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Biomedical subjects

J Wissel

Publications and source records attributed to J Wissel.

At least 37 records · Page 2Linked to original sources

Nociceptive fingertip stimulation inhibits synergistic motoneuron pools in the human upper limb.

BACKGROUND: Activation of distinct muscle groups organized in a stereotyped manner ("muscle synergies") is thought to underlie the production of movement by the vertebrate spinal cord. This results in movement with minimum effort and maximum efficiency. The question of how the vertebrate nervous system inhibits ongoing muscle activity is central to the study of the neural control of movement. OBJECTIVE: To investigate the strategy used by the human spinal cord to rapidly inhibit muscle activation in the upper limb. METHODS: The authors performed a series of experiments in 10 healthy subjects to assess the effect of nociceptive cutaneous stimulation on voluntarily contracting upper limb muscles. They recorded the electromyogram (EMG) with surface electrodes placed over various upper limb muscles. RESULTS: The authors found evidence of a simple inhibitory strategy that 1) was dependent on the intensity of the stimulus, 2) was maximally evoked when stimulation was applied to the fingertips, 3) preceded the earliest onset of voluntary muscle relaxation, and 4) produced inhibition of EMG activity in specific upper limb muscle groups. Nociceptive fingertip stimulation preferentially inhibited contraction of synergistic muscles involved in reaching and grasping (intrinsic hand muscles, forearm flexors, triceps) while having little effect on biceps or deltoid. CONCLUSIONS: Neural circuitry within the human spinal cord is organized to inhibit movement by rapidly deactivating muscles that constitute distinct muscle synergies. This strategy of selective and concurrent deactivation of the same basic elements that produce synergistic movement greatly simplifies motor control.

Adult↗

Progressive multifocal leukoencephalopathy presenting with an isolated focal movement disorder.

Progressive multifocal leukoencephalopathy (PML) is a rare but fatal papovavirus infection of the central nervous system predominantly affecting immunocompromised patients. Although the basal ganglia circuitry may be involved in the pathology of PML, movement disorders are exceedingly rare as presenting symptoms and have not been described as isolated features in such patients. We report a previously healthy, immunocompetent 24-year-old woman with histologically proven PML who presented with a focal movement disorder of the left arm as an isolated symptom for many months before diagnosis.

Adult↗

Quantification of sensory trick impact on tremor amplitude and frequency in 60 patients with head tremor.

Head tremor with an obvious head deviation is the typical clinical picture of tremulous cervical dystonia (TCD), whereas head tremor without any significant head deviation allows for the differential diagnosis of dystonic head tremor (DHT) as well as essential head tremor (EHT). Clinical and polyelectromyographic (poly-EMG) studies have shown a suppression of dystonic muscle activity in patients with TCD performing a maneuver called geste antagonistique. The effect of these trick maneuvers on head tremor has not been investigated in patients with DHT and EHT. We studied the impact of sensory trick maneuvers on head tremor amplitude and frequency clinically by using the tremor subscore of the Tsui scale and by means of computer-based accelerometry in 60 patients with head tremor as their major disorder. Based on clinical data (modified Tsui scale: rating of spontaneous head deviation [rotation + lateroflexion + ante-/retroflexion]), pharmacologic response of tremor (propranolol, primidone, or alcohol), family history (postural hand tremor in first-degree relatives), and poly-EMG findings (reciprocal inhibition in neck muscles during voluntary head rotation), 34 patients were diagnosed as having TCD, 14 were classified as having DHT, and 12 patients were diagnosed as having EHT. Using a clinical rating scale, head tremor amplitudes showed a significant decrease compared with baseline during the performance of sensory trick maneuvers in patients with TCD and DHT, but not in patients with EHT. This clinically observed effect was accompanied by a significant reduction in the mean peak power of the dominant frequency in patients with TCD (decrease by 83%, p = 0.0001) and DHT (decrease by 90%, p = 0.01), but not in patients with EHT (decrease by 6%, p = 0.6). Head tremor frequencies showed no significant changes in relation to the trick maneuvers. We conclude that a significant reduction of head tremor amplitude during a sensory trick maneuver is a useful quantitative criterion to distinguish TCD and DHT from EHT.

