Tremor-related motor unit firing in Parkinson's disease: implications for tremor genesis.

Muscle tremors reflect rhythmical motor unit (MU) activities. Therefore, the MU firing patterns and synchrony determine the properties of the parkinsonian force tremor (FT) and the neurogenic components of associated limb tremors. They may also be indicative of the neural mechanisms of tremor genesis which to date remain uncertain. We examined these MU behaviours during isometric contractions of a finger muscle in 19 parkinsonian subjects. Our results reveal that the parkinsonian FT is abnormally large. Like the physiological FT, it is accompanied by in-phase rhythms in all MU activities. However, there exist two important differences. Firstly, the synchrony during the parkinsonian FT is stronger than the normal one and therefore contributes to the FT enhancement. Secondly, the synchronous MU components partly represent rhythmical sequences of spike doublets and triplets whose incidences directly reflect the differences of the MU firing rates to the FT frequency. According to our analyses, the latter frequency coincides with the MU recruitment rate. Consequently, the numerous medium- and small-sized active MUs contribute rhythmical twitch doublets and triplets, i.e. large force pulses, to the parkinsonian FT. The impact of this effect on the FT amplitude is found to predominate over the impact of the augmented synchrony. Importantly, apart from the rule governing the occurrence of doublets/triplets, the mean interspike intervals within such spike events are fairly fixed around 50 ms. Such regularities in MU activities may reflect properties of the neural input underlying the FT, and thus represent a basis for more focused studies of the generator(s) of parkinsonian tremors.

A minute demyelinating lesion causing acute positional vertigo.

Clinico-anatomical correlations in multiple sclerosis patients presenting with central positional vertigo are lacking. We report on a patient with acute onset positional vertigo mimicking benign paroxysmal positional vertigo with a single enhancing lesion in the inner part of the superior cerebellar peduncle, disclosed only after thin slice MR-imaging. This location appears to be a common cause of central positional vertigo and should be regarded as characteristic for demyelinating rather than vascular pathology. In cases presenting with positional nystagmus and vertigo without other cerebellar deficits one should look explicitly for signal abnormalities in the inner part of the superior cerebellar peduncle. High spatial resolution-MRI seems to be mandatory for lesion detection.

[Benign paroxysmal positional vertigo with and without manifest positional nystagmus: an 18-month follow-up study of 70 patients]. / Benigner paroxysmaler Lagerungsschwindel mit und ohne manifesten Lagerungsnystagmus: Achtzehnmonatige Verlaufsbeobachtung von 70 Patienten.

BACKGROUND: In this follow-up study of approximately 18 months we assessed parameters of medical management in a sample of 70 patients suffering from benign paroxysmal positional vertigo. METHODS: Apart from demographic data, we evaluated the time interval from the appearance of the first symptoms until a diagnostic positional manoeuvre was performed, the efficacy of liberatory manoeuvres, the prescription of medication, the use of technical diagnostic resources and the relapse rate. RESULTS: None of the patients had received a diagnostic positioning test until then. Moreover, in one out of three cases a further unnecessary technical diagnostic procedure was carried out. There was a tendency for the right labyrinth to be more frequently affected, a fact that was statistically independent from age and sex, as well as from overall prognosis, which was characterized by a 15.6% recurrence rate. All patients with manifest positional nystagmus were successfully treated: 87.2% immediately after the repositioning manoeuvre and the rest within 10 days by self-performing Brandt-Daroff exercises. Our retrospective analysis revealed that, given a normal neuro-otological examination, a typical medical history without manifest positioning nystagmus leads safely to the correct diagnosis. CONCLUSION: The delay between the onset of symptoms and the diagnosis of BPPV is very often unduly long. A focused medical history may be diagnostic even in the absence of nystagmus during the Dix-Hallpike manoeuvre.

Positional nystagmus and vertigo due to a solitary brachium conjunctivum plaque.

