Kognitive Mechanismen beeinflussen die Schmerzwahrnehmung erheblich. Wir haben zuvor zeigen konne... more Kognitive Mechanismen beeinflussen die Schmerzwahrnehmung erheblich. Wir haben zuvor zeigen konnen, dass sich neuronale Antworten auf fremdzugefuhrte Schmerzreize z.T. erheblich unterscheiden, wenn sie selbst ausgelost werden, z.B. durch die bessere Pradiktion der sensorischen Konsequenz. Bei Allodynie-Patienten kommt es bereits bei Reizen in ihrer naturlichen Umwelt zur schmerzhaften Reizung. Diese Studie vergleicht daher neuronale Antwortmuster zwischen selbst und fremd zugefuhrten Schmerzreizen bei der experimentellen thermischen Allodynie. Mit der fMRT wurden 17 gesunde, mannliche Rechtshander in einem parametrischen Block-Design mit unterschiedlichen thermischen Stimuli (37°, 40°, 43°C) untersucht. Die thermische Allodynie wurde mit einer topisch aufgetragenen Capsaicinlosung am rechten Oberschenkel ausgelost. Neben der besseren Pradiktabilitat des Stimulationsvorgangs bei der selbst zugefuhrten Stimulation unterschied sich die fremd zugefuhrte Stimulation durch die fehlende Kontrollierbarkeit des Stimulus. Fur beide Versuchsbedingungen wurde eine high-level baseline (HLB) eingefuhrt, um den durch Capasaicin ausgelosten Spontanschmerz und andere kognitive Variablen (z.B. Antizipation) zu kontrollieren. Subtraktionsanalysen mit der HLB konnten wahrend der thermischen Allodynie parametrische Antwortmuster in der anterioren Insula, im anterioren zingularen Kortex (ACC), nicht aber im primaren (SI) und sekundaren somatosensorischen Kortex (SII) nachweisen. Eine steilere Antwortfunktion fur selbst zugefuhrte Schmerzreize fand sich in der posterioren Insel. Dagegen zeigten der prafrontale Kortex und der Kleinhirnwurm steilere Antwortfunktionen bei fremd zugefuhrten Schmerzen. Diese Studie zeigt parametrisch modulierte Antwortfunktionen bei der cerebralen Verarbeitung allodyner Schmerzen. Interessanterweise zeigten die mit der affektiv-emotionalen Komponente des Schmerzes assoziierten Hirnregionen (anteriore Insula, ACC) in der Allodynie eine parametrische Antwortfunktion, nicht jedoch diejenigen fur die sensorisch-diskriminativen Funktionen (SI, SII). Vor allem die Aktivitat der posterioren Insel unterschied sich bei der fremd vs. selbst zugefuhrten Allodynie. Diese Ergebnisse legen nahe, dass Kontrollierbarkeit und Selbstkontrolle bei Patienten mit anhaltenden allodynen Schmerzen berucksichtigt werden mussen, da sie zu unterschiedlichen Aktivierungen und Wahrnehmungen fuhren.
Right hemisphere stroke patients frequently experience spatial neglect, a severe lack of awarenes... more Right hemisphere stroke patients frequently experience spatial neglect, a severe lack of awareness for contralesional hemispace. Although neglect counts among the strongest predictors for poor functional outcome after stroke, there is no established therapy, particularly not for the acute stage. In a randomized controlled trial, we compared the combined treatment of hemifield eye patching and repetitive optokinetic stimulation in acute stroke patients with neglect to the spontaneous course. Outcome measures were a neuropsychological test battery for neglect as well as scales of functional independence and clinical impairment. Outcomes were assessed at baseline (day 1), post treatment (day 8), and at 1-month follow-up (day 30). Final analysis included 21 acute right hemisphere stroke patients with neglect (23 enrolled, 2 lost to follow-up) allocated either to the treatment (1 week hemifield eye patching and daily sessions of optokinetic stimulation, n=11) or the control group (no neg...
