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Magnetic resonance imaging findings in mild mucopolysaccharidosis II (Hunter's syndrome)
European
Journal
CASE
STUDY
of Paediatric
Neurology
1998;
2: 153-l
56
Magnetic resonance imaging findings in mild mucopolysaccharidosis II (Hunter’s syndrome) DI ZAFEIRIOU, PA AUCOUSTIDOU-SAVVOPOULOU, GS KATZOS, EE KONTOPOULOS, OP VAN DICCELEN’ 7st Pediatric Rotterdam,
Clinic,
University
of Thessaloniki,
Greece;
‘Clinical
FA PAPADOPOULOU,
Genetics
Department,
Erasmus
NP COMBAKIS, University,
The Netherlands
Introduction Hunter’s syndrome (mucopolysaccharidosis (MPS) type II) is a rare X-linked recessive metabolic disorder caused by deficiency in alpha-Liduronatesulphate sulphatase.’ Neuroimaging in Hunter’s syndrome, as well as in the rest of the mucopolysaccharidoses, is usually carried out when hydrocephaly or spinal cord compression is suspected. *J The mild form of Hunter’s syndrome (MPS Ilb) is characterized by minimal or no central nervous system (CNS) involvement, preservation of intelligence and a prolonged life span.’ We report two patients with mild Hunter’s syndrome and extensive white matter abnormalities in magnetic resonance imaging (MRI).
Case study Both patients were ,males, born to healthy nonconsanguineous parents with a negative family history for neurometabolic or neurodegenerative disorders. Pregnancy and delivery were uneventful and they had normal developmental milestones. The first meaningful word was spoken at the age of 19 and 22 months, respectively. Early childhood of the first patient was complicated by frequent middle ear infections which led to adenoidectomy. At the age 3.5 and 5.5 years, respectively, they were admitted to our Department because of delay in language development and dysmorphic features. On admission, both patients had coarse facial features suggestive of MPS, thick tongue and
Received 13.1.98. Correspondence:
Revised 17.3.98. DI Zafeiriou, MD,
1090-3798/98/020153+4
$18.00
Accepted 18.3.98. PhD, Child Neurologist,
Egnatia
SI. 106,
skin, short neck and an abdominal protuberance with hepatosplenomegaly. An umbilical hernia and an ivory-coloured skin lesion on the back were also noted in the first patient. Height was below the 3rd percentile for age, while weight and head circumference were within normal limits. Regarding skeletal findings, they both had short and wide fingers and toes, a brachycephalic skull and mild contractions of the elbow and knee joints with limitation in the range of motility. The neurological examination was unremarkable revealing only exaggerated deep tendon reflexes with no evidence of pyramidal, extrapyramidal or cerebellar tract involvement. There was a light atrophy of the thenar muscles in the first patient. Cardiac auscultation revealed no heart murmur and there was no evidence of cataract, retinopathy or optic atrophy in the ophthalmological examination. Electroencephalogram (EEG), electrocardiogram (ECG), brain computed tomography (CT), as well as visual evoked potential, somatosensory evoked potential and brainstem auditory evoked potential studies, demonstated no abnormalities. However, in the audiological examination, both patients demonstrated a mild conductive hearing loss bilaterally. Radiological investigations demonstrated features of dysostosis multiplex (deformity of the vertebral bodies, hyperostosis of the skull, enlargement of the sella turcica and widening of the midshafts of the long bones). Developmental and intelligence quotients according to Griffiths (first patient) and Wechsler Intelligence Scale for Children-Revised (second patient), were 89 and 84, respectively. Nerve conduction velocity studies were consistent with a mild
54622
Thessaloniki,
Greece
0 1998
European
Paediatric
Neurology
Society
Case study:
DI Zafeiriou
et al.
(a)
(c)
Cd) Fig. 1
(a-d)
Fig. 1.
Patient 7: (a) axial T2-weighted images through the centrum semiovale demonstrating diffuse and focal white matter abnormalities with abnormal high signal resulting in diminished contrast between cortex and underlying white matter; (b) axial PD-weighted images through the centrum semiovale and through the supraventricular white matter cc) demonstrating focal areas isointense with CSF. Patient 2: (d) axial T2-weighted images through the centrum semiovale demonstrating
diffuse
and
focal
white
matter
abnormalities
with
abnormal
high
signal.
