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NEURORADIOLOGY Table of Contents   
Year : 2005  |  Volume : 15  |  Issue : 4  |  Page : 503-506
Characteristic CT and MR features of Krabbe's disease : A case report.


Department of Radiology & Imaging, Vardhman Mahavir Medical College and Safdarjang Hospital, New Delhi -110029 and MR Centre, Green Park, New Delhi - 110 016, India

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Keywords: Krabbe′s, CT, MR

How to cite this article:
Grover S B, Gupta P, Jain M, Kumar A, Gulati P. Characteristic CT and MR features of Krabbe's disease : A case report. Indian J Radiol Imaging 2005;15:503-6

How to cite this URL:
Grover S B, Gupta P, Jain M, Kumar A, Gulati P. Characteristic CT and MR features of Krabbe's disease : A case report. Indian J Radiol Imaging [serial online] 2005 [cited 2018 Nov 18];15:503-6. Available from: http://www.ijri.org/text.asp?2005/15/4/503/28783

   Introduction Top


Globoid cell leukodystrophy (GLD) was first described by Krabbe in 1916 (1). It is a rare autosomal recessive disease with an incidence ranging from one in 100,000 to one in 200,000 live births [1],[2]. It is caused by congenital deficiency of a lysosomal enzyme, galactosylceramidase I, which is responsible for hydrolyzing the galactose moiety in galactocerebroside and for the hydrolysis of galactosylphingosine (psychosine) [1],[2],[3],[4]. The defect is due to a mutation in the GALC gene locus which has been mapped to chromosome 14 by genetic linkage studies [1],[2],[3],[4]. The enzyme deficiency causes abnormal accumulation of galatosylcerebrosides, which induce macrophages to become globoid cells. The same deficiency also causes accumulation of galactosylphingosine (psychosine) which is extremely toxic to oligodendroglia. The cumulative effect of multinucleated globoid cells and the direct toxic effect of psychosine results in extensive demyelination and severe astrogliosis [4],[5]. We report a new case of Krabbe's disease, diagnosed by characteristic CT and MR features. In our report we also discuss the pathogenesis of imaging features, the relevant differential diagnosis and antenatal diagnosis.


   Case report Top


A one year old girl was brought by her parents with history of excessive crying, recurrent seizures and tonic posturing since birth and complaints of fever and vomiting for two days. There was distinct history of delayed mental and physical milestones in the baby. On examination, she had of grade III coma, hypertonicity in all four limbs with bilaterally up-going plantars and brisk deep tendon reflexes. Fundus examination revealed bilateral papilledema. Routine laboratory investigations were normal. CSF proteins were raised to 150mg %. A provisional diagnosis of meningo- encephalitis was made and the patient was referred for CT scan of brain. Non Contrast CT revealed diffuse, bilaterally symmetrical hyperdensities in cerebellar white matter, basal ganglia and thalami. Right corona radiata also showed similar changes. Concurrent global cerebral and cerebellar atrophy and ventricular dilatation were present [Figure - 1]a,b. No enhancement was seen in the hyperdense areas following intravenous administration of contrast agent [Figure - 2]a,b. A CT diagnosis of Krabbe's leukodystrophy was made. On MR basal ganglia and thalami were hyperintense on T1 W [Figure - 3],[Figure - 5] and hypointense on T2W images [Figure - 4]. The periventricular and cerebellar white matter showed hyperintensity on T2W FLAIR images [Figure - 6].The clinical and neuroimaging findings were consistent with infantile Krabbe's disease.


   Discussion Top


The disorder is present at birth, with exclusively neurological clinical presentation consisting of prominent white matter signs including early onset seizures, spasticity, psychomotor deterioration and optic atrophy [2],[3],[4]. It is clinically classified into early infantile form, which presents between 1 to 12 months of age, the late infantile form (early childhood form), presenting between 1-3 yrs of age and the juvenile variety, manifesting in older children [1]. The early infantile form is most common and the late onset form is rare [3]. The infantile (early and late) forms of Krabbe's disease show increased CSF proteins and delayed nerve conduction, whereas in the juvenile form, CSF findings remain normal with minimal peripheral neuropathy [1].

The infantile form has 3 clinical stages. Stage I, is characterized by irritability, unmotivated crying, hypertonicity, recurrent fever and regression of psychomotor development. Within two to four months of onset, most patients reach stage II, which is characterized by opisthotonus, hypertonic flexion of limbs, exaggerated deep tendon reflexes and clonic seizures. Visual failure and optic atrophy now begin to appear and the CSF proteins are elevated. In Stage III or the "burnt out stage" infants are decerebrate and blind and death soon occurs. There is evidence of parallel progression of CT, MR and pathological findings [1].

