Pseudobulbar laughter as a levodopa off phenomenon exacerbated by subthalamic deep brain stimulation.

Pseudobulbar affect is a common symptom in neurodegenerative diseases and can also result from lesions in cortical, subcortical and brainstem regions. In Parkinson's disease (PD), pseudobulbar affect (PBA) can occur as a wearing off phenomenon, manifested usually as crying without emotionality. In addition, subthalamic (STN) deep brain stimulation (DBS) has been reported to induce PBA in PD patients with no prior history of such episodes. We present a case of inappropriate laughter lacking mirth as a levodopa OFF phenomenon in a patient with PD, whose laughter also worsened with STN-DBS in his non-medicated state. Levodopa ameliorated his PBA both with and without stimulation. The case demonstrates pseudobulbar laughter as a levodopa OFF phenomenon that is also exacerbated by STN-DBS.

A Community Health Advisor Program to reduce cardiovascular risk among rural African-American women.

The Uniontown, Alabama Community Health Project trained and facilitated Community Health Advisors (CHAs) in conducting a theory-based intervention designed to reduce the risk for cardiovascular disease (CVD) among rural African-American women. The multiphased project included formative evaluation and community organization, CHA recruitment and training, community intervention and maintenance. Formative data collected to develop the training, intervention and evaluation methods and materials indicated the need for programs to increase knowledge, skills and resources for changing behaviors that increase the risk of CVD. CHAs worked in partnership with staff to develop, implement, evaluate and maintain strategies to reduce risk for CVD in women and to influence city officials, business owners and community coalitions to facilitate project activities. Process data documented sustained increases in social capital and community capacity to address health-related issues, as well as improvements in the community's physical infrastructure. This project is unique in that it documents that a comprehensive CHA-based intervention for CVD can facilitate wide-reaching changes in capacity to address health issues in a rural community that include improvements in community infrastructure and are sustained beyond the scope of the originally funded intervention.

Dietetic guidelines on food and nutrition in the secondary prevention of cardiovascular disease - evidence from systematic reviews of randomized controlled trials (second update, January 2006).

AIM: To update dietetic guidelines based on systematic review evidence on dietary advice to prevent further events in people with existing cardiovascular disease (CVD) (secondary prevention). METHODS: The Cochrane Library, MEDLINE and EMBASE were comprehensively searched to January 2005 for systematic reviews on aspects of diet and heart health. Reviews were included if they searched systematically for randomized controlled trials relating to diet and secondary prevention of CVD. Each review was critically appraised by at least two members of the UK Heart Health and Thoracic Dietitians Group. The quality and results of each review were discussed and summarized at a group meeting. RESULTS: Evidence-based strategies that reduce cardiovascular events in those with CVD include reduction in saturated fat and substitution with unsaturated fats. Individuals who have suffered a myocardial infarction may also benefit from adopting a Mediterranean type diet and increasing intake of omega 3 fats, but it is not clear whether they are beneficial for all patients with CVD. There is no systematic review evidence to support the use of antioxidant vitamins supplements, low glycaemic index diets, or homocysteine lowering therapies in this group. CONCLUSION: There remains good evidence that reducing saturated fat reduces morbidity in patients with CVD. This advice is consistent for most manifestations of CVD, with the addition of Mediterranean dietary advice and increased omega 3 fats for those who have had a myocardial infarction.

Tratamiento con verteporfin de la membrana neovascular coroidea en miopía: serie retrospectiva de 3 años / Verteporfin therapy of myopic subfoveal choroidal neovascularization: retrospective series of 3 years

