A careful physical examination including general, neurologic, and ophthalmologic examinations can yield important clues to the underlying diagnosis.
Head circumference: Serial measurement of the head circumference is needed to determine the trajectory of head growth. Leukoencephalopathies may be associated with macrocephaly (enlarged head size)/megalencephaly (enlarged brain size) (Table 1). Many infants, children, and adults with leukoencephalopathy have normal or small head size (microcephaly).
Dysmorphic features: Specific metabolic or genetic syndromes may present with typical dysmorphic features. Chromosome microdeletions or microduplications can be associated with variable dysmorphic features and static leukoencephalopathy.
Skin: Distinctive skin manifestations have been described in specific inherited leukoencephalopathies (Table 2). These may be difficult to treat with standard dermatologic approaches suggesting the possibility of an underlying condition. Bronzing of the skin may be a clue to adrenal insufficiency in patients with peroxisomal disorders, including X-linked adrenoleukodystrophy and peroxisomal biogenesis defects.
Assessment of other organ systems: Hepatomegaly or hepatosplenomegaly may be an indication of a lysosomal storage disorder or peroxisomal disorder. Mitochondrial disorders can involve multiple organs including the liver, kidneys, or heart.
Ophthalmology examination: The eye has been described as the window to the brain. Ophthalmologic manifestations involving the cornea, lens, retina, and optic nerve are present in several inborn errors of metabolism associated with leukoencephalopathy. Retinal vascular changes have been described in leukoencephalopathies associated with hereditary small vessel diseases. Ophthalmologic manifestations associated with leukoencephalopathies are listed in Table 3.
Neurologic features: Although progressive spasticity is one of the hallmark signs of leukodystrophy, patients may present with hypotonia or a mixed tone disorder (central hypotonia with increased tone in the extremities). Dystonia or rigidity may also be present depending on the underlying cause of the leukoencephalopathy. Peripheral neuropathy coexists in several leukoencephalopathies, which may result in decreased deep tendon reflexes despite the presence of spasticity (Table 4). Myopathy may also be present and may be detected on electromyography (EMG) or by an elevated creatine kinase. Focal findings or stroke-like episodes may be important clues. Seizures, although not strongly associated with white matter disorders, may be present as part of the underlying cause of leukoencephalopathy.
Semin Neurol. 2012;32(1):29-33. © 2012 Thieme Medical Publishers