Characteristic CT and MR features, as were present in our patient make the diagnosis. The abnormalities on CT and MR occur in basal ganglia, cerebellum and white matter. CT features known to characterize early infantile Krabbe disease are increased attenuation in cerebellum, brainstem, thalami, caudate nuclei and corona radiata on non contrast CT [4],[6],[7]. Kevan et al in 1984 attributed these hyperdensities to alterations in the ratio of lipids, water and proteins in response to breakdown of myelin and the associated astrogliosis [4]. Some investigators have reported histological evidence of minute calcification in these hyperdense regions [4]. These hyperdensities may precede progressive white matter hypoattenuation and atrophy [4].

The thalami, central white matter and cerebellum which show hyperdensities on CT, are seen on MR as decreased signal intensity on T2 and increased on T1 W images, possibly due to a paramagnetic effect of calcium deposition. MR also shows abnormalities in the periventricular white matter, which are non specific and resemble those seen in other dysmyelinating disorders (4). Paradoxically, MR may be deceptively normal in early infantile Krabbe's disease when basal ganglia hyperdensity on CT may suggest the diagnosis (4). However, with progression of disease the hyperdense areas seen on CT gradually disappear. The differential diagnosis of CT hyperdensities of basal ganglia and cerebellum include Alexander's disease, Fahr's syndrome, tuberous sclerosis and Cockayne's disease, Sandhoff and Tay Sach's disease [5],[8].

Confirmatory diagnosis of Krabbe's disease requires enzymatic assays, for which galactosylceramidase activity is estimated photometrically either in peripheral blood leucocytes or skin fibroblasts [2]. However, in centres where enzymatic assays are not available the neuroimaging diagnosis is considered to suffice. Antenatal diagnosis is performed by enzyme assays or mutation analysis in chorionic villus sampling, which also facilitates antenatal genetic counseling [2]. Bone marrow transplantation is being attempted for the treatment of the more benign, late onset form [3].

In conclusion, therefore, Krabbe's disease should be considered in the diagnosis of early onset infantile seizures and in older children with spasticity and ataxia. Characteristic CT and MR imaging features help to clinch the diagnosis.

 
   References Top

1.Bernardi B, Fonda C., Franzoni E, Marchiani V, Della GE, Zimmerman RA. MRI and CT in Krabbe's disease: case report. Neuroradiology. 1994; 36(6): 477-9.   Back to cited text no. 1    
2.Kleijer WJ, van Diggelen OP, Halley DJ, van der Ploeg AT, Mancini GM. From gene to disease; Krabbe disease and galactosylceramidase deficiency. Ned Tijdschr Geneeskd.2004; 148(17): 826-828. (Article in Dutch, English abstract)   Back to cited text no. 2    
3.Suzuki K. Globoid cell leukodystrophy (Krabbe's disease) : update. J Child Neurol. 2003;18(9):595-603   Back to cited text no. 3    
4.Finelli DA, Tarr RW, Sawyer RN, Horwitz SJ. Deceptively normal MR in early infantile Krabbe disease. AJNR Am J Neuroradiol. 1994;15(1): 167-71.   Back to cited text no. 4    
5.Choi S, Enzmann DR. Infantile Krabbe disease: complementary CT and MR findings. AJNR Am J Neuroradiol. 1993;14(5):1164-1166.   Back to cited text no. 5    
6.Sasaki M, Sakuragawa N, Takashima S, Hanaoka S, Arima M. MRI and CT findings in Krabbe disease. Pediatr Neurol. 1991;7(4):283-288.   Back to cited text no. 6    
7.Barone R, Bruhl K, Stoeter P, Fiumara A, Pavone L, Beck M. Clinical and neuroradiological findings in classic infantile and late onset globoid cell leukodystrophy (Krabbe disease). Am J Med Genet. 1996;63(1):209-217.   Back to cited text no. 7    
8.Lee SH, Rao KCVG, Zimmerman RA, Eds: Cranial MRI and CT:4th edition; McGraw Hill;USA.   Back to cited text no. 8    

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Correspondence Address:
S B Grover
E-81, Kalkaji, New Delhi-110019
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-3026.28783

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    Figures

[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6]



 

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    Introduction
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