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Dental disease is more extensive in adults with chronic kidney disease, but whether dental health and behaviors are associated with survival in the setting of hemodialysis is unknown.

Summary.: In thirty patients with idiopathic Parkinson's disease (PD) we examined in a prospectively designed study the effect on motor performance and cognitive functions of amantadine sulphate, applied intravenously over a period of 14 days. Prior to the introduction of amantadine and post infusionem the motor function was measured by the Unified Parkinson Disease Rating Scale (UPDRS) and the Motor Performance Test Series (MPS); the simple and the choice reaction time were assessed using the Vienna Reaction Unit (VRU). The primary endpoint of efficacy was the change in the UPDRS part III (motor examination) after 14 days of amantadine sulphate administration compared with baseline. Secondary endpoints were changes in the variables of the MPS and VRU at the end of administration interval compared with baseline. Overall, after 14 days of intravenous amantadine administration (200 mg/day), a significant improvement was obtained in motor performance with respect to the semiquantitative motor scores of the UPDRS (p = 0.002) and the quantitative motor variables in the pertinent subtests of the MPS, reflecting precision and speed of arm-hand movement as well as manual and finger dexterity, for the right (p < 0.01) and the left hand (p < 0.05). However, all patients being viewed collectively, it was observed that there was a widely differing time delay of efficient motor response to amantadine from 4 to 9 days between individuals, whilst the quality of motor response remained stable for the follow-up period. Although simple reaction time showed no significant improvement, choice reaction time shortened significantly in less affected PD patients staging Hoehn and Yahr I to III (p < 0.05). We conclude that apart from efficacy on motor performance, amantadine sulphate – applied intravenously – has a positive effect on cognitive functions, particularly in less affected PD patients.

Summary.: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) with a quadripolar electrode was carried out in 9 patients with advanced idiopathic Parkinson's disease (PD) affected with severe diurnal motor fluctuations. The effect of bilateral STN stimulation was evaluated by clinical methods in all patients after 3 and 12 months. Assessment was based on the Unified Parkinson's Disease Rating Scale (UPDRS), timed motor tests, the Schwab and England Activities of Daily Living and a diary chart to document motor fluctuations. Alterations in parkinsonian signs, motor performance and functional outcome were recorded postoperatively (1) under temporary complete withdrawal of both STN stimulation and medication; (2) in the presence of STN stimulation only; and (3) in the presence of both STN stimulation and medication. The results were compared with the preoperative data assessed in defined on-phase and defined off-phase. STN stimulation on (compared to STN stimulation off) results in a significant improvement in UPDRS motor scores: after 3 months from 50.5 ± 14.3 to 27.8 ± 5.8, and after 12 months from 49.4 ± 14.1 to 27.1 ± 7.1 (p < 0.01). There was a significant decrease in the average duration of off-periods from 8.82 ± 2.47 hours to 1.00 ± 1.06 hours (p < 0.001), a marked increase in on-periods without dyskinesia from 4.62 ± 2.72 to 14.62 ± 1.51 hours (p < 0.01), and a sharp drop in on-periods with dyskinesia from 2.87 (± 4.18) to 0.25 (± 0.97) hours (p < 0.05), which remained stable up to 12 months (off-periods: 1.25 ± 1.58 hours, p < 0.001; on-periods without: 13.87 ± 1.95 hours, p < 0.001; and on-periods wth dyskinesia: 0.37 ± 1.06 hours, p < 0.05). However, our first PD patient with an implanted DBS electrode within the STN died from cardiac infarction two days after surgery. This sudden death was not linked either to surgery nor to stimulation – and happened by chance. Our findings confirm that STN stimulation is a suitable functional neurosurgical procedure for the modulation and control of PD signs associated with severe motor fluctuations, in that they demonstrate a beneficial effect which was fully sustained over a one year follow-up period.

The value of the apomorphine test as a predictor of the clinical outcome of deep brain stimulation of the subthalamic nucleus (STN) was evaluated in patients with advanced idiopathic Parkinson’s disease (IPD) or multiple system atrophy (MSA). Thirteen IPD patients with severe diurnal fluctuations and one MSA patient not responding to dopaminergic drugs were assessed with the Unified Parkinson’s Disease Rating Scale (UPDRS) and the timed finger tapping test (FTT), measured preoperatively on and off apomorphine and postoperatively on and off STN stimulation. UPDRS motor items 20–25 were assessed intraoperatively on and off STN stimulation when the clinically effective target was approached. The motor response to immediate intraoperative and long-term STN stimulation was correlated with results of the apomorphine test. The response to immediate intraoperative STN stimulation was accurately predicted by apomorphine challenge in all 13 IPD patients. Clinical outcome following long-term STN stimulation was correlated significantly with preoperative changes due to apomorphine measured with the UPDRS motor scores (r= 0.7125, P< 0.01) and FTT (r= 0.9276, P< 0.001). Moreover, comparison of long-term STN stimulation to preoperative drug treatment displayed a significant reduction in the duration of off-phases and a significant increase in the duration of on-phases. However, in the single patient with MSA no beneficial response was obtained either to apomorphine or to STN stimulation intraoperatively and during the postoperative externalized test period. Our results indicate that the apomorphine test can predict the outcome of immediate and long-term STN stimulation and may help in the selection of candidates for surgery.

