Clinical Approach to Leukoencephalopathies
Clinical Approach to Leukoencephalopathies
The term demyelination refers to the loss or damage of previously formed myelin. Acute demyelination secondary to acquired causes, such as infections or inflammatory conditions, including multiple sclerosis and acute disseminated encephalomyelitis (ADEM), is generally asymmetric and nonconfluent ([Fig. 1]). Chronic demyelination associated with inherited leukoencephalopathies is more commonly bilateral, symmetric, and confluent in distribution ([Fig. 2]). Regions of demyelination have increased signal intensity on magnetic resonance imaging (MRI) fluid-attenuated inversion recovery (FLAIR) imaging and may be accompanied by contrast enhancement or restricted diffusion. Defects of myelin biosynthesis and metabolism result in dysmyelination, which may coexist with demyelination or hypomyelination. Hypomyelination refers to a lack of myelin formation. Patients with delayed myelination demonstrate a gradual increase in myelin over time, which is delayed in maturity for age. Serial MRI scans at least 6 months apart are required to distinguish between hypomyelination and delayed myelination. On MRI scan, hypomyelination has the signal intensity of immature white matter and is inconspicuous on FLAIR. Conditions associated with hypomyelination are listed in Table 5.
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Figure 1.
Magnetic resonance images of a patient with multiple sclerosis demonstrating asymmetric white matter lesions with contrast enhancement (Courtesy of Dr. Jan-Mendelt Tillema and Dr. Orhun Kantarci).
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Figure 2.
T2-weighted fluid-attenuated inversion recovery axial magnetic resonance image of a patient with X-linked adrenoleukodystrophy demonstrating confluent symmetric signal abnormality in the parietooccipital regions.
Calcifications are more clearly ascertained using computed tomography (CT) scan imaging than MRI. The differential diagnosis of central nervous system calcifications includes congenital disorders such as Sturge-Weber syndrome and tuberous sclerosis; infectious causes including TORCH infections, disorders of parathyroid metabolism, and calcifications associated with neoplasms and vascular disorders. Aicaridi-Goutieres syndrome is an autosomal recessive condition, associated with at least four different genes, presenting with an early encephalopathy followed by stabilization of neurologic symptoms. Neuroimaging reveals leukoencephalopathy with calcifications and cerebral atrophy. Cerebrospinal fluid analysis reveals chronic lymphocytosis, elevated INF-α, and neopterin. Other leukoencephalopathies associated with calcifications are listed in Table 6.
Cystic changes may be characteristic of the underlying condition or may represent progressive cystic degeneration of the white matter (Table 7).
Magnetic Resonance Imaging Findings
The term demyelination refers to the loss or damage of previously formed myelin. Acute demyelination secondary to acquired causes, such as infections or inflammatory conditions, including multiple sclerosis and acute disseminated encephalomyelitis (ADEM), is generally asymmetric and nonconfluent ([Fig. 1]). Chronic demyelination associated with inherited leukoencephalopathies is more commonly bilateral, symmetric, and confluent in distribution ([Fig. 2]). Regions of demyelination have increased signal intensity on magnetic resonance imaging (MRI) fluid-attenuated inversion recovery (FLAIR) imaging and may be accompanied by contrast enhancement or restricted diffusion. Defects of myelin biosynthesis and metabolism result in dysmyelination, which may coexist with demyelination or hypomyelination. Hypomyelination refers to a lack of myelin formation. Patients with delayed myelination demonstrate a gradual increase in myelin over time, which is delayed in maturity for age. Serial MRI scans at least 6 months apart are required to distinguish between hypomyelination and delayed myelination. On MRI scan, hypomyelination has the signal intensity of immature white matter and is inconspicuous on FLAIR. Conditions associated with hypomyelination are listed in Table 5.
(Enlarge Image)
Figure 1.
Magnetic resonance images of a patient with multiple sclerosis demonstrating asymmetric white matter lesions with contrast enhancement (Courtesy of Dr. Jan-Mendelt Tillema and Dr. Orhun Kantarci).
(Enlarge Image)
Figure 2.
T2-weighted fluid-attenuated inversion recovery axial magnetic resonance image of a patient with X-linked adrenoleukodystrophy demonstrating confluent symmetric signal abnormality in the parietooccipital regions.
Calcifications are more clearly ascertained using computed tomography (CT) scan imaging than MRI. The differential diagnosis of central nervous system calcifications includes congenital disorders such as Sturge-Weber syndrome and tuberous sclerosis; infectious causes including TORCH infections, disorders of parathyroid metabolism, and calcifications associated with neoplasms and vascular disorders. Aicaridi-Goutieres syndrome is an autosomal recessive condition, associated with at least four different genes, presenting with an early encephalopathy followed by stabilization of neurologic symptoms. Neuroimaging reveals leukoencephalopathy with calcifications and cerebral atrophy. Cerebrospinal fluid analysis reveals chronic lymphocytosis, elevated INF-α, and neopterin. Other leukoencephalopathies associated with calcifications are listed in Table 6.
Cystic changes may be characteristic of the underlying condition or may represent progressive cystic degeneration of the white matter (Table 7).
