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Normal subjects can completely eliminate resistance upon imposed head-on-trunk rotations when they are asked to relax. It is not, however, clear how neck reflexes to stretch can be voluntarily suppressed. Reflexive responses might be modified by adjusting the gain of the reflex loop through descending control. Theoretically, necessary corrections upon interfering disturbances during coordinated motor performance requiring the interplay of relaxation/activation may be missing if muscle relaxation is taking place exclusively by this mechanism. It has been alternatively proposed that sensory information from the periphery may be allowed to “neutralize” neck reflexes if it is fed back with opposite sign to the structures driving the reflexes. Six healthy subjects were asked to relax while subjected to head-on-trunk rotations generated by a head motor. After any initial resistance had completely subsided, the head was unexpectedly exposed to “ramp-and-hold” perturbations of up to 2° amplitude and 0.7 s duration. Resistance to stretch consistently reappeared thereupon, suggesting that stretch reflex gain had not been set to zero during the previously achieved complete relaxation. Resistance to perturbations under these circumstances was compared with the forces generated when the same ramp-and-hold displacements were delivered unpredictably to the head held stationary. A quantitative model of neck proprioceptive reflexes suppression has been thus constructed. Gain scheduling or “motor set” cannot sufficiently account for the voluntary reflex suppression during slow passive head rotations. Instead, we propose as underlying mechanism, the “neutralization” of the controlling servo by means of continuous feedback tracking displacement and force signals from the periphery. NEW & NOTEWORTHY Head stabilizing neck reflexes can be voluntarily suppressed or activated depending on the task at hand. By applying brief perturbations unexpectedly, both during passive head-on-trunk movements and at rest, we investigated the mechanism of voluntary suppression of resistance to stretch. A physiologically plausible, neuromechanical model of voluntary/reflexive interactions was constructed favoring feedback over reflex gain adjustments. Accordingly, muscle relaxation during imposed head movements is based on sensory feedback similarly to muscle contractions during purposeful movements. Copyright © 2022 the American Physiological Society.

The role of the hippocampus in spatial navigation and the presence of vestibular-responsive neurons in limbic areas are well-established from animal experiments. However, hippocampal spatial processing in humans is not fully understood. Here, we employed real whole body and head-on-trunk rotations to investigate how vestibular signals, either alone or in combination with neck-proprioceptive stimulation, shape the spatial frame of reference in patients with unilateral hippocampal sclerosis (HS). Patients were asked to point in darkness with a light spot, moved on a cylindrical screen by means of a joystick, into their visual straight-ahead direction (VSA), to remember this direction in space, and to revert back to this point after the rotations. Estimates in patients with HS were compared with those of healthy controls and of patients with epilepsy without hippocampal involvement. All groups produced similar errors after low-frequency vestibular stimuli. These errors were eliminated when rotations involved concurrent neck stimulation. Significantly increased variability was observed, however, in both the VSA and reposition estimates after the rotations in patients with HS compared with controls. These results suggest that cognitive processing of idiothetic signals for self-motion perception is inaccurate in patients with HS. Importantly, however, the responses of patients with HS showed no spatial lateralization with regard to right or left HS, suggesting that the underlying neuronal loss attenuates the precision of head-direction signal decoding in a nondirectional manner. Hence, patients are unable to use these signals as efficiently as normal subjects in the construction of a stable head-centric spatial frame of reference. NEW & NOTEWORTHY Spatial perception relies on combined processing of various idiothetic (vestibular and proprioceptive) and allothetic (visual and auditory) sensory signals. Despite the established knowledge of rodent vestibular-hippocampal interactions, human data are lacking. We investigated idiothetic orientational processing in subjects with unilateral hippocampal sclerosis using various combinations of vestibular and proprioceptive stimuli. Hippocampal impairment leads to less accurate, noisy decoding of the signal related to idiothetic orientation. However, patients did not show any lateralized deficits of visual straight-ahead perception or of target/self-displacement perception after idiothetic stimulation. © 2018 American Physiological Society. All rights reserved.

