What is the recommended treatment for a patient with a leptomeningial (inflammation of the leptomeninges) infection of the spine?

Treatment of Leptomeningeal Infection of the Spine

The treatment approach depends critically on the underlying etiology: infectious causes (tuberculosis, fungal, bacterial) require prolonged antimicrobial therapy with adjunctive corticosteroids, while malignant leptomeningeal disease requires systemic therapy with CNS penetration plus focal radiotherapy for symptomatic lesions. 1

Diagnostic Workup Before Treatment

Gadolinium-enhanced MRI of the entire spine is mandatory, showing characteristic leptomeningeal enhancement along nerve roots and in the basilar cisterns. 1 The imaging should include post-gadolinium sagittal T1-weighted sequences of the spine, with axial T1-weighted images of regions of interest. 2

Lumbar puncture with CSF analysis is essential unless contraindicated by coagulopathy, infection at the LP site, or signs of severe sepsis. 2 Collect a minimum of 5-10 mL of CSF and process within 30 minutes. 2, 1 The CSF profile typically shows:

• Elevated opening pressure
• Low glucose (less than half of serum glucose)
• Elevated protein (commonly >150 mg/dL)
• Lymphocytic pleocytosis 2, 1

Send CSF for: acid-fast bacilli smear and culture, fungal culture, bacterial culture, cryptococcal antigen, VDRL, and cytology to exclude malignancy. 1 If the initial CSF cytology is negative but clinical suspicion remains high, perform a second lumbar puncture. 2

Treatment Based on Etiology

Infectious Leptomeningitis

For tuberculous meningitis (the most common infectious cause worldwide):

• Initiate multi-drug anti-tuberculous therapy: isoniazid, rifampin, pyrazinamide, and ethambutol for a minimum of 12 months 1
• Add adjunctive corticosteroids (prednisone 1 mg/kg/day) to reduce inflammation and prevent complications 1
• This combination reduces mortality from the 20-50% range even with treatment alone 1

For fungal meningitis (Cryptococcus, Histoplasma, Coccidioides, Aspergillus):

• Administer prolonged organism-specific antifungal therapy 1
• For coccidioidal meningitis specifically, untreated disease is nearly always fatal 2
• Continue treatment based on clinical response and CSF parameters 2

For bacterial meningitis:

• Start empiric IV antibiotics immediately if bacterial meningitis is suspected, ideally within the first hour if signs of severe sepsis are present 2
• Ceftriaxone 2 grams IV daily (or divided every 12 hours) is a standard empiric choice for adults 3
• For meningitis in children, use ceftriaxone 100 mg/kg/day (not to exceed 4 grams daily) 3
• Do not delay antibiotics for imaging or LP if the patient has signs of severe sepsis or rapidly evolving rash 2
• If LP is performed within 4 hours of starting antibiotics, CSF culture remains likely positive (73% yield), but drops to 11% after 4 hours and 0% after 8 hours 4

For neurosarcoidosis (non-infectious granulomatous cause):

• First-line: high-dose corticosteroids (prednisone 1 mg/kg/day) 1
• Maintenance: steroid-sparing immunosuppressants (methotrexate, azathioprine, mycophenolate) 1
• Neurosarcoidosis typically responds well with good long-term outcomes if diagnosed early 1

Malignant Leptomeningeal Disease (Leptomeningeal Carcinomatosis)

For patients with reasonable performance status (KPS ≥70) and life expectancy >1 month:

Systemic therapy is the fundamental pillar - prioritize agents with CNS penetration and blood-CSF barrier permeability: 5

• HER2+ breast cancer: trastuzumab deruxtecan or tucatinib combinations 5
• EGFR-mutated lung cancer: osimertinib or almonertinib 5
• BRAF-mutated melanoma: BRAF/MEK inhibitors with CNS penetration 5

Intrathecal chemotherapy is most effective for thin linear leptomeningeal deposits with unobstructed CSF flow: 5

• Methotrexate 15 mg per dose: twice weekly for 4 weeks, then weekly for 4 weeks, then monthly 5
• Administer via Ommaya reservoir (ventricular route) rather than lumbar route when feasible, as this is associated with better survival 5
• Do not give intrathecal chemotherapy if CSF flow obstruction is present - radiotherapy must restore flow first 5, 6

Focal radiotherapy for symptomatic lesions (cranial neuropathies, spinal cord compression, nodular disease): 5

• Standard palliative dose: 30-36 Gy in 10-12 daily fractions 5
• Radiotherapy provides faster symptom relief than chemotherapy 5

For patients with poor prognosis (KPS <70 or life expectancy <1 month):

• Prioritize best supportive care and palliative measures over disease-directed therapy 5, 6
• Consider palliative radiotherapy only if symptomatic benefit clearly outweighs treatment toxicities 6
• Do not pursue intrathecal chemotherapy in dying patients 6

Surgical Interventions

Ventriculoperitoneal shunt placement should be offered for symptomatic hydrocephalus and elevated intracranial pressure as a palliative procedure. 1, 5 This relieves symptoms in most treated patients and improves quality of life. 1

For vertebral body involvement with spinal instability:

• Surgical debridement and stabilization with instrumentation may be required 2, 7, 8
• Titanium constructs are preferred as they are biologically inert with smooth surfaces that resist organism adherence 2
• Complete sterilization before hardware implantation is desirable but not a practical expectation 2

Duration and Monitoring

Antimicrobial therapy duration:

• Tuberculous meningitis: minimum 12 months 1
• Bacterial spinal infections: minimum 6 weeks, initially IV then oral 7, 8
• Continue until signs and symptoms resolve, typically 4-14 days for uncomplicated bacterial meningitis, longer for complicated infections 3

Serial MRI surveillance is essential for monitoring treatment response and detecting complications. 2, 9

Critical Pitfalls to Avoid

• Do not delay antibiotics for CT scanning in patients with suspected bacterial meningitis and signs of severe sepsis - 67% of unnecessary delays are due to CT scans 4
• Do not perform LP if platelet count <40 × 10⁹/L, INR >1.4, or within 12 hours of prophylactic LMWH 2
• Do not combine craniospinal radiation with intrathecal or systemic chemotherapy (especially methotrexate) due to increased leukoencephalopathy risk 5
• Do not use calcium-containing IV solutions with ceftriaxone due to precipitation risk, especially in neonates 3
• Do not administer intrathecal chemotherapy in patients with symptomatic hydrocephalus requiring VP shunt or with CSF flow obstruction 5, 6