Nicte I. Mejia

Long-term botulinum toxin efficacy, safety, and immunogenicity.

To determine the long‐term efficacy of botulinum toxin (BTX) treatments, we analyzed longitudinal follow‐up data on 45 patients (32 women; mean age, 68.8 years) currently followed in the Baylor College of Medicine Movement Disorders Clinic, who have received BTX treatments continuously for at least 12 years (mean 15.8 ± 1.5 years). Their mean response rating after the last injection, based one a previously described scale 0‐to‐4 scale (0 = no effect; 4 = marked improvement) was 3.7 ± 0.6 and the mean total duration of response was 15.4 ± 3.4 weeks. Although the latency and total duration of the response to treatment have not changed over time, the peak duration of response (P < 0.005) and dose per visit (P < 0.0001) have increased since the initial visit. Furthermore, global rating (P < 0.02) and peak effect (P < 0.05) have improved. In total, 20 adverse events occurred in 16 of 45 (35.6%) patients after their initial visit and 11 adverse events in 10 of 45 (22.2%) patients at their most recent injection visit. Antibody (Ab) testing was carried out in 22 patients due to nonresponsiveness; blocking Abs were confirmed by the mouse protection assay in 4 of 22 (18%) patients. Of the Ab‐negative patients, 16 resumed responsiveness after dose adjustments and2 persisted as nonrespondents. Except for 1 patient, the 4 Ab‐positive and the 2 clinical nonresponders are being treated with BTX‐B. This longest reported follow‐up of BTX injections confirms the long‐term efficacy and safety of this treatment.

Unrecognized vitamin D3 deficiency is common in Parkinson disease Harvard Biomarker Study

Objective: To conclusively test for a specific association between the biological marker 25-hydroxy-vitamin D3, a transcriptionally active hormone produced in human skin and liver, and the prevalence and severity of Parkinson disease (PD). Methods: We used liquid chromatography/tandem mass spectrometry to establish an association specifically between deficiency of 25-hydroxy-vitamin D3 and PD in a cross-sectional and longitudinal case-control study of 388 patients (mean Hoehn and Yahr stage of 2.1 ± 0.6) and 283 control subjects free of neurologic disease nested in the Harvard Biomarker Study. Results: Plasma levels of 25-hydroxy-vitamin D3 were associated with PD in both univariate and multivariate analyses with p values = 0.0034 and 0.047, respectively. Total 25-hydroxy-vitamin D levels, the traditional composite measure of endogenous and exogenous vitamin D, were deficient in 17.6% of patients with PD compared with 9.3% of controls. Low 25-hydroxy-vitamin D3 as well as total 25-hydroxy-vitamin D levels were correlated with higher total Unified Parkinson’s Disease Rating Scale scores at baseline and during follow-up. Conclusions: Our study reveals an association between 25-hydroxy-vitamin D3 and PD and suggests that thousands of patients with PD in North America alone may be vitamin D–deficient. This finding has immediate relevance for individual patients at risk of falls as well as public health, and warrants further investigation into the mechanism underlying this association.

Tiques secundários e touretismo

Motor and phonic tics are most frequently due to Tourette syndrome, but there are many other causes of tics. We analyzed data on 155 patients with tics and co-existent disorders (101M/54F; mean age 40.5 ± 20.2 years). Fourteen (9.0%) patients had tics associated with an insult to the basal ganglia, such as head trauma (N = 4, 2.5%), stroke (N = 2, 1.2%), encephalitis (N = 3, 1.9%) and other causes. In addition, certain drugs, toxins, and post-infectious causes were associated with tics. Rarely, peripheral injury can cause movement disorders, including tics (N = 1, 0.6%). Pervasive developmental disorders, including Aspergers syndrome (N = 13, 8.3%), mental retardation (N = 4, 2.5%), autism (N = 3, 1.9%), and Savants syndrome (N = 1, 0.6%), also may be associated with tics, as noted in 21 of the 155 patients (13.5%). Genetic and chromosomal disorders, such as Downs syndrome 5 (3.2%), neuroacanthocytosis (N = 2, 1.2%), and Huntingtons disease (N = 1, 0.6%), were associated with tics in 16 patients (10.3%). We have also examined the co-existence of tics and other movement disorders such as dystonia (N = 31, 20.0%) and essential tremor (N = 17, 10.9%). Sixteen (10.3%) patients presented psychogenic tics, and one (0.6%) psychogenic tics and dystonia; conversely, Tourette syndrome preceded the onset of psychogenic dystonia (N = 1, 0.6%), and psychogenic tremor (N = 1, 0.6%) in two patients. Finally, 12 (7.7%) patients had tics in association with non-movement related neurological disorders, such as static encephalopathy (N = 2, 1.2%) and seizures (N = 3, 1.9%). To understand the physiopathology of tics and Tourette syndrome, it is important to recognize that these may be caused or associated with other disorders.

