OBJECTIVE:We assessed the therapeutic potential of the plasma-cell-depleting proteasome inhibitor bortezomib in severe and therapy-refractory cases of anti–NMDA receptor (anti-NMDAR) encephalitis.
...METHODS:Five severely affected patients with anti-NMDAR encephalitis with delayed treatment response or resistance to standard immunosuppressive and B-cell-depleting drugs (corticosteroids, IV immunoglobulins, plasma exchange, immunoadsorption, rituximab, cyclophosphamide) who required medical treatment and artificial ventilation on intensive care units were treated with 1–6 cycles of 1.3 mg/m bortezomib. Occurrence of adverse events was closely monitored.
RESULTS:Bortezomib treatment showed clinical improvement or disease remission, which was accompanied by a partial NMDAR antibody titer decline in 4 of 5 patients. With respect to disease severity, addition of bortezomib to the multimodal immunosuppressive treatment regimen was associated with an acceptable safety profile.
CONCLUSIONS:Our study identifies bortezomib as a promising escalation therapy for severe and therapy-refractory anti-NMDAR encephalitis.
CLASSIFICATION OF EVIDENCE:This retrospective case series provides Class IV evidence that bortezomib reduces antibody titers and improves the clinical course of patients with severe anti-NMDAR encephalitis.
Hepatitis E–induced severe myositis Mengel, Annerose M.; Stenzel, Werner; Meisel, Andreas ...
Muscle & nerve,
February 2016, 2016-Feb, 2016-02-00, 20160201, Letnik:
53, Številka:
2
Journal Article
Recenzirano
ABSTRACT
Introduction
Hepatitis E virus (HEV) is endemic in Asian and African countries but is rarely reported in Western countries. Although there are some prominent neurological manifestations, HEV ...is rarely recognized by neurologists.
Methods
This is a case report of myositis induced by HEV.
Results
We report the life‐threatening case of a 57‐year‐old man with flaccid tetraparesis due to myositis, acute hepatitis, and renal failure caused by HEV infection. Muscle biopsy revealed scattered myofiber necrosis with a diffuse, mild lymphomonocytic infiltrate in the endomysium and perimysium. Because the patient suffered from an acute HEV infection with a rapidly progressive course of severe myopathy, we started ribavirin treatment. He recovered partially within 3 weeks and recovered fully within 6 months.
Conclusion
This case highlights a neurological manifestation of endemic HEV infection with severe myositis in a patient with alcoholic chronic liver disease. Ribavirin treatment is effective in severe HEV infection and may also lead to rapid neurological recovery. Muscle Nerve 53: 317–320, 2016
Delirium is recognized as a severe complication of coronavirus-disease-2019 (COVID-19). COVID-19-associated delirium has been linked to worse patient outcomes and is considered to be of ...multifactorial origin. Here we sought to evaluate the incidence and risk factors of delirium in hospitalized COVID-19 patients, along with its impact on clinical outcome.
Consecutive adult COVID-19 patients admitted to a tertiary academic referral hospital between March 1st and December 31st, 2020 were included. Potential risk factors for delirium were evaluated, including: age, gender, disease severity (as per the highest WHO grading reached during admission), laboratory parameters for infection and renal function (as per their most extreme values), and presence of comorbidities. To assess the relative strength of risk factors for predicting the occurrence of delirium, we performed a random-forest survival analysis.
347 patients with positive COVID-19 PCR test and median age 68.2 IQR 55.5, 80.5 years were included. Of those, 79 patients (22.8%) developed delirium, 81 (23.3%) were transferred to ICU, 58 (16.7%) died. 163 (73.8%) patients were discharged home, 13 (5.9%) to another hospital, 32 (14.5%) to nursing homes, 13 (5.9%) to rehabilitation with an overall median admission-to-discharge time of 53 IQR 14, 195 days. The strongest predictors for the occurrence of delirium were blood urea nitrogen (minimal depth value (MD): 3.33), age (MD: 3.75), disease severity (as captured by WHO grading; MD: 3.93), leukocyte count (MD: 4.22), the presence of a neurodegenerative history (MD: 4.43), ferritin (MD: 4.46) and creatinine (MD: 4.59) levels.
The risk of delirium in COVID-19 can be stratified based on COVID-19 disease severity and-similar to delirium associated with other respiratory infections-the factors advanced age, neurodegenerative disease history, and presence of elevated infection and renal-retention parameters. Screening for these risk factors may facilitate early identification of patients at high-risk for COVID-19-associated delirium.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Within the past 10 years, immune mechanisms associated with acute ischemic stroke (AIS) have been brought into focus, but data on B cell activation and intrathecal Ig production is still scarce. In ...this study, we determined the prevalence of an elevated IgG index, positive oligoclonal bands (OCBs) and chemokine C-X-C motif ligand 13 (CXCL13) levels in the cerebrospinal fluid (CSF) as markers of intrathecal IgG synthesis and B cell activation in patients with AIS.
