[Video-based head impulse test. Importance for routine diagnostics of patients with vertigo]. / Videobasierter Kopfimpulstest. Bedeutung für die Routinediagnostik von Schwindelerkrankungen.

Dizziness is one of the most common complaints in Germany which leads to medical consultation. Diagnosis is based on patient history, clinical examination and laboratory tests. In order to find or exclude a vestibular lesion, methods such as caloric irrigation, rotational chair tests or vestibular-evoked myogenic potentials were previously applied. Recently, a new diagnostic tool has been made available for application in daily practice: the video head impulse test (vHIT). Due to the easy and fast application for the examiner, good tolerance by the patient and high sensitivity for vestibular lesions, the vHIT has the potential to improve the diagnosis and therapy of patients suffering from vertigo in widespread medical care in Germany. This article reports on experiences with this new method after examination of over 1,500 patients in the academic vertigo centre in Lübeck. The principles and application of the vHIT in daily clinical routine are described and the many advantages but also some pitfalls are highlighted. As a consequence of a wider clinical use it is expected that the vHIT will lead to an increased detection of vestibular dysfunctions not only in clinically suspected vestibular diseases but also in other common neurological diseases (e.g. polyneuropathy or cerebellar ataxia). This may change the prevalence of different vestibular diseases, broaden knowledge about other common diseases with gait imbalance as the leading symptom and provide a quantitative measure that can be used to longitudinally assess the effects of therapeutic interventions.

Somatosensory function in asymptomatic Parkin-mutation carriers.

BACKGROUND AND PURPOSE: It is a matter of debate whether somatosensory abnormalities in Parkinson's disease (PD) precede or follow PD motor signs and whether they are of central or peripheral origin. The sensory sural nerve action potential amplitude (SNAP) was previously reported to be reduced in symptomatic Parkin-associated PD. The aim of our study was to investigate asymptomatic Parkin-mutation carriers to elucidate whether putative somatosensory abnormalities precede motor symptoms therewith helping to determine the origin of somatosensory signs. METHODS: Nine subjects with Parkin-mutations and nine healthy controls were examined clinically, with quantitative sensory testing (QST) and neurography. RESULTS: There was a higher frequency of cold pain threshold abnormalities and hypofunction of Abeta-fibres/central afferent pathways in Parkin-mutation carriers compared to controls. Neurography of Parkin-mutation carriers did not indicate peripheral neuropathy. CONCLUSIONS: Sensory abnormalities of asymptomatic Parkin-mutation carriers as obtained by QST suggest impairment of either small and large peripheral pathways or central somatosensory processing. In contrast to Parkin-associated PD, asymptomatic Parkin-mutation carriers do not show a reduced SNAP.

Vergence deficits in patients with cerebellar lesions.

The cerebellum is part of the cortico-ponto-cerebellar circuit for conjugate eye movements. Recent animal data suggest an additional role of the cerebellum for the control of binocular alignment and disconjugate, i.e. vergence eye movements. The latter is separated into two different components: fast vergence (to step targets) and slow vergence (to ramp and sinusoidal targets). The aim of this study was to investigate whether circumscribed cerebellar lesions affect these dynamic vergence eye movements. Disconjugate fast and slow vergence, conjugate smooth pursuit and saccades were binocularly recorded by a scleral search coil system in 20 patients with acute cerebellar lesions (all ischemic strokes except for one) and 20 age-matched healthy controls. Patients showed impairment of slow vergence while fast vergence was unaffected. Slow vergence gain to sinusoidal targets was significantly reduced, both in convergence and divergence direction. Divergence but not convergence velocity to ramp targets was reduced. Conjugate smooth pursuit eye movements to sinusoidal and to step-ramp targets were impaired. Patients had saccadic hypometria. All defects were particularly expressed in patients with vermis lesions. In contrast to recent animal data fast vergence was not impaired in any of our patient subgroups. We conclude that (i) the human cerebellum, in particular the vermis, is involved in the processing of dynamic vergence eye movements and (ii) cerebellar lesions elicit dissociable effects on fast and slow vergence.

Somatosensory processing in a German family with PINK1 mutations: its potential role in Parkinson disease.