The authors describe two patients suffering from demyelinating central nervous system disease who developed intense vertigo and downbeat nystagmus upon tilting their heads relative to gravity. Brain MRI revealed in both cases a single, small active lesion in the right brachium conjunctivum. The disruption of otolithic signals carried in brachium conjunctivum fibres connecting the fastigial nucleus with the vestibular nuclei is thought to be causatively involved, in agreement with a recently formulated model simulating central positional nystagmus. Insufficient otolithic information results in erroneous adjustment of the Listing's plane in off-vertical head positions, thus producing nystagmic eye movements.

Smooth pursuit rather than visual signals mediate short-term adaptation of the cervico-ocular reflex in humans.

Cervical stimulation in the horizontal plane induces small and variable eye movements in normal human adults [cervico-ocular reflex (COR)]. In patients with bilateral vestibular loss, the slow COR component increases in amplitude and is thought to contribute to gaze stabilization during head movements, as it is directed opposite to head-on-trunk excursions. The procedures underlying COR slow phase gain enhancement in the compensatory direction remain unclear. We studied the horizontal COR during passive trunk oscillations of +/-16 degrees under the stationary head at 0.1 Hz in ten normal subjects, aged 24-30 years, before and immediately after the application of an adaptation procedure engaging various combinations of sinusoidal neck-proprioceptive, pursuit and retinal slip signals. The duration of this adaptation period was 40 min. A significant gain increase and phase modulation in the compensatory direction were observed in four out of eight subjects after exposing them to neck-proprioceptive stimulation, while pursuing a spot moving in-phase with their trunk. In contrast, staring at the rotating optokinetic pattern or fixating at a stationary spot, while being subjected to combined cervical and optokinetic stimulation, failed to result in any significant modification of the subjects' COR gain and phase. Conceivably, the contribution of the pursuit system was greatly reduced in the paradigm using optokinetic stimulation, while full engagement of retinal slip signals, in the absence of any pursuit contribution, was obtained in the latter adaptation paradigm. These results indicate that motor responses of target tracking rather than simply sensory signals of retinal slip may represent the 'error signal' modifying the COR in humans.

Vestibular memory-contingent saccades involve somatosensory input from the body support.

Humans use vestibular head-in-space information when redirecting gaze towards remembered target location in space. This study shows that neck input is also involved. Normal subjects performed saccades towards remembered locations in space of a previously seen target following passive horizontal rotations of the head or trunk. Saccades based on vestibular input alone fell short at low stimulus frequencies. Addition of neck input modified the responses, making them more accurate when the head was rotated on the stationary trunk. The results support a concept according to which vestibular input is channeled via proprioceptive coordinate transformations through the haptically perceived body support before yielding a sense of head motion in space. The loop is also involved in the saccadic gaze mechanism.

Opposite rotation induced by dopamine agonists in rats with unilateral lesions of the globus pallidus or substantia nigra.

Normal rats with a unilateral ibotenic acid lesion of substantia nigra pars reticulata (SNR, n = 12) or globus pallidus (GP, n = 12) were challenged systemically with the mixed dopaminergic agonist apomorphine (0.5 and 1.5 mg/kg) and the indirect acting d-amphetamine (1.5 mg/kg). The low dose of apomorphine produced a weak contralateral rotation only in the SNR-lesioned group, which showed an intense ipsilateral rotation following the administration of the higher dose. GP-lesioned rats also showed ipsilateral rotation after the high dose of apomorphine. d-Amphetamine produced ipsilateral rotation in GP-lesioned rats, contrasting with a vigorous contralateral rotation in SNR-lesioned rats. The unexpected opposite rotation after apomorphine and d-amphetamine, observed only in SNR-lesioned animals, indicates that the role of SNR in basal ganglia functions is less clear and more complex than what is expected from our current model of basal ganglia circuitry and functions. On the other hand, the GP lesion resulted in a consistent and predictable ipsilateral rotation after both apomorphine and d-amphetamine, indicating a more determinant effect on the output of the basal ganglia than heretofore believed. Our results may contribute to the recently expressed views challenging the established model of basal ganglia organisation.

