Excessive psychological stress preceding the onset of idiopathic cervical dystonia.

Idiopathic cervical dystonia (ICD) is the largest subgroup of dystonia. Psychological stress as a triggering factor has long been discussed, but detailed descriptions are lacking. We report on a group of 13 patients with ICD and preceding excessive psychological stress (age at ICD onset 39.0 ± 13.9 years, 7 females, 6 males). The observation period was 7.8 ± 5.0 years. Excessive psychological stress included partner conflicts (divorce and separation, domestic violence), special familial burdens, legal disputes and migration. It started 8.3 ± 3.9 months before ICD onset. In 85% of our patients (typical cases), ICD developed within 5.8 ± 4.4 weeks, then lasted 18.5 ± 8.3 months, before it started to remit 2.7 ± 0.8 years after its onset to 54.5 ± 35.3% of its maximal severity. Idiopathic dystonia is thought to be based upon a genetic predisposition triggered by epigenetic factors. Our study suggests that excessive psychological stress could be one of them. Pathophysiologic elements are only vaguely identified, but could include the endoplasmic reticulum stress response, cerebellar 5HT-2A receptors and the metabolism of heat shock proteins. Whilst the clinical presentation of ICD preceded by excessive psychological stress is typical, its course is atypical with rapid onset and fast and substantial remission.

Botulinum toxin antibody titres: measurement, interpretation, and practical recommendations.

Botulinum toxin (BT) therapy may be blocked by antibodies (BT-AB) resulting in BT-AB induced therapy failure (ABF). BT-AB may be detected by the mouse lethality assay (MLA), the mouse diaphragm assay (MDA) and the sternocleidomastoid test (SCMT). For the first time, we wanted to compare all three BT-AB tests and correlate them to subjective complaint of complete or partial secondary therapy failure in 37 patients with cervical dystonia (25 females, 12 males, age 51.2 ± 11.4 years, disease duration 12.4 ± 6.3 years). Complaint of therapy failure was not correlated with any of the BT-AB tests. MDA and MLA are closely correlated, indicating that the MDA might replace the MLA as the current gold standard for BT-AB measurement. The SCMT is closely correlated with MDA and MLA confirming that BT-AB titres and BT's paretic effect are in a functional balance: low BT-AB titres are reducing BT's paretic effect only marginally, whereas high BT-AB titres may completely block it. When therapy failure is classified as secondary and permanent, BT-AB evaluation is recommended and any BT-AB test may be applied. For MDA > 10 mU/ml, MLA > 3 and SCMT < 25%, ABF is highly likely. MDA < 0.6 mU/ml are therapeutically irrelevant. They are neither correlated with pathologic MLA nor with pathologic SCMT. They should not be the basis for treatment decisions, such as switching dystonia therapy to deep brain stimulation. All other results are intermediate results. Their interactions with therapy efficacy is unpredictable. In these cases, BT-AB tests should be repeated or one or two additional test methods should be applied.

The epidemiology of dystonia: the Hannover epidemiology study.

The prevalence of dystonia has been studied since the 1980s. Due to different methodologies and due to varying degrees of awareness, resulting figures have been extremely different. We wanted to determine the prevalence of dystonia according to its current definition, using quality-approved registries and based on its relevance for patients, their therapy and the health care system. We applied a service-based chart review design with the City of Hannover as reference area and a population of 525,731. Barrier-free comprehensive dystonia treatment in few highly specialised centres for the last 30 years should have generated maximal dystonia awareness, a minimum of unreported cases and a high degree of data homogeneity. Prevalence [n/1mio] and relative frequency is 601.1 (100%) for all forms of dystonia, 251.1 (42%) for cervical dystonia, 87.5 (15%) for blepharospasm, 55.2 (9%) for writer's cramp, 38.0 (6%) for tardive dystonia, 32.3 (5%) for musician's dystonia, 28.5 (5%) for psychogenic dystonia, 26.6 (4%) for generalised dystonia, 24.7 (4%) for spasmodic dysphonia, 20.9 (3%) for segmental dystonia, 15.2 (3%) for arm dystonia and 13.3 (2%) for oromandibular dystonia. Leg dystonia, hemidystonia and complex regional pain syndrome-associated dystonia are very rare. Compared to previous meta-analytical data, primary or isolated dystonia is 3.3 times more frequent in our study. When all forms of dystonia including psychogenic, generalised, tardive and other symptomatic dystonias are considered, our dystonia prevalence is 3.7 times higher than believed before. The real prevalence is likely to be even higher. Having based our study on treatment necessity, our data will allow better allocation of resources for comprehensive dystonia treatment.

