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Review
A practical approach to diagnosing adult onset leucodystrophies
  1. R M Ahmed1,
  2. E Murphy2,
  3. I Davagnanam3,
  4. M Parton4,
  5. J M Schott1,
  6. C J Mummery1,
  7. J D Rohrer1,
  8. R H Lachmann2,
  9. H Houlden5,
  10. N C Fox1,
  11. J Chataway6
  1. 1Department of Neurodegenerative Disease, Dementia Research Centre, National Hospital for Neurology & Neurosurgery and UCL Institute of Neurology, London, UK
  2. 2The Charles Dent Metabolic Unit, National Hospital for Neurology & Neurosurgery and UCL Institute of Neurology, London, UK
  3. 3Lysholm Department of Neuroradiology, National Hospital for Neurology & Neurosurgery and UCL Institute of Neurology, London, UK
  4. 4Queen Square Centre for Neuromuscular Diseases, National Hospital for Neurology & Neurosurgery and UCL Institute of Neurology, London, UK
  5. 5Department of Molecular Neurosciences, National Hospital for Neurology & Neurosurgery and UCL Institute of Neurology, London, UK
  6. 6Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre, National Hospital for Neurology & Neurosurgery and UCL Institute of Neurology, London, UK
  1. Correspondence to Dr J Chataway, Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre, National Hospital for Neurology & Neurosurgery and University College London Institute of Neurology, Queen Square, London WC1N 3BG, UK; jeremy.chataway{at}uclh.nhs.uk

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Introduction

The term leucodystrophy refers to a group of conditions that are inherited and involve the progressive destruction or loss of previously acquired myelin.1 The most commonly reported of these disorders have a metabolic origin and are associated with abnormalities on specialist biochemical testing. Recently, a number of conditions caused by genes coding for proteins not directly involved in metabolic pathways and for which the diagnosis relies directly on gene analysis have also been described. In clinical practice, distinguishing ‘classical’ inherited leucodystrophies from other causes of white matter disease, including vascular and inflammatory disorders, may not always be straightforward.

Although individually rare, with no single condition having a prevalence of >1 in 20 000, the reported prevalence of adult onset leucodystrophies is rising. This is likely to be related to the increased use of brain MRI and new genetic insights. Collectively their incidence may rival that of multiple sclerosis (MS).2 Nonetheless, the rarity of each condition and the wide differential means that diagnosis can be challenging and most clinicians will lack experience in the area. Currently, a significant proportion of individuals may remain without a precise diagnosis despite intensive investigations.

Much has been written in the paediatric literature about leucodystrophies,3 but the adult neurologist, with a new case, is often left with an extensive and detailed table of rare disorders to consider, without an obvious diagnostic pathway to follow. In addition, leucodystrophies that classically present in infancy or childhood may have a very different or attenuated clinical presentation in adulthood, making diagnostic features less familiar. In this review, taking a clinical case as a starting point, we address:

  • ▸ most commonly presenting leucodystrophies in adults

  • ▸ clinical presentations

  • ▸ MRI patterns for specific leucodystrophies

  • ▸ method of investigating leucodystrophies in an adult

  • ▸ current and future treatment possibilities.

Table 1 summarises the most frequent of …

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