When are steroids indicated in adult central nervous system diseases and what are the recommended dosing regimens for acute bacterial meningitis, tuberculous meningitis, malignant brain tumor edema, multiple sclerosis relapse, acute spinal cord injury, and traumatic brain injury, including contraindications and monitoring?

Steroid Use in CNS Patients

Brain Tumors (Primary and Metastatic)

Dexamethasone is the preferred corticosteroid for brain tumor-associated edema, and should only be initiated in symptomatic patients at 4-8 mg/day for mild symptoms or 16 mg/day for moderate-to-severe symptoms, then tapered to the lowest effective dose as rapidly as possible. 1, 2

Dosing Strategy

• Asymptomatic patients with radiographic edema do not require steroids, even with extensive edema on imaging 3, 2
• For mild neurological deficits: Start dexamethasone 4-8 mg/day as a single daily dose (preferably morning to minimize sleep disturbance) 1, 2
• For moderate-to-severe symptoms with significant mass effect: Start 16 mg/day or higher 3, 1, 2
• For acute neurologic emergencies: Doses up to 100 mg/day in divided doses may be considered 3
• Patients with extensive mass effect should receive steroids for at least 24 hours before radiotherapy 3

Critical Management Principles

• Taper steroids as quickly as clinically tolerated - typically over 2-4 weeks once symptoms improve 4, 2
• Use the lowest dose for the shortest time possible to minimize toxicity 3, 2
• Prophylactic steroid use is increasingly discouraged as evidence links steroid use to inferior survival in glioblastoma 2
• Steroids may be detrimental in patients receiving immunotherapy for brain tumors 3, 2

Important Caveats

• Exception for CNS lymphoma: Avoid steroids prior to biopsy where possible, as they can interfere with diagnosis 3
• Long-term use (>3-4 weeks) requires Pneumocystis jiroveci pneumonia (PJP) prophylaxis with trimethoprim-sulfamethoxazole 2
• Also provide PJP prophylaxis for patients with lymphocyte count <1000/mL or those receiving concurrent radiation/chemotherapy 2
• Patients at high risk for GI complications (perioperative, prior ulcers/GI bleed, receiving NSAIDs or anticoagulation) should receive H2 blockers or proton pump inhibitors 3

Why Dexamethasone

Dexamethasone is preferred over other corticosteroids due to its high potency, minimal mineralocorticoid activity (reducing fluid retention), and superior blood-brain barrier penetration 1, 2, 5

Acute Bacterial Meningitis

Dexamethasone should be administered with the first dose of antibiotics in adults with suspected acute community-acquired bacterial meningitis, particularly pneumococcal meningitis. 6, 7

Dosing Regimen

• Administer dexamethasone 10 mg IV every 6 hours for 4 days, starting with or just before the first antibiotic dose 6, 8
• Treatment reduces mortality by 40% (relative risk 0.6) and neurological sequelae in bacterial meningitis 6
• In pneumococcal meningitis specifically, case-fatality is reduced by 21% 6

Evidence Strength

• The benefit is most conclusive for pneumococcal meningitis in adults 6, 8
• For meningococcal meningitis, mortality and neurological sequelae trends favor steroids but are not statistically significant 6
• Adverse events (particularly GI bleeding) occur equally in steroid and placebo groups, with GI bleeding in only 1% of steroid-treated patients 6

Tuberculous Meningitis

Adjunctive glucocorticoid therapy reduces mortality in tuberculous meningitis, particularly in patients with more severe infection. 8, 7

Clinical Application

• Steroids reduce mortality through mechanisms that remain incompletely understood 7
• The benefit is most pronounced in patients with more severe disease presentation 8
• Effects on morbidity are less clear than mortality benefits 7
• Specific dosing regimens vary, but dexamethasone or prednisolone are typically used for several weeks with gradual taper 8

Multiple Sclerosis Relapse

While the provided evidence does not contain specific MS relapse guidelines, standard practice uses high-dose methylprednisolone 1000 mg IV daily for 3-5 days for acute relapses, based on general medical knowledge.

Acute Spinal Cord Injury

Methylprednisolone administered within 8 hours of acute spinal cord injury improves neurologic recovery, but must follow a specific dosing protocol. 9

Specific Protocol

• Bolus: 30 mg/kg IV over 15 minutes 9
• Maintenance: 5.4 mg/kg/hour continuous infusion for 23 hours if started within 3 hours of injury 9
• Extended protocol: Continue maintenance infusion for 48 hours total (instead of 24 hours) if treatment starts between 3-8 hours post-injury for additional benefit 9
• Critical time window: Must be initiated within 8 hours of injury; no benefit demonstrated beyond this window 9

Evidence Quality

• This protocol has been replicated in Japanese trials but not in French trials 9
• Meta-analysis of three trials shows significant motor function recovery with this regimen 9
• This is the only pharmacological therapy with Phase III randomized trial efficacy for acute spinal cord injury 9

Traumatic Brain Injury

The provided evidence does not contain specific guidelines for steroid use in traumatic brain injury. Based on general medical knowledge, the CRASH trial demonstrated that corticosteroids are contraindicated in moderate-to-severe traumatic brain injury as they increase mortality.

Monitoring and Side Effects

Common Adverse Effects

• Hyperglycemia (monitor blood glucose closely) 1, 2
• Sleep disturbances (give morning dosing) 1
• Increased infection risk 1, 2
• GI complications (bleeding, perforation) 3, 5
• Steroid myopathy (most frequent serious side effect in neuro-oncology patients) 5
• Personality changes and psychiatric effects 4, 2
• Impaired wound healing 3, 4
• Metabolic derangements 3, 4

Long-term Toxicity (>3 weeks)

• Suppressed immunity 3, 4
• Osteoporosis 2
• Diabetes and hypertension 2
• Opportunistic infections (particularly PJP) 2, 5

Drug Interactions

• Phenytoin is the most important interaction with dexamethasone 5
• Enzyme-inducing antiepileptic drugs (phenytoin, phenobarbital, carbamazepine) should be avoided where possible in favor of non-enzyme-inducing agents (levetiracetam, valproic acid) 3

Common Pitfalls to Avoid

• Underdosing in severe symptoms: Ensure adequate initial dosing based on symptom severity 1, 4
• Failure to taper gradually: Abrupt discontinuation can cause adrenal insufficiency 1, 4
• Using steroids in asymptomatic patients: This adds toxicity without benefit 3, 2
• Prolonged high-dose therapy: Increases toxicity and may worsen survival in glioblastoma 2
• Forgetting PJP prophylaxis: Required for steroid use >4 weeks 2
• Using steroids before biopsy in suspected CNS lymphoma: Interferes with diagnosis 3