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Gliotic, nodular lesions in phenylketonuria: MR imaging findings
Computerized Medical Imaging and Graphics, Vol. 20, No. 5, pp. 399-401, 1996 Copyrijjht 0 1996Elsevicr ScienceLtd. All rights rcscfycd Prhted in Great Britain 0895-6111/% $15.00 + .oo
GLIOTIC,
NODULAR
LESIONS
IN PHENYLKJZTONURIk FINDINGS
MR IMAGING
R. Nuri Sener* Department of Radiology, Ege University Hospital, Bomova, Izmir 35100, Turkey (Received
4 August
1995; revised
12 August
1996)
Abstract-Pbensa represeatswe of the amino acid disorders.In this condition, and in other $I Mlt imaglngstadksare generallyncmpe&k We report a patient with pheay&etontiria -as, who bad nodularI~&~IEslesionsasodated with the usualdeepwhite matter involvementseenin tbe condition.We suggestthat time nodalar ksiorasmay repmseatfoci of gliotic hue, as previouslyshownby ntmopathlogical studieson phenyiketormrla.Copyright 0 1996ElsevierScienceLtd. Key
Words:
Brain, MR studies, Phenylketonuria, Brain, White matter, Amino acid disorders, Gliosis
recovery) MR images involved a relatively small area compared to those seen on corresponding T2weighted images (Figs 3 and 4). Spin-echo Tlweighted MR images were negative for these. No clinical evidence of multiple sclerosis was noted.
INTRODUCTION
Phenylketonuria, an uncommon autosomal recessive condition, represents one of the amino acid disorders which usually results from a deficiency of phenylalanine hydroxylase, an enzyme that is required to convert phenylalanine to tyrosin. In this condition, and in other aminoacidurias, findings in MR imaging studies are generally nonspecific (l-3). We report a patient with phenylketonuria who had gliotic nodular lesions associated with the usual deep white matter involvement seen in the condition.
DISCUSSION
Elevated blood levels of phenylalanine and production of its organic acid metabolites are toxic to the developing brain, which result in delayed or defective myelination (l-3). Neuropathological studies indicated that the myelin reduction in phenylketonuria results from a reduced myelin synthesis, characterizing the condition as dysmyelination rather than demyelination. It has been cited that these areas of defective myelination may be accompanied by foci of gliosis (4-6). Previous MR imaging studies reported that the lesions related to phenylketonuria showed increased signal on spin-echo T2-weighted MR images. Spinecho Tl-weighted images, however, were generally unremarkable. The lesions were usually located in the periventricular white matter, and were most evident posteriorly, particularly in the periatrial zone (l-3). In our patient with phenylketonuria these lesions were hypointense on heavily Tl-weighted MR images obtained utilizing the inversion recovery pulse sequence (Fig. 4), and were hype&tense on spinecho T2-weighted MR images (Figs l-3). A similar signal pattern was also noted with a number of scattered nodular lesions mimicking those seen in multiple sclerosis. None of these were seen on spinecho Tl-weighted MR images.
CASE REPORT
The present patient is an 11-yr-old boy suffering from phenylketonuria. He was under dietary control since infancy, however, he had moderate mental retardation and seizures. On a cranial MR imaging examination obtained at 0.5 Tesla, bilateral lesions were seen in the deep white matter involving the periventricular regions and optic radiations (Figs 1 and 3). Resides this a number of scattered nodular lesions mimicking those seen in multiple sclerosis were evident (Figs l-4). All the lesions were hypointense on Tl-weighted MR images obtained utilizing the inversion recovery pulse sequence (Fig. 4), and were hyperintense on spin-echo T2-weighted MR images (Figs l-3). The lesions that were hypointense on heavily Tl-weighted (inversion
*Department of Radiology, Ege University Hospital, Bornova, Izmir, 35100, Turkey. Tel.: 90-232 388 1390. Fax.: 90-232 342 0001. 399
Computerized Medical Imaging and Graphics
Fig. 1. Coronal, TZ-weighted MR image shows bilateral hyperintense periventricular lesions of phenylketonuria (open arrows). Hyperintense, small, nodular lesions mimicking multiple sclerosis are also noted (arrows).
