Quantitative evaluation of cerebellar ataxia based on pathological patterns of the muscle activities.

Quantitative evaluation of cerebellar ataxia is crucial for precise evaluation of cerebellar diseases. In particular, it is essential to capture anomaly of the causal motor commands as well as the resultant movement for the ataxia. In this paper, we propose a new method to make a quantitative evaluation of the cerebellar ataxia based on EMG signals. As an experimental task, we asked subjects to perform step-tracking wrist movements with a manipulandum, and recorded wrist joint movements and muscle activities of four wrist prime movers with surface electrodes. The subjects included fourteen patients with cerebellar diseases and thirteen normal controls. We succeeded to extract two parameters from the EMG signals of the four wrist prime movers, which characterize the pathological patterns of muscle activities for the cerebellar ataxia, Total Co-contraction Level (TCL) and Directionality of Muscle Activity (DMA). We found that the two parameters were useful to characterize pathological patterns of muscle activities in cerebellar ataxia. Consequently, it is expected that our proposed method is useful not only in tracking condition of cerebellar patients but also in evaluating the effects of a treatment or neuro-rehabilitation aiming at the normalization of motor commands.

Fixation-sensitive myoclonus in Lafora disease.

The authors report a patient with Lafora disease, whose myoclonus was suppressed by passive eye closure. Neurophysiologic studies disclosed that fixation was the most important enhancer of myoclonus. Magnetoencephalographic studies of visual evoked fields revealed abnormal activation of the visual corticocortical pathway via the insular cortex not seen in controls. The authors hypothesize that abnormal activation of the insular cortex may be involved in triggering the mechanism of fixation-sensitive myoclonus.

Post-activation depression of the soleus H-reflex in stroke patients.

PURPOSE: We examined post-activation depression in 35 stroke patients and 10 healthy subjects, and investigated whether their clinical symptoms were correlated to post-activation depression. METHODS: Post-activation depression of the soleus H-reflex evoked by electrical stimulation of the common peroneal nerve with supramaximal intensity of motor response on the tibialis anterior muscle. RESULTS: Post-activation depression was decreased on the affected side of the stroke patients. There was a significant difference between the affected and unaffected sides of the patients with post-activation depression, but no difference between the unaffected sides of the patients and healthy subjects. The presence of ankle clonus and the decrease in post-activation depression were correlated. CONCLUSION: Decreased post-activation depression in stroke patients suggests that a mechanism other than postsynaptic inhibition, such as reciprocal Ia inhibition and Ib inhibition, and presynaptic inhibition, may contribute to the exaggerated stretch reflexes, in particular, the manifestation of clonus.

[A case of Guillain-Barré syndrome (GBS) following human parvovirus B19 infection].

Human parvovirus B19 (HPV-B19) infection is recently known to produce variable clinical manifestations, but neurological disorder associated with this infection is uncommon. We reported a case of GBS associated with transient lupus-like status following HPV-B19 infection. This is the first report describing an adult case of GBS following HPV-B19 infection. A healthy female, aged 33, developed erythema infectiosum simultaneously with her 5-year-old daughter. On the same day, she noticed leg fatigue, which worsened in the following days. On the day 11th, she became unable to walk. Mild pancytopenia, liver injury, proteinuria, hypocomplementemia, and increased anti-nuclear antibody (ANA) were revealed at a hospital. Polymerase chain reaction detected HPV-B19 DNA in the serum. On the day 17th, she was admitted to our hospital because of moderate generalized weakness and mild sensory disturbance, which were symmetrical and distal-dominant. The deep tendon reflexes were absent. Analysis of cerebrospinal fluid showed albuminocytologic dissociation. Other laboratory data were normal except positive ANA. Enzyme-linked immunosorbent assay (ELISA) showed high titer of the serum IgM antibody to GM1 and GD1b. Serum anti HPV-B19 IgM and IgG tested by ELISA were also positive. She improved gradually after 2 courses of double filtrated plasma pheresis.

