Clinical severity grading of NF2-related schwannomatosis

Abstract

Background: NF2-related schwannomatosis (NF2) is associated with various tumors of the central and peripheral nervous system. There is a wide range of disabilities these patients may suffer from and there is no validated clinical classification for disease severity. We propose a clinical classification consisting of three severity grades to assist in patient management.

Methods: Patient records from 168 patients were screened for most common diagnoses with severe impact on everyday tasks, social interactions and life expectancy. Eight main categories were identified. One point was assigned to each category. Three severity grades were differentiated as follows: grade 1 (mild NF2): 0 points; grade 2 (moderate NF2): < 3 points; grade 3 (severe NF2): ≥ 3 points. This grading system was then evaluated with respect to inter-rater reliability and clinical significance.

Results: The patients were grouped according to our new clinical grading system into grade 1 in 48% (n = 80), grade 2 in 43% (n = 72), and grade 3 in 10% of patients (n = 16). There was substantial inter-rater reliability between 3 raters with different levels of clinical experience (Fleiss' kappa = 0.62). The severity grades correlated significantly with hospitalization, number of operations and dependency on implants (such as cochlear implant, auditory brain-stem implants or ventriculoperitoneal shunts).

Conclusions: Clinical disease severity of NF2 patients is reflected in a simplified and rater-independent score with three grades. The score facilitates communication for medical personnel of varying experience and backgrounds, and adds a clinical tool to decision-making and research.

Keywords: Grading; Neurofibromatosis 2; Schwannomatosis; nf2-related schwannomatosis.

Fig. 1

The median number of annual out-patient contacts ± standard deviation (SD) was 1 ± 0.7 for grade 1, 0 ± 0.5 for grade 2 and 0 ± 0.1 for grade 3, respectively. There was a significant difference between grade 1 and grade 2 as well as grade 1 and grade 3 (** p < 0.01)

Fig. 2

The median number of annual admissions to the hospital ± SD was 0 ± 0.6 for grade 1, 1 ± 1.5 for grade 2 and 2 ± 2.3 for grade 3, respectively. There was a significant difference between grade 1 and grade 2, grade 1 and grade 3 as well as grade 2 and grade 3 (** p < 0.01)

Fig. 3

The median number of annual operations ± SD was 0 ± 0.3 for grade 1, 0 ± 1.0 for grade 2 and 1.5 ± 1.4 for grade 3, respectively. There was a significant difference between grade 1 and grade 2 as wells as grade 1 and grade 3 (** p < 0.01)