Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disease of the CNS, which develops almost exclusively in immunocompromised patients and is caused by JC virus (JCV), a common polyomavirus. 1 So far, treatment efficacy is only modest if the compromised immune system cannot be restored. 2-4 A potential treatment target is the programmed cell death protein 1 (PD-1) whose expression on CD4 + and CD8 + T lymphocytes has been shown to be elevated in patients with PML. Moreover, blocking of the PD-1 receptor resulted in increased JCV-specific T-cell immune response in a subgroup of patients with PML. 5 Recently, pembrolizumab, a humanized monoclonal antibody directed against PD-1, was reported for the first time to be a promising option for PML with treatment responses in 6 of 9 patients. 6,7 Here, we describe another patient with PML who did not benefit from treatment with pembrolizumab.

IntroductionSo far there is no uniform, commonly accepted diagnostic and therapeutic algorithm for patients with embolic stroke of undetermined source (ESUS). Recent clinical trials on secondary stroke prevention in ESUS did not support the use of oral anticoagulation. As ESUS comprises heterogeneous subgroups including a wide age-range, concomitant patent foramen ovale (PFO), and variable probability for atrial fibrillation (AF), an individualised approach is urgently needed. This prospective registry study aims to provide initial data towards an individual, structured diagnostic and therapeutic approach in ESUS patients.Methods and analysisThe open-label, investigator-initiated, prospective, single-centre, observational registry study (Catch-up-ESUS) started in 01/2018. Consecutive ESUS patients ≥18 years who give informed consent are included and will be followed up for 3 years. Stratified by age <60 or ≥60 years, the patients are processed following a standardised diagnostic and treatment algorithm with an interdisciplinary design involving neurologists and cardiologists. Depending on the strata, patients receive a transesophageal echocardiogram; all patients receive an implantable cardiac monitor. Patients <60 years with PFO and without evidence of concomitant AF are planned for PFO closure within 6 months after stroke. The current diagnostic and therapeutic workup of ESUS patients requires improvement by both standardisation and a more individualised approach. Catch-up-ESUS will provide important data with respect to AF detection and PFO closure and will estimate stratified stroke recurrence rates after ESUS.Ethics and disseminationThe study has been approved by the responsible ethics committee at the Ludwig Maximilian University, Munich, Germany (project number 17–685). Catch-Up-ESUS is conducted in accordance with the Declaration of Helsinki. All patients will have to give written informed consent or, if unable to give consent themselves, their legal guardian will have to provide written informed consent for their participation. The first observation period of the registry study is 1 year, followed by the first publication of the results including follow-up of the patients. Further publications will be considered according the predefined individual follow-up dates of the stroke patients up to 36 months.Trial registration numberClinicaltrialsregister.gov registry (NCT03820375).

ObjectiveTo determine feasibility and safety of stroke care organization within our Neurovascular Network of Southwest Bavaria (NEVAS) in a rural area with distances of up to 100 kilometers, we compared patients who underwent mechanical thrombectomy (MT) in large vessel occlusion admitted directly to our center (direct to center [DTC]) to patients who were transferred for MT via NEVAS (drip and ship [DS]).MethodsThis is a retrospective analysis of prospectively collected data of all MT patients between January 2015 and May 2018. Successful recanalization was defined as a thrombolysis in cerebral infarction score of 2b-3. Symptomatic intracerebral hemorrhage (sICH) was defined according to European Cooperative Acute Stroke Study 3. Modified Rankin Scale (mRS) score of 0–2 at 3 months indicated good outcome.ResultsMT was performed in 410 patients: 221 DTC and 189 DS. Median NIH Stroke Scale (NIHSS) score was 16 and premorbid mRS score was 0. Thrombolysis was applied in 62.2% with the same time from symptom onset in both groups (94.5 vs 95 minutes). Successful recanalization (79.3% vs 77.8%) and NIHSS score reduction from admission to discharge (16–7 vs 17–6) were comparable. Time delay from onset to revascularization was 96 minutes in DS (212 vs 308 minutes, p = 0.001). At follow-up, DTC patients had a trend to better outcome (33.5% vs 24.3%, p = 0.056). Neither sICH (6.3% vs 5.9%, p = 0.840) nor mortality (31.2% vs 34.4%, p = 0.387) differed between the groups.ConclusionDS patients benefit from MT without relevant safety concerns, but with a trend to unfavorable outcome compared to DTC patients. These results suggest that DS is suitable to provide MT in rural areas where DTC is not possible.