ABSTRACT
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) produces an electrophysiological signature called evoked resonant neural activity (ERNA); a high-frequency oscillation that has been linked to treatment efficacy. However, the single-neuron and synaptic bases of ERNA are unsubstantiated. This study proposes that ERNA is a subcortical neuronal circuit signature of DBS-mediated engagement of the basal ganglia indirect pathway network. In people with Parkinson's disease, we: (i) showed that each peak of the ERNA waveform is associated with temporally-locked neuronal inhibition in the STN; (ii) characterized the temporal dynamics of ERNA; (iii) identified a putative mesocircuit architecture, embedded with empirically-derived synaptic dynamics, that is necessary for the emergence of ERNA in silico; (iv) localized ERNA to the dorsal STN in electrophysiological and normative anatomical space; (v) used patient-wise hotspot locations to assess spatial relevance of ERNA with respect to DBS outcome; and (vi) characterized the local fiber activation profile associated with the derived group-level ERNA hotspot.
Subject(s)
Deep Brain Stimulation , Parkinson Disease , Subthalamic Nucleus , Humans , Parkinson Disease/therapy , Deep Brain Stimulation/methods , Subthalamic Nucleus/physiology , Basal Ganglia/physiology , Neurons/physiologyABSTRACT
Parkinson's disease (PD) is a common neurodegenerative disorder whose etiology remains largely unexplained. Several studies have aimed to describe a causative effect in the interactions between the gastrointestinal tract and the brain, for both PD pathogenesis and disease course. However, the results have been controversial. Helicobacter pylori and small intestinal bacterial overgrowth (SIBO) are theorized to be agents capable of triggering chronic proinflammatory changes with a possible neurotoxic effect, as well as a cause of erratic L-dopa response in PD patients. This review evaluates the individual and possibly synergistic influence of H. pylori and SIBO on PD, to provide an opportunity to consider prospective therapeutic approaches.
Subject(s)
Helicobacter pylori , Parkinson Disease , Humans , Parkinson Disease/drug therapy , Levodopa/therapeutic useABSTRACT
One in 10 patients with ischemic stroke has comorbid cancer. Our goal was to compare stroke patients with cancer against those without cancer in terms of clinical and radiological features, and the underlying mechanism. We conducted a retrospective case-control study in patients admitted with ischemic stroke between July 2013 and September 2018. Cases had a concomitant diagnosis of cancer and acute ischemic stroke, controls only of ischemic stroke. Age, gender, vascular risk factors (VRF), pattern of ischemic lesion in neuroimaging, etiology and clinical outcome were compared between groups. Fifty-seven cases were identified, 61% were male (n = 35), and mean age was 75 ± 11. Fiftytwo had known oncologic disease at the onset of stroke. Most of them had solid tumors (91%, n = 52), and 54% (n = 31) had a non-metastatic tumor at the time of stroke. Prevalence of common VRF between groups was not significantly different. Previous deep venous thrombosis and pulmonary thromboembolism were more frequent in the cancer cohort (8% vs. 1%, p = 0.01). The average NIHSS was 3.8 ± 4 in the cancer group and 9 ± 7 in the control group (p = 0.01). Small artery disease as the etiology of stroke was significantly less common in the cancer group (2% vs. 26%, p = 0.001). Regarding neuroimaging, the embolic pattern was more frequent in patients with cancer (82% vs. 35%, p = 0.001). In these patients recurrence and mortality at 90 days was three and six times higher (10% vs. 3%, and 18% vs. 3%. p = 0.08 and 0.001, respectively).
Aproximadamente uno de cada 10 pacientes que sufre un accidente cerebrovascular isquémico (ACVi) padece cáncer concomitantemente. Nuestro objetivo fue evaluar características clínicoradiológicas del ACVi en pacientes con cáncer y compararlas con otros sin cáncer. Fue un estudio caso-control retrospectivo que incluyó pacientes con ACVi entre julio 2013 y septiembre 2018. Los casos tenían diagnóstico de cáncer y ACVi, y los controles solamente ACVi. Se comparó edad, sexo, factores de riesgo vascular, patrones radiológicos de lesiones, etiología y evolución clínica entre ambos grupos. Hubo 57 casos, 61% (n = 35) eran varones. La edad media fue 75 ± 11 años, sin diferencias en prevalencia de factores de riesgo vascular. En los casos hubo más pacientes con antecedentes de trombosis venosa profunda y/o tromboembolismo pulmonar (8% vs. 1%, p = 0.01). En 52 se conocía la presencia del cáncer antes del ACVi. El 91% se trató de tumores sólidos (n = 52) y en 54% el tumor no presentaba metástasis. El puntaje NIHSS promedio fue 3.8 ± 4 en los casos, y 9 ± 7 en los controles (p = 0.01). Las lesiones de pequeña arteria fueron menos frecuentes en los casos (2% vs. 26%, p = 0.001). Las lesiones de aspecto embólico fueron más comunes entre los casos (82% vs. 35%, p = 0.001). Aquellos con cáncer tuvieron menor NIHSS, menor frecuencia de lesiones de pequeña arteria, y mayor frecuencia de lesiones de aspecto embólico. La recurrencia a 90 días fue 3 veces mayor y la mortalidad 6 veces mayor en pacientes con cáncer (10% vs. 3%, y 18% vs. 3%. p = 0.08 y 0.001 respectivamente).
