Acute ischemic strokes in patients with developmental disabilities: A cross-sectional analysis.

OBJECTIVE: Patients with developmental disabilities (DD) are frequently excluded from acute ischemic stroke (AIS) randomized control trials. We sought to evaluate the impact of having DD on this patient cohort. METHODS: The National Inpatient Sample was analyzed to explore the impact of AIS and treatment on discharge dispositions in patients with DD. Clinical characteristics, treatments, and outcomes were compared to fully-abled patients with AIS. RESULTS: 1,605,723 patients with AIS were identified from 2010-2019, of whom 4094 (0.30%) had a DD. AIS patients with DD were younger (60.31 vs 70.93 years, p < 0.01), less likely to be Caucasian (66.37%vs 68.09%, p = 0.01), and had higher AIS severity (0.63 vs 0.58, p < 0.01). Tissue plasminogen activator (tPA) was administered in 99,739 (6.2%) fully-abled patients and 196 (4.79%) of patients with DD (p < 0.01). Endovascular thrombectomy (EVT) was performed in 21,066 (1.31%) of fully-abled patients and 35 (0.85%) of patients with DD (p < 0.01). The presence of developmental disabilities were predictive of lower rates of tPA (OR:0.71,CI:0.56-0.87,p < 0.01) and EVT (OR:0.24,CI:0.16-0.36,p < 0.01). In a propensity score-matched cohort of all AIS patients who underwent EVT, there was no difference in functional outcome (p = 0.41), in-hospital mortality (0.10), and LOS (p = 0.79). CONCLUSION: AIS patients with DD were less likely to receive tPA and EVT compared to fully-abled patients. Individuals with DD had higher mortality and worse discharge disposition. There was no significant difference in post-EVT outcomes between fully-abled patients and patients with developmental disabilities. In the absence of prospective clinical trials, population based cross-sectional analyses such as the present study provide valuable clinical insight.

Cardiac arrest in spontaneous subarachnoid hemorrhage and associated outcomes.

OBJECTIVE: The authors sought to analyze a large, publicly available, nationwide hospital database to further elucidate the impact of cardiopulmonary arrest (CA) in association with subarachnoid hemorrhage (SAH) on short-term outcomes of mortality and discharge disposition. METHODS: This retrospective cohort study was conducted by analyzing de-identified data from the National (Nationwide) Inpatient Sample (NIS). The publicly available NIS database represents a 20% stratified sample of all discharges and is powered to estimate 95% of all inpatient care delivered across hospitals in the US. A total of 170,869 patients were identified as having been hospitalized due to nontraumatic SAH from 2008 to 2014. RESULTS: A total of 5415 patients (3.2%) were hospitalized with an admission diagnosis of CA in association with SAH. Independent risk factors for CA included a higher Charlson Comorbidity Index score, hospitalization in a small or nonteaching hospital, and a Medicaid or self-pay payor status. Compared with patients with SAH and not CA, patients with CA-SAH had a higher mean NIS Subarachnoid Severity Score (SSS) ± SD (1.67 ± 0.03 vs 1.13 ± 0.01, p < 0.0001) and a vastly higher mortality rate (82.1% vs 18.4%, p < 0.0001). In a multivariable model, age, NIS-SSS, and CA all remained significant independent predictors of mortality. Approximately 18% of patients with CA-SAH survived and were discharged to a rehabilitation facility or home with health services, outcomes that were most predicted by chronic disease processes and large teaching hospital status. CONCLUSIONS: In the largest study of its kind, CA at onset was found to complicate roughly 3% of spontaneous SAH cases and was associated with extremely high mortality. Despite this, survival can still be expected in approximately 18% of patients.

Reduced Dopamine Signaling Impacts Pyramidal Neuron Excitability in Mouse Motor Cortex.

Dopaminergic modulation is essential for the control of voluntary movement; however, the role of dopamine in regulating the neural excitability of the primary motor cortex (M1) is not well understood. Here, we investigated two modes by which dopamine influences the input/output function of M1 neurons. To test the direct regulation of M1 neurons by dopamine, we performed whole-cell recordings of excitatory neurons and measured excitability before and after local, acute dopamine receptor blockade. We then determined whether chronic depletion of dopaminergic input to the entire motor circuit, via a mouse model of Parkinson's disease, was sufficient to shift M1 neuron excitability. We show that D1 receptor (D1R) and D2R antagonism altered subthreshold and suprathreshold properties of M1 pyramidal neurons in a layer-specific fashion. The effects of D1R antagonism were primarily driven by changes to intrinsic properties, while the excitability shifts following D2R antagonism relied on synaptic transmission. In contrast, chronic depletion of dopamine to the motor circuit with 6-hydroxydopamine induced layer-specific synaptic transmission-dependent shifts in M1 neuron excitability that only partially overlapped with the effects of acute D1R antagonism. These results suggest that while acute and chronic changes in dopamine modulate the input/output function of M1 neurons, the mechanisms engaged are distinct depending on the duration and origin of the manipulation. Our study highlights the broad influence of dopamine on M1 excitability by demonstrating the consequences of local and global dopamine depletion on neuronal input/output function.