Adrenergic beta-Antagonists↗

The DYT1 GAG deletion is infrequent in sporadic and familial writer' s cramp.

A 3-base pair (GAG) deletion in the DYT1 gene has recently been found to be responsible for most cases of early-onset primary generalized dystonia. In some cases, this mutation has been associated with writer's cramp. To determine the frequency of this mutation in a larger series of patients, we examined 44 index patients with sporadic or familial (seven patients) writer's cramp for the presence of the DYT1 GAG deletion, including eight patients with segmental dystonia involving at least one upper limb. We found the mutation in none of these index patients, which confirms that isolated writer's cramp is only in rare cases a phenotypic manifestation of this mutation, even if a positive family history of writer's cramp is present.

Adult↗

Impaired dopaminergic neurotransmission in patients with traumatic brain injury: a SPECT study using 123I-beta-CIT and 123I-IBZM.

Structural imaging suggests that traumatic brain injury (TBI) may be associated with disruption of neuronal networks, including the nigrostriatal dopaminergic pathway. However, to date deficits in pre- and/or postsynaptic dopaminergic neurotransmission have not been demonstrated in TBI using functional imaging. We therefore assessed dopaminergic function in ten TBI patients using [123I]2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane (beta-CIT) and [123I]iodobenzamide (IBZM) single-photon emission tomography (SPET). Average Glasgow Coma Scale score (+/-SD) at the time of head trauma was 5.8+/-4.2. SPET was performed on average 141 days (SD +/-92) after TBI. The SPET images were compared with structural images using cranial computerised tomography (CCT) and magnetic resonance imaging (MRI). SPET was performed with an ADAC Vertex dual-head camera. The activity ratios of striatal to cerebellar uptake were used as a semiquantitative parameter of striatal dopamine transporter (DAT) and D2 receptor (D2R) binding. Compared with age-matched controls, patients with TBI had significantly lower striatal/cerebellar beta-CIT and IBZM binding ratios (P< or =0.01). Overall, the DAT deficit was more marked than the D2R loss. CCT and MRI studies revealed varying cortical and subcortical lesions, with the frontal lobe being most frequently affected whereas the striatum appeared structurally normal in all but one patient. Our findings suggest that nigrostriatal dysfunction may be detected using SPET following TBI despite relative structural preservation of the striatum. Further investigations of possible clinical correlates and efficacy of dopaminergic therapy in patients with TBI seem justified.

Adolescent↗

Survival with full neurologic recovery and no cerebral pathology after prolonged cardiopulmonary resuscitation with vasopressin in pigs.

OBJECTIVES: We sought to determine the effects of vasopressin and saline placebo in comparison with epinephrine on neurologic recovery and possible cerebral pathology in an established porcine model of prolonged cardiopulmonary resuscitation (CPR). BACKGROUND: It is unknown whether increased cerebral blood flow during CPR with vasopressin is beneficial with regard to neurologic recovery or detrimental owing to complications such as cerebral edema after return of spontaneous circulation. METHODS: After 4 min of cardiac arrest, followed by 3 min of basic life support CPR, 17 animals were randomly assigned to receive every 5 min either vasopressin (0.4, 0.4 and 0.8 U/kg; n = 6), epinephrine (45, 45 and 200 microg/kg; n = 6) or saline placebo (n = 5). The mean value +/- SEM of aortic diastolic pressure was significantly (p < 0.05) higher 90 s after each of three vasopressin versus epinephrine versus saline placebo injections (60 +/- 3 vs. 45 +/- 3 vs. 29 +/- 2 mm Hg; 49 +/- 5 vs. 27 +/- 3 vs. 23 +/- 1 mm Hg; and 50 +/- 6 vs. 21 +/- 3 vs. 16 +/- 3 mm Hg, respectively). After 22 min of cardiac arrest, including 18 min of CPR, defibrillation was attempted to achieve return of spontaneous circulation. RESULTS: All the pigs that received epinephrine and saline placebo died, whereas all pigs on vasopressin survived (p < 0.05). Neurologic evaluation 24 h after successful resuscitation revealed only an unsteady gait in all vasopressin-treated animals; after 96 h, magnetic resonance imaging revealed no cerebral pathology. CONCLUSIONS: During prolonged CPR, repeated vasopressin administration, but not epinephrine or saline placebo, ensured long-term survival with full neurologic recovery and no cerebral pathology in this porcine CPR model.

