Rotigotine transdermal patch in early Parkinson's disease: a randomized, double-blind, controlled study versus placebo and ropinirole.

Rotigotine is a new, non-ergot dopamine agonist formulated in a transdermal delivery system. The present study was to investigate the efficacy and safety of the rotigotine transdermal patch in the treatment of early Parkinson's disease. Patients (n = 561) were randomized to rotigotine, ropinirole, or placebo. The titration period was up to 13 weeks, and there was a minimum dose-maintenance period of 24 weeks for ropinirole and 33 weeks for rotigotine. The primary endpoint was the proportion of patients with a minimum of 20% decrease in the combined Unified Parkinson's Disease Rating Scale Part II and Part III scores. The responder rate in the rotigotine group was significantly higher than in the placebo group (52% vs. 30%, P < 0.0001). Transdermal rotigotine at doses < or =8 mg/24 h did not show noninferiority to ropinirole at doses < or =24 mg/day. In a post-hoc subgroup analysis, rotigotine < or =8 mg/24 hours had a similar efficacy to ropinirole at doses < or =12 mg/day. The rotigotine transdermal patch was well tolerated. The most common adverse events were application-site reactions, nausea, and somnolence. Application-site reactions were predominantly mild or moderate in intensity. In conclusion, the rotigotine transdermal patch represents an effective and safe option for the treatment of patients with early Parkinson's disease.     

Interhemispheric and ipsilateral connections in Parkinson's disease: relation to mirror movements.

Mirror movements (MM) occur in early, asymmetric Parkinson's disease (PD). To examine the pathophysiology of MM in PD, we studied 13 PD patients with MM (PD-MM), 7 PD patients without MM (PD-NM), and 14 normal subjects. Cross-correlogram did not detect common synaptic input to motoneuron pools innervating homologous hand muscles in PD-MM patients. Transcranial magnetic stimulation studies showed no significant difference in ipsilateral motor-evoked potentials between PD-MM patients and normal subjects. The MM side of PD-MM patients showed a slower increase in ipsilateral silent period area with higher level of muscle contraction than the non-MM side and normal subjects. There was less interhemispheric inhibition (IHI) at long interstimulus intervals of 20 to 50 ms in PD-MM than PD-NM. IHI reduced short interval intracortical inhibition in normal subjects and PD-NM, but not in PD-MM. IHI significantly increased intracortical facilitation in PD-MM and PD-NM patients, but not in normal subjects. Our results suggest that MM in PD is due to activation of the contralateral motor cortex. PD-MM patients had reduced transcallosal inhibitory effects on cortical output neurons and on intracortical inhibitory circuits compared to PD-NM patients and controls. These deficits in transcallosal inhibition may contribute to MM in PD patients.     

Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan.

This article presents the revision process, major innovations, and clinimetric testing program for the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (UPDRS), known as the MDS-UPDRS. The UPDRS is the most widely used scale for the clinical study of Parkinson's disease (PD). The MDS previously organized a critique of the UPDRS, which cited many strengths, but recommended revision of the scale to accommodate new advances and to resolve problematic areas. An MDS-UPDRS committee prepared the revision using the recommendations of the published critique of the scale. Subcommittees developed new material that was reviewed by the entire committee. A 1-day face-to-face committee meeting was organized to resolve areas of debate and to arrive at a working draft ready for clinimetric testing. The MDS-UPDRS retains the UPDRS structure of four parts with a total summed score, but the parts have been modified to provide a section that integrates nonmotor elements of PD: I, Nonmotor Experiences of Daily Living; II, Motor Experiences of Daily Living; III, Motor Examination; and IV, Motor Complications. All items have five response options with uniform anchors of 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Several questions in Part I and all of Part II are written as a patient/caregiver questionnaire, so that the total rater time should remain approximately 30 minutes. Detailed instructions for testing and data acquisition accompany the MDS-UPDRS in order to increase uniform usage. Multiple language editions are planned. A three-part clinimetric program will provide testing of reliability, validity, and responsiveness to interventions. Although the MDS-UPDRS will not be published until it has successfully passed clinimetric testing, explanation of the process, key changes, and clinimetric programs allow clinicians and researchers to understand and participate in the revision process.     

The Relationship Between Psychogenic Cough and the Diagnosis and Misdiagnosis of Asthma: A Review

The differential diagnoses of persistent nonproductive cough include numerous pulmonary and nonpulmonary organic disorders as well as functional illnesses. Many diseases can cause cough, and several studies have shown asthma among the most common etiologies associated with chronic cough in adult nonsmokers, as well as children. Psychogenic cough and its relationship to asthma and other asthma-like illnesses is complex since distinct maladies with similar features may coexist individually or in combination in any given patient. While chronic cough may occur as a sole presenting manifestation of bronchial asthma in all age groups, recent findings suggest that most children with persistent cough without other respiratory symptoms do not have asthma. Since several organic, as well as functional diseases, may present with persistent cough as their sole manifestation in either adults or children, cough should not be used as a single or major determinant to diagnose and treat asthma, especially when empirically focused therapy trials fail. Given the range of illnesses causing cough, no single management guideline can be expected to be universally effective.     

