Levodopa is effective for the motor symptoms of Parkinson's disease (PD), but is associated with motor fluctuations and dyskinesia. Many patients require add-on therapy to improve motor fluctuations without exacerbating dyskinesia. The objective of this Phase III, multicenter, double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy and safety of safinamide, an α-aminoamide with dopaminergic and nondopaminergic mechanisms, as add-on to l-dopa in the treatment of patients with PD and motor fluctuations. Patients were randomized to oral safinamide 100 mg/day (n = 224), 50 mg/day (n = 223), or placebo (n = 222) for 24 weeks. The primary endpoint was total on time with no or nontroublesome dyskinesia (assessed using the Hauser patient diaries). Secondary endpoints included off time, Unified Parkinson's Disease Rating Scale (UPDRS) Part III (motor) scores, and Clinical Global Impression-Change (CGI-C). At week 24, mean ± SD increases in total on time with no or nontroublesome dyskinesia were 1.36 ± 2.625 hours for safinamide 100 mg/day, 1.37 ± 2.745 hours for safinamide 50 mg/day, and 0.97 ± 2.375 hours for placebo. Least squares means differences in both safinamide groups were significantly higher versus placebo. Improvements in off time, UPDRS Part III, and CGI-C were significantly greater in both safinamide groups versus placebo. There were no significant between-group differences for incidences of treatment-emergent adverse events (TEAEs) or TEAEs leading to discontinuation. The addition of safinamide 50 mg/day or 100 mg/day to l-dopa in patients with PD and motor fluctuations significantly increased total on time with no or nontroublesome dyskinesia, decreased off time, and improved parkinsonism, indicating that safinamide improves motor symptoms and parkinsonism without worsening dyskinesia.

Objectives-Oromandibular dystonia (OMD) is a focal dystonia manifested by involuntary muscle contractions producing repetitive, patterned mouth, jaw, and tongue movements. Dystonia is usually idiopathic (primary), but in some cases it follows peripheral injury. Peripherally induced cervical and limb dystonia is well recognised, and the aim of this study was to characterise peripherally induced OMD. Methods-The following inclusion criteria were used for peripherally induced OMD: (1) the onset of the dystonia was within a few days or months (up to 1 year) after the injury; (2) the trauma was well documented by the patient's history or a review of their medical and dental records; and (3) the onset of dystonia was anatomically related to the site of injury (facial and oral). Results-Twenty seven patients were identified in the database with OMD, temporally and anatomically related to prior injury or surgery. No additional precipitant other than trauma could be detected. None of the patients had any litigation pending. The mean age at onset was 50.11 (SD 14.15) (range 23-74) years and there was a 2:1 female preponderance. Mean latency between the initial trauma and the onset of OMD was 65 days (range 1 day-1 year). Ten (37%) patients had some evidence of predisposing factors such as family history of movement disorders, prior exposure to neuroleptic drugs, and associated dystonia aVecting other regions or essential tremor. When compared with 21 patients with primary OMD, there was no diVerence for age at onset, female preponderance, and phenomenology. The frequency of dystonic writer's cramp, spasmodic dysphonia, bruxism, essential tremor, and family history of movement disorder, however, was lower in the posttraumatic group (p<0.05). In both groups the response to botulinum toxin treatment was superior to medical therapy (p<0.005). Surgical intervention for temporomandibular disorders was more frequent in the post-traumatic group and was associated with worsening of dystonia. Conclusion-The study indicates that oromandibular-facial trauma, including dental procedures, may precipitate the onset of OMD, especially in predisposed people. Prompt recognition and treatment may prevent further complications. (J Neurol Neurosurg Psychiatry 1998;65:722-728)

Immunoresistance (Ab+) to botulinum toxin type A (BTX‐A) has been a serous concern since the introduction of BTX‐A in the treatment of dystonia and other disorders associated with abnormal muscle contractions. We studied seven patients who developed Ab+ and later reverted to antibodynegative (Ab‐) status. These seven patients, six women (mean age, 56 years; range, 41–80 years), with an average duration of dystonia for all patients of 197 months (range, 84–360 months), received a total mean cumulative dose of 1659 units (U) (range,810‐1975 U), with an average dose of 207 U per visit. All of these patients became unresponsive to BTX‐A treatment and became Ab+ as determined by mouse bioassay. Their response to BTX‐A after they revertedd to Ab‐ was analyzed. The average latency between the initial BTX‐A treatment and development of Ab+ was 27 months (range, 15–43 months). The average duration between the detection of Ab+ status and subsequent reversal to Ab‐ status was 30 months (range, 10–78 months). Six of these Ab‐ patients were reinjected with BTX‐A, and all six benefited from repeat injections comparable with their earlier response. Three patients lost their clinical response to subsequent injections and were found to be again Ab+. Two of the five patients who became immunoresistant to BTX‐A received botulinum toxin type F (BTX‐F) injections and one patient received a single session of BTX‐B with improvement in their symptoms. In conclusion, this unique group of patients who were Ab+ and became Ab‐ responded favorably to repeat BTX‐A injections, but some lost the benefit with subsequent injections. These observations suggest that the anamnestic immunologic response to BTX‐A can wane, but can be reactivated by repeat BTX‐A treatments. The presence of antibodies did not interfere with the response to BTX‐F or BTX‐B injections, thus confirming the antigenic specificity of various BTX serotypes.

Magnetic Resonance Parkinsonism Index is more sensitive, specific, and accurate in differentiating PSP from PD in the early stages on an individual basis.