Botulinum toxin dosing in arm muscles: contextual factors.

Botulinum toxin (BT) has been successfully used for many years to treat various muscle hyperactivity disorders including dystonia and spasticity. Its dosing is guided by dosing tables describing target muscles and dose ranges. To refine the BT dosing, we wanted to analyse how contextual factors may influence the injector's final dosing decision.In a retrospective review of real-life data of 1170 BT treatments, we studied the influence of various contextual factors on the BT doses in 21 arm muscles of 252 patients receiving BT therapy for different muscle hyperactivity disorders.We found that BT arm doses are significantly higher in treatment of spasticity than in treatment of dystonia. We also found that spontaneous arm dystonia requires higher BT doses in a proximal application pattern, whereas task specific writer's cramp requires considerably reduced BT doses with a distal application pattern. Injections of non-arm muscles influence the BT dosing in arm muscles only marginally.Our study demonstrates that BT dosing does not only depend on the particularities of the individual target muscle injected, such as its volume and its static or phasic function. BT dosing and its application pattern rather depend on additional contextual factors such as the aetiology and pathophysiology of the muscle hyperactivity treated. These contextual factors need to be included in dosing tables and may improve the outcome of BT therapy.

Botulinum toxin therapy of dystonia.

Botulinum toxin (BT) is used to treat a large number of muscle hyperactivity syndromes. Its use in dystonia, however, is still one of the most important indications for BT therapy. When BT is injected into dystonic muscles, it produces a peripheral paresis which is localised, well controllable and follows a distinct and predictable time course of around 3 months. Adverse effects are always transient and usually mild, long-term application is safe. With this profile BT can be used to treat cranial dystonia, cervical dystonia and limb dystonia including writer's and musician's cramps. The recent introduction of BT high dose therapy also allows to treat more wide-spread dystonia including segmental and generalised dystonia. BT can easily be combined with other anti-dystonic treatments such as deep brain stimulation and intrathecal baclofen application. Best treatment results are obtained when BT therapy is integrated in the multimodal and long-term 'multilayer concept of treatment of dystonia'. The biggest challenge for the future will be to deliver state of the art BT therapy to all dystonia patients in need, regardless of whether they live in developed countries or beyond.

Botulinum toxin therapy in the SARS-CoV-2 pandemic: patient perceptions from a German cohort.

The SARS-CoV-2 virus pandemic has provoked drastic countermeasures including shutdowns of public services. We wanted to describe the effects of a 6 week shutdown of a large German botulinum toxin (BT) outpatient clinics on patients and their well-being. 45 patients (age 61.9 ± 9.8 years, 29 females, 16 males) receiving BT therapy (319.3 ± 201.9MU-equivalent, treatment duration 8.3 ± 5.5 years) were surveyed with a standardised questionnaire. The shutdown delayed BT therapy by 6.6 ± 2.3 weeks. 93% of the patients noticed increased muscle cramps and 82% increased pain reducing their quality of life by 40.2 ± 19.5%. For 23 patients with cervical dystonia this reduction was 41.1 ± 18.3%, for 3 patients with blepharospasm 33.3 ± 15.3%, for 9 patients with spasticity 37.8 ± 15.6%, for 4 patients with pain conditions 37.4 ± 35.7% and for 3 patients with hemifacial spasm 27.5 ± 17.1%. After the shutdown 66% of patients perceived BT therapy as more important than before, 32% perceived it as unchanged. For all patients long-term availability of BT therapy was very important or important. 98% of the patients perceived the shutdown as inadequate and felt their patient rights not respected. The shutdown confirmed the considerable burden of disease caused by dystonia, spasticity, hemifacial spasm and various pain conditions and the importance of BT therapy to treat them. Any shutdown severely affects these patients and needs to be avoided.