The neural mechanisms responsible for resting and postural tremor in Parkinson’s disease (PD) have been the object of considerable study, much of it focusing on supraspinal sites. Here, we adopted an alternative approach that emphasizes motor unit (MU) firing synchrony and patterns of discharge. To explore if these could account for known features of PD tremor, we recorded the instantaneous acceleration of the upper limb of 23 PD patients at rest or while they tried to hold a stable posture together with surface EMG and single MU discharges of upper limb muscles. Spectral, coherence and cross-correlation analyses of the recorded signals demonstrated alternating epoch- I and epoch-II intervals in PD patients both at rest and while they held a stable posture. Epoch-II intervals are characterized by the presence of 4-8 Hz overt tremor, enhanced MU synchrony and spike-doublets or triplets bearing a one-to-one relation to each tremor cycle. Epoch-I resembled physiological tremor in that it was characterized by 6-10 Hz non-overt tremor, lower MU synchrony and rhythmical MU firing at the intrinsic rate of the unit. The frequency of overt and non-overt tremor remained the same whether the patient was at rest or held a stable posture and the same was true of the remaining characteristics of epoch-I and epoch-II. The mean interval between spikes of a doublet/triplet varied between 30 and 50 ms and, for any given patient, remained roughly constant throughout measurements. This is the first time that enhanced MU synchrony and spike doublets/triplets characterized by relatively stable interspike intervals, are shown to accompany the overt tremor of PD patients. To account for our findings we propose that a two-state oscillatory spinal stretch reflex loop generates overt parkinsonian tremor in response to intermittent, descending, relatively high frequency oscillatory signals. © 2018 Agapaki, Christakos and Anastasopoulos.

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. © 2012 Elsevier Ltd.

We have investigated how the abnormal head posture and motility in spasmodic torticollis interferes with ecological movements such as combined eye-to-foot whole-body reorientations to visual targets. Eight mildly affected patients and 10 controls voluntarily rotated eyes and body in response to illuminated targets of eccentricities up to ±180. The experimental protocol allowed separate evaluation of the effects of target location, visibility and predictability on movement parameters. Patients' latencies of eye, head, trunk and foot motion were prolonged but showed a normal modification pattern when target location was predictable. Peak head-on-trunk displacement and velocity were reduced both ipsi- and contralaterally with respect to the direction of torticollis. Surprisingly, peak trunk velocity was also reduced, even more than in previously studied patients with Parkinson's disease. As a consequence, patients made short, hypometric gaze saccades and only exceptionally foveated initially nonvisible targets with a single large gaze shift (4 % of predictable trials as opposed to 30 % in controls). Foveation of distant targets was massively delayed by more than half a second on average. Spontaneous dystonic head movements did not interfere with the execution of voluntary gaze shifts. The results show that neck dystonia does not arise from gaze (head-eye) motor centres but the eye-to-foot turning synergy is seriously compromised. For the first time we identify significant 'secondary' complications of torticollis such as trunk bradykinesia and foveation delays, likely to cause additional disability in patients. Eye movements per se are intact and compensate for the reduced head/trunk performance in an adaptive manner. © 2013 The Author(s).

Conclusions: These findings are in line with previous data on the horizontal vestibulo-ocular reflex (VOR) from this laboratory and suggest that eye position signals do not modulate natural vestibular responses. Hence, the Alexander's law (AL) phenomenon cannot be interpreted simply as a consequence of vestibular or oculomotor nuclei activity modulation with desired gaze. Background: AL states that the intensity of the spontaneous nystagmus of a patient with a unilateral vestibular lesion grows with increasing gaze in the direction of the fast phase. Some of the mechanisms proposed to account for the gaze effects assume a direct modification of the normal VOR by eye position signals. We tested the validity of these assumptions and investigated the effects of gaze direction on the normal vertical human VOR in the behaviorally relevant high frequency range. Methods: Head and eye movements were recorded with the search coil method during passive head impulses in pitch, while subjects were asked to hold gaze at various elevation angles in 8° steps within ± 16° from the straight ahead reference position. Results: Upward and downward head rotations produced VOR gains of similar magnitude. Furthermore, the gain remained unaffected by eye-in-orbit position for both upward and downward head impulses. © 2012 Informa Healthcare.

