Andres Ceballos-Baumann

Botulinum toxin A for axillary hyperhidrosis (excessive sweating).

BACKGROUND Treatment of primary focal hyperhidrosis is often unsatisfactory. Botulinum toxin A can stop excessive sweating by blocking the release of acetylcholine, which mediates sympathetic neurotransmission in the sweat glands. METHODS We conducted a multicenter trial of botulinum toxin A in 145 patients with axillary hyperhidrosis. The patients had rates of sweat production greater than 50 mg per minute and had had primary axillary hyperhidrosis that was unresponsive to topical therapy with aluminum chloride for more than one year. In each patient, botulinum toxin A (200 U) was injected into one axilla, and placebo was injected into the other in a randomized, double-blind manner. (The units of the botulinum toxin A preparation used in this study are not identical to those of other preparations.) Two weeks later, after the treatments were revealed, the axilla that had received placebo was injected with 100 U of botulinum toxin A. Changes in the rates of sweat production were measured by gravimetry. RESULTS At base line, the mean (+/-SD) rate of sweat production was 192+/-136 mg per minute. Two weeks after the first injections the mean rate of sweat production in the axilla that received botulinum toxin A was 24+/-27 mg per minute, as compared with 144+/-113 mg per minute in the axilla that received placebo (P< 0.001). Injection of 100 U into the axilla that had been treated with placebo reduced the mean rate of sweat production in that axilla to 32+/-39 mg per minute (P<0.001). Twenty-four weeks after the injection of 100 U, the rates of sweat production (in the 136 patients in whom the rates were measured at that time) were still lower than base-line values, at 67+/-66 mg per minute in the axilla that received 200 U and 65+/-64 mg per minute in the axilla that received placebo and 100 U of the toxin. Treatment was well tolerated; 98 percent of the patients said they would recommend this therapy to others. CONCLUSIONS Intradermal injection of botulinum toxin A is an effective and safe therapy for severe axillary hyperhidrosis.

Transmodal Sensorimotor Networks during Action Observation in Professional Pianists

Audiovisual perception and imitation are essential for musical learning and skill acquisition. We compared professional pianists to musically naive controls with fMRI while observing piano playing fingerhand movements and serial fingerthumb opposition movements both with and without synchronous piano sound. Pianists showed stronger activations within a fronto-parieto-temporal network while observing piano playing compared to controls and contrasted to perception of serial fingerthumb opposition movements. Observation of silent piano playing additionally recruited auditory areas in pianists. Perception of piano sounds coupled with serial fingerthumb opposition movements evoked increased activation within the sensorimotor network. This indicates specialization of multimodal auditory sensorimotor systems within a fronto-parieto-temporal network by professional musical training. Musical language, which is acquired by observation and imitation, seems to be tightly coupled to this network in accord with an observation execution system linking visual and auditory perception to motor performance.

What is the optimal dose of botulinum toxin A in the treatment of cervical dystonia? Results of a double blind, placebo controlled, dose ranging study using Dysport®

OBJECTIVES Botulinum toxin injections have become a first line therapeutic approach in cervical dystonia. Nevertheless, published dosing schedules, responder rates, and frequency of adverse events vary widely. The present prospective multicentre placebo controlled double blind dose ranging study was performed in a homogenous group of previously untreated patients with rotational torticollis to obtain objective data on dose-response relations. METHODS Seventy five patients were randomly assigned to receive treatment with placebo or total doses of 250, 500, and 1000 Dysport® units divided between one splenius capitis (0, 175, 350, 700 units) and the contralateral sternocleidomastoid (0, 75, 150, 300 units) muscle. Assessments were obtained at baseline and weeks 2, 4, and 8 after treatment and comprised a modified Tsui scale, a four point pain scale, a checklist of adverse events, global assessment of improvement, and a global rating taking into account efficacy and adverse events. At week 8 the need for retreatment was assessed and then the code was unblinded. For those still responding, there was an open follow up until retreatment to assess the duration of effect. RESULTS seventy nine per cent reported subjective improvement at one or more follow up visits. Decreases in the modified Tsui score were significant at week 4 for the 500 and 1000 unit groups versus placebo (p<0.05). Additionally positive dose-response relations were found for the degree of subjective improvement, duration of improvement, improvement on clinical global rating, and need for reinjection at eight weeks. A significant dose relation was also established for the number of adverse events overall and for the incidence of neck muscle weakness and voice changes. CONCLUSION Magnitude and duration of improvement was greatest after injections of 1000 units Dysport®; however, at the cost of significantly more adverse events. Therefore a lower starting dose of 500 units Dysport® is recommended in patients with cervical dystonia, with upward titration at subsequent injection sessions if clinically necessary.