Dissociation between the perception of body verticality and the visual vertical in acute peripheral vestibular disorder in humans.

Estimates of the subjective visual and postural vertical were obtained from five patients with acute peripheral vestibular lesions and 20 normal subjects. The visual vertical was assessed by asking the subjects to align a target line to earth vertical by means of remote control. Postural vertical judgments were obtained by exposing them to rotational displacements in the roll plane while sitting on a motor-driven chair and requiring them to align their body to vertical using a joystick control. While the patients showed strong deviations of the visual vertical towards the lesion side, their postural vertical judgments remained veridical. We conclude that the above perceptions are not processed identically and that the participating sensory systems are differently weighted during these tasks.

Effect of carpal tunnel syndrome on median nerve proximal conduction estimated by F-waves.

Slowing of median nerve proximal motor conduction in patients with carpal tunnel syndrome (CTS) could be considered as an indicator of an additional proximal lesion (double crush syndrome). The effect of CTS on proximal conduction was assessed by comparing motor velocities calculated by F-waves obtained from muscles with the same root and nerve supply but different median branches, one emerging before the carpal tunnel (pronator quadratus muscle) and one passing through the tunnel (abductor pollicis brevis). Data were obtained from 26 patients with CTS and 21 age-matched healthy subjects. In the control group, the proximal (spinal cord and elbow) F-wave maximal velocity calculated when recording from abductor pollicis brevis (FCVmax-APB) was not different from the F-wave maximal velocity calculated when recording from pronator quadratus (FCVmax-PQ), while it was significantly different in the group of CTS patients, especially in patients with terminal motor latency greater than 4.5 ms (approximately 9% less, p = 0.001, Wilcoxon signed rank test). The study showed that median nerve proximal conduction velocity slowing in patients with CTS is restricted to the fibers that distally pass through the carpal tunnel and does not necessarily imply an additional proximal lesion. We suggest that comparison of FCVmax-APB and FCVmax-PQ could be useful when the question arises if a single (distal) or two (one distal, one proximal) lesions are responsible for a patient's symptoms.

Discrimination between trunk and head rotation; a study comparing neuronal data from the cat with human psychophysics.

Kinesthetic information from labyrinthine and neck receptors is required for reflex control and conscious perception of posture and movement. This study considers (1) the neuronal responses to horizontal labyrinthine and neck stimulation and their interaction both in the anterior suprasylvian (AS) cortex and in the vestibular nuclei (VN) of cats, and (2) human turning sensation related to these stimuli. Convergence of labyrinthine (L) and neck (N) input of comparable sensitivity was found in 80% of the AS neurons and in only 27% of the VN neurons. At both sites, the on-direction of L-responses as well as N-responses was either to the ipsilateral or to the contralateral side (type I and type II responses, respectively). When combining the two stimuli during head rotation, the two inputs could be synergistic (same on-direction) or antagonistic (opposite on-directions). Their interaction consisted of either an additive or subtractive summation leading to enhanced or depressed interaction responses. These interaction patterns are compatible with the subtractive and additive mechanisms which have been proposed to be essential for the stabilisation of the trunk and of the head, respectively. The psychophysical experiments showed that human turning sensations depend on the part of the body to which they are referred. Subjects taking the trunk as reference, reported similar turning sensations during both labyrinthine and neck stimulation, and weak or no turning sensation during head rotation. This suggests an antagonistic interaction of the two inputs. In subjects taking the head as reference, neck stimulation induced an illusionary sensation of head turning. Its direction was such that it would be synergistic with the vestibularly induced sensation of head turning during isolated head rotation. Thus, there appear to exist parallels between the basic operations performed by neurons in cat and by human subjects during labyrinthine-neck interactions.

