2004

Reciprocal inhibition and corticospinal transmission in the arm and leg in patients with autosomal dominant pure spastic paraparesis (ADPSP).

The pathophysiological mechanisms underlying the development of spasticity are not clear, but the excitability of the disynaptic reciprocal inhibitory pathway is affected in many patients with spasticity of different origin. Patients with genetically identified autosomal dominant pure spastic paraparesis (ADPSP) develop spasticity and paresis in the legs, but usually have no symptoms in the arms. Comparison of the spinal and supraspinal control of the legs and arms in these patients may therefore provide valuable information about the pathophysiology of spasticity. In the present study, we tested the hypothesis that one of the pathophysiological mechanisms of spasticity in these patients is abnormal corticospinal transmission and that this may lead to decreased reciprocal inhibition. Ten patients and 15 healthy age-matched control subjects were investigated. The patients were all spastic in the legs (with hyperactive tendon reflexes, increased muscle tone and Babinski sign), but had no neurological symptoms in the arms (except for one patient). Disynaptic reciprocal Ia inhibition of flexor carpi radialis (FCR) and soleus (SOL) motoneurons was measured (as the depression of the background FCR and SOL EMG activity and as the short latency inhibition of the FCR and SOL H-reflex evoked by radial and peroneal nerve stimulation). In addition, the latency of motor evoked potentials (MEPs) in the FCR muscle and the tibialis anterior (TA) muscle was measured. In the patients, the mean reciprocal inhibition was normal in the arms, while it was significantly decreased in the leg compared with the healthy subjects. In the patients, the average latency of MEPs in the FCR muscle was normal, while the latency to the MEP in TA muscle was significantly longer than that found in healthy subjects. Four patients, however, differed from the other patients by having significant reciprocal inhibition in the leg and a significantly shorter latency of TA MEPs than found in the other patients. The six patients without reciprocal inhibition in the leg instead had significant short latency facilitation of the SOL H-reflex and a longer TA MEP latency than seen in the healthy subjects and in the four patients with retained reciprocal inhibition. These findings support the hypothesis that disynaptic reciprocal inhibition and short latency facilitation are involved in the development of spasticity and, furthermore, they suggest a positive correlation between impairment of corticospinal transmission and decrease of reciprocal inhibition/appearance of reciprocal facilitation.

Adult↗
PubMed2003

Appearance of reciprocal facilitation of ankle extensors from ankle flexors in patients with stroke or spinal cord injury.

The purpose of the present study was to investigate the pathophysiological role of reciprocal facilitation between antagonistic motoneuron pools in spasticity. The soleus H-reflex was conditioned by prior stimulation of the peroneal nerve in 15 healthy subjects, six hemiplegic patients and 11 spinal cord injured (SCI) patients. The hemiplegic patients were tested from soon after the onset of hemiplegia and up to 2 years later. Whereas stimulation of the peroneal nerve produced short-latency inhibition of the soleus H-reflex in healthy subjects, it produced facilitation in spastic SCI and hemiplegic patients. This facilitation was demonstrated to have a low threshold compatible with activation of group I afferents and was most likely mediated by an oligosynaptic (reciprocal) excitatory pathway. The facilitation appeared in parallel with the development of hyperactive Achilles tendon reflexes, which was the only clinical finding that could be correlated positively with the facilitation. It is suggested that the appearance of reciprocal excitation plays a role in the pathophysiology of spasticity.

Achilles Tendon↗
PubMed2002

Corticospinal transmission to leg motoneurones in human subjects with deficient glycinergic inhibition.

