title: Early Diagnosis and Monitoring of Neurodegenerative Langerhans Cell Histiocytosis.
abstract: BACKGROUND
  Neurodegenerative Langerhans Cell Histiocytosis (ND-LCH) is a rare, unpredictable consequence that may devastate the quality of life of patients cured from LCH. We prospectively applied a multidisciplinary diagnostic work-up to early identify and follow-up patients with ND-LCH, with the ultimate goal of better determining the appropriate time for starting therapy.
  
  
  METHODS
  We studied 27 children and young adults with either ND-LCH verified by structural magnetic resonance imaging (MRI) (group 1) or specific risk factors for (diabetes insipidus, craniofacial bone lesions), but no evidence of, neurodegenerative MRI changes (group 2). All patients underwent clinical, neurophysiological and MRI studies.
  
  
  RESULTS
  Seventeen patients had MRI alterations typical for ND-LCH. Nine showed neurological impairment but only three were symptomatic; 11 had abnormal somatosensory evoked potentials (SEPs), and five had abnormal brainstem auditory evoked potentials (BAEPs). MR spectroscopy (MRS) showed reduced cerebellar NAA/Cr ratio in nine patients. SEPs showed sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for predicting ND-LCH of 70.6% (95%CI, 44.0%-89.7%), 100% (69.2%-100%), 100% (73.5%-100%), and 66.7% (38.4%-88.2%), respectively. Repeated investigations in group 1 revealed increasingly abnormal EP parameters, or neurological examination, or both, in nine of fifteen patients while MRI remained unchanged in all but one patient.
  
  
  CONCLUSIONS
  A targeted MRI study should be performed in all patients with risk factors for ND-LCH for early identification of demyelination. The combined use of SEPs and careful neurological evaluation may represent a valuable, low-cost, well-tolerated and easily available methodology to monitor patients from pre-symptomatic to symptomatic stages. We suggest a multidisciplinary protocol including clinical, MRS, and neurophysiological investigations to identify a population target for future therapeutic trials.
authors.affiliation: Pediatric Hematology Oncology, Meyer Children's University Hospital, Florence, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Sieni
authors.affiliation: Pediatric Neurology, Meyer Children's University Hospital, Florence, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Barba
authors.affiliation: Pediatric Radiology, Meyer Children's University Hospital, Florence, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Mortilla
authors.affiliation: Pediatric Radiology, Meyer Children's University Hospital, Florence, Italy; Department of Diagnostic Imaging, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Savelli
authors.affiliation: Department of Statistics, Informatics and Applications "G. Parenti", University of Florence, Florence, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Grisotto
authors.affiliation: Pediatric Neurology, Meyer Children's University Hospital, Florence, Italy.
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Di Giacomo
authors.affiliation: Pediatric Neurology, Meyer Children's University Hospital, Florence, Italy.
authors.forename: Katiuscia
authors.initials: K
authors.lastname: Romano
authors.affiliation: Pediatric Radiology, Meyer Children's University Hospital, Florence, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Fonda
authors.affiliation: Department of Statistics, Informatics and Applications "G. Parenti", University of Florence, Florence, Italy; Biostatistics Unit, ISPO Cancer Prevention and Research Institute, Florence, Italy.
authors.forename: Annibale
authors.initials: A
authors.lastname: Biggeri
authors.affiliation: Pediatric Neurology, Meyer Children's University Hospital, Florence, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
authors.affiliation: Pediatric Hematology Oncology, Meyer Children's University Hospital, Florence, Italy; Direzione Generale, Azienda Sanitaria Provinciale 7, Ragusa, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Aricò
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D042241:Early Diagnosis; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory; D005073:Evoked Potentials, Somatosensory; D005260:Female; D005500:Follow-Up Studies; D006646:Histiocytosis, Langerhans-Cell / Q000175:diagnosis*; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D019636:Neurodegenerative Diseases / Q000175:diagnosis*; D012372:ROC Curve; D012307:Risk Factors; D012680:Sensitivity and Specificity; D055815:Young Adult