Animals↗

Management of spasticity associated pain with botulinum toxin A.

Lesions of the central nervous system often result in an upper motor neuron syndrome including spasticity, paresis with pyramidal signs, and painful spasms. Pharmacological treatment with oral antispasticity drugs is frequently associated with systemic side effects which limit their clinical use. Botulinum Toxin A (BtxA) injected in spastic muscles has been shown to be effective in reducing muscle tone, but only few studies have reported pain relief as additional benefit. Therefore, we investigated the effects of local BtxA injections in 60 patients with acute (< 12 months) and chronic spasticity and pain in a prospective multicenter study. Target muscles for BtxA were selected on the basis of clinical examination. Intramuscular BtxA injections were placed in muscles exhibiting increased muscle tone in combination with pain during passive joint movement. Patients received a mean total dose of 165.7 +/- 108.2 [30-400] units BOTOX((R)) per treatment session in a mean 3.4 +/- 1.5 muscles. Baseline and follow-up (mean 5.9 weeks) measures included a patient self-assessment of pain and function on a five-level scale, a physician's evaluation of function, and a global rating of response to BtxA. Fifty-four of sixty patients experienced improvement in pain without subjective functional improvement. The effects were comparable in acute (n = 17) and chronic (n = 43) spasticity. Physician's assessment of gain in function increased significantly (p < 0.05) only in patients with chronic spasticity. No serious adverse event was observed. Mild reversible side effects (local pain, hematoma, edema, mild weakness) were observed in four patients. In conclusion, we found that intramuscular BtxA injections are a potent, well-tolerated treatment modality to significantly reduce spasticity-related local pain. This problem may be a main indication, especially in patients with poor response or intolerable side effects to oral medication.

Adolescent↗

Recommendations for the use of botulinum toxin type A in the management of cerebral palsy.

Botulinum toxin type A (BTX-A) is increasingly being used for the treatment of childhood spasticity, particularly cerebral palsy. However, until very recently, all such use in this indication has been unapproved with no generally accepted treatment protocols, resulting in considerable uncertainty and variation in its use as a therapeutic agent. In view of the increasing awareness of, and interest in, this approach to the treatment of spasticity, and also the recent licensing in a number of countries of a BTX-A preparation for treating equinus deformity in children, it would seem timely to establish a framework of guidelines for the safe and efficacious use of BTX-A for treating spasticity in children. This paper represents an attempt, by a group of 15 experienced clinicians and scientists from a variety of disciplines, to arrive at a consensus and produce detailed recommendations as to appropriate patient selection and assessment, dosage, injection technique and outcome measurement. The importance of adjunctive physiotherapy, orthoses and casting is also stressed.

Animals↗

Botulinum toxin (Dysport) treatment of hip adductor spasticity in multiple sclerosis: a prospective, randomised, double blind, placebo controlled, dose ranging study.

