Alexander Holl

Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized clinical trial.

IMPORTANCE Low vitamin D status is linked to increased mortality and morbidity in patients who are critically ill. It is unknown if this association is causal. OBJECTIVE To investigate whether a vitamin D3 treatment regimen intended to restore and maintain normal vitamin D status over 6 months is of health benefit for patients in ICUs. DESIGN, SETTING, AND PARTICIPANTS A randomized double-blind, placebo-controlled, single-center trial, conducted from May 2010 through September 2012 at 5 ICUs that included a medical and surgical population of 492 critically ill adult white patients with vitamin D deficiency (≤20 ng/mL) assigned to receive either vitamin D3 (n = 249) or a placebo (n = 243). INTERVENTIONS Vitamin D3 or placebo was given orally or via nasogastric tube once at a dose of 540,000 IU followed by monthly maintenance doses of 90,000 IU for 5 months. MAIN OUTCOMES AND MEASURES The primary outcome was hospital length of stay. Secondary outcomes included, among others, length of ICU stay, the percentage of patients with 25-hydroxyvitamin D levels higher than 30 ng/mL at day 7, hospital mortality, and 6-month mortality. A predefined severe vitamin D deficiency (≤12 ng/mL) subgroup analysis was specified before data unblinding and analysis. RESULTS A total of 475 patients were included in the final analysis (237 in the vitamin D3 group and 238 in the placebo group). The median (IQR) length of hospital stay was not significantly different between groups (20.1 days [IQR, 11.1-33.3] for vitamin D3 vs 19.3 days [IQR, 11.1-34.9] for placebo; P = .98). Hospital mortality and 6-month mortality were also not significantly different (hospital mortality: 28.3% [95% CI, 22.6%-34.5%] for vitamin D3 vs 35.3% [95% CI, 29.2%-41.7%] for placebo; hazard ratio [HR], 0.81 [95% CI, 0.58-1.11]; P = .18; 6-month mortality: 35.0% [95% CI, 29.0%-41.5%] for vitamin D3 vs 42.9% [95% CI, 36.5%-49.4%] for placebo; HR, 0.78 [95% CI, 0.58-1.04]; P = .09). For the severe vitamin D deficiency subgroup analysis (n = 200), length of hospital stay was not significantly different between the 2 study groups: 20.1 days (IQR, 12.9-39.1) for vitamin D3 vs 19.0 days (IQR, 11.6-33.8) for placebo. Hospital mortality was significantly lower with 28 deaths among 98 patients (28.6% [95% CI, 19.9%-38.6%]) for vitamin D3 compared with 47 deaths among 102 patients (46.1% [95% CI, 36.2%-56.2%]) for placebo (HR, 0.56 [95% CI, 0.35-0.90], P for interaction = .04), but not 6-month mortality (34.7% [95% CI, 25.4%-45.0%] for vitamin D3 vs 50.0% [95% CI, 39.9%-60.1%] for placebo; HR, 0.60 [95% CI, 0.39-0.93], P for interaction = .12). CONCLUSIONS AND RELEVANCE Among critically ill patients with vitamin D deficiency, administration of high-dose vitamin D3 compared with placebo did not reduce hospital length of stay, hospital mortality, or 6-month mortality. Lower hospital mortality was observed in the severe vitamin D deficiency subgroup, but this finding should be considered hypothesis generating and requires further study. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01130181.

Short-term effects of high-dose oral vitamin D3 in critically ill vitamin D deficient patients: a randomized, double-blind, placebo-controlled pilot study