Do complexing proteins provide mechanical protection for botulinum neurotoxins?

Botulinum toxin (BT) consists of botulinum neurotoxin and complexing proteins (CPs). CPs might provide mechanical protection for botulinum neurotoxin. As incobotulinumtoxinA (INCO, Xeomin®) does not contain CPs, we wanted to compare its mechanical stability to that of onabotulinumtoxinA (ONA, Botox®) containing CPs. For this, ONA and INCO were reconstituted without mechanical stress (NS) and with mechanical stress (WS) generated by a recently introduced stress test. Potencies were then measured by the paralysis times (PTs) in the mouse diaphragm assay. ONA-PT was 75.8 ± 10.3 min (n = 6) under NS and 116.7 ± 29.8 min (n = 6) under WS (two-tailed t test, p = 0.002). Mechanical stress increased the ONA-PT by 35.0% on the Growth Percentage Index. INCO-PT was 66.0 ± 7.0 min for NS and 76.0 ± 1.0 min for WS (t test, p = 0.129). Mechanical stress increased the INCO-PT by 13.2% on the Growth Percentage Index. Our data show that mechanical stress inactivates a CP-containing BT drug, but not a CP-free BT drug. We conclude that CPs do not provide protection against mechanical stress, supporting the view that CPs are not necessary for therapeutic purposes.

Antibody-induced failure of botulinum toxin therapy: re-start with low-antigenicity drugs offers a new treatment opportunity.

Botulinum toxin (BT) can stimulate formation of BT antibodies (BTAB) thus producing Antibody-Induced Therapy Failure (ABTF). BTAB titres may drop eventually. When BT therapy is then re-started with conventional BT drugs, BTAB titres re-increase promptly. We wanted to study whether the use of the low-antigenicity BT drug incobotulinumtoxinA (INCO) can prevent this re-increase. 8 patients with cervical dystonia and ABTF with maximal BTAB titres (6 women, 2 men, age 41.4 ± 12.1 years, disease duration 6.6 ± 4.7 years) were studied. ABTF ocurred under onabotulinumtoxinA (ONA) in five patients and under abobotulinumtoxinA (ABO) in 3 after 8.8 ± 3.8 injection series and a treatment time of 962.0 ± 473.2 days. After 3881.5 ± 2468.3 days without BT, all BTAB titres had dropped to insignificant levels before BT therapy was re-started with INCO. Treatment parameters before and after re-start were as follows: single dose 219.2 ± 90.7 MU vs 252.6 ± 109.0 MU (ns), interinjection interval 119.7 ± 18.4 vs 104.5 ± 14.7 days (ns), cumulative dose 1893.8 ± 1161.6 MU vs 5130.4 ± 3602.5 MU (ns), treatment time 962.0 ± 505.9 vs 1895.4 ± 1211.4 days (ns) and number of injection series 8.8 ± 3.8 vs 19.3 ± 11.8 (ns). Repeated BTAB measurements and clinical examinations did not reveal any signs of ABTF after re-start. INCO offers a new and long-term treatment opportunity for ABTF patients when their BTAB titres have dropped. Our observations also confirm lower antigenicity of INCO compared to conventional BT drugs.

Botulinum toxin therapy in patients with oral anticoagulation: is it safe?

