Early brain biopsy in neurological diseases of unknown etiology improves functional outcome.

BACKGROUND

The indications and timing of brain biopsy in adults with neurological diseases of unknown etiology remain controversial. We aimed to determine diagnostic yield, complications, outcomes, and survival after brain biopsy and evaluate whether early biopsy improves prognosis.

METHODS

We analyzed adults who underwent brain biopsy (2008-2024) after non-diagnostic workup at our institution. Primary outcomes were diagnostic yield, 6-month functional status using modified Rankin Scale (mRS), and overall survival (OS). Early biopsy was defined as ≤1 month after symptom onset. Multivariable logistic regression identified predictors of favorable outcomes (mRS≤2), and Cox models assessed OS.

RESULTS

Among 3014 biopsies, 294 met inclusion criteria (mean age 50.6 ± 15.3 years; 47% immunocompromised). Biopsy provided a contributory diagnosis in 69% of patients and changed management in 71%. Symptomatic complications occurred in 3.4% of patients. Functional independence (mRS≤2) increased from 44.6% at biopsy to 54.1% at 6 months (p = 0.003), with 22% mortality. Baseline independence (OR 7.15, 95%CI 3.94-12.97) and early biopsy (OR 2.03, 95%CI 1.05-3.93) predicted favorable outcomes, whereas solid organ tumor history (OR 0.32) and altered consciousness (OR 0.53) predicted worse recovery. Early biopsy yielded a higher diagnostic success rate (82% vs. 65%, p = 0.005). During 37.9-month follow- up, 31% died (mean OS 9.3 months). Longer OS was associated with baseline independence and autoimmune/inflammatory diagnosis, whereas solid-organ tumors, altered consciousness, and coma predicted shorter OS.

CONCLUSIONS

Brain biopsy is safe and diagnostically useful for cryptogenic neurological diseases. Early biopsy independently predicts better functional outcomes and higher diagnostic yield, supporting earlier tissue sampling after inconclusive noninvasive evaluation.