This prospective study investigated whether plasma ionized calcium concentration abnormalities and other electrolyte disturbances represent risk factors for the development of critical illness polyneuromyopathy (CIPNM) in ICU patients. One hundred and ninety consecutive adult critically ill patients with prolonged ICU stay (longer than 7 days) were prospectively evaluated. Patients with acute weakness and/or weaning difficulties were subjected to extensive electrophysiological measurements in order to establish the diagnosis of CIPNM. All recognized and/or possible risk factors for development of CIPNM were recorded. The diagnosis of CIPNM was confirmed in 40 patients (21.05%). By applying a logistic regression model, hypocalcemia (P = 0.02), hypercalcemia (P = 0.01) and septic shock (P = 0.04) were independently associated with the development of CIPNM in critically ill patients. We found that septic shock and abnormal fluctuations of plasma Ca2+ concentration represent significant risk factors for the development of CIPNM in critically ill patients.

Alexander's law states that the amplitude of the spontaneous nystagmus grows with increasing gaze in the direction of the fast phase. Using the search-coil method we employed head impulses at various eye-in-orbit azimuth angles to test (i) whether the normal vestibulo-ocular reflex (VOR) in the behaviorally relevant high-frequency range has intrinsic properties that could account for Alexander's law and (ii) whether such properties can also be shown in patients with unilateral vestibulopathy. We showed that the gain of the VOR remained unaffected by eye-in-orbit position in contols and in patients, both on ipsilesional and contralesional stimuli. These findings suggest that eye-in-orbit position does not directly modulate the activity in VOR pathways, neither during unbalanced but reciprocal (in controls), nor during unbalanced and nonreciprocal natural vestibular stimulation (in patients). © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

We investigated whether turning problems in Parkinson's disease may be the result of abnormal horizontal multisegmental angular coordination. Ten mildly affected patients and controls stood upright and voluntarily reoriented eyes and body to illuminated targets of eccentricities up to ±180 degrees. The effects of target location, visibility, and predictability on movement parameters were evaluated. Patients' latencies were normal. Control subjects foveated large eccentricity targets with a single gaze shift in approximately 30% of predictable trials. Patients rarely did so (10% of predictable trials) because of reduced head-in-space and trunk velocity. This resulted in massive foveation delays in patients-an average of half a second for displacements of 180 degrees. The covariation of eye, head, and trunk rotations was quantified statistically by means of principal components analysis. In both groups, the combined movement was initially stereotyped and two principal components accounted for nearly all data variance-the original three mechanical degrees of freedom (i.e., eye-head-trunk) are reduced to two kinematic degrees of freedom. However, in patients, the eye contributed more, and the head and trunk less, to the gaze shift than in control subjects. Although the eye-to-foot turning synergy is preserved in early-stage parkinsonism, quantitative differences are prominent, particularly a larger ocular (and smaller head-trunk) contribution in patients. Turning problems in Parkinson's disease do not result from inability to assemble multisegmental movements, as patients' ability to control numerous degrees of freedom is preserved. However, trunk bradykinesia reduces the frequency of single-step gaze shifts, thus prolonging target acquisition time. Preserved eye motion compensates for trunk slowness. © 2011 Movement Disorder Society.

A 43-year-old man with infantile nystagmus syndrome complained of "head tremor" that would occur during attempted reading. Three-dimensional, combined eye and head recordings were performed with the magnetic search coil technique in two conditions: 1) looking straight-ahead under photopic conditions without a particular attentional focus and 2) reading a simple text held one meter away. A mainly vertical-horizontal spontaneous nystagmus was evident in both conditions, whereas head nodding emerged in the second condition. The head oscillated only in the vertical plane and concomitant analysis of eye and head displacement revealed a counterphase, compensatory pattern of the first harmonic of the INS waveform. This was verified by the significant negative peak of the crosscorrelogram at zero lag. Eye-in-space (gaze) displacement during nystagmic oscillations was thereby reduced suggesting a central adaptive behavior that may have evolved to partly compensate for the abnormal eye movements during reading. © 2011 Elsevier B.V. All rights reserved.

