The patient was a 30-year-old Vietnamese woman with no relevant medical history who was studying in Japan. She presented with common cold symptoms for 2 weeks and a fever of about 38C, followed by right hemiplegia. These prompted consultation and subsequent admission to our hospital. The patient had undergone fertility treatment at a private obstetrics-gynecology clinic and was about 19 weeks pregnant. She had hyperemesis with a poor nutritional status, however, no weight gain during pregnancy was observed.
The general physical findings were as follows: height 157 cm, weight 52 kg, body mass index 21.1, blood pressure 116/57 mmHg, heart rate 128/min, respiration rate 30/min, body temperature 38.0C, and oxygen saturation of 95%. There were no pertinent thoracic or abdominal findings, except for the signs of pregnancy. The neurologic findings were lucid consciousness, spontaneous pain in the posterior cervical region, nuchal rigidity, right central facial palsy, right hemiplegia (Brunnstrom stage I in the arm and fingers, Brunnstrom stage II in the leg), hyperreflexia of the right upper and lower limbs, and right leg sensory deficit. Blood inflammatory markers showed a white blood cell count of 6,920 /muL and C-reactive protein of 3.42 mg/dL. Blood biochemistry results indicated mild liver dysfunction (aspartate aminotransferase 43 IU/L, alanine aminotransferase 46 IU/L) and undernutrition, with albumin at 2.3 g/dL. There were no abnormal findings related to the kidney or pancreas function. Testing for human immunodeficiency virus was negative.
The cerebrospinal fluid (CSF) findings were as follows: pale yellow color, initial pressure 290 mmH2O, final pressure 150 mmH2O, cell count 100 /muL with a lymphocyte-to-polymorphonuclear leukocyte ratio of 67:33, protein 229 mg/dL, sugar 11 mg/dL, and positive Ziehl-Neelsen staining. Cranial magnetic resonance imaging (MRI) on diffusion-weighted images revealed acute cerebral infraction of the left putamen; magnetic resonance angiography (MRA) revealed stenosis of the left middle cerebral artery (LMCA) (Fig. 1a and b). Ground glass opacities in both lung fields were noted on chest radiograph and computed tomography (CT) (Fig. 1c and d). Cerebral infarction secondary to vasculitis from tuberculous meningitis and miliary tuberculosis were suspected.
Fig. 2 shows the clinical course of the patient's hospitalization. Treatment was started with dexamethasone (19.6 mg/day) and four anti-tuberculosis drugs: INH (200 mg/day), rifampicin (RFP) (450 mg/day), ethambutol (EB) (750 mg/day), and pyrazinamide (PZA) (1.2 g/day). Because bacterial meningitis could not be ruled out, meropenem (6 g/day) was also administered. Taking into consideration the patient's pregnancy, acute cerebral infarction was treated with continuous heparin infusion at 10,000 units/day. Based on positive tubercle bacilli DNA on polymerase chain reaction and positive culture for Mycobacterium tuberculosis, the patient was given a definitive diagnosis of tuberculous meningitis. After five days of treatment, liver dysfunction ensued. When the liver dysfunction improved after a week, the administration of the four drugs was continued, with PZA being replaced by levofloxacin (LVFX) (500 mg/day). The fever and right hemiplegia promptly improved. Although Ziehl-Neelsen staining was performed only once and showed positivity and susceptibility to all anti-tuberculous drugs, the presence of Mycobacterium tuberculosis in the CSF was sustained for up to one month, despite the administration of anti-tuberculosis drugs.
On hospital day 25, at 22 weeks and 1 day of gestation, the patient gave birth to a stillborn. Examination of the uterine contents revealed tubercule bacilli, confirming an intrauterine infection. After the stillbirth, the fever and meningitis signs recurred. Despite treatment with 5 anti-tuberculosis agents (with the addition of streptomycin at 1 g/day) and restarting dexamethasone administration (19.6 mg/day), no improvement in the signs of meningeal irritation was observed. On hospital day 33, aphasia and right hemiplegia appeared; on hospital day 37, right abducens nerve palsy developed. Repeat cranial MRI revealed recurrent cerebral infarction on the left parietal lobe; MRA showed peripheral occlusion of the horizontal segment of the LMCA. Findings indicative of inflammation of the cranial base and lateral sinus thrombosis were also observed (Fig. 3). These were treated with edaravone and heparin; administration of aspirin (100 mg/day) was also continued to prevent recurrence.
However, the meningitis symptoms persisted and did not improve despite increasing the INH dosage from 300 mg/day to 500 mg/day. Therefore, intrathecal administration of 100 mg of INH 3 times per week was started. Furthermore, 15 mL of CSF was intermittently drained by lumbar puncture to relieve intracranial pressure. The signs of meningeal irritation started to improve after starting intrathecal INH. Serial cranial MRI indicated resolution of the venous sinus thrombosis and reduction of the inflammatory findings in the cranial base (Fig. 4). On hospital day 98, the visual acuity on the left decreased, suggesting left optic neuritis caused by inflammation of the cranial base. As the possibility of optic neuropathy could not be ruled out, EB was discontinued. Intrathecal INH administration was tapered to once a week and eventually was discontinued as the patient's symptoms improved.
The patient was discharged for home on hospital day 191. Three anti-tuberculosis drugs (INH, RFP, and LVFX) were continuously administered for 1 year. The residual neurologic deficits were mild aphasia, decreased visual acuity on the left side, and hypoesthesia in both legs, which was suspected to be secondary to INH. Nevertheless, the patient was able to independently engage in her activities of daily living. Cranial MRI 2 years after onset showed that the occlusion in the horizontal segment of the LMCA was unchanged; therefore, the administration of aspirin (100 mg/day) was continued to prevent the recurrence of cerebral infarction. Approximately 2.5 years later, the patient returned to her home country. She was able to walk without assistance and carry out her usual duties and activities.
Radiologic imaging findings in a 30-year-old woman with refractory tuberculous meningitis. (d) On chest CT, there were diffuse ground glass opacities in both lung fields. MRI: magnetic resonance imaging, MRA: magnetic resonance angiography, CT: computed tomography.