History and Physical
A male infant with no prior history developed generalized tonic-clonic seizures with multifocal EEG changes at 2 months of life. He also demonstrated feeding difficulties with poor weight gain. Physical examination revealed global developmental delay with axial hypotonia. He started treatment with sodium valproate and oxcarbazepine. One month later, he had persistent epileptic seizures and low weight/height for his age with microcephaly. There was notable axial hypotonia with delayed motor milestones. In addition, he had unusual hair in both temporal regions with a poor, brittle, silvery appearance that fell out easily. On microscopy, the hair showed findings of pili torti and trichorexis nodosa. Blood work showed very low values of copper at 34 ug/L (normal 620–1544) and ceruloplasmin at 35 mg/L (normal 200–470). Brain MRI and genetic testing were ordered.
Diagnostic Workup
Skeletal survey showed widened metaphyses with osteoporosis and multiple fractures ( Fig. 32.1 ).
Menkes disease. (A and B) Skeletal survey shows broad ribs and metaphyseal spurs.
Brain MRI showed abnormal myelination and white matter lesions with involvement of the neostriatum. There was tortuosity and elongation of major cerebral arteries ( Fig. 32.2 ).
Menkes disease. Brain MRI, (A and B) axial T2, (C) MRA at 6 months, and (D) axial T2 at 18 months show delayed myelination, tortuous cerebral arteries, and wide Sylvian fissures.
Clinical Differential Diagnosis
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Early brain injury
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Epileptic or developmental encephalopathies
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Gray matter neurodegenerative diseases such as neuronal ceroid lipofuscinosis
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Mitochondrial disorders such as Alpers disease
Imaging Differential Diagnosis
Abusive head trauma: Can present with subdural hematohygromas and other injuries of the central nervous and skeletal systems. Evaluate for mechanical injuries ( Fig. 32.3 ).
Abusive head trauma. Brain MRI, (A) axial T2 and (B) ADC show bilateral subdural fluid collections ( asterisks ) with cortical restricted diffusion ( arrowheads ) indicating hypoxic-ischemic injury. (C) Axial SWI shows irregular and thrombosed cortical and bridging veins (“lollipop” and “tadpole” signs) ( arrows ).
Glutaric aciduria type 1: Bilateral abnormalities of the deep gray nuclei, progressing from edema to atrophy. The Sylvian fissures are underopercularized with shallow morphology and prominent CSF spaces. This increases the risk of cortical vein rupture with minor trauma, resulting in subdural hemorrhages ( Fig. 32.4 ).
