Outcome of Hospitalized Parkinson's Disease Patients with and without COVID-19.

Background: The Parkinson's disease (PD) patient population, with an already reduced life expectancy, is rendered particularly vulnerable by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Objectives: We determined the risk factors that increase the risk of death in patients with Parkinson's disease who are infected by SARS-CoV-2. Methods: Patients with a diagnosis of PD admitted to Montefiore Hospital (Bronx, New York) and tested for SARS-CoV-2 were identified. Retrospective review of electronic medical records confirmed the diagnosis; patients were classified by severity of PD. PD severity, demographic, socioeconomic factors, and co-morbidities were correlated with mortality rates in patients with SARS-CoV-2. Results: We identified 162 patients meeting criteria; chart review confirmed a diagnosis of PD in 70 patients. Of the 70 patients, 53 were positive for SARS-CoV-2 and 17 were negative. PD patients with SARS-CoV-2 infection had a higher mortality rate (35.8%) compared to PD patients without the infection (5.9%, P = 0.028). PD patients older than 70 years of age, those with advanced Parkinson's disease, those with reductions in their medications, and non-Hispanics (largely comprised of Black/African- Americans) had a statistically significant higher mortality rate, if infected. Conclusions: PD did not increase mortality rates from SARS-CoV-2 infection when age was controlled. However, certain unalterable factors (advanced disease and age greater than 70 years) and alterable ones (reductions in PD medications) placed PD patients at increased risk for mortality. Also several socioeconomic factors contributed to mortality, for example, non-Hispanic patients with SARS-CoV-2 infection fared worse, likely driven by poorer outcomes in the Black/African-American cohort.

Comparison of VIM and STN DBS for Parkinsonian Resting and Postural/Action Tremor.

BACKGROUND: Resting tremor is common in Parkinson's disease (PD), but up to 47% of PD patients have action tremor, which is sometimes resistant to medications. Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus or subthalamic nucleus (STN) is effective for medication-refractory tremor in PD, though it remains unclear whether STN DBS is as effective as VIM DBS for postural/action tremor related to PD. METHODS: We carried out a single-center retrospective review of patients with medication-refractory resting, postural, and action PD tremor, treated with either VIM or STN DBS between August 2004 and March 2014. We assessed the degree of improvement using items 20 and 21 of the Unified Parkinson's Disease Rating Scale (UPDRS) motor scale and examined the proportion of patients achieving tremor arrest. RESULTS: A total of 18 patients were analyzed, 10 treated with STN and eight treated with VIM, with similar off-medication motor UPDRS scores. There was no significant difference in improvement in tremor scores or in the proportion of patients experiencing tremor arrest between the two stimulation sites. Overall, 56% and 72% of patients experienced complete absence of postural/action tremor and resting tremor, respectively, at last follow-up. DISCUSSION: This study demonstrated excellent outcomes on both resting and postural/action tremor after either VIM or STN DBS. Resting tremor improved to a greater degree than postural/action tremor in both groups. These results suggest that a large randomized controlled trial is needed to show a superior effect of one target on PD tremor.

Prenatal cocaine exposure uncouples mGluR1 from Homer1 and Gq Proteins.

Cocaine exposure during gestation causes protracted neurobehavioral changes consistent with a compromised glutamatergic system. Although cocaine profoundly disrupts glutamatergic neurotransmission and in utero cocaine exposure negatively affects metabotropic glutamate receptor-type 1 (mGluR1) activity, the effect of prenatal cocaine exposure on mGluR1 signaling and the underlying mechanism responsible for the prenatal cocaine effect remain elusive. Using brains of the 21-day-old (P21) prenatal cocaine-exposed rats, we show that prenatal cocaine exposure uncouples mGluR1s from their associated synaptic anchoring protein, Homer1 and signal transducer, Gq/11 proteins leading to markedly reduced mGluR1-mediated phosphoinositide hydrolysis in frontal cortex (FCX) and hippocampus. This prenatal cocaine-induced effect is the result of a sustained protein kinase C (PKC)-mediated phosphorylation of mGluR1 on the serine residues. In support, phosphatase treatment of prenatal cocaine-exposed tissues restores whereas PKC-mediated phosphorylation of saline-treated synaptic membrane attenuates mGluR1 coupling to both Gq/11 and Homer1. Expression of mGluR1, Homer1 or Gα proteins was not altered by prenatal cocaine exposure. Collectively, these data indicate that prenatal cocaine exposure triggers PKC-mediated hyper-phosphorylation of the mGluR1 leading to uncoupling of mGluR1 from its signaling components. Hence, blockade of excessive PKC activation may alleviate abnormalities in mGluR1 signaling and restores mGluR1-regulated brain functions in prenatal cocaine-exposed brains.

RELATIONSHIP OF GAIT AND COGNITION IN THE ELDERLY.

Gait and cognitive impairments in older adults mostly reflect the co-occurrence of two geriatric syndromes linked by common underlying brain substrates and pathologies. Gait control is predominately mediated by frontal subcortical circuits, which overlap with circuits controlling executive control and attention functions. These circuits are vulnerable to multiple age-related pathologies such as ischemia, inflammation, and neurodegeneration, which could ultimately cause cognitive, gait, or combined cognitive and gait impairments. The following review aims to describe various gait and cognitive classifications, gait based phenotypes, common underlying pathological processes, and provide a link between motor and cognitive impairments in an effort to predict the risk of dementia, as well as remediate impairments by applying appropriate interventions.