Journal of Neurology

, Volume 257, Issue 12, pp 1955–1962 | Cite as

The clinical spectrum of late-onset Alexander disease: a systematic literature review

  • Pietro BalbiEmail author
  • Silvana Salvini
  • Cira Fundarò
  • Giuseppe Frazzitta
  • Roberto Maestri
  • Dibo Mosah
  • Carla Uggetti
  • GianPietro Sechi


Following the discovery of glial fibrillary acidic protein (GFAP) mutations as the causative factor of Alexander disease (AxD), new case reports have recently increased, prompting a more detailed comprehension of the clinical features of the three disease subtypes (infantile, juvenile and adult). While the clinical pattern of the infantile form has been substantially confirmed, the late-onset subtypes (i.e., juvenile and adult), once considered rare manifestations of AxD, have displayed a wider clinical spectrum. Our aim was to evaluate the clinical phenotype of the adult and juvenile forms by reviewing the previously reported cases. Data were collected from previously published reports on 112 subjects affected by neuropathologically or genetically proven adult and juvenile Alexander disease. Although the late-onset forms of AxD show a wide clinical variability, a common pattern emerges from comparing previously reported cases, characterized by pseudo-bulbar signs, ataxia, and spasticity, associated with atrophy of the medulla and upper cervical cord on neuroimaging. Late-onset AxD cases can no longer be considered as rare manifestations of the disease. The clinical pattern usually reflects the topographic localization of the lesions, with adult cases displaying a predominant infratentorial localization of the lesions. Juvenile cases show clinical and radiological features which are intermediate between adult and infantile forms.


Systematic review Alexander disease GFAP Nosology Diagnostic criteria 


Conflict of interest


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Pietro Balbi
    • 1
    Email author
  • Silvana Salvini
    • 1
  • Cira Fundarò
    • 1
  • Giuseppe Frazzitta
    • 2
  • Roberto Maestri
    • 3
  • Dibo Mosah
    • 1
  • Carla Uggetti
    • 4
  • GianPietro Sechi
    • 5
  1. 1.Clinical NeurophysiologyScientific Institute of Montescano IRCCS ‘Fondazione S. Maugeri’MontescanoItaly
  2. 2.Department of NeurorehabilitationScientific Institute of Montescano IRCCS ‘Fondazione S. Maugeri’MontescanoItaly
  3. 3.Department of Biomedical EngineeringScientific Institute of Montescano IRCCS ‘Fondazione S. Maugeri’MontescanoItaly
  4. 4.Neuroradiological DepartmentNeurological Institute IRCCS ‘Fondazione C. Mondino’PaviaItaly
  5. 5.Institute of Clinical NeurologyUniversity of SassariSassariItaly

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