In a retrospective study we analyzed the cerebrospinal fluid (CSF) from 212 patients with AIS from December 2013 to May 2018 assessing intrathecal Ig synthesis, OCBs and CXCL13 concentrations.
Overall, 5.7% (12/212) of AIS patients showed an intrathecal IgG synthesis, 0.5% (1/212) with isolated elevated IgG index, 5.2% (7/136) isolated positive OCBs and 2.9% (4/136) both elevated IgG index and positive OCBs. CXCL13 levels were elevated in 3.6% (3/83) of the patients. Approximately one third of these patients had simultaneously chronic inflammatory CNS disease (multiple sclerosis, neuromyelitis optica spectrum disorder, neurosarcoidosis). There was no significant association between CSF findings and stroke characteristics including vascular territory, localization, volume, etiology, acute treatment, or blood-brain barrier dysfunction. Intrathecal IgG synthesis was more common in patients with prior stroke. Longitudinal CSF analysis did not reveal any newly-occurring, but instead mostly persistent or even disappearing intrathecal IgG synthesis after AIS.
We found no evidence of a relevant B cell recruitment and intrathecal IgG synthesis in patients with AIS. In fact, the occurrence of intrathecal IgG synthesis was associated with concurrent chronic inflammatory CNS disease or previous stroke. Consequently, in patients with first-ever AIS and intrathecal IgG synthesis, physicians should search for concomitant inflammatory CNS disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and aims:
Intravenous thrombolysis (IVT) is standard of care for disabling acute ischemic stroke (AIS) within a time window of ⩽ 4.5 h. Some AIS patients cannot be treated with IVT due to ...limiting contraindications, including heparin usage in an anticoagulating dose within the past 24 h or an elevated activated prothrombin time (aPTT) > 15 s. Protamine is a potent antidote to unfractionated heparin.
Objectives:
The objective of this study was to investigate the safety and efficacy of IVT in AIS patients after antagonization of unfractionated heparin with protamine.
Methods:
Patients from our stroke center (between January 2015 and September 2021) treated with IVT after heparin antagonization with protamine were analyzed. National Institutes of Health Stroke Scale (NIHSS) was used for stroke severity and modified Rankin Scale (mRS) for outcome assessment. Substantial neurological improvement was defined as the difference between admission and discharge NIHSS of ⩾8 or discharge NIHSS of ⩽1. Good outcome at follow-up after 3 months was defined as mRS 0–2. Safety data were obtained for mortality, symptomatic intracerebral hemorrhage (sICH), and for adverse events due to protamine. Second, a systematic review was performed searching PubMed and Scopus for studies and case reviews presenting AIS patients treated with IVT after heparin antagonization with protamine. The search was limited from January 1, 2011 to September 29, 2021. Furthermore, we conducted a propensity score matching comparing protamine-treated patients to a control IVT group without protamine (ratio 2:1, match tolerance 0.2).
Results:
A total of 16 patients, 5 treated in our hospital and 11 from literature, 65.2 ± 13.1 years, 37.5% female, median premorbid mRS (pmRS) 1 (IQR 1, 4) treated with IVT after heparin antagonization using protamine were included and compared to 31 IVT patients 76.2 ± 10.9 years, 45% female, median pmRS 1 (IQR 0, 2). Substantial neurological improvement was evident in 68.8% of protamine-treated patients versus 38.7% of control patients (p = 0.028). Good clinical outcome at follow-up was observed in 56.3% versus 58.1% of patients (p = 0.576). No adverse events due to protamine were reported, one patient suffered sICH after secondary endovascular thrombectomy of large vessel occlusion. Mortality was 6.3% versus 22.6% (p = 0.236).
Conclusion:
IVT after heparin antagonization with protamine seems to be safe and, prospectively, may extend the number of AIS patients who can benefit from reperfusion treatment using IVT. Further prospective registry trials would be helpful to further investigate the clinical applicability of heparin antagonization.
Cardiac myxoma (CM) is the most frequent, cardiac benign tumor and is associated with enhanced risk for cerebrovascular events (CVE). Although surgical CM excision is the only curative treatment to ...prevent CVE recurrence, in recent reports conservative treatment with antiplatelet or anticoagulant agents in high-risk patients with CM-related CVE has been discussed.
Case records at the University Hospital of Tübingen between 2005 and 2017 were screened to identify patients with CM-related CVE. Clinical features, brain and cardiac imaging findings, histological reports, applied treatments and long-term neurological outcomes were assessed.
