Joseph K.C. Tsui

Botulinum toxin A as treatment for drooling saliva in PD

Article abstract The authors evaluated intraparotid injections of botulinum toxin A in reducing salivary secretions and drooling in nine patients with PD. There was a marked objective reduction in secretion, and two thirds of the patients had subjective improvement in drooling. No side effects were observed. The authors conclude that botulinum toxin A promises to be a simple and effective treatment for the common problem of drooling saliva in chronic neurologic disease.

Comparison of botulinum toxin serotypes A and B for the treatment of cervical dystonia

Objective: To directly compare two serotypes of botulinum toxin (BoNTA and BoNTB) in cervical dystonia (CD) using a randomized, double-blind, parallel-arm study design. Methods: Subjects with CD who had a previous response from BoNTA were randomly assigned to BoNTA or BoNTB and evaluated in a blinded fashion at baseline, 4 weeks, 8 weeks, and 2-week intervals thereafter until loss of 80% of clinical effect or completion of 20 weeks of observation. CD severity was measured with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), and adverse events were assessed by structured interview. Statistical analysis included Wilcoxon rank sum test, log rank tests, and Kaplan–Meier survival curves for duration of effect. Results: A total of 139 subjects (BoNTA, n = 74; BoNTB, n = 65) were randomized at 19 study sites. Improvement in TWSTRS score was found at 4 weeks after injection and did not differ between serotypes. Dysphagia and dry mouth were more frequent with BoNTB (dysphagia: BoNTA 19% vs BoNTB 48%, p = 0.0005; dry mouth (BoNTA 41% vs BoNTB 80%, p < 0.0001). In clinical responders, BoNT A had a modestly longer duration of benefit (BoNTA 14 weeks, BoNTB 12.1 weeks, p = 0.033). Conclusion: Both serotypes of botulinum toxin (BoNTA and BoNTB) had equivalent benefit in subjects with cervical dystonia at 4 weeks. BoNTA had fewer adverse events and a marginally longer duration of effect in subjects showing a clinical response.

Occupational and environmental risk factors for Parkinson's disease

The etiology of Parkinsons disease (PD) remains obscure. Current research suggests that a variety of occupational and environmental risk factors may be linked to PD. This paper provides an overview of major occupational and environmental factors that have been associated with the development of PD and tries to assess current thinking about these factors and their possible mechanisms of operation. While clear links to rural living, dietary factors, exposure to metals, head injury, and exposure to infectious diseases during childhood have not been established, there is general agreement that smoking and exposure to pesticides affect the probability of developing PD.

Botulinum toxin in the treatment of writer's cramp A double‐blind study

We treated 20 patients with writers cramp in a double-blind, placebo-controlled study. Each patient received two treatments in tandem, one with botulinum-A toxin (BTX-A) injections and another with normal saline, separated by 3 months. Treatment order was randomized and unknown to the patient and physician. Patients were assessed before each treatment and 2 and 6 weeks after each treatment by objective measurements of pen control. Twelve patients had improvement in pen control after treatment with BTX-A, but only four had significant improvement in writing. BTX-A injections are effective in relieving symptoms in selected cases of writers cramp, particularly in those with significant wrist-joint deviation.

Botulinum toxin as a therapeutic agent

Botulinum toxin is a presynaptic neuromuscular blocking agent that, when injected intramuscularly in minute quantities, can produce selective muscle weakness. This property is employed therapeutically to provide symptomatic relief in conditions related to excessive muscle activities in strabismus, blepharospasm, hemifacial spasm, cervical dystonia, spasmodic dysphonia (adductor type), and jaw closing dystonia. It is investigational for a long list of medical conditions. It is a marketed drug in a number of countries in the world, but its use has only been approved by different regulatory agencies for use in a limited number of conditions. The long-term effects, appropriate dose for children, and in pregnancy, and maximum dose without causing toxicity remain unclear.

Local Treatment of Spasmodic Torticollis with Botulinum Toxin

Fifty-six patients with spasmodic torticollis were treated with local injections of botulinum toxin. The drop out rate was 21%. The remaining 44 patients were followed for a period of 3 to 21 months. Thirty-two patients (76%) had pain relief out of 42 presenting with pain; 37 (66%) improved in the amount of sustained movements of torticollis. The efficacy was reproducible after repeated injections.

Transdermal dopaminergic D2 receptor agonist therapy in Parkinson's disease with N-0923 TDS: A double-blind, placebo-controlled study

N‐0923 is a non‐ergot, dopaminergic D2 agonist designed to be transdermally available. It has anti‐parkinsonian effects when infused intravenously. An adhesive matrix patch was developed to deliver N‐0923 transdermally (N‐0923 TDS).