Summary: Collateralization and termination of single C3-C4 propriospinal neurones (PNs) have been studied in the C6-Th1 segments of the cat using two methods: threshold mapping for antidromic activation of C3-C4 PNs and intra-axonal injection of horseradish peroxidase. Low threshold points for antidromic activation of C3-C4 PNs were found in the region of different motor nuclei in lamina IX both at one level and at different segmental levels, in all parts of lamina VII, in the lateral part of lamina VI and in the dorsal and ventral parts of lamina VIII. Collaterals were found from C6 to Th1. A marked decrease of conduction velocity of the stem axon occurred in the caudal region of termination, while it was almost constant in the rostral region of termination. HRP was injected iontophoretically in C6-Th1 into stem axons of neurones, which were activated antidromically from the ventral part of the lateral funiculus in C5/C6, from the lateral reticular nucleus (LRN) and monosynaptically from the corticospinal fibres (stimulated in the contralateral pyramid) which were transected in C5/C6. Reconstruction of successfully stained stem axons, revealed collaterals with terminals on presumed motoneurones in different parts of lamina IX and on interneurones in laminae IV–VIII. These findings confirm previous results which showed monosynaptic projections from C3-C4 PNs to forelimb motoneurones and Ia inhibitory interneurones. With respect to termination in the region of the motoneurones in lamina IX and in the region of Ia inhibitory interneurones in lamina VII, three patterns were found: 1) termination mainly in lamina IX (n=1) 2) termination in laminae IX and VII (n=15) and 3) termination mainly in lamina VII (n=2). However, in some cases the same stem axon gave off collaterals which terminated either on motoneurones in lamina IX or on presumed Ia inhibitory interneurones in lamina VII. Furthermore, when the stem axons had collaterals which terminated in different motor nuclei only some of these collaterals had additional terminations on presumed Ia inhibitory interneurones. This result suggest that C3-C4 PNs do not follow a strict Ia pattern of reciprocal innervation. It is tentatively proposed that the difference of innervation may be related to the type of multi-joint movement, such as target-reaching with the forelimb, which has been shown to be controlled by the C3-C4 PNs. Termination in laminae VI, VIII and different parts of lamina VII indicates that C3-C4 PNs also project to other types of neurones than motoneurones and Ia inhibitory interneurones. Injection of wheat germ agglutinated horseradish peroxidase (WGA-HRP) laterally in laminae VI-VII in C3 and C4 caused anterograde labelling of axonal bundles from neurones in these segments. Labelled axons were found mainly in the lateral funiculus with the highest density in the ventral part. These axons could be traced throughout the forelimb segments and also to the LRN.

1. The mechanical properties of motor units of the cat superior oblique muscle and axonal conduction velocities of trochlear motoneurons have been studied at several postoperative times after intracranial axotomy of the trochlear nerve. 2. Whole muscle twitch forces were generally within the normal range by approximately 4 mo postoperative, indicating that reinnervation is complete at this time. 3. Among animals studied 3.5-4.5 months after trochlear axotomy, average motor-unit tetanic forces were increased by a factor of approximately 2.5 compared with units studied in normal superior oblique muscle. Average motor-unit tetanic forces in animals studied 14.5-23 mo after axotomy were also increased relative to normal, but the difference was not significant. Among all reinnervated motor units, there was a tendency for increased twitch time-to-peak relative to control. Reinnervated motor-unit fatigue properties were similar to normal. 4. Average trochlear motoneuron conduction velocities for animals at all postoperative intervals remained significantly lower than the average conduction velocities from three of four normal animals. 5. Counts of Nissl-stained cell bodies in axotomized and control, contralateral trochlear nuclei showed that some cell loss had occurred, averaging approximately 17% 3.5-4.5 mo postoperative and 24% 14.5-23 mo postoperative. Associated with this loss was an increase (10%) of axotomized motoneuron soma cross-sectional area. 6. Muscle fiber cross-sectional areas (CSA) were measured in reinnervated superior oblique muscles and compared with CSAs from contralateral, control muscles. Average CSA was significantly decreased in all reinnervated muscles, with the relative decreases ranging from approximately 10 to 28%. 7. The results are discussed in terms of factors that determine motor-unit force; muscle fiber CSA, specific force, and innervation ratio. We conclude that the increases of average motor-unit force in short-term reinnervated superior oblique muscles are most likely related to polyneuronal innervation of muscle fibers and that the return of these forces to normal levels in long-term muscles is related to synapse elimination. Our results are compared with those of other self-reinnervation studies, and the potential role played by the time muscle remains denervated in determining the persistence of polyneuronal innervation after reinnervation is considered.