BACKGROUND: It is unclear whether sensory symptoms in Parkinson disease (PD) are of primary or of secondary origin attributable to motor symptoms such as rigidity and bradykinesia. OBJECTIVE: The aim of this study was to elucidate whether sensory abnormalities are present and may precede motor symptoms in familial parkinsonism by characterizing sensory function in symptomatic and asymptomatic PINK1 mutation carriers. METHODS: Fourteen family members with PINK1 mutation and 14 healthy controls were examined clinically, with nerve conduction studies and quantitative sensory testing (QST). RESULTS: Thresholds for mechanical detection, mechanical pain and pressure pain were higher in PINK1 mutation carriers compared to controls. Higher thresholds for mechanical detection, mechanical pain and pressure pain were even found in asymptomatic, clinically not or only mildly affected PINK1 mutation carriers. CONCLUSIONS: Data suggest that PINK1-associated PD is associated with a primary hypofunction of nociceptive and non-nociceptive afferent systems that can already be found at the time when motor signs of PD are only subtle. As nerve conduction studies did not reveal differences between PINK1 mutation carriers and controls, we propose that the somatosensory impairment is related to abnormal central somatosensory processing.

Dissociable neural activity to self- vs. externally administered thermal hyperalgesia: a parametric fMRI study.

Little is known regarding how cognitive strategies help to modulate neural responses of the human brain in ongoing pain syndromes to alleviate pain. Under pathological pain conditions, any self-elicited contact with usually non-painful stimuli may become painful. We examined whether the human brain is capable of dissociating self-controlled from externally administered thermal hyperalgesia in the experimental capsaicin model. Using functional magnetic resonance imaging, 17 male subjects were investigated in a parametric design with heat stimuli at topically capsaicin-sensitized skin. In contrast to external stimulation, self-administered pain was controllable. For both conditions application trials without noticeable thermal stimulation were introduced and used as high-level baseline (HLB) to account for the capsaicin-induced ongoing pain and other covariables. Following subtraction of the HLB, the anterior insula and the anterior cingulate cortex (ACC) but not the somatosensory cortices maintained parametric neural responses to thermal hyperalgesia. A stronger pain-related activity increase during self-administered stimuli was observed in the posterior insula. In contrast, prefrontal cortex showed stronger increases to uncontrollable external heat stimuli. In the state of ongoing pain (capsaicin), pain-intensity-encoding regions (anterior insula, ACC) but not those with sensory discriminative functions (SI, SII) showed graded, pain-intensity-related neural responses in thermal hyperalgesia. Some areas were able to dissociate between self- and externally administered stimuli in thermal hyperalgesia, which might be related to differences in perceived controllability. Thus, neural mechanisms maintain the ability to dissociate external from self-generated states of injury in thermal hyperalgesia. This may help to understand how cognitive strategies potentially alleviate chronic pain syndromes.

The eyelid and its contribution to eye movements.

Lid and electromyographic recordings have contributed significantly to our understanding of clinical lid disorders. Tonic lid disorders (e.g. ptosis, blepharospasm, lid retraction, blepharocolysis) can be distinguished from dynamic lid disorders (lid lag) and from specific deficits of eye-lid coordination (e.g. lid nystagmus). Electromyographic recordings allow the identification of specific lid disorders that benefit from effective therapeutic interventions, e.g., botulinum toxin injections. Rapid lid closure (blink), which exerts substantial neural influence on oculomotor systems without obscuring vision, can be used for the diagnosis of brainstem disease.

Blink amplitude but not saccadic hypometria indicates carriers of Parkin mutations.

We investigated saccades, eyelid blinks, and their interaction in symptomatic (n = 22) and asymptomatic (n = 31) subjects with (n = 19) and without (n = 34) Parkin mutations. Saccadic hypometria was correlated with clinical symptoms of Parkinson's disease, irrespective of mutational status. By contrast, blink amplitude was increased in carriers of Parkin mutations independent of their clinical status. Saccade main sequence and blink effects on saccades were normal. We propose that increased blink amplitude may serve as an endophenotype in carriers of Parkin mutations.

The anterior cingulate cortex contains distinct areas dissociating external from self-administered painful stimulation: a parametric fMRI study.

The anterior cingulate cortex (ACC) has a pivotal role in human pain processing by integrating sensory, executive, attentional, emotional, and motivational components of pain. Cognitive modulation of pain-related ACC activation has been shown by hypnosis, illusion and anticipation. The expectation of a potentially noxious stimulus may not only differ as to when but also how the stimulus is applied. These combined properties led to our hypothesis that ACC is capable of distinguishing external from self-administered noxious tactile stimulation. Thermal contact stimuli with noxious and non-noxious temperatures were self-administered or externally applied at the resting right hand in a randomized order. Two additional conditions without any stimulus-eliciting movements served as control conditions to account for the certainty and uncertainty of the impending stimulus. Calculating the differences in the activation pattern between self-administered and externally generated stimuli revealed three distinct areas of activation that graded with perceived stimulus intensity: (i) in the posterior ACC with a linear increase during external but hardly any modulation for the self-administered stimulation, (ii) in the midcingulate cortex with activation patterns independent of the mode of application and (iii) in the perigenual ACC with increasing activation during self-administered but decreasing activation during externally applied stimulation. These data support the functional segregation of the human ACC: the posterior ACC may be involved in the prediction of the sensory consequences of pain-related action, the midcingulate cortex in pain intensity coding and the perigenual ACC is related to the onset uncertainty of the impending stimuli.

