Case History
An 11-year-old girl was brought by her mother to the Emergency Room because of altered mental status, described as abnormal movements and staring with a period unresponsiveness lasting 15 minutes.
One week previously, she had returned from a 6 week trip to Ghana with her family to visit other family members there. Malaria prophylaxis had been prescribed but was not taken during the trip. Since coming back, she had constant frontal and bilateral headaches with retro-orbital pain, accompanied by nausea, poor appetite, and several episodes of vomiting. She did not have cough, congestion, earaches, or fever. Past medical history was unremarkable. Nobody else in the family was sick. She had some mostquito bites while in Ghana, but no fever or illness.Confusion, fever, and neck stiffness were noted on physical exam.
A spinal tap was done, with the following results: wbc 46 per mm3 (lymphocytes 98%, monocytes 2%), rbc 25 per mm3, glu 41 mg/dL, pro 72 mg/dL, no organisms on Gram stain and Kinyoun stains, meningitis/encephalitis PCR panel negative, and PCR for Mycobacterium tuberculosis negative. The bacterial culture had no growth after 5 days of incubation.
A CT scan of the head done without contrast was normal. An MRI of the brain done with contrast showed focal contrast enhancement in the left corona radiata and several other small foci of contrast enhancement, including within the right occipital lobe and cerebellum, alsong with possible leptomeningeal contrast enhancement along several sulci.
After 4 weeks, growth was observed in the Mycobacterial Growth Indicator Tube (MGIT) culture. A Kinyoun stain of the growth is shown in Figure 1, and colony morphology is shown in Figure 2. The organism was subcultured on the Middlebrook 7H10 (the growth shown in Figure 2) and identified by MALDI-ToF (Matrix assisted laser desorption ionization Time of Flight) as Mycobacterium tuberculosis complex (MTBc). The antimicrobial susceptibility test was performed at the department of health, which reported out susceptible to all first-line agents, except resistance to INH.
Discussion
Tuberculous (TB) meningitis is a severe form of extrapulmonary tuberculosis caused by Mycobacterium tuberculosis (Mtb). It typically presents with a subacute onset of constitutional symptoms, including malaise, fever, headache, and altered mental status, which can progress to stupor, coma, and death if untreated. Clinical features often include headache, vomiting, meningeal signs, focal neurological deficits, cranial nerve palsies (our case has cranial nerve 6 palsy), and raised intracranial pressure.
The diagnosis of TB meningitis is generally based on clinical suspicion, CSF analysis, and neuroimaging. CSF analysis is typically non-specific and shows lymphocytic pleocytosis, elevated protein, and low glucose levels. Confirmatory tests include CSF smear, culture, and nucleic acid amplification tests for Mtb. While mycobacterial culture is still a gold-standard method for the definitive diagnosis, it usually takes long for growth detection and the downstream diagnostic methods, such as MALDI-ToF (Matrix Assisted Laser Desorption Ionization Time of Flight). Since laboratories are reliant on (MALDI-ToF) after the discontinuation of Hologic GenProbe products, subculturing the organism from the liquid growth for MALDI-ToF results in additional delay in identification.
The cording characteristics of MTB from culture growth was a classic tell-tale sign for preliminary laboratory identification. While the presence of “cord factor” denotes the virulence of mycobacterial species (particularly MTBc) and was thought to be unique to MTBC, it was later demonstrated to be present in non-tuberculous mycobacterial (NTM) species. Therefore, care should be taken, and the time of growth should be considered when interpreting the Kinyon stain of positive cultures.
On the other hand, Xpert MTB/RIF is FDA-approved only on sputum samples, although studies show off-label utilization on CSF. The sensitivity of this test in CSF is mediocre due to the paucibacillary nature of the infection. Neuroimaging, such as MRI or CT, can reveal meningeal enhancement and hydrocephalus, which are suggestive of TB meningitis; however, clinicians still rely heavily on microbiologic results for definitive diagnosis.
As TB meningitis is a fatal disease and the confirmed diagnosis may take a long time, treatment should be initiated promptly based on clinical suspicions. Treatment includes anti-tuberculous medications with steroids for 2 months. Then NIH and RIF for an additional 7-10 months. It is noteworthy to mention that susceptibility is important as some MTB strains are drug-resistant, as is the case for our patient, whose isolate is resistant to INH.
References
- https://www.uptodate.com/contents/tuberculous-meningitis-clinical-manifestations-and-diagnosis
- Theorn et al. Scientific Reports. 2014. DOI: 10.1038/srep05658. Accessed. June 19, 2024
- Wilhelm Hedin et al., JID, 2023
- Lablogatory – a cording too cording by Richard Davis
-Dr. Mahmoud Ali, MD, is a pediatric infectious disease fellow at Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY.
-Phyu Thwe, Ph.D, D(ABMM), MLS(ASCP)CM is Associate Director of Infectious Disease Testing Laboratory at Montefiore Medical Center, Bronx, NY. She completed her medical and public health microbiology fellowship in University of Texas Medical Branch (UTMB), Galveston, TX. Her interests includes appropriate test utilization, diagnostic stewardship, development of molecular infectious disease testing, and extrapulmonary tuberculosis.