Normal coordinated movement requires that the activity of antagonistic motoneurones may be depressed at appropriate times during the movement. Both glycinergic and GABAergic inhibitory mechanisms participate in this control. Patients with the major form of hyperekplexia (hereditary startle disease) have impaired inhibition of spinal motoneurones from local glycinergic interneurones and represent an ideal opportunity for studying the role of glycinergic inhibition in the control of antagonistic muscles. In the present study we investigated whether impaired glycinergic inhibition affects the corticospinal control of antagonistic spinal motoneurones in 10 patients with hyperekplexia and whether there are mechanisms that may compensate for the lack of glycinergic inhibition. In healthy subjects transcranial magnetic stimulation (TMS) produced a short-latency inhibition of the soleus H-reflex at rest and during tonic dorsiflexion. This inhibition, which has been shown to be mediated by spinal (glycinergic) inhibitory interneurones, was absent in all four patients in whom this experiment was performed. This confirms that glycinergic transmission is impaired in the patients. During voluntary dorsiflexion subthreshold TMS produced a depression of the ongoing EMG activity in the tibialis anterior (TA) muscle in both healthy subjects and all of the six tested patients. This is consistent with the idea that this EMG depression is caused by activation of cortical (GABAergic) inhibitory interneurones. Cross-correlation analysis revealed normal short-term synchronization of TA motor units accompanied by coherence in the 8-12 Hz and 18-35 Hz frequency bands in the 10 patients. As in healthy subjects, 8-12 Hz coherence accompanied by decreased tendency to discharge synchronously (de-synchronization) was found in recordings from the antagonistic TA and soleus muscles in 2 of the 10 patients. This suggests that glycinergic inhibition is not responsible for de-synchronization of antagonistic motor units, but that other GABAergic-inhibitory mechanisms must be involved. We propose that such mechanisms may compensate for the lack of glycinergic reciprocal inhibition in the hyperekplectic patients and explain why voluntary movements are not more severely affected.

Adult↗
PubMed2002

Neurophysiological studies in malignant disease with particular reference to involvement of peripheral nerves.

Neurological and neuromuscular disorders are frequent complications in patients with neoplasms and may involve the neuromuscular system, including motor and sensory nerve cell bodies, axons, myelin, neuromuscular transmission and muscle alone or in combination. Electrophysiological studies are of value in delineating the type, degree and extent of involvement, and may be of assistance in pointing towards the underlying cause: paraneoplastic factors, treatment with chemotherapy or radiation or metastatic infiltration. Though some electrophysiological features may be characteristic of certain syndromes, they rarely can stand alone but require clinical, pathological, radiological, and laboratory studies to obtain a diagnosis. Even in cases where such studies are obtained, a final diagnosis may only be ascertained during follow up, since the neuromuscular disorders frequently occur before the neoplasm is detected.

Animals↗
PubMed2001

Accumulation of cardiolipin and lysocardiolipin in fibroblasts from Tangier disease subjects.

Tangier disease (TD) is an inherited disorder of lipid metabolism characterized by very low high density lipoprotein (HDL) plasma levels, cellular cholesteryl ester accumulation and reduced cholesterol excretion in response to HDL apolipoproteins. Molecular defects in the ATP binding cassette transporter 1 (ABCA1) have recently been identified as the cause of TD. ABCA1 plays a key role in the translocation of cholesterol across the plasma membrane, and defective ABCA1 causes cholesterol storage in TD cells. Not only cholesterol efflux, but also phospholipid efflux was shown to be impaired in TD cells. By use of thin layer chromatography, high performance liquid chromatography and time-of-flight secondary ion mass spectrometry, we characterized the cellular phospholipid content in fibroblasts from three homozygous TD patients. The cellular content of the major phospholipids was not found to be significantly altered in TD fibroblasts. However, the two phospholipids cardiolipin and lysocardiolipin, which make up minute amounts in normal cells, were at least 3-5-fold enriched in fibroblasts from TD subjects. A structurally closely related phospholipid (lysobisphosphatidic acid) has recently been shown to be enriched in Niemann-Pick type C, another lipid storage disorder. Altogether these data may indicate that the role of these phospholipids is a regulatory one rather than that of a bulk mediator of cholesterol solubilization in sterol trafficking and efflux.

ATP Binding Cassette Transporter 1↗
PubMed2001

Patients with the major and minor form of hyperekplexia differ with regards to disynaptic reciprocal inhibition between ankle flexor and extensor muscles.

The aim of the present study was to investigate the contribution of reciprocal inhibition to muscle tone by examining the transmission in the reciprocal inhibitory pathway in patients with a known defect in the glycine receptor. The study was performed in eight patients with hereditary hyperekplexia, six with the major form and two with the minor form of the disease. A mutation in the alpha1-subunit of the glycine receptor had been demonstrated in the patients with the major form, whereas no mutation was seen in the patients with the minor form. Disynaptic reciprocal inhibition, which is presumed to be mediated by glycine, was not seen in the patients with the major form of the disease, while it could be evoked in the patients with the minor form of the disease. Presynaptic inhibition, which is presumed to be mediated by GABA, was seen in both types of patients. It is concluded that the major form of hereditary hyperekplexia is associated with impaired transmission in glycinergic reciprocal inhibitory pathways. The findings demonstrate the importance of reciprocal inhibition for the muscle tone in man, and it is suggested that the impaired reciprocal inhibition seen in patients with a defect in the glycine receptor may contribute to the increased muscle stiffness that is observed in these patients.

