The Determining Factors for Outcome of Pediatric Intensive Care Admitted Children After Stem Cell Transplantation.

INTRODUCTION: Requiring pediatric intensive care unit (PICU) admission relates to high mortality and morbidity in patients who received hematopoietic stem cell transplantation (HSCT). In this study, we aimed to evaluate the indications for PICU admission, treatments, and the determining risk factors for morbidity and mortality in patients who had allogeneic HSCT from various donors. MATERIALS AND METHODS: In this retrospective study, we enrolled to patients who required the PICU after receiving allogeneic HSCT at our Pediatric Bone Marrow Transplantation Unit between 2005 and 2020. We evaluated to indication to PICU admission, applications, mortality rate, and the determining factors to outcomes. RESULTS: Thirty-three (7%) patients had 47 PICU admissions and 471 patients underwent bone marrow transplantation during 16-year study period. Also, 14 repeated episodes were registered in 9 different patients. The median age of PICU admitted patients was 4 (0.3 to 18) years and 29 (62%) were male. The main reasons for PICU admission were a respiratory failure, sepsis, and neurological event in 20, 8, and 7 patients, respectively. The average length of PICU stay was 14.5 (1 to 80) days, 14 (43%) of patients survived and the mortality rate was 57%. Multiple organ failure ( P =0.001), need for respiratory support ( P =0.007), inotrope agents ( P =0.001), and renal replacement therapy ( P =0.013) were found as significant risk factors for mortality. CONCLUSIONS: Allogeneic HSCT recipients need PICU admission because of its related different life-threatening complications. But there is a good chance of survival with quality PICU care and different advanced organ support methods.

Electroceutically induced subthalamic high-frequency oscillations and evoked compound activity may explain the mechanism of therapeutic stimulation in Parkinson's disease.

Despite having remarkable utility in treating movement disorders, the lack of understanding of the underlying mechanisms of high-frequency deep brain stimulation (DBS) is a main challenge in choosing personalized stimulation parameters. Here we investigate the modulations in local field potentials induced by electrical stimulation of the subthalamic nucleus (STN) at therapeutic and non-therapeutic frequencies in Parkinson's disease patients undergoing DBS surgery. We find that therapeutic high-frequency stimulation (130-180 Hz) induces high-frequency oscillations (~300 Hz, HFO) similar to those observed with pharmacological treatment. Along with HFOs, we also observed evoked compound activity (ECA) after each stimulation pulse. While ECA was observed in both therapeutic and non-therapeutic (20 Hz) stimulation, the HFOs were induced only with therapeutic frequencies, and the associated ECA were significantly more resonant. The relative degree of enhancement in the HFO power was related to the interaction of stimulation pulse with the phase of ECA. We propose that high-frequency STN-DBS tunes the neural oscillations to their healthy/treated state, similar to pharmacological treatment, and the stimulation frequency to maximize these oscillations can be inferred from the phase of ECA waveforms of individual subjects. The induced HFOs can, therefore, be utilized as a marker of successful re-calibration of the dysfunctional circuit generating PD symptoms.

Subthalamic Single Cell and Oscillatory Neural Dynamics of a Dyskinetic Medicated Patient With Parkinson's Disease.

Single cell neuronal activity (SUA) and local field potentials (LFP) in the subthalamic nucleus (STN) of unmedicated Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) surgery have been well-characterized during microelectrode recordings (MER). However, there is limited knowledge about the changes in the firing patterns and oscillations above and within the territories of STN after the intake of dopaminergic medication. Here, for the first time, we report the STN single cell and oscillatory neural dynamics in a medicated patient with idiopathic PD using intraoperative MER. We recorded LFP and SUA with microelectrodes at various depths during bilateral STN-DBS electrode implantation. We isolated 26 neurons in total and observed that tonic and irregular firing patterns of individual neurons predominated throughout the territories of STN. While burst-type firings have been well-characterized in the dorsal territories of STN in unmedicated patients, interestingly, this activity was not observed in our medicated subject. LFP recordings lacked the excessive beta (8-30 Hz) activity, characteristic of the unmedicated state and signal energy was mainly dominated by slow oscillations below 8 Hz. We observed sharp gamma oscillations between 70 and 90 Hz within and above the STN. Despite the presence of a broadband high frequency activity in 200-400 Hz range, no cross-frequency interaction in the form of phase-amplitude coupling was noted between low and high frequency oscillations of LFPs. While our results are in agreement with the previously reported LFP recordings from the DBS lead in medicated PD patients, the sharp gamma peak present throughout the depth recordings and the lack of bursting firings after levodopa intake have not been reported before. The lack of bursting in SUA, the lack of excessive beta activity and cross frequency coupling between HFOs and lower rhythms further validate the link between bursting firing regime of neurons and pathological oscillatory neural activity in PD-STN. Overall, these observations not only validate the existing literature on the PD electrophysiology in healthy/medicated animal models but also provide insights regarding the underlying electro-pathophysiology of levodopa-induced dyskinesias in PD patients through demonstration of multiscale relationships between single cell firings and field potentials.

Unsupervised clustering reveals spatially varying single neuronal firing patterns in the subthalamic nucleus of patients with Parkinson's disease.

INTRODUCTION: Subthalamic nucleus (STN) is an effective target for deep brain stimulation (DBS) to reduce the motor symptoms of Parkinson's disease (PD). It is important to identify firing patterns within the structure for a better understanding of the electro-pathophysiology of the disease. Using recently established metrics, our study aims to autonomously identify the discharge patterns of individual cells and examine their spatial distribution within the STN. METHODS: We recorded single unit activity (SUA) from 12 awake PD patients undergoing a standard clinical DBS surgery. Three extracted features from raw SUA (local variation, bursting index and prominence of peak) were used with k-means clustering to achieve the aforementioned unsupervised grouping of firing patterns. RESULTS: 279 neurons were isolated and four distinct firing patterns were identified across patients: tonic (11%), irregular (55%), periodic (9%) and non-periodic bursts (25%). The mean firing rates for irregular discharges were significantly lower (p < 0.05) than the rest. Tonic firings were significantly ventral (p < 0.05) while periodic (p < 0.05) and non-periodic (p < 0.01) bursts were dorsal. The percentage of periodically bursting neurons in dorsal region and entire STN were significantly correlated with off state UPDRS tremor scores (r = 0.51, p = 0.04) and improvement in bradykinesia and rigidity (r = 0.57, p = 0.02) respectively. CONCLUSION: Strengthening the application of unsupervised clustering for firing patterns of individual cells, this study shows a unique spatial affinity of tonic activity towards the ventral and bursting activity towards the dorsal region of STN in PD patients. This spatial preference, together with the correlation of clinical scores, can provide a clue towards understanding Parkinsonian symptom generation.

Interferon ß associated nephropathy in a Multiple Sclerosis patient: A case and review.

BACKGROUND: Interferon beta (IFN ß) subtypes are largely used as immunomodulatory agents in Multiple Sclerosis (MS) treatment. While being generally well tolerated, they can cause various side effects. Adverse effects related to kidney are rarely reported. CASE REPORT: We report a 32 years old male patient who developed nephrotic syndrome while receiving IFN ß for MS. Biopsy showed focal segmental glomerulosclerosis. He went into remisson after cessation of drug and with the aid of angiotensin II antagonists. Here, we report this case and a review of similar cases reported in literature. CONCLUSIONS: Although it's a rare adverse effect and tend to show good prognosis physicians should pay careful attention to symptoms and findings of nephropathy during follow ups of patients under treatment with these agents.