Tuberculous meningitis initially presented with low levels of pleocytosis and protein in the cerebrospinal fluid: a case report

Article information

encephalitis. 2025;.encephalitis.2025.00010

Publication date (electronic) : 2025 March 11

doi : https://doi.org/10.47936/encephalitis.2025.00010

Hyung-Kyum Kim, Byung-Kun Kim, Jung-Ju Lee, Kyusik Kang, Woong-Woo Lee, Ilhan Yoo, Namoh Kim

Department of Neurology, Nowon Eulji Medical Center, Eulji University, Seoul, Korea

Correspondence: Jung-Ju Lee Department of Neurology, Nowon Eulji Medical Center, Eulji University, 68 Hangeulbiseok-ro, Nowon-gu, Seoul 01830, Korea E-mail: sss331@eulji.ac.kr

Received 2025 January 6; Revised 2025 February 24; Accepted 2025 March 1.

Abstract

Introduction

Tuberculous meningitis (TBM) is a disease characterized by leptomeningeal involvement of the brain and spinal cord due to infection by Mycobacterium tuberculosis. If not treated promptly, it may lead to high morbidity and mortality. To diagnose it, cerebrospinal fluid (CSF) examination and brain imaging are mandatory. In most cases, CSF findings in TBM include a moderate level of lymphocytic pleocytosis (100–500 cells/μL), elevated protein concentration (100–500 mg/dL), and low glucose concentration (<45 mg/dL) [1]. Due to these findings, patients with TBM can be treated with antituberculous medications (ATM) in the early stages. In patients with atypical CSF manifestations, ATM may be administered in the later stages and can be detrimental to their health [2].

Seizures are common in patients with TBM [3]; however, nonconvulsive status epilepticus (NCSE) associated with TBM is rare but can cause altered consciousness in patients with TBM. Without clinical suspicion, diagnosis of NCSE is difficult.

We experienced a patient with atypical CSF findings and describe their characteristic clinical features, discussing the differential points.

This study was approved by the Institutional Review Board of Nowon Eulji Medical Center, Eulji University School of Medicine (EMCS 2025-03-017). Written informed consent was obtained for publication of this case report and accompanying images.

Case Report

A 26-year-old female visited the emergency department (ED) due to a headache, fever, chills, rhinorrhea, sore throat, and myalgia that had developed 2 days prior. She had been experiencing an insidious onset of continuous and progressively worsening headaches since then. She reported that the most severe location of the headache was in the occipital area, where it had a dull and intermittently pulsating nature. She had been prescribed cold medicine by a local clinic, but it showed little effect on her symptoms. She did not complain of weight loss.

In the ED, her blood pressure, pulse rate, respiratory rate, and body temperature were measured at 136/88 mmHg, 92 beats/min, 20 breaths/min, and 37.6 °C, respectively. On auscultation, her breath sounds were clear, and no murmurs were audible. On the neurological examination, she was alert, and no focal neurological deficits were observed other than severe neck stiffness.

Suspecting meningitis, a brain computed tomography (CT) scan and CSF tapping were performed. The brain CT revealed no abnormalities, but the CSF examination showed mild pleocytosis (65/μL, 90% lymphocytes; normal value, 0–5/μL), mild elevation of the protein level (46.1 mg/dL; normal value, 8.0–32.0 mg/dL), and a normal glucose level (67 mg/dL; normal value, 40–70 mg/dL) with clear appearance. The ratio of CSF glucose to serum glucose was 0.58. The CSF adenosine deaminase (ADA) level was 2.2 IU/L. Fungus culture, cryptococcal antigen, and viral markers such as antibodies against herpes simplex virus were all negative. Based on these findings, the patient was tentatively diagnosed with viral meningitis and treated with analgesics (naproxen 275 mg twice per day). However, her symptoms persisted despite the treatment. She complained of a continuous severe headache with accompanying nausea and mild fever (37.3–37.7 °C).

On the 6th day of admission, follow-up CSF tapping was performed, which showed aggravated pleocytosis (450/μL, 85% of lymphocyte) and protein elevation (225.3 mg/dL). CSF glucose measured 51 mg/dL, and the ratio of CSF glucose to serum glucose was 0.49. The CSF ADA level increased to 8.4 U/L.

A few hours after the follow-up CSF tapping, the patient became drowsy and mute. She could not obey the commands of medical personnel. During the mute period, blank staring and looking-around behavior were observed. She also urinated in bed. Brain magnetic resonance imaging with diffusion-weighted imaging showed no organic brain lesions except mild leptomeningeal enhancement (Figure 1). Based on these clinical, laboratory, and neuroimaging findings, the patient was suspected of having NCSE complicated by TBM.

Figure 1.

Enhanced T1 sequence of brain MRI with DWI of the patient

Axial (A) and coronal (B) views of enhanced T1 sequence of brain MRI show increased basal enhancement (arrows). Diffusion restriction is not definitely observed on DWI (C).

MRI, magnetic resonance imaging; DWI, diffusion-weighted imaging.