The relations among passive membrane properties have been examined in cat motoneurones utilizing exclusively electrophysiological techniques. A significant relation was found to exist between the input resistance and the membrane time constant. The estimated electrotonic length showed no evident tendency to vary with input resistance but did show a tendency to decrease with increasing time constant. Detailed analysis of this trend suggests, however, that a variation in dendritic geometry is likely to exist among cat motoneurones, such that the dendritic trees of motoneurones projecting to fast‐twitch muscle units are relatively more expansive than those of motoneurones projecting to slow‐twitch units. Utilizing an expression derived from the Rall neurone model, the total capacitance of the equivalent cylinder corresponding to a motoneurone has been estimated. With the assumption of a constant and uniform specific capacitance of 1 mu F/cm2, the resulting values have been used as estimates of cell surface area. These estimates agree well with morphologically obtained measurements from cat motoneurones reported by others. Both membrane time constant (and thus likely specific membrane resistivity) and electrotonic length showed little tendency to vary with surface area. However, after‐hyperpolarization (a.h.p.) duration showed some tendency to vary such that cells with brief a.h.p. duration were, on average, larger than those with longer a.h.p. durations. Apart from motoneurones with the lowest values, axonal conduction velocity was only weakly related to variations in estimated surface area. Input resistance and membrane time constant were found to vary systematically with the a.h.p. duration. Analysis suggested that the major part of the increase in input resistance with a.h.p. duration was related to an increase in membrane resistivity and a variation in dendritic geometry rather than to differences in surface area among the motoneurones. The possible effects of imperfect electrode seals have been considered. According to an analysis of a passive membrane model, soma leaks caused by impalement injury will result in underestimates of input resistance and time constant and over‐estimates of electrotonic length and total capacitance. Assuming a non‐injured resting potential of ‐80 mV, a comparison of membrane potentials predicted by various relative leaks (leak conductance/input conductance) with those actually observed suggests that the magnitude of these errors in the present material will not unduly affect the presented results.+4

Previously obtained experimental results concerning the effect of axotomy on motoneurone passive electrical properties have been re‐analysed. As shown earlier, axotomy causes an average increase of motoneurone input resistance, membrane time constant and after‐hyperpolarization duration. The present analysis suggests that the increased input resistance is related to a higher specific membrane resistivity, a decreased cell size and an altered dendritic geometry. The results also suggest that the change takes place only in neurones projecting to fast‐twitch muscle units and produces in them passive electrical properties normally exhibited only by motoneurones projecting to slow‐twitch units. Based on the notion that axotomy causes a 'dedifferentiation' of motoneurone properties, the present results might be taken to indicate that undifferentiated motoneurones are slow in character. A possible scheme in which a post‐natal differentiation of motoneurone properties may lead to muscle differentiation is discussed.

In anaesthetized cats, thresholds for long (rheobase) and brief duration current pulses have been obtained from spinal motoneurones and compared with other cell parameters and membrane properties. Rheobase showed only weak over‐all relationships with conduction velocity and with cell size, estimated as the total capacitance of individual motoneuronal equivalent cylinders. Rheobase showed a clear tendency to vary inversely with after‐hyperpolarization (a.h.p.) duration and was strongly correlated with the input conductance and with the inverse of the membrane time constant. However, the range of rheobase current exceeded that of input conductance by almost a factor of 2. Part of this range discrepancy arose because threshold depolarization tended to increase with rheobase current. Thus, among motoneurones grouped according to rheobase magnitude (three groups), those within the lowest rheobase group had threshold depolarizations about 6 mV on average lower than those within the highest rheobase group. Even though this difference was not directly related to resting potential differences between the groups, further analysis suggested that it may have arisen secondarily to impalement‐induced depolarization. The finding that experimentally estimated threshold depolarizations in individual motoneurones were generally larger than those predicted by the product of input resistance and rheobase indicated that a subthreshold rectification process also contributed to the range of rheobase. The difference was largest in the low‐rheobase group and smallest in the high‐rheobase group. Because these differences were proportional to the differences in input resistance between the separate motoneurone groups, it is suggested that the magnitude of the current underlying the rectification process does not differ systematically among motoneurones. Within groups of motoneurones classified on the basis of rheobase or a.h.p. duration, significant correlations existed between rheobase current and input conductance. An analysis of variance indicated that even within such functional subgroups of motoneurones, rheobase was appreciably better correlated with membrane time constant than with estimated cell size. Although showing a range approximately half that of rheobase, the brief current threshold was similar to rheobase in its relations with total cell capacitance, a.h.p. duration and the inverse of membrane time constant.(ABSTRACT TRUNCATED AT 400 WORDS)

The effects of contralateral pyramidal stimulation have been investigated with intracellular recording from cat alpha‐motoneurones that innervate the dorsal neck musculature. A short train of stimuli evoked three types of synaptic effects: predominant excitation or inhibition and mixed effects characterized chiefly by early excitation followed by inhibition. Latency measurements indicated a minimal disynaptic linkage for excitation and for inhibition. Splenius motoneurones received primarily excitation whereas biventer cervicis‐complexus motoneurones received a more varied input characterized by mixed effects or inhibition. Following transection of the pyramid just rostral to the decussation (lower pyramidal lesion) pyramidal stimulation above the lesion still produced disynaptic excitation and longer latency (possibly trisynaptic) inhibition. Pyramidal stimulation just caudal to this transection evoked inhibition with a minimal disynaptic latency, as well as longer latency excitation. The incidence of longer latency excitation was found to be reduced in cats with corticospinal tract transections at the level of the second cervical spinal segment. No post‐synaptic potentials were evoked by pyramidal stimulation rostral to a pyramidal transection at the level of the trapezoid body. It is suggested that disynaptic excitation evoked by pyramidal stimulation above the lower pyramidal lesion is mediated by medullary reticulospinal neurones possessing monosynaptic excitatory connexions with neck motoneurones. Longer latency excitation appears to be mediated by neurones that receive corticospinal tract input and are located in the spinal segments containing the neck motoneurones. Disynaptic inhibition is mediated by neurones likely to be situated between the second cervical spinal segment and the level of the lower pyramidal lesion. The results also suggest that the first neurone in the chain mediating longer latency inhibition is located in the brain stem. The differences in pyramidal synaptic input between splenius and biventer cervicis‐complexus motoneurones are considered in relation to the roles these muscles may serve in head position control.

