paediatric neuropatho.html


    
        
            
                Paediatric neuropathology: Diagnosis

                S K Misser, MB ChB, FCRad (D)
            

            Lake Smit and Partners, Durban

            J F Roos, MB ChB, MMed (Paed)
        

        Parklands Hospital, Durban

        
            Corresponding author: S Misser (shalendramisser@hotmail.com)

            Please refer to page 101 of the September 2011 issue of the SAJR
            (also available online at
            http://www.sajr.org.za/index.php/sajr/article/view/610/459) for the
            presentation details. We congratulate Dr S Moosa (Department of
            Radiology, 2 Military Hospital, Wynberg, Cape Town) for a
            well-researched and comprehensive diagnosis, for which he receives an
            award of R1 000 from the RSSA. Dr Misser elaborates below on the
            condition and its imaging.

            Presentation and diagnosis

            (Because of space constraints, the images referred to below are not reproduced here but are in the September 2011 issue of the SAJR and online at the above URL.)

            The patient presented here was a 10-month-old girl,
            delivered pre-term by caesarean section, with a birthweight of 2.4 kg
            and good Apgar scores. In her first year, she was treated for
            gastro-oesophageal reflux and had one life-threatening episode of
            reflux-associated apnoea with aspiration pneumonia. Fundoplication
            surgery was succesfully performed. In the late neonatal period,
            progressive loss of neurological milestones was observed. Baseline and
            preliminary special investigations(including chromosomal analysis,
            lacate and pyruvate) were non-contributory.

            On visual testing, cortical blindness was
            suspected. Hearing was normal. The paediatric neurologist noted marked
            irritability and exaggerated response to basic stimuli, prompting
            further testing. MRI scan showed marked generalised cerebral atrophy
            and proportional ventriculomegaly. T2-weighted high signal was noted
            extensively in the white matter, thalami and basal ganglia, with
            relative sparing of the U-fibres. Inversion recovery sequence showed
            reduced ventral pontine signal, sparing the transverse pontine fibres.
            After gadolinium administration, symmetrical cranial nerve enhancement
            was demonstrated of the optic, oculomotor and trigeminal nerves.
            Questionable focal enhancement was noted at the left brachium pontis
            (Fig. 4b). Serum galactocerebrosidase levels were found to be very low,
            confirming suspected Krabbe leucodystrophy.

            Discussion

            White matter disease in childhood is broadly
            classified as demyelinating or dysmyelinating. The dysmyelinating
            diseases, or leukodystrophies, result in abnormal production and
            breakdown of myelin. These are usually caused by an enzyme deficiency
            and are best sub-divided based on the cellular organelle involved.1 See Table I.

            Krabbe disease, or globoid cell leukodystrophy, is
            a neurodegenerative illness of infancy, with 4 clinical subtypes,
            distinguished by age of onset viz. infantile, late infantile, juvenile
            and adult. It is an autosomal recessive disorder, with the gene fault
            mapped to chromosome 14, resulting in deficiency of galactocerebroside-β-galactosidase.
            This enzyme degrades cerebrosides, a normal constituent of myelin.
            Accumulation of cerebrosides in the lysosmes of macrophages results in
            formation of globoid cells, typical of this disease. Clinically, the
            infantile subtype is the most common, manifesting with irritability,
            progressive spasticity, blindness, dysphagia, mental deterioration and
            milestone regression.

            MRI has been shown to play a fundamental role in
            diagnosis and follow-up imaging of children with Krabbe’s
            disease. Provenzale et al.2  showed good correlation of MRI findings (using Loes scores3 )
            with clinical scoring systems. Centrum ovale, basal ganglia, thalami,
            internal capsule, cerebellum and brainstem are all areas that
            demostrate T2 and FLAIR sequence hyperintensity. Thalamic involvement
            is a useful sign to differentiate from metachromatic leukodystrophy.4  Optic nerve hypertrophy and/or enhancement , as well as enhancement of other cranial nerves, is a feature of the disease.5 
            Severe progressive atrophy, involvement of U-fibres, cortical blindness
            and seizures are usually late phenomena. Diagnosis is made by detecting
            enzyme deficiency in leukocytes or cultured skin fibroblasts. Treatment
            includes bone marrow transplantation, supportive therapy and
            physiotherapy.

            
            

            1. Cheon J, Kim IO, Hwang YS, et al. Leukodystrophy in children: A
            pictorial review of MR Imaging features. RadioGraphics 2002;22:461-476.

            1. Cheon J, Kim IO, Hwang YS, et al. Leukodystrophy in children: A
            pictorial review of MR Imaging features. RadioGraphics 2002;22:461-476.

            2. Provenzale JM. Correlation of neurodevelopmental features and MRI
            findings in infantile Krabbe’s disease. AJR 2009;192:59-65.

            2. Provenzale JM. Correlation of neurodevelopmental features and MRI
            findings in infantile Krabbe’s disease. AJR 2009;192:59-65.

            3.	Loes DJ, Hite S, Moser H, et al. Adrenoleukodystrophy: a scoring method for brain MR observations. AJNR 1994;15:1761-1766.

            3.	Loes DJ, Hite S, Moser H, et al. Adrenoleukodystrophy: a scoring method for brain MR observations. AJNR 1994;15:1761-1766.

            4. Candy S. An Approach to White and Grey Matter Disease in Children.
            In: Baby Steps into Paediatric Neuroradiology. Andronikou S,
            Wieselthaler N, Kader E (eds). 1st ed. Pretoria: SAMA Press, 2004.

            4. Candy S. An Approach to White and Grey Matter Disease in Children.
            In: Baby Steps into Paediatric Neuroradiology. Andronikou S,
            Wieselthaler N, Kader E (eds). 1st ed. Pretoria: SAMA Press, 2004.

            5.	Jones BV, Barron TF, Towfighi J. Optic nerve enlargement in Krabbe’s disease. AJNR 1999;20:1228-1231.

            5.	Jones BV, Barron TF, Towfighi J. Optic nerve enlargement in Krabbe’s disease. AJNR 1999;20:1228-1231.

        

        
            
                Table I. White matter diseases according to cellular organelle involved
            

            	
                        
                            Lysosomal storage 

                            diseases with white 

                            matter involvement
                        

                    	
                        
                            Peroxisomal disorders
                        

                    	
                        
                            Mitochondrial dysfunction 

                            with leukoencephalopathy
                        

                    	
                        
                            Other white matter 

                            dysmyelinating disorders
                        

                    
	
                        Metchromatic leukodystrophy

                    	
                        Zellweger syndrome

                    	
                        Leigh disease

                    	
                        Canavan disease

                    
	
                        Krabbe disease

                    	
                        X-Linked adrenoleukodystrophy

                    	
                        MELAS

                    	
                        Alexander disease

                    
	
                        Niemann-Pick disease

                    	
                        Neonatal adrenoleukodystrophy 

                        (ALD)

                    	
                        MERRF

                    	
                        Congenital muscular 

                        dystrophy (Fukuyama)

                    
	
                        Fabry disease

                    	
                        Pseudoneonatal ALD

                    	
                    	
                    
	
                        GM1 and GM2 gangliosidosis

                    	
                        Classic Refsum disease

                    	
                    	
                        Pelizaeus-Merzbacher disease

                    
	
                        Mucopolysaccharidosis

                    	
                    	
                    	
                    
	
                        Fucosidosis

                    	
                    	
                    	
                    
	
                        Mucolipidosis

                    	
                    	
                    	
                    
	
                        Wolman disease

                    	
                    	
                    	
                    
	
                        Ceroid lipofuscinosis