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Spinal TB surgery now includes Vitamin D as the standard of care (5,000 IU daily) – Sept 2024

Complete neurological recovery of spinal tuberculosis after spinal surgery and vitamin D supplementary: A case series

International Journal of Surgery Case Reports, Volume 122, September 2024, https://doi.org/10.1016/j.ijscr.2024.110053
Nyoman Semita a, Heni Fatmawati b, Al Munawir c, Ni Njoman Juliasih d

Highlights

  • Surgery, anti-TB drugs, vitamin D in spinal TB results in neurological recovery, normal ADLs, normal levels of vitamin D.
  • Vitamin D plays a role in shortening the duration of oral anti-TB drug use and increasing the incidence of bone fusion
  • Use of anti-TB drugs and vitamin D as standard of care for spinal TB cases.

Introduction and importance
Deaths from tuberculosis (TB) in Indonesia are nearly 200,000 per year and higher than those from COVID-19. The problems associated with spinal TB are vitamin D deficiency, neurological deficit, disruption of daily living activities and long-term anti-TB treatment (24 months). Vitamin D acts as an anti-inflammatory, maintains vascular health, and increases calcium levels.

Case presentation
We reported 130 cases series spinal TB, neurological problems, vitamin D deficiencies; after surgery, anti-TB drugs and vitamin D adjuvant for 12 months. A TB diagnosis was confirmed by radiology, microbial and histopathology investigations.

Clinical discussion
After the treatment is shorter than standard conventional, patients had 100 % normal motor function, 3 % stiffness, 97.4 % fusion rate, 98.5 % normal vitamin D, minimal disability based on Oswestry Disability Index (ODI) scores, and normal function based on Japanese Orthopaedic Association (JOA) scores.

Conclusion
Vitamin D should be considered an adjuvant in spinal TB treatment, although further research is still needed to determine its efficacy and safety. Surgery and the administration of anti-TB drugs are still the standard procedures.

Portions of the text PDF provided FREE by the publisher (some images are online)


Introduction
The list of spinal tuberculosis (TB) problems includes infection, poor general condition, multiple lesions, cold abscess, pain, pathologic fracture, instability, neurological deficit, deformity, kyphosis progression by growth, socioeconomic and psychogenic problems [1,2]. Spinal TB constitutes 15 % of all extrapulmonary TB cases by Mycobacterium TB. The pathogenesis is a secondary focus of infection from the other organs via blood transmission (hematogenic), small tubercle (superior or inferior-anterior site of the subchondral vertebral body), activated chaperonin 10, high stimulation of bone resorption, destruction of the anterior part of the vertebral body, resulting in kyphosis, respiratory problems, and paraplegia [3]. A granulomatous reaction blocks bone formation, resulting in relatively avascular and sequestration formation [4]. The application of 1.25-dihydroxyvitamin D3 has an anti-inflammatory effect, promotes angiogenesis, protects the health of peripheral arteries and boosts neurogenesis [5], [6], [[7]].
Our rural hospital has not yet used vitamin D as an adjuvant chemotherapy and surgery in spinal TB treatment. In this case series, we report neurological recovery, activities of daily living (ADL) based on Japanese Orthopaedic Association (JOA) and Oswestry Disability Index (ODI) scores, and vitamin D improvement in spinal TB cases. The case series has been reported in line with the PROCESS criteria 2023 [8].

Case presentation
All procedures performed in this study were in accordance with the ethical standards of the institution and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patients for publication, including any accompanying images. A copy of the written consent form is available for review by the editor-in-chief of this journal upon request. This case series was designed as a descriptive study, and data were collected retrospectively for six years between January 2017 and December 2023 in a general hospital in East Java, Indonesia.
In this case series, we treated 130 spinal TB cases and neurological deficit complications associated with vitamin D deficiency. The list of spinal TB problems includes infection, poor general condition, multiple lesions, cold abscess, pain, pathologic fracture, instability, neurological deficit, deformity, kyphosis progression by growth, and socioeconomic and psychogenic problems. The average patient age was 33.5 years old, with 51 % females and 49 % males. The average body mass index was 19.43 kg/m2, which is considered underweight. The patients had 72 % paraparesis and 27 % paraplegia, 33 % grade C (according to the ASIA scale), 1.5/5 average motoric function and 41.12 % of participants had a history of pulmonary TB. The ADLs before treatment were severe, the average ODI score was 58/100 (severe disability) and the average JOA score was 5/18 (severe disability). Laboratory findings included increased leukocytes, prolonged erythrocyte sedimentation rates (ESR), increased C-reactive proteins, vitamin D deficiencies with an average level of 14.79 ng/mL, positive polymerase chain reactions, positive tuberculin tests (Mantoux), positive mycobacterium tuberculosis in cultures, positive granulomas and caseous appearances in histopathological examinations (Fig. 1, Fig. 2). All patients underwent X-rays, CT scans and MRIs (Fig. 3).

The treatment involved a combination of surgical treatment, anti-TB drugs and vitamin D. The indications of surgery are spinal TB associated with a neurological deficit, paravertebral segment abscesses, posterior lesions with abscesses or sinus, and vertebral instability with progressive kyphosis. Chemotherapy consisted of INH (5–15 mg/KgBW/day), rifampicin (10–15 mg/KgBW/day), pyrazinamide (25–35/KgBW/day) and ethambutol (15–20 mg/KgBW/day), all administered orally. Vitamin D was given at a dose of 5000 IU every day for 12 months. Evaluations were conducted on motor function, stiffness, bowel and urinary function, serum vitamin levels, fusion rate, and ADLs.
The results showed that patients had 100 % normal motor function power after 12 months of treatment. They had no urinary or bowel function disturbance, 3 % lower extremity stiffness and 98.5 % had normal serum vitamin D levels. The spinal fusion rate was 97.4 %, and pseudarthrosis was 2.6 % under plain X-rays after 12 months (Fig. 4). The ADLs after treatment were 5/100 (minimal disability) by ODI score and 17/18 (normal function) by JOA score (Fig. 5).

