Endovascular stroke treatment does not preclude high thrombolysis rates.

BACKGROUND AND PURPOSE: In 1995 intravenous recombinant tissue plasminogen activator (IVRTPA) was the first reperfusion therapy to be approved in patients with acute ischaemic stroke (AIS). The significance and impact of IVRTPA in times of modern endovascular stroke treatment (EST) were analysed in a German academic stroke centre. METHODS: A retrospective observational cohort analysis of 1034 patients with suspected AIS presenting at the emergency department in 2014 was performed. Patients were evaluated for baseline characteristics, reperfusion procedures, IVRTPA eligibility, clinical outcome, symptomatic intracranial haemorrhage (sICH) and mortality. Data acquisition was part of an investigator-initiated, prospective and blinded end-point registry. RESULTS: In 718 (69%) patients the diagnosis of symptomatic AIS was confirmed. 419 (58%) patients presented within 4.5 h of symptom onset and of those 260 (62%) received reperfusion therapy (IVRTPA alone, n = 183; combination or bridging therapy, n = 60; EST alone, n = 17). Subtracting cases with absolute contraindications for IVRTPA resulted in an effective thrombolysis rate of 82%. sICH occurred in two patients treated with IVRTPA alone (1.1%). The median door-to-needle interval was 30 min. Fifty (17%) non-EST eligible AIS patients presenting within 4.5 h without absolute contraindications did not receive IVRTPA mainly due to mild or regressive symptoms. Most of these untreated IVRTPA eligible patients (82%) were discharged with a good clinical outcome (modified Rankin Scale ≤ 2). CONCLUSIONS: Intravenous recombinant tissue plasminogen activator remains the most frequently applied reperfusion therapy in AIS patients presenting within 4.5 h of onset in a tertiary stroke centre. An effective thrombolysis rate of over 80% can be achieved without increased rates of sICH.

HIV encephalopathy: glial activation and hippocampal neuronal apoptosis, but limited neural repair.

OBJECTIVES: HIV infection affects the central nervous system (CNS), frequently causing cognitive impairment. Hippocampal injury impedes the ability to transfer information into memory. Therefore, we aimed to examine neuronal injury and repair in the hippocampal formation in HIV encephalopathy. METHODS: We compared neuropathological findings in 14 autopsy cases after death from systemic complications of HIV infection and in 15 age-matched HIV-negative control cases after sudden death from nonneurological causes using immunohistochemistry. RESULTS: The density of apoptotic granule cells in the dentate gyrus was higher in HIV-infected than in control cases (P = 0.048). Proliferation of neural progenitor cells in the dentate gyrus was increased in HIV infection (P = 0.028), whereas the density of recently generated TUC-4 [TOAD (turned on after division)/Ulip/CRMP family 4]-expressing neurons in this region was not significantly elevated in HIV-infected cases (P = 0.13). HIV infection caused microglial activation and astrocytosis in the neocortex and hippocampal formation. Conversely, we were unable to detect more pronounced axonal injury in HIV-infected than in control cases. CONCLUSIONS: As in other infections involving the CNS, apoptosis of hippocampal neurons accompanied by microglial activation and astrocytosis is a prominent feature of HIV encephalopathy. The regenerative potential, assessed using the density of young neurons in the hippocampal dentate gyrus, in HIV infection appears to be lower than in acute bacterial meningitis and septic encephalitis.

Neurothrombectomy in acute ischaemic stroke: a prospective single-centre study and comparison with randomized controlled trials.

BACKGROUND AND PURPOSE: In the last few months five multicentre, randomized controlled trials (RCTs) unequivocally showed the superiority of mechanical thrombectomy in large vessel occlusion acute ischaemic stroke compared to systemic thrombolysis. Despite varying inclusion criteria and time intervals from onset to revascularization overall increases of good functional outcome between 55% and 81% were reported. However, only a minority of screened patients (approximately 1%) were eligible for intra-arterial (IA) therapy. METHODS: An investigator-initiated, single-centre, prospective and blinded end-point analysis was performed of 3123 consecutive patients with acute ischaemic stroke presenting between February 2010 and December 2014. RESULTS: One hundred and fifty-four patients [4.9%, age (years) mean (SD), median (interquartile range) 71.2 (±14), 74.7 (65.9-81.4)] met the inclusion criteria of sparse early ischaemic signs on initial standard cranial computed tomography (CT) (ASPECT score ≥7), large vessel occlusion in the anterior circulation on CT angiography and start of treatment within 6 h of onset of symptoms. After consensual interdisciplinary treatment decisions 130 patients (4.2%) received IA treatment - in the majority stent-assisted thrombectomy in combination with intravenous (IV) recombinant tissue plasminogen activator - and 24 patients (0.7%) standard IV thrombolysis. On 3 months' follow-up an overall significant improvement of disability (P = 0.05) as measured by the modified Rankin Scale was shown in favour of the IA treatment group. Good functional outcome was achieved in about twice as many patients (IA vs. IV, 41.2% vs. 21.2%; P = 0.078). CONCLUSION: By choosing pragmatic inclusion criteria state-of-the-art IA therapy of a specialized tertiary stroke centre can be safely applied under real-world conditions to a higher percentage of patients with similar success to the recently published RCTs.