Reassessment of H-reflex recovery curve using the double stimulation procedure.

We conducted two types of experiments to assess the validity of the H-reflex recovery test, using double stimulation to test soleus motoneuron pool excitability in healthy and spastic subjects. One type dealt with the mechanical effect of the conditioning H reflex on the ankle joint; the other type with the effect of change in reflex size. The mechanical effect was tested both with the ankle joint fixed (FX) and free to move (FR). Differences between FX and FR conditions commenced with relaxation of soleus muscle contraction by the conditioning H reflex. In the FR condition, abrupt facilitation occurred, and changed to marked depression. We conclude that specific facilitation and inhibition in the FR condition were secondary effects of group Ia inflows caused by the ankle extensor muscle stretching on relaxation. In some spastic patients as well as in controls, facilitation due to the mechanical effect in the FR condition was observed despite the FX condition. The effects of systematic changes on soleus H-reflex size were investigated at conditioning-test intervals of 80 ms, so as to avoid mechanical effects. When conditioning and test reflexes were the same size, the amount of recovery increased as the H-reflex size increased. Comparison of the relation between amount of recovery and H-reflex size, expressed as a percentage of Mmax, showed no significant difference between the two groups. We speculate that the stronger recovery of spasticity mentioned in previous literature may have resulted from the fact that relatively greater H reflexes were tested in those studies. In conclusion, the present study indicates that double stimulation is not appropriate for assessing spinal motoneuron pool "excitability increase" in spasticity.

Discharge of muscle afferents during voluntary co-contraction of antagonistic ankle muscles in man.

The discharge of 38 tibialis anterior (TA) muscle spindle endings was recorded at rest and during isometric voluntary contraction of the ankle joint in eight healthy human subjects. With the ankle joint in 110 degrees plantarflexion, 24 endings (61%) were tonically active in the resting subject. During weak voluntary dorsiflexion, seven additional endings were activated, so that a total of 31 endings were active (82%). 24 of these were either newly recruited or discharged at a faster rate than at rest (average discharge rate 6.6 Hz at rest, 9.7 Hz during contraction). At matched levels of TA EMG, one ending was newly recruited and 10 were more active during co-contraction of dorsi and plantar flexors than during isolated dorsiflexion. 26 endings were equally active during the two tasks and one ending decreased its firing rate with co-contraction. Four of the 11 endings, which had a higher discharge rate during co-contraction than during dorsiflexion, discharged faster during plantarflexion than at rest although slower than during co-contraction. Plantarflexion had no effect on the discharge of three endings. The remaining four endings were not investigated during plantarflexion. It is suggested that the increased discharge rate of muscle endings during co-contraction is caused either by small changes in the length of the TA muscle or by a disproportionately high fusimotor drive during co-contraction.

[A 64-year-old man with recurrent blurred vision and an abdominal mass].

We report a 64-year-old man with recurrent bouts of blurred vision who died after developing an abdominal mass. He was well until June of 1985 when he was 59-years-old when he had an acute onset of loss of vision in his right eye. He was treated by prednisolone with a complete remission. In August of 1986, he had another bout of blurring of vision in his left eye. Once he lost his left vision completely, from which he showed slow recovery. In January of 1987, he developed blurring of his right eye and loss of pain and touch sensation in his right leg. Since then he repeated loss of vision in his right or left eye five times, and he was admitted to our hospital in May of 1990. On admission, he was alert and oriented. General physical examination was unremarkable. Neurologic examination revealed bilateral optic nerve atrophy. He could not discriminate light or dark by either eye. Other cranial nerves were unremarkable. He could walk in a wide-base only with support; spasticity was noted in his left leg. Muscle strength was preserved. Deep reflexes were exaggerated in both legs with extensor plantar reflex bilaterally. Pain and touch sensation was decreased in the left leg by 30%, and vibration was diminished in both feet. Position sense was preserved. Routine blood counts and chemistries were unremarkable. Cranial MRI scans revealed multiple high-signal intensity lesions in both pontine bases, basal ganglia, thalami, and in the deep cerebral white matters. He was treated with oral prednisolone, plasmapheresis, lymphocytapheresis, and then immuran. His vision showed only slight recovery to discriminate light and dark. In October of 1990, slight weakness appeared in his both legs. In December of that year, he developed nausea, and a fiber colonoscopic study revealed a stenosis in the transverse colon. In March of 1991, he developed anemia and liver dysfunction. In July of that year, jaundice appeared, and his serum bilirubin was increased. In October, his leg weakness became more prominent, and his cranial CT scans at that time revealed a low density change in the right cerebellum in the right superior cerebellar artery territory; in addition, multiple low density spots were scattered to be seen in both cerebral hemispheres including the basal ganglia and thalamic areas with ventricular dilatation and cortical atrophy.(ABSTRACT TRUNCATED AT 400 WORDS)