Adult↗
PubMed2001

Modulation of presynaptic inhibition and disynaptic reciprocal Ia inhibition during voluntary movement in spasticity.

The aim of the study was to investigate whether impaired control of transmission in spinal inhibitory pathways contributes to the functional disability of patients with spasticity. To this end, transmission in the pathways mediating disynaptic reciprocal Ia inhibition and presynaptic inhibition was investigated in 23 healthy subjects and 20 patients with spastic multiple sclerosis during ankle dorsiflexion and plantar flexion. In healthy subjects, but not in spastic patients, the soleus H reflex was depressed at the onset of dorsiflexion (300 ms rise time, 20% of maximal voluntary effort). At the onset of plantar flexion, the soleus H reflex was more facilitated in the healthy subjects than in the patients. The H reflex increased more with increasing level of tonic plantar flexion and decreased more with dorsiflexion in the healthy subjects than in the spastic patients. Transmission in the disynaptic Ia reciprocal inhibitory pathway from ankle dorsiflexors to plantar flexors was investigated by conditioning the soleus H reflex by previous stimulation of the common peroneal nerve (conditioning-test interval 2-3 ms; stimulation intensity 1.05 times the motor response threshold). At the onset of dorsiflexion, stimulation of the common peroneal nerve evoked a significantly larger inhibition than at rest in the healthy subjects but not in the spastic patients. At the onset of plantar flexion the inhibition decreased in the healthy subjects, but because only weak inhibition was observed at rest in the patients it was not possible to determine whether a similar decrease occurred in this group. There were no differences in the modulation of inhibition during tonic plantar flexion and dorsiflexion in the two populations. Presynaptic inhibition of Ia afferents terminating on soleus motor neurones was evaluated from the monosynaptic Ia facilitation of the soleus H reflex evoked by femoral nerve stimulation. Femoral nerve facilitation was decreased at the onset of dorsiflexion and increased at the onset of plantar flexion in the healthy subjects and patients, but the changes were significantly greater in the healthy subjects. There was no difference between the two populations in the modulation of presynaptic inhibition during tonic plantar flexion and dorsiflexion. It is suggested that the abnormal regulation of disynaptic reciprocal inhibition and presynaptic inhibition in patients with spasticity is responsible for the abnormal modulation of stretch reflexes in relation to voluntary movement in these patients. Lack of an increase in reciprocal inhibition and presynaptic inhibition at the onset of dorsiflexion may be responsible for the tendency to elicitation of unwanted stretch reflex activity and co-contraction of antagonistic muscles in patients with spasticity.

Adult↗
PubMed2000

The effect of baclofen on the transmission in spinal pathways in spastic multiple sclerosis patients.

OBJECTIVES: To measure the effect of baclofen on the transmission in different spinal pathways to soleus motoneurones in spastic multiple sclerosis patients. METHODS: Baclofen was administered orally in 14 and intrathecally in 8 patients. H(max)/M(max), presynaptic inhibition by biceps femoris tendon tap of femoral nerve stimulation, depression of the soleus H-reflex following previous activation of the Ia afferents from the soleus muscle (i.e. postactivation depression), disynaptic reciprocal Ia inhibition of the soleus H-reflex and the number of backpropagating action potentials in primary afferents, which may be a sign of presynaptic inhibition, were examined. RESULTS: Baclofen depressed the soleus H(max)/M(max) ratio significantly following oral and intrathecal baclofen. None of the two tests of presynaptic inhibition, or the postactivation depression or the disynaptic reciprocal Ia inhibition of the soleus H-reflex were affected by baclofen administration. Also the action potentials of the primary afferents were unchanged during baclofen administration. CONCLUSIONS: The antispastic effect of baclofen is not caused by an effect on the transmitter release from Ia afferents or on disynaptic reciprocal Ia inhibition. One possible explanation of the depression of the H-reflex by baclofen is suggested to be a direct depression of motoneuronal excitability.

Administration, Oral↗
PubMed1999

High expression of MHC I in the tibialis anterior muscle of a paraplegic patient.

A long-term paraplegic man presented exclusively (>99%) myosin heavy chain I (MHC I) in the tibialis anterior muscle (TA). This was coupled to a slow speed of contraction, a high resistance to fatigue, and a rapid resynthesis of phosphocreatine after an electrically evoked fatiguing contraction when compared with the TA muscles of 9 other paraplegic individuals. In contrast, the MHC composition of his vastus lateralis, gastrocnemius, and soleus muscles was that expected of a muscle from a spinal cord injured individual. This information may be of clinical importance in terms of the expected morphological and functional adaptations of skeletal muscle to different types of electrical stimulation therapy.

