Computed Tomography and Magnetic Resonance Imaging of the Brain in Hurler’s Disease Adel K. Afifi, MD; Yutaka Sato, MD;
Mary
H.
Waziri, MD;
William E. Bell, MD
Abstract
Computed tomographic (CT) and magnetic resonance imaging (MRI) scans of the brain in five patients with Hurler’s disease are described and compared to the few available reports in the literature. Computed tomographic scans revealed low attenuation areas in the centrum semiovale and peritrigonal white matter. Ventriculomegaly was not a prominent feature in our patients, compared to those previously reported. In two patients, CT scans were normal. The most prominent magnetic resonance imaging abnormalities were the presence of radially oriented cystic areas in the centrum semiovale, peritrigonal white matter, corpus callosum, and pericallosal region. Magnetic resonance imaging abnormalities were present in all patients, even when CT scans were normal. Abnormalities on CT and MRI scans tended to be more prevalent in the posterior regions. Magnetic resonance imaging proved to be a more reliable imaging method in Hurler’s disease. T -weighted images delineated the cystic areas more clearly, whereas T 1 -weighted images were more sensitive in 2 abnormalities. resonance small white-matter abnormalities correlated well with known neuMagnetic imaging detecting ropathologic alteration in this disease. It is suggested that the cystic areas seen on MRI correspond to perivascular lacunae seen in histopathologic material. ( J Child Neurol 1990;5:235-241).
(MPS) Thegroupmucopolysaccharidoses inherited, progressive
are
a
of
disorders characterized by deficiency of lysosomal enzymes. In Hurler’s disease (MPSI-H), reduced activity of . a-~-iduronidase leads to intralysosomal accumulation of dermatan and heparan sulfate in different tissues and organs including the brain. Patients with Hurler’s disease thus develop a severe mental handicap associated with extensive neuronal, glial, and meningeal lesions, in addition to hydrocephalus. The clinical picture, biochemistry, histopathology, and cytopathology of Hurler’s disease are well established. Findings on brain computed tomographic (CT) scans in this disorder have been described in eight patients.’-3 In contrast, there are only two reports in the literature describing magnetic resonance imaging (MRI) of the brain in three patients with
Received Sept 28, 1989. Received revised Dec 18, 1989. Accepted for publication Dec 19, 1989. From the Departments of Pediatrics, Neurology, Radiology and Anatomy, College of Medicine, University of Iowa, Iowa IA. Address correspondence to Dr Adel K. Afifi, Division of Child Neurology, Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, IA 52242.
City,
disease. 3,4 We present CT scan and MRI in findings the brains of five patients with Hurler’s disease and correlate those findings with the known published neurohistology and neurocyto!ogy of this
Hurler’s
’
disorder. _
Patients
-
Case 1 S.~V. is a 15-month-old white girl (younger sibling of a brother with flurler’s disease) in whom the diagnosis of Hurler’s disease was made at age 4 months on the basis of enzyme deficiency. The diagnosis of Hurler’s syndrome was made in her older male sibling shortly after S. W, was born. No other siblings are affected and the remainder of the family history is noncontributory. She was admitted for bone marrow transplantation at age 15 months. 1’riur to this admission, she was in general good health except for hospitalization at age 2’/ months for a suspected viral illness. She had coarse facial features, cloudy corneas, hepatosplenorneg,ily’, a protuberant abdomen and stubby fingers. A CT scan at the time of admission (Figure I) showed areas of low attenuation in peritrignnal white matter and in frontal and occipital white matter of the centrum semiovale, as well as moderate 1’l’11tr1C111llnlt’~u11’. Magnetic resonance imaging performed at the same time showed. on Tj-weighted images (Figure 2), multiple small c,’v,eighted images were
Discussion Hurlefs disease is characterized by chondrodystrophic skeletal changes, corneal opacities, hepatosplenomegaly, and menial deficiency. Patients are readily recognized by their large heads, coarse
facies, hypertelorism, prominent bushy eyebrows, stiffened limbs, and kyphoscoliosis. Diagnosis is confirmed by decreased or absent a-L-iduronidase in fibroblasts or leukocytes. Although Thompson is credited with being the first to recognize, as early as 1900, the combination of clinical signs in this disorder,’ it was f~~xrier, in 1919, who described the condition in its fully developed form,’ Early on, the term gargoylism was used to refer to this disease because of the grotesque appearance of body structures in affected patients. Later, the term ~~3&dquo;Ier’S
syndrome was used.7 Computed tomographic y
studies of the brain in have reported ventricuthe frontal subarachnoid lomegalyfl-3 spaces enlargement of the interhemispheric space and of cortical suici,l and lovv-attenuation areas in the peritrigonal white matter and in the centrum semiovale.’ In our patients, iT scans confirmed the presence of iow-attenuation areas in the centrum semiovale and peritrigonai white matter described by Watts et al.1 Ventriculomegalv was not a promi-
Hurler’s disease
(Table 1) expansion of
finding in our patieWs. it was seen in only one patient and was mii~.~. It did not correlate with either the age of the patient or severity of the disease. In two of our patients, the CT scans were normal. In both patients, an MRI study, done at the same time as the CT scan in one patient and 5 months earlier in nent
FIGURE 6
~’1-~~ig~i~e~ (T~, 500 ms; Tu, 20 ms) parasagittat MRI from case 3 shows multiple small cysts in the pericallosal region.