OBJECTIVE: To define a safe and effective dose of Dysport for treating hip adductor spasticity. METHODS: Patients with definite or probable multiple sclerosis, and disabling spasticity affecting the hip adductor muscles of both legs, were randomised to one of four treatment groups. Dysport (500, 1000, or 1500 Units), or placebo was administered by intramuscular injection to these muscles. Patients were assessed at entry, and 2, 4 (primary analysis time-point), 8, and 12 weeks post-treatment. RESULTS: A total of 74 patients were recruited. Treatment groups were generally well matched at entry. The primary efficacy variables-passive hip abduction and distance between the knees-improved for all groups. The improvement in distance between the knees for the 1500 Unit group was significantly greater than placebo (p = 0.02). Spasm frequency was reduced in all groups, but muscle tone was reduced in the Dysport groups only. Pain was reduced in all groups, but improvements in hygiene scores were evident only in the 1000 Unit and 1500 Unit groups. Duration of benefit was significantly longer than placebo for all Dysport groups (p<0.05). Adverse events were reported by 32/58 (55%) Dysport patients, and by 10/16 (63%) placebo patients. Compared with the two lower dose groups, twice as many adverse events were reported by the 1500 Unit group (2.7/patient). The incidence of muscle weakness was higher for the 1500 Unit group (36%) than for placebo (6%). The response to treatment was considered positive by two thirds of the patients in the 500 Unit group, and by about half the patients in the other groups. CONCLUSION: Dysport reduced the degree of hip adductor spasticity associated with multiple sclerosis, and this benefit was evident despite the concomitant use of oral antispasticity medication and analgesics. Although evidence for a dose response effect was not statistically significant, there was a clear trend towards greater efficacy and duration of effect with higher doses of Dysport. Dysport treatment was well tolerated, with no major side effects seen at doses up to 1500 Units. The optimal dose for hip adductor spasticity seems to be 500-1000 Units, divided between both legs.

Adult↗

A randomized, double-blind, placebo-controlled, dose-ranging study to compare the efficacy and safety of three doses of botulinum toxin type A (Dysport) with placebo in upper limb spasticity after stroke.

BACKGROUND AND PURPOSE: We sought to define an effective and safe dose of botulinum toxin type A (Dysport) for the treatment of upper limb muscle spasticity due to stroke. METHODS: This was a prospective, randomized, double-blind, placebo-controlled, dose-ranging study. Patients received either a placebo or 1 of 3 doses of Dysport (500, 1000, 1500 U) into 5 muscles of the affected arm. Efficacy was assessed periodically by the Modified Ashworth Scale and a battery of functional outcome measures. RESULTS: Eighty-three patients were recruited, and 82 completed the study. The 4 study groups were comparable at baseline with respect to their demographic characteristics and severity of spasticity. All doses of Dysport studied showed a significant reduction from baseline of muscle tone compared with placebo. However, the effect on functional disability was not statistically significant and was best at a dose of 1000 U. There were no statistically significant differences between the groups in the incidence of adverse events. CONCLUSIONS: The present study suggests that treatment with Dysport reduces muscle tone in patients with poststroke upper limb spasticity. Treatment was effective at doses of Dysport of 500, 1000, and 1500 U. The optimal dose for treatment of patients with residual voluntary movements in the upper limb appears to be 1000 U. Dysport is safe in the doses used in this study.

Arm↗

[Safety and tolerance of single-dose botulinum toxin Type A treatment in 204 patients with spasticity and localized associated symptoms. Austrian and German botulinum toxin A spasticity study group].

High dose oral anti-spastic medication is effective in the treatment of spasticity but has the disadvantage of frequent systemic side effects such as drowsiness and general weakness. Therefore, neurolytic and chemodenervation procedures are further therapeutic options, especially in cases of local spasticity. Apart from phenol blocks with the risk of persisting painful dysesthesia, botulinum toxin type A (BtxA) appears to be a safe and effective treatment. In 204 patients (mean age, 41.5 years [range 3-91 years]) with acute (n = 29, mean duration of disease 2.9 months [range, 1-6 months]) and chronic (n = 175, mean duration of disease 111 months [range, 7-500 months]) spasticity due to stroke, traumatic brain and spinal injury and other lesions of the upper motor neuron, the effects of single-dose BtxA treatment were studied. An overall dose of 181.2 units [range, 15-600 units] of BtxA (Botox) was injected in a mean of 3.3 [1-14] muscles per patient. Results were assessed using a modified Rating of Response to BtxA (RRB, Brin et al. 1995). The RRB includes a pre- and post BtxA assessment of the severity of spasticity-associated problems (patient's self-assessment), a rating of the current percentage of normal function in the region of the body selected for BtxA and a global rating of changes induced by BtxA. 191 (93.6%) patients demonstrated improvement over a mean of 7.7 weeks [1-36]; no deterioration was observed. Mean overall severity and function improved significantly (p < 0.001). No systemic or severe side effects were registered. Only in 5.9% of the patients were mild (n = 10) or moderate (n = 2) reversible adverse events reported. We conclude that BtxA injections are safe and effective in the treatment of local spasticity.