Segmental reflexes and ankle joint stiffness during co-contraction of antagonistic ankle muscles in man.

The size of soleus H-reflexes and short-latency stretch reflexes was measured at different levels of plantar flexion or co-contraction (simultaneous activation of dorsi- and plantar flexors) in seven healthy subjects. In four of seven subjects the short-latency stretch reflex was smaller during weak co-contraction than during isolated plantar flexion at matched background electromyogram (EMG) levels in the soleus muscle. In three of these four subjects the stretch reflex was larger during strong co-contraction than during plantar flexion, whereas it had the same size during the two tasks in the last subject. In the remaining subjects the stretch reflex either had the same size or was larger at all levels of co-contraction than at similar levels of plantar flexion. In contrast, the H-reflex was found to decrease with co-contraction at all contraction levels in all subjects. The decrease in the reflexes during weak co-contraction might be caused by presynaptic inhibition of Ia afferents. It is unclear why only the H-reflex decreased during strong co-contraction. The stiffness of the ankle joint was measured from the torque increment following the stretch of the plantar flexors divided by the stretch amplitude. In all subjects the total stiffness of the ankle joint was larger during strong co-contraction than during plantar flexion of similar strength. The stiffness was smaller during weak co-contraction than during weak plantar flexion in three out of seven subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Synchronization of human leg motor units during co-contraction in man.

Cross-correlograms were constructed from the spike trains of pairs of individual motor units recorded from the tibialis anterior (TA) and soleus (Sol) muscles. In most correlograms the synchronization consisted of a central peak with a short duration. When the motor units were recorded from the same muscle this synchronization was seen in almost 100% of the cases (TA 92%, Sol 89%) and the peak of synchronization was large (TA 0.060 extra sample spikes per trigger spike, Sol 0.030). In contrast, clear peaks of short duration synchronization was seen in only 4 out of 30 antagonistic TA and Sol motor unit pairs (0.025 extra sample spikes per trigger spike). In another 4 motor unit pairs central troughs were seen. In approximately 10% of all combinations of motor unit pairs a low-amplitude long-duration synchronization was seen. This type of synchronization was seen either as the only type of synchronization or at the same time as the short-duration synchronization. Finally, secondary peaks on both sides of the central peak were seen in a few cases. The distance between the sites of recording of TA motor unit pairs was systematically varied. The latency of the short-duration synchronization became longer and the amount of synchronization smaller the longer the distance between the recording sites. The amount of synchronization of two motor units recorded from the same muscle was shown to be larger when the muscle was activated in co-contraction rather than in an isolated agonist movement. The results are discussed in relation to the organization of the descending command eliciting co-contraction.

The regulation of presynaptic inhibition during co-contraction of antagonistic muscles in man.