Head tremor in cervical dystonia

OBJECTIVE To compare the clinical characteristics, natural history, and therapeutic outcome of patients with cervical dystonia (CD) with head tremor (HT+) and without head tremor (HT-). METHODS We prospectively evaluated 114 consecutive patients of CD over a 9-month period with a detailed questionnaire. Chi-square and t-tests were employed for statistical analysis. RESULTS Seventy-eight (68.4%) patients had head tremor and 27 of them (34.6%) had tremor as one of the first symptoms. Age at onset of symptoms were similar in HT+ and HT- groups; however there was a higher prevalence in women in the former group (66.7% vs. 41.7%; p=0.01). HT+ patients had more frequent positive family history of essential-like hand/head tremor (21.8% vs. 5.5%; p<0.05), associated neck pain (92.3% vs. 77.8%: p<0.05), and essential-like hand tremor (40% vs. 8.3%; p<0.001). They also appeared to have more frequent history of preceding head/neck trauma (14.1% vs. 8.3%), frequent head rotation (88.5% vs. 69.4%) and antecollis (12.8% vs. 5.5%) but less often head tilt (37.2% vs. 47.2%) and gestes antagonistes (60.2% vs. 75%) than the HT- patients; however these differences were not statistically significant. The frequency of prior psychiatric illnesses, the incidence of dystonias in other parts of the body, frequency of retrocollis and shoulder elevation, and spontaneous remission were similar in the two groups. CONCLUSION Head tremor is common in CD and is more commonly associated with hand tremor and family history of tremor or other movement disorders. This supports a possible genetic association between CD and essential tremor (ET). Linkage studies are required to evaluate the genetic association between CD and ET.

Endothelin upregulates the expression of vasopressin V2 mRNA in the inner medullary collecting duct of the rat.

Recent studies in our laboratory have demonstrated that bosentan, a mixed endothelin ET(A)/ET(B) receptor antagonist, prevented the upregulation of the arginine vasopressin (AVP) V(2) receptor in the inner medullary collecting duct (IMCD) of cardiomyopathic hamsters. These results suggested that endothelin-1 (ET-1) is involved in the upregulation of AVP V(2) receptors. Studies were performed to detect the effect of ET-1 on the expression of AVP V(2) receptors and the ET receptor mediating these effects within the IMCD of the rat. Rat IMCD tissue was isolated and incubated with the following: ET-1, or ET-1 in combination with ET(A) and ET(B) receptor antagonists BQ-123 and BQ-788, respectively, and sarafotoxin c (S6c), an ET(B) receptor-specific agonist. Tissue samples were then analyzed using quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blotting. ET-1 treatment resulted in increased V(2) mRNA from a control level of 186.8 +/- 15.0 amol/microg total RNA to 430.7 +/- 49.0 amol/microg total RNA (P <.003). ET-1/ET(A) treatment resulted in no significant decrease in V(2) mRNA expression 335.0 +/- 38.0 amol/microg total RNA. Whereas ET-1/ET(B), and ET-1/ET(B)/ET(A) treatment resulted in V(2) mRNA approaching control 256.0 +/- 15.0 amol/microg total RNA, and 215.6 +/- 42.3 amol/microg total RNA. However, ET-3 treatment produced no significant changes in V(2) receptor mRNA expression. Sarafotoxin treatment corroborated both the ET-1 and ET receptor antagonist data, demonstrating striking significant increases in V(2) receptor mRNA and protein expression. S6c treatment increased V(2) mRNA expression from a control level of 199 +/- 17.3 amol/microg total RNA to 284.3 +/- 42.1 amol/microg total RNA (P < 05). Western blotting revealed that changes in V(2) mRNA expression in the various treatment conditions were similar to changes in protein expression. Overall, these data indicate that in the IMCD ET-1 increases AVP V(2) receptor expression and these changes are mediated by the ET(B) receptor.

Lamotrigine trial in idiopathic parkinsonism A double‐blind, placebo‐controlled, crossover study

Increased glutamatergic transmission in the basal ganglia is implicated in the pathophysiology of idiopathic parkinsonism (IP). We investigated the effects of lamotrigine (LTG), a glutamate-release inhibitor, in the symptomatic treatment of IP in two double-blind, placebo-controlled studies. Single doses of L-dopdcarbidopa (equal to 50% of the usual morning dose) were administered together with either LTG (100, 200, or 400 mg) or two random placebo doses in 14 patients with IP. The patients were assessed using the Modified Columbia Rating Scale (MCRS) and the Purdue Pegboard Test (PPBT) at multiple intervals over 8 hours. There were no significant differences between the placebo doses and the three doses of LTG on the MCRS and PPBT scores. In a 3-month study, 12 patients took LTG titrated up to 400 mg or placebo with their antiparkinsonian medication for 3 months and were then crossed over. Nine of 12 patients did not complete the study because of dyskinesia (n = 2), hallucinations (n = 31, and deterioration of parkinsonian symptoms (n = 4) on LTG. There was no significant difference between placebo and LTG on the MCRS and PPBT in the three patients who completed the study. The results failed to demonstrate any symptomatically beneficial effects of LTG in IP.