It is known that the small oval or round lesions associated with multiple sclerosis, a demyelinating disorder, are usually asymmetrically distributed in the periventricular area (7). In our patient with phenylketonuria we noted a number of similar lesions simulating multiple sclerosis. However, no clinical evidence of an associated multiple sclerosis was evident. Therefore, we speculate that these small round lesions possibly represent foci of gliotic tissue, which reportedly may accompany areas of defective myelination in phenylketonuria, as shown by neuropathological studies (4-6). Similarly, the lesions seen in the deep white matter involving the periventricular regions and optic radiations may partly consist of foci of gliotic tissue within areas of defective myelination, as they had identical signal pattern with the multiple sclerosis-like lesions. They were
September-&tober/l996, Volume 20, Number 5
Fig. 3. Axial, T2-weighted MR image shows bilateral, hyperintense lesions of phenylketonuria at the region of optic radiations (open arrows). Note a left frontal, hyperintense, nodular lesion (arrow).
hypointense on heavily Tl -weighted (inversion recovery) MR images, and involved a relatively smaller area compared to those seen on TZ-weighted images.
SUMMARY An Il-yr-old boy is reported suffering from phenylketonuria. who was under dietary control since infancy. On a cranial MR imaging examination
Fig. 4. Axial, Tl-weighted MR image (inversion recovery pulse sequence; TRjTQTE, 2800/850/30/ one excitation; slice thickness = 5 mm, matrix= 160 x 224) shows the left frontal lesion to be hypointense (arrow). Similar signal pattern is noted in the lesions at the region of optic radiations (open arrows), which involves a smaller area
Fig. 2. Coronal, T2-weighted MR image shows hyperintense nodular lesions (arrows).
compared to that seen on the TZ-weighted image (see Fig. 3). These could represent the presenceof gliotic tissue in the regions of defective myelination in phenylketonuria.
Gliotic, nodular lesions in phenylketonuria
bilateral lesions were seen in the deep white matter involving the periventricular regions and optic radiations, an expected finding in phenylketonuria. Besides this a number of scattered nodular lesions mimicking those seen in multiple sclerosis were noted. We speculate that these small round lesions, unrelated to multiple sclerosis, possibly represent foci of gliotic tissue, as previous neuropathological studies indicated that the myelin reduction in phenylketonuria results from a reduced myelin synthesis, leading to a dysmyelinating condition, and that these areas of defective myelination may be accompanied by foci of gliosis. REFERENCES 1. Pwx~. K.D.; Gean-Marton, A.D.; Levy, H.L.; Davis, K.R. Phenylketomuia: MR imaging of the - brain with rkical correlation. Radioloav 177:437+lO: 1990. 2. Shaw, D.W.; Mara&, K.R.; We&berger, E.; Garretson, J.; Trahms. C.M.; Scott, C.R. MR imaging in phenylketonuria. AJNR 12:403-406; 1991.
l
R. N. SENER
401
3. Kendall, B.E. Disorders of lysosomes, peroxisomes, and mitochondria. AJNR 13:621-653; 1992. 4. Corselis, J.A.N. The pathological report of a case of phenylpyruvic oligophrenia. J. Neurol. Neurosurg. Psych. 163139-143; 1953. 5. Alford, E.C.; Stevenson, L.D.; Vogel, F.S.; Engle, R.L. Neuropathological findings in phenylpyruvic oligophrenia (phenylketonuria). J. Neurouathol. Exn. Neurol. 9:298-310: 1950. 6. Poser, C.M.; Van Bogaert, L. Neuropathological observations in nhenvlketonuria. Brain 8211-g: 1959. 7. Osborn: A.G. Diagnostic neurdradiology. St Louis: Mosby; 1994: 755-761.
About the Author-R. NURI SENERserves as the Chief of Pediatric Radiology and Neuroradiology Sections, and of the Magnetic Resonance Unit, at the D&artment of Radiology of Ege University, Izmir. Turkey, where he is Professor of Radioloav. He com&ted a Neurorkiology Research Fellowship be&v& 1990 and 1991 at the Neuroradiology Section of the University of Texas, Health Science Center, San Antonio, Texas. His primary field of research is Podiatric Neuroradiology. Dr Sener has served as a Visiting Professor at the Radiology Departments of the Ullevaal Hospital of Oslo University, Oslo, Norway, Royal Alexandra Hospital for Children, Sydney, Australia, and Hospital of !%o Paula University, SBo Paulo, Brazil.