Treatment with anti-seizure medication (valproic acid, loading dose of 1,500 mg and maintenance dose of 300 mg three times per day), ATM (isoniazid 300 mg per day, rifampin 600 mg per day, ethambutol [EMB] 1,200 mg per day, and pyrazinamide [PZA] 1,500 mg per day), and steroid (intravenous dexamethasone 4 mg four times per day) was initiated the following day. After 1 day of treatment, the patient became alert and oriented. She could obey the commands of medical personnel, and the abnormal behaviors, including blank staring and looking around, disappeared. Electroencephalography (EEG), performed after loading of valproic acid, showed diffuse slowing superimposed by fast rhythm in the left temporal area (Figure 2). Chest and abdominal CT revealed no abnormality. Sputum smear and culture for M. tuberculosis were negative.

Figure 2.

Electroencephalography findings

The electroencephalography of the patient shows diffuse slowing intervened by intermittent fast rhythm in the left temporal area (between arrows).

On the 10th day of admission, her headache and neck stiffness diminished significantly. A second follow-up CSF tapping was performed on the same day and showed a significant reduction in pleocytosis (120/μL, 57% lymphocytes) and protein level (161.2 mg/dL). CSF glucose measured 53 mg/dL, and the ratio of CSF glucose to serum glucose was 0.31.

The third follow-up tapping was performed on the 18th day of admission, which showed further reduction in pleocytosis (95/μL, 70% lymphocytes) and protein level (20.3 mg/dL). CSF glucose measured 55 mg/dL, and the ratio of CSF glucose to serum glucose was 0.48. The CSF ADA level was below 1.0 U/L. Polymerase chain reaction and culture for M. tuberculosis were negative in all CSF examinations.

The following week, the patient was discharged nearly free of symptoms. After discharge, treatment for TBM continued for 1 year. EMB and PZA were used for 3 months, while the other medications continued until the last day of treatment. Valproic acid was used for one month and then tapered off after confirming normalization of the EEG. The last follow-up tapping performed after 1 year of treatment revealed no pleocytosis and a normal protein level (all performed CSF profiles of the patient are summarized in Table 1). The patient was free of symptoms at the last follow-up visit.

Table 1

Cerebrospinal fluid profiles of the patient

Discussion

TBM usually shows typical CSF findings of moderate levels of lymphocytic pleocytosis, moderate to high elevation of protein levels, and low glucose levels [1]. The atypical findings observed in our patient can lead to misdiagnosis. In cases of viral encephalitis, clinical features similar to those of our patient may be observed; however, lymphocytic pleocytosis usually does not exceed 250/μL, and the ratio of CSF glucose to serum glucose is usually greater than 0.5 [4]. Herpes simplex viral encephalitis, the most common form of viral encephalitis, commonly shows periodic discharges in the frontotemporal area on the EEG and frontotemporal lesions on brain imaging [5,6], which were absent in our patient.

CSF ADA levels may be helpful for the diagnosis of TBM. In a meta-analytic study, values >8 U/L showed improved diagnostic accuracy for TBM [7]. Our patient’s results were consistent with this finding; however, there was a delay of a few days in obtaining the results. In an emergent clinical situation, such a delay can be harmful. Clinical suspicion and the CSF profile are two critical factors in the diagnosis.

In the diagnosis of TBM, the Lancet scoring system (LSS) can be utilized [8]. Points of 12 or more are considered probable for TBM, while points ranging from 6 to 11 are possible for TBM. Our patient initially scored 3 at the ED (clear appearance of CSF, 1 point; cell count of 10–500/μL, 1 point; lymphocyte predominance, 1 point) and 11 on the sixth day of admission (symptom duration longer than 5 days, 4 points; altered consciousness, 1 point; clear CSF, 1 point; cell count of 10–500/μL, 1 point; lymphocyte predominance, 1 point; CSF to plasma glucose ratio less than 50%, 1 point; and basal meningeal enhancement, 2 points). The initial LSS score was atypical for TBM and misled us into an incorrect diagnosis.

TBM can induce altered consciousness in various ways, including tuberculoma, vasculitis, or metabolic derangement, such as the syndrome of inappropriate secretion of antidiuretic hormone or cerebral salt-wasting syndrome [1]. NCSE is a rare cause of altered consciousness in TBM [9,10]. Because the EEG was obtained after anti-seizure medication, it was not consistent with the Salzburg criteria for NCSE. However, the intermittent fast rhythm in the left temporal area may be indicative of residual seizure activity. After treatment with valproic acid, the patient regained consciousness, and the abnormal behaviors suggesting focal seizures resolved, which supports the diagnosis of NCSE complicated by TBM. ATM would improve the symptoms, but one dose of ATM is usually not sufficient for clinical improvement in TBM. The causes of NCSE in TBM include focal lesions, hydrocephalus, leptomeningeal irritation, or metabolic derangement such as hyponatremia [10]. Our patient had no definite lesions in the brain, except basal enhancement, and no metabolic derangement. Leptomeningeal irritation is the most probable cause of NCSE in our patient. In patients with TBM showing an altered mental state, NCSE might have been undiagnosed.

In conclusion, TBM is fatal in the absence of an early diagnosis. Seizures may be common, but NCSE is uncommon in TBM. NCSE should be excluded in patients with altered consciousness due to TBM. The presence of persistent headache and fever necessitates comprehensive follow-up CSF examinations in cases of meningitis.

Article information Continued