Shifting the direction of the line of sight in everyday life often involves rotations not only of the eyes and head but also of the trunk. Here, we investigated covariation patterns of eye-in-orbit, head-on-trunk and trunk-in-space angular horizontal displacements during whole-body rotations to targets of up to 180° eccentricity performed by standing healthy human subjects. The spatial covariation was quantified statistically across various behavioral task conditions (unpredictable, memory driven predictable, visual feedback) and constraints (accuracy) by principal components (PC) analysis. Overall, the combined movement was stereotyped such that the first two PCs accounted for essentially the whole data variance of combined gaze transfers up to about 400 ms, suggesting that the three mechanical degrees of freedom under consideration are reduced to two kinematic degrees of freedom. Moreover, quantification of segment velocity variability across repetitions showed that velocities of eye-in-space and head-in-space (i.e. 'end-point' velocity) were less variable than those of the elemental variables composing them. In contrast, three statistically significant PCs accounted for the covariation of the three segments during presumably vestibularly mediated nystagmic transfers, suggesting control by a separate driving circuit. We conclude that progression of the line of sight is initially stereotypic and fulfills criteria defining a motor synergy. © 2010 Springer-Verlag.

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. © 2009 The Authors. Journal compilation © 2009 The Physiological Society.

Displacements of the visual axis and multi-segmental (eye-to-foot) coordination in the yaw plane were studied in ten human subjects (Ss) during voluntary reorientations to illuminated targets of eccentricities up to 180°. We also investigated how knowledge of target location modifies the movement pattern. Eccentric targets (outbound trials) elicited eye, head, trunk and foot movements at latencies ca. 0.5, 0.6, 0.7 and 1.1 s, respectively. Knowledge of target location (return trials) reduced latencies for foot and trunk (but not eye and head) thus eye, head and trunk moved more en bloc. In most trials, the initial gaze shift fell short of the target and more than 50% of the visual angle was covered by the sum of vestibular nystagmic fast phases and head-in-space displacement, until target fixation. This indicates that during large gaze shifts the 'anticompensatory' role of the vestibulo-ocular reflex in target acquisition is prominent. During some predictable trials Ss acquired targets with a single large gaze shift, shortening target acquisition time by more than 200 ms. In these, gaze velocity (trunk-in-space + head-on-trunk + eye-in-orbit) remained often fairly constant for durations of up to 500 ms, suggesting that gaze velocity is a controlled parameter. Such pattern occurred during trunk mobilization, thus eye velocity co-varied with head-in-space rather than head-on-trunk velocity. Foot rotations were stereotyped and of constant frequency, suggesting they are generated by locomotor pattern generators. However, knowledge of target location reduced foot latencies indicating that local and supraspinal mechanisms interact for foot control. We propose that a single controller is responsible for the coupling of the multiple body segments and gaze velocity control during gaze shifts. © 2008 Springer-Verlag.

Muscle rigidity in PD (Parkinson's disease) patients represents an involuntary increase in muscle tone that stands out upon passive rotation of a joint. The pathophysiology of rigidity is still not well understood. We measured head-trunk torque in PD patients and normal controls during transient passive head rotations by means of servomotors under the instruction to the subjects to relax the neck muscles. We observed that rotation onset was followed by an initial rapid rise in resistive torque, similarly in both subject groups. It then leveled off or declined in controls. With PD patients, in contrast, the rise continued roughly proportional to head eccentricity almost until the end of the rotation. These observations led us to the hypothesis that the initial rise in torque represents reflexive head stabilization that normal subjects in the course of the rotational stimulus are able to suppress, whereas PD patients are less effective in doing so. The hypothesis was implemented into a dynamic control model of active and passive head rotation. Model simulations successfully reproduced the torque responses of normal subjects and PD patients in the present and previous studies. © 2009 Elsevier Inc. All rights reserved.

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° apart, ranging from ±45 to 360°. 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. © 2008 Elsevier B.V. All rights reserved.