When used therapeutically, botulinum toxin (BT) has to be injected into its target tissues. All manufacturers warn not to do so in patients with oral anticoagulation to avoid haematoma. We wanted to study the haematoma frequency (HF) in patients with anticoagulation receiving BT therapy. 32 patients (16 females, 16 males, age 69.3 ± 10.0 years) with blepharospasm (n = 6), hemifacial spasm (n = 8), post-stroke spasticity (n = 16), and cervical dystonia (n = 2) received BT therapy (needle size 27G, post-injection tissue compression) whilst on anticoagulation (anticoagulation group, AG). 32 patients matched for disease, target muscles, age, and gender received identical BT therapy without anticoagulation (control group, CG). Anticoagulation was performed with phenprocoumon. International normalised ratio (INR) at the time of BT injection was in all patients within the recommended margins of 2.0 and 3.0 (mean 2.6 ± 0.27). Overall HF was 3.0% in AG and 1.8% in CG (not significant). All hematomas occurred in blepharospasm patients (AG 5.2%, CG 2.6%, not significant) and hemifacial spasm patients (AG 3.9%, CG 2.9%, not significant). In cervical dystonia and spasticity there were no haematomas. Throughout an observation period of 4 years, none of the haematomas was surgically relevant. Haematomas are a rare complication of BT therapy, mainly occurring in periocular injections. Anticoagulation only marginally increases HF, provided INR is controlled and appropriate injection techniques are used. Surgically relevant haematomas do not occur. Interruption of oral anticoagulation to perform BT therapy is not justified.

Economics of botulinum toxin therapy: influence of the abobotulinumtoxinA package size on the costs of botulinum toxin therapy.

BACKGROUND: AbobotulinumtoxinA (Dysport®) was distributed for many years in vials containing 500MU (D500). Recently a new 300MU vial (D300) was additionally introduced (introduction). We wanted to explore whether more differentiated package sizes allow for more economic use of Dysport® in a large neurological botulinum toxin (BT) outpatient clinic. METHODS: The study followed a retrospective chart review design based on our digital BT therapy data bank. All patients receiving Dysport® exclusively in a constant dose during the observation period (introduction ± 7 months) were included. Economic calculations are based on Dysport® prices as officially advertised in Germany. Sharing of vials between patients was not allowed. RESULTS: Altogether 83 patients (51 with dystonia, 25 with spasticity, 3 with hemifacial spasm, 4 with other diagnoses) were included in this study. The total amount of BT used before and after introduction was 102525MU, the amount prescribed 138000MU and 116300MU (-21700MU, -15.7%), the costs €146103 and €125250 (-€ 20853, -14.3%). The price for D500 before and after introduction was €529.36, for D300 €339.71. The D500 price for 1MU before and after introduction is €1.0587, the D300 price for 1MU €1.1324 (+ €0.073, +7.0% against D500). CONCLUSIONS: More flexible packaging reduces drug costs for BT therapy considerably. Introducing smaller packaging sizes is technically possible and should be encouraged. Extra costs for registration and logistics are moderate. Further cost reductions may be possible by introduction of even smaller packaging sizes. They can be calculated based on our model.

Botulinum toxin therapy: reduction of injection site pain by pH normalisation.

Botulinum toxin (BT) is injected intramuscularily and may produce injection site pain (ISP). We wanted to explore whether the pH value of the reconstituted BT drug contributes to ISP and, if so, what strategies can be applied to reduce it. In part 1 of the study, pH values of different reconstitution solutions and of major BT drugs reconstituted with different reconstitution solutions were assessed. In part 2, the effects of reconstitution with normal saline (NS) and Ringer acetate (RA) were compared intraindividually and in a double blind fashion in 34 patients with blepharospasm. pH values of reconstitution solutions were 5.52 ± 0.02 for NS, 6.98 for RA, 6.31 for Ringer lactate, 6.56 for electrolyte and 5.31 for bacteriostatic solution. pH values for NS-reconstitution were 6.09 ± 0.20 for Botox(®), 5.95 ± 0.24 for Dysport(®) and 5.81 ± 0.18 for Xeomin(®). pH values for RA-reconstitution were 6.95 ± 0.03 for Botox(®), 7.01 ± 0.02 for Dysport(®) and 6.87 ± 0.06 for Xeomin(®). By using RA instead of NS the pH could be increased by 0.86 for Botox(®), by 1.06 for Dysport(®) and by 1.06 for Xeomin(®). 47 % of the patients experienced less ISP when Botox(®)-RA was given rather than Botox(®)-NS, 76 % when Xeomin(®)-RA was given rather than Xeomin(®)-NS. None of the patients reported a difference in efficacy between NS- and RA-reconstitution. Despite previous reports, reconstituted BT type A drugs show acidic pH values. Normalising these pH values by use of RA instead of NS reduces ISP considerably without sacrificing clincial efficacy.

