The definitive diagnosis of tuberculous spondylitis is based on the result of cultural and pathological tests conducted in tissues collected from lesions. However, this method is only found to be positive at 50–75%, and it is often necessary to conduct re-examination due to the high risk of false negatives [3, 9]. Sputum microscopy is available in pulmonary TB to determine treatment response, but it is not suitable in tuberculous spondylitis. Repeated biopsy and culture studies for detecting residual infectious lesion are neither reasonable nor perfect. Evaluation of therapeutic response in patients with tuberculous spondylitis TB usually indirectly depends on clinical and hematological features [6, 10, 11].
An MRI is a highly sensitive test, and it can also be used to determine therapeutic response. Recent study has defined a significant regression in the epidural or paraspinal abscess/granulation tissues, marrow reconversion, and fatty reconstitution of the diseased bone as features of radiological healing [12]. Le Page et al. reported gradual conversion of initial vertebral body edemas to fatty signals in 40% of cases at six months and 75% at 12 months [13]. However, the radiological findings of healing are a process of long-term imaginal changes without regard to clinical symptoms. Marrow edema and vertebral involvement can worsen by six months, and changes can even be observed at up to 14 months [14, 15]. MRIs cannot differentiate active lesion from sterile residual ones, and many patients continue to present pain due to several reasons even after they have been healed of TB [12]. Additionally, MRIs cannot reveal when anti-TB medication therapy should be discontinued. In the first patient, specific MRI features, including decrease in marrow edema, abscess size, and paraspinal soft tissues associated with the healing process were shown after 12 months of anti-TB medication therapy. In the second patient, however, TB existed continuously even though MRI features were related to the healing process.
For this reason, many efforts have been made to apply the 18F-FDG PET to evaluating therapeutic response, and several reports have recently been introduced. Using 18F-FDG PET measures the metabolic activity of the tissues in a non-invasive and semi-quantitative way, providing very accurate localization of the hypermetabolic activity. Active TB lesions are often proliferative lesions composed of epithelioid cells, Langerhans giant cells, and lymphocytes. These cells have high metabolisms of glucose and show a high uptake of FDG [16, 17]. Changes in FDG accumulation may be an important sign indicating the effect of anti-TB medication therapy. Metabolic responses may indicate therapeutic response and guide duration of antimicrobial therapy [18, 19].
From the results of the 18F-FDG PET in our patients, we expected the therapeutic response and completion of anti-TB medication therapy to accord with the SUVmax. The first patient, whose treatment had been completed, showed SUVmax of 1.83, which is a very low as much as physiological FDG uptake in normal structures. In the second and third cases, SUVmax of 4.14 and 7.02, respectively, were found to be the higher uptake of SUVmax continuously within the paravertebral abscesses. These are judged to be a more accurate and consistent indication of the state of the TB lesion than MRI. The lesion presenting higher uptake of FDG can be explained by the overpopulation of the inflammatory cells described above, which are consistently present within the infected structures such as abscesses or vertebrae.
The optimal duration of anti-TB medication therapy is controversial. The Medical Research Council (MRC) advocates short-course chemotherapy (six months) for uncomplicated spinal TB [20]. However, Cormican et al. reported that mean duration of treatment was 13 months (range: 9–24 months) [21]. The region of the authors of this paper shows higher incidence and prevalence of drug resistance in TB. Therefore, the determination of the treatment duration should consider the regional characteristics and severity of the lesion, and discontinuation of anti-TB medication therapy should be prudent and conservative. When a relapse occurs, it usually happens within 12 months after the completion of therapy, indicating that the disease was incompletely treated [22].
There is a difference in the degree of FDG uptake depending on the presence of TB even after 12 months of anti-TB medication therapy. Especially in the third patient with active TB, the SUVmax (7.02) was kept very high regardless of the treatment duration, which meant that active TB was sustained and eventually led to abscess discharge through fistula again. However, as with the second patient, it was difficult to determine whether anti-TB medication should be discontinued, considering the healing process of the overall lesions and constantly reduced SUVmax (4.14). Successfully treated pyogenic spondylitis sometimes shows sustained high level of FDG uptake of 18F-FDG PET following weeks of antibiotics treatment, which can be explained by severe tissue damage and its healing process. Unlike pyogenic spondylitis, tuberculous spondylitis takes more time to sterilize than pyogenic spondylitis. The damaged tissues are also expected to be restored over long periods of sterilizing TB, resulting in lower FDG uptake (SUVmax 1.83 of the first patient) at the end of treatment than that of pyogenic spondylitis. Given this, the second patient can be determined to have a continuous TB and require further anti-TB medication therapy.
We think that 18F-FDG PET/MRI can be considered as a helpful independent and alternative method for determining the appropriate time to discontinue anti-TB medication. However, 18F-FDG PET/MRI is still very expensive examination and has low accessibility, which is limited to apply generally in the patients with TB spondylitis. Further studies with more patients are required to demonstrate our results and to overcome the limitations.