Pontine lesions may cause selective deficits of "slow" vergence eye movements.

To address the role of pontine nuclei in vergence control, eye movements to ramp ('slow vergence') and step targets ('fast vergence') were recorded in two patients with unilateral mediolateral pontine infarctions and in ten healthy controls. 'Slow' vergence and conjugate smooth pursuit eye movements were impaired while 'fast' vergence was not. We conclude that like smooth pursuit signals, vergence signals are distributed in the pontine nuclei.

Dissociable cerebellar activity during spatial navigation and visual memory in bilateral vestibular failure.

OBJECTIVE: Spatial orientation and navigation depends on information from the vestibular system. Previous work suggested impaired spatial navigation in patients with bilateral vestibular failure (BVF). The aim of this study was to investigate event-related brain activity by functional magnetic resonance imaging (fMRI) during spatial navigation and visual memory tasks in BVF patients. METHODS: Twenty-three BVF patients and healthy age- and gender matched control subjects performed learning sessions of spatial navigation by watching short films taking them through various streets from a driver's perspective along a route to the Cathedral of Cologne using virtual reality videos (adopted and modified from Google Earth). In the scanner, participants were asked to respond to questions testing for visual memory or spatial navigation while they viewed short video clips. From a similar but not identical perspective depicted video frames of routes were displayed which they had previously seen or which were completely novel to them. RESULTS: Compared with controls, posterior cerebellar activity in BVF patients was higher during spatial navigation than during visual memory tasks, in the absence of performance differences. This cerebellar activity correlated with disease duration. CONCLUSIONS: Cerebellar activity during spatial navigation in BVF patients may reflect increased non-vestibular efforts to counteract the development of spatial navigation deficits in BVF. Conceivably, cerebellar activity indicates a change in navigational strategy of BVF patients, i.e. from a more allocentric, landmark or place-based strategy (hippocampus) to a more sequence-based strategy. This interpretation would be in accord with recent evidence for a cerebellar role in sequence-based navigation.

Diverse effects of Purkinje cell loss on deep cerebellar and vestibular nuclei neurons in Purkinje cell degeneration mutant mice: a possible compensatory mechanism.

The genetic defect in the Purkinje cell degeneration (PCD) mutant mouse completely disrupts the cerebellar corticonuclear connection through intrinsic action on the final integrating unit of the cerebellar cortex, the Purkinje cell (PC). The postsynaptic target neurons of the PC in the deep cerebellar nuclei (DCN) and the vestibular nuclei (VN) are denervated by this PC loss by more than two-thirds of their total y-aminobutyric acid (GABA)-ergic innervation. This massive disinhibition should be reflected in an increased and thus electrophysiologically detectable activity of the respective neurons. To address this question, we performed extracellular recordings of PCD mutant and corresponding wild-type VN neurons under sinusoidal vestibular stimulation. The response amplitudes (neuronal response to sinusoidal rotation) of VN neurons in PCD mutant mice showed a decrease rather than the expected increase. The same was true for the mean resting rate, whereas the phase relationships were unaffected for the most part. This finding is a clear indication of compensatory reactions in the VN that substitute quantitatively for the lost PC inhibition. The expression of the calcium-binding protein parvalbumin (Parv) is assumed to correlate with the physiological activity of neurons, and Parv is localized predominantly in inhibitory neurons. Because inhibitory inter- or projecting neurons are also largely denervated by the PC loss, Parv immunocytochemistry also was performed. In wild-type mice, only very few Parv-immunopositive (Parv+) somata were present in the VN, and none were present in the DCN. In PCD mutant mice, a substantial number of Parv+ neuronal somata were visible in the VN, and even more were visible in the DCN. This increase in Parv+ somata in PCD mutant mice is closely related temporally and spatially to the extent of denervation caused by the PCD. Parv+ neuronal somata are first visible in the dentate nucleus at postnatal day (P) 24 and appear in the other cerebellar and VN up to P29. Direct double labeling of Parv and GABA and of Parv and glycine reveals that the large majority of Parv + neurons colocalize GABA, glycine, or both inhibitory transmitters. These results show that neurons that are postsynaptic to cerebellar PC develop diverse physiological and biochemical reactions in the course of genetically determined PCD. These mechanisms are likely to contribute to the phenotypically mild motor disturbances observed in PCD mutant mice.