Objective: To assess the diagnostic value of eye-head coupling in seesaw nystagmus(SSN). Back-gro... more Objective: To assess the diagnostic value of eye-head coupling in seesaw nystagmus(SSN). Back-ground: 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.
The role of pontine nuclei in vergence eye movements to "step&am... more The role of pontine nuclei in vergence eye movements to "step" targets ("fast" vergence) is unknown. Eye movements were recorded in two patients with unilateral pontine infarctions and in 11 healthy controls. In addition to the deficit of "slow" vergence, "fast" vergence was particularly impaired. However, conjugate saccades did not differ from controls, but smooth pursuit eye movements did. The authors conclude that "fast" vergence palsy is not only caused by midbrain but also upper pontine lesions.
Auditory and vestibular function was examined in 29 patients with unilateral sensorineural hearin... more Auditory and vestibular function was examined in 29 patients with unilateral sensorineural hearing loss to identify characteristic vestibulocochlear lesion patterns. In 45%, a vestibular lesion was found, of which 53% had a combined impairment of the cochlea and the ipsilateral posterior semicircular canal, possibly reflecting vascular disease in the common cochlear artery.
It is controversial whether opsoclonus is a cerebellar or brainstem disorder. Two patients whose ... more It is controversial whether opsoclonus is a cerebellar or brainstem disorder. Two patients whose opsoclonus largely disappeared on eye closure underwent fMRI. A comparison of these two states revealed neither vermal nor brainstem activation but rather a bilateral activation in the deep cerebellar nuclei in excess of what the authors found in healthy subjects. The results support a crucial role of the fastigial nucleus in opsoclonus.
Vergence eye movements were recorded with the scleral search-coil system in 32 healthy subjects (... more Vergence eye movements were recorded with the scleral search-coil system in 32 healthy subjects (ages 19-73 years) to characterize the age-related effects on the dynamic parameters of vergence responses to step (transient components) and ramp or sinusoidal targets (sustained components) under natural viewing conditions. Transient vergence showed an age-related increase in latency and decreases in peak velocity and acceleration in the binocular stimulus condition but not in accommodative vergence. Sustained vergence showed no age-related effect in the binocular condition, but there was an age-related decrease in accommodative vergence steady-state velocity and an increase in latency. Age-related changes of the transient and sustained components were very similar to those reported for saccades and smooth pursuit; they thus might support a distinction between a sustained and transient vergence system. Furthermore, such age-related effects have to be taken into account when assessing eye movement disorders in neurodegenerative and cerebrovascular diseases.
Journal of Neurology, Neurosurgery & Psychiatry, 2009
It is unclear whether sensory symptoms in Parkinson disease (PD) are of primary or of secondary o... more 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. 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. Fourteen family members with PINK1 mutation and 14 healthy controls were examined clinically, with nerve conduction studies and quantitative sensory testing (QST). 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. 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.
Journal of Neurology, Neurosurgery & Psychiatry, 2005
Background: Spontaneous nystagmus caused by dorsolateral medullary infarction may be of vestibula... more Background: Spontaneous nystagmus caused by dorsolateral medullary infarction may be of vestibular origin. Objectives: To test if imbalance of the central pathways of the semicircular canals contributes to spontaneous nystagmus in dorsolateral medullary syndrome. Methods: We examined four patients with dorsolateral medullary syndrome and recorded spontaneous nystagmus binocularly at gaze straight ahead with the three-dimensional search coil technique. The median slow phase velocity of the nystagmus was analysed in the light and in the dark, and the normalised velocity axes were compared with the rotation axes as predicted from anatomical data of the semicircular canal. Results: The slow phase rotation axes of all patients aligned best with the rotation axes resulting from stimulation of the contralesional posterior and horizontal semicircular canals. This alignment cannot be explained by pure otolith imbalance. Conclusion: We propose that vestibular imbalance caused by an ipsilesional lesion of the central semicircular canal pathways of the horizontal and anterior semicircular canals largely accounts for spontaneous nystagmus in dorsolateral medullary syndrome.