IncobotulinumtoxinA (Xeomin(®)) can produce antibody-induced therapy failure in a patient pretreated with abobotulinumtoxinA (Dysport(®)).

IncobotulinumtoxinA has not produced a single case of antibody-induced therapy failure after 8 years of worldwide usage. We are reporting a patient with progressive hereditary juvenile onset generalised dystonia who was pretreated with abobotulinumtoxinA for 15 years, before she received incobotulinumtoxinA. To the fifth and sixth applications, she responded with complete therapy failure. Mouse hemidiaphragm assay testing revealed a maximal botulinum toxin antibody titre. Improved specific biological activity and lack of complexing proteins seem to reduce the antigenicity of incobotulinumtoxinA. However, this first ever report indicates that it does not eliminate it entirely.

Botulinum toxin in myotonia congenita: it does not help against rigidity and pain.

Botulinum toxin (BT) is a potent local muscle relaxant with analgetic properties. Myotonia congenita (MC) is a genetic disorder producing muscle rigidity and pain. BT injected into the trapezius produced mild paresis, but no effect on rigidity and pain. There were no signs of systemic effects. Lack of BT efficacy on MC rigidity confirms its origin from muscle membrane dysfunction rather than from inappropriate neuromuscular activation. Lack of BT efficacy on pain could be caused by lack of anti-rigidity effect. It could also be due to separate non-muscular pain mechanisms unresponsive to BT.

Botulinum toxin therapy of cervical dystonia: comparing onabotulinumtoxinA (Botox(®)) and incobotulinumtoxinA (Xeomin (®)).

Several botulinum toxin (BT) drugs are licensed for the treatment of cervical dystonia (CD). We wanted to compare the efficacy and the potency labelling of incobotulinumtoxinA (Xeomin(®)) and onabotulinumtoxinA (Botox(®)) by analysing the duration of their therapeutic effect in a cross-over study. For this we studied 40 CD patients (26 females, 14 males, age at therapy onset 52.6 ± 12.0 years, duration of dystonia at therapy onset 10.0 ± 9.2 years, Tsui score 9.1 ± 3.9) who first received Botox(®) and then Xeomin(®) for at least 4 injection series each. BT doses were exchanged based on a 1:1 conversion ratio. Altogether 1,101 treatment cycles were evaluated. For each patient 27.5 ± 13.1 treatment cycles were recorded. Patients received 18.4 ± 12.4 treatment cycles with Botox(®) and 9.2 ± 4.5 with Xeomin(®). The treatment duration (TD) throughout the treatment course was 11.3 ± 1.0 weeks (Botox(®) 11.2 ± 1.1 weeks, Xeomin(®) 11.4 ± 1.3 weeks). The interinjection interval (II) throughout the treatment course was 14.8 ± 1.9 weeks (Botox(®) 14.7 ± 1.6 weeks, Xeomin(®) 15.0 ± 2.2 weeks). The mean difference between Botox(®) and Xeomin(®) was 0.3 weeks for TD (two-sided 95 % confidence interval [-0.3; 0.9]) and 0.5 weeks for II (two-sided 95 % confidence intervals [-0.4; 1.4]). The confidence intervals of both parameters were within the predefined therapeutic equivalence range set to ±1.5 weeks, thus indicating similar efficacy of both BT drugs. Having based the exchange of Botox(®) and Xeomin(®) on a conversion factor of 1:1 our data confirm previous findings of an identical potency labelling of both products, thus allowing comparisons of efficacy, adverse effects and costs.

