Peter Schnider

EUROPEAN CONSENSUS TABLE ON THE USE OF BOTULINUM TOXIN TYPE A IN ADULT SPASTICITY

A group of clinicians from across Europe experienced in the use of botulinum toxin type A for the treatment of spasticity following acquired brain injury gathered to develop a consensus statement on best practice in managing adults with spasticity. This consensus table summarizes the current published data, which was collated following extensive literature searches, their assessment for level of evidence and discussion among the whole group. Published information is supplemented by expert opinion based on clinical experience from 16 European countries, involving 28 clinicians, who treat an average of approximately 200 patients annually, representing many thousand spasticity treatments with botulinum toxin per year.

A Lack of Antinociceptive or Antiinflammatory Effect of Botulinum Toxin A in an Inflammatory Human Pain Model

Several in vitro and in vivo investigations have shown that botulinum toxin A (BoNT/A) can inhibit the release of substance P and excitatory amino acids. Recently, a marked antinociceptive effect of BoNT/A and inhibition of glutamate release was observed in an animal pain model with inflammatory sensitization. In the present study, we tested the antiinflammatory and antihyperalgetic effect of BoNT/A in a well-characterized human inflammatory pain model. Using a randomized, double-blind, paired study design, we compared the effects of 100 mouse units of BoNT/A versus pure saline. Thermal and mechanical pain testings and superficial skin blood flow measurements were performed at baseline, at 48 h (in normal skin), and at 72 h (in inflamed skin) thereafter. Ultraviolet B irradiation resulted in a local inflammation with significant primary and secondary hyperalgesia. However, despite the evidence of efficacy on sudomotor function, BoNT/A had no effect on pain measures in either normal or inflamed skin. Signs of inflammation and primary and secondary hyperalgesia were found to be unaffected by BoNT. We have confirmed that BoNT/A has no direct effect on acute, noninflammatory pain. Furthermore, despite highly promising data from animal research, we have not observed antiinflammatory or antinociceptive effects of BoNT/A in human inflammatory pain.

C677T MTHFR Mutation and Factor V Leiden Mutation in Patients with TIA/Minor Stroke: A Case-Control Study

A common C677T mutation in the gene for the enzyme 5,10-methylenetetrahydrofolate reductase (5,10-MTHFR) has been linked to elevated levels of homocysteine and was therefore suspected to be a candidate genetic risk factor for arterial occlusive disease. Another mutation, factor V Leiden, has been established as a common hereditary risk factor for venous thrombosis, but its role in arterial disease remains controversial. We investigated the prevalence of both the C677T MTHFR mutation and the factor V Leiden mutation in 81 patients with transient ischemic attack (TIA) or minor stroke (MS) and in 81 age- and sex-matched control subjects free from clinically manifest vascular disease. We further compared clinical and laboratory data as well as clinical course of patients carrying the factor V Leiden mutation alone or in combination with the C677T MTHFR mutation and mutation-free patients. The prevalence of the MTHFR mutation did not differ between patients and control subjects with 11.1% homozygous carriers in both groups (OR for homozygous carriers 1.0; 95% CI 0.38-2.66). However, there was a trend towards a higher prevalence of carriers of factor V Leiden in patients (12.3%) than in control subjects (4.9%) (OR 2.75; 95% CI 0.83-9.17;p=0.09). Furthermore, we found some evidence that the combined occurrence of the C677T MTHFR mutation and factor V Leiden might unfavorably affect the clinical course of the disease, but the number of respective patients was small. Larger studies with a greater number of carriers of both the C677T MTHFR mutation and factor V Leiden seem therefore warranted.

Respective Potencies of Botox® and Dysport® in a Human Skin Model : A Randomized, Double-blind Study

Mouse units used to quantify the activity of botulinum A toxin preparations are not equivalent and issues concerning efficacy and safety remain with regard to their respective potencies and diffusion qualities in human tissue. We compared the effects of Botox® (BOT) and Dysport® (DYS) in different doses and dilutions in a human skin model. Eighteen (8 women, 10 men) healthy volunteers, aged 28.4 years ± 5.7 years were injected intradermally with pure saline, BOT and DYS at 16 points in the abdomen in random order and in a double‐blind condition, using two conversion ratios (1:3 and 1:4) and three different dilution schemes. For an objective outcome, the Ninhydrin sweat test was used to compare the anhidrotic areas. Both preparations showed a linear dose and dilution relationship with similar variances of responses for anhidrosis and hypohidrosis, indicating the same reliability of response. The dose equivalence conversion ratios (BOT: DYS) were 1:1.3 for anhidrosis and 1:1.6 for hypohidrosis (1:1.1‐1.5 and 1:1.4‐1.8 95% confidence intervals). The diffusion characteristics of both products were similar. A dose equivalence factor of more than 1:2 (BOT:DYS) is not supported by these objective and reproducible data.