1. The size of the soleus, tibialis anterior and medial gastrocnemius H reflexes were measured at different levels of EMG activity in ankle plantar- and dorsiflexors. At similar levels of EMG activity in the agonist muscle, the soleus and tibials anterior H reflexes were found to be smaller during co-contraction than during an isolated agonist contraction. In contrast to this, the medial gastrocnemius H reflex had the same size during co-contraction as during an isolated plantarflexion at comparable EMG levels. 2. Peaks occurred at monosynaptic reflex latency in the post-stimulus time histogram (PSTH) of firing of soleus and tibialis anterior motor units following stimulation of their respective motor nerves. These homonymous Ia peaks were found to be smaller during co-contraction than during isolated agonist contraction, whereas that of medial gastrocnemius motor units was unchanged. As the monosynaptic peak in the PSTH may give an indirect measure of the size of the monosynaptic EPSP in the motoneurone, it is suggested that these findings reflect a differential control of presynaptic inhibition of soleus and tibialis anterior motor units with respect to medial gastrocnemius motor units. 3. The monosynaptic Ia facilitation of the soleus H reflex evoked by a stimulation of the femoral nerve, was also found to be smaller during co-contraction of tibials anterior and soleus than during isolated plantarflexion. This suggests that presynaptic inhibition of heteronymous Ia fibres from the quadriceps muscle projecting to soleus motoneurones is regulated in the same way as presynaptic inhibition of homonymous Ia fibres during co-contraction. 4. The femoral nerve-induced monosynaptic facilitation of the soleus H reflex was found to decrease with increasing tonic levels of both co-contraction and isolated dorsi- and plantarflexion. The amount of facilitation decreased to the same degree with increasing levels of dorsiflexion and co-contraction. For the same level of EMG in the dorsiflexors there was thus no difference in the amount of facilitation whether the dorsiflexors were activated separately or in a co-contraction. 5. Whereas the soleus H reflex increased in size 50 ms prior to the onset of a dynamic plantarflexion, it did not change prior to the onset of a co-contraction. The femoral nerve-induced facilitation increased prior to the plantarflexion, but decreased prior to the co-contraction.(ABSTRACT TRUNCATED AT 400 WORDS)

Differential projection of the sural nerve to early and late recruited human tibialis anterior motor units: change of recruitment gain.

The effect of a stimulation of the cutaneous sural nerve [three shocks, 2.5 x perception threshold (PT)] was studied on the tibialis anterior (TA) H-reflex and single voluntarily activated TA motor units using post-stimulus time histograms (PSTH). In both cases, when studying only the first recruited motor units, an inhibition with a delay of 10 ms, in relation to the monosynaptic latency of Ia afferents in the common peroneal nerve, was observed. This inhibition had a duration of 10-20 ms. The inhibition was evoked by low-threshold cutaneous fibres, since it could be seen at a stimulation strength close to the perception threshold. The central delay of the inhibition was calculated in two subjects to be 1.8 ms and 1.2 ms respectively. The TA motor units were characterized by their recruitment threshold and minimal firing frequency and the effect of the sural nerve stimulation was subsequently investigated. Early recruited low frequency motor units were found to be inhibited, whereas later recruited motor units with a higher minimal firing frequency were facilitated. Similarly small TA H-reflexes were inhibited, whereas large reflexes were facilitated. This difference in the effect of the sural nerve stimulation was not caused by a difference in the descending command, since the same early recruited motor unit was still inhibited when firing at a high frequency and at a high torque level. Stimulation of the femoral nerve was found to produce a monosynaptic facilitation of the TA H-reflex and a heteronymous monosynaptic peak in the PSTH of single motor units. A stimulation of the sural nerve increased the size of the reflex facilitation, but had no effect on the size of the monosynaptic peak in the PSTH of the single motor units. It is concluded that the effect of the sural nerve stimulation on human TA motor units is similar to observations in the cat and that a similar interneuronal system may be responsible. It is furthermore suggested that the sural nerve stimulation increases the recruitment gain of the TA motoneuronal pool.

The regulation of disynaptic reciprocal Ia inhibition during co-contraction of antagonistic muscles in man.