The activity patterns in self- and cross-reinnervated flexor digitorum longus (FDL) and soleus (SOL) muscles were examined during natural movements in awake, unrestrained cats in which electromyographic (EMG) electrodes, tendon-force gauges, and muscle-length gauges had been chronically implanted under anesthesia and aseptic conditions. Kinesiological data were recorded between 13 and 22 mo after nerve surgery. Self-reinnervated FDL and SOL muscles (i.e., FDL----FDL and SOL----SOL, respectively) exhibited locomotor activity patterns that were the same as observed in normal, unoperated FDL and SOL muscles (26). FDL----FDL muscles exhibited primarily brief bursts of activity in early swing, just after the toes had left the ground, whereas SOL----SOL muscles showed bursts of activity just before and during stance. In contrast, the cross-reinnervated muscles (both SOL----FDL and FDL----SOL) that had little or no unwanted self-reinnervation showed the patterns of activity that are associated with the innervating foreign motoneurons. That is, cross-reinnervated SOL----FDL muscles were intensely active in quadrupedal standing and, during the stance phase of stepping, producing large force transients while actively lengthening. Conversely, cross-reinnervated FDL----SOL muscles were active mainly in short bursts at the onset of the swing phase of stepping, just after the foot had left the ground. There was considerable modulation of EMG and peak force output in FDL----SOL muscles with changing speed of locomotion, whereas little modulation was evident in SOL----FDL muscles. The activity patterns in self- and cross-reinnervated FDL and SOL muscles were also recorded during scratch and paw-shaking reflexes. As in locomotion, the observed patterns were in all cases consistent with those expected for the innervating motor pool rather than the innervated muscle. Muscles that had been dually reinnervated by both the original and foreign motor pools displayed activity patterns that were a mixture of the FDL and SOL activity patterns described above. The present results demonstrate that motoneuron activation patterns remain qualitatively unaltered when their motor axons reinnervate foreign muscles. In addition, the observations permit some quantitative estimates of the degree to which cross-reinnervated muscles are subjected to patterns of motoneuron activity and to conditions of mechanical loading that are markedly different from those in the self-reinnervated or normal conditions.

The properties of whole soleus (SOL) muscles and of individual motor units were studied in cats 30-50 wk after self-reinnervation by soleus (SOL) motoneurons (SOL----SOL) or cross-reinnervation by flexor digitorum longus (FDL) motoneurons (FDL----SOL). As in the preceding paper (22), intracellular and glycogen-depletion methods were used to examine the physiological and histochemical properties of individual motor units. The results were compared with data from normal SOL motor units (8, 12). Intentionally self-reinnervated SOL muscles (SOL----SOL; n = 6) were normal in size and wet weight, and all of the five SOL----SOL motor units studied had physiological and histochemical characteristics that matched those of normal SOL units. Cross-reinnervation of SOL by FDL alpha-motoneurons (FDL----SOL; n = 7) produced muscles with wet weights and appearance essentially identical to normal SOL. However, whole-muscle twitch contraction times were much shorter (mean 60.4 ms) than those of normal (mean 136.9 ms, n = 18) or SOL----SOL muscles (mean 115.3 ms; n = 6). Despite this difference, none of the FDL----SOL muscles contained more than 7% histochemical type II muscle fibers, all of which were type IIA. Normal cat SOL muscles can contain up to 5% type IIA fibers, but none of our SOL----SOL muscles showed any type II fibers. Two FDL----SOL muscles had significant amounts of unintended self-reinnervation, permitting side-by-side comparison of FDL----SOL and SOL----SOL muscle fibers. The twitch contraction times of the two populations differed markedly, but they were histochemically indistinguishable except for the fact that SOL----SOL fibers had high neutral fat content (as do normal SOL fibers), whereas FDL----SOL showed much lower fat content. The 23 FDL----SOL muscle units studied were classified as physiological type S by criteria ("sag" test and fatigue resistance) used to identify motor-unit types in normal cat muscles. All five of the FDL----SOL units studied histochemically after glycogen depletion showed the type I histochemical profile, which is characteristic of the normal cat SOL. In marked contrast to the preceding study, cross-reinnervation of cat SOL by FDL motoneurons produced no conversion of muscle-unit properties into those associated with fast-twitch unit types, despite significant decreases in isometric twitch contraction time. The altered twitch speed was not associated with evident changes in conventional myofibrillar adenosine triphosphatase (ATPase) histochemistry.(ABSTRACT TRUNCATED AT 400 WORDS)

Posttetanic potentiation (PTP) of composite Ia excitatory postsynaptic potentials (EPSPs) has been studied in normal cat alpha-motoneurons and in motoneurons axotomized 2-3 wk earlier by ventral root section. The maximal amount of PTP of EPSP amplitude (expressed relative to unpotentiated amplitude) was considerably less in the axotomized population compared with the normal population. The decrease in PTP provoked by axotomy occurs in association with a postaxotomy increase of input resistance, the net effect being that PTP in axotomized cells was much the same as that observed by others in normal motoneurons possessing similarly high input resistance. In agreement with previous results, EPSP peak amplitudes were decreased after axotomy. This decrease seemed to be largely related to an absence of the largest EPSPs, since otherwise the EPSP distributions of normal and axotomized motoneurons showed considerable overlap. It is suggested that the observed decrease in PTP after axotomy is related to a change in synaptic release properties and not secondary to changes in the electrical properties of motoneurons. A previous analysis has suggested that axotomy causes an alteration of the distribution of passive electrical properties among motoneurons such that axotomized cells resemble normal high-resistance motoneurons. The present results suggest that axotomy may affect the distribution of Ia synaptic release properties in a similar manner, since PTP in axotomized motoneurons resembles that observed in normal high-resistance motoneurons.