Case study: MRI findings
in mild
Hunter’s
syndrome
155
Fig. 1
Fig. 1 with
(e) Patient 2: sagittal
CSF at the corpus
Tl-weighted callosum (note
also
images through the enlarged
(e)
the corpus callosum cisterna magna).
carpal tunnel syndrome. Blood chemistry was normal except for a mild elevation of aspartate and alanine aminotransferases in both patients. A marked urinary excretion of dermatan and heparan sulphate, as well as deficiency of iduronatesulphate sulfatase in plasma (Patient I: 0.2nmol/l7h/ml; Pntielzt 2: 0.1 nmol/l7h/ml; control range: 5-18) confirmed the diagnosis of Hunter’s syndrome. Magnetic resonance imaging of the brain was performed in both patients; Tl-weighted images were obtained with SE 500/25, I’D-weighted images with SE 2000/35 and T2-weighted images were obtained with SE 2000/100. Extensive white matter abnormalities (diffuse and focal areas of prolonged Tl and T2 relaxation times) were demonstrated in both children, while diffuse white matter haziness on T2-weighted images resulted in diminished contrast between cortex and underlying white matter. Well defined foci, isointense with cerebrospinal fluid (CSF) on all imaging sequences, were seen in the corpus callosum and the cerebral white matter. There was no evidence of ventriculomegaly or cortical atrophy in either of the patients.
demonstrating
well
defined
foci
isointense
Discussion In view of the relatively mild clinical course and CNS involvement, both patients were considered to have the mild form of Hunter’s syndrome, which is considered quite rare; neuroradiological findings have been ocassionally reported, with most studies using CT scans.If2 Age-dependent ventricular dilatation and white-matter low density with no involvement of the basal ganglia and thalami are the predominant CT findings demonstrated.2 There are few reports regarding MRI findings in the severe type of MI’S II,2-5 most of them demonstrating ventricular enlargement, cortical atrophy and increased signal density in the Tland T2-weighted images in the periventricular white matter. The well defined foci, isointense with CSF, seen in the cerebral white matter on all imaging sequences, are believed to represent mucopolysaccharide-filled perivascular spaces; the high signals in the white matter in the T2weighted sequences could be attributed to demyelination, gliosis and increased fluid content. To our knowledge this is the first MRI study in children
Case study:
156
with mild Hunter’s syndrome. Shimoda-Matsubayashi et aL6 first demonstrated MRI findings in a 44year adult with the mild form of Hunter’s syndrome, whose MRI revealed high signals of the deep white matter in the T2-weighted images, as well as patchy areas of increased and decreased signals in Tl- and T2-weighted images in the thalamus and basal ganglia, which gave rise to a honeycomb-like appearance. Subsequently, Parsons et ~1.’ reported five adult patients considered to have the mild variant of Hunter’s syndrome, who demonstrated ventriculomegaly and cortical atrophy in MRI, additionally to the white matter lesions. The difference between severe and mild Hunter’s syndrome is primarily reflected in the extent of the CNS involvement.* Therefore, one could speculate that preserved intelligence and absence of severe neurological abnormalities, as in our patients at the time of the study, could be compatible with ‘silent’ MRI lesions, while appearance of signs such as ventriculomegaly and cortical atrophy already in childhood, may indicate a more severe clinical course. However, the presence of severe CNS involvement also in mildly affected adult patients’ and the borderline intelligence of our patients imposes difficulties in predicting accurately the further evolution of both clinical and MRI findings. Serial MRI studies are needed in
DI Zafeiriou
et al.
order to establish the prognostic significance of the above MRI findings in the severity of Hunter’s syndrome in childhood.
References Neufeld EF, Muenzer J. The mucopolysaccharidoses. In: Striver CR, Beaudet AL, Sly WS, Valle D (eds) Tile Metabolic Basis of Inherited Disease (7th edn). New York: McGraw-Hill, 1995: 2465-2494. Barkovich AJ. Pediatric Neuroimaging. Lippincott-Raven, 1996: pp. 87-91.
Philadelphia:
Kendall BE. Disorders of lysosomes, peroxisomes, and mitochondria. Am J Neuroradiol 1992; 13: 621-653. Lee C, Dineen TE, Brack M et al. Mucopolysaccharidoses: characterization by cranial MRI imaging. Am ] Neuroradiol 1993; 14: 1285-1292. Murata R, Nakajima S, Tanaka A et al. MR imaging of the brain in patients with mucopolysaccharidosis. AJNR 1989; 10: 1165-1170. Shimoda-Matsubayashi S, Kuru Y, Sumie H et al. MRI findings in the mild type of mucopolysaccharidosis II (Hunter’s syndrome). Neuroradiology 1990; 32: 328-
330. Parsons VJ, Hughes DG, Wraith JE. Magnetic resonance imaging of the brain, neck and cervical spine in mild Hunter’s syndrome (mucopolysaccharidoses type II). Clin Radio1 1996; 51: 719-723.