Subthalamic nucleus stimulation affects a frontotemporal network: A PET study

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an effective strategy in the treatment of motor symptoms in advanced Parkinsons disease. However, clinical studies have shown that DBS can affect verbal fluency. Seven Parkinsons disease patients with bilateral DBS of the STN were studied with positron emission tomography (PET) to investigate the effects of STN stimulation on regional cerebral blood flow during a verbal fluency task. Activation of the right orbitofrontal cortex and verbal fluency‐associated activation within a left‐sided frontotemporal network were decreased during STN stimulation compared with the OFF state. Our results offer an explanation for the commonest neuropsychological side effect of STN stimulation and show that STN stimulation affects a frontotemporal network during a fluency task. Ann Neurol 2003;54:000–000

Cortical Correlates of Gesture Processing: Clues to the Cerebral Mechanisms Underlying Apraxia during the Imitation of Meaningless Gestures

The clinical test of imitation of meaningless gestures is highly sensitive in revealing limb apraxia after dominant left brain damage. To relate lesion locations in apraxic patients to functional brain activation and to reveal the neuronal network subserving gesture representation, repeated H2(15O)-PET measurements were made in seven healthy subjects during a gesture discrimination task. Observing paired images of either meaningless hand or meaningless finger gestures, subjects had to indicate whether they were identical or different. As a control condition subjects simply had to indicate whether two portrayed persons were identical or not. Brain activity during the discrimination of hand gestures was strongly lateralized to the left hemisphere, a prominent peak activation being localized within the inferior parietal cortex (BA40). The discrimination of finger gestures induced a more symmetrical activation and rCBF peaks in the right intraparietal sulcus and in medial visual association areas (BA18/19). Two additional foci of prominent rCBF increase were found. One focus was located at the left lateral occipitotemporal junction (BA 19/37) and was related to both tasks; the other in the pre-SMA was particularly related to hand gestures. The pattern of task-dependent activation corresponds closely to the predictions made from the clinical findings, and underlines the left brain dominance for meaningless hand gestures and the critical involvement of the parietal cortex. The lateral visual association areas appear to support first stages of gesture representation, and the parietal cortex is part of the dorsal action stream. Finger gestures may require in addition precise visual analysis and spatial attention enabled by occipital and right intraparietal activity. Pre-SMA activity during the perception of hand gestures may reflect engagement of a network that is intimately related to gesture execution.

The Link between Facial Feedback and Neural Activity within Central Circuitries of Emotion—New Insights from Botulinum Toxin–Induced Denervation of Frown Muscles

Afferent feedback from muscles and skin has been suggested to influence our emotions during the control of facial expressions. Recent imaging studies have shown that imitation of facial expressions is associated with activation in limbic regions such as the amygdala. Yet, the physiological interaction between this limbic activation and facial feedback remains unclear. To study if facial feedback effects on limbic brain responses during intentional imitation of facial expressions, we applied botulinum toxin (BTX)-induced denervation of frown muscles in combination with functional magnetic resonance imaging as a reversible lesion model to minimize the occurrence of afferent muscular and cutaneous input. We show that, during imitation of angry facial expressions, reduced feedback due to BTX treatment attenuates activation of the left amygdala and its functional coupling with brain stem regions implicated in autonomic manifestations of emotional states. These findings demonstrate that facial feedback modulates neural activity within central circuitries of emotion during intentional imitation of facial expressions. Given that people tend to mimic the emotional expressions of others, this could provide a potential physiological basis for the social transfer of emotion.