Discussion
After 12 months of treatment, patients had 100 % normal motor function ASIA E with a remaining 3 % in stiffness. Patients had 98.5 % normal vitamin D serum levels and a 97.4 % fusion rate. ADLs were 5/100 (minimal disability) by ODI score and 17/18 (normal function) by JOA score. Before treatment, most of the patients had a motoric disorder, ASIA C, as their chief complaint.
Neurogenic dysfunction is caused by compression of the sequester, abscess, fibrotic tissue and vascular thrombosis [9,10]. The process is initially apparent in the inferior-anterior portion of the vertebral body, spreading into the body's central portion or disks [11].
Surgical treatment consists of debridement, circumferential decompression, stabilisation, and fusion; result in proper vascularisation, perfusion, to prevent ischemia and inflammation. It will promote healing of bone and spinal cord lesion [3]. The expressions are recovery of neurologic function and fusion of the bone. The indications of surgery are spinal TB associated with a neurological deficit, paravertebral abscesses, posterior lesions with abscesses or sinus, and vertebral instability with progressive kyphosis. The surgical technique for spinal TB uses 10 alternative treatments from Prof. Soebroto Sapardan, which are adjusted to the degree of objection in each case. The 10 alternative treatments aim to combat infection in a stable and painless spine without unacceptable deformity, enabling the restoration of spinal function and a return to society, family, and occupation [10].
TB chemotherapy must be based on two microbiological principles, namely, a combination of drugs to prevent resistance and long-term therapy to prevent relapse [12,13]. Anti-TB drug treatment must be given in the form of a combination of several types of medications in sufficient quantities and in the correct dosages according to the treatment category. Single anti-TB drugs (monotherapy) should not be used, but rather, a fixed-dose combination of anti-TB drugs is more beneficial and is highly recommended [14]. The fixed-dose combination has several advantages in TB treatment, including dose adjustment according to body weight (ensuring the effectiveness of the drug and reducing side effects), prevention of multidrug resistance by the use of a single drug and a reduction in prescription errors and the number of tablets swallowed (simplifying drug administration and increasing patient compliance) [14,15].
The active form of vitamin D has an anti-inflammatory effect, promotes angiogenesis, boosts neurogenesis, protects the health of peripheral arteries and increases calcium serum levels [7,[[16], [17], [[18]]. Anti-inflammatory effects are caused by vitamin D receptors in immune cells and affect toll-like receptors [7,19]. Vitamin D can control autophagy in immature macrophages with the assistance of Ca2+/calmodulin-dependent kinase β (CaMKK β) [18]. The active form of vitamin D promotes angiogenesis by increasing vascular endothelial growth factor (VEGF) expression in vascular smooth muscle cells to the VEGF inducer via the immediate attachment of the vitamin D receptor and transcription factor [17]. A deficiency of vitamin D could cause undeveloped neurons to expand, reduce glutamate-glutamine and increase gamma-aminobutyric acid levels. This process indicates how vitamin D supplementation may boost neurogenesis [18]. Vitamin D also plays a recovery role in cases of Fahr's syndrome with dissociative amnesia, which is accompanied by calcification in the brain [6]. Therefore, vitamin D plays a role in shortening the duration of oral anti-TB drug use and increasing the incidence of bone fusion [20].
Vitamin D and anti-TB drug therapy need further research in the treatment of spinal TB in terms of efficacy, side effects and patient safety.
Conclusion
This case series shows neurological function recovery, normal ADLs, normal levels of vitamin D serum and spinal fusion after 12 months of spinal TB treatment by surgery, anti-TB drugs and vitamin D supplementation.

11 References (from DeepDyve)
  • Krishna (2019) - Vitamin D as a protector of arterial health: potential role in peripheral arterial disease formation - Int. J. Mol. Sci., 20
  • Sileshi (2021) - The impact of first-line anti-tubercular drugs ’ pharmacokinetics on treatment outcome: a systematic review

Clin. Pharmacol. Adv. Appl. ISSN, 13

  • Huang (2017) - Vitamin D deficiency and the risk of tuberculosis: a meta-analysis - Drug Des. Devel. Ther., 11
  • Ao (2021) - The effects of vitamin D on immune system and inflammatory diseases - Biomolecules, 11
  • Achour (2022) - Pathophysiology of tuberculosis and microbiological diagnosis - Imaging Tuberc.
  • Muhammad (2022) - A rare case of Fahr's syndrome with dissociative amnesia - J. Keperawatan Padjadjaran, 10


Groves (2017)
The impact of vitamin D deficiency on neurogenesis in the adult brain
Neural Regen. Res., 12

Dartois (2022)
Anti- tuberculosis treatment strategies and drug development: challenges and
Microbilogy, 20

Azadi (2018)
Mycobacteriosis and tuberculosis: laboratory diagnosis
Open Microbiol. J., 12

Metzger (2015)
The relationship between serum vitamin D levels and spinal fusion success: a quantitative analysis
Spine (Phila Pa 1976), 40

Bishop (2021)
Vitamin D and immune regulation: antibacterial
Am. Soc. Bone Miner. Res., 5

VitaminDWiki wonders why they did not just treat the TB with vitamin D, and skip the surgery

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Spinal TB surgery now includes Vitamin D as the standard of care (5,000 IU daily) – Sept 2024        
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