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J Wissel

Publications and source records attributed to J Wissel.

At least 19 recordsLinked to original sources
PubMed2006

Using translational medicine to understand clinical differences between botulinum toxin formulations.

When using botulinum toxin-based products, the physician must decide the optimal location and dose required to alleviate symptoms and improve the patient's quality of life. To deliver effective treatment, the physician needs to understand the importance of accurate target muscle selection and localization and the implications of each product's migration properties when diluted in different volumes. Pre-clinical mouse models of efficacy and safety have been utilized to compare local and distal muscle relaxation effects following defined intramuscular administration. Data from the model allow the products to be ranked based on their propensity for local efficacy versus their distal migration properties. Using standardized dilutions, the non-parallel dose-response curves for the various formulations demonstrate that they have different efficacy profiles. Distal effects were also noted at different treatment doses, which are reflected in the different safety and/or therapeutic margins. Based on these pre-clinical data, the safety and therapeutic margin rankings are ordered, largest to smallest, as BOTOX, Dysport and Myobloc. The results of subsequent clinical trials are variable and dose comparisons are inconclusive, thus supporting the regulatory position that the dose units of the individual preparations are unique and cannot be simply converted between products.

Animals↗
PubMed2004

Craniocervical dystonia questionnaire (CDQ-24): development and validation of a disease-specific quality of life instrument.

OBJECTIVE: To develop and test a questionnaire for measuring quality of life in patients with craniocervical dystonia. METHODS: A 29-item pool was developed based on semi-structured interviews of patients with cervical dystonia (CD) and blepharospasm (BSP). This preliminary questionnaire was administered to 203 consecutive patients with CD and BSP from Austrian dystonia and botulinum toxin outpatient clinics. For scale generation, a combination of exploratory factor and cluster analysis was applied. This resulted in the 24-item version of the instrument (CDQ-24) based on five subscales: Stigma, Emotional wellbeing, Pain, Activities of daily living, and Social/family life. The validity and reliability of the CDQ-24 was assessed in 231 consecutive patients with CD and BSP different from those examined with the preliminary questionnaire. This second survey included the CDQ-24, a generic QoL instrument (SF-36) and clinical rating scales. Sensitivity to change was analysed in 51 previously untreated (de novo) patients four weeks and one year following the first botulinum toxin treatment. RESULTS: Internal consistency reliability was satisfactory for all subscales, with values of Cronbach's alpha ranging from 0.77 to 0.89. The CDQ-24 subscales showed moderate to high correlations with those SF-36 subscales measuring similar aspects (Pearson's correlation r = 0.50-0.73; p<0.001, each). Sensitivity to change was confirmed by highly significant improvements of all CDQ-24 subscores in the de novo patients from baseline to four week follow up. One year follow up data revealed a stable improvement. CONCLUSION: The CDQ-24 is the first fully validated and disease specific questionnaire to evaluate quality of life of patients with cervical dystonia and blepharospasm and we propose its use in clinical trials as well as in daily clinical practice.

Activities of Daily Living↗
PubMed2002

The prevalence of primary dystonia in the general community.

The prevalence of primary dystonia was assessed in a random population sample of individuals aged 50 and over in Bruneck, South Tyrol. The diagnosis of primary dystonia was confirmed by videotaped review. Primary dystonia was present in 6 of 707 cases resulting in a prevalence rate of 732 per 100,000 (95% CI 319-1,564) in the general population aged 50 and over. Only two cases (33%) had been previously diagnosed. These results indicate that the true prevalence of primary dystonia is significantly higher than published rates.

Adult↗
PubMed2002

The impact of blepharospasm and cervical dystonia on health-related quality of life and depression.