Administration, Oral↗

Interference of rhythmic constraint on gait in healthy subjects and patients with early Parkinson's disease: evidence for impaired locomotor pattern generation in early Parkinson's disease.

Patients in the early stages of Parkinson's disease have been shown to walk slower with smaller steps, resembling the gait of normal elderly subjects, but specific disorders of dynamic equilibrium or rhythmic gait patterning have not yet been identified. In the present study, gait control in 22 healthy subjects and 22 patients with early Parkinson's disease was challenged by means of a paradigm requiring subjects to decrease their step rate (cadence) by 20% in response to a metronome signal (rhythmic constraint). Control subjects and patients were matched for age, sex, and body height. Eleven patients were receiving standard antiparkinsonian therapy and were assessed under their ongoing medication, whereas the remaining 11 patients had not yet been started on dopaminergic therapy ("de novo" Parkinson's disease). Gait parameters reflecting dynamic equilibrium (double-support time) and locomotor patterning (step length, stride duration) were recorded by means of a mechanical device (locometer). Sixteen patients and 16 control subjects were able to accomplish the task. Whereas regulation of step length became irregular during rhythmic constraint in both patients and control subjects, irregular timing of steps was only observed in patients suggesting disturbance of periodic locomotor activity generation.

Aged↗

Worsening of motor performance in patients with Parkinson's disease following transdermal nicotine administration.

Nicotine has been reported to have positive effects on motor performance in patients with Parkinson's disease. In this study, motor performance was evaluated in 16 patients with idiopathic Parkinson's disease during a practical off-period using the motor part of the Unified Parkinson's Disease Rating Scale after 12 hours' exposure to a transdermal patch containing 35 mg nicotine or placebo. The study was performed using a double-blind crossover design. In contrast to previous reports, nicotine exposure was followed by a worsening of symptoms compared with placebo. A negative response to subthreshold dopaminergic stimulation, resulting from an inhibitory effect of low striatal dopamine concentrations acting on a subset of dopamine receptors, might possibly account for this finding.

Administration, Cutaneous↗

Trick maneuvers in cervical dystonia: investigation of movement- and touch-related changes in polymyographic activity.

Antagonistic gestures or trick maneuvers are well-known clinical features to reduce or abolish dystonic posturing in cervical dystonia (CD). The maneuvers typically consist of a finger touch to the facial skin but their physiology remains unknown. To determine the temporal profile of geste maneuver performance, 25 patients with idiopathic CD were studied by means of polymyography of six cervical muscles prior to any botulinum toxin treatment. Two piezoelectric elements fixed to a fingertip of the hand involved in the trick maneuver and to the facial target region, respectively, were used to relate the essential points of the trick maneuver time course (start of geste-arm movement, facial contact, end of contact, end of movement) to changes in polymyographic activity. Thirteen patients (52%) showed marked reductions of electromyographic (EMG) activity (> or =50% in at least one muscle) during arm movement, definitely prior to contact between fingers and facial target area; in the remaining 12 patients (48%), geste-related EMG effects were confined to facial-finger contact. These results might indicate different physiological mechanisms in clinically indistinguishable antagonistic gestures.

Adult↗

[Torticollis spasmodicus, blepharospasm and hemifacial spasm. Subjective evaluation of therapy by patients].