Is there a gender gap in clinical neurosciences? A cross-sectional analysis of female participation in academic neurology, neurosurgery, and psychiatry.

Gender equality or the lack thereof is a constantly recurring theme. Here, we sought to provide an overview of the status with respect to the participation and leadership of female doctors in clinical neuroscience analyzing different disciplines (neurosurgery, neurology and psychiatry). A total of 1910 articles published in six representative journals (07-12/2020) were reviewed. Of these, 1327 were original research papers, 145 invited publications and 303 letters/comments. Out of a total of 15,080 authors, 4365 (29%) were women. The percentage of female authors was found to differ significantly between the different specialties (19% in neurosurgery, 39% in neurology and 45% in psychiatry). Women were last authors in 9.5% of the papers in neurosurgery, 29% in neurology and 39% in psychiatry Based on these findings, it can be concluded that gender disparity in academic neuroscience is quite conspicuous. Our review seeks to address the reasons behind this phenomenon in the context of new publications as well as various cultural and historical underpinnings.

Septic metastatic encephalitis: coexistence of brain damage and repair.

AIMS: Septic metastatic encephalitis (SME) arises from systemic bacterial infections and is a severe complication of sepsis with a high mortality. In this study, we examined the neuropathological findings in humans suffering from SME including white matter pathology and proliferation of neural precursor cells in the hippocampal dentate gyrus. METHODS: The brains of 10 autopsy cases with SME and 10 control cases after sudden death from non-neurological causes were studied by means of immunohistochemistry. RESULTS: We found diffuse axonal injury and demyelination in the frontal cortex (P = 0.01) as well as increased numbers of recently generated TUC-4 expressing neurones in the hippocampal dentate gyrus in SME cases (P = 0.01). The median density of apoptotic granule cells in the dentate gyrus also was higher in SME cases, the difference, however, failed to reach statistical significance (P = 0.25). CONCLUSION: The coexistence of degenerative processes predominantly in the neocortex and regenerative activity in the hippocampal formation known from bacterial meningitis also characterizes the pathology of SME.

Increased neuronal proliferation in human bacterial meningitis.

OBJECTIVE: Neurogenesis is increased in experimental models of bacterial meningitis. In this study, neurogenesis was examined after bacterial infection of the CNS, and after stroke and brain trauma in humans. METHODS: Brain sections of patients after death from bacterial meningitis, stroke, or brain trauma and from autopsy cases after death from nonneurologic diseases were investigated by immunohistochemistry. RESULTS: In the dentate gyrus, the density of proliferating cellular nuclear antigen-expressing cells was higher after bacterial meningitis compared to the control group (p = 0.0075). Furthermore, the number of cells expressing the immature neuronal marker proteins TUC-4 and doublecortin were increased in brain sections of patients after death from meningitis compared to control cases (p = 0.0067 and p = 0.045). After stroke and brain trauma, higher densities of proliferating cells were observed (p = 0.031 and p = 0.018), while an increase of TUC-4-expressing cells was detected after stroke only (p = 0.0012 and p = 0.47). CONCLUSIONS: The increased proliferation of neural progenitors suggests an endogenous mechanism in response to noxious stimuli. Stimulation of neurogenesis might help to alleviate the consequences of neuronal destruction in bacterial meningitis and other diseases of the brain.

Immunomodulatory properties of antibiotics.

There is growing evidence that certain antibiotics exert their beneficial effects not only by killing or inhibiting the growth of bacterial pathogens but also indirectly by immunomodulation. This review aims at giving an overview of the immunomodulatory properties of antibiotics in different diseases: The antiinflammatory properties of macrolides in chronic inflammatory pulmonary disorders were recognized more than 15 years ago and have been well documented in the last decade. Recent data suggest that several antibiotics such as tetracyclines and cephalosporins may have a beneficial immunomodulatory or neuroprotective effect on neuroimmunological and neurodegenerative diseases including multiple sclerosis and amyotrophic lateral sclerosis. Moreover, the non-bacteriolytic but bactericidal antibiotics rifampicin, clindamycin and aminoglycosides kill bacteria without releasing high quantities of proinflammtory cell wall components. The use of bactericidal, non-bacteriolytic protein synthesis inhibitors reduces mortality and long-term sequelae in experimental bacterial sepsis, plague and meningitis. Clinically, macrolides have been well established as an adjunctive treatment to beta-lactam antibiotics in pulmonary diseases. For other indications, appropriate clinical trials are necessary before using the immunomodulatory properties of antibiotics in clinical practice.