Perceived control over pain can attenuate pain perception by mechanisms of endogenous pain contro... more Perceived control over pain can attenuate pain perception by mechanisms of endogenous pain control and emotional reappraisal irrespective of whether this control is exerted or only perceived. Self-initiated termination of pain elicits different expectations of subsequent pain relief as compared to perceived pain control. It is unknown whether and how this perceived vs. exerted control on pain differs and affects subsequent pain relief. Using fMRI, we studied two factors of pain control on pain relief: the (i) sense of control (perceived control but no execution) and (ii) the execution of control (exerted control). To account for the impact of factual execution of pain control on pain relief we applied bearable short and hardly bearable long contact-heat stimuli which were applied either controllable or not. Using controllability as factor, there was dissociable neural activity during pain relief: following the perceived control condition neural activity was found in the orbitofrontal and mediofrontal cortex and, following the exerted control condition, in the anterolateral and dorsolateral prefrontal cortex and posterior parietal cortex. We conclude that (i) pain controllability has an impact on pain relief and (ii) the prefrontal cortex shows dissociable neural activity during pain relief following exerted vs. perceived pain control. This might reflect the higher grade of uncertainty during pain relief following perceived pain control mediated by the orbitofrontal and medial prefrontal cortex and processes of working memory and updating expectations during pain relief following exerted control mediated by the lateral prefrontal cortex.
Neuregulins and their Erbb receptors have been implicated in neuromuscular synapse formation by r... more Neuregulins and their Erbb receptors have been implicated in neuromuscular synapse formation by regulating gene expression in subsynaptic nuclei. To analyze the function of Erbb2 in this process, we have inactivated the Erbb2 gene in developing muscle fibers by Cre/Lox-mediated gene ablation. Neuromuscular synapses form in the mutant mice, but the synapses are less efficient and contain reduced levels of acetylcholine receptors. Surprisingly, the mutant mice also show proprioceptive defects caused by abnormal muscle spindle development. Sensory Ia afferent neurons establish initial contact with Erbb2-deficient myotubes. However, functional spindles never develop. Taken together, our data suggest that Erbb2 signaling regulates the formation of both neuromuscular synapses and muscle spindles.
ABSTRACT It is a matter of debate whether somatosensory abnormalities in Parkinson's dise... more ABSTRACT 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. Nine subjects with Parkin-mutations and nine healthy controls were examined clinically, with quantitative sensory testing (QST) and neurography. 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. 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.
The cerebellum is part of the cortico-ponto-cerebellar circuit for conjugate eye movements. Accor... more The cerebellum is part of the cortico-ponto-cerebellar circuit for conjugate eye movements. Accordingly, cerebellar lesions cause smooth pursuit deficits and saccadic dysmetria. In contrast, the role of the cerebellum for disconjugate, i.e. vergence eye movements in humans are still unknown. The aim of this study was to investigate whether cerebellar lesions affect vergence eye movements. Similar to conjugate eye movements, vergence can be separated into two different components: vergence to step targets (fast vergence) and vergence to ramp and sinusoidal targets (slow vergence). Eye movements (fast and slow vergence, smooth pursuit, saccades) were binocularly recorded with the scleral search coil system in 20 patients with acute cerebellar lesions (ischemic strokes) and agematched healthy controls. Small dim laser stimuli were presented on an earth horizontal platform at the level of the subject’s nose. Smooth pursuit always had a constant vergence angle (isovergence). The majority of patients had unilateral lesions in the territory of the posterior inferior cerebellar artery (3 patients with infarctions in the superior cerebellar artery territory, one cavernoma patient). Group analysis revealed impairment of both conjugate and disconjugate eye movements as well as reduced saccadic gain (Table 1).
1. Clin Neurophysiol. 2010 Oct;121(10):1786-7. Epub 2010 May 6. Overestimation of saccadic peak v... more 1. Clin Neurophysiol. 2010 Oct;121(10):1786-7. Epub 2010 May 6. Overestimation of saccadic peak velocity recorded by electro-oculography compared to video-oculography and scleral search coil. Lappe-Osthege M, Talamo S, Helmchen C, Sprenger A. ...