52 patients with CM were identified and among them, 13 patients with transient ischemic attack, ischemic stroke or retinal ischemia were included to the (to our knowledge) largest reported retrospective study of CM-related CVE. In all identified patients, CVE was the first manifestation of CM; 61% suffered ischemic stroke, 23% transient ischemic attack and 15% retinal ischemia. In 46% of the patients, CVE occurred under antiplatelet or anticoagulation treatment, while 23% of the patients developed recurrent CVE under bridging-antithrombotic-therapy prior to CM surgical excision. Prolonged time interval between CVE and CM-surgery was significantly associated with CVE recurrence (
= 0.021). One patient underwent i.v. thrombolysis, followed by thrombectomy, with good post-interventional outcome and no signs of hemorrhagic transformation.
Our results suggest that antiplatelet or anticoagulation treatment is no alternative to cardiac surgery in patients presenting with CM-related CVE. We found significantly prolonged time-intervals between CVE and CM surgery in patients with recurrent CVE. Therefore, we suggest that the waiting- or bridging-interval with antithrombotic therapy until curative CM excision should be kept as short as possible. Based on our data and review of the literature, we suggest that in patients with CM-related CVE, i.v. thrombolysis and/or endovascular interventions may present safe and efficacious acute treatments.
Purpose
Patients with Moyamoya Angiopathy (MMA) require hemodynamic evaluation to assess the risk of stroke. Assessment of cerebral blood flow with
15
Owater PET and acetazolamide challenge is the ...diagnostic standard for the evaluation of the cerebral perfusion reserve (CPR). Estimation of the cerebrovascular reactivity (CVR) by use of breath-hold-triggered fMRI (bh-fMRI) as an index of CPR has been proposed as a reliable and more readily available approach. Recent findings suggest the use of resting-state fMRI (rs-fMRI) which requires minimum patient compliance. The aim of this study was to compare rs-fMRI to bh-fMRI and
15
Owater PET in patients with MMA.
Methods
Patients with MMA underwent rs-fMRI and bh-fMRI in the same MRI session. Maps of the CVR gained by both modalities were compared retrospectively by calculating the correlation between the mean CVR of 12 volumes of interest. Additionally, the rs-maps of a subgroup of patients were compared to CPR-maps gained by
15
Owater PET.
Results
The comparison of the rs-maps and the bh-maps of 24 patients revealed a good correlation (Pearson’s
r
= 0.71 ± 0.13; preoperative patients: Pearson’s
r
= 0.71 ± 0.17; postoperative patients: Pearson’s
r
= 0.71 ± 0.11). The comparison of 7 rs-fMRI data sets to the corresponding
15
Owater PET data sets also revealed a high level of agreement (Pearson’s
r
= 0.80 ± 0.19).
Conclusion
The present analysis indicates that rs-fMRI might be a promising non-invasive method with almost no patient cooperation needed to evaluate the CVR. Further prospective studies are required.
It is believed that stroke occurring due to posterior circulation large vessel occlusion (PCLVO) and that occurring due to anterior circulation large vessel occlusion (ACLVO) differ in terms of their ...pathophysiology and the outcome of their acute management in relation to endovascular mechanical thrombectomy (MT). Limited sample size and few randomized controlled trials (RCTs) with respect to PCLVO make the safety and efficacy of MT, which has been confirmed in ACLVO, difficult to assess in the posterior circulation. We therefore conducted a meta-analysis to study to which extent MT in PCLVO differs from ACLVO.
We searched the databases PubMed, Cochrane, and EMBASE for studies published between 2010 and January 2021, with information on risk factors, safety, and efficacy outcomes of MT in PCLVO vs. ACLVO and conducted a systematic review and meta-analysis; we compared baseline characteristics, reperfusion treatment profiles including rates of intravenous thrombolysis (IVT) and onset-to-IVT and onset-to-groin puncture times, recanalization success Thrombolysis In Cerebral Infarction scale (TICI) 2b/3, symptomatic intracranial hemorrhage (sICH), and favorable functional outcome modified Rankin Score (mRS) 0-2 and mortality at 90 days.
Sixteen studies with MT PCLVO (1,172 patients) and ACLVO (7,726 patients) were obtained from the search. The pooled estimates showed higher baseline National Institutes of Health Stroke Scale (NIHSS) score (SMD 0.32, 95% CI 0.15-0.48) in the PCLVO group. PCLVO patients received less often IVT (OR 0.65, 95% CI 0.53-0.79). Onset-to-IVT time (SMD 0.86, 95% CI 0.45-1.26) and onset-to-groin puncture time (SMD 0.59, 95% CI 0.33-0.85) were longer in the PCLVO group. The likelihood of obtaining successful recanalization and favorable functional outcome at 90 days was comparable between the two groups. PCLVO was, however, associated with less sICH (OR 0.56, 95% CI 0.37-0.85) but higher mortality (OR 1.92, 95% CI 1.46-2.53).