Objetivo: Presentar los resultados visuales del tratamiento con Terapia Fotodinámica (TFD) de la membrana neovascular coroidea (MNVC) subfoveal por miopía patológica en nuestra institución. Material y Método: Análisis retrospectivo de las fichas de los pacientes sometidos a TFD entre agosto del año 2000 y diciembre del año 2003. La TFD se aplicó según las indicaciones y recomendaciones publicadas. Resultados: Se recolectaron los resultados de 131 tratamientos aplicados a 57 ojos de 55 pacientes. Los pacientes fueron seguidos en promedio 20,75 meses (6 a 51). A 2 años de seguimiento con 21 ojos, el 28,6 por ciento ganó más de 3 líneas de agudeza visual ETDRS. El 42,9 por ciento de los ojos ganó menos de tres líneas o perdió menos de tres líneas ETDRS. El 28,6 por ciento de los ojos perdió más de tres líneas ETDRS. El número de tratamientos promedios fue de 2,25. Las complicaciones atribuidas a la TFD fueron infrecuentes: dolor lumbar leve (3,6 por ciento) y atrofia coriorretinal (1,8 por ciento). Discusión: Los pacientes de esta serie pierden en promedio menos de 3 líneas ETDRS a 2 años de seguimiento. El único factor que demostró una correlación significativa con el resultado visual final fue la edad. En el 70 por ciento de los ojos se indicó más de una sesión de TFD. Las complicaciones y efectos adversos atribuibles a la TFD son infrecuentes.

Tratamiento con verteporfin de la membrana neovascular coroidea en degeneración macular relacionada con la edad: serie retrospectiva de 3 años / Verteporfin therapy of subfoveal choroideal neovascularization in age related macular degeneration: retrospective series of 3 years

Objetivo: Presentar los resultados visuales del tratamiento con Terapia Fotodinámica (TFD) de la membrana neovascular coridea (MNVC) subfoveal por Degeneración Macular Relacionada con la Edad (DAME) en nuestra institución. Material y Métodos: Análisis retrospectivo de las fichas de los pacientes sometidos a TFD entre agosto del año 2000 y diciembre del año 2003. La TFD se aplicó según las indicaciones y recomendaciones publicadas. Los retratamientos se aplicaron según criterios clínicos y de laboratorio. Resultados: Se recolectaron los resultados de 328 tratamientos aplicados a 152 ojos de 136 pacientes. Los pacientes fueron seguidos en promedio 20,9 meses (6 a 53 meses). A dos años de seguimiento con 61 ojos, el 11,5 por ciento de los ojos gana más de 3 líneas de agudeza visual ETDRS. El 40,91 por ciento de los ojos pierde más de 3 líneas ETDRS. En el subgrupo de pacientes con una cicatriz disciforme en el ojo contralateral, la agudeza visual promedio en el ojo tratado con TFD fue de 20/200 en comparación con la agudeza visual de cuenta dedos en el ojo con cicatriz disciforme sin tratamiento. El número de tratamientos promedio fue de 2,16. El 33,6 por ciento recibió sólo una sesión de TFD. Las complicaciones atribuidas a la TFD fueron infrecuentes: dolor lumbar leve (5,1 por ciento) y hemorragia macular (2,2 por ciento). Discusión: Los pacientes de esta serie pierden en promedio menos de 3 líneas ETDRS a dos años de seguimientos. El único factor que demostró una correlación significativa con el resultado visual final fue la agudeza visual inicial. En el 70 por ciento de los ojos se indicó más de una sesión de TFD. Las complicaciones y efectos adversos severos atribuibles a la TFD son infrecuentes.

A single-blind, open-label trial of sodium oxybate for myoclonus and essential tremor.

The authors performed an open-label, rater-blinded, add-on study of sodium oxybate in 20 patients with ethanol-responsive myoclonus or essential tremor. Blinded ratings of videotaped examinations showed improvements in myoclonus at rest, stimulus-sensitive myoclonus, action myoclonus, functional performance, and postural and kinetic tremor. Tolerability was acceptable, and more than half of the patients chose to continue treatment after the trial. Double-blind placebo-controlled studies in these disorders are warranted.

Subthalamic nucleus stimulation in advanced Parkinson's disease: blinded assessments at one year follow up.

