Although herpes simplex encephalitis is not classically considered an opportunistic infection, reactivation of herpes simplex is being seen increasingly in patients with cancer or immunosuppression. The authors present a patient with malignant glioma and HSV-1 encephalitis whose PCR-proven encephalitis recurred after temozolomide (TMZ) chemoradiation despite acyclovir therapy, and summarize details of four other cases of HSV-1 encephalitis associated with TMZ. The similarity among these cases raises the likely need for longer treatment courses and/or oral suppressive therapy in patients at risk for herpes simplex infections who are receiving TMZ.

A 51-year-old man developed coma, bilateral pupillary dilation, ophthalmoplegia and quadriplegia 4 weeks after testing positive for COVID-19. MRI demonstrated a symmetric midline pontine non-enhancing T2-FLAIR hyperintense lesion. The patient was treated with intravenous methylprednisolone, which resulted in improvement of his Glasgow Coma Scale (GCS) from 3 to 15 over the next 5 days. To our knowledge, this is the first case of a post-infectious steroid-responsive brainstem lesion associated with COVID-19. The clinical picture best fits in the family of a steroid-responsive encephalopathy and reminds us that COVID-19 may cause severe post-infectious neurological complications.

A 64-year-old woman presented with progressive cognitive decline over 7 months. Her family noted a general slowing of her speech and thought process. She had developed a flat affect and difficulty with daily activities such as driving. There was no history of neurologic or psychiatric disorders.On admission, the patient was alert and oriented to person, time, and place, but had hypophonic speech, impaired attention, and severely impaired short-term recall. Cranial nerves were normal, including reactive pupils bilaterally. Strength, sensation, and coordination were normal. Deep tendon reflexes were normal and symmetric. The gait was slow but not ataxic. The Romberg sign was not present.An MRI demonstrated bilateral multifocal white matter T2 signal abnormalities involving the mesiotemporal lobes, insular and subinsular regions, and external and extreme capsules ( figure). Spinal fluid analysis demonstrated elevated protein (104 mg/dL), pleocytosis (28 leukocytes/mm 3 with 88% lymphocytes), and a glucose level of 95 mg/dL.The differential diagnosis for the patient's subacute encephalopathy, in light of the imaging and CSF findings, included autoimmune/paraneoplastic (anti-Hu, anti-NMDA, and anti-LGI1 antibodies) or infectious causes (herpes encephalitis). C-reactive protein and erythrocyte sedimentation rate were mildly elevated to 5.3 mg/L and 25 mm/hour, respectively. CSF Gram stain, culture, and CSF viral studies for varicella-zoster virus (VZV), herpes simplex virus, cytomegalovirus, and West Nile virus were negative. Serum HIV, Epstein-Barr virus, VZV, Lyme, thyroid peroxidase, and antinuclear antibodies, thyroid, renal, and liver function, and toxicology screen were unremarkable. CT of the patient's chest, abdomen, and pelvis was normal.While the patient's syphilis and paraneoplastic laboratory panels were pending, the patient was treated empirically for a presumed inflammatory or autoimmune process with 1 g IV methylprednisolone daily for 5 days. She demonstrated improved memory, attention, and concentration.Two days after the patient completed steroid therapy, the previously submitted serum treponemal immunoglobulin G returned positive and rapid plasma reagin was reactive at 1:64 dilution. In addition, the serum Treponema pallidum particle agglutination test and spinal fluid Venereal Disease Research Laboratory (VDRL) assays were positive (VDRL CSF titer 1:32). The patient received a 2-week course of IV penicillin G 4M units. At 1-month follow-up, her mental status had improved but moderate attention Figure MRI demonstrates bilateral mesiotemporal lobe enhancement in neurosyphilis Axial brain MRI of a 64-year-old woman with bilateral multifocal white matter T2 signal abnormalities involving the mesiotemporal lobes, insular and subinsular regions, and external and extreme capsules. Pathologic gadolinium enhancement was not present.