Electromyography↗
PubMed1999

Amplitude of the maximum motor response (Mmax) in human muscles typically decreases during the course of an experiment.

It was shown that the amplitude of the soleus Mmax and Hmax responses decreases in the course of long-lasting H-reflex studies. The peak-to-peak amplitudes of the Mmax and Hmax responses in the soleus muscle (and the Mmax in the tibialis anterior muscle and small hand muscles) were measured repeatedly for 1-3 h in 20 subjects. 3-5 Mmax responses and 5-10 Hmax responses were elicited about every 3 min while the subject was at rest. Decreases in the soleus Mmax response of up to 50.5% (mean 20.5% SEM 2.2) and of the soleus Hmax of up to 49.7% (mean 19.1% SEM 3.7) in relation to the amplitudes measured at the beginning of the experiment were seen in 17 subjects. In 3 subjects no Mmax amplitude decrease was seen. The maximum decrease was reached between 10 and 100 min (mean 44.2 min SEM 4.3). An Mmax amplitude decrease was also seen in the tibialis anterior muscle and in two small hand muscles. In some subjects the decrease of the Mmax response seemed to be initiated by the infrequent supramaximal stimulations. The possible causes for this amplitude reduction, as well as the methodological consequences of these findings for H-reflex studies and fatigue studies, are briefly discussed.

Action Potentials↗
PubMed1998

[Diagnosis of polyneuropathies].

The accurate diagnosis of peripheral neuropathy is important with respect to the therapeutic possibilities and limitations, which are especially relevant in immune-mediated polyneuropathies. These polyneuropathies may be axonal or demyelinating and have an acute or chronic course, and they may be difficult to distinguish from non-treatable neuropathies on clinical grounds. Efforts have been made to establish clinical, neurophysiological, morphological, biochemical, immunological and molecular biological criteria to attain specific diagnosis. This has shown heterogeneity not only within the treatable neuropathies, which may have implications for the treatment. It has also been shown that hereditary or diabetic polyneuropathy may have features which respond to immunosuppressive treatment. Molecular biology studies have revealed markers for the diagnosis of hereditary neuropathy, and have in some instances also delineated the gene product.

Axons↗
PubMed1995

Central control of reciprocal inhibition during fictive dorsiflexion in man.

The size of the soleus Hoffmann reflex (H-reflex) was measured in six healthy human subjects before and after transmission in the common peroneal nerve (CPN) was blocked reversibly by local injection of lidocaine. It was found that the H-reflex at rest increased after the block. When the subjects attempted to perform a dorsiflexion while the CPN was blocked ("fictive dorsi flexion"), the soleus H-reflex was strongly depressed. Stimulation of the CPN proximal to the block elicited a short-latency inhibition of the soleus H-reflex, which was probably mediated by reciprocal Ia interneurones. This inhibition never increased during dorsiflexion relative to rest prior to the CPN block, but after the block a significant increase in inhibition was seen during fictive dorsiflexion in three subjects. Stimulation of the femoral nerve (FN) elicited a short-latency monosynaptic Ia facilitation of the soleus H-reflex. This facilitation was found to decrease during dorsiflexion relative to rest before the block as well as during fictive dorsiflexion after the block. The decrease in the H-reflex during fictive dorsiflexion demonstrates that although an increased Ia-afferent feedback via the gamma-loop may contribute to reciprocal inhibition when transmission in the CPN is intact, a noticeable, centrally mediated inhibition may occur in the absence of this feedback. It is suggested that this inhibition is caused by central facilitation of interneurones mediating disynaptic Ia inhibition as well as interneurones mediating presynaptic inhibition of Ia afferents.

Adult↗
PubMed1995

Changes in transmission across synapses of Ia afferents in spastic patients.