Hearing loss and vestibular dysfunction in childhood from the use of streptomycin in Albania.

With the entry of a large number of Albanians in the area of Epirus over the past 8 months, a significant number of children with hearing problems or deafness has been examined in the out patient ward of the University Hospital of Ioannina. From the Pediatric-Neurologic-Psychiatric and Otorhinolaryngologic examination of these children, 18 cases with hearing problems and vestibular dysfunction due to administration of streptomycin sulfate have been defined. This article reports the ototoxic drug which has been used and is still being used in Albania, the procedure of audiological and vestibular investigation, and the damage which has been evoked in the auditory and vestibular pathway of the children in whom it has been administered.

Proprioceptive influence on the optokinetic nystagmus.

The influence of neck and leg proprioceptive inputs on optokinetic-induced quick phases was studied in humans. Ten subjects received unidirectional horizontal optokinetic stimulation (10-20%/s) during sinusoidal neck, leg and combined neck + leg proprioceptive stimulation. The optokinetic reflex was measured by electro-oculography. Neck stimulation induced a shift in the nystagmus beating field in the opposite direction to body movement (gain 0.3 0.4, phase 140-180 degrees). The beating field shift resulted totally from the amplitude and frequency modulation of optokinetic quick phases, as slow phases were not affected. Leg proprioceptive stimulation induced a similar effect, but the phase of the response lagged by approximately 90 degrees compared with that of neck response. With combined neck + leg stimulation, the amplitude of the effect was a sum of the separate effects, but the phase coincided with that of the leg response. This suggests that neck and leg proprioceptive signals do not add linearly and that the leg signal determines the time of the response.

Horizontal otolith-ocular responses to lateral translation in benign paroxysmal positional vertigo.

Benign paroxysmal positional vertigo (BPPV) is assumed to result from utricular damage, but it is controversial if patients have manifest utricular dysfunction. Therefore, we investigated linear vestibulo-ocular reflexes (LVORs) during lateral whole-body translation in 14 patients with unilateral BPPV. Patients were subjected to linear acceleration steps of 0.24 g along the interaural axis, which were applied randomly to the left and right, both in the dark and in the light with a visual target at a distance of 60 cm. The LVOR was measured by EOG from the slow phase velocity of the averaged and desaccaded compensatory eye movement. In normal cases, maximum asymmetry of LVOR velocity was 13% in the dark and 10% in the light. In patients, LVOR velocities were normal in the dark but mildly reduced in the light (p < 0.05). Five patients had mild LVOR asymmetries in the dark (range 18-38%) and two in the light (11 and 13%), but there was no consistent relationship to the affected side. The absence of gross changes of the LVOR may be explained either by minor utricular damage that is functionally irrelevant or by central compensation of a chronic unilateral deficit.

Influence of postural constraints on eye and head latency during voluntary rotations.

Redirecting gaze towards new targets often requires not only eye movements, but also synergistic rotations of the head, trunk and feet. This study investigates the influence of postural constraints on eye and head latency during voluntary refixations in the horizontal plane in 14 normal subjects. Three postural conditions were presented, (1) sitting in a chair using only eye and head movements, (2) standing without feet movements and (3) standing with feet movement. Head-eye reorientations towards eccentric un-predictable locations were performed towards ±45° and ±90° targets and back towards a central, spatially predictable target. Results showed that postural constraints affected eye latency but only when subjects knew the future location of the target (recentering "return" trials). Specifically, relatively longer eye latencies were observed when subjects had to turn their feet back towards the predictable central target. These findings suggest that the additional CNS processing required to reduce degrees of freedom during predictive motion introduces delays to the eye movement in order to efficiently assemble the components of a new motor synergy.

[The concept of time and its relation to the psychoanalytic-psychotherapeutic setting].