Contralesionally beating torsional nystagmus in a unilateral rostral midbrain lesion.

The rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal (iC) are involved in the generation of vertical and torsional saccades and gaze holding. Midbrain lesions involving either riMLF or iC produce a tonic torsional ocular deviation to the contralesional side. Lesions of the iC are associated with an ipsilesional torsional nystagmus (TN). For the first time, we describe a patient with a unilateral midbrain lesion showing a contralesionally beating torsional nystagmus. This nystagmus was probably caused by a lesion involving the riMLF.

Seesaw nystagmus associated with involuntary torsional head oscillations.

OBJECTIVE: To assess the diagnostic value of eye-head coupling in seesaw nystagmus (SSN). BACKGROUND: SSN is a rare binocular disorder characterized by alternating skew deviation and conjugate ocular torsion. METHODS: We examined a patient with a congenital nystagmus that switched to a pendular SSN on near viewing and was associated with involuntary torsional head oscillations. RESULTS: The binocular torsional eye movements were in phase with the clinically visible head oscillations (i.e., head movements were not compensatory for the torsional eye movements). CONCLUSION: This finding suggests that torsional eye-head coupling in pendular SSN has a common pathologic origin. We suggest that alternating vertical disparity of both eyes in pendular SSN is compatible with an oscillating signal acting on an intact vestibular system. The absence of brainstem lesions on high-resolution MRI supports this assumption.

Perilymph fistula associated with pulse-synchronous eye oscillations.

Three-dimensional eye movements (scleral search coil system) were recorded in a patient with a surgically acquired perilymph fistula of the left horizontal semicircular canal. Spontaneous horizontal pendular nystagmus was found to be related to the heart rate and may be caused by pressure transfer of blood pulses to the labyrinth. In addition, a contralesional horizontal jerk nystagmus was elicited by Valsalva maneuver, indicating that Ewald's first law may not only be valid for excitation but also for inhibition.

Localizing value of torsional nystagmus in small midbrain lesions.

BACKGROUND: The topodiagnostic value and specificity of nystagmus in patients with mesencephalic lesions and its relation to tonic torsional deficits and vertical saccade deficits is controversial and anecdotal. METHODS: The authors examined 11 patients with vascular MRI-identified mesencephalic lesions and clinical evidence of vertical-torsional nystagmus on gaze straight ahead, focusing on the three-dimensional nystagmus components recorded with the three-dimensional search coil technique. RESULTS: Combined lesions of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal (iC) are much more frequent than riMLF and, in particular, iC lesions alone. Eight patients showed contralesional torsional nystagmus with a conjugate vertical component on gaze straight ahead and had anatomic (MRI) and clinical evidence (slowing of vertical saccades) for riMLF involvement. Tonic ocular torsion and the subjective visual vertical were shifted to the contralesional side (n = 7). Torsional nystagmus to the ipsilesional side was uncommon (n = 3) and found in patients with midbrain lesions involving the iC, all of whom also had decreased time constants of the slow phases of gaze-evoked nystagmus. CONCLUSIONS: Contrary to previous proposals, contralesional torsional nystagmus was the most frequent direction and is probably not compensatory for contralesional tonic ocular torsion. Small amplitude vertical saccades with normal velocities in association with ipsilesional torsional nystagmus may indicate isolated iC lesions. Torsional nystagmus following mesencephalic lesions may last for years and may help to distinguish rostral (riMLF) from caudal (iC) midbrain lesions.

Disappearance of central thalamic pain syndrome after contralateral parietal lobe lesion: implications for therapeutic brain stimulation.

At present there is hardly any appropriate therapy for central pain syndromes available. We report on a unique case of a central thalamic pain syndrome that did not respond to any therapy but disappeared after an additional contralateral parietal lobe lesion. This example indicates that lesions affecting the bilateral balance of thalamo-parietal circuits may lead to pain relief in patients with central pain syndrome, which probably constitutes a bilateral disorder of functional plasticity. This should be taken into account in chronic brain stimulation for persistent pain states.

Pentobarbital, in subanesthetic doses, depresses spinal transmission of nociceptive information but does not affect stimulation-produced descending inhibition in the cat.

