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. 2006 Apr;27(4):904-11.

MR characteristics and neuropathology in adult-onset autosomal dominant leukodystrophy with autonomic symptoms

A Melberg  1 , L Hallberg, H Kalimo, R Raininko
Affiliations

MR characteristics and neuropathology in adult-onset autosomal dominant leukodystrophy with autonomic symptoms

A Melberg et al. AJNR Am J Neuroradiol. 2006 Apr.

Abstract

Background and purpose: Three families with adult-onset autosomal dominant leukodystrophy (ADLD) presenting autonomic dysfunction as the first symptom are reported. We describe detailed MR appearances of the brain in 2 new families and neuropathology in 2 patients and compare the findings with those in other adult-onset leukodystrophies.

Methods: Twenty subjects (12 women and 8 men; age range, 29-70 years) from 2 unrelated families with ADLD were examined with MR. Six subjects were asymptomatic. Fourteen had autonomic dysfunction. Eleven of them also had pyramidal signs and ataxia. The brains of 2 autopsied patients were examined histopathologically.

Results: Two subjects manifested no neurologic symptoms, signs, or MR pathology. Eighteen subjects displayed radiologic abnormalities ranging from subtle T2 high-signal-intensity changes in the upper corticospinal tract to extensive confluent white matter changes, predominantly in a frontoparietal distribution, along the corticospinal tracts down to the medulla oblongata and in the upper and middle cerebellar peduncles. Periventricular white matter was spared or less affected than the adjacent white matter. Histopathology revealed marked loss of cerebral and cerebellar myelin without signs of inflammation. Oligodendrocytes were relatively spared, the number of axons not markedly decreased, and reactive gliosis was modest. The number of Purkinje cells in the cerebellum was reduced.

Conclusions: Two families with adult-onset ADLD with the disease entity originally reported by Eldridge et al. (N Engl J Med 1984;311:948-53) were described. We propose naming the disease "adult-onset ADLD with autonomic symptoms." The characteristic radiologic findings, combined with the clinical symptoms and mode of inheritance, enable the diagnosis.

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Figures

Fig 1.
Fig 1.
T2 signal-intensity alterations in a 37-year-old asymptomatic family member. Subtle high-signal-intensity lesions in the corticospinal tracts under the motor cortex (A), in the posterior limb of the internal capsule (B, arrow), mesencephalon (C, arrow), pons (D, arrow), and medulla oblongata (E, arrow). Only a tiny signal-intensity abnormality is seen in the right corticospinal tract at the level of the pons. Note the lesions in the upper cerebellar peduncles (C, arrowhead). Fluid-attenuated inversion recovery (FLAIR), 10,000/140/2500.
Fig 2.
Fig 2.
More extensive signal-intensity alterations in a 34-year-old asymptomatic subject. A, Frontoparietal changes are less severe in the periventricular region. B, Increased signal intensity in the internal capsules, in the anterior and posterior corpus callosum and in the vicinity of the atria (arrow). C, Changes in the middle cerebellar peduncles and in the pontine nuclei. Turbo spin-echo (TSE), 5000/90.
Fig 3.
Fig 3.
A 48-year-old woman with a history of urinary bladder dysfunction for the past 2 years. Frontoparietal white matter alteration does not involve the periventricular area (A and B). Increased signal intensity in the corticospinal tracts in the internal capsules (B, arrow). A, Fluid-attenuated inversion recovery (FLAIR), 10,000/140/2500. B, Turbo spin-echo (TSE), 8116/100.
Fig 4.
Fig 4.
A 55-year-old man with a history of impotence, urinary bladder dysfunction, and obstipation for the past 6 years. Most of the frontoparietal and occipital white matter is affected (A–D and G). The periventricular white matter looks less pathologic (B, C, G). The circular periventricular layers are best seen in a coronal plane (G). The leukodystrophic area continues in the temporal lobes (D, arrow). The corticospinal tracts show a high signal intensity in the internal capsules (C), mesencephalon (D), pons (E), and medulla oblongata (F). The upper (arrowhead) and middle cerebellar peduncles are affected (D and E). High signal intensities are seen in the corpus callosum (B). Its posterior part (B) is very thin. A–F, Fluid-attenuated inversion recovery (FLAIR), 10,000/140/2500. G, Turbo spin-echo (TSE), 8116/100.
Fig 5.
Fig 5.
A, Coronal formalin-fixed section at the level of the basal ganglia of a 69-year-old man. White matter is reduced and there are irregularly shaped miscolored areas of demyelination (asterisk). B, Whole-brain microscopic section from the same level. Widespread diffuse loss of myelin (pallor of the blue color) in the centrum semiovale bilaterally (asterisk, arrows) with sparing of the U fibers (arrows). The myelin is better preserved in the temporal lobes (T). The Sylvian fissures are widened and the lateral ventricles moderately dilated, which indicates mild brain atrophy. C–F, Consecutive sections from the parietal white matter of a 56-year-old woman. C, Diffuse loss of myelin. Note the less severe pallor around the blood vessel (bv), which indicates that the myelin loss is not perivascular as in multiple sclerosis. Luxol fast blue-cresyl violet (LFB-CV) staining. D, There is only minor astrogliosis in the demyelinated area. The astrocytes (brown cells) are rather plump with irregular processes. Anti-glial fibrillar acidic protein (GFAP) + hematoxylin counterstain. E, No lymphocyte infiltrates are present, but scattered macrophages (brown cells) are seen in the demyelinated area. Anti-CD68 + hematoxylin counterstain. The number of oligodendroglial nuclei (blue) in panels D and E appears the same irrespective of the intensity of the myelin stain (C). F, The density of neurofilament positive axons did not appear to be affected by demyelination. Anti-neurofilament + hematoxylin counterstain. Scale bar, 100 μm. G, Cerebellum of the 69-year-old man. Severe diffuse loss of myelin in the cerebellar white matter, more marked centrally (C) than in the folia (asterisk). The number of Purkinje cells (2 preserved cells marked with arrows) is greatly decreased, but there is only slightly increased number of reactive Bergmann astrocytes. LFB-CV. Scale bar, 100 μm.
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