Subject(s)
Brain Ischemia/epidemiology , Neoplasms/epidemiology , Stroke/epidemiology , Aged , Aged, 80 and over , Case-Control Studies , Female , Humans , Male , Middle Aged , Neoplasms/complications , Retrospective Studies , Stroke/diagnostic imaging , Stroke/etiologyABSTRACT
Resumen Aproximadamente uno de cada 10 pacientes que sufre un accidente cerebrovascular isquémico (ACVi) padece cáncer concomitantemente. Nuestro objetivo fue evaluar características clínicoradiológicas del ACVi en pacientes con cáncer y compararlas con otros sin cáncer. Fue un estudio caso-control retrospectivo que incluyó pacientes con ACVi entre julio 2013 y septiembre 2018. Los casos tenían diagnóstico de cáncer y ACVi, y los controles solamente ACVi. Se comparó edad, sexo, factores de riesgo vascular, patrones radiológicos de lesiones, etiología y evolución clínica entre ambos grupos. Hubo 57 casos, 61% (n = 35) eran varones. La edad media fue 75 ± 11 años, sin diferencias en prevalencia de factores de riesgo vascular. En los casos hubo más pacientes con antecedentes de trombosis venosa profunda y/o tromboembolismo pulmonar (8% vs. 1%, p = 0.01). En 52 se conocía la presencia del cáncer antes del ACVi. El 91% se trató de tumores sólidos (n = 52) y en 54% el tumor no presentaba metástasis. El puntaje NIHSS promedio fue 3.8 ± 4 en los casos, y 9 ± 7 en los controles (p = 0.01). Las lesiones de pequeña arteria fueron menos frecuentes en los casos (2% vs. 26%, p = 0.001). Las lesiones de aspecto embólico fueron más comunes entre los casos (82% vs. 35%, p = 0.001). Aquellos con cáncer tuvieron menor NIHSS, menor frecuencia de lesiones de pequeña arteria, y mayor frecuencia de lesiones de aspecto embólico. La recurrencia a 90 días fue 3 veces mayor y la mortalidad 6 veces mayor en pacientes con cáncer (10% vs. 3%, y 18% vs. 3%. p = 0.08 y 0.001 respectivamente).
Abstract One in 10 patients with ischemic stroke has comorbid cancer. Our goal was to compare stroke patients with cancer against those without cancer in terms of clinical and radiological features, and the underlying mechanism. We conducted a retrospective case-control study in patients admitted with ischemic stroke between July 2013 and September 2018. Cases had a concomitant diagnosis of cancer and acute ischemic stroke, controls only of ischemic stroke. Age, gender, vascular risk factors (VRF), pattern of ischemic lesion in neuroimaging, etiology and clinical outcome were compared between groups. Fifty-seven cases were identified, 61% were male (n = 35), and mean age was 75 ± 11. Fiftytwo had known oncologic disease at the onset of stroke. Most of them had solid tumors (91%, n = 52), and 54% (n = 31) had a non-metastatic tumor at the time of stroke. Prevalence of common VRF between groups was not significantly different. Previous deep venous thrombosis and pulmonary thromboembolism were more frequent in the cancer cohort (8% vs. 1%, p = 0.01). The average NIHSS was 3.8 ± 4 in the cancer group and 9±7 in the control group (p = 0.01). Small artery disease as the etiology of stroke was significantly less common in the cancer group (2% vs. 26%, p = 0.001). Regarding neuroimaging, the embolic pattern was more frequent in patients with cancer (82% vs. 35%, p = 0.001). In these patients recurrence and mortality at 90 days was three and six times higher (10% vs. 3%, and 18% vs. 3%. p = 0.08 and 0.001, respectively).