Left inferior parietal dominance in gesture imitation : an fMRI study

The inability to imitate gestures is an essential feature of apraxia. However, discrepancies exist between clinical studies in apraxic patients and neuroimaging findings on imitation. We therefore aimed to investigate: (1) which areas are recruited during imitation under conditions similar to clinical tests for apraxic deficits; (2) whether there are common lateralized areas subserving imitation irrespective of the acting limb side; and also (3) whether there are differences between hand and finger gestures. We used fMRI in 12 healthy, right handed subjects to investigate the imitation of four types of variable gestures that were presented by video clips (16 different finger and 16 different hand gestures with either the right or the left arm). The respective control conditions consisted of stereotyped gestures (only two gestures presented in pseudorandom order). Subtraction analysis of each type of gesture imitation (variable>stereotyped) revealed a bilateral activation pattern including the inferior parietal cortex Brodmann Area (BA 40), the superior parietal cortex, the inferior frontal cortex (opercular region), the prefrontal motor cortex, the lateral occipito-temporal junction, and the cerebellum. These results were supported by statistical conjunction of all four subtraction analyses and by the common analysis of all four types of gesture imitation. The direct comparison of the right and left hemispheric activation revealed a lateralization to the left only of the inferior parietal cortex. Comparisons between different types of gesture imitation yielded no significant results. In conclusion, gesture imitation recruits bilateral fronto-parietal regions, with significant lateralization of only one area, namely the left inferior parietal cortex. These in vivo data indicate left inferior parietal dominance for gesture imitation in right handers, confirming lesion-based theories of apraxia.

Reduced recruitment of motor association areas during bimanual coordination in concert pianists.

Bimanual motor coordination is essential for piano playing. The functional neuronal substrate for high‐level bimanual performance achieved by professional pianists is unclear. We compared professional pianists to musically naïve controls while carrying out in‐phase (mirror) and anti‐phase (parallel) bimanual sequential finger movements during functional magnetic resonance imaging (fMRI). This task corresponds to bimanually playing scales practiced daily by pianists from the beginning of piano playing. Musicians and controls showed significantly different functional activation patterns. When comparing performance of parallel movements to rest, musically naïve controls showed stronger activations than did pianists within a network including anterior cingulate cortex, right dorsal premotor cortex, both cerebellar hemispheres, and right basal ganglia. The direct comparison of bimanual parallel to mirror movements between both groups revealed stronger signal increases in controls within mesial premotor cortex (SMA), bilateral cerebellar hemispheres and vermis, bilateral prefrontal cortex, left ventral premotor cortex, right anterior insula, and right basal ganglia. These findings suggest increased efficiency of cortical and subcortical systems for bimanual movement control in musicians. This may be fundamental to achieve high‐level motor skills allowing the musician to focus on artistic aspects of musical performance. Hum. Brain Mapping 22:206–215, 2004.

The role of lateral premotor-cerebellar-parietal circuits in motor sequence control: a parametric fMRI study.

Functional characterisation of higher order motor systems can be obtained by modulating the processing demands imposed onto relevant motor circuitries. Here we performed whole-brain functional magnetic resonance imaging (fMRI) and parametric statistical analyses in eight healthy volunteers to study task-related recruitment of motor circuits associated with unilateral finger movement sequences of increasing length and complexity, but with equal basic motor parameters. Statistical parametric mapping software was applied for analysis. Categorical analysis of the main effect of motor action showed cerebral activation in the established cortical and subcortical motor network. Parametric analyses of the blood-oxygen-level-dependent (BOLD) contrast revealed significant signal increases correlating to sequence length and complexity in a subset of activated areas, notably contralateral ventral and dorsal premotor cortex, bilateral superior parietal cortex, left inferior frontal gyrus/Brocas area, right dentate nucleus, and left visual association cortex. These data underscore the importance of ventral premotor-cerebellar-parietal circuits in processing length and complexity of sequential finger movements.

“Silent event-related” fMRI reveals reduced sensorimotor activation in laryngeal dystonia

Objective: To study with fMRI the pattern of sensorimotor activation in patients with spasmodic dysphonia (laryngeal dystonia) compared to healthy controls. Methods: The authors performed fMRI measurements during vocal motor tasks in 12 patients with laryngeal dystonia and compared them with those of 12 healthy volunteers. Patients were scanned before (pre) and after (post) treatment with local injections of botulinum toxin (BTX). They examined two different motor tasks: simple vocalization inducing dystonia and whispering without appearance of dystonic symptoms. To avoid movement artifacts with oral motor tasks, the authors used a silent event-related fMRI approach involving noncontinuous sampling with no data acquisition during task performance. Results: They found reduced activation of primary sensorimotor as well as of premotor and sensory association cortices during vocalization in patients with laryngeal dystonia pre-BTX. This was partly observed also during the asymptomatic whispering task. BTX treatment did not result in reversal of reduced cortical activation. Conclusion: fMRI signal is reduced in sensorimotor cortices associated with movement of the affected body part in laryngeal dystonia, supporting a dystonic basis for this voice disorder.