The aim of the study was to evaluate and compare health-related quality of life (HR-QoL) and depression in essential blepharospasm (BSP) and idiopathic cervical dystonia (CD), to identify the clinical and demographic factors associated with poor HR-QoL in both disorders and to analyse the effect of Botulinum Toxin A (BtxA) therapy. Two hundred-twenty consecutive patients with BSP (N = 89, 62 % women, mean age 64 years, mean disease duration 7 years) and CD (N = 131, 64 % women, mean age 53 years, mean disease duration 8 years) recruited from routine referrals to eight Austrian dystonia clinics were included. HR-QoL was measured by the Short Form 36 (SF-36) and depression by the Beck Depression Inventory (BDI). At baseline, patients with CD and BSP scored significantly worse in all eight SF-36 domains compared with an age-matched community sample. In addition, 47 % of patients with CD and 37 % of those with BSP were depressed. Women with BSP scored significantly lower in all SF-36 domains and were more depressed than male patients. In contrast, there was no significant effect of gender on HR-QoL and depression in CD. Neck pain had a significant impact on all SF-36 domains and represented the main determinant of depression in CD. Although BtxA therapy resulted in a significant improvement of clinical symptoms in BSP and CD, HR-QoL did not improve in BSP and only two of the eight SF-36 domains improved significantly in patients with CD. The present study for the first time demonstrated that BSP has a substantial impact on health status emphasizing the need for psychological support with interventions aimed at treating depression in these patients. Our results provide further evidence for the profound impact of CD on HR-QoL and indicate the importance of an adequate management of neck pain in addition to reducing the severity of dystonia in CD. The mismatch between objective BtxA derived improvement of dystonia and lack of change of HR-QoL as determined by the SF-36 illustrates the need for optimized disease specific quality of life rating scales in patients with craniocervical dystonia.

Aged↗
PubMed2002

Botulinum toxin treatment in atypical parkinsonian disorders associated with disabling focal dystonia.

We investigated the efficacy of botulinum toxin A (BtxA) therapy in patients with atypical parkinsonian disorders (APD) exhibiting different types of disabling focal dystonia unresponsive to oral drug therapy. Eight patients with functionally disabling focal dystonia out of a series of 60 consecutive patients with APDs regularly treated at our outpatient movement disorders clinic were included. Patients were diagnosed according to established criteria and had disabling limb dystonia (n=4) or craniocervical dystonia (n=4) unresponsive to oral pharmacological treatment. Localization and dose of BtxA injections was determined individually based on clinical examination as well as EMG in patients with limb dystonia. BtxA reduced dystonic symptoms in all patients; only one developed a transient local side-effect. BtxA was particularly effective in the long-term treatment (up to 50 months) of blepharospasm associated with progressive supranuclear palsy (PSP). BtxA also alleviated PSP-associated retrocollis and orofacial dystonia with lower lip retraction associated with PSP and multiple system atrophy. BtxA treatment of limb dystonia in corticobasal degeneration (CBD) temporarily improved hand and arm function in early-disease stages while treatment in advanced stages reduced pain, facilitated hygiene and prevented secondary contractures. Limb dystonia was also alleviated by BtxA therapy in one patient with neuronal multisystem degeneration of undetermined cause. The results suggest that BtxA therapy may represent an effective means of alleviating disabling focal dystonia in different APDs. Particularly in early stage APD with disabling limb dystonia local BtxA injections may result in functional improvement.

Adult↗
PubMed2001

Dynamic balance function in phasic cervical dystonia following Botulinum toxin therapy.

Previous research by our group revealed normal dynamic balance function in pure tonic cervical dystonia (CD) with impaired equilibrium in phasic CD patients investigated at least 3 months following Botulinum toxin (BtxA) treatment. The current study was performed to determine whether impaired dynamic equilibrium in phasic CD is influenced by symptomatic treatment with BtxA. Dynamic balance was tested in 20 patients with phasic CD on a dynamic platform with a cylindrical curved base (stabilometer) 4 weeks following BtxA treatment. Balance was assessed by the linear displacement of the platform and the maximum amplitude of platform displacement with open and closed eyes and compared with pre-BtxA data. Despite a clinically significant BtxA-induced reduction of phasic head movements, none of the platform measures improved significantly. In addition, there was no correlation between the BtxA-induced clinical improvement and changes in any of the dynamic balance measures pre- vs. post-BtxA. In conclusion, the persistent dynamic balance impairment after effective BtxA therapy may indicate that disequilibrium in phasic CD does not simply reflect disturbed vestibular input from repetitive head oscillations, but argues in favour of different sensorimotor processing in tonic and phasic CD.