Kognitive Mechanismen beeinflussen die Schmerzwahrnehmung erheblich. Wir haben zuvor zeigen konne... more Kognitive Mechanismen beeinflussen die Schmerzwahrnehmung erheblich. Wir haben zuvor zeigen konnen, dass sich neuronale Antworten auf fremdzugefuhrte Schmerzreize z.T. erheblich unterscheiden, wenn sie selbst ausgelost werden, z.B. durch die bessere Pradiktion der sensorischen Konsequenz. Bei Allodynie-Patienten kommt es bereits bei Reizen in ihrer naturlichen Umwelt zur schmerzhaften Reizung. Diese Studie vergleicht daher neuronale Antwortmuster zwischen selbst und fremd zugefuhrten Schmerzreizen bei der experimentellen thermischen Allodynie. Mit der fMRT wurden 17 gesunde, mannliche Rechtshander in einem parametrischen Block-Design mit unterschiedlichen thermischen Stimuli (37°, 40°, 43°C) untersucht. Die thermische Allodynie wurde mit einer topisch aufgetragenen Capsaicinlosung am rechten Oberschenkel ausgelost. Neben der besseren Pradiktabilitat des Stimulationsvorgangs bei der selbst zugefuhrten Stimulation unterschied sich die fremd zugefuhrte Stimulation durch die fehlende Kontrollierbarkeit des Stimulus. Fur beide Versuchsbedingungen wurde eine high-level baseline (HLB) eingefuhrt, um den durch Capasaicin ausgelosten Spontanschmerz und andere kognitive Variablen (z.B. Antizipation) zu kontrollieren. Subtraktionsanalysen mit der HLB konnten wahrend der thermischen Allodynie parametrische Antwortmuster in der anterioren Insula, im anterioren zingularen Kortex (ACC), nicht aber im primaren (SI) und sekundaren somatosensorischen Kortex (SII) nachweisen. Eine steilere Antwortfunktion fur selbst zugefuhrte Schmerzreize fand sich in der posterioren Insel. Dagegen zeigten der prafrontale Kortex und der Kleinhirnwurm steilere Antwortfunktionen bei fremd zugefuhrten Schmerzen. Diese Studie zeigt parametrisch modulierte Antwortfunktionen bei der cerebralen Verarbeitung allodyner Schmerzen. Interessanterweise zeigten die mit der affektiv-emotionalen Komponente des Schmerzes assoziierten Hirnregionen (anteriore Insula, ACC) in der Allodynie eine parametrische Antwortfunktion, nicht jedoch diejenigen fur die sensorisch-diskriminativen Funktionen (SI, SII). Vor allem die Aktivitat der posterioren Insel unterschied sich bei der fremd vs. selbst zugefuhrten Allodynie. Diese Ergebnisse legen nahe, dass Kontrollierbarkeit und Selbstkontrolle bei Patienten mit anhaltenden allodynen Schmerzen berucksichtigt werden mussen, da sie zu unterschiedlichen Aktivierungen und Wahrnehmungen fuhren.
Right hemisphere stroke patients frequently experience spatial neglect, a severe lack of awarenes... more Right hemisphere stroke patients frequently experience spatial neglect, a severe lack of awareness for contralesional hemispace. Although neglect counts among the strongest predictors for poor functional outcome after stroke, there is no established therapy, particularly not for the acute stage. In a randomized controlled trial, we compared the combined treatment of hemifield eye patching and repetitive optokinetic stimulation in acute stroke patients with neglect to the spontaneous course. Outcome measures were a neuropsychological test battery for neglect as well as scales of functional independence and clinical impairment. Outcomes were assessed at baseline (day 1), post treatment (day 8), and at 1-month follow-up (day 30). Final analysis included 21 acute right hemisphere stroke patients with neglect (23 enrolled, 2 lost to follow-up) allocated either to the treatment (1 week hemifield eye patching and daily sessions of optokinetic stimulation, n=11) or the control group (no neg...
