The use of TNF-α antagonists in tuberculosis to control severe paradoxical reaction or immune reconstitution inflammatory syndrome: a case series and literature review.

Paradoxical reaction (PR) and immune reconstitution inflammatory syndrome (IRIS) are common complications of tuberculosis treatment. Corticosteroids are first-line treatment for severe PR or IRIS, particularly neurological. We report four cases of severe PR or IRIS during tuberculosis treatment who required TNF-α antagonists, and identified 20 additional cases through literature review. They were 14 women and 10 men, with a median age of 36 years (interquartile range, 28-52). Twelve were immunocompromised before tuberculosis: untreated HIV infection (n=6), or immunosuppressive treatment (TNF-α antagonists, n=5; tacrolimus, n=1). Tuberculosis was mostly neuromeningeal (n=15), pulmonary (n=10), lymph node (n=6), and miliary (n=6), multi-susceptible in 23 cases. PR or IRIS started after a median time of 6 weeks (IQR, 4-9) following anti-tuberculosis treatment start, and consisted primarily of tuberculomas (n=11), cerebral vasculitis (n=8), and lymphadenitis (n=6). First-line treatment of PR or IRIS was high-dose corticosteroids in 23 cases. TNF-α antagonists were used as salvage treatment in all cases, with infliximab (n=17), thalidomide (n=6), and adalimumab (n=3). All patients improved, but 6 had neurological sequelae, and 4 had TNF-α antagonist-related severe adverse events. TNF-α antagonists are safe and effective as salvage or corticosteroid-sparing therapeutic for severe PR or IRIS during tuberculosis treatment.

Infectious encephalitis in elderly patients: a prospective multicentre observational study in France 2016-2019.

PURPOSE: Data on encephalitis in elderly patients are scarce. We aimed to describe the characteristics, aetiologies, management, and outcome of encephalitis in patients older than 65 years. METHODS: We performed an ancillary study of ENCEIF, a prospective cohort that enrolled all cases of encephalitis managed in 46 clinical sites in France during years 2016-2019. Cases were categorized in three age groups: (1) 18-64; (2) 65-79; (3) ≥ 80 years. RESULTS: Of the 494 adults with encephalitis enrolled, 258 (52%) were ≥ 65 years, including 74 (15%) ≥ 80 years. Patients ≥ 65 years were more likely to present with coma, impaired consciousness, confusion, aphasia, and rash, but less likely to present with fever, and headache (P < 0.05 for each). Median cerebrospinal fluid (CSF) white cells count was 61/mm3[13-220] in 65-79 years, 62 [17-180] in ≥ 80 years, vs. 114 [34-302] in < 65 years (P = 0.01). The proportion of cases due to Listeria monocytogenes and VZV increased after 65 years (P < 0.001), while the proportion of tick-borne encephalitis and Mycobacterium tuberculosis decreased with age (P < 0.05 for each). In-hospital mortality was 6/234 (3%) in < 65 years, 18/183 (10%) in 65-79 years, and 13/73 (18%) in ≥ 80 years (P < 0.001). Age ≥ 80 years, coma on admission, CSF protein ≥ 0.8 g/L and viral encephalitis were independently predictive of 6 month mortality. CONCLUSION: Elderly patients represent > 50% of adults with encephalitis in France, with higher proportion of L. monocytogenes and VZV encephalitis, increased risk of death, and sequels. The empirical treatment currently recommended, aciclovir and amoxicillin, is appropriate for this age group.

Cerebral nocardiosis in a patient treated with pembrolizumab: a first case report.

BACKGROUND: Checkpoints inhibitors (CPIs) are increasingly used for the treatment of several malignancies. The most common side effects are Immune Related Adverse Events, while infectious complications are rare, especially cerebral nocardiosis. CASE PRESENTATION: Here, we report the first clinical case of a cerebral nocardiosis revealed after seizure in a patient treated by pembrolizumab for a metastatic lung cancer, in the absence of any additional immunosuppressive therapy or risk factors for cerebral nocardiosis. The extended evaluation including a brain CT-scan did not reveal any lesion before pembrolizumab. Nevertheless, the 3-month delay between the start of Pembrolizumab and the diagnosis of cerebral nocardiosis suggests that the infection occurred prior to the CPI. Unfortunately, the patient died during treatment for cerebral nocardiosis, while the lung cancer tumor mass had decreased by 80% after the sixth cycle of pembrolizumab. CONCLUSIONS: This case report emphasizes that clinicians should consider diagnoses other than metastasis in a patient with a brain mass and metastatic cancer treated with CPI, such as opportunistic infections or IRAE.

Neurologic manifestations associated with COVID-19: a multicentre registry.

OBJECTIVES: To provide an overview of the spectrum, characteristics and outcomes of neurologic manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We conducted a single-centre retrospective study during the French coronavirus disease 2019 (COVID-19) epidemic in March-April 2020. All COVID-19 patients with de novo neurologic manifestations were eligible. RESULTS: We included 222 COVID-19 patients with neurologic manifestations from 46 centres in France. Median (interquartile range, IQR) age was 65 (53-72) years and 136 patients (61.3%) were male. COVID-19 was severe or critical in 102 patients (45.2%). The most common neurologic diseases were COVID-19-associated encephalopathy (67/222, 30.2%), acute ischaemic cerebrovascular syndrome (57/222, 25.7%), encephalitis (21/222, 9.5%) and Guillain-Barré syndrome (15/222, 6.8%). Neurologic manifestations appeared after the first COVID-19 symptoms with a median (IQR) delay of 6 (3-8) days in COVID-19-associated encephalopathy, 7 (5-10) days in encephalitis, 12 (7-18) days in acute ischaemic cerebrovascular syndrome and 18 (15-28) days in Guillain-Barré syndrome. Brain imaging was performed in 192 patients (86.5%), including 157 magnetic resonance imaging (70.7%). Among patients with acute ischaemic cerebrovascular syndrome, 13 (22.8%) of 57 had multiterritory ischaemic strokes, with large vessel thrombosis in 16 (28.1%) of 57. Brain magnetic resonance imaging of encephalitis patients showed heterogeneous acute nonvascular lesions in 14 (66.7%) of 21. Cerebrospinal fluid of 97 patients (43.7%) was analysed, with pleocytosis found in 18 patients (18.6%) and a positive SARS-CoV-2 PCR result in two patients with encephalitis. The median (IQR) follow-up was 24 (17-34) days with a high short-term mortality rate (28/222, 12.6%). CONCLUSIONS: Clinical spectrum and outcomes of neurologic manifestations associated with SARS-CoV-2 infection were broad and heterogeneous, suggesting different underlying pathogenic processes.