IntroductionVitamin D deficiency is encountered frequently in critically ill patients and might be harmful. Current nutrition guidelines recommend very low vitamin D doses. The objective of this trial was to evaluate the safety and efficacy of a single oral high-dose vitamin D3 supplementation in an intensive care setting over a one-week observation period.MethodsThis was a randomized, double-blind, placebo-controlled pilot study in a medical ICU at a tertiary care university center in Graz, Austria. Twenty-five patients (mean age 62 ± 16yrs) with vitamin D deficiency [25-hydroxyvitamin D (25(OH)D) ≤20 ng/ml] and an expected stay in the ICU >48 hours were included and randomly received either 540,000 IU (corresponding to 13.5 mg) of cholecalciferol (VITD) dissolved in 45 ml herbal oil or matched placebo (PBO) orally or via feeding tube.ResultsThe mean serum 25(OH)D increase in the intervention group was 25 ng/ml (range 1-47 ng/ml). The highest 25(OH)D level reached was 64 ng/ml, while two patients showed a small (7 ng/ml) or no response (1 ng/ml). Hypercalcemia or hypercalciuria did not occur in any patient. From day 0 to day 7, total serum calcium levels increased by 0.10 (PBO) and 0.15 mmol/L (VITD; P < 0.05 for both), while ionized calcium levels increased by 0.11 (PBO) and 0.05 mmol/L (VITD; P < 0.05 for both). Parathyroid hormone levels decreased by 19 and 28 pg/ml (PBO and VITD, ns) over the seven days, while 1,25(OH)D showed a transient significant increase in the VITD group only.ConclusionsThis pilot study shows that a single oral ultra-high dose of cholecalciferol corrects vitamin D deficiency within 2 days in most patients without causing adverse effects like hypercalcemia or hypercalciuria. Further research is needed to confirm our results and establish whether vitamin D supplementation can affect the clinical outcome of vitamin D deficient critically ill patients.EudraCT Number2009-012080-34German Clinical Trials Register (DRKS)DRKS00000750

Efficacy and safety of radiosurgical callosotomy: a retrospective analysis.

Summary:  Purpose: Anterior callosotomy is a surgical option for the treatment of generalized tonic or atonic seizures associated with drop attacks. Besides open surgery, a radiosurgical callosal disconnection using the gamma knife (GK) also can be performed, but reliable data about tolerability and efficacy are sparse.

Novel pathomechanisms of cardiomyocyte dysfunction in a model of heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is increasingly common, but the underlying cellular mechanisms are not well understood. We investigated cardiomyocyte function and the role of SEA0400, an Na+/Ca2+ exchanger (NCX) inhibitor in a rat model of chronic kidney disease (CKD) with HFpEF.

Automatic and Remote Controlled Ictal SPECT Injection for Seizure Focus Localization by Use of a Commercial Contrast Agent Application Pump

Summary:  Purpose: In the presurgical evaluation of patients with partial epilepsy, the ictal single photon emission computed tomography (SPECT) is a useful noninvasive diagnostic tool for seizure focus localization. To achieve optimal SPECT scan quality, ictal tracer injection should be carried out as quickly as possible after the seizure onset and under highest safety conditions possible. Compared to the commonly used manual injection, an automatic administration of the radioactive tracer may provide higher quality standards for this procedure. In this study, therefore, we retrospectively analyzed efficiency and safety of an automatic injection system for ictal SPECT tracer application.

No effect of immunomodulatory therapy in focal epilepsy with positive glutamate receptor type 3-—antibodies

Antibodies against the glutamate receptor type 3-(GluR3) have been found in association with Rasmussens encephalitis (RE) but were also detected in patients with non-inflammatory focal epilepsies. We report the case of an 18-year-old patient with treatment refractory left mesial temporal lobe epilepsy accompanied by high levels of GluR3 antibodies. Different from experiences in patients with RE immunomodulatory therapy by use of intravenous gammaglobulines neither altered GluR3 serum levels nor had any effect on seizure frequency in our patient. Interestingly, GluR3 serum levels remained positive after successful surgical intervention leading to patients seizure freedom.

