•Surgery is a promising therapeutic option in drug refractory epilepsy in older age.•Longer duration of epilepsy before surgery did not correlate with poorer outcome.•Patients of older age may be at ...greater risk for postoperative memory disturbances.•The risk for postoperative hygroma was higher in the older patient group.•In older patients, invasive EEG monitoring was as effective as in younger patients.
The incidence of epilepsy in older adults is growing, as does the incidence of comorbidities. Therefore, when it comes to epilepsy surgery in medically intractable epilepsy, age is often seen as a limiting factor. To investigate the outcome after epilepsy surgery in a population of older adults, we compared the benefit for patients aged 50–59 years with those aged 60 years and older in respect of efficacy and safety.
Patients aged ≥50 years with medically intractable epilepsy who underwent epilepsy surgery from 1990 to 2013 were selected from the database of a German epilepsy center. All of them received a standardised and detailed presurgical diagnostic evaluation. Follow-up included at least four scheduled visits with EEG, MRI and neuropsychological testing. Outcome was assessed using the Engel outcome scale.
79 patients aged between 50 and 67 years were followed-up for a median of 4.7 years (2–16 years). 68% of patients were free of disabling seizures (Engel class I, ≥60 years: 75%) and 58% were seizure-free (Engel class IA, ≥60 years: 70%). 90% of our patients suffered from temporal lobe epilepsy (TLE), 9% from frontal lobe epilepsy (FLE) and one occipital lobe epilepsy (OLE). After surgery, 9% discontinued or tapered their medication. Permanent surgical complications occurred in 10% of cases and transient neurological deficits were seen in 11%. Older patients had a higher risk for postoperative hygroma (≥60 years 15%; <60 years 8%) and were more prone to postoperative memory deficits (≥60 years 45%), especially after resection of the dominant temporal lobe. Verbal and figural memory testing did not differ significantly between the groups.
The results support the view that in selected older patients, epilepsy surgery shows equal or even higher success rates as compared to younger patients. However, patients of older age may be at greater risk for postoperative hygroma and memory deficits, especially after dominant temporal lobe resections.
Critical illness polyneuropathy (CIP) and critical illness myopathy (CIM) are major complications that occur in severely ill patients who require intensive care treatment. CIP and CIM affect the limb ...and respiratory muscles, and, as a consequence, they characteristically complicate weaning from the ventilator, increase the length of stay on the intensive care unit, and prolong physical rehabilitation. The basic pathophysiology of both disorders is complex and involves metabolic, inflammatory and bioenergetic alterations. It is unclear at present whether CIP and CIM are distinct entities, or whether they just represent different 'organ' manifestations of a common pathophysiological mechanism. This article provides an overview of the clinical and diagnostic features of CIP and CIM and discusses current pathophysiological and therapeutic concepts relating to these neuromuscular disorders.
Aneurysmal subarachnoid hemorrhage (SAH) may be complicated by delayed cerebral ischemia, which is a major cause of unfavorable clinical outcome and death in SAH-patients. Delayed cerebral ischemia ...is presumably related to the development of vasospasm triggered by the presence of blood in the basal cisterns. To date, oral application of the calcium antagonist nimodipine is the only prophylactic treatment for vasospasm recognized under international guidelines.In retrospective trials lumbar drainage of cerebrospinal fluid has been shown to be a safe and feasible measure to remove the blood from the basal cisterns and decrease the incidence of delayed cerebral ischemia and vasospasm in the respective study populations. However, the efficacy of lumbar drainage has not been evaluated prospectively in a randomized controlled trial yet.
This is a protocol for a 2-arm randomized controlled trial to compare an intervention group receiving early continuous lumbar CSF-drainage and standard neurointensive care to a control group receiving standard neurointensive care only. Adults suffering from a first aneurysmal subarachnoid hemorrhage whose aneurysm has been secured by means of coiling or clipping are eligible for trial participation. The effect of early CSF drainage (starting < 72 h after securing the aneurysm) will be measured in the following ways: the primary endpoint will be disability after 6 months, assessed by a blinded investigator during a personal visit or standardized telephone interview using the modified Rankin Scale. Secondary endpoints include mortality after 6 months, angiographic vasospasm, transcranial Doppler sonography (TCD) mean flow velocity in both middle cerebral arteries and rate of shunt insertion at 6 months after hospital discharge.