Injections with botulinum toxin type A (BTX) are considered the first-line treatment for spasmodic torticollis (ST), blepharospasm (BL) and hemifacial spasm (HFS). Because BTX brings only temporary and partial relief, patients frequently try other additional therapies to minimize their symptoms. The subjective rating of all therapies ever tried by patients with ST, BL and HFS was evaluated by using a simple questionnaire. Two hundred questionnaires were considered (112 TS, 54 BL, 34 HFS). BTX was rated subjectively the best therapy in all three diagnostic groups (median: 2 = good effect). Despite Citalopram and physiotherapy (median: 3 = average effect), all other therapies were rated with a median of > or = 4 (= minimal effect). Patients with ST tried 7.7, patients with BL 2.4 and patients with HFS 2.6 different types of therapy. In conclusion, BTX is the most effective treatment for patients with ST, BL and HFS, as rated subjectively. Further evaluation of therapies additional to BTX injections is recommended.

Blepharospasm↗

Botulinum toxin A in the management of spastic gait disorders in children and young adults with cerebral palsy: a randomized, double-blind study of "high-dose" versus "low-dose" treatment.

The present study was performed to assess dose-response relationships of local botulinum toxin A (BtxA) treatment in children and teenagers with spastic gait due to cerebral palsy (CP) in a randomized, double-blind study employing a "high-dose" (200 units Botox per leg) and a "low-dose" (100 units Botox per leg) treatment arm in 33 patients with CP. Response parameters included changes in muscle tone assessed by the Ashworth scale at knee joint, range-of-motion (ROM) measurements at knee and ankle joint, objective analysis of longitudinal gait parameters as well as subjective assessments of improvement. Patients in the "high-dose" arm received 40-80 units Botox/muscle versus 20-40 units Botox/muscle in the "low-dose" group. Patients in both treatment arms showed significant improvement of Ashworth score (p<0.001) and ROM (p<0.01), while gait analysis revealed significant increase in gait velocity (p<0.01) and stride-length (p<0.001) over baseline. Subjects in the "high-dose" group showed significantly greater improvement on objective response measurements compared to "low-dose" patients. Also, children aged 7 years or less had greater functional benefit compared to the subgroup of patients older than 7 years. Incidence and severity of side-effects were similar in both treatment groups. The present study demonstrated dose-dependent functional improvement of dynamic deformities and spastic gait pattern in children and young adults with CP treated with local injections of botulinum toxin. A dose of 200 units Botox per leg distributed to 4 or 5 muscle bellies per leg is superior compared to 100 units Botox per leg without significantly affecting the risk of side-effects.

Adolescent↗

Comparative analysis of gait in Parkinson's disease, cerebellar ataxia and subcortical arteriosclerotic encephalopathy.

Quantitative gait analysis has been used to elucidate characteristic features of neurological gait disturbances. Although a number of studies compared single patient groups with controls, there are only a few studies comparing gait parameters between patients with different neurological disorders affecting gait. In the present study, gait parameters were compared between control subjects, patients with parkinsonian gait due to idiopathic Parkinson's disease, subjects suffering from cerebellar ataxia and patients with gait disturbance due to subcortical arteriosclerotic encephalopathy. In addition to recording of baseline parameters during preferred walking velocity, subjects were required to vary velocity from very slow to very fast. Values of velocity and stride length from each subject were then used for linear regression analysis. Whereas all patient groups showed slower walking velocity and reduced step length compared with healthy controls when assessed during preferred walking, patients with ataxia and subcortical arteriosclerotic encephalopathy had, in addition, increased variability of amplitude and timing of steps. Regression analysis showed that with changing velocity, subjects with Parkinson's disease changed their stride length in the same proportion as that measured in controls. In contrast, patients with ataxia and subcortical arteriosclerotic encephalopathy had a disproportionate contribution of stride length when velocity was increased. Whereas the findings in patients with Parkinson's disease can be explained as a reduction of force gain, the observations for patients with ataxia and subcortical arteriosclerotic encephalopathy reflect an altered spatiotemporal gait strategy in order to compensate for instability. The similarity of gait disturbance in subcortical arteriosclerotic encephalopathy and cerebellar ataxia suggests common mechanisms.

Adult↗