Electro-clinical features and magnetic resonance imaging correlates in Menkes disease

Brain Dev. 2013 May;35(5):398-405. doi: 10.1016/j.braindev.2012.07.016. Epub 2012 Aug 24.


Background: Epilepsy is an early and important feature in Menkes disease (MD), an X-linked recessive neurodegenerative disorder of childhood with defect in copper metabolism. There are only few reports on the electro-clinical and magnetic resonance imaging correlates in Menkes disease. The current study describes the electro-clinical features in MD in relation with the structural findings on MRI.

Patients and methods: Six patients from five families were evaluated between 2005 and 2011. Their diagnosis was based on the characteristic morphological features, microscopic evidence of pili torti and low copper and ceruloplasmin levels. All the patients underwent MRI and EEG as part of the evaluation.

Results: All patients had classical form of MD with typical morphological features. All but one patient had refractory seizures. Seizure types included multifocal clonic seizures (n=3), myoclonic jerks (n=4) and tonic spasms (n=1). EEG was markedly abnormal in all except in the patient without clinical seizures. While focal epileptiform discharges predominated before six months of age modified hypsarrhythmia was characteristically noted thereafter. MR Imaging revealed abnormalities in all patients, with cerebral atrophy and delayed myelination being the most common observations. Other features noted were subdural effusion (n=3), leukoencephalopathy (n=3) and basal ganglia signal changes (n=1). Follow up imaging in three patients showed resolution of white matter signal intensity changes.

Conclusions: Electro-clinical features in Menkes disease are age dependent and evolve sequentially. White matter changes coincided with acute exacerbation of seizures. There was fair correlation between the electro-clinical features and structural findings on MRI.

MeSH terms

  • Brain / pathology
  • Brain / physiopathology
  • Brain Waves / physiology*
  • Diffusion Magnetic Resonance Imaging
  • Electroencephalography
  • Follow-Up Studies
  • Humans
  • Infant
  • Magnetic Resonance Imaging*
  • Male
  • Menkes Kinky Hair Syndrome / complications*
  • Menkes Kinky Hair Syndrome / pathology*
  • Nerve Fibers, Myelinated / pathology
  • Seizures / etiology*