Is history of depression a contraindication to treatment with tetrabenazine

Objective: To determine whether a history of depression predisposes hyperkinetic patients treated with tetrabenazine (TBZ) to a recurrence or worsening of this symptom. Methods: We retrospectively reviewed the charts of 518 patients treated with TBZ to determine the frequency of depression and other adverse events. Charts were screened for the preexistence, development, or exacerbation of depression during the course of treatment. Results: The most common adverse events related to TBZ were somnolence (27.4%), depression (15.1%), parkinsonism (11.8%), and akathisia (8.9%); 78 patients (15.1%) experienced depression for the first time or an exacerbation of existing depression. Of those patients with no history of depression, 28 (11.4%) of 246 were newly diagnosed with depression. Patients with a documented history of depression experienced a significantly higher rate of worsening in 50 (18.4%) of 272 cases (P = 0.03). However, patients with a history of depression experienced more improvement of their hyperkinesia compared to those without a history of depression (P < 0.01). Conclusions: Depression, an adverse event of TBZ, is more likely to occur or worsen in patients with a preexisting history of depression.

Metoclopramide‐induced tardive dyskinesia in an infant

We describe a 1‐year‐old girl who developed orofaciolingual stereotypy at age 2 months after a 17‐day treatment with metoclopramide for gastroesophageal reflux. The stereotypy, documented by sequential videos, persisted for at least 9 months after the drug was discontinued. This patient represents the first documented case of tardive dyskinesia in an infant. We also review previous reports of tardive dyskinesia in children.

Tardive dyskinesia and withdrawal emergent syndrome in children

Tardive dyskinesia (TD) is a well-recognized and sometimes permanent adverse effect of treatment with dopamine receptor-blocking drugs (DRBDs), also referred to as neuroleptics. This iatrogenic disorder has been well characterized in adults, but not extensively studied in children. Withdrawal emergent syndrome (WES) is another pediatric movement disorder related to the use of DRBDs. TD and WES are among the most feared adverse effects of DRBD treatment, and have important medical and legal implications. We review published studies of children under the age of 18 years who were exposed to DRBD to determine the clinical spectrum and estimate the possible prevalence of TD and WES. We particularly wish to draw attention to the phenomenology, clinical course and treatment of these childhood-onset disorders. Although avoiding DRBDs is the best strategy for minimizing the risk of TD and WES, physicians who evaluate children exposed to DRBDs must be vigilant and recognize the early symptoms and signs of these syndromes to provide appropriate clinical management.

Association between α-synuclein blood transcripts and early, neuroimaging-supported Parkinson’s disease

There are no cures for neurodegenerative diseases and this is partially due to the difficulty of monitoring pathogenic molecules in patients during life. The Parkinsons disease gene α-synuclein (SNCA) is selectively expressed in blood cells and neurons. Here we show that SNCA transcripts in circulating blood cells are paradoxically reduced in early stage, untreated and dopamine transporter neuroimaging-supported Parkinsons disease in three independent regional, national, and international populations representing 500 cases and 363 controls and on three analogue and digital platforms with P < 0.0001 in meta-analysis. Individuals with SNCA transcripts in the lowest quartile of counts had an odds ratio for Parkinsons disease of 2.45 compared to individuals in the highest quartile. Disease-relevant transcript isoforms were low even near disease onset. Importantly, low SNCA transcript abundance predicted cognitive decline in patients with Parkinsons disease during up to 5 years of longitudinal follow-up. This study reveals a consistent association of reduced SNCA transcripts in accessible peripheral blood and early-stage Parkinsons disease in 863 participants and suggests a clinical role as potential predictor of cognitive decline. Moreover, the three independent biobank cohorts provide a generally useful platform for rapidly validating any biological marker of this common disease.