This meta-analysis indicates that MT in PCLVO may be comparably efficient in obtaining successful recanalization and 90 day favorable functional outcome just as in ACLVO. Less sICH in MT-treated PCLVO patients might be the result of the lower IVT rate in this group. Higher baseline NIHSS and longer onset-to-IVT and onset-to-groin puncture times may have contributed to a higher 90 day mortality in PCLVO patients.
Over 50% of acute ischemic stroke (AIS) patients present with minor neurological deficits, and optimal treatment is still debated. The randomized PRISMS trial did not show beneficial effects of ...intravenous thrombolysis (IVT) in unselected patients with minor stroke and non-disabling neurological deficits.
The study aimed to evaluate if AIS patients with minor stroke may benefit from computed-tomography-perfusion (CTP)-guided IVT. The primary endpoint was good functional outcomes, defined as a modified Rankin Scale score of 0-2 at 90 days.
AIS patients with a NIHSS of ≤5 presenting within 4.5 h underwent multimodal CT-imaging including CTP. CTP mismatch was defined as hypoperfusion on CTP with time-to-peak delay >6 s without corresponding hypoperfusion in cerebral blood volume. IVT decision was left to the attending stroke physicians. Patients with large vessel occlusion (LVO) and absolute contraindications to IVT were excluded.
In total, 267 consecutive patients were included mean age: 72 ± 14 years, 45.3% female patients, 75.3% received IVT, median NIHSS on admission: 3 (IQR 2, 4). CTP mismatch was detected in 41.8% of IVT- treated patients (IVT+) and 28.8% of standard treatment patients (IVT-) (
= 0.06). IVT+ had favorable outcomes at 90 days compared to IVT- (
= 0.006), but no interaction with an existing CTP mismatch was detected (OR
: 1.676; 95% CI: 0.644-4.364). No symptomatic intracranial hemorrhage according to ECASS-III criteria occurred.
Although selected AIS patients with minor stroke may benefit from IVT, CTP mismatch does not correlate with functional outcomes. No benefit from CTP mismatch in guiding IVT was detected in patients without LVO presenting with minor neurological deficits.
Interhospital transfer for endovascular treatment (EVT) within neurovascular networks might result in transfer of patients who will not undergo EVT (futile transfer). Limited evidence exists on ...factors associated with the primary patient selection for interhospital transfer from primary stroke centers (PSCs) to comprehensive stroke centers (CSCs), or EVT-workflow parameters that may render a transfer futile.
A prospective, registry-based study was performed between July 1, 2017 and June 30, 2018, at a hub-and-spoke neurovascular network in southwest Germany, comprising 12 referring PSCs and one designated CSC providing round-the-clock EVT at the University Hospital Tübingen. Patients with acute ischemic stroke due to suspected large artery occlusion (LAO) were included upon emergency interhospital transfer inquiry (ITI).
ITI was made for 154 patients, 91 (59%) of whom were transferred to the CSC. Non-transferred patients (41%) had significantly higher premorbid modified Rankin scale scores (mRS) compared to transferred patients median (IQR): 2 (1-3) vs. 0 (0-1),
< 0.001. Interhospital transfer was denied due to: distal vessel occlusion (44.4%), or non-verifiable LAO (33.3%) in computed tomography angiography (CTA) upon teleconsultation by CSC neuroradiologists; limited Stroke-Unit or ventilation capacity (9.5%), or limited neuroradiological capacity at the CSC (12.7%). The CT-to-ITI interval was significantly longer in patients denied interhospital transfer median (IQR): 43 (29-56) min compared to transferred patients 29 (15-55),
= 0.029. No further differences in EVT-workflow, and no differences in the 3-month mRS outcomes were noted between non-transferred and transferred patients median (IQR): 2 (0-5) vs. 3 (1-4),
= 0.189. After transfer to the CSC, 44 (48%) patients underwent EVT. The Alberta stroke program early CT score ORadj (95% CI): 1.786 (1.573-2.028),
< 0.001 and the CT-to-ITI interval 0.994 (0.991-0.998),
= 0.001 were significant predictors of the likelihood of EVT performance.
Our findings show that hub-and-spoke neurovascular network infrastructures efficiently enable access to EVT to patients with AIS due to LAO, who are primarily admitted to PSCs without on-site EVT availability. As in real-world settings optimal allocation of EVT resources is warranted, teleconsultation by experienced endovascular interventionists and prompt interhospital-transfer-inquiries are crucial to reduce the futile transfer rates and optimize patient selection for EVT within neurovascular networks.
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