1. Intracellular recordings were made from 116 splenius (SPL) and 103 biventer cervicis and complexus (BCC) alpha‐motoneurones in nineteen cats anaesthetized with alpha‐chloralose. 2. Electrical stimulation in the contralateral tectum evoked disynaptic excitatory postsynaptic potentials (EPSPs) in the motoneurones when a train of stimuli was applied in the ventral layers throughout the superior colliculus. In the rostral half of the superior colliculus, these EPSPs were due to stimulation of ascending collaterals of tectofugal neurones. EPSPs of a presumed trisynaptic linkage could only be evoked from the dorsal and intermediate tectal layers in the caudal half of the superior colliculus. It is concluded that the tectofugal neurones which evoked the disynaptic EPSPs are mainly located in the caudal half of the superior colliculus. 3. Disynaptic EPSPs were evoked in the motoneurones by a train of stimuli in the contralateral fields of Forel and Zona incerta, which were due to stimulation of ascending collaterals from the tectofugal neurones. 4. Spatial facilitation experiments revealed that tectal disynaptic EPSPs in the neck motoneurones were mediated via reticulospinal neurones with convergent input from cortico‐reticular neurones. 5. A train of stimuli in the ipsilateral tectum evoked EPSPs with latencies compatible with a trisynaptic linkage, while disynaptic EPSPs at low threshold could be elicited from the underlying tegmentum. Similar disynaptic EPSPs could be evoked from the ipsilateral fields of Forel. It is suggested that some of the disynaptic tegmental EPSPs in SPL and BCC motoneurones can be mediated via a tegmento‐reticulospinal pathway which originates in the cuneiform nucleus.

Summary: We examined the characteristics of postsynaptic potentials (PSPs) produced in antidromically-identified medial gastrocnemius (MG) agr-motoneurons by electrical stimulation of low threshold (< 3×T) distal limb cutaneous afferents in the sural (SUR) nerve in adult cats anesthetized with agr-chloralose, together with the effects on SUR PSPs of supraspinal conditioning stimulation of the contralateral red nucleus (RN) and pyramidal tract (PT). In the majority of MG motoneurons, SUR afferents with electrical thresholds < 1.5×T produced early excitatory synaptic potentials (EPSPs) with minimum central latency of about 2.0 ms, suggesting activation of a trisynaptic segmental pathway with two interposed interneurons. Such early EPSPs were often detectable with stimuli < 1.2×T, as determined by recording the compound action potential in the sciatic nerve and from the first appearance of the N1 wave of the cord dorsum potential. Inhibitory synaptic potentials (IPSPs) were regularly produced by SUR volleys of only slightly greater strength (often as low as 1.3×T) and these had minimum central latencies of about 3.0 ms (about 1.0 ms longer than the earliest EPSPs), suggesting a three interneuron central pathway.Repetitive stimulation of RN and PT regularly produced facilitation of both EPSP and IPSP components in the SUR response, suggesting that these supraspinal systems directly or indirectly excite some of the same interneurons that convey the SUR effects to MG motoneurons. When using very low strength SUR stimuli, PT conditioning produced relatively pure facilitation of the SUR EPSPs but with larger SUR volleys, PT clearly facilitated both EPSPs and IPSPs. RN conditioning produced more parallel facilitation of SUR EPSPs and IPSPs. Supraspinal control of the polysynaptic pathway producing SUR EPSPs is of particular interest because of earlier evidence that this pathway is differentially distributed to motoneurons of fast twitch versus slow twitch MG motor units.

Summary Based on Benabid's experimental and clinical findings that low-frequency (50 Hz) electrical stimulation of the ventral intermediate thalamic nucleus may increase tremor, while higher frequencies (>100 Hz) lead to suppression of the tremor, we implanted a stimulation electrode in 33 thalami among 27 patients. Six patients were implanted bilaterally. 23 suffered from Parkinson's disease, 4 from essential tremor. All patients had a drug-resistant tremor.

Intracellular recording has been performed to examine whether any differences in apparent initial-segment voltage threshold exist between types F and S cat triceps surae motoneurons. Voltage threshold was estimated using orthodromic action potentials initiated by large, monosynaptic excitatory postsynaptic potentials (EPSPs) evoked by dorsal root stimulation. No significant differences in voltage threshold could be detected between types F and S motoneurons. Further, voltage thresholds did not covary with motoneuron input resistance, afterhyperpolarization duration, or the twitch contraction time of functionally isolated muscle units. Significant positive correlations were observed between voltage threshold and the motoneuron resting potential. Utilizing a compartmental neuron model, a theoretical analysis has been performed that examines the influence of specific passive membrane properties on current threshold for action potentials initiated by large, monosynaptic EPSPs. This analysis indicates that total membrane capacitance will be the primary determinant of these thresholds. Further analysis of available data suggests that active membrane properties will play a minimal role in setting these thresholds. Since specific membrane capacitance is likely to be similar among cat motoneurons, it is concluded that only size or surface area-related current threshold differences will exist among these cells for activation with brief currents such as those underlying large EPSPs. For motoneurons thus activated, it is suggested that variations in the excitatory/inhibitory balance or density of synaptic input would be the major mechanisms for producing differential recruitment thresholds among the motoneuron population. Other available evidence is discussed that indicates that factors intrinsic to the motoneurons themselves will contribute to the setting of functional recruitment thresholds for activation with longer duration currents.