The present study evaluates the effect of systemic pentobarbital on the spinal transmission of nociceptive information and on stimulation-produced descending inhibition in the deeply anesthetized, paralyzed cat. Single neuronal responses to noxious skin heating were recorded extracellulary in the lumbar dorsal horn and found to be depressed by pentobarbital at subanesthetic doses (4.0, 8.0, 17.0 and 24.5 mg/kg) in a dose-dependent manner. At 0.5 and 1.5 mg/kg, depression by pentobarbital was positively correlated with the depth of the recording site in the spinal cord (laminae IV-VI), i.e., neurons in deeper laminae (V-VI) were attenuated, while neurons in lamina IV were unaffected. At all doses tested, pentobarbital failed to affect stimulation-produced descending inhibition from either the midbrain periaqueductal gray or the medullary nucleus raphe magnus. The present data furnish evidence for the antinociceptive potency of pentobarbital, they do not support the view that a 'partial pharmacological spinal cord transection' would attenuate stimulation-produced descending inhibition of nociceptive dorsal horn neurons.

Spinal somatostatin superfusion in vivo affects activity of cat nociceptive dorsal horn neurons: comparison with spinal morphine.

A controversy exists concerning the role of the neuropeptide somatostatin for the transmission or inhibition of nociceptive information in the spinal cord. To better correlate electrophysiological effects of somatostatin at single cell level with results obtained with intrathecal injections of somatostatin in behaving animals and human pain patients we applied somatostatin to the spinal cord by controlled superfusion of the recording segment in vivo. The hypothesis of an opioid link and possible neurotoxic effects of somatostatin were also addressed. In cats deeply anaesthetized with pentobarbitone, halothane and nitrous oxide, extracellular recordings were made from 27 neurons located in laminae I-VI. All neurons responded to both innocuous mechanical and noxious radiant heat stimuli applied to the glabrous skin of the ipsilateral hindpaw. The dorsal surface of the spinal cord was superfused at the recording segment by means of a Perspex chamber (7 x 7 mm). Somatostatin superfusions at 1.2 microM had no effect on responses to noxious heat. Responses were, however, depressed by somatostatin at 61 microM to 59.7 +/- 5.1% of control and by somatostatin at 1.53 mM to 39.9 +/- 9.5% of control. This inhibition was not antagonized by the mu-opiate antagonist naloxone applied to the spinal cord at concentrations of 2.7 mM, either together with somatostatin, or after the inhibition by somatostatin had fully developed. Neuronal responses were linear functions of the skin temperatures for stimulation intensities between 42 degrees C and 52 degrees C. The slopes of these stimulus response functions were reduced during somatostatin superfusion at 61 microM to 46.8 +/- 9.3% of control, without changing the temperature thresholds for responding (42.5 +/- 0.6 degrees C). Somatostatin superfusion at 61 microM had no effect on the number of action potentials evoked by innocuous skin brushing, or by electrical stimulation of primary afferent A-fibres in cutaneous nerves. The amplitude of intraspinally recorded field potentials evoked by these electrical nerve stimuli was also unaffected by somatostatin. The inhibition of nociceptive spinal dorsal horn neurons by spinally administered morphine was assessed in eight experiments. Morphine reduced noxious heat-evoked responses to 42.1 +/- 9.6% of control at 0.3 mM and to 51.8 +/- 6.9% of control at 3.0 mM. The slopes of the stimulus-response functions were reduced by morphine at 0.3 mM to 53.1 +/- 11.3% of control, without changing the temperature thresholds (42.7 degrees C). Naloxone superfusion (2.7 mM) reliably antagonized the inhibition by morphine. Brush-evoked responses were not, or much less, affected by spinal morphine.(ABSTRACT TRUNCATED AT 400 WORDS)

Vestibular influence on the binocular control of vertical-torsional nystagmus after lesions in the interstitial nucleus of Cajal.

The interstitial nucleus of Cajal (iC) is a center of the velocity-to-position integration for vertical and torsional eye movements. In addition, iC has projections to and from the vestibular nuclei. Therefore the vestibular influence on the binocular alignment of vertical-torsional nystagmus after unilateral reversible iC inactivations was investigated in the alert monkey using 3D binocular search-coil recordings. The nystagmus was compared with the eye muscle rotation axes, which were corrected for the tonic ocular torsion elicited by the iC inactivation. Rotation axes of nystagmus were different for both eyes and revealed a co-activation of eye muscles similar to the effects of electrical stimulation of the anterior canal nerve. This suggests that, in addition to the deficient neural integrator, a vestibular imbalance contributes to the vertical-torsional nystagmus after iC inactivations.