A clinical diagnostic algorithm for early onset cerebellar ataxia

R Brandsma; C C Verschuuren-Bemelmans; D Amrom; N Barisic; P Baxter; E Bertini; L Blumkin; V Brankovic-Sreckovic; O F Brouwer; K Bürk; C E Catsman-Berrevoets; D Craiu; I F M de Coo; J Gburek; C Kennedy; T J de Koning; H P H Kremer; R Kumar; A Macaya; A Micalizzi; M Mirabelli-Badenier; A Nemeth; S Nuovo; B Poll-The; T Lerman-Sagie; M Steinlin; M Synofzik; M A J Tijssen; G Vasco; M A A P Willemsen; G Zanni; E M Valente; E Boltshauser; D A Sival

doi:10.1016/j.ejpn.2019.08.004

A clinical diagnostic algorithm for early onset cerebellar ataxia

Eur J Paediatr Neurol. 2019 Sep;23(5):692-706. doi: 10.1016/j.ejpn.2019.08.004. Epub 2019 Aug 10.

Authors

R Brandsma¹, C C Verschuuren-Bemelmans², D Amrom³, N Barisic⁴, P Baxter⁵, E Bertini⁶, L Blumkin⁷, V Brankovic-Sreckovic⁸, O F Brouwer⁹, K Bürk¹⁰, C E Catsman-Berrevoets¹¹, D Craiu¹², I F M de Coo¹³, J Gburek¹⁴, C Kennedy¹⁵, T J de Koning¹⁶, H P H Kremer¹, R Kumar¹⁷, A Macaya¹⁸, A Micalizzi¹⁹, M Mirabelli-Badenier²⁰, A Nemeth²¹, S Nuovo²², B Poll-The²³, T Lerman-Sagie⁷, M Steinlin²⁴, M Synofzik²⁵, M A J Tijssen¹, G Vasco²⁶, M A A P Willemsen²⁷, G Zanni⁶, E M Valente²⁸, E Boltshauser²⁹, D A Sival³⁰

Affiliations

¹ Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
² Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
³ Department of Neurology, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Brussels, Belgium; Neurology Unit, Kannerklinik Centre Hospitalier de Luxembourg, Luxembourg, Grand Duchy of Luxembourg.
⁴ Department of Pediatrics, Clinical Medical Centre Zagreb, University of Zagreb Medical School, Croatia.
⁵ Department of Paediatric Neurology, Sheffield Children's Hospital, UK.
⁶ Unit of Neuromuscular and Neurodegenerative Disorders, Bambino Gesu' Children's Research Hospital, Rome, Italy.
⁷ Pediatric Neurology Unit, Wolfson Medical Center, Holon and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
⁸ Clinic for Child Neurology and Psychiatry, Medical Faculty, University of Belgrade, Belgrade, Serbia.
⁹ Department of Paediatric Neurology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
¹⁰ Paracelsus-Elena-Klinik Kassel, University of Marburg, Germany.
¹¹ Department of Pediatric Neurology, Erasmus University Hospital/Sophia Children's Hospital, Rotterdam, the Netherlands.
¹² Carol Davila University of Medicine Bucharest, Department of Clinical Neurosciences, Pediatric Neurology II Discipline, Alexandru Obregia Hospital, Bucharest, Romania.
¹³ Department of Genetics and Cell Biology, University of Maastricht, Maastricht, the Netherlands.
¹⁴ Centre for Paediatrics and Adolescent Medicine, Hannover Medical School, Hannover, Germany.
¹⁵ Clinical Neurosciences, Faculty of Medicine, University of Southampton, UK.
¹⁶ Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Department of Paediatric Neurology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
¹⁷ Department of Pediatric Neurology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
¹⁸ Grup de Recerca en Neurologia Pediàtrica, Institut de Recerca Vall d'Hebron, Universitat Autònoma de Barcelona, Secció de Neurologia Pediàtrica, Hospital Universitari Vall d'Hebron, 08002, Barcelona, Spain.
¹⁹ Laboratory of Medical Genetics, Bambino Gesu Children's Hospital, Rome, Italy.
²⁰ DINOGMI Department-University of Genoa/Unit of Child Neuropsychiatry, G. Gaslini Institute, Genoa, Italy.
²¹ Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom; Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Trust, Oxford, United Kingdom.
²² Neurogenetics Unit, IRCCS Santa Lucia Foundation, Rome, Italy; Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
²³ Department of Pediatric Neurology, Emma Children's Hospital, Academic Medical Centre (AMC), University of Amsterdam, the Netherlands.
²⁴ Division of Neuropediatrics, Development and Rehabilitation, University Children's Hospital Bern, Inselspital, Bern University Hospital, University of Bern, Switzerland.
²⁵ Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany.
²⁶ Division of Neurorehabilitation, Bambino Gesu' Children's Research Hospital, Rome, Italy.
²⁷ Department of Pediatric Neurology, Radboud University Medical Center/Amalia Children's Hospital, Nijmegen, the Netherlands.
²⁸ Neurogenetics Unit, IRCCS Santa Lucia Foundation, Rome, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy.
²⁹ Department of Pediatric Neurology, University Children's Hospital, Zürich, Switzerland.
³⁰ Department of Paediatric Neurology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic address: d.a.sival@umcg.nl.

PMID: 31481303
DOI: 10.1016/j.ejpn.2019.08.004

Abstract

Early onset cerebellar Ataxia (EOAc) comprises a large group of rare heterogeneous disorders. Determination of the underlying etiology can be difficult given the broad differential diagnosis and the complexity of the genotype-phenotype relationships. This may change the diagnostic work-up into a time-consuming, costly and not always rewarding task. In this overview, the Childhood Ataxia and Cerebellar Group of the European Pediatric Neurology Society (CACG-EPNS) presents a diagnostic algorithm for EOAc patients. In seven consecutive steps, the algorithm leads the clinician through the diagnostic process, including EOA identification, application of the Inventory of Non-Ataxic Signs (INAS), consideration of the family history, neuro-imaging, laboratory investigations, genetic testing by array CGH and Next Generation Sequencing (NGS). In children with EOAc, this algorithm is intended to contribute to the diagnostic process and to allow uniform data entry in EOAc databases.

Keywords: Algorithm; Cerebellum; Child; Diagnosis; Early Onset Ataxia; NGS techniques.

Publication types

Review

MeSH terms

Adolescent
Algorithms*
Child
Decision Support Systems, Clinical*
Diagnosis, Differential
Female
Humans
Male
Spinocerebellar Degenerations / diagnosis*