We have reinvestigated the phenomenon of posttetanic potentiation (PTP) of group Ia monosynaptic excitatory postsynaptic potentials (EPSPs) in medial gastrocnemius (MG) alpha-motoneurons of pentobarbital-anesthetized cats. The results generally confirm earlier reports by Lüscher and colleagues (43, 44) of a negative correlation between the maximum percentage potentiation of Ia EPSP amplitude (Pmax) and 1) the mean amplitude of the pretetanic control EPSP in the same cell and 2) the input resistance of the postsynaptic motoneuron. These negative correlations, which we will refer to as "differential distribution of PTP" within the MG motor pool, were less strong in the present work than reported by Lüscher et al. (43, 44). We also found a relatively strong negative correlation between posttetanic EPSP depression, assessed by the amplitude of the first posttetanic EPSP, and the level of Pmax subsequently attained. We found no evidence that posttetanic depression is caused by failure of presynaptic action potentials. We investigated a second type of depression, referred to as "specific" synaptic depression, in which the second EPSP of paired responses (interval 250 ms) is, on average, smaller in peak amplitude than the first EPSP. This phenomenon appears to reflect decreases in the probability of transmitter release from previously activated synapses. Specific synaptic depression was consistently increased when paired responses were conditioned by a high-frequency tetanus. This is most easily explained by postulating that PTP results, at least in part, from an increase in the statistical probability of transmitter liberation from group Ia synapses that are activated (i.e., presumably invaded by action potentials) both before and after afferent tetanization. On the basis of the present results and other available evidence, we conclude that the differential distribution of PTP can be explained by two main factors: 1) the nonlinear relation between conductance and voltage changes inherent in all chemical synapses and 2) systematic variations in the properties of group Ia synapses that innervated different motoneurons, which remain to be clarified.

1. Composite excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of heteronymous group Ia afferents have been studied at various postoperative times in axotomized motoneurons that were denied the opportunity to reinnervate muscle. 2. The medial gastrocnemius (MG) nerve was transected and sutured onto the surface of the normally innervated lateral gastrocnemius (LG) muscle. The denervated MG muscle was excised thereby eliminating access of regenerating MG motor axons to vacant end-plates. 3. The mean amplitude of monosynaptic Ia EPSPs evoked by electrical stimulation of the LG-soleus (LGS) nerve and recorded in axotomized MG motoneurons showed an initial decline at 20 days postoperative (DPO) that was not significant. At 44 DPO, mean amplitude had declined significantly to 43% of the control mean amplitude. At 90 DPO, mean EPSP amplitude was not significantly different from control. At the latest postoperative time (150-180 DPO), mean amplitude was significantly less than the control amplitude. 4. Mean EPSP rise time (time-to-peak) was significantly increased (27%) at the earliest postoperative times (20-44 DPO). At later postoperative times (90-180), mean EPSP rise time was not significantly different from mean control rise time. 5. "Partial responses" superimposed on EPSPs were not observed at any postoperative time. 6. Mean posttetanic potentiation (PTP) of the LGS EPSP was significantly depressed at 20 DPO. At later postoperative times, PTP did not differ significantly from mean control PTP. 7. The possibility is considered that postaxotomy alterations in the electrical properties of motoneurons may explain these complex variations of mean EPSP amplitude and rise time.

1. The intent of this study was to determine the effect on the electrical properties of axotomized spinal motoneurons when motor axons are allowed to regenerate but are denied the opportunity to reinnervate muscle. 2. The nerve supplying the medial gastrocnemius (MG) muscle in cats was served close to its entry into the muscle and sutured onto the surface of the lateral gastrocnemius (LG) muscle. The MG muscle was excised to prevent availability of vacant end-plates to the regenerating MG axons. The electrical properties of antidromically identified MG motoneurons were studied using intracellular recording at various postoperative intervals. 3. In 9 of 12 experimental animals, no sign of functional innervation by MG axons of the LG muscle could be detected. In three experimental animals, electrical and contraction activity in the LG muscle was observed following electrical stimulation of the transplanted MG nerve. The observed electrical and contraction activity was, however, negligible compared to the effects of electrical stimulation of the intact LG-soleus nerve. 4. At the earliest postoperative interval studied (20 days), MG motoneuron electrical properties [input resistance, afterhyperpolarization (AHP) duration, conduction velocity, time constant, rheobase current, and sag] exhibited significant changes that were nearly identical to those described for spinal motoneurons following section of ventral roots or motor nerves or in the earliest stages of reinnervation. 5. At the 44-60 day postoperative (DPO) intervals, several motoneuron electrical properties showed signs of recovery to control levels. At 44 DPO, average values of input resistance, time constant, and AHP duration declined from the significant increases observed at 20 DPO and could not be distinguished statistically from control mean values. 6. These indications of an early recovery of normal electrical properties were not sustained. At subsequent postoperative intervals (90, 120, and 150-180 DPO), average values of motoneuron electrical properties tended to be similar to those observed at 20 DPO. 7. Correlations observed among control motoneuron electrical properties were weakened and the pattern of correlation was disrupted at all postoperative intervals. 8. In conjunction with previous results demonstrating recovery of normal electrical properties following reinnervation (Foehring et al. 1986b), our findings suggest that functional contact with muscle is required for the full expression of the normal range of motoneuron electrical properties.(ABSTRACT TRUNCATED AT 400 WORDS)

