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    Positron emission tomography (PET) shows reduced binding of the dopamine D(2/3) antagonist [(11) C]raclopride in striatum of withdrawn psychostimulant abusers, but not consistently in patients with alcohol dependence (AD). We make first... more
    Positron emission tomography (PET) shows reduced binding of the dopamine D(2/3) antagonist [(11) C]raclopride in striatum of withdrawn psychostimulant abusers, but not consistently in patients with alcohol dependence (AD). We make first use of the high affinity ligand [(18) F]fallypride to obtain serial measures of D(2/3) receptor availability in striatal and extrastriatal regions of AD patients undergoing detoxification. Seventeen patients (mean age 44 ± 5y) with AD and 14 age-matched healthy volunteers participated. Each patient underwent [(18) F]fallypride PET upon hospital admission, and again 1-2 weeks later; two patients achieving abstinence, and two with substantial harm reduction had additional PET follow-up at 1 year. Dynamic 180-minute PET recordings were used for volume of interest (VOI)-based and voxel-wise analysis of [(18) F]fallypride binding potential (BP(ND) ). Mean baseline BP(ND) in striatum of the AD patients (15.7 ± 3.6) was unaltered during short-term follow-up, and did not differ from that in healthy controls (16.8 ± 3.0); however, BP(ND) was 10-20% lower in thalamus, hippocampus, and insular and temporal cortex of the AD patients (P < 0.05). Age-dependent declines in BP(ND) were very small in controls, but more pronounced and widespread in the AD group. Striatal and thalamic BP(ND) increased by 30% in four patients with long-term abstinence or reduced alcohol consumption. VOI-based [(18) F]fallypride PET analyses revealed group differences in D(2/3) receptor availability primarily in extra-striatal regions. Age-related loss of dopamine D(2/3) receptors was more pronounced in AD patients. Receptor availability was unaltered by acute withdrawal, but increased in the subgroup of patients with long-term follow-up, suggesting reversibility of receptor changes.
    There are currently eight groups of drugs for the pharmacotherapy of vertigo, nystagmus, and cerebellar disorders: antiemetics; anti-inflammatories, antimenieres, and antimigraineous medications; antidepressants, anticonvulsants,... more
    There are currently eight groups of drugs for the pharmacotherapy of vertigo, nystagmus, and cerebellar disorders: antiemetics; anti-inflammatories, antimenieres, and antimigraineous medications; antidepressants, anticonvulsants, aminopyridines, and acetyl-DL-leucine ("the eight A's"). In acute unilateral vestibulopathy, corticosteroids improve the recovery of peripheral vestibular function, but there is not sufficient current evidence for a general recommendation. There is also insufficient evidence that 48 or 144 mg/day betahistine has an effect in Ménière's disease. Therefore, higher dosages are currently recommended; in animal studies, it was shown that betahistine increases cochlear blood flow. In vestibular paroxysmia, oxcarbazepine was effective (one yet not randomized controlled trial (RCT)). Aminopyridines are recommended for the treatment of downbeat nystagmus (two RCTs) and episodic ataxia type 2 (EA2, one RCT). There are so far no RCTs on vestibular mig...
    An acute unilateral vestibular lesion leads to a vestibular tone imbalance with nystagmus, head roll tilt and postural imbalance. These deficits gradually decrease over days to weeks due to central vestibular compensation (VC). This study... more
    An acute unilateral vestibular lesion leads to a vestibular tone imbalance with nystagmus, head roll tilt and postural imbalance. These deficits gradually decrease over days to weeks due to central vestibular compensation (VC). This study investigated the effects of i.v. N-acetyl-DL-leucine, N-acetyl-L-leucine and N-acetyl-D-leucine on VC using behavioural testing and serial [18F]-Fluoro-desoxyglucose ([18F]-FDG)-μPET in a rat model of unilateral chemical labyrinthectomy (UL). Vestibular behavioural testing included measurements of nystagmus, head roll tilt and postural imbalance as well as sequential whole-brain [18F]-FDG-μPET was done before and on days 1,3,7 and 15 after UL. A significant reduction of postural imbalance scores was identified on day 7 in the N-acetyl-DL-leucine (p < 0.03) and the N-acetyl-L-leucine groups (p < 0.01), compared to the sham treatment group, but not in the N-acetyl-D-leucine group (comparison for applied dose of 24 mg i.v. per rat, equivalent to...
    Oculomotor disturbances and nystagmus are seen in many diseases of the nervous system, the vestibular apparatus, and the eyes, as well as in toxic and metabolic disorders. They often indicate a specific underlying cause. The key to... more
    Oculomotor disturbances and nystagmus are seen in many diseases of the nervous system, the vestibular apparatus, and the eyes, as well as in toxic and metabolic disorders. They often indicate a specific underlying cause. The key to diagnosis is systematic clinical examination of the patient's eye movements. This review deals mainly with central oculomotor disturbances, i.e., those involving smooth pursuit, saccades, gaze-holding, and central types of nystagmus. We searched the current literature for relevant publications on the diagnosis and treatment of oculomotor disturbances and nystagmus, and discuss them selectively in this review along with the German Neurological Society's guidelines on the topic. A detailed knowledge of the anatomy and physiology of eye movements usually enables the physician to localize the disturbance to a specific area in the brainstem or cerebellum. The examination of eye movements is an even more sensitive method than magnetic resonance imaging ...