The transmission across synapses of Ia afferents on spinal motor neurons was investigated in 30 healthy subjects and 25 spastic multiple sclerosis patients. Slow passive stretch (17 degrees/s of the soleus muscle evoked a pronounced depression of the soleus Hoffmann reflex (H-reflex) lasting for more than 10 s in the healthy subjects. This depression was less pronounced and had a shorter duration in the spastic patients. A tap applied to the biceps femoris tendon also produced an inhibition of the soleus H-reflex, which was larger in the healthy subjects than in the spastic patients. This inhibition only lasted for 300-400 ms. Finally, stimulation of the femoral nerve (FN) produced a facilitation of the soleus H-reflex, which was larger in the spastic patients than in the healthy subjects. The inhibition of the H-reflex evoked by the biceps femoris tendon tap is known to be caused by presynaptic inhibition of the Ia afferents, which mediate the reflex. The facilitation of the soleus H-reflex produced by FN stimulation has also been shown to be influenced by changes in presynaptic inhibition. The increased facilitation from the FN and the decreased inhibition from the biceps femoris tendon tap onto the soleus H-reflex in spastic patients are thus both compatible with a deficient presynaptic inhibition in these subjects. The long lasting depression of the reflex evoked by a previous slow stretch of the soleus muscle is most likely caused by a decrease of the probability of transmitter release from the Ia afferents. The decrease of this depression in spastic patients suggests that mechanisms other than presynaptic inhibition may contribute to changes in the efficiency of transmission across the synapses of Ia afferents in spastic patients and thus contribute to the exaggeration of stretch reflexes seen in these patients.

Adult↗
PubMed1994

Disynaptic reciprocal inhibition of ankle extensors in spastic patients.

The soleus Hoffmann-reflex (H-reflex) was conditioned by a preceding stimulation of the common peroneal nerve in 74 healthy control subjects and 39 patients with spasticity in the lower extremities due to multiple sclerosis. At a conditioning-test interval of 1-3 ms a decrease of the size of the soleus H-reflex was seen in the healthy subjects. The decrease was most likely caused by disynaptic reciprocal Ia inhibition (Crone et al., 1987). In the spastic patients a similar short-latency inhibition was rarely seen. On the contrary, in several patients a facilitation was seen at a conditioning-test interval of 3-4 ms. A short-latency inhibition as pronounced as in healthy subjects was seen in four patients. These four patients did not differ from the other patients regarding the degree of spasticity or any other clinical parameter. However, they all used an external peroneal nerve stimulator daily as a walking aid. It is suggested that the lack of short-latency reciprocal inhibition reflects a deficient control of the interneurons which mediate this inhibitory spinal mechanism between antagonistic muscles in man. This might contribute to the pathophysiology of spasticity and it might be related to the frequent occurrence of co-contraction of functionally antagonistic muscles during gait in spastic patients. The existence of a pronounced reciprocal inhibition in patients receiving frequent stimulation of the peroneal nerve may suggest that regular activation of peripheral nerves is of importance for the maintenance of the activity in spinal pathways.

Adult↗
PubMed1994

Central control of disynaptic reciprocal inhibition in humans.

The disynaptic pathway from muscle spindle Ia afferents to motoneurones of the antagonist muscle is one of the best studied pathways in the spinal cord. Early animal studies--mainly in the cat--have provided a detailed knowledge of the pathway itself and of the integration of segmental and supraspinal convergence at the interneuronal level. Although this knowledge was used to formulate hypotheses on the function of the pathway during natural movements, the reduced animal preparation limited the possibilities of testing these ideas. However, such information has more recently been obtained from human subjects by using indirect electrophysiological techniques. In most of these experiments the disynaptic Ia inhibition was demonstrated as a short-latency depression of a monosynaptic test reflex (H-reflex) following a conditioning stimulation of the antagonist nerve. Changes in the size of this depression during voluntary tasks were then taken as evidence of a central regulation of the pathway. It has for example been demonstrated in this way that the brain regulates the Ia inhibitory interneurones in parallel with their corresponding motoneurones during extension-flexion movements, but not during co-contraction of antagonistic muscles. The importance of the central control of the pathway has also been emphasized by the finding of a disordered regulation of its activity in patients with lesions of the brain. This may possibly contribute to the inappropriate co-contraction of antagonistic muscles observed in some of these patients. It seems reasonable to expect that this kind of experiment in the future may contribute significantly to the knowledge of the central control of spinal motor mechanisms.

Humans↗
PubMed1993

H-reflexes are smaller in dancers from The Royal Danish Ballet than in well-trained athletes.

The size of the maximal H-reflex (Hmax) was measured at rest and expressed as a percentage of the maximal M-response (Mmax) in 17 untrained subjects, 27 moderately trained subjects, 19 well-trained subjects and 7 dancers from the Royal Danish Ballet. The Hmax/Mmax was significantly larger in the moderately and well-trained subjects than in the untrained subjects but smaller in the ballet dancers. It is therefore suggested that both the amount and the type of habitual activity may influence the excitability of spinal reflexes.

Adolescent↗