Summary.: In one of our first patients with severely disabling and fluctuating Parkinson's disease (PD) we observed a transient pancreatic enzymes increase 6 months after continuous apomorphine therapy. Since this adverse effect had not been previously reported, we systematically investigated the course of pancreas and liver functions in response to apomorphine: laboratory and neurological assessments were conducted before initiation of apomorphine therapy, during the increment phase up to the optimal motor effective level and at all follow-up visits. We found in five out of 29 PD patients a transient increase of pancreatic enzymes during the initial phase of continuous subcutaneous apomorphine application. Peaks of pathological plasma levels were apparent from the first day up to the fifth day after apomorphine initiation, and returned to normal levels within 10 days in all 5 patients. Otherwise, this pancreatic enzymes increase was not accompanied by any raising in plasma levels of corresponding liver enzymes. No pathological signs in the endoscopic-retrograde cholangiopancreatography, the abdominal ultrasonography and the computed tomography of the abdomen were found in any of the affected PD patients. Furthermore, there was no evidence of pancreato-hepatal risk factors in the previous history in any of the PD patients studied. With respect to the course of PD, no differences were obtained upon comparison of affected and non-affected PD patients. Considering the patients' history, clinical course and current knowledge about the effect of apomorphine on pancreato-hepatal function, we conclude that a possible cumulative pathomechanism between transient pancreato-hepatal enzymes and continuous applied apomorpine, especially in the titrating phase, might cause this adverse event in about 20% of PD patients treated with apomorphine continuously.

Excitation of dorsal neck motoneurones evoked by electrical stimulation of primary trigeminal afferents in the Gasserian ganglion has been investigated with intracellular recording from a-motoneurones in the cat. Single stimulation in the Gasserian ganglion ipsi-and contralateral to the recording side evoked excitatory postsynaptic potentials (EPSPs) in motoneurones innervating the lateral head flexor muscle splenius (SPL) and the head elevator muscles biventer cervicis and complexus (BCC). The gasserian EPSPs were composed of early and late components which gave the EPSPs a hump-like shape. A short train of stimuli, consisting of two to three volleys, evoked temporal facilitation of both the early and late EPSP components. The latencies of the gasserian EPSPs ranged from 1.6 to 3.6 ms in SPL motoneurones and from 1.6 to 5.8 ms among BCC motoneurones. A rather similar latency distribution between 1.6 and 2.4 ms was found for ipsi- and contralateral EPSPs in SPL and BCC motoneurones, which is compatible with a minimal disynaptic linkage between primary trigeminal afferents and neck motoneurones. Systematic transections of the ipsi- and contralateral trigeminal tracts were performed in the brain stem between 3 and 12 mm rostral to the level of obex. The results demonstrate that both the ipsi- and contralateral disynaptic and late gasserian EPSPs can be mediated via trigeminospinal neurones which take their origin in the nucleus trigeminalis spinalis oralis. Transection of the midline showed that the contralateral trigeminospinal neurones cross in the brain stem. Systematic tracking in and around the ipsilateral trigeminal nuclei demonstrated that the axons of ipsilateral trigeminospinal neurones descend just medial to and/or in the medial part of the nucleus. Spinal cord lesions revealed a location of the axons of the ipsilateral trigeminospinal neurones in the lateral and ventral funiculi. Interaction between the ipsi- and contralateral gasserian EPSPs showed complete summation of the disynaptic EPSP component, while the late components were occluded by about 45%. These results show that the disynaptic EPSPs are mediated by separate trigeminospinal neurones from the ipsi- and contralateral side, while about half of the late EPSPs are mediated by common neurones which receive strong bilateral excitation from commissural neurones in the trigeminal nuclei. Spatial facilitation was found in the late gasserian EPSP but not in the disynaptic gasserian EPSP by conditioning stimulation of cortico- and tectofugal fibres. Disynaptic pyramidal and tectal EPSPs, which are mediated by reticulospinal neurones, were facilitated by a single stimulation in the gasserian ganglion at an optimal interval of 2 ms. It is suggested that primary trigeminal afferents can excite the reticulospinal neurones via a disynaptic trigeminoreticular pathway.

It was the purpose of the present study to quantify the expected motor deficit in parkinsonian patients with the computer assisted Motor Performance Test Series (MPS), version 05.87 by Schuhfried (1987) and to examine which of the motor test variables found correlate at a significance level of p<0.01 with items of “motor examination” recorded at neurological examination and “activities of daily living” of the Unified Parkinson's Disease Rating Scale (UPDRS), version 3.0.

Seven patients with idiopathic Parkinson's disease, aged 62 to 76 years, average duration of the disease approximately eleven years, suffering from severe hallucinosis and paranoid delusions of different degree, in whom conventional therapeutic strategies (administration of benzodiazepines and mild neuroleptics) had no antipsychotic effect, received clozapine, a non-classical highly potent neuroleptic, while blood count was strictly monitored. Paranoid ideas disappeared in all seven patients after a maximum of four days administration of 25–125 mg/day. No deterioration of parkinsonian symptoms, quantified according to UPDRS was seen. Given the protection of clozapine, we could increase the L-dopa dose in two cases, thereby improving the patients' motor function. Blood count showed no abnormalities in any of the patients during an average observation period of seventeen months.