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. (C) 2007 Elsevier B.V. All rights reserved.

Central nervous system (CNS) involvement in Langerhans' cell histiocytosis (LCH) has been described as a progressive neurological disorder marked by motor and cognitive decline. Detailed analysis of ocular motor abnormalities is lacking. We report on a 60-year-old male with histologically confirmed LCH who developed oscillopsia and gait ataxia over a 1-year period. Eye movements recorded with infrared oculography revealed a high rate of square-wave jerks (SWJ) with frequencies of 41 min-1 on average and amplitudes between 1° and 7°, as well as marked impairment of smooth tracking of sinusoidally moving targets. Furthermore, static posturography disclosed increased body sway, with an abnormally high sway path. The initial brain MRI was unremarkable. Due to the presumed cerebellar dysfunction we performed a second MRI 1 year later that disclosed deep cerebellar lesions compatible with LCH relapse within the CNS. The abnormal high SWJ rate and the impaired smooth pursuit performance correctly heralded later involvement of the cerebellum anticipating lesion appearance in the MRI. © 2007 Elsevier B.V. All rights reserved.

Intact cerebellum cytoarchitecture and cellular communication are indispensable for successful motor coordination and certain forms of memory. Cytosine arabinoside (AraC), often used as an anti-neoplastic agent in humans, can have cerebellum-targeting adverse effects. In order to characterize the nature of AraC-induced cerebellar lesions in an adult rodent model, we have administered AraC (400 mg/kg b.w., i.p.) in adult male Wistar rats for 5 days. The animals' walking pattern, motor coordination, locomotion, spatial navigation and cognition were evaluated, along with neurofilament- and calbindin-like distribution in the cerebellum. AraC-treated rats demonstrated a disturbed walking pattern and a reduced ability of motor learning and coordination, indicative of a mild cerebellar deficit. Although the general locomotion and spatial cognition of AraC-treated rats was not significantly altered, their navigation into the water, in terms of swimming velocity, was irregular, compared to vehicle-treated animals. Neurofilament-like immunostaining was reduced in the molecular cerebellar layer, while calbindin D 28 kDa levels were increased in Purkinje neurons, following AraC treatment. Administration of the antioxidant N-acetylcysteine (NAC) (200 mg/kg b.w., p.o.), for 14 days (prior to and during AraC treatment) largely prevented the AraC-induced behavioral deficits. Our in vivo model of neurotoxicity provides data on the AraC-induced behavioral and cellular alterations concerning the adult rat cerebellum. Furthermore, it provides evidence of a possible neuroprophylactic role of the antioxidant N-acetylcysteine in this model of chemotherapy-induced toxicity. © 2006 Elsevier Inc. All rights reserved.

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.

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° 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. © Springer-Verlag 2005.

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.

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.

In order to reduce the examination time of the Distortion Product Otoacoustic Emissions (DPOAE) test, we investigated the applicability of the multiple-tone pairs method by comparing the DPOAE evoked by 4- and 3-tone pairs (Sim) with the conventional 1-tone pair (Seq) in 116 ears of human adults with normal hearing (NH) and 86 ears with sensorineural hearing loss (SNHL). We found that: (1) DPOAE amplitudes in the NH group obtained with the Sim method were strongly correlated with those of Seq. (2) DPOAE amplitude and noise level mean values obtained with the Seq method were significantly higher than those obtained with Sim. (3) DPOAE amplitude was independent of the stimulation side (right vs. left ears). (4) Both methods can equally distinguish ears with NH and a low degree of SNHL from those with higher degrees of SNHL. (5) Examination time was shorter with the Sim method in both groups. In conclusion, the Sim method produces results similar to those of Seq. However, a significant difference between the two methods in relation to DPOAE amplitudes and noise levels was found. Because of this, normal data for both the DPOAE amplitude and noise level are required to improve the sensitivity of the Sim method. The mean examination time in both groups (NH and SNHL) was shorter with the Sim method. Therefore, the multiple-tone pairs stimulation method seems to be more suitable when it is used as an auditory screening test.