Psychoanalysis is fundamentally related to time because it is an ef for t to understand how disturbances in the present are determined by events in the past. This paper represents an attempt to delineate the developmental line of time sense from birth to object constancy, concentrating on those maturational and environmental factors which determine psychotemporal adaptation in infancy and early childhood until the age of adolescence. Patients' distortions of time can frequently and readily be observed in clinical psychoanalysis reflecting both their psychopathology and their reactions to the temporal aspects of the psychoanalytic setting.

Foot rotation contribution to trunk and gaze stability during whole-body mediated gaze shifts: a principal component analysis study.

Large gaze displacements are mediated by combined motion of the eye, head, trunk, and foot. We applied principal component analysis (PCA) to examine the degree of variability and linearity in the angular velocity pattern of the various segments involved that participate in this task. Ten normal subjects stood up and had to visually fixate and realign their bodies with LED targets separated 45 degrees apart, ranging from +/-45 to 360 degrees. The outbound movement in this paradigm is unpredictable whereas the return (inbound) movement occurs under spatially predictable conditions. Under such predictable conditions, subjects generate in approximately 15% of the trials gaze shifts, with periods of fairly constant high gaze velocity (single-step gaze shifts). PCA showed that gaze velocity variability did not change if the feet were rotating or not. Foot velocity was variable and showed additional PCs suggestive of non-linear motion components. Trunk and head-in-space velocity showed intermediate levels of variability but its variability decreased during the foot stepping movements. The results suggest that the feet, trunk, and head are less tightly controlled by the central nervous system than gaze velocity. Movements of the feet seem to aid trunk stability and motion rather than gaze control.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in a Greek family.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult-onset inherited disease, characterised by recurrent strokes, migraine and cognitive impairment. We present the first Greek family with CADASIL, caused by the R153C mutation at exon 4 of the Notch3 gene. A member of this family carrying this mutation was also found to be heterozygotic for the MTHFR mutation, factor V Leiden mutation and had low serum levels of antithrombin III, thus resulting in the appearance of recurrent strokes and thrombotic episodes since his early adulthood. The co-existence of these thrombophilic disorders with CADASIL in a single person poses serious therapeutic dilemmas, as the administration of anticoagulant agents may correlate with increased risk of potentially fatal intracerebral haemorrhage.

Canal-neck interaction in vestibular nuclear neurons of the cat.

The convergence and interaction of horizontal semicircular canal and neck proprioceptive inputs were studied in neurons of the caudal two thirds of the vestibular nuclear complex. Extracellular neuron activity was recorded under muscle relaxation and slight anesthesia in chronically prepared cats. The following stimulations were applied: horizontal rotations of (a) the whole body (labyrinth stimulation), (b) the trunk vs. the stationary head (neck stimulation), and (c) the head vs. the stationary trunk (combined labyrinth and neck stimulation). Of 152 neurons investigated, 83 (55%) showed convergence of the two inputs. In about half of these neurons, the neck input was very weak and hardly affected the labyrinthine response during head rotation. Judged from the response pattern, several of these neurons presumably were related to vestibulo-oculomotor function (i.e., vestibular nystagmus). In the other half (i.e., 27% of all neurons), sensitivity of the two inputs was similar. Both labyrinthine and neck responses contained a dynamic ("velocity") component; neck responses of more than half of these neurons had, in addition, a static ("position") component. The dynamic components were either "antagonistic" or "synergistic" as to their convergence during head rotation. When applying this combined stimulation, the dynamic components summed linearly, yielding subtration in case of antagonistic convergence and addition in case of synergistic convergence. In contrast, the static components of the neck responses remained largely unchanged during head rotation. However, the static head-to-trunk deflection determined the tonic discharge level in such neurons and thus facilitated or disfacilitated the dynamic responses to superimposed labyrinth stimulation. We suggest that the two patterns of labyrinthine neck interaction observed in vestibular nuclear neurons, i.e., subtration and addition, may be involved in the postural control of the trunk and head, respectively. In contrast, interference of the neck input with vestibulo-oculomotor function appears to be almost negligible in the intact cat.