Clinical features, neurologic recovery, and risk factors of postoperative posterior fossa syndrome and delayed recovery: a prospective study

Abstract

Background: Posterior fossa syndrome (PFS) is a known consequence of medulloblastoma resection. Our aim was to clinically define PFS, its evolution over time, and ascertain risk factors for its development and poor recovery.

Methods: Children with medulloblastoma treated at St Jude Children's Research Hospital from 6/2013 to 7/2019 received standardized neurological examinations, before and periodically after radiation therapy. Most (98.3%) were enrolled on the ongoing multi-institutional protocol (SJMB12; NCT01878617).

Results: Sixty (34%) of 178 evaluated children had PFS. Forty (23%) had complete mutism (PFS1) and 20 (11%) had diminished speech (PFS2). All children with PFS had severe ataxia and 42.5% of PFS1 had movement disorders. By multivariable analysis, younger age (P = .0005) and surgery in a low-volume surgery center (P = .0146) increased PFS risk, while Sonic Hedgehog tumors had reduced risk (P = .0025). Speech and gait returned in PFS1/PFS2 children at a median of 2.3/0.7 and 2.1/1.5 months, respectively, however, 12 (44.4%) of 27 PFS1 children with 12 months of follow-up were nonambulatory at 1 year. Movement disorder (P = .037) and high ataxia score (P < .0001) were associated with delayed speech recovery. Older age (P = .0147) and high ataxia score (P < .0001) were associated with delayed gait return. Symptoms improved in all children but no child with PFS had normal neurologic examination at a median of 23 months after surgery.

Conclusions: Categorizing PFS into types 1 and 2 has prognostic relevance. Almost half of the children with PFS1 with 12-month follow-up were nonambulatory. Surgical experience was a major modifiable contributor to the development of PFS.

Keywords: cerebellar mutism; medulloblastoma; outcome; posterior fossa syndrome; risk factors.

Fig. 1

(A) Risk factors for the development of posterior fossa syndrome. (B) Methylation tumor subgroups. Much larger representation of Sonic Hedgehog group in the children without posterior fossa syndrome. (C) Distribution of posterior fossa types 1 + 2 among low- and high-volume surgery centers. P value represents Cochran-Armitage exact trend test. (D) MRI comparison of a child with almost normal neurologic examination post tumor resection (left image) and a child who did not regain speech and sitting balance 12 months after tumor resection (right image). Note severe injury to dorsal midbrain and bilateral superior cerebellar peduncles. Both had midline fourth ventricular tumor.

Fig. 2

(A) Cumulative incidence plots showing recovery of independent gait in all 178 children and by different clinical subgroups. (B) Profile plots of scale for the assessment and rating of ataxia (SARA) scores in posterior fossa syndrome PFS1 + 2 cohort (n = 60) and non-PFS cohort (n = 118). A score of 0 is normal and 40 is inability to sit, speak, stand, and reach. Spikes represent children who developed treatment-related complications such as radiation necrosis. Orange straight lines represent fitted lines based on change-point linear mixed-effects model. (C) Risk factors for delayed recovery of independent gait.

Fig. 3

Proportions of children affected with neurologic deficits at baseline and 12 months after surgery in posterior fossa syndrome type 1 (PFS1), posterior fossa syndrome type 2 (PFS2), severe ataxia group with or without behavior change, and those with normal language and without severe ataxia (others).