Cardiac Autonomic Function in Patients Suffering from Primary Focal Hyperhidrosis

Cardiac autonomic function in patients (n = 63) with primary focal hyperhidrosis and healthy controls (n = 28) was investigated by short-term frequency domain power spectral analysis of heart rate variability. The power of the very-low-frequency band (0.01–0.05 Hz) was significantly lower in patients with axillary hyperhidrosis than in controls. No differences between groups could be observed at investigation of the low-frequency band (0.05–0.15 Hz), which was a surprising finding because this band represents also sympathetic cardiac innervation. At the high-frequency band (0.15–0.5 Hz), which represents parasympathetic cardiac innervation, an interaction of type and position influencing spectral power was detected. Our highly interesting findings indicate that primary focal hyperhidrosis is based on a much more complex autonomic dysfunction than generalised sympathetic overactivity and seems to involve the parasympathetic nervous system as well.

Tension-type headache in different age groups at two headache centers

&NA; At two headache centers, one for children and adolescents and the other for adults, we investigated patients aged 5–80 years with episodic or chronic tension‐type headache to evaluate the relation between age and headache characteristics as well as analgesics intake. We found an increasing headache frequency and duration, an increasing variability of the headache location, and an increasing frequency of nausea with increasing age. All other headache features did not depend on age. Additionally, our study revealed a marked increase of analgesics use in adults compared to children and adolescents. In conclusion, children, adolescents, and adults referred for tension‐type headache show minor differences in some headache features, but a marked change of analgesics intake. The different headache symptoms may be causally related to age, but an influence of medication or other factors must also be considered.

Bladder Volume Determination: Portable 3-D Versus Stationary 2-D Ultrasound Device

OBJECTIVE To investigate how accurately a portable three-dimensional (3-D) scanner and a multipurpose two-dimensional (2-D) real-time scanner determined bladder volumes. STUDY DESIGN Prospective, controlled clinical trial, single-blind, crossover design. SETTING AND PARTICIPANTS Twenty-three inpatients with permanent bladder catheters participated voluntarily in this study. METHODS The bladders of 20 patients were filled through an indwelling catheter with 60, 110, 160, 210, and 260 mL sterile normal saline. Volumes were measured twice with each device. Measurements were compared with the actual bladder volumes. RESULTS The 2-D device showed better reproducibility, particularly at lower bladder volumes. The 3-D scanner showed a significant difference between the two measurements at 160 mL (p<.05) and had poor reproducibility at 110, 210, and 260 mL. Both devices overestimated actual bladder volume at fillings of <160 mL and underestimated it at fillings of > or =160 mL. The range between the 25th and 75th percentiles was always larger for the 3-D scanner, except for the 210 mL reading. CONCLUSION Both devices showed sufficient accuracy for clinical practice. Ultrasound measurements of >110 mL should be followed by catheterization to detect potentially harmful bladder volumes.

Physical therapy and adjunctive botulinum toxin type A in the treatment of cervical headache: a double-blind, randomised, placebo-controlled study

Abstract We examined the efficacy of physical therapy and adjunctive botulinum toxin type A (BTX-A) injections in the treatment of cervical headache. We performed a doubleblind, randomised, placebo-controlled study over a 12-week period in a university clinic outpatients department. A total of 33 patients with cervical headache, diagnosed according to International Headache Society classification were enrolled. All patients received standardized physical therapy over a three-week period. Patients were randomised to receive either BTX-A (Botox) or placebo. The BTX-A group received a total dose of 90 mouse units (mu) BTX-A at six trigger points while the placebo group received saline. Pain characteristics were reported in a headache diary. Tenderness in the neck muscles, the sagittal range of motion and biofeedback measurement were also documented. Both groups showed significant improvement in terms of headache severity (p<0.05), number of headache-free days (p=0.005) and number of headache hours per day (p<0.05). Trends towards an increase in the number of headache-free days and a decrease in headache hours per day were observed in the BTX-A group. No major side effects were observed. Physical measures and BTX-A injections are safe and effective in the treatment of cervical headache.

Posturographic findings in patients with idiopathic cervical dystonia before and after local injections with botulinum toxin.

In this posturographic study, whole-body postural control was impaired in more than 75% of patients with idiopathic cervical dystonia (ICD) before local injections with botulinum toxin type A (BTX-A) and the impairment was independent of the direction of the torticollis. Six weeks after therapy with BTX-A, the number of pathological posturographic parameters had decreased by almost 30%, and the improvement reached statistical significance for sway path, sway area and anteroposterior sway during stance on foam with eyes closed. From a pathophysiological point of view, this improvement may be explained – at least in part – by a reduction of abnormal proprioceptive input from the neck. Accordingly, it seems possible that neck proprioceptive input plays a role in whole-body postural control in ICD patients, even though previous studies suggested that the neck input is relatively ignored in these patients.

Improvement of Decreased Critical Flicker Frequency (CFF) in Headache Patients With Drug Abuse After Successful Withdrawal

A considerable proportion of headache patients fulfill the criteria of “drug abuse” (definition according to the International Headache Society [IHS] criteria). These patients exhibit markedly reduced vigilance and continuous performance, as shown by the results of critical flicker frequency (CFF) analysis.