Does diabetes mellitus affect the safety profile of valproic acid for the treatment of status epilepticus? A retrospective cohort study.

BACKGROUND: In the treatment of status epilepticus less is known about the influence of comorbidities on the safety profile of anticonvulsive drugs. Especially patients with diabetes mellitus may be predisposed to certain adverse events that have been related to therapy with valproic acid. In this single-center retrospective cohort study we examined if the complications of the intravenous treatment with valproic acid is different in patients with or without diabetes. METHODS: Patients who were treated for status epilepticus with intravenous valproic acid between 2008 and 2020 were identified. Primary endpoint was the discontinuation of therapy with valproic acid due to adverse events. Relevant secondary endpoints were the functional status at the time of discharge from hospital in comparison to the premorbid state and the in-hospital mortality. Both groups (patients with or without diabetes) were compared by Mann-Whitney U-Test or Pearson´s Chi2 test. To identify therapy with valproic acid as a risk factor of in-hospital mortality, a binary regression model was used. RESULTS: During the study period 408 patients and 482 episodes of status epilepticus were treated with intravenous valproic acid. Group comparisons did not reveal a significant difference in the rates of discontinuation of therapy. A difference was found in the rate of thrombocytopenia (p = 0.015), which occurred more often in patients with diabetes. In total, 36 hypoglycemic episodes could be identified, two occurred spontaneously under intravenous valproic acid. After correction for potential confounders, continuous therapy with valproic acid could not be confirmed as an independent risk factor for in-hospital mortality (p = 0.079). In patients with diabetes, the proportion of patients with a good functional state, indicated by the modified Rankin Scale, was significantly lower in both times (premorbid: 55% vs. 69%, p = 0.008; at discharge: 22% vs. 36%, p = 0.004). CONCLUSIONS: Tolerability of the treatment with valproic acid was similar in patients with or without diabetes. Diabetes as a relevant comorbidity can signal a potentially increased risk of a poor outcome after status epilepticus. TRIAL REGISTRATION: The study was registered at the German Clinical Trials Register on 8 April 2022 (DRKS 00,027,836).

Long-term cognitive impairment after ICU treatment: a prospective longitudinal cohort study (Cog-I-CU).

In this prospective cohort study we aimed to investigate the trajectory of the cognitive performance of patients after discharge from an intensive care unit (ICU). Special consideration was given to patients with suspected premorbid cognitive impairment who might be at risk for the development of dementia. Clinical characteristics were collected until discharge. The premorbid cognitive state was estimated by a structured interview with a close relative. Cognitive outcome was assessed using the Consortium to Establish a Registry of Alzheimer's Disease (CERAD) Plus battery and the Stroop Color and Word Test at the time of discharge from ICU and 9 months later. The results of the study group were compared to an established healthy control group and to normative data. A total number of 108 patients were finally included. At the time of discharge, patients underperformed the healthy control group. In linear regression models, delirium during the ICU stay and the factor premorbid cognitive impairment were associated with poorer cognitive outcome (p = 0.047 and p = 0.001). After 9 months, in 6% of patients without evidence of premorbid cognitive impairment long-lasting deficits were found. In patients with suspected premorbid cognitive impairment, performance in tests of executive function failed to improve.

Delirium Screening in Neurocritical Care and Stroke Unit Patients: A Pilot Study on the Influence of Neurological Deficits on CAM-ICU and ICDSC Outcome.

BACKGROUND/OBJECTIVE: Delirium is a common complication in critically ill patients with a negative impact on hospital length of stay, morbidity, and mortality. Little is known on how neurological deficits affect the outcome of commonly used delirium screening tools such as the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) in neurocritical care patients. METHODS: Over a period of 1 month, all patients admitted to a neurocritical care and stroke unit at a single academic center were prospectively screened for delirium using both CAM-ICU and ICDSC. Tool-based delirium screening was compared with delirium evaluation by the treating clinical team. Additionally, ICD-10 delirium criteria were assessed. RESULTS: One hundred twenty-three patients with a total of 644 daily screenings were included. Twenty-three patients (18.7%) were diagnosed with delirium according to the clinical evaluation. Delirium incidence amounted to 23.6% (CAM-ICU) and 26.8% (ICDSC). Sensitivity and specificity of both screening tools were 66.9% and 93.3% for CAM-ICU and 69.9% and 93.9% for ICDSC, respectively. Patients identified with delirium by either CAM-ICU or ICDSC presented a higher proportion of neurological deficits such as impaired consciousness, expressive aphasia, impaired language comprehension, and hemineglect. Subsequently, generalized estimating equations identified a significant association between impaired consciousness (as indexed by Richmond Agitation and Sedation Scale) and a positive delirium assessment with both CAM-ICU and ICDSC, while impaired language comprehension and hemineglect were only associated with a positive CAM-ICU result. CONCLUSIONS: A positive delirium screening with both CAM-ICU and ICDSC in neurocritical care and stroke unit patients was found to be significantly associated with the presence of neurological deficits. These findings underline the need for a more specific delirium screening tool in neurocritical care patients.

Dual-Site Transcranial Magnetic Stimulation for the Treatment of Parkinson's Disease.

Abnormal oscillatory activity in the subthalamic nucleus (STN) may be relevant for motor symptoms in Parkinson's disease (PD). Apart from deep brain stimulation, transcranial magnetic stimulation (TMS) may be suitable for altering these oscillations. We speculated that TMS to different cortical areas (primary motor cortex, M1, and dorsal premotor cortex, PMd) may activate neuronal subpopulations within the STN via corticofugal neurons projecting directly to the nucleus. We hypothesized that PD symptoms can be ameliorated by a lasting decoupling of STN neurons by associative dual-site repetitive TMS (rTMS). Associative dual-site rTMS (1 Hz) directed to PMd and M1 ("ADS-rTMS") was employed in 20 PD patients treated in a blinded, placebo-controlled cross-over design. Results: No adverse events were noted. We found no significant improvement in clinical outcome parameters (videography of MDS-UPDRS-III, finger tapping, spectral tremor power). Variation of the premotor stimulation site did not induce beneficial effects either. A single session of ADS-rTMS was tolerated well, but did not produce a clinically meaningful benefit on Parkinsonian motor symptoms. Successful treatment using TMS targeting subcortical nuclei may require an intervention over several days or more detailed physiological information about the individual brain state and stimulation-induced subcortical effects.