the other, showed definite abnormalities.
Magnetic resonance imaging findings in Hurler’s
238
Downloaded from jcn.sagepub.com at PENNSYLVANIA STATE UNIV on May 26, 2015
Figure
7A
7B
FIGURE 7
Comparable axial MRI scans of T1-weighted (T., 750 ms; TE, 20 ms) (A) and T2weighted (T., 2200 ms; TE, 80 ms) (B) sequences. Note that white-matter lesions are better demonstrated on the T,-i~,eigh,Led image. disease (Table 2) have been described previously in three patients.3,4 In the patients or ~~hr~sc~r~ et 3 MRI revealed ventriculomegaly (more marked posteriorly), prominent cortical s-~ici, reduced gray-white contrast, and a mild prolongation in periventricular T2-Weighted images in the white matter adjacent to the posterior horns or diffusely in the periventricular region. In the patient reported by Kulkarni et al,~ MRI revealed ventriculomegaly and periventricular high signal intensity on T2-weighted images. All five of our patients showed abnormalities on MRI. In two patients, the MRI studies were abnormal although CT studies done at the same time or few months later were normal. This indicates that MRI is a more reliable imaging methods for the detection of brain lesions in Hurler’s disease. The most prominent lB1RI abnormalities in our patients consisted of cystic areas in the white matter on T1-weighted images and corresponding areas of high signal intensity on ~2-~~T~ibht~d images. Such areas were seen in the peritrigonal white matter, centrum semiovale, corpus caii~s;.~~, and perical10sal region. They were oriented radially from the subependymal region toward the cortex. The occur’2
of cystic areas in the corpus c:~~los~~n and pericallosai area has not been reported previously, nor has the radial orientation of the cystic areas. In the periventricular white matter and centrum semiovale, lesions tended to be more prominent ~aosteri~rl~. In the corpus callvsum, punched out cystic areas were present in the rostrum, genu, and body, best visualized on the sagittal images. T1-weighted images delineated the cystic areas better and showed their radial orientation clearly, whereas ~~-weig~Eed images were more sensitive in detecting small whitematter abnormalities, even when T,-weighted images were normal. The reduced gray-white matter contrast described by Johnson et a13 in their two cases were not seen in any of our patients. In contrast to findings in previous reports,3,’1 ventricutomegaly was not a prominent feature in our patients. The cerebellum, brain stem, basal ganglia, and thalamus were normal in MRI scans of our patients and in those reported in the literature. The nature of the observed radially oriented, round or oval, cystic white-matter structures and the rationale for their apparent posterior predilection are not discernible from MRI studies. Similar structures rence
239
Downloaded from jcn.sagepub.com at PENNSYLVANIA STATE UNIV on May 26, 2015
TABLE 1 Brain CT
X
=
Findings
present;
+
=
in Hurler’s Disease
mild;
++
=
moderate;
+++
=
severe;
N
=
normal.
and orientations have, however, been described in the literature in histopathologic studies of brain tissue in Hurler’s patients. Our patients are all still alive; hence, no histopathologic data is available from them to compare with the findings on imaging studies. Pathologic studies in Hurler’s disease were initially reported by Tuthill,8 who described brain pathology in one of Hurler’s original patients. He observed perivascular lacunation confined to the white matter and unusually thick adventitia of vesTABLE 2 Brain MRI
X
=
Findings in
present;
+
=
mild;
sels in the centrum semiovale and basal ganglia. The adventitia consisted of a delicate fibrous network with numerous large cells containing clear, poorly defined cytoplasm. Unfortunately, this case was complicated by coexisting tuberculous meningitis. In 1948, Green9 presented the second detailed neurohistologic account in an uncomplicated case of Hurler’s disease. In addition to neuronal distension and leptomeningeal thickening, he described perivascular accumulation of ground substance in large blood vessels and loss of myelin in corresponding areas.