OBJECTIVE: To measure the effect of deep brain stimulation (DBS) of the subthalamic nucleus in patients with advanced Parkinson's disease. DESIGN: Open label follow up using blinded ratings of videotaped neurological examinations. PATIENTS: 30 patients with advanced Parkinson's disease (19 male, 11 female; mean age 58.8 years; mean disease duration 12.8 years), complicated by intractable wearing off motor fluctuations and dopaminergic dyskinesias. MAIN OUTCOME MEASURES: Unified Parkinson's disease rating scale (UPDRS), part III (motor), score at one year, from blinded reviews of videotaped neurological examinations. Secondary outcomes included the other UPDRS subscales, Hoehn and Yahr scale, activities of daily living (ADL) scale, mini-mental state examination (MMSE), estimates of motor fluctuations and dyskinesia severity, drug intake, and patient satisfaction questionnaire. RESULTS: Subthalamic nucleus stimulation was associated with a 29.5% reduction in motor scores at one year (p<0.0001). The only important predictors of improvement in UPDRS part III motor scores were the baseline response to dopaminergic drugs (p = 0.015) and the presence of tremor (p = 0.027). Hoehn and Yahr scores and ADL scores in the "on" and "off" states did not change, nor did the mean MMSE score. Weight gain occurred in the year after surgery, from (mean) 75.8 kg to 78.5 kg (p = 0.028). Duration of daily wearing off episodes was reduced by 69%. Dyskinesia severity was reduced by 60%. Drug requirements (in levodopa equivalents) declined by 30%. CONCLUSIONS: The 30% improvement in UPDRS motor scores was a more modest result than previously reported. DBS did not improve functional capacity independent of drug use. Its chief benefits were reduction in wearing off duration and dyskinesia severity.

Dietetic guidelines: diet in secondary prevention of cardiovascular disease (first update, June 2003).

AIM: To update dietetic guidelines summarizing the systematic review evidence on dietary advice to prevent further events in people with existing cardiovascular disease (CVD) (secondary prevention). METHODS: The Cochrane Library, MEDLINE and EMBASE were comprehensively searched to November 2002 for systematic reviews on aspects of diet and heart health. Reviews were included if they searched systematically for randomised controlled trials relating to diet and secondary prevention of CVD. Two members of the UK Heart Health and Thoracic Dietitians Group critically appraised each review. The quality and results of each review were discussed and summarized in a meeting of the whole group. RESULTS: Providing evidence-based dietary information (including increasing omega-3 fat intake) to all people who have had a myocardial infarction will save more lives than concentrating dietary advice on just those in need of weight loss or lipid lowering. The practice of prioritizing dietetic time in secondary prevention to those with raised lipids is out of date since the advent of statin therapy. However, effective dietary advice for those with angina, stroke, peripheral vascular disease or heart failure is less clear. CONCLUSION: There is good systematic review evidence that dietary advice to those with coronary heart disease can reduce mortality and morbidity as well as modify some risk factors. Dietary advice that does this most effectively should be prioritized.

Cognition following bilateral implants of embryonic dopamine neurons in PD: a double blind study.

OBJECTIVES: To determine if bilateral transplantation of embryonic mesencephalic dopamine cells into the putamen of patients with PD significantly affected their cognitive functioning when compared with patients receiving sham surgery and to examine the effect of age on cognitive performance after implantation. METHODS: Forty patients (19 women, 21 men; age 34 to 75 years) with idiopathic PD of at least 7 years' duration (mean 14 years) who had disabling motor signs despite optimal drug management were randomly assigned to tissue implants or sham craniotomies in a double-blind design. Neuropsychological tests assessing orientation, attention, language, verbal and visual memory, abstract reasoning, executive function, and visuospatial and construction abilities were administered before and 1 year after surgery. Treatment groups did not differ at baseline in demographic, neuropsychological, motor, depression, or levodopa equivalent measures. RESULTS: Postsurgical change in cognitive performance was not significantly different for real or sham surgery groups. Performance in both groups remained unchanged at follow-up for most measures. CONCLUSIONS: Embryonic dopamine producing neurons can be implanted safely into the putamen bilaterally without impairing cognition in patients with PD, but within the first year, improved cognition should not be expected.

The natural history of embouchure dystonia.

Focal task-specific dystonias are unusual disorders of motor control, often affecting individuals who perform complex repetitive movements. Musicians are especially prone to develop these disorders because of their training regimens and intense practice schedules. Task-specific dystonia occurring in keyboard or string instrumentalists usually affects the hand. In contrast, there have been few descriptions of musicians with task-specific dystonia affecting the muscles of the face and jaw. We report detailed clinical observations of 26 professional brass and woodwind players afflicted with focal task-specific dystonia of the embouchure (the pattern of lip, jaw, and tongue muscles used to control the flow of air into a mouthpiece). This is the largest and most comprehensively studied series of such patients. Patients developed embouchure dystonia in the fourth decade, and initial symptoms were usually limited to one range of notes or style of playing. Once present, dystonia progressed without remission and responded poorly to oral medications and botulinum toxin injection. Patients with embouchure dystonia could be separated by the pattern of their abnormal movements into several groups, including embouchure tremor, involuntary lip movements, and jaw closure. Dystonia not infrequently spread to other oral tasks, often producing significant disability. Effective treatments are needed for this challenging and unusual disorder.

