A 26-year-old man was transferred to our hospital with complaints of dizziness, headache, insomnia for 1 month, and exacerbated limb weakness for half a month. One month ago, the patient first presented to the local hospital for these symptoms. Enhanced MRI of the brain showed a negative result while enhanced MRI of the cervical spine showed slight thickening of the cervical spinal cord. Upon lumbar puncture, the opening pressure was found to be more than 330 mmH2O and the cerebrospinal fluid (CSF) was transparent yellow, with a glucose (GLU) level of 3.8 mmol/L (reference range, 2.5-4.4 mmol/L), a microprotein level of 3.4 g/L (reference range, 0.15-0.45 g/L), and a chloride ion level of 112 mmol/L(reference range, 120-130 mmol/L). There were 50 nucleated cells per mul (reference range, 0-10), of which 95% were monocytes and 5% were coenocytes (Table 1). Considering the results of the CSF analysis (mononuclear-predominant CSF pleocytosis and a high protein level), the high open pressure, symptoms of intracranial hypertension, the inflammatory lesion on MRI findings, and the high incidence of tuberculosis in China [age-standardized incidence of tuberculosis, 54.18 per 100,000 population from 1990 to 2007 ], the patient was initially diagnosed with tuberculous meningitis and myelitis. He then received empirical antituberculosis therapy (a standard four-drug regimen of isoniazid, linezolid, moxifloxacin, and tigecycline). However, empirical treatment with anti-tuberculous drugs, antibiotics, antiviral drugs, and drugs to reduce the intracranial pressure (Figure 4), did not improve his condition. Thereafter, the patient was transferred to another hospital and, a lumbar puncture was repeated, the opening pressure was more than 330 mmH2O. The CSF was slightly yellow, with a GLU level of 5.35 mmol/L (reference range, 2.5-4.4 mmol/L), a microprotein level of 5.179 g/L (reference range, 0.08-0.43 g/L), a chloride ion level of 106.5 mmol/L (reference range, 120-130 mmol/L), there were 129 nucleated cells per microliter (reference range, 0-10), of which 94% were monocytes and 6% multinucleated cells (Table 1). The acid-fast staining, mycobacterium culture, Xpert MTB, and RT-PCR of the CSF samples were negative. M. houstonense was identified in the CSF by metagenomic next-generation sequencing (mNGS) in a company for gene sequencing named Smicere Diagnostics and the report is attached as a Supplementary material 1 which showed the reads of 264 (Supplementary material 1). The pathogen's data were aligned to the National Center for Biotechnology Information GenBank database and revealed sequence homology above 96.825 and 97.183% with M. houstonense (GenBank accession no. NZ_LT546208.1 and no. NZ_LT546207.1), respectively (Supplementary material 2). After 7 days, the CSF sample pathogen cultures in blood agar at 35 C from another lumbar puncture were negative. Despite empirical treatments with anti-tuberculous drugs (isoniazid, linezolid, moxifloxacin, and tigecycline) which are the same treatment in the previous hospital due to insufficient course (Figure 4), the patient's condition worsened (decreasing myodynamia of limbs and endorsed racing thoughts) and he was transferred to our hospital. This patient did not have any underlying diseases or past medical history, and he was employed in the field of information technology.
After being admitted to our hospital, the patient's neurological examination showed the myodynamia of the left limb was grade 2, the right upper limb was grade 4, and less than grade 4. The muscle tension on the left side was decreased and that on the right side was normal. Poor abduction of the eyes and tongue deviation to the left was observed. The symmetry of the tendon reflexes in the extremities was weakened, and the craniocervical flexion test and bilateral Kerning sign were positive. The finger-to-nose test, heel-knee-shin test, Romberg test, and other ataxic tests could not be performed. The laboratory tests showed that there were 6.11 x 109 erythrocytes per L, 312 x 109 platelets per L, and 23.11 x 109 leukocytes per L, of which 93.4% were neutrophils. His blood biochemistry was normal except for the raised glutamic-pyruvic transaminase level of 201 IU/ L (reference range, <40 IU/L) and glutamic oxalacetic transaminase of 53 IU/L (reference range, <35 international IU/L), and a mild reduced albumin level of 34.7 g/L (reference range, 40-55 g/L). His inflammatory biomarkers showed an elevated procalcitonin level of 4.03 n/ml (reference range, <0.046 ng/ml), C-reaction protein level of 15 mg/L (reference range, <5 mg/L), interleukin-6 level of 5.81 pg per ml (reference range, 0-7 pg per ml). His HIV antibody test was negative, but there were 502 CD3+ T cells per mul (reference range, 941-2,226), 269 CD4+ T cells per mul (reference range, 471-1,220), and 200 CD8+ T cells per mul (reference range, 303-1,003) in blood. The first lumbar puncture in our hospital revealed the opening pressure was 150 mmH2O, with a microprotein level of 11.8 g/L (reference range, 0.15-0.45 g/L), a chloride ion level of 108 mmol/L (reference range, 120-130 mmol/L), GLU was 5.04 mmol/L (reference range, 2.5-4.4 mmol/L). There were 10 nucleated cells per microliter (Table 1). The six subsequent lumbar punctures performed at our hospital revealed a high opening pressure and mononuclear-predominant CSF pleocytosis, hyperglycorrhachia, a high level of protein, and a low level of chloride ion. Nevertheless, the acid-fast staining, mycobacterium cultures, Xpert MTB and RT-PCRs of all CSF samples were negative (Table 1). Enhanced MRI of the brain and cervicothoracic region revealed abnormal enhanced meningeal pia and subarachnoid spaces with signs of communicating hydrocephalus (Figures 1, 2). Enhanced MRI of the lumbar spine (performed on 17 February 2022) revealed nodules and irregularly thickened meninges (Figure 3).
It is difficult to diagnose infections caused by NTM since these diseases are rare and their clinical manifestations lack specificity. Most patient with NTM-CNS has been diagnosed with an immunocompromised disease, such as HIV. Meanwhile, it is not helpful to distinguish nervous system infections caused by NTM from other infection types, such as tuberculous infections, on radiological images. Some NTM-CNS infections could present with hydrocephalus or brain atrophy, which is unexplained and not age-related, radiological images may also show nodular basal enhancement in NTM-CNS infection. On the basis of these radiological and clinical manifestations, as well as the mNGS CSF result in the second hospital, this patient was considered to have a CNS infection caused by M. houstonense, which is an NTM. According to the Chinese NTM guidelines, amikacin, tigecycline, clarithromycin, and imipenem were administered (Figure 4). After 25 days of therapy, the patient still had intracranial hypertension (CSF pressure > 300 mmH2O, the number of nucleated cells in the CSF ranged from 10 to 70/mul, and vision was impaired), and epileptic seizure occurred once. Therefore, we placed continuous lumbar cisterns to drain ~200 ml/day, and the draining CSF was slightly flocculent. Levetiracetam was also administered. Imipenem was then replaced with meropenem on the 27th hospital day.
The patient's CSF culture and mNGS (performed three times in the Precision Medicine Center of our hospital) remained negative throughout the course of therapy in our hospital. The patient did not improve despite appropriate empirical treatment. Finally, the patient lost confidence and requested discharge. The patient still had poor visual acuity, intermittent headaches, and vomiting, and his condition gradually worsened after discharge. Unfortunately, he died 19 days after discharge.