Here, we present the study design of a multicenter prospective randomized controlled trial to investigate whether early application of a lumbar drainage improves clinical outcome after aneurysmal subarachnoid hemorrhage.
The hyperintense acute reperfusion marker (HARM) on fluid-attenuated inversion recovery MRI is believed to be caused by gadolinium-based contrast agents crossing a disrupted blood-brain barrier. ...However, this hypothesis has never been directly verified in humans.
In this study, we analyzed cerebrospinal fluid samples of patients with HARM on imaging regarding the presence and concentration of gadolinium-based contrast agents.
Gadobutrol was found in concentrations of approximately 50 μmol/L. Using phantom MRI experiments, we demonstrate that the detected concentrations are consistent with the observed HARM imaging pattern.
Our study yields first direct evidence in humans that the imaging phenomenon HARM is indeed caused by leakage of gadolinium-based contrast agents into the cerebrospinal fluid.
Microcephaly is often caused by an impairment of the generation of neurons in the brain, a process referred to as neurogenesis. While most neurogenesis in mammals occurs during brain development, it ...thought to continue to take place through adulthood in selected regions of the mammalian brain, notably the hippocampus. However, the generality of neurogenesis in the adult brain has been controversial. While studies in mice and rats have provided compelling evidence for neurogenesis occurring in the adult rodent hippocampus, the lack of applicability in humans of key methods to demonstrate neurogenesis has led to an intense debate about the existence and, in particular, the magnitude of neurogenesis in the adult human brain. Here, we demonstrate the applicability of a powerful method to address this debate, that is, the in vivo labeling of adult human patients with 15 N-thymidine, a non-hazardous form of thymidine, an approach without any clinical harm or ethical concerns. 15 N-thymidine incorporation into newly synthesized DNA of specific cells was quantified at the single-cell level with subcellular resolution by Multiple-isotype imaging mass spectrometry (MIMS) of brain tissue resected for medical reasons. Two adult human patients, a glioblastoma patient and a patient with drug-refractory right temporal lobe epilepsy, were infused for 24 h with 15 N-thymidine. Detection of 15 N-positive leukocyte nuclei in blood samples from these patients confirmed previous findings by others and demonstrated the appropriateness of this approach to search for the generation of new cells in the adult human brain. 15 N-positive neural cells were easily identified in the glioblastoma tissue sample, and the range of the 15 N signal suggested that cells that underwent S-phase fully or partially during the 24 h in vivo labeling period, as well as cells generated therefrom, were detected. In contrast, within the hippocampus tissue resected from the epilepsy patient, none of the 2,000 dentate gyrus neurons analyzed was positive for 15 N-thymidine uptake, consistent with the notion that the rate of neurogenesis in the adult human hippocampus is rather low. Of note, the likelihood of detecting neurogenesis was reduced because of (i) the low number of cells analyzed, (ii) the fact that hippocampal tissue was explored that may have had reduced neurogenesis due to epilepsy, and (iii) the labeling period of 24 h which may have been too short to capture quiescent neural stem cells. Yet, overall, our approach to enrich NeuN-labeled neuronal nuclei by FACS prior to MIMS analysis provides a promising strategy to quantify even low rates of neurogenesis in the adult human hippocampus after in vivo 15 N-thymidine infusion. From a general point of view and regarding future perspectives, the in vivo labeling of humans with 15 N-thymidine followed by MIMS analysis of brain tissue constitutes a novel approach to study mitotically active cells and their progeny in the brain, and thus allows a broad spectrum of studies of brain physiology and pathology, including microcephaly.