Hurler’s Disease
++
=
moderate;
+++ = severe.
240
Downloaded from jcn.sagepub.com at PENNSYLVANIA STATE UNIV on May 26, 2015
These changes occurred in deep cerebral white mat&dquo;: ter, basal ganglia, and thalamus. Subsequent histo-
pathologic reports described perivascular cysts containing mucoid translucent materiall°; enlarged perivascular spaces in subcortical white matter containing gelatinous material similar to that in the subarachnoid space, most pronounced in the occipital region 11; radially arranged oval cystic spaces (lacunae) of varying sizes limited to the white matter, with their long axes in the direction of radiating white fibers and with demyelination of the cyst wall6; elongated cystic lesions in the corpus callosum 6; perivascular lacunae in white matter of the centrum semiovale 12 ; perivascular white matter cavitation’3,14
secondary to mucopolysaccharide storage 13 ; accentuation of perivascular pallor and splitting of capillary basement membrane due to distended perithelial cell processes15,16; perithelial cell inclusious distending the cytoplasm17; thickened leptomeninges, ventriculomegaly, gyral atrophy, and neuronal distension’8; and foam cells in Virchow Robin spaces around small blood vessels in the centrum semiovale, giving the appearance of cribriform changes in the white
matter. 3,19 Thus, other than the established neuronal and
leptomeningeal pathology, there is consensus, from light and electron microscopic pathologic studies, on the presence of perivascular lacunar spaces in cortical white matter in this disease. In one pathologic study,2° the perivascular lacunae seen at autopsy corresponded to the low attenuation areas seen on CT scan. In another pathologic study,li the lacunae were more prevalent in posterior regions. In one other pathologic study,6 lacunae were demonstrated in the corpus callosum. It is evident from the above that MRI is the more sensitive imaging tool for the detection of brain abnormalities in Hurler’s disease. It is also one that correlates well with reported neuropathologic alterations in this condition, including gyral atrophy, ventriculomegaly, and the white matter lacunae in the centrum semiovale, as well as in callosal and peritrigonal regions. Based on the cited pathologic alterations in white matter and on the appearance, location, and orientation of corresponding whitematter lesions on MRI, it is suggested that the MRI abnormalities represent the perivascular lacunae seen in pathologic material. There is no obvious explanation for the apparent selective involvement of posterior white-matter regions in the pathologic
process.
1. Watts
2. 3.
References E, Kendall BE,
et al: Computed tomogRWE, Spellacy raphy studies on patients with mucopolysaccharidoses. Neuroradiology 1981;21:9-23. Shinnar S, Singer HS, Valle D: Acute hydroccphatus in Hurler’s syndrome. Am J Dis Child 1982;136:556-557. Johnson MA, Desai S, Hugh-Jones K, Starer F: Magnetic resonance imaging of the brain in Hurler syndrome. AJNR
1984;5:816-819. 4. Kulkarni MV, Williams JC, Yeakley JW, et al: Magnetic resonance imaging in the diagnosis of the cranio-cervical manifestations of the mucopolysaccharidoses. Magn Reson Imag
1987;5:317-323. 5. Henderson JL: Gargoylism. A review of the principal features with a report of five cases. Arch Dis Child 1940;15:201-214. 6. Naidoo D: Gargoylism (Hurler’s disease): A neuropathological report. J Ment Sci 1953;99:74-83. 7. Ashby WR, Stewart RM, Watkin JH: Chondro-osteo-dystrophy of the Hurler type (gargoylism). A pathological study. Brain 1937;60:149-179. 8. Tuthill CR: Juvenile amaurotic idiocy. Marked adventitial growth associated with skeletal malformations and tuberculomas. Arch Neurol Psychiatry 1934;32:198-209. 9. Green MA: Gargoylism (lipochondrodystrophy). J
10.
