Validated age-specific reference values for CSF total protein levels in children.

OBJECTIVE: To define age-specific reference values for cerebrospinal fluid (CSF) total protein levels for children and validate these values in children with Guillain-Barré syndrome (GBS), acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS). METHODS: Reference values for CSF total protein levels were determined in an extensive cohort of diagnostic samples from children (<18 year) evaluated at Erasmus Medical Center/Sophia Children's Hospital. These reference values were confirmed in children diagnosed with disorders unrelated to raised CSF total protein level and validated in children with GBS, ADEM and MS. RESULTS: The test results of 6145 diagnostic CSF samples from 3623 children were used to define reference values. The reference values based on the upper limit of the 95% CI (i.e. upper limit of normal) were for 6 months-2 years 0.25 g/L, 2-6 years 0.25 g/L, 6-12 years 0.28 g/L, 12-18 years 0.34 g/L. These reference values were confirmed in a subgroup of 378 children diagnosed with disorders that are not typically associated with increased CSF total protein. In addition, the CSF total protein levels in these children in the first 6 months after birth were highly variable (median 0.47 g/L, IQR 0.26-0.65). According to these new reference values, CSF total protein level was elevated in 85% of children with GBS, 66% with ADEM and 23% with MS. CONCLUSION: More accurate age-specific reference values for CSF total protein levels in children were determined. These new reference values are more sensitive than currently used values for diagnosing GBS and ADEM in children.

Recognizing Guillain-Barre syndrome in preschool children.

OBJECTIVE: To determine whether recognition of Guillain-Barré syndrome (GBS) is delayed in preschool children, what causes this delay, and if the clinical presentation differs from older children. METHODS: In a retrospective cohort study, standardized data from all children with GBS seen at the Erasmus MC Sophia Children's University Hospital in Rotterdam from 1987 to 2009 were collected regarding clinical presentation, patient's delay, initial diagnosis, and doctor's delay to the diagnosis. We compared preschool children (<6 years old) with older children (6-18 years old). RESULTS: GBS was diagnosed in 23 preschool children and in 32 older children. Fifteen (68%) of the preschool children were initially misdiagnosed compared to 6 (21%) of the older children (p = 0.001). Median patient delay to consult a pediatrician in both age groups was the same (5.0 days). The median doctor's delay to diagnose possible GBS in preschool children was significantly longer than in older children (3 days vs 0 days). In one-quarter of preschool children, this doctor's delay was more than 1 week, up to 22 days. In preschool children, refusal to walk and pain in the legs were the most frequent presenting symptoms (65%), while older children presented with more classic symptoms of weakness and paresthesias. The preschool children were initially misdiagnosed with myopathy, tonsillitis, meningitis, rheumatoid disorders, coxitis, or discitis. CONCLUSION: The diagnosis of GBS in preschool children is delayed compared to older children. This delay is partly explained by the nonspecific clinical presentation, challenging neurologic examination, and alternative diagnoses in preschool children.