Faculty Bibliography

BACKGROUND:Glial fibrillary acidic protein (GFAP) autoimmune astrocytopathy is characterized by GFAP autoantibody positive encephalitis, meningoencephalitis or meningoencephalomyelitis. The initial clinical presentation may be similar to central nervous system infections making early diagnosis challenging. CASE PRESENTATION/METHODS:A Chinese female patient presented with subacute meningitis with symptoms of headache, vomiting, and fever. Cerebrospinal fluid (CSF) analysis showed monocytic pleocytosis, elevated protein level, low glucose level, and negative basic microbiological studies including Xpert MTB/RIF. Brain magnetic resonance imaging (MRI) showed bilateral cerebral cortical and white matter hyperintensities on FLAIR sequences. The patient was diagnosed with possible tuberculous meningitis and started on anti-tuberculosis therapy (ATT). Three months later, the patient developed cervical myelopathy and encephalopathy with persistent CSF pleocytosis. Five months later, tissue-based and cell-based assays demonstrated GFAP antibodies in blood and CSF. Her symptoms improved with repeated administration of intravenous immunoglobulin (IVIG) and corticosteroids. One-and-a-half -year follow-up showed neither clinical progression nor relapses. CONCLUSIONS:Anti-GFAP astrocytopathy should be included in the differential diagnosis of patients who present with subacute meningitis with negative microbiological studies and a progressive clinical course including encephalitis and/or myelitis.

The spectrum of symptoms of COVID-19 continues to expand as more clinical observations are reported. Neurological manifestations including headache are increasingly described. However, headache as the sole presenting symptom of COVID-19 pneumonia has not been reported. We describe a patient in Tanzania who experienced severe headache for seven days before the onset of other symptoms of COVID-19 that led to her isolation, diagnosis, and treatment.

Blindness and vision impairment are unpredictable complications of tuberculous meningitis (TBM) that are often unrecognized in the acute stages of illness due to inability to assess vision in patients with depressed levels of consciousness or confusion. We present a patient with definite TBM confirmed by positive Xpert MTB/RIF assay of cerebrospinal fluid (CSF) who developed binocular blindness two weeks after diagnosis and initiation of standard anti-tuberculosis treatment (ATT). Ophthalmological exam demonstrated complete bilateral abducens nerve palsies, impaired pupillary responses to light, normal optic discs, and visual acuity of hand motion only in each eye. Brain CT showed progressive enlargement of the third and lateral ventricles. We managed the patient medically with dexamethasone, acetazolamide, and substitution of moxifloxacin for ethambutol. Serial brain CTs confirmed gradual resolution of hydrocephalus. The patient had complete neurological recovery at six months except for residual blindness in the right eye. Visual acuity in the left eye recovered to normal (20/20). The assessment and management of vision impairment in TBM is discussed.

In September 2018, the United Nations General Assembly held the first ever meeting to discuss the global epidemic of tuberculosis (TB) and adopted a political declaration titled "United to end tuberculosis: an urgent global response to a global epidemic." The timing of the meeting was prescient but overdue since Mycobacterium tuberculosis surpassed the human immunodeficiency virus as the world's leading infectious killer in 2014. Infection of the central nervous system by Mycobacterium tuberculosis, herein referred to as neurotuberculosis, is the most feared and dangerous form of tuberculosis, requiring a high level of suspicion and clinical experience for prompt diagnosis and treatment. Neurologists, infectious disease specialists, orthopedic surgeons, neurosurgeons, and hospitalists in all countries need to recognize the spectrum of neurotuberculosis and be able to integrate clinical information, laboratory data, and radiological findings to make a diagnosis with or without microbiological confirmation.

Tuberculosis (TB) surpassed HIV as the world's leading infectious cause of death in 2014. Although billions of dollars have been invested to reduce the global burden of pulmonary TB, tuberculous meningitis (TBM), the most lethal manifestation of the disease, has remained largely neglected with a paucity of evidence-based guidelines. Research is urgently needed to obtain reliable estimates of the global incidence of TBM, develop high performance technologies to detect TBM in CSF, and evaluate drug regimens with greater penetration of the CNS.

Tuberculosis is the leading infectious cause of death globally and extra-pulmonary disease occurs in 15% of incident cases annually. Tuberculous meningitis (TBM) is arguably the most lethal form of tuberculosis and requires prompt diagnosis and initiation of treatment to prevent death and serious neurological disability. The development of rapid diagnostic tests using polymerase chain reaction (PCR) technology for the detection of Mycobacterium tuberculosis (MTB), including the World Health Organization (WHO) - endorsed Xpert MTB/RIF Ultra assay, has allowed earlier definite diagnosis of TBM than conventional culture methods which usually take two weeks or longer for positive identification of MTB. Detection of MTB in cerebrospinal fluid (CSF) using PCR assays requires special attention to the collection, handling, and processing of CSF. Herein we present best practices guidance to maximize the detection rate of MTB in CSF using Xpert MTB/RIF Ultra.