NORSE seasonality may vary geographically in adults.

The mechanisms causing new onset refractory status epilepticus (NORSE) are often unknown. Recently, a seasonal variation with NORSE peaking during the summer was described in a mixed cohort of adults and children why we here studied the seasonal variation in a Danish status epilepticus (SE) cohort. This retrospective cohort study comprised SE patients aged ≥18 diagnosed and treated 2008-2017 at the Odense University Hospital. Clinical characteristics and seasonality of patients fulfilling the diagnostic criteria for NORSE were compared with patients with refractory SE (RSE) due to other reasons and with the seasonal variation of autoantibodies associated with autoimmune encephalitis in the Danish autoimmune encephalitis register. In this cohort, 26 patients met NORSE criteria. As compared to RSE patients not fulfilling NORSE criteria (n = 152), NORSE patients were more likely to have symptoms of systemic inflammation (C-reactive protein concentrations ≥10 mg/L or fever ≥38°C) at admission; nine fulfilled the criteria for febrile infection related epilepsy syndrome (FIRES). In contrast to the even seasonal distribution of patients with RSE not fulfilling the NORSE criteria, admissions due to NORSE peaked during the winter (46.1%, p = 0.04 as compared to non-NORSE RSE); six out of nine FIRES episodes occurred in the winter season. The seasonal variation was not explained by a seasonal variation of the detection rates of autoantibodies associated with autoimmune encephalitis (incl. NMDAR, LGI1, CASPR2, GABAR, GFAP) in a Danish nationwide register (n = 259). In conclusion, we confirm the seasonality of NORSE in a Danish cohort, however, with a peak during winter suggesting a geographical variation not solely explained by autoimmune encephalitis associated with known autoantibodies. PLAIN LANGUAGE SUMMARY: The study investigated the seasonal patterns of new-onset refractory status epilepticus (NORSE), i.e. severe seizures that occur without an obvious cause and require very intensive treatment. In contrast to the previously observed peak frequency in summer, this Danish study found that NORSE cases peak in winter. Furthermore, the seasonal variation in NORSE cases was not found to be associated with autoimmune encephalitis caused by known autoantibodies. Together with the high rate of patients showing symptoms of systemic inflammation compared to other status epilepticus patients, the data suggest a link between misdirected immune system responses and NORSE. The study can therefore help in the further search for the currently unknown causes of NORSE.

Tick-borne encephalitis as a trigger for anti-N-Methyl-d-aspartate receptor encephalitis.

Tick Borne Encephalitis (TBE) is endemic to an increasing number of countries and is a common cause of meningoencephalitis in Europe and Asia making any potential complications of the disease increasingly relevant to clinicians. We present, what is to our knowledge, the second reported case of N-methyl-d-aspartate receptor (NMDAR) encephalitis following Tick Borne Encephalitis (TBE) in a 47-year-old Lithuanian man. The case provides further evidence of TBE being a possible trigger of NMDAR encephalitis and highlights the importance of being aware of symptoms of autoimmune encephalitis in patients with infectious encephalitis.

Comparison of international guideline recommendations for the diagnosis of pulmonary embolism.

Pulmonary embolism is one of the leading causes of death due to cardiovascular disease. Timely diagnosis is crucial, but challenging, as the clinical presentation of pulmonary embolism is unspecific and easily mistaken for other common medical emergencies. Clinical prediction rules and D-dimer measurement allow stratification of patients into groups of expected prevalence and are key elements in adequate selection of patients for diagnostic imaging; however, the strengths and weaknesses of the multiple proposed prediction rules, when to measure D-dimer, and which cutoff to apply might be elusive to a significant proportion of physicians. 13 international guidelines authored by medical societies or expert author groups provide recommendations on facets of the diagnostic investigations in suspected pulmonary embolism, some of which are hallmarked by pronounced heterogeneity. This Review summarises key recommendations of each guideline, considers the most recent evidence on the topic, compares guideline recommendations on each facet of the diagnosis of pulmonary embolism, and provides a synthesis on the most common recommendations.

Diagnostic accuracy of focused deep venous, lung, cardiac and multiorgan ultrasound in suspected pulmonary embolism: a systematic review and meta-analysis.

OBJECTIVE: To determine the diagnostic accuracy of point-of-care ultrasound in suspected pulmonary embolism. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, Embase, CINAHL and Cochrane library were searched on 2 July 2020 with no restrictions on the date of publication. Subject headings or subheadings combined with text words for the concepts of pulmonary embolism, ultrasound and diagnosis were used. ELIGIBILITY CRITERIA AND DATA ANALYSIS: Eligible studies reported sensitivity and specificity of deep venous, lung, cardiac or multiorgan ultrasound in patients with suspected pulmonary embolism, using an adequate reference-test. Prospective, cross-sectional and retrospective studies were considered for eligibility. No restrictions were made on language. Studies were excluded if a control group consisted of healthy volunteers or if transesophageal or endobronchial ultrasound was used. Risk of bias was assessed using quality assessment of diagnostic accuracy studies-2. Meta-analysis of sensitivity and specificity was performed by construction of hierarchical summary receiver operator curves. I2 was used to assess the study heterogeneity. MAIN OUTCOME MEASURES: The primary outcome was overall sensitivity and specificity of reported ultrasound signs, stratified by organ approach (deep venous, lung, cardiac and multiorgan). Secondary outcomes were stratum-specific sensitivity and specificity within subgroups defined by pretest probability of pulmonary embolism. RESULTS: 6378 references were identified, and 70 studies included. The study population comprised 9664 patients with a prevalence of pulmonary embolism of 39.9% (3852/9664). Risk of bias in at least one domain was found in 98.6% (69/70) of included studies. Most frequently, 72.8% (51/70) of studies reported >24 hours between ultrasound examination and reference test or did not disclose time interval at all. Level of heterogeneity ranged from 0% to 100%. Most notable ultrasound signs were bilateral compression of femoral and popliteal veins (22 studies; 4708 patients; sensitivity 43.7% (36.3% to 51.4%); specificity 96.7% (95.4% to 97.6%)), presence of at least one hypoechoic pleural-based lesion (19 studies; 2134 patients; sensitivity 81.4% (73.2% to 87.5%); specificity 87.4% (80.9% to 91.9%)), D-sign (13 studies; 1579 patients; sensitivity 29.7% (24.6% to 35.4%); specificity 96.2% (93.1% to 98.0%)), visible right ventricular thrombus (5 studies; 995 patients; sensitivity 4.7% (2.7% to 8.1%); specificity 100% (99.0% to 100%)) and McConnell's sign (11 studies; 1480 patients; sensitivity 29.1% (20.0% to 40.1%); specificity 98.6% (96.7% to 99.4%)). CONCLUSION: Several ultrasound signs exhibit a high specificity for pulmonary embolism, suggesting that implementation of ultrasound in the initial assessment of patients with suspected pulmonary embolism may improve the selection of patients for radiation imaging. PROSPERO REGISTRATION NUMBER: CRD42020184313.

[Antibodies in patients with chronic inflammatory demyelinating polyneuropathy].

Recent studies have identified specific immunoglobulin (Ig) G4 antibodies against the paranodal proteins neurofascin 155 and contactin 1 in subgroups of patients with chronic inflammatory demyelinating polyneuropathy (CIDP). These patients present with distinct clinical phenotypes and poor response to first-line therapy with intravenous Ig. Detection of these antibodies in patients with CIDP has diagnostic, prognostic, and therapeutic implications. This review summarises the current knowledge on clinical characteristics, pathogenesis and treatment of these patients.