Journal
CASE
STUDY
of Paediatric
Neurology
1998;
2: 153-l
56
Magnetic resonance imaging findings in mild mucopolysaccharidosis II (Hunter’s syndrome) DI ZAFEIRIOU, PA AUCOUSTIDOU-SAVVOPOULOU, GS KATZOS, EE KONTOPOULOS, OP VAN DICCELEN’ 7st Pediatric Rotterdam,
Clinic,
University
of Thessaloniki,
Greece;
‘Clinical
FA PAPADOPOULOU,
Genetics
Department,
Erasmus
NP COMBAKIS, University,
The Netherlands
Introduction Hunter’s syndrome (mucopolysaccharidosis (MPS) type II) is a rare X-linked recessive metabolic disorder caused by deficiency in alpha-Liduronatesulphate sulphatase.’ Neuroimaging in Hunter’s syndrome, as well as in the rest of the mucopolysaccharidoses, is usually carried out when hydrocephaly or spinal cord compression is suspected. *J The mild form of Hunter’s syndrome (MPS Ilb) is characterized by minimal or no central nervous system (CNS) involvement, preservation of intelligence and a prolonged life span.’ We report two patients with mild Hunter’s syndrome and extensive white matter abnormalities in magnetic resonance imaging (MRI).
Case study Both patients were ,males, born to healthy nonconsanguineous parents with a negative family history for neurometabolic or neurodegenerative disorders. Pregnancy and delivery were uneventful and they had normal developmental milestones. The first meaningful word was spoken at the age of 19 and 22 months, respectively. Early childhood of the first patient was complicated by frequent middle ear infections which led to adenoidectomy. At the age 3.5 and 5.5 years, respectively, they were admitted to our Department because of delay in language development and dysmorphic features. On admission, both patients had coarse facial features suggestive of MPS, thick tongue and
Received 13.1.98. Correspondence:
Revised 17.3.98. DI Zafeiriou, MD,
1090-3798/98/020153+4
$18.00
Accepted 18.3.98. PhD, Child Neurologist,
Egnatia
SI. 106,
skin, short neck and an abdominal protuberance with hepatosplenomegaly. An umbilical hernia and an ivory-coloured skin lesion on the back were also noted in the first patient. Height was below the 3rd percentile for age, while weight and head circumference were within normal limits. Regarding skeletal findings, they both had short and wide fingers and toes, a brachycephalic skull and mild contractions of the elbow and knee joints with limitation in the range of motility. The neurological examination was unremarkable revealing only exaggerated deep tendon reflexes with no evidence of pyramidal, extrapyramidal or cerebellar tract involvement. There was a light atrophy of the thenar muscles in the first patient. Cardiac auscultation revealed no heart murmur and there was no evidence of cataract, retinopathy or optic atrophy in the ophthalmological examination. Electroencephalogram (EEG), electrocardiogram (ECG), brain computed tomography (CT), as well as visual evoked potential, somatosensory evoked potential and brainstem auditory evoked potential studies, demonstated no abnormalities. However, in the audiological examination, both patients demonstrated a mild conductive hearing loss bilaterally. Radiological investigations demonstrated features of dysostosis multiplex (deformity of the vertebral bodies, hyperostosis of the skull, enlargement of the sella turcica and widening of the midshafts of the long bones). Developmental and intelligence quotients according to Griffiths (first patient) and Wechsler Intelligence Scale for Children-Revised (second patient), were 89 and 84, respectively. Nerve conduction velocity studies were consistent with a mild
54622
Thessaloniki,
Greece
0 1998
European
Paediatric
Neurology
Society
Case study:
DI Zafeiriou
et al.
(a)
(c)
Cd) Fig. 1
(a-d)
Fig. 1.
Patient 7: (a) axial T2-weighted images through the centrum semiovale demonstrating diffuse and focal white matter abnormalities with abnormal high signal resulting in diminished contrast between cortex and underlying white matter; (b) axial PD-weighted images through the centrum semiovale and through the supraventricular white matter cc) demonstrating focal areas isointense with CSF. Patient 2: (d) axial T2-weighted images through the centrum semiovale demonstrating
diffuse
and
focal
white
matter
abnormalities
with
abnormal
high
signal.