    In 2009 the German BMBF (German Ministry of Education and Research) established an Integrated Center for Research and Treatment (IFB(LMU)) of Vertigo, Balance and Ocular Motor Disorders in Munich. After the 10-year period of funding by... more
    In 2009 the German BMBF (German Ministry of Education and Research) established an Integrated Center for Research and Treatment (IFB(LMU)) of Vertigo, Balance and Ocular Motor Disorders in Munich. After the 10-year period of funding by the BMBF, it is envisioned that the (IFB(LMU)) will continue over the long term with the joint support of the University Hospital, the Medical Faculty, and the Bavarian State. Vertigo is one of the most common complaints in medicine. Despite its high prevalence, patients with vertigo generally receive either inappropriate or inadequate treatment. This deplorable situation is internationally well known and its causes are multiple: insufficient interdisciplinary cooperation, no standardized diagnostics and therapy, the failure to translate findings of basic science into clinical applications, and the scarcity of clinical multicenter studies. The (IFB(LMU)) will constitute a suitable tool with which these structural, clinical, and scientific deficits can...
    Unilateral inner ear damage is followed by a rapid behavioural recovery due to central vestibular compensation. In this study, we utilized serial [(18)F]Fluoro-deoxyglucose ([(18)F]FDG)-µPET imaging in the rat to visualize changes in... more
    Unilateral inner ear damage is followed by a rapid behavioural recovery due to central vestibular compensation. In this study, we utilized serial [(18)F]Fluoro-deoxyglucose ([(18)F]FDG)-µPET imaging in the rat to visualize changes in brain glucose metabolism during behavioural recovery after surgical and chemical unilateral labyrinthectomy, to determine the extent and time-course of the involvement of different brain regions in vestibular compensation and test previously described hypotheses of underlying mechanisms. Systematic patterns of relative changes of glucose metabolism (rCGM) were observed during vestibular compensation. A significant asymmetry of rCGM appeared in the vestibular nuclei, vestibulocerebellum, thalamus, multisensory vestibular cortex, hippocampus and amygdala in the acute phase of vestibular imbalance (4 h). This was followed by early vestibular compensation over 1-2 days where rCGM re-balanced between the vestibular nuclei, thalami and temporoparietal cortice...
    Absence of peripheral vestibular input in bilateral vestibular failure (BVF) has been suggested to induce plastic reorganization in various brain regions. Among several neurotransmitters, dopamine is known to play a key role in... more
    Absence of peripheral vestibular input in bilateral vestibular failure (BVF) has been suggested to induce plastic reorganization in various brain regions. Among several neurotransmitters, dopamine is known to play a key role in cortico-striatal-sensorimotor processing. However, the role of dopamine in vestibular plasticity is scantly documented. Assessment of D<formula>_{2/3}</formula>-receptors in patients with BVF. D<formula>_{2/3}</formula>-receptor-PET using [<formula>^{18}</formula>F]fallypride and MRI examinations were performed in 12 BVF-patients and 13 healthy controls. BVF-patients showed reduced D<formula>_{2/3}</formula>-receptor availability (approximately 40%) in the temporo-parieto-occipital cortex bilaterally, including the multisensory vestibular cortex and visual motion-sensitive areas (MT/MST), as well as in the striatum and the right thalamus. Longer illness duration was associated with bilaterally lower D<formula...
    Early symptomatic treatment of acute unilateral vestibulopathy is thought to impede the course of ensuing central vestibular compensation (VC). Despite the great clinical importance of this hypothesis there is no experimental evidence of... more
    Early symptomatic treatment of acute unilateral vestibulopathy is thought to impede the course of ensuing central vestibular compensation (VC). Despite the great clinical importance of this hypothesis there is no experimental evidence of its validity. The present study addressed this question by investigating the direct effect of 4-aminopyridine (4-AP) on ocular motor and postural symptoms in acute unilateral vestibulopathy as well as its long-term consequences for VC in a rat model of chemical unilateral labyrinthectomy (UL). After UL, one group of Sprague-Dawley rats was treated with 4-AP p.o. (1mg/kg/day), another with 0.9% NaCl solution p.o. for 3days. Behavioural testing for symptoms of vestibular tone imbalance was done 1day before and 1, 2, 3, 5, 7, 9, 15, 21, and 30days after UL. In addition, sequential whole-brain [(18)F]-FDG-μPET was performed before and 1, 3, 7, 15, and 30days after UL to examine and visualize 4-AP-induced modulation of VC. Administration of 4-AP on days ...