Adult↗
PubMed2001

Efficacy and safety of a standardised 500 unit dose of Dysport (clostridium botulinum toxin type A haemaglutinin complex) in a heterogeneous cervical dystonia population: results of a prospective, multicentre, randomised, double-blind, placebo-controlled, parallel group study.

Results from a dose-ranging study in a selected group of de novo patients with rotational cervical dystonia (CD) suggest that 500 units of Dysport (Clostridium botulinum toxin type A haemaglutinin complex) is the optimal starting dose. The present study aimed to confirm the efficacy and safety profile of this dose in a population of CD patients more representative of those seen in a typical dystonia clinic. A total of 68 patients with moderate to severe CD (Tsui score > or = 9) were randomly assigned to receive placebo or Dysport 500 units. Treatment was administered according to the clinical pattern of head deviation, using a standardised injection protocol. A total of 21 patients (11 Dysport, 10 placebo) had not previously received botulinum toxin type A (BtxA) injections, and 47 patients (24 Dysport, 23 placebo) had received BtxA more than 12 weeks previously. Assessments were performed at baseline and weeks 4, 8 and 16. Patients defined as non-responders at week 4 were re-treated in an open phase with 500 units of Dysport at week 6, and were followed up at week 10. Significant between-group differences in Tsui scores were present at weeks 4 (p=0.001) and 8 (p=0.002). Similarly, there were significant between-group differences (p < 0.001) in patient and investigator assessments of response in favour of Dysport at weeks 4 and 8. Also, more Dysport (49%) than placebo (33%) patients were pain-free at week 4 (p=0.02). Overall, 30/35 (86 %) Dysport patients and 14/33 (42%) placebo patients were classified as responders at week 4. Adverse events were reported by 15/35 Dysport patients and 9/33 placebo patients. Open phase treatment produced improvements in Tsui (p < 0.001) and pain scores (p=0.011), and 23/24 patients were classified as responders. Although individual dose titration and muscle selection is desirable, this study demonstrated that a dose of 500 units of Dysport injected into clinically identified neck muscles without electromyographic guidance is safe and effective in the treatment of patients with the major clinical types of cervical dystonia.

Adolescent↗
PubMed2001

Clinical characteristics of the geste antagoniste in cervical dystonia.

The geste antagoniste (moving an arm to the face or head) is a well-known clinical feature in cervical dystonia (CD) to alleviate the abnormal posture. The clinical phenomenology of these manoeuvres has not so far been assessed systematically. Fifty patients with idiopathic CD aware of at least one geste antagoniste (60% women, mean age at onset 44.1 years, mean disease duration 7.5 years) were subjected to a standardized investigation including a semiquantitative clinical rating scale and polymyographic recordings of six cervical muscles. Twenty-seven patients (54%) demonstrated more than one geste antagoniste (range 2-5). A clinically significant (> or = 30%) reduction of head deviation was observed in 41 patients (82 %). Dystonic head posture improved by a mean of 60 % along all planes by the geste manoeuvre with a complete cessation of head oscillations in nine of 33 patients (27 %) with phasic CD. No significant laterality of the "geste-arm" or the facial target area was found. The duration of geste-effects depended significantly on disease duration and determined the patient's self-rating of the benefit of the manoeuvre. EMG-polygraphy revealed two types of geste-induced polymyographic changes: a decrease in recruitment density and amplitude in at least one dystonic muscle (66%), and an increased tonic muscle activation in the remaining patients. The remarkable efficacy of the geste antagoniste and the considerable variety in performance, duration, and EMG-pattern of these manoeuvres warrant further investigation of the therapeutic use of sensorimotor stimulation, in particular for those CD patients who experience limited or no effect from botulinum toxin therapy.

Adolescent↗
PubMed2001

Modulation of upper extremity motor evoked potentials by cutaneous afferents in humans.