1948;7:399-416. Exp Neurol Lindsay S, Reilly WA, Gotham TJ, Study of pathologic lesions and
Neuropathol
Skahen R: Gargoylism. II. clinical review of twelve
cases. Am J Dis Child 1948;76:239-306. 11. Henderson JL, MacGregor AR, Thannhauser
SJ, Holden R: The pathology and biochemistry of gargoylism. A report of three cases with a review of the literature. Arch Dis Child 1952;27:230-253.
12. Bishton RL, Norman RM, Tingey A: The pathology and chemistry of a case of gargoylism. J Clin Pathol 1956;9: 305-314. 13. Norman RM, Urich H, France NE: Perivascular cavitation of the basal ganglia in gargoylism. J Ment Sci 1959;105:10701077. 14. Crome L, Stern J: Pathology of Mental Retardation , 2nd ed. Baltimore, Williams & Witkins, 1972, pp 295-351. 15. Aleu FP, Terry RD, Zellweger H: Electron microscopy of two cerebral biopsies in gargoylism. J Neuropathol Exp Neurol
1965;24:304-317. 16. Dekaban AS, Constantopoulos G: Mucopolysasccharidosis types 1, II, IIIA and V. Pathological and biochemical abnormalities in the neural and mesenchymal elements of the brain. Acta Neuropathol 1977;39.1-7. 17. Loeb H, Jonniaux G, Resibois A, et al: Biochemical and ultrastructural studies in Hurler’s syndrome. J Pediatr 1968;73: 860-874. 18. Doshi R, Sandry SA, Churchill W, Brownell B: The cerebellum in mucopolysaccharidosis. A histological, histochemical, and ultrastructural study. J Ncurol Neurosurg Psychiatry
1974;34:1133-1138. 19. Winters PR, Harrod MJ, Molenich-Heetred SA, et al: α-L-iduronidase deficiency and possible Hurler-Scheie genetic compound. Clinical, pathologic, and biochemical findings.
Neurology 1976;26:1003-1007. 20. Watts RWE, Spellacy E, Adams JH: Neuropathological and clinical correlations in Hurler disease. J Inherited Metab Dis
1986;9:261-272.
241
Downloaded from jcn.sagepub.com at PENNSYLVANIA STATE UNIV on May 26, 2015
Mary
H.
Waziri, MD;
William E. Bell, MD
Abstract
Computed tomographic (CT) and magnetic resonance imaging (MRI) scans of the brain in five patients with Hurler’s disease are described and compared to the few available reports in the literature. Computed tomographic scans revealed low attenuation areas in the centrum semiovale and peritrigonal white matter. Ventriculomegaly was not a prominent feature in our patients, compared to those previously reported. In two patients, CT scans were normal. The most prominent magnetic resonance imaging abnormalities were the presence of radially oriented cystic areas in the centrum semiovale, peritrigonal white matter, corpus callosum, and pericallosal region. Magnetic resonance imaging abnormalities were present in all patients, even when CT scans were normal. Abnormalities on CT and MRI scans tended to be more prevalent in the posterior regions. Magnetic resonance imaging proved to be a more reliable imaging method in Hurler’s disease. T -weighted images delineated the cystic areas more clearly, whereas T 1 -weighted images were more sensitive in 2 abnormalities. resonance small white-matter abnormalities correlated well with known neuMagnetic imaging detecting ropathologic alteration in this disease. It is suggested that the cystic areas seen on MRI correspond to perivascular lacunae seen in histopathologic material. ( J Child Neurol 1990;5:235-241).
(MPS) Thegroupmucopolysaccharidoses inherited, progressive
are
a
of
disorders characterized by deficiency of lysosomal enzymes. In Hurler’s disease (MPSI-H), reduced activity of . a-~-iduronidase leads to intralysosomal accumulation of dermatan and heparan sulfate in different tissues and organs including the brain. Patients with Hurler’s disease thus develop a severe mental handicap associated with extensive neuronal, glial, and meningeal lesions, in addition to hydrocephalus. The clinical picture, biochemistry, histopathology, and cytopathology of Hurler’s disease are well established. Findings on brain computed tomographic (CT) scans in this disorder have been described in eight patients.’-3 In contrast, there are only two reports in the literature describing magnetic resonance imaging (MRI) of the brain in three patients with
Received Sept 28, 1989. Received revised Dec 18, 1989. Accepted for publication Dec 19, 1989. From the Departments of Pediatrics, Neurology, Radiology and Anatomy, College of Medicine, University of Iowa, Iowa IA. Address correspondence to Dr Adel K. Afifi, Division of Child Neurology, Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, IA 52242.