National Randomized Controlled Trial of Virtual House Calls for People with Parkinson's Disease: Interest and Barriers

BACKGROUND Delivering specialty care remotely directly into peoples homes can enhance access for and improve the healthcare of individuals with chronic conditions. However, evidence supporting this approach is limited. MATERIALS AND METHODS Connect.Parkinson is a randomized comparative effectiveness study that compares usual care of individuals with Parkinsons disease in the community with usual care augmented by virtual house calls with a Parkinsons disease specialist from 1 of 18 centers nationally. Individuals in the intervention arm receive four virtual visits from a Parkinsons disease specialist over 1 year via secure, Web-based videoconferencing directly into their homes. All study activities, including recruitment, enrollment, and assessments, are conducted remotely. Here we report on interest, feasibility, and barriers to enrollment in this ongoing study. RESULTS During recruitment, 11,734 individuals visited the studys Web site, and 927 unique individuals submitted electronic interest forms. Two hundred ten individuals from 18 states enrolled in the study from March 2014 to June 2015, and 195 were randomized. Most participants were white (96%) and college educated (73%). Of the randomized participants, 73% had seen a Parkinsons disease specialist within the previous year. CONCLUSIONS Among individuals with Parkinsons disease, national interest in receiving remote specialty care directly into the home is high. Remote enrollment in this care model is feasible but is likely affected by differential access to the Internet.

Racial disparities in neurologic health care access and utilization in the United States

Objective: To evaluate racial and ethnic differences in the utilization of neurologic care across a wide range of neurologic conditions in the United States. Methods: We analyzed nationally representative data from the 2006–2013 Medical Expenditure Panel Survey (MEPS), including information on demographics, patient-reported health conditions, neurology visit rates, and costs. Using diagnostic codes, we identified persons with any self-identified neurologic disorder except back pain, as well as 5 subgroups (Parkinson disease, multiple sclerosis, headache, cerebrovascular disease, and epilepsy). To assess disparities in neurologic care utilization, we performed logistic regression analyses of outpatient department neurologic care visit rates and expenditures for each racial ethnic group controlling for age, sex, health status, socioeconomic characteristics, and geographic region of care. Results: Of the 279,103 MEPS respondents, 16,936 (6%) self-reported a neurologic condition; 5,890 (2%) received a total of 13,685 outpatient neurology visits. Black participants were nearly 30% less likely to see an outpatient neurologist (odds ratio [OR] 0.72, confidence interval [CI] 0.64–0.81) relative to their white counterparts, even after adjustment for demographic, insurance, and health status differences. Hispanic participants were 40% less likely to see an outpatient neurologist (OR 0.61, CI 0.54–0.69). Among participants with known neurologic conditions, blacks were more likely to be cared for in the emergency department, to have more hospital stays, and to have higher per capita inpatient expenditures than their white counterparts. Conclusions: Our findings highlight racial and ethnic inequalities in the utilization of neurologic care in the United States.

The Disability Burden Associated With Stroke Emerges Before Stroke Onset and Differentially Affects Blacks: Results From the Health and Retirement Study Cohort

BACKGROUND Few longitudinal studies compare changes in instrumental activities of daily living (IADLs) among stroke-free adults to prospectively document IADL changes among adults who experience stroke. We contrast annual declines in IADL independence for older individuals who remain stroke free to those for individuals who experienced stroke. We also assess whether these patterns differ by sex, race, or Southern birthplace. METHODS Health and Retirement Study participants who were stroke free in 1998 (n = 17,741) were followed through 2010 (average follow-up = 8.9 years) for self- or proxy-reported stroke. We used logistic regressions to compare annual changes in odds of self-reported independence in six IADLs among those who remained stroke free throughout follow-up (n = 15,888), those who survived a stroke (n = 1,412), and those who had a stroke and did not survive to participate in another interview (n = 442). We present models adjusted for demographic and socioeconomic covariates and also stratified on sex, race, and Southern birthplace. RESULTS Compared with similar cohort members who remained stroke free, participants who developed stroke had faster declines in IADL independence and lower probability of IADL independence prior to stroke. After stroke, independence declined at an annual rate similar to those who did not have stroke. The black-white disparity in IADL independence narrowed poststroke. CONCLUSION Racial differences in IADL independence are apparent long before stroke onset. Poststroke differences in IADL independence largely reflect prestroke disparities.