Case study: MRI findings
in mild
Hunter’s
syndrome
155
Fig. 1
Fig. 1 with
(e) Patient 2: sagittal
CSF at the corpus
Tl-weighted callosum (note
also
images through the enlarged
(e)
the corpus callosum cisterna magna).
carpal tunnel syndrome. Blood chemistry was normal except for a mild elevation of aspartate and alanine aminotransferases in both patients. A marked urinary excretion of dermatan and heparan sulphate, as well as deficiency of iduronatesulphate sulfatase in plasma (Patient I: 0.2nmol/l7h/ml; Pntielzt 2: 0.1 nmol/l7h/ml; control range: 5-18) confirmed the diagnosis of Hunter’s syndrome. Magnetic resonance imaging of the brain was performed in both patients; Tl-weighted images were obtained with SE 500/25, I’D-weighted images with SE 2000/35 and T2-weighted images were obtained with SE 2000/100. Extensive white matter abnormalities (diffuse and focal areas of prolonged Tl and T2 relaxation times) were demonstrated in both children, while diffuse white matter haziness on T2-weighted images resulted in diminished contrast between cortex and underlying white matter. Well defined foci, isointense with cerebrospinal fluid (CSF) on all imaging sequences, were seen in the corpus callosum and the cerebral white matter. There was no evidence of ventriculomegaly or cortical atrophy in either of the patients.
demonstrating
well
defined
foci
isointense
Discussion In view of the relatively mild clinical course and CNS involvement, both patients were considered to have the mild form of Hunter’s syndrome, which is considered quite rare; neuroradiological findings have been ocassionally reported, with most studies using CT scans.If2 Age-dependent ventricular dilatation and white-matter low density with no involvement of the basal ganglia and thalami are the predominant CT findings demonstrated.2 There are few reports regarding MRI findings in the severe type of MI’S II,2-5 most of them demonstrating ventricular enlargement, cortical atrophy and increased signal density in the Tland T2-weighted images in the periventricular white matter. The well defined foci, isointense with CSF, seen in the cerebral white matter on all imaging sequences, are believed to represent mucopolysaccharide-filled perivascular spaces; the high signals in the white matter in the T2weighted sequences could be attributed to demyelination, gliosis and increased fluid content. To our knowledge this is the first MRI study in children
Case study:
156
with mild Hunter’s syndrome. Shimoda-Matsubayashi et aL6 first demonstrated MRI findings in a 44year adult with the mild form of Hunter’s syndrome, whose MRI revealed high signals of the deep white matter in the T2-weighted images, as well as patchy areas of increased and decreased signals in Tl- and T2-weighted images in the thalamus and basal ganglia, which gave rise to a honeycomb-like appearance. Subsequently, Parsons et ~1.’ reported five adult patients considered to have the mild variant of Hunter’s syndrome, who demonstrated ventriculomegaly and cortical atrophy in MRI, additionally to the white matter lesions. The difference between severe and mild Hunter’s syndrome is primarily reflected in the extent of the CNS involvement.* Therefore, one could speculate that preserved intelligence and absence of severe neurological abnormalities, as in our patients at the time of the study, could be compatible with ‘silent’ MRI lesions, while appearance of signs such as ventriculomegaly and cortical atrophy already in childhood, may indicate a more severe clinical course. However, the presence of severe CNS involvement also in mildly affected adult patients’ and the borderline intelligence of our patients imposes difficulties in predicting accurately the further evolution of both clinical and MRI findings. Serial MRI studies are needed in
DI Zafeiriou
et al.
order to establish the prognostic significance of the above MRI findings in the severity of Hunter’s syndrome in childhood.
References Neufeld EF, Muenzer J. The mucopolysaccharidoses. In: Striver CR, Beaudet AL, Sly WS, Valle D (eds) Tile Metabolic Basis of Inherited Disease (7th edn). New York: McGraw-Hill, 1995: 2465-2494. Barkovich AJ. Pediatric Neuroimaging. Lippincott-Raven, 1996: pp. 87-91.
Philadelphia:
Kendall BE. Disorders of lysosomes, peroxisomes, and mitochondria. Am J Neuroradiol 1992; 13: 621-653. Lee C, Dineen TE, Brack M et al. Mucopolysaccharidoses: characterization by cranial MRI imaging. Am ] Neuroradiol 1993; 14: 1285-1292. Murata R, Nakajima S, Tanaka A et al. MR imaging of the brain in patients with mucopolysaccharidosis. AJNR 1989; 10: 1165-1170. Shimoda-Matsubayashi S, Kuru Y, Sumie H et al. MRI findings in the mild type of mucopolysaccharidosis II (Hunter’s syndrome). Neuroradiology 1990; 32: 328-
330. Parsons VJ, Hughes DG, Wraith JE. Magnetic resonance imaging of the brain, neck and cervical spine in mild Hunter’s syndrome (mucopolysaccharidoses type II). Clin Radio1 1996; 51: 719-723.