Blinded positron emission tomography study of dopamine cell implantation for Parkinson's disease.

We assessed nigrostriatal dopaminergic function in Parkinson's disease (PD) patients undergoing a double-blind, placebo-controlled surgical trial of embryonic dopamine cell implantation. Forty PD patients underwent positron emission tomography (PET) imaging with [18F]fluorodopa (FDOPA) prior to randomization to transplantation or placebo surgery. The 39 surviving patients were rescanned one year following surgery. Images were quantified by investigators blinded to treatment status and clinical outcome. Following unblinding, we determined the effects of treatment status and age on the interval changes in FDOPA/PET signal. Blinded observers detected a significant increase in FDOPA uptake in the putamen of the group receiving implants compared to the placebo surgery patients (40.3%). Increases in putamen FDOPA uptake were similar in both younger (age < or = 60 years) and older (age > 60 years) transplant recipients. Significant decrements in putamen uptake were evident in younger placebo-operated patients (-6.5%) but not in their older counterparts. Correlations between the PET changes and clinical outcome were significant only in the younger patient subgroup (r = 0.58). The findings suggest that patient age does not influence graft viability or development in the first postoperative year. However, host age may influence the time course of the downstream functional changes that are needed for clinical benefit to occur.

Dynamics of symmetry breaking and tachyonic preheating.

We reconsider the old problem of the dynamics of spontaneous symmetry breaking (SSB) using 3D lattice simulations. We develop a theory of tachyonic preheating, which occurs due to the spinodal instability of the scalar field. Tachyonic preheating is so efficient that SSB typically completes within a single oscillation as the field rolls towards the minimum of its effective potential. We show that, contrary to previous expectations, preheating in hybrid inflation is typically tachyonic. Our results may also be relevant for the theory of the formation of topological defects and of disoriented chiral condensates in heavy ion collisions.

Transplantation of embryonic dopamine neurons for severe Parkinson's disease.

BACKGROUND: Transplantation of human embryonic dopamine neurons into the brains of patients with Parkinson's disease has proved beneficial in open clinical trials. However, whether this intervention would be more effective than sham surgery in a controlled trial is not known. METHODS: We randomly assigned 40 patients who were 34 to 75 years of age and had severe Parkinson's disease (mean duration, 14 years) to receive a transplant of nerve cells or sham surgery; all were to be followed in a double-blind manner for one year. In the transplant recipients, cultured mesencephalic tissue from four embryos was implanted into the putamen bilaterally. In the patients who received sham surgery, holes were drilled in the skull but the dura was not penetrated. The primary outcome was a subjective global rating of the change in the severity of disease, scored on a scale of -3.0 to 3.0 at one year, with negative scores indicating a worsening of symptoms and positive scores an improvement. RESULTS: The mean (+/-SD) scores on the global rating scale for improvement or deterioration at one year were 0.0+/-2.1 in the transplantation group and -0.4+/-1.7 in the sham-surgery group. Among younger patients (60 years old or younger), standardized tests of Parkinson's disease revealed significant improvement in the transplantation group as compared with the sham-surgery group when patients were tested in the morning before receiving medication (P=0.01 for scores on the Unified Parkinson's Disease Rating Scale; P=0.006 for the Schwab and England score). There was no significant improvement in older patients in the transplantation group. Fiber outgrowth from the transplanted neurons was detected in 17 of the 20 patients in the transplantation group, as indicated by an increase in 18F-fluorodopa uptake on positron-emission tomography or postmortem examination. After improvement in the first year, dystonia and dyskinesias recurred in 15 percent of the patients who received transplants, even after reduction or discontinuation of the dose of levodopa. CONCLUSIONS: Human embryonic dopamine-neuron transplants survive in patients with severe Parkinson's disease and result in some clinical benefit in younger but not in older patients.

Database: relevant or not.