City,
disease. 3,4 We present CT scan and MRI in findings the brains of five patients with Hurler’s disease and correlate those findings with the known published neurohistology and neurocyto!ogy of this
Hurler’s
’
disorder. _
Patients
-
Case 1 S.~V. is a 15-month-old white girl (younger sibling of a brother with flurler’s disease) in whom the diagnosis of Hurler’s disease was made at age 4 months on the basis of enzyme deficiency. The diagnosis of Hurler’s syndrome was made in her older male sibling shortly after S. W, was born. No other siblings are affected and the remainder of the family history is noncontributory. She was admitted for bone marrow transplantation at age 15 months. 1’riur to this admission, she was in general good health except for hospitalization at age 2’/ months for a suspected viral illness. She had coarse facial features, cloudy corneas, hepatosplenorneg,ily’, a protuberant abdomen and stubby fingers. A CT scan at the time of admission (Figure I) showed areas of low attenuation in peritrignnal white matter and in frontal and occipital white matter of the centrum semiovale, as well as moderate 1’l’11tr1C111llnlt’~u11’. Magnetic resonance imaging performed at the same time showed. on Tj-weighted images (Figure 2), multiple small c,’v,eighted images were
Discussion Hurlefs disease is characterized by chondrodystrophic skeletal changes, corneal opacities, hepatosplenomegaly, and menial deficiency. Patients are readily recognized by their large heads, coarse
facies, hypertelorism, prominent bushy eyebrows, stiffened limbs, and kyphoscoliosis. Diagnosis is confirmed by decreased or absent a-L-iduronidase in fibroblasts or leukocytes. Although Thompson is credited with being the first to recognize, as early as 1900, the combination of clinical signs in this disorder,’ it was f~~xrier, in 1919, who described the condition in its fully developed form,’ Early on, the term gargoylism was used to refer to this disease because of the grotesque appearance of body structures in affected patients. Later, the term ~~3&dquo;Ier’S
syndrome was used.7 Computed tomographic y
studies of the brain in have reported ventricuthe frontal subarachnoid lomegalyfl-3 spaces enlargement of the interhemispheric space and of cortical suici,l and lovv-attenuation areas in the peritrigonal white matter and in the centrum semiovale.’ In our patients, iT scans confirmed the presence of iow-attenuation areas in the centrum semiovale and peritrigonai white matter described by Watts et al.1 Ventriculomegalv was not a promi-
Hurler’s disease
(Table 1) expansion of
finding in our patieWs. it was seen in only one patient and was mii~.~. It did not correlate with either the age of the patient or severity of the disease. In two of our patients, the CT scans were normal. In both patients, an MRI study, done at the same time as the CT scan in one patient and 5 months earlier in nent
FIGURE 6
~’1-~~ig~i~e~ (T~, 500 ms; Tu, 20 ms) parasagittat MRI from case 3 shows multiple small cysts in the pericallosal region.
the other, showed definite abnormalities.