Ictal dystonic posturing in mesial versus neocortical temporal lobe seizures

PURPOSE Ictal contralateral dystonic posturing is a frequently observed clinical feature in temporal lobe seizures. It is generally interpreted as the result of spread of the ictal discharge into basal ganglia structure. In previous reports, analysing ictal behavior, a precise definition and description of the upper limb ictal dystonia is often lacking or contradictory. In our study we aimed to determine whether different subtypes of dystonia and their latency from the clinical onset of seizure might be of value for the differentiation between mesial temporal lobe epilepsy (MTLE) and neocortical temporal lobe epilepsy (NTLE). METHODS Eighty seizures (51 MTLE and 29 NTLE) and 30 patients (20 MTLE and 10 NTLE) were analyzed with regard to dystonic posturing of the upper limb. Ictal dystonia was subdivided into different subtypes according to distinct clinical features. Their frequency and latency from the clinical onset of seizure were assessed. RESULTS Frequencies of all subtypes were similar in MTLE and NTLE. Concerning the latencies contralateral dystonic posturing characterized by sustained muscle contractions with flexion of the wrist and fist closure, a frequently appearing feature, occurred significantly earlier in NTLE than in MTLE seizures. CONCLUSIONS This difference between the two groups may provide a differentiation between an epileptic focus of mesial from neocortical temporal lobe origin.

Future Aspects of the Presurgical Evaluation in Epilepsy

Epilepsy surgery is a successful therapeutic approach in patients with medically intractable epilepsy. The presurgical evaluation aims to detect the epileptogenic brain area by use of different diagnostic techniques. In this review article the current diagnostic procedures applied for this purpose are described. The diagnostic armamentarium can be divided conceptually into three different groups: assessment of function/dysfunction, structural/morphologic imaging methods and functional neuroimaging techniques. Properties, diagnostic power and limits of all diagnostic tools used in the diagnostic evaluation are discussed. In addition, future perspectives and the diagnostic value of new technologies are mentioned. Some are increasingly gaining acceptance in the routine preoperative diagnostic procedure like MR volumetry or MR spectroscopy of the hippocampus in patients with temporal lobe epilepsy. Some, on the other hand, like MEG and 11C-flumazenil PET, still remain experimental diagnostic tools as they are technically demanding and cost intensive. Besides the refinement of established techniques, co-registration of different modalities like spike-triggered functional MRI will play an important role in the non-invasive detection of the epileptic seizure focus and may change the regimen of the preoperative diagnostic work up of epilepsy patients in the future.

Immunological Markers in Plasma and CSF distinguish Vascular Parkinsonism from Idiopathic Parkinson's Disease

Abstract Activation of the cellular immune system is discussed to be partly responsible in the neurodegenerative process of Parkinsons disease. We determined concentrations of neopterin, of cytokine interleukin-6, and of soluble cytokine receptors sIL-2Rα, sTNF-R75α in plasma and cerebrospinal fluid in controls and patients with vascular parkinsonism and idiopathic Parkinsons disease diagnosed according to published clinical diagnostic criteria, to examine if the cellular immune system is activated locally or peripherally or both. Our results show no activation in idiopathic Parkinsons disease and controls, but a significant increased activation in vascular parkinsonism, where concomitant signs of cerebrovascular disease are present.

Reversible Posterior Leukoencephalopathy Syndrome Following Surgery

Introduction The reversible posterior leukoencephalopathy syndrome (RPLS) is an increasingly recognized cliniconeuroradiologic syndrome. The syndrome was first described by Hinchey et al. in 1996 [1]. The common clinical features are acute or subacute headache, nausea, vomiting, a disturbed level of consciousness ranging from drowsiness to stupor, seizures, and, occasionally, focal neurologic deficits. Patients often report blurred vision, but also hemianopsia, visual neglect, and cortical blindness [1]. Magnetic resonance imaging (MRI) often reveals reversible, usually symmetric, hyperintense lesions on T2-weighted scans, which involve especially the posterior regions of the brain with a predominance for the white matter, although gray matter structures may also be affected. Occasionally, the cerebellum and pons and the parietal and temporal lobes can be involved as well. The lesions are best visualized on fluid-attenuated inversion-recovery (FLAIR) sequences [2]. RPLS is usually considered to be a reversible condition if promptly recognized and appropriately treated. Otherwise, a delayed or incorrect diagnosis may lead to irreversible brain damage [3]. Several risk factors for the RPLS have been identified. They consist of acute hypertension, eclampsia, immunosuppressive therapy and renal disease, but the exact pathophysiology of RPLS is still unknown [1, 4]. Here, we describe three cases with clinical and imaging findings consistent with RPLS that occurred after surgery without any of the common risk factors. These