Can true monocular keratoconus occur?

Evidence increasingly supports keratoconus as an inherited, genetic disorder. If this is the case, it would be expected to express itself as a binocular condition even though variable expression of the gene may show differing levels in the two eyes. It is a common occurrence in specialist contact lens practices to see pseudo‐monocular keratoconus, that is, an overt clinical level of the condition in one eye and forme fruste keratoconus in the other. The advent of videokeratoscopy has shown almost every case of apparent monocular keratoconus to be different expressions of the condition in the two eyes. Nevertheless, rare cases of the condition are seen that appear to be truly monocular. Such a case is presented in which the condition has been present for more than 23 years. The age of the subject makes the future onset of keratoconus highly unlikely and videokeratoscopy does not show the presence of forme fruste in the ‘good’ eye. There is no history of monocular eye rubbing. Pachymetry shows the normal eye to be well within the range of normal corneal thickness, while the keratoconus in the other eye is sufficiently advanced to warrant corneal grafting. Thus, it is a case of true monocular keratoconus and represents an extreme example of variable gene expression.     

Atypical absences and recurrent absence status in an adult with Angelman syndrome due to the UBE3A mutation.

Angelman syndrome is a neurogenetic disorder resulting in refractory epilepsy and profound psychomotor retardation in its most prevalent form, caused by deletion of maternal chromosome 15q11-13. We report the case of a 29-year-old, mentally retarded man with unusual electroencephalographic changes during periods of atypical absence status epilepticus, a previously unreported manifestation of the usually milder, drug-responsive epilepsy associated with Angelman syndrome due to the UBE3A mutation.[Published with video sequences].     

Murine skin flap survival may not be affected by underlying fat viability.

One problem in the treatment of degloving injuries is the accurate prediction of the survivability of the avulsed tissue. Initial evaluation frequently underestimates the degree of eventual flap loss, and in many cases, there is a progressive necrosis that continues over the ensuing days. The pathophysiology of this phenomenon is unclear. We undertook this study to test the theory that underlying devascularised fat contributes to overlying skin necrosis. A dorsal random skin flap model was used in the rat. Sixty-six rats were divided into three groups: flaps with viable fat and silicone sheeting underneath, flaps with devascularised fat and silicone sheeting underneath and control flaps with only silicone sheeting underneath. Flap necrosis (% area+/-SEM) was evaluated at one week, and found to be 27.1+/-4% in the live fat group, 33.2+/-4% in the dead fat group and 33.6+/-5% in the control group. One-way analysis of variance showed no statistically significant difference between the three groups at a power of 80%. In this study, we have shown that neither live nor dead fat has a significant influence on the survival of an overlying random skin flap in the rat.     

Levodopa-induced hyperactivity in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

The present study examines the motor responses of 10- to 12-month-old, male C57 mice that were either given intraperitoneal (IP) injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 30 mg/kg per day) or vehicle for 10 consecutive days, followed by IP injections of levodopa (200 mg/kg) plus carbidopa (25 mg/kg). Five days of MPTP exposure resulted in the Straub tail phenomenon and pronounced hypokinesia. However, during the next 5 days, motor activity returned to baseline, even with continued MPTP treatment. After 10 to 14 days of rest, all mice were then treated with levodopa/carbidopa twice daily for multiple, consecutive days. However, only the previously MPTP-treated animals became hyperkinetic, as compared to levodopa-treated control animals that were not previously exposed to MPTP. Abnormal activity included scratching, running, gnawing, and jumping movements. Hyperactivity lasted for approximately 2 hours after each levodopa injection and then returned to baseline, but the amount of hyperkinesia increased with additional days of levodopa treatment, even though the daily levodopa dose was not changed. These results demonstrate that levodopa can cause reproducible hyperactivity in mice that were previously exposed to MPTP.     

Adhesive small bowel obstruction: epidemiology, biology and prevention

Intraabdominal adhesions develop after abdominal surgery as part of the normal healing processes that occur after damage to the peritoneum. Over the last 2 decades, much research has gone into understanding the biochemical and cellular processes that lead to adhesion formation. The early balance between fibrin deposition and degradation seems to be the critical factor in adhesion formation. Although adhesions do have some beneficial effects, they also cause significant morbidity, including adhesive small bowel obstruction, infertility and increased difficulty with reoperative surgery. Several strategies have been employed over the years to prevent adhesion formation while not interfering with wound healing. This article summarizes much of our current understanding of adhesion formation and strategies that have been employed to prevent them.