Progress in the field of ventricular assist devices requires a more rigorous and systematic method of collecting outcomes data. A worldwide registry of device implants and results is proposed. With widespread participation, data from this registry would improve the identification of risk factors and complications, and allow for the creation of predictive models that would enhance patient selection. Professional societies should lead the development of a registry in close partnership with government and industry. Data collection using the Web, with rigorous security measures to protect patient privacy, would offer numerous advantages in efficiency and immediacy of communication for all participants.

Community supports for individuals with challenging behavior after brain injury: an analysis of the New York state behavioral resource project.

OBJECTIVE: To articulate a framework for supporting individuals with behavioral challenges following brain injury, to describe a state-funded clinical intervention program established to provide community support to individuals with challenging behaviors following brain injury using such a framework, to present data from which it can be concluded that such a program is cost-effective, and to offer policy recommendations. DESIGN: Retrospective analysis of cost data and living arrangements for individuals with behavioral challenges served for a period of 3-4 years through the New York State Home and Community-Based Services Traumatic Brain Injury (HCBS-TBI) Waiver program and the State Behavioral Resource Project. SUBJECTS: 80 individuals with TBI and severe behavioral challenges that included criminal behavior, physical threats, assault and physical aggression, sexually inappropriate behavior, substance abuse, refusal to participate in intervention programs, and psychiatric disturbances, all of whom were at least 2 years postinjury (X = 7.33 years postinjury). RESULTS: The majority of individuals (82% of the 1996 cohort; 89% of the 1997 cohort) with challenging behaviors were living successfully in their home communities 3-4 years after the initiation of behavioral supports. In addition, the costs of serving these individuals decreased in the first year of community integration and for that last year that a cost analysis was completed. CONCLUSIONS: Many individuals with behavioral impairments can be supported successfully in community settings, so long as those supports are flexibly implemented to meet the changing needs of those individuals. Moreover, even with intensive supports, it is cost-effective to serve this population in the community.

A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar disorder. Lamictal 614 Study Group.

BACKGROUND: Patients with rapid-cycling bipolar disorder are often treatment refractory. This study examined lamotrigine as maintenance monotherapy for rapid-cycling bipolar disorder. METHOD: Lamotrigine was added to patients' current psychotropic regimens and titrated to clinical effect during an open-label treatment phase. Stabilized patients were tapered off other psychotropics and randomly assigned to lamotrigine or placebo monotherapy for 6 months. Time to additional pharmacotherapy for emerging symptoms was the primary outcome measure. Secondary efficacy measures included survival in study (time to any premature discontinuation), percentage of patients stable without relapse for 6 months, and changes in the Global Assessment Scale and Clinical Global Impressions-Severity scale. Safety was assessed from adverse event, physical examination, and laboratory data. RESULTS: 324 patients with rapid-cycling bipolar disorder (DSM-IV criteria) received open-label lamotrigine, and 182 patients were randomly assigned to the double-blind maintenance phase. The difference between the treatment groups in time to additional pharmacotherapy did not achieve statistical significance in the overall efficacy population. However, survival in study was statistically different between the treatment groups (p = .036). Analyses also indicated a 6-week difference in median survival time favoring lamotrigine. Forty-one percent of lamotrigine patients versus 26% of placebo patients (p = .03) were stable without relapse for 6 months of monotherapy. Lamotrigine was well tolerated; there were no treatment-related changes in laboratory parameters, vital signs, or body weight. No serious rashes occurred. CONCLUSION: This was the largest and only prospective placebo-controlled study of rapid-cycling bipolar disorder patients to date; results indicate lamotrigine monotherapy is a useful treatment for some patients with rapid-cycling bipolar disorder.

Enhancing therapeutic impact and therapeutic alliance through electronic mail homework assignments.

Homework assignments can enhance therapeutic impact and increase therapy effectiveness by encouraging patients to focus on therapy-related issues between sessions. Computer technology provides a new avenue for reporting, monitoring, and feedback of patient homework assignments through electronic mail (e-mail). In two case examples, e-mail was used as an extension of therapy to enhance patient involvement in treatment. In both cases, patient reports suggest that therapeutic alliance and therapeutic impact improved with the use of e-mail homework reporting. The costs and benefits of the use of e-mail as an adjunct to therapy are discussed.