We compared 21 idiopathic, pharmaceutically well managed parkinsonian patients, neurological stages I and II on the Hoehn and Yahr scale with 21 parkinsonian patients stage III and 19 healthy controls group-matched for age, sex and education to study to what extent impairments of fluid intelligence in parkinsonian patients are due to a slowing of cognitive processes, i.e. to bradyphrenia (a deficit in the speed component) or to a true performance deficit (a deficit in the power component). The Vienna Matrices Test, which is similar to Raven's Standard Progressive Matrices was presented to the patients in a modified form. The Cognitrone was used to measure the influence of vigilance and perception on the cerebral function assessed. With increasing neurological severity of the disease, the dimension examined showed true deficits in the power component. There was no bradyphrenia in the sense of slower performance which would otherwise be equal to that of the control subjects. Vigilance and perception did not change in the course of the disease.

Several rat medial gastrocnemius (MG) motor axons were allowed to regenerate into normally innervated muscle. Under these conditions, synapse formation is known to be prevented by the existence of the original innervation of the host muscle. A study was made of the ability of the implanted spinal motoneurons to acquire and retrogradely transport horseradish peroxidase (HRP) injected into the host muscle at various postoperative intervals. HRP-labeled MG motoneurons on the implanted side were observed at postoperative intervals as long as 290 days. A comparison of the number of labeled MG motoneurons on the implanted side versus the number on the unoperated, control side indicated no significant differences. At all investigated postoperative intervals except the earliest (7 DPO), a significant decrease in the mean MG motoneuron soma cross-sectional area was observed relative to the unoperated, control side. Analysis of labeled motoneuron size distributions showed that postoperative atrophy of larger, presumably alpha, motoneurons occurred at a significantly faster rate than in smaller, presumably gamma, motoneurons. These results demonstrate that axotomized adult spinal motoneurons survive and remain viable for prolonged periods when denied the opportunity to reinnervate muscle but do so in an atrophied state. The results indicate further that alpha and gamma motoneurons differ quantitatively in their responses to peripheral axotomy. Copyright 1993, 1999 Academic Press

1. The aim of the present study was to determine whether synapses formed by dorsal root afferents that regenerate into intraspinal transplants of fetal spinal cord are functional. Severed L4 or L5 dorsal root stumps were placed at the bottom of dorsal quadrant cavities made in the lumbar spinal cords of adult rats and juxtaposed to embryonic day 14 spinal cord transplants. 2. In animals examined 5-10 weeks later, we recorded extracellularly in transplants from 43 units that fired in response to electrical stimulation of the implanted dorsal root. Latency fluctuations of extracellular firing that increase with stimulus and failure to follow high-frequency and posttetanic potentiation of extracellular firing stimulation suggest that synapses with conventional properties are formed between regenerating afferents and transplant neurons. Limited intracellular recordings confirmed the existence of excitatory postsynaptic potentials in transplant neurons after dorsal root stimulation. 3. In 16 units, extracellular firing occurred in response to single shock stimulation. The remainder of the units required two or more dorsal root shocks to evoke firing; some of these connections also may be monosynaptic. 4. Under the assumption that single shock firing was most likely the result of monosynaptic connections between transplant neurons and regenerated dorsal root fibers, we estimated the conduction velocities of regenerated fibers. These estimates suggest that fibers with conduction velocities in the C, A delta, and A alpha/beta ranges regenerate into transplants of embryonic spinal cord. 5. The results demonstrate that regenerated dorsal root axons establish functional synaptic connections with transplant neurons. The implications for using fetal transplants to help rebuild spinal reflex circuits after spinal cord injury are considered.

Growth hormone hypersecretion, as in acromegaly, features heart hypetrophy. Despite long experience, heart changes are not regarded as adverse effects of GH therapy: however, increasing doses are being used, owing to increased availability and extension to indications other than GH deficiency. In order to ensure the safety of hGH at higher dose than in the past, we have performed echocardiography in 71 children and adolescents: 22 before treatment, 49 having received hGH (0.4-0.96 IU/kg/wk) for a period ranging 0.5 to 15.5 yrs. M-mode (left ventricle diameter, LV Posterior Wall [LVPW] and Septum [LVSW] in diastole and systole, systolic shortening [LVS] and thickening, aonic root diameter) and Doppler mode (cardiac output and index, protodiastolic to end-diastolic mitral flow ratio) have been recorded and evaluated for relationship to body size, duration of therapy, weekly and cumulated GH dose. The M-mode parameters of left heart size (LV, LVPW, LVSW) were well related to the body growth, and hence indirectly to the therapy. The cardiac index showed a negative correlation with the body size. The other dynamic parameters (LVS, LVPW and LVSW thickening) were, by contrast, not related to the body size. Univariate and multivariate linear regression analysis did not show any correlation between dynamic parameters and duration and dose of GH therapy. However, when the subjects were divided into five groups according to the duration of therapy (A, baseline; B. up to 1 year; C. 1 to 2 years; D. 2 to 4; E, over 4), analysis of variance disclosed a trend of decrease of the LVS and wall thickening during the first period of therapy (groups B and C), and subsequent return to baseline values or above. This phenomenon, which was somewhat unexpected, can hardly be explained by a direct negative inotropic effect of GH. A positive correlation between the LVS and the systolic blood pressure suggests the tentative explanation that the improvement of the lean body mass, due to the therapy, may explain the reduction of the peripheral resistance. A prospective study is in progress.