Objective: To assess the diagnostic value of eye-head coupling in seesaw nystagmus(SSN). Back-gro... more Objective: To assess the diagnostic value of eye-head coupling in seesaw nystagmus(SSN). Back-ground: 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.
The role of pontine nuclei in vergence eye movements to "step&am... more The role of pontine nuclei in vergence eye movements to "step" targets ("fast" vergence) is unknown. Eye movements were recorded in two patients with unilateral pontine infarctions and in 11 healthy controls. In addition to the deficit of "slow" vergence, "fast" vergence was particularly impaired. However, conjugate saccades did not differ from controls, but smooth pursuit eye movements did. The authors conclude that "fast" vergence palsy is not only caused by midbrain but also upper pontine lesions.
Auditory and vestibular function was examined in 29 patients with unilateral sensorineural hearin... more Auditory and vestibular function was examined in 29 patients with unilateral sensorineural hearing loss to identify characteristic vestibulocochlear lesion patterns. In 45%, a vestibular lesion was found, of which 53% had a combined impairment of the cochlea and the ipsilateral posterior semicircular canal, possibly reflecting vascular disease in the common cochlear artery.
It is controversial whether opsoclonus is a cerebellar or brainstem disorder. Two patients whose ... more It is controversial whether opsoclonus is a cerebellar or brainstem disorder. Two patients whose opsoclonus largely disappeared on eye closure underwent fMRI. A comparison of these two states revealed neither vermal nor brainstem activation but rather a bilateral activation in the deep cerebellar nuclei in excess of what the authors found in healthy subjects. The results support a crucial role of the fastigial nucleus in opsoclonus.
Vergence eye movements were recorded with the scleral search-coil system in 32 healthy subjects (... more Vergence eye movements were recorded with the scleral search-coil system in 32 healthy subjects (ages 19-73 years) to characterize the age-related effects on the dynamic parameters of vergence responses to step (transient components) and ramp or sinusoidal targets (sustained components) under natural viewing conditions. Transient vergence showed an age-related increase in latency and decreases in peak velocity and acceleration in the binocular stimulus condition but not in accommodative vergence. Sustained vergence showed no age-related effect in the binocular condition, but there was an age-related decrease in accommodative vergence steady-state velocity and an increase in latency. Age-related changes of the transient and sustained components were very similar to those reported for saccades and smooth pursuit; they thus might support a distinction between a sustained and transient vergence system. Furthermore, such age-related effects have to be taken into account when assessing eye movement disorders in neurodegenerative and cerebrovascular diseases.
Journal of Neurology, Neurosurgery & Psychiatry, 2009
It is unclear whether sensory symptoms in Parkinson disease (PD) are of primary or of secondary o... more 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. 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. Fourteen family members with PINK1 mutation and 14 healthy controls were examined clinically, with nerve conduction studies and quantitative sensory testing (QST). 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. 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.
Journal of Neurology, Neurosurgery & Psychiatry, 2005
Background: Spontaneous nystagmus caused by dorsolateral medullary infarction may be of vestibula... more Background: Spontaneous nystagmus caused by dorsolateral medullary infarction may be of vestibular origin. Objectives: To test if imbalance of the central pathways of the semicircular canals contributes to spontaneous nystagmus in dorsolateral medullary syndrome. Methods: We examined four patients with dorsolateral medullary syndrome and recorded spontaneous nystagmus binocularly at gaze straight ahead with the three-dimensional search coil technique. The median slow phase velocity of the nystagmus was analysed in the light and in the dark, and the normalised velocity axes were compared with the rotation axes as predicted from anatomical data of the semicircular canal. Results: The slow phase rotation axes of all patients aligned best with the rotation axes resulting from stimulation of the contralesional posterior and horizontal semicircular canals. This alignment cannot be explained by pure otolith imbalance. Conclusion: We propose that vestibular imbalance caused by an ipsilesional lesion of the central semicircular canal pathways of the horizontal and anterior semicircular canals largely accounts for spontaneous nystagmus in dorsolateral medullary syndrome.
