Severe headache • neck pain • intermittent cough • Dx?

THE CASE

A 32-year-old Chinese woman sought care from our family medicine clinic because she had a headache, neck pain, and an intermittent cough that had produced white sputum for 7 days. She described the headache as severe and pressure-like, and said that it had progressively worsened over the previous 3 weeks, coinciding with her first trip outside of China to the United States. The patient indicated that she also had occasional vomiting, dizziness, a low-grade fever, chills, night sweats, and increasing fatigue.

Prior to this visit, the patient had gone to the emergency department (ED) twice in one week, but was told that she had a migraine headache and a viral syndrome and was sent home. She was also told to make a follow-up appointment at our family medicine outpatient clinic.

Besides the symptoms that brought her to our clinic, the only other notable element of the patient’s history was a “neck mass” resection in China 8 years earlier. (The diagnosis of the neck mass was unknown.)

Concerned about her presenting signs and symptoms, we sent the patient to the ED, where she was admitted for further evaluation and treatment of possible meningitis. In the ED, she had a temperature of 101.5° F; her other vital signs were normal. A physical exam revealed mild neck stiffness.

THE DIAGNOSIS

A chest computed tomography (CT) scan demonstrated extensive confluent nodular infiltrates in the lung apices bilaterally with the largest confluent nodule measuring 6 cm (FIGURE 1). A chest x-ray demonstrated extensive bilateral pulmonary interstitial infiltrates that were most pronounced in the upper lung fields (FIGURE 2).

Lumbar puncture results revealed lymphocytic pleocytosis with elevated protein and low glucose levels (TABLE). Based on these results, the family medicine team suspected that our patient had tuberculous meningitis (TBM).

The team consulted with Infectious Diseases for management of TBM, and they placed our patient in a negative pressure room on airborne isolation. In addition, she was started on rifampin 450 mg/d, pyrazinamide 1000 mg/d, ethambutol 800 mg/d, and isoniazid (INH) 800 mg/d, as well as pyridoxine and intravenous dexamethasone.

DISCUSSION

TBM accounts for approximately 1% of all cases of TB and 5% of extrapulmonary diseases in immunocompetent individuals.¹ In 2015, there were approximately 10.4 million cases of TB worldwide, and 6 countries accounted for 60% of the global total: India, Indonesia, China, Nigeria, Pakistan, and South Africa.² TBM is typically a subacute disease with symptoms that can persist for weeks before diagnosis.³ An early diagnosis is critical, as the mortality rate remains relatively high (as high as nearly 70% in underdeveloped and developed countries) despite effective treatment regimens.³ (For updated recommendations on TB screening, see this month’s Practice Alert.)

Once you suspect tuberculous meningitis, isolate the patient, obtain appropriate cultures and smears, and start anti-tuberculosis drugs and adjunctive corticosteroids immediately.

Most health care facilities use AFB smears to determine when patients with suspected TB should be isolated. However, AFB smears are positive in only 60% of TB cases.⁴ One study indicated that nucleic acid amplification by PCR can improve sensitivity from 60% to 87% and specificity from 98% to 100%.⁵

The presentation of TBM varies by phase of disease:

• The prodromal phase typically lasts for 2 to 3 weeks. It is characterized by an insidious onset of malaise, headache, low-grade fever, irritability, and personality changes.
• The meningitis phase is characterized by pronounced neurologic features such as meningismus, protracted headache, confusion, myelopathy, and sensory deficits, as well as vomiting, lethargy, and urinary retention.
• During the paralytic phase, patients experience profound confusion, followed by stupor, coma, seizures, progressive paraplegia, and often, hemiparesis.^1,3,6