The excitability of motoneurons controlling upper limb muscles in humans may vary with cutaneous nerve stimulation. We investigated the effect of noxious and non-noxious conditioning stimuli applied to right and left digit II and right digit V on motor evoked potentials (MEPs) recorded from right thenar eminence, abductor digiti minimi, biceps and triceps brachii muscles in twelve healthy subjects. Transcranial magnetic stimulation (TMS) was applied at interstimulus intervals (ISI) ranging from 40 to 160 ms following conditioning distal digital stimulation. TMS and transcranial electrical stimulation (TES) were compared at ISI 80 ms. Painful digital stimulation caused differential MEP amplitude modulation with an early maximum inhibition in hand muscles and triceps brachii followed by a maximum facilitation in arm muscles. Stimulation of different digits elicited a similar pattern of MEP modulation, which largely paralleled the behavior of cutaneous silent periods in the same muscles. Contralateral digital stimulation was less effective. MEPs following TMS and TES did not differ in their response to noxious digital stimulation. MEP latencies were shortened by cutaneous stimuli. The observed effects were stimulus intensity dependent. We conclude that activation of A-alpha and A-delta fibers gives rise to complex modulatory effects on upper limb motoneuron pools. A-delta fibers initiate a spinal reflex resulting in MEP amplitude reduction in muscles involved in reaching and grasping, and MEP amplitude facilitation in muscles involved in withdrawal. These findings suggest a protective reflex mediated by A-delta fibers that protects the hand from harm. A-alpha fibers induce MEP latency shortening possibly via a transcortical excitatory loop.

Adult↗
PubMed2001

[Treatment of focal dystonia with botulinum toxin A].

Local injections with Botulinum toxin A (BtxA) are safe and effective in the treatment of focal dystonia. In cervical dystonia and blepharospasm, BtxA injections have become the treatment of choice. However, good results have also been reported with oromandibular dystonia, spasmodic dysphonia and writer's cramp. In cervical dystonia, muscles for injection are selected by clinical presentation or in complex forms with EMG guidance. Several studies have shown that 500 units Dysport are safe and effective in the treatment of cervical dystonia. In blepharospasm, injections are performed in the periorbital part of the orbicularis oculi muscle with good results for 12-14 weeks. The most frequently employed starting dose is 120 units Dysport per eye, divided in three periorbital injection sites. In case of levator inhibition, the pretarsal part of the orbicularis oculi muscle should be injected in a lower dose. EMG guidance is not necessary. By contrast, BtxA treatment of spasmodic dysphonia and writer's cramp require EMG-guided injections in order to avoid side-effects. Dose recommendations for the various types of dystonia are given in the text. In up to 5% of patients with dystonia, the development of neutralising antibodies is reported following repetitive injections with BtxA. Patients with antibodies had a shorter interval between injections, more "boosters", a higher dose per 3-month interval, and a higher total dose injected. In case of neutralizing antibodies against the A toxin, the treatment with Botulinum toxin B (Neurobloc) is a possible alternative.

Biomechanical Phenomena↗
PubMed2001

[Measuring outcome in spasticity rehabilitation].

Spasticity is a frequent consequence of upper motor neuron lesion and is associated with a variety of symptoms such as pain, muscle stiffness and reflex patterns that interfere with activities of daily living, dexterity and gait. As therapy strategies in managing spasticity-associated problems have been evolving there is an increasing need for a practicable documentation system which describes spasticity and related symptoms on different levels in order to evaluate especially the level of functioning. In daily routine the single-case-design reflects a useful technique to evaluate the status in terms of technical, functional and individual goals for treatment. However, there is no single tool to measure the different types of changes due to treatment, therefore a variety of selecting tests, based on the functional changes expected from the selected treatment, is recommended. The sensitivity of the selected tests should match the range of expected improvements related to the specific treatment. Technical goals should be evaluated by validated spasticity rating scales. As changes in technical measures of spasticity such as muscle tone, muscle length, range of motion or repetitive voluntary movements may not correlate with clinical improvements, individual functional goals should be defined. Those functional goals should reflect the patients' and care-givers' individual perception of the actual problem. A treatment diary is a useful tool to document subjective perception of changes over time. Some practical issues are adressed below. Reliable outcome measures enable patients and doctors to select further treatment strategies and gives health care providers information on treatment expectations in return for their investments.

Activities of Daily Living↗
PubMed2001

[Botulinum toxin type A treatment of upper limb spasticity].