1. The disynaptic reciprocal inhibition from ankle dorsiflexors to ankle plantarflexors was investigated at rest, during tonic plantar- and dorsiflexion and during co-contraction. In relation to rest, it was found to be decreased during plantarflexion and co-contraction, but unchanged during dorsiflexion. 2. When increasing the strength of plantarflexion the amount of inhibition became progressively smaller. Already during weak co-contraction, the amount of inhibition was very small and it did not become smaller during stronger contraction. The decrease of inhibition during co-contraction could not be explained by an addition of the changes of inhibition observed during plantar- and dorsiflexion individually. 3. The disynaptic reciprocal inhibition was also found to be decreased when the peripheral feedback from the muscles was blocked by inducing ischaemia in the leg and at the beginning of a dynamic co-contraction before sensory feedback could interfere. This implies that the observed decrease is caused by a central inhibition of the transmission in the pathway. 4. The amount of disynaptic reciprocal inhibition was also investigated during standing. No significant difference in the amount of inhibition was found when the subjects were standing up at rest as compared to sitting down at rest. When the subjects were forced to make a co-contraction in order to maintain balance, i.e. when they were standing on one leg, leaning backwards or standing on an unstable platform, a decrease of disynaptic reciprocal inhibition was seen. When the subjects leaned forward, thus forcing a contraction of the soleus muscle, a decrease was also seen, but it was smaller than in the co-contraction tasks. Finally, when the subjects lifted the examined leg, thus contracting the tibialis anterior muscle, either no change or a small increase of inhibition was seen. 5. A similar control of the disynaptic reciprocal inhibition as described for the pathway from ankle dorsiflexors to ankle plantarflexors was also observed for the pathway from ankle plantarflexors to dorsiflexors and from wrist extensors to wrist flexors. 6. It is concluded that when co-contraction is used in order to stabilize a joint, i.e. to maintain posture, a specific co-contraction motor programme is activated that depresses the transmission in the disynaptic reciprocal pathway thereby ensuring a high excitability level in the motoneurones of both antagonistic muscles.

Facilitation of agonist motoneurons upon initiation of rapid and slow voluntary movements in man.

The time course of facilitation of the agonist motoneurons upon initiation of voluntary ankle dorsiflexion was investigated in eight healthy subjects. The H-reflex and visually guided tracking methods were used for testing the excitability of the motoneuron pool and for controlling the initiation of movement as well as speed and force. Since the onset of voluntary EMG activity (EMG reaction time: EMGvRT) was delayed and/or obscured by test H-reflexes which were evoked very close to the behavioral responses, the subject was instructed to make response movements bilaterally, and EMGvRT was measured on the side without stimulation. In every subject, the EMGvRT was invariably longer in the ramp movement than in the step movement. The onset of H-reflex facilitation prior to EMG onset, which was regarded as indicating the arrival time of the descending motor command to the motoneuron pool, always started earlier in the ramp movement than in the step movement. The difference in facilitation onset between the two tasks was smaller than that in EMGvRT. Since the amplitude of the H-reflex at the onset of the voluntary EMG was equivalent in both movements, the development of H-reflex towards the behavioral EMG onset was more gradual in the ramp movement than in the step movement. The present results demonstrate that the longer reaction time in the slow ramp task depends on 2 factors: delay in the arrival of descending facilitatory impulses to the agonist motoneuron pool, and its slow recruitment thereafter.

Nicotine-sensitive paresis.

Immediately after a patient with myoclonus epilepsy smoked a nicotine-containing cigarette, tetraparesis and hyperreflexia with ankle clonus developed, but disappeared within several minutes. During paresis, the H-reflex size of the soleus muscle increased, EEG showed more slow waves than before smoking, and the cerebral perfusion increased around the motor cortex as shown by single photon emission CT. A similar effect occurred when the patient chewed nicotine gum, and smoking a cigarette with a high nicotine content induced severe positive and negative myoclonus after the development of tetraparesis. Administration of the C6-type nicotinic antagonist mecamylamine not only countered the smoking effect, but ameliorated the spontaneous positive and negative myoclonus. Mecamylamine may prove useful for the treatment of positive and negative myoclonus in myoclonus epilepsy.