Perceived control over pain can attenuate pain perception by mechanisms of endogenous pain contro... more Perceived control over pain can attenuate pain perception by mechanisms of endogenous pain control and emotional reappraisal irrespective of whether this control is exerted or only perceived. Self-initiated termination of pain elicits different expectations of subsequent pain relief as compared to perceived pain control. It is unknown whether and how this perceived vs. exerted control on pain differs and affects subsequent pain relief. Using fMRI, we studied two factors of pain control on pain relief: the (i) sense of control (perceived control but no execution) and (ii) the execution of control (exerted control). To account for the impact of factual execution of pain control on pain relief we applied bearable short and hardly bearable long contact-heat stimuli which were applied either controllable or not. Using controllability as factor, there was dissociable neural activity during pain relief: following the perceived control condition neural activity was found in the orbitofrontal and mediofrontal cortex and, following the exerted control condition, in the anterolateral and dorsolateral prefrontal cortex and posterior parietal cortex. We conclude that (i) pain controllability has an impact on pain relief and (ii) the prefrontal cortex shows dissociable neural activity during pain relief following exerted vs. perceived pain control. This might reflect the higher grade of uncertainty during pain relief following perceived pain control mediated by the orbitofrontal and medial prefrontal cortex and processes of working memory and updating expectations during pain relief following exerted control mediated by the lateral prefrontal cortex.
Neuregulins and their Erbb receptors have been implicated in neuromuscular synapse formation by r... more Neuregulins and their Erbb receptors have been implicated in neuromuscular synapse formation by regulating gene expression in subsynaptic nuclei. To analyze the function of Erbb2 in this process, we have inactivated the Erbb2 gene in developing muscle fibers by Cre/Lox-mediated gene ablation. Neuromuscular synapses form in the mutant mice, but the synapses are less efficient and contain reduced levels of acetylcholine receptors. Surprisingly, the mutant mice also show proprioceptive defects caused by abnormal muscle spindle development. Sensory Ia afferent neurons establish initial contact with Erbb2-deficient myotubes. However, functional spindles never develop. Taken together, our data suggest that Erbb2 signaling regulates the formation of both neuromuscular synapses and muscle spindles.
ABSTRACT It is a matter of debate whether somatosensory abnormalities in Parkinson's dise... more ABSTRACT 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. Nine subjects with Parkin-mutations and nine healthy controls were examined clinically, with quantitative sensory testing (QST) and neurography. 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. 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.
The cerebellum is part of the cortico-ponto-cerebellar circuit for conjugate eye movements. Accor... more The cerebellum is part of the cortico-ponto-cerebellar circuit for conjugate eye movements. Accordingly, cerebellar lesions cause smooth pursuit deficits and saccadic dysmetria. In contrast, the role of the cerebellum for disconjugate, i.e. vergence eye movements in humans are still unknown. The aim of this study was to investigate whether cerebellar lesions affect vergence eye movements. Similar to conjugate eye movements, vergence can be separated into two different components: vergence to step targets (fast vergence) and vergence to ramp and sinusoidal targets (slow vergence). Eye movements (fast and slow vergence, smooth pursuit, saccades) were binocularly recorded with the scleral search coil system in 20 patients with acute cerebellar lesions (ischemic strokes) and agematched healthy controls. Small dim laser stimuli were presented on an earth horizontal platform at the level of the subject’s nose. Smooth pursuit always had a constant vergence angle (isovergence). The majority of patients had unilateral lesions in the territory of the posterior inferior cerebellar artery (3 patients with infarctions in the superior cerebellar artery territory, one cavernoma patient). Group analysis revealed impairment of both conjugate and disconjugate eye movements as well as reduced saccadic gain (Table 1).
1. Clin Neurophysiol. 2010 Oct;121(10):1786-7. Epub 2010 May 6. Overestimation of saccadic peak v... more 1. Clin Neurophysiol. 2010 Oct;121(10):1786-7. Epub 2010 May 6. Overestimation of saccadic peak velocity recorded by electro-oculography compared to video-oculography and scleral search coil. Lappe-Osthege M, Talamo S, Helmchen C, Sprenger A. ...
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