Background and Purpose- In patients with ischemic stroke on therapy with vitamin K antagonists, stroke severity and clinical course are affected by the quality of anticoagulation at the time of ...stroke onset, but clinical data for patients using direct oral anticoagulants (DOACs) are limited. Methods- Data from our registry including all patients admitted with acute cerebral ischemia while taking oral anticoagulants for atrial fibrillation between November 2014 and October 2017 were investigated. The activity of vitamin K antagonists was assessed using the international normalized ratio on admission and categorized according to a threshold of 1.7. DOAC plasma levels were measured using the calibrated Xa-activity (apixaban, rivaroxaban, and edoxaban) or the Hemoclot-assay (dabigatran) and categorized into low (<50 ng/mL), intermediate (50-100 ng/mL), or high (>100 ng/mL). Primary objective was the association between anticoagulant activity and clinical and imaging characteristics. Results- Four hundred sixty patients were included (49% on vitamin K antagonists and 51% on DOAC). Patients on vitamin K antagonists with low international normalized ratio values had higher scores on the National Institutes of Health Stroke Scale and a higher risk of large vessel occlusion on admission. For patients on DOAC, plasma levels were available in 75.6% and found to be low in 49 (27.7%), intermediate in 41 (23.2%), and high in 87 patients (49.2%). Low plasma levels were associated with higher National Institutes of Health Stroke Scale scores on admission (low: 8 interquartile range, 3-15 versus intermediate: 4 1-11 versus high: 3 0-8; P<0.001) and higher risk of persisting neurological deficits or cerebral infarction on imaging (85.7% versus 75.6% versus 54.0%; P<0.001). Low DOAC plasma levels were an independent predictor of large vessel occlusion (odds ratio, 3.84 95% CI, 1.80-8.20; P=0.001). Conclusions- The activity of anticoagulation measured by specific DOAC plasma levels on admission is associated with stroke severity and presence of large vessel occlusion.
Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of unknown etiology that affects the central nervous system and can lead to neurological impairment. Our aim was to determine ...whether MS patients also show inflammatory changes in the oral cavity more frequently than healthy individuals. For this purpose, we examined plaque samples for various mediators and their correlation with clinical findings. A study group (MS) and a control group were examined and compared. The plaque samples were analyzed for the expression of interleukins (IL-2, -6, -10), matrix metalloproteinases (MMP-7, MMP-9), and a surface antigen CD90 by quantitative real-time PCR. The clinical parameters examined were the Mombelli plaque index; bleeding on probing (BOP) index; periodontal pocket depth; and decayed, missing, and filled tooth (DMFT) index. The expression of MMP9 was significantly (
= 0.035) higher in the control group. The expression of IL-2 was increased four-fold in the MS group; however, this difference was not statistically significant. The mean PD (
< 0.001) and BOP index (
= 0.029) values were increased in the study group. The clinical parameters of the BOP index and PD were significantly amplified in the MS patients. However, no causal relationship between the investigated inflammatory mediators and the clinical findings could be established in this case series.
Rationale and hypothesis
Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) is an effective and approved therapy for acute ischemic stroke within 4.5 h of onset except for ...USA, Canada, Croatia, and Moldovia with a current 3 h label. We hypothesized that ischemic stroke patients selected with significant penumbral mismatch on magnetic resonance imaging (MRI) at 4.5–9 h after onset of stroke will have improved clinical outcomes when given intravenous rt-PA (alteplase) compared to placebo.
Study design
ECASS-4: ExTEND is an investigator driven, phase 3, randomized, multi-center, double-blind, placebo-controlled study. Ischemic stroke patients presenting within 4.5 and 9 h of stroke onset, who fulfil clinical requirements (National Institutes of Health Stroke Score (NIHSS) 4–26 and pre-stroke modified Rankin Scale (mRS) 0–1) will undergo MRI. Patients who meet imaging criteria (infarct core volume <100 ml, perfusion lesion: infarct core mismatch ratio >1.2 and perfusion lesion minimum volume of 20 ml) additionally will be randomized to either rt-PA or placebo.
