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ABSTRACT: Present pathophysiological concepts of neuropathic tremor assume mistimed and defective afferent input resulting in deregulation of cerebello-thalamo-cortical motor networks. Here, we provide direct evidence of central tremor processing in a 76-year-old female who underwent bilateral deep brain stimulation of the ventral intermedial nucleus of the thalamus (Vim-DBS) because of neuropathic tremor associated with IgM paraproteinemia. Electrophysiological recordings of EEG and EMG were performed in three perioperative sessions: (1) preoperatively, (2) intraoperatively, and (3) 4 days after surgery in both rest and postural tremor conditions. Tremor-related synchronization (coherence) between motor cortex (M1) and muscles (M. extensor digitorum, M. flexor digitorum) was assessed, and additional intraoperative local field potential (LFP) recordings from Vim allowed comprehensive coherence mapping in thalamo-cortico-muscular networks. Directionality of information flow was determined by directed transfer function (DTF) and phase analyses. Stimulation effects on tremor and corticomuscular coherence were assessed and the patient was followed for 12 months on clinical outcome measures (Tremor Rating Scale, CADET-Score). Vim-DBS reduced tremor (59%) and improved motor functionality in daily activities (31%, CADET-A) after 12 months. Intraoperative recordings demonstrated significant coherence in the tremor frequency (4 Hz) between M1 and contralateral muscle, Vim and ipsilateral M1, Vim and contralateral muscle, but not between Vim and contralateral M1. Information flow was directed from M1 to Vim and bidirectional between M1 and muscle and between Vim and muscle, respectively. Corticomuscular coherence at tremor frequency was completely suppressed by Vim-DBS. Our case study demonstrates central oscillators underlying neuropathic tremor and implies a strong pathophysiological rationale for Vim-DBS.
Movement Disorders 10/2010; 26(2):323-7. · 4.51 Impact Factor
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ABSTRACT: This case report describes the use of transcranial magnetic theta burst stimulation (TBS) in the treatment of incapacitating tinnitus accompanied by symptoms of severe depression. Tinnitus is known to be associated with hyperactivity and maladaptive cortical reorganization of the central auditory system. Combined with anxiety and depression, it can occasionally constitute a psychiatric emergency. Recently, it has been demonstrated that tinnitus can be temporarily suppressed by non-invasive transcranial magnetic stimulation. TBS is a newly developed technique for rapid and lasting modulation of cortical excitability. Herein, we present a case of a 54-year-old woman with incapacitating tinnitus that has significantly decreased after three cycles of 1-week treatment with continuous TBS to the temporo-parietal auditory association cortex. According to the Tinnitus Questionnaire, tinnitus intensity decreased from 84 points before to 59 points after treatment. Hamilton Rating Scale for Depression score dropped from 44 to 23 points. TBS showed to be efficient, well-tolerated, and practical in the management of distressing tinnitus accompanied by symptoms of severe depression.
CNS spectrums 05/2009; 14(4):208-11. · 2.20 Impact Factor
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The International Journal of Neuropsychopharmacology 09/2008; 11(8):1181-3. · 4.58 Impact Factor
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ABSTRACT: To investigate short-term visual effects of a single 100-mg dose of Viagra (sildenafil citrate) in healthy men.
Randomized, double-blind, placebo-controlled clinical trial of drug effects on normal volunteers conducted by a single center.
Twenty men, aged 20 to 40 years, were treated with either a placebo or 100 mg sildenafil. Visual function tests included electroretinogram (ERG) recordings, on-/off- and 3.3 Hz-flicker-ERG recordings, anomaloscope matches, and measurements of cone contrast sensitivities and transient tritanopia.
Most visual tests did not differ between the sildenafil and placebo groups. However, statistically significant increases in sensitivity during transient tritanopia were observed as well as significant prolongations in the implicit times of scotopic a-wave, photopic b-wave, and 3.3 Hz-flicker a-wave and b-wave ERG recordings. The magnitude of the differences correlated with peak sidenafil plasma concentration. Although rod amplitudes of the ERG recordings tended to be higher and cone amplitudes lower in the sildenafil group after drug ingestion, the differences were nonsignificant. There were no reports of visual side effects, and all electrophysiologic and psychophysical measurements returned to the normal range within 24 hours.
A single oral dose of 100-mg sildenafil given to healthy young men led to small but statistically significant transient changes of outer and inner retinal function, as detected by ERG and psychophysical methods. Although the acute effects were fully reversible within 24 hours, it would be worthwhile to compare them with those induced by other PDE5 and PDE6 inhibitors.
American Journal of Ophthalmology 06/2004; 137(5):842-9. · 4.22 Impact Factor
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ABSTRACT: In developmental biology, zebrafish are widely used to study the impact of mutations. The fast pace of development allows for a definitive morphological evaluation of the phenotype usually 5 days post fertilization (dpf). At that age, a functional analysis is already feasible using electroretinographic (ERG) methods. Corneal Ganzfeld ERGs were recorded with a glass microelectrode in anaesthetized, dark-adapted larvae aged 5 dpf, using a platinum wire beneath a moist paper towel as reference. ERG protocols included flash, flicker, and ON/OFF stimuli, both under scotopic and photopic conditions. Repetitive, isoluminant stimuli were used to assess the dynamic effect of pharmacological agents on the ERG. Single flash, flicker, and ON/OFF responses had adequately matured at this point to be informative. Typical signs of the cone dominance were the small scotopic a-wave and the large OFF responses. The analysis of consecutive single traces was possible because of the lack of EKG, breathing, and blink artefacts. After application of APB, which selectively blocks the ON channel via the mGluR6 receptor, the successive loss of the b-wave could be observed, which was quite different from the deterioration of the ERG after a circulatory arrest. The above techniques allowed to reliably obtain Ganzfeld ERGs in larvae aged 5 dpf. This underlines the important role of the zebrafish as a model for the functional analysis of mutations disrupting the visual system.
Documenta Ophthalmologica 02/2002; 104(1):57-68. · 2.11 Impact Factor