In recent years, local injections with Botulinum toxin type A (BtxA) have become the treatment of choice for dystonia. However, several studies have demonstrated its efficacy and safety in the treatment of focal spasticity as well. These studies have shown efficacy and safety in upper limb spasticity treatment at a total dose between 500 and 1500 units of Dysport per injection session. While injections in upper arm muscles are easily administered without EMG-guidance, we recommend EMG-guidance for lower arm and finger muscles. In addition to functional improvement, BtxA treatment may also be considered for the following reasons: treatment of spasticity associated pain or painful muscle spasms, improved hygiene, facilitation of care, prevention of skin breakdown, and improved positioning of the upper limb. The definition of a realistic treatment goal, in agreement with the patient, as well as adjunctive physiotherapy are prerequisites for a successful BtxA treatment. Dose recommendations are given in Table 1.

Arm↗
PubMed2001

[Botulinum toxin treatment of hip adductor spasticity in multiple sclerosis].

Spasticity results in a resistance to passive movement and decrease of passive mobility of the involved joints and is defined as a state of hypertonicity with exaggeration of tendon reflexes mediated by a loss of inhibitory control of upper motor neurons. In patients with severe stages of multiple sclerosis (MS) spasticity of the lower limbs often leeds to a spastic pattern with hip adduction resulting in decreased range-of-motion (ROM), increased pain, spasms, and functional disability (disturbed gait and sitting position) as well as difficulties with perineal hygiene. Local botulinum toxin type A (Btx-A) injections in spastic muscles offer a new treatment approach for managing spasticity and associated problems. Up to now Btx-A is approved for the treatment of blepharospasm and cervical dystonia and the treatment of equinous gait in children with cerebral palsy in Austria and Germany. Up to now only in Switzerland Botox is licensed for the treatment of focal spasticity. Btx-A is a neurotoxin derived from Clostridium botulinum. In most european countries Btx-A is available as Dysport (vial = 500 units) and Botox (vial = 100 units). In prospective studies a ratio of 1 unit Botox to 3-4 units Dysport was found. Following intramuscular injection Btx-A blocks the release of acetylcholine at the neuromuscular junctions, thereby inhibiting muscle contraction, and decreases spastic muscle tone and muscle spindles afferent information to the spinal cord. The spectrum of side effects includes local weakening of the injected and adjacent muscles as well as pain and haematoma at the injection site. At therapeutic doses side effects are local and transient. According to a double blind, placebo controlled, dose ranging study published by Hyman et al. (2000, Dysport in a dose of 500, 1000 and 1500 units reduced the degree of hip adductor spasticity associated with MS, and this benefit was evident despite concomitant use of oral antispasticity medication. According to the results of the study there was a clear trend towards greater efficacy and duration of effects with higher doses of Dysport. Taking efficacy and adverse events into account (incidence of muscle weakness was higher for the 1500 units group than for placebo) the optimal dose for hip adductor spasticity seems to be 1000 units Dysport divided between the adductor magnus, longus and brevis muscles and between both legs. To increase Btx-A effects following injection of hip adductors additional physiotherapy and casting or orthosis to increase passive hip-abduction is recommended. According to the literature anatomical localisation of the adductor muscles for injection and aspiration following insertion of the needle, to avoid injection of the toxin into a vessel, should be performed. A maximum dose of 1500 units Dysport (400 units Botox) per treatment session and 250 units Dysport (50 units Botox) per injection site is recommended. See table for dose-range of Dysport, and Botox in the treatment of adult patients with hip-adductor spasticity. For evaluation of treatment effects in hip adductor spasticity clinical examination with specific scales and measurements (see Appendix) at baseline, 4 and 12 weeks following BtxA injection is recommended:--Global rating of severity (0-4; patient's self assessment and physician's rating) --Global rating of response (-4 - +4; patient's self assessment and physician's rating)--Visual Analogue Scale (patient's self assessment of pain)--Active and passive ROM (manual goniometer)--Distance between the medial femur condyles in thigh extension (distance in cm)--Modified Ashworth scale (0-4)--Ten meter walking time (seconds)--Functional Ambulation Categories (0-5)--Score of perineal hygiene (0-5).

Adult↗