Towards a dose optimisation of botulinum toxin therapy for axillary hyperhidrosis: comparison of different Botox(®) doses.

Botulinum toxin is considered the treatment of choice for axillary hyperhidrosis. Its dosing, however, varies widely. We wanted to study differences in efficacy and adverse effects when Botox(®) 100 MU (B100) or Botox(®) 50 MU (B50) per axilla is applied. In a prospective double blind intraindividual side to side comparison design, we studied 51 patients (38 females, 13 males, age 32.8 ± 13.0 years) with symmetric axillary hyperhidrosis receiving B100 bilaterally the baseline period (BP), B100 unilaterally and B50 contralaterally at direct comparison (DC) and B50 bilaterally during the extension period (EP). 90 % of the patients reported the overall therapeutic effect as 'excellent', 10 % as 'good' during throughout the study. The duration of the therapeutic effect until it began to decline was 3.2 ± 1.3 months at BP, 3.2 ± 1.1 months at DC and 3.3 ± 1.4 months at EP. At DC none of the patients reported side to side differences of the therapeutic effect with respect to onset latency, intensity and duration. Injection site pain was identical on both sides. The clinical examination at the time of the re-injections did not reveal any side differences of the therapeutic effect. Throughout the study none of the patients reported adverse effects. Data suggest that the therapeutic effect of Botox(®) saturates at B50. Higher Botox(®) doses seem not to be necessary thus reducing costs for the treatment substantially.

Interdisziplinärer Arbeitskreis Bewegungsstörungen (IAB): an interdisciplinary working group for promoting multimodal therapy of movement disorders.

Increasing complexity of therapeutic strategies for movement disorders (MD) requires multimodal therapies involving various health care professionals and physicians. Coordinating all professions involved is difficult. An interdisciplinary working group (Interdisziplinärer Arbeitskreis Bewegungsstörungen, IAB) serves to promote and improve multimodal therapies of MD. IAB was started 6 years ago in Hamburg, Germany as an interdisciplinary special interest group with about 25 physiotherapists, occupational therapists, speech therapists, nurse specialists, physicians and invited guests regularly meeting each quarter. IAB expanded and now also includes a webpage with data bases, a special interest group for Parkinson assistants, a meeting arm for organising meetings accredited by continuous medical education authorities and a publication arm for production of educational materials including a communication form and a communication calendar developed by IAB. Recently, IAB acquired a video production enterprise producing educational MD videos. In the meantime, two more IAB groups were founded in other regions of Germany. IAB's stability over more than 6 years and its expansion into more regions and other tasks documents the demand for promotion of multimodal therapies for MD.

Prevalence of neutralising antibodies in patients treated with botulinum toxin type A for spasticity.

Botulinum toxin (BT) has been used with great success to treat various muscle hyperactivity disorders. Occasionally, antibodies against BT (BT-AB) can be formed. When they are directed against the neurotoxin component of the BT drug, they are called neutralising antibodies. They can reduce the therapeutic effect partially or completely. We have measured neutralising BT-AB by use of the mouse diaphragm assay (MDA) in 42 adult patients with spasticity in the order of their appearance in the clinic. The patients had been treated for at least 2 years with BT type A (BT-A) and received on an average 14.2 +/- 6.1 BT-A injection series. BT-A was applied as Botox only, Dysport only or by sequential application of both preparations. The mean cumulative doses were 4,610 +/- 1,936 units Botox and 14,033 +/- 7,566 units Dysport, respectively. The mean treatment time was 4.5 +/- 1.8 (2-8) years. All patients were initially responsive to BT-A therapy. MDA detected BT-AB in 12% (5/42) of patients. However, in three patients the BT-AB titre was very low (<0.3 mIU/ml), in one it was intermediate (0.6 mIU/ml) and in one patient it was high (>1.0 mIU/ml). All BT-AB negative patients and also two of the patients with low BT-AB titre remained clinically responsive to BT therapy throughout the study. In conclusion, prevalence of BT-AB formation with clinical relevance (6%, 3/42) in adult patients with spasticity is not higher than that of BT-treated patients with cervical dystonia and much lower than that of BT-treated patients with infantile cerebral palsy.