Central facilitation of Ia inhibition during tonic ankle dorsiflexion revealed after blockade of peripheral feedback.

Recent studies have reported that no increase of the disynaptic reciprocal inhibition can be observed during tonic voluntary dorsiflexion of the foot as compared to rest, when the size of the control H-reflex is kept constant. Other studies have, however, shown that a voluntary contraction evokes a strong and long-lasting depression of the synaptic transmission from Ia afferents to motoneurones, most likely secondary to activation of these afferents during the contraction (post-activation depression). It was thought that this effect could also interfere with the demonstration of a central facilitation of the reciprocal inhibition during movement. The amount of disynaptic Ia reciprocal inhibition from the pretibial flexors to the soleus H-reflex was therefore estimated in normal human subjects at rest and during voluntary tonic dorsiflexion before, during and after blocking the peripheral feedback from the investigated muscles. It was observed that the reciprocal inhibition measured during dorsiflexion increased during occlusion of the blood supply to the leg, reaching a maximum of inhibition after 30 min of ischaemia. After release of the ischaemia the inhibition gradually decreased to its pre-ischaemic level. It is therefore suggested that the brain facilitates transmission in the Ia disynaptic reciprocal pathway during tonic voluntary dorsiflexion of the foot, but that this facilitation is normally not observed due to a post-activation depression following the peripheral feedback activation during the movement.

Disorder in reciprocal innervation upon initiation of voluntary movement in patients with Parkinson's disease.

Reciprocal innervation of the soleus motoneurones upon initiation of voluntary ankle dorsiflexion was investigated in eight patients with Parkinson's disease. H-reflex and visually guided step tracking methods were used for testing motoneurone excitability and for controlling the timing of movement initiation, respectively. While reciprocal inhibition appeared almost simultaneously with the agonist electromyographic (EMG) onset in normal subjects (Kagamihara and Tanaka 1985), facilitation appeared in the majority of patients under the same onset condition. It increased slowly, reaching a maximum at about 100 ms after the EMG onset. It then subsided slowly at around 200-300 ms, and was replaced thereafter by an inhibitory effect. No coactivation of the soleus muscle was detected electromyographically. The facilitation between the EMG onset and the onset of mechanical contraction was attributed to the direct effect of the descending command from the brain, suggesting a certain disorder in controlling the system for reciprocal innervation.

The effect of L-threo-DOPS on synaptic transmission to soleus motoneuron in normal subjects and patients with Parkinson's disease.

The effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) on synaptic transmission to the soleus motoneurons was studied using the H-reflex method in 12 normal subjects and in 4 patients with Parkinson's disease. A long-lasting depression of the test H-reflex, which was evoked by a conditioning group I volley in the homonymous tibial nerve with an onset latency of ca. 30 ms and a duration of more than 1 s and was regarded to represent the transmitter depletion caused by a preceding volley, diminished significantly after the oral administration of L-threo-DOPS both in the normal subjects and in the patients. On the other hand, no change was recognized in the slow depression which was caused by a group I volley of the heteronymous common peroneal nerve and was regarded as the presynaptic inhibition. The findings suggest that L-threo-DOPS influences the reduction of transmitter depletion.

Reciprocal inhibition upon initiation of voluntary movement.

Phasic changes in reciprocal inhibition of the soleus motoneurons upon initiation of active ankle dorsiflexion was investigated in normal man. H-reflex and reaction time methods were combined. Two phases of reciprocal inhibition were observed. The first inhibition appeared almost simultaneously with the activity of agonist EMG but was so weak as to be cancelled with a strong test stimulus or a slight stretch of the test muscle. The second inhibition developed 100 ms after EMG onset, in the early stage of dynamic contraction, and was strong. These inhibitions increased as the voluntary effort was strengthened. The neural mechanism of these inhibitions is discussed.