Study outcome
The primary outcome measure will be the categorical shift in the mRS at day 90. Clinical secondary outcomes will be disability at day 90 dichotomized as favorable outcome mRS 0–1 at day 90. Tertiary endpoints include reduction in the NIHSS by 11 or more points or reaching 0–1 at day 90, reperfusion and recanalization at 24 h post stroke as well as depression, life quality, and cognitive impairment at day 90. Safety endpoints will include symptomatic intracranial hemorrhage (ICH) and death.
One major objective of the St. Vincent Declaration was to reduce excess risk of stroke in people with diabetes mellitus. The aim of this study is to estimate the trend of incidence and relative risk ...of stroke in the diabetic and the non-diabetic populations in Germany over a 17-year period. We estimated age-sex standardised incidence rates of all stroke and ischaemic stroke in people with and without diabetes based on an ongoing prospective community-based stroke register covering 105,000 inhabitants. Time trends were analysed using Poisson regression. In total, 3,111 individuals (diabetes: 28.4%, men 46.9%, mean age 73.1 years (SD 13.2)) had a first stroke, 84.9% of which were ischaemic stroke. Among people with diabetes we observed a significant reduction in all stroke incidence by 1.5% per year (relative risk: 0.985; 95% confidence interval 0.972-0.9995) Likewise, this incidence tended to decrease for ischaemic stroke by 1% per year (0.993; 0.979-1.008). In contrast, the incidence rate for all stroke remained nearly stable among people without diabetes (1.003; 0.993-1.013) and for ischaemic stroke (1.002; 0.991-1.013). The relative risk comparing diabetic and non-diabetic population decreased for all stroke (two percent annual reduction) but not for ischaemic stroke. Time trends were similar for both sexes regarding all and ischaemic strokes. We found a reduction in risk of stroke in the diabetic population while this rate did not materially change in the non-diabetic population.
Background and Purpose:
The optimal acute management of patients with large vessel occlusion (LVO) and minor clinical deficits on admission National Institutes of Health Stroke Scale (NIHSS) ≤ 4 ...remains to be elucidated. The aim of the present study was to investigate the prognostic factors and therapeutic management of those patients.
Methods:
In this retrospective cohort study, we investigated (1) all patients with acute ischemic stroke due to an LVO who underwent mechanical thrombectomy (MT) and (2) all patients with minor clinical deficits (NIHSS ≤ 4) on admission due to an LVO between January 2013 and December 2016 at the University Medical Center Erlangen. We dichotomized management of patients with minor deficits treated with MT for analysis according to immediate mechanical thrombectomy (IT) and initial medical management with rescue intervention (MM) in case of secondary deterioration. Primary endpoints were secondary deterioration, in-hospital mortality, and functional outcome on day 90 (dichotomized modified Rankin Scale 0–2: favorable, 3–6: poor).
Results:
Two hundred twenty-three patients (83% with anterior circulation stroke, 13 (6%) with minor deficits) treated with MT and 88 patients with minor deficits due to LVO 13 (15%) treated with MT were included. Secondary deterioration (
n
= 19) was independently associated with poor outcome in patients with minor deficits and LVO odds ratio (OR), 0.060; 95% confidence interval (CI), 0.013–0.280, which in turn was associated with the occlusion site especially M1 occlusion: 11 (58%) vs. 3 (4%) in patients without secondary deterioration,
p
< 0.0001. IT (
n
= 8) was associated with a lower intrahospital mortality compared to MM (
n
= 5; 13 vs. 80%; OR, 0.036; 95% CI, 0.002–0.741). Seven of eight patients with IT survived until discharge, with 29% showing a favorable functional outcome on day 90.
Conclusions:
Secondary deterioration is associated with poor outcome in patients with LVO and minor deficits, which in turn was associated with occlusion site. Future randomized controlled trials should assess whether selected patients, depending on occlusion site and associated characteristics, may benefit from MT.
PDF