Botulinum toxin: mechanisms of action.

Botulinum toxin (BT) has been perceived as a lethal threat for many centuries. In the early 1980s, this perception completely changed when BT's therapeutic potential suddenly became apparent. We wish to give an overview over BT's mechanisms of action relevant for understanding its therapeutic use. BT's molecular mode of action includes extracellular binding to glycoprotein structures on cholinergic nerve terminals and intracellular blockade of the acetylcholine secretion. BT affects the spinal stretch reflex by blockade of intrafusal muscle fibres with consecutive reduction of Ia/II afferent signals and muscle tone without affecting muscle strength (reflex inhibition). This mechanism allows for antidystonic effects not only caused by target muscle paresis. BT also blocks efferent autonomic fibres to smooth muscles and to exocrine glands. Direct central nervous system effects are not observed, since BT does not cross the blood-brain barrier and since it is inactivated during its retrograde axonal transport. Indirect central nervous system effects include reflex inhibition, normalisation of reciprocal inhibition, intracortical inhibition and somatosensory evoked potentials. Reduction of formalin-induced pain suggests direct analgesic BT effects possibly mediated by blockade of substance P, glutamate and calcitonin gene-related peptide.

Botulinum toxin type B for treatment of axillar hyperhidrosis.

Recently, botulinum toxin type B (BT-B) became commercially available for treatment of cervical dystonia. It is the aim of this study to explore its use for treatment of bilateral axillar hyperhydrosis (HH). For this we directly compared the antihyperhydrotic effect of BT-B (NeuroBloc)/MyoBloc) with that of botulinum toxin type A (BT-A) (Botox). 9 patients (HD group) received BT-A 100MU unilaterally and BT-B 4000MU contralaterally. 10 patients (LD group) received BT-A 100MU and BT-B 2000MU. All patients were blinded as to which preparation was used in which side. All patients except one reported excellent HH improvement in both axillae. None of the patients had residual HH on clinical examination. The duration of HH improvement until first recurrence in the HD group was 16.0 +/-4.3 weeks in the BT-A treated axillar and 16.4 +/-4.5 weeks in the BT-B treated axillae (Wilcoxon rank-sum test, p = 0.336). In the LD group it was 16.4 +/-5.3 weeks in the BT-B treated axillae and 17.1 +/-5.7 weeks in the BT-A treated axillae (Wilcoxon rank-sum test, p = 0.059). There was also no difference in the duration of HH improvement between the axillae treated with BT-B 4000MU and BT-B 2000MU (Wilcoxon rank-sum test, p = 0.712). 5 out of 9 patients in the HD group (chi-square test, p = 0.025) and 7 out of 10 patients in the LD group (chi-square test, p = 0.008) reported more application discomfort in the BT-B treated axillae. In 6 out of 9 patients in the HD group (chi-square test, p = 0.014) and in 6 out of 10 patients in the LD group (chi-square test, p = 0.014) the onset of HH improvement appeared earlier in the BT-B treated axillae. One patient in the HD group reported dryness of the mouth and eyes and accomodation difficulties.BT-B is a safe and efficient treatment for axillar HH. Doses of BT-B 2000MU per axilla seem sufficient indicating a conversion factor between BT-A and BT-B in the order of 1:20. With a conversion factor for cervical dystonia in the order of 1:40 the autonomic nervous system seems to be relatively more sensitive to BT-B than to BT-A compared with the motor system.