Magnetic resonance imaging findings in Hurler’s
238
Downloaded from jcn.sagepub.com at PENNSYLVANIA STATE UNIV on May 26, 2015
Figure
7A
7B
FIGURE 7
Comparable axial MRI scans of T1-weighted (T., 750 ms; TE, 20 ms) (A) and T2weighted (T., 2200 ms; TE, 80 ms) (B) sequences. Note that white-matter lesions are better demonstrated on the T,-i~,eigh,Led image. disease (Table 2) have been described previously in three patients.3,4 In the patients or ~~hr~sc~r~ et 3 MRI revealed ventriculomegaly (more marked posteriorly), prominent cortical s-~ici, reduced gray-white contrast, and a mild prolongation in periventricular T2-Weighted images in the white matter adjacent to the posterior horns or diffusely in the periventricular region. In the patient reported by Kulkarni et al,~ MRI revealed ventriculomegaly and periventricular high signal intensity on T2-weighted images. All five of our patients showed abnormalities on MRI. In two patients, the MRI studies were abnormal although CT studies done at the same time or few months later were normal. This indicates that MRI is a more reliable imaging methods for the detection of brain lesions in Hurler’s disease. The most prominent lB1RI abnormalities in our patients consisted of cystic areas in the white matter on T1-weighted images and corresponding areas of high signal intensity on ~2-~~T~ibht~d images. Such areas were seen in the peritrigonal white matter, centrum semiovale, corpus caii~s;.~~, and perical10sal region. They were oriented radially from the subependymal region toward the cortex. The occur’2
of cystic areas in the corpus c:~~los~~n and pericallosai area has not been reported previously, nor has the radial orientation of the cystic areas. In the periventricular white matter and centrum semiovale, lesions tended to be more prominent ~aosteri~rl~. In the corpus callvsum, punched out cystic areas were present in the rostrum, genu, and body, best visualized on the sagittal images. T1-weighted images delineated the cystic areas better and showed their radial orientation clearly, whereas ~~-weig~Eed images were more sensitive in detecting small whitematter abnormalities, even when T,-weighted images were normal. The reduced gray-white matter contrast described by Johnson et a13 in their two cases were not seen in any of our patients. In contrast to findings in previous reports,3,’1 ventricutomegaly was not a prominent feature in our patients. The cerebellum, brain stem, basal ganglia, and thalamus were normal in MRI scans of our patients and in those reported in the literature. The nature of the observed radially oriented, round or oval, cystic white-matter structures and the rationale for their apparent posterior predilection are not discernible from MRI studies. Similar structures rence
239
Downloaded from jcn.sagepub.com at PENNSYLVANIA STATE UNIV on May 26, 2015
TABLE 1 Brain CT
X
=
Findings
present;
+
=
in Hurler’s Disease
mild;
++
=
moderate;
+++
=
severe;
N
=
normal.
and orientations have, however, been described in the literature in histopathologic studies of brain tissue in Hurler’s patients. Our patients are all still alive; hence, no histopathologic data is available from them to compare with the findings on imaging studies. Pathologic studies in Hurler’s disease were initially reported by Tuthill,8 who described brain pathology in one of Hurler’s original patients. He observed perivascular lacunation confined to the white matter and unusually thick adventitia of vesTABLE 2 Brain MRI
X
=
Findings in
present;
+
=
mild;
sels in the centrum semiovale and basal ganglia. The adventitia consisted of a delicate fibrous network with numerous large cells containing clear, poorly defined cytoplasm. Unfortunately, this case was complicated by coexisting tuberculous meningitis. In 1948, Green9 presented the second detailed neurohistologic account in an uncomplicated case of Hurler’s disease. In addition to neuronal distension and leptomeningeal thickening, he described perivascular accumulation of ground substance in large blood vessels and loss of myelin in corresponding areas.
Hurler’s Disease
++
=
moderate;
+++ = severe.
240
Downloaded from jcn.sagepub.com at PENNSYLVANIA STATE UNIV on May 26, 2015
These changes occurred in deep cerebral white mat&dquo;: ter, basal ganglia, and thalamus. Subsequent histo-
pathologic reports described perivascular cysts containing mucoid translucent materiall°; enlarged perivascular spaces in subcortical white matter containing gelatinous material similar to that in the subarachnoid space, most pronounced in the occipital region 11; radially arranged oval cystic spaces (lacunae) of varying sizes limited to the white matter, with their long axes in the direction of radiating white fibers and with demyelination of the cyst wall6; elongated cystic lesions in the corpus callosum 6; perivascular lacunae in white matter of the centrum semiovale 12 ; perivascular white matter cavitation’3,14
secondary to mucopolysaccharide storage 13 ; accentuation of perivascular pallor and splitting of capillary basement membrane due to distended perithelial cell processes15,16; perithelial cell inclusious distending the cytoplasm17; thickened leptomeninges, ventriculomegaly, gyral atrophy, and neuronal distension’8; and foam cells in Virchow Robin spaces around small blood vessels in the centrum semiovale, giving the appearance of cribriform changes in the white
matter. 3,19 Thus, other than the established neuronal and
leptomeningeal pathology, there is consensus, from light and electron microscopic pathologic studies, on the presence of perivascular lacunar spaces in cortical white matter in this disease. In one pathologic study,2° the perivascular lacunae seen at autopsy corresponded to the low attenuation areas seen on CT scan. In another pathologic study,li the lacunae were more prevalent in posterior regions. In one other pathologic study,6 lacunae were demonstrated in the corpus callosum. It is evident from the above that MRI is the more sensitive imaging tool for the detection of brain abnormalities in Hurler’s disease. It is also one that correlates well with reported neuropathologic alterations in this condition, including gyral atrophy, ventriculomegaly, and the white matter lacunae in the centrum semiovale, as well as in callosal and peritrigonal regions. Based on the cited pathologic alterations in white matter and on the appearance, location, and orientation of corresponding whitematter lesions on MRI, it is suggested that the MRI abnormalities represent the perivascular lacunae seen in pathologic material. There is no obvious explanation for the apparent selective involvement of posterior white-matter regions in the pathologic
process.
