Pediatr Radiol (1991) 21:133-134

Pediatric Radiology 9 Springer-Verlag 1991

Alexander's disease: cranial MRI and ultrasound findings V. Schuster, A. E. Horwitz and H. W. Kreth Department of Pediatrics and Pediatric Radiology, University of Wiirzburg, FRG Received: 22 May 1990; accepted: 20 June 1990

Abstract. Cranial ultrasound (US) findings and magnetic resonance imaging (MRI) are presented in an infant with Alexander's disease. Both methods may help the clinician with the early diagnosis of this rare disease.

Infantil Alexander's disease is a rare dysmyelinogenetic leukodystrophy of still unknown etiology characterized clinically by megalencephaly, psychomotor retardation, and later on by seizures and spasticity. There are only few reports on M R I [1-3] and US [4] findingsin Alexander's disease. These reports are also slightly different. We report a 15 months old boy who presented with increasing megalencephaly and mild delayed motor development. The characteristic brain findings by cranial US and M R I led to the diagnosis of Alexander's disease at an early stage.

Case report Patient B.M., a boy, was the 2nd child of healthy, non-consanguinous parents. Pregnancy and delivery were normal. The Apgar score was 10-10, the birth weight 3350 g and the head circumference 35 cm (50th percentile). During the first year of life head size increased disproportionately. At 11 months of age mild delayed motor milestones were noted. At the age of 14 months the child was admitted to the pediatric department. The head circumference was 52 cm (1.8 cm above the 97th percentile). At that time the child could sit up alone and stand with support; walking was not possible. The anterior fontanelle was 4 • 4 cm in diameter, the palpable consistence of tissue under the anterior fontanelle seemed to be "increased". The posterior fontanelle was closed. The scalp veins were prominent and the patient exhibited a mild "setting-sun" sign. The patient showed no

organomegaly or neurocutaneous stigmata. Examination of eyes and ears was normal. EEG, peripheral motor nerve conduction velocity (NCV) (median nerve), and auditory evoked potentials (AEPs) were normal. Blood, serum and urine tests for amino and organic acids (including glutaracid and Nacetylaspartic add), mucopolysaccharides, metachromatic leukodystrophy, adrenoleukodystrophy and different peroxisomal disorders were negative. Peripheral blood smears showed no vacuolized lymphocytes. The CSF was normal. A diagnostic brain biopsy was denied by the parents. A skull X-ray showed macrocephaly without splitting of the sutures. Cranial US revealed megalencephaly with increased brain mass and narrow lateral ventricles. In addition, the cerebral tissue appeared to be relatively homogenous and coarsened. The definition of gyri, sulci and interhemispheric fissure was reduced (Fig. 1). Cranial MRI studies revealed generalized diffuse demyelination and proliferation in the white brain matter, most markedly in the frontal regions (Fig. 2).

Discussion US and M R I findings showed abnormal patterns of the brain substance. Similar US changes have been reported re-

cently by others [4]. In addition, our patient had narrow ventricles, probably reflecting a very early stage of Alexander's disease. M R I changes of the white matter were most pronounced in the frontal regions (Figs.2,3). The structure of gyri and sulci appeared coarsened and partly abolished suggesting a diffuse infiltrating process and probably caused by gliosis of abnormal astrocytes and deposition of Rosenthal fibres. Since the biochemical defect in Alexander's disease is still unknown, definitive diagnosis normally requires brain biopsy. However, clinical and biochemical findings in our case, (megalencephaly, no vacuolized leucocytes, no cherry-red spot, normal N C V and CSE exclusion of other similar metabolic degenerative disorders), in conjunction with the relatively specific US and M R I findings, led with high accuracy to the diagnosis of early infantil Alexander's disease. M R I studies of leukodystrophies are still rare. Valk et al. [1] have proposed several M R I criteria highly suggestive for the diagnosis of Alexander's disease: Spread of the disease from frontal regions in a rostrocaudal direction,

Fig.la, b. US of the brain: Sagittal (a) and coronal (b) projection. Increasedbrain mass; nearly homogeneous echogenicity of the brain, narrow lateral ventricles, reduced definition of gyri, sulci and interhemispheric fissure

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V. Schuster et al.: Alexander's disease of A l e x a n d e r ' s disease w i t h o u t brain biopsy.

Acknowledgement. We wish to thank Dr. W.Keil, private radiologic practice, Wtirzburg, FRG, for performing MRI examinations. References

Fig. 2. T2-weighted axial MRI sections of the patient's brain (Magnetom 1.0 Tesla, TR 2.8 ms, TE 120 ms). Symmetric confluent lesions and proliferation in the white matter of the temporal, parietal, and, most markedly, o f the frontal lobes. Cerebellar white matter is less affected. Basal ganglia and brain stem are spared. Ventricles are narrow

Fig. 3. T1 -weighted sagittal MRI section (Magnetom 1.0 Tesla, T R 0.45 ms, TE 17 ms). Loss of definition of sulci and gyri in the frontal brain

relatively well p r e s e r v e d occipital lobes and g e n u of the corpus callosum, the i n v o l v e m e n t of the a r c u a t e fibres, and n o n i n v o l v e m e n t of the c e r e b e l l u m and b r a i n stem. W e and o t h e r s [3] could also d e m o n s t r a t e i n v o l v e m e n t of t h e c e r e b e l l u m . In contrast, M R I findings indicate that C a n a v a n ' s disease s p r e a d p r e d o m i n a n t l y in a c e n t r i p e t a l [1], a d r e n o l e u k o d y s t r o p h y [1,2] in a d o r s o v e n t r a l direction, and m e t a -

c h r o m a t i c l e u k o d y s t r o p h y and K r a b be's disease [1, 5] in a centrifugal direction. In conclusion, cranial U S and M R I studies m a y suggest infantile l e u k o d y s t r o p h y early in the course of the disease. I n addition, w h i t e m a t t e r c h a n g e s and int e n s e gliosis m a i n l y in t h e frontal b r a i n regions in c o n j u n c t i o n w i t h b i o c h e m i c a l e x c l u s i o n of o t h e r similar l e u k o d y s t r o phies m a y lead to the exact diagnosis

1. Valk J, van der Knaap MS (1989) Magnetic resonance of myelin, myelination, and myelin disorders. Chap 30: Alexander's disease. Springer, Berlin Heidelberg New York, p 165 2. Bydder G (1990) Demyelinating disease and infection. In: Bradley WG, Bydder G (eds) MRI atlas of the brain. Deutscher Arzte-Verlag, KOln, p 182 3. Howell MA, Grossmann RI, Hackney DB, Zimmerman RA, Goldberg HI, Bilaniuk LT (1988) MR imaging of white matter disease in children. A m J Radiol 151:359 4. Harbord MG, LeQuesne G W (1988) Alexander's disease: cranial ultrasound findings. Pediatr Radiol 18:341 5. Baram TZ, Goldman AM, Percy AK (1986) Krabbe disease, Specific MRI and CT findings, Neurology 36:111 Dr. V. Schuster Department of Pediatrics and Pediatric Radiology University of WOrzburg Josef-Schneider-Strage 2 W-8700 Wiirzburg FRG

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