1. Watts
2. 3.
References E, Kendall BE,
et al: Computed tomogRWE, Spellacy raphy studies on patients with mucopolysaccharidoses. Neuroradiology 1981;21:9-23. Shinnar S, Singer HS, Valle D: Acute hydroccphatus in Hurler’s syndrome. Am J Dis Child 1982;136:556-557. Johnson MA, Desai S, Hugh-Jones K, Starer F: Magnetic resonance imaging of the brain in Hurler syndrome. AJNR
1984;5:816-819. 4. Kulkarni MV, Williams JC, Yeakley JW, et al: Magnetic resonance imaging in the diagnosis of the cranio-cervical manifestations of the mucopolysaccharidoses. Magn Reson Imag
1987;5:317-323. 5. Henderson JL: Gargoylism. A review of the principal features with a report of five cases. Arch Dis Child 1940;15:201-214. 6. Naidoo D: Gargoylism (Hurler’s disease): A neuropathological report. J Ment Sci 1953;99:74-83. 7. Ashby WR, Stewart RM, Watkin JH: Chondro-osteo-dystrophy of the Hurler type (gargoylism). A pathological study. Brain 1937;60:149-179. 8. Tuthill CR: Juvenile amaurotic idiocy. Marked adventitial growth associated with skeletal malformations and tuberculomas. Arch Neurol Psychiatry 1934;32:198-209. 9. Green MA: Gargoylism (lipochondrodystrophy). J
10.
1948;7:399-416. Exp Neurol Lindsay S, Reilly WA, Gotham TJ, Study of pathologic lesions and
Neuropathol
Skahen R: Gargoylism. II. clinical review of twelve
cases. Am J Dis Child 1948;76:239-306. 11. Henderson JL, MacGregor AR, Thannhauser
SJ, Holden R: The pathology and biochemistry of gargoylism. A report of three cases with a review of the literature. Arch Dis Child 1952;27:230-253.
12. Bishton RL, Norman RM, Tingey A: The pathology and chemistry of a case of gargoylism. J Clin Pathol 1956;9: 305-314. 13. Norman RM, Urich H, France NE: Perivascular cavitation of the basal ganglia in gargoylism. J Ment Sci 1959;105:10701077. 14. Crome L, Stern J: Pathology of Mental Retardation , 2nd ed. Baltimore, Williams & Witkins, 1972, pp 295-351. 15. Aleu FP, Terry RD, Zellweger H: Electron microscopy of two cerebral biopsies in gargoylism. J Neuropathol Exp Neurol
1965;24:304-317. 16. Dekaban AS, Constantopoulos G: Mucopolysasccharidosis types 1, II, IIIA and V. Pathological and biochemical abnormalities in the neural and mesenchymal elements of the brain. Acta Neuropathol 1977;39.1-7. 17. Loeb H, Jonniaux G, Resibois A, et al: Biochemical and ultrastructural studies in Hurler’s syndrome. J Pediatr 1968;73: 860-874. 18. Doshi R, Sandry SA, Churchill W, Brownell B: The cerebellum in mucopolysaccharidosis. A histological, histochemical, and ultrastructural study. J Ncurol Neurosurg Psychiatry
1974;34:1133-1138. 19. Winters PR, Harrod MJ, Molenich-Heetred SA, et al: α-L-iduronidase deficiency and possible Hurler-Scheie genetic compound. Clinical, pathologic, and biochemical findings.
Neurology 1976;26:1003-1007. 20. Watts RWE, Spellacy E, Adams JH: Neuropathological and clinical correlations in Hurler disease. J Inherited Metab Dis
1986;9:261-272.
241
Downloaded from jcn.sagepub.com at PENNSYLVANIA STATE UNIV on May 26, 2015