GLIOTIC,
NODULAR
LESIONS
IN PHENYLKJZTONURIk FINDINGS
MR IMAGING
R. Nuri Sener* Department of Radiology, Ege University Hospital, Bomova, Izmir 35100, Turkey (Received
4 August
1995; revised
12 August
1996)
Abstract-Pbensa represeatswe of the amino acid disorders.In this condition, and in other $I Mlt imaglngstadksare generallyncmpe&k We report a patient with pheay&etontiria -as, who bad nodularI~&~IEslesionsasodated with the usualdeepwhite matter involvementseenin tbe condition.We suggestthat time nodalar ksiorasmay repmseatfoci of gliotic hue, as previouslyshownby ntmopathlogical studieson phenyiketormrla.Copyright 0 1996ElsevierScienceLtd. Key
Words:
Brain, MR studies, Phenylketonuria, Brain, White matter, Amino acid disorders, Gliosis
recovery) MR images involved a relatively small area compared to those seen on corresponding T2weighted images (Figs 3 and 4). Spin-echo Tlweighted MR images were negative for these. No clinical evidence of multiple sclerosis was noted.
INTRODUCTION
Phenylketonuria, an uncommon autosomal recessive condition, represents one of the amino acid disorders which usually results from a deficiency of phenylalanine hydroxylase, an enzyme that is required to convert phenylalanine to tyrosin. In this condition, and in other aminoacidurias, findings in MR imaging studies are generally nonspecific (l-3). We report a patient with phenylketonuria who had gliotic nodular lesions associated with the usual deep white matter involvement seen in the condition.
DISCUSSION
Elevated blood levels of phenylalanine and production of its organic acid metabolites are toxic to the developing brain, which result in delayed or defective myelination (l-3). Neuropathological studies indicated that the myelin reduction in phenylketonuria results from a reduced myelin synthesis, characterizing the condition as dysmyelination rather than demyelination. It has been cited that these areas of defective myelination may be accompanied by foci of gliosis (4-6). Previous MR imaging studies reported that the lesions related to phenylketonuria showed increased signal on spin-echo T2-weighted MR images. Spinecho Tl-weighted images, however, were generally unremarkable. The lesions were usually located in the periventricular white matter, and were most evident posteriorly, particularly in the periatrial zone (l-3). In our patient with phenylketonuria these lesions were hypointense on heavily Tl-weighted MR images obtained utilizing the inversion recovery pulse sequence (Fig. 4), and were hype&tense on spinecho T2-weighted MR images (Figs l-3). A similar signal pattern was also noted with a number of scattered nodular lesions mimicking those seen in multiple sclerosis. None of these were seen on spinecho Tl-weighted MR images.
CASE REPORT
The present patient is an 11-yr-old boy suffering from phenylketonuria. He was under dietary control since infancy, however, he had moderate mental retardation and seizures. On a cranial MR imaging examination obtained at 0.5 Tesla, bilateral lesions were seen in the deep white matter involving the periventricular regions and optic radiations (Figs 1 and 3). Resides this a number of scattered nodular lesions mimicking those seen in multiple sclerosis were evident (Figs l-4). All the lesions were hypointense on Tl-weighted MR images obtained utilizing the inversion recovery pulse sequence (Fig. 4), and were hyperintense on spin-echo T2-weighted MR images (Figs l-3). The lesions that were hypointense on heavily Tl-weighted (inversion
*Department of Radiology, Ege University Hospital, Bornova, Izmir, 35100, Turkey. Tel.: 90-232 388 1390. Fax.: 90-232 342 0001. 399
Computerized Medical Imaging and Graphics
Fig. 1. Coronal, TZ-weighted MR image shows bilateral hyperintense periventricular lesions of phenylketonuria (open arrows). Hyperintense, small, nodular lesions mimicking multiple sclerosis are also noted (arrows).
It is known that the small oval or round lesions associated with multiple sclerosis, a demyelinating disorder, are usually asymmetrically distributed in the periventricular area (7). In our patient with phenylketonuria we noted a number of similar lesions simulating multiple sclerosis. However, no clinical evidence of an associated multiple sclerosis was evident. Therefore, we speculate that these small round lesions possibly represent foci of gliotic tissue, which reportedly may accompany areas of defective myelination in phenylketonuria, as shown by neuropathological studies (4-6). Similarly, the lesions seen in the deep white matter involving the periventricular regions and optic radiations may partly consist of foci of gliotic tissue within areas of defective myelination, as they had identical signal pattern with the multiple sclerosis-like lesions. They were
September-&tober/l996, Volume 20, Number 5
Fig. 3. Axial, T2-weighted MR image shows bilateral, hyperintense lesions of phenylketonuria at the region of optic radiations (open arrows). Note a left frontal, hyperintense, nodular lesion (arrow).
hypointense on heavily Tl -weighted (inversion recovery) MR images, and involved a relatively smaller area compared to those seen on TZ-weighted images.
SUMMARY An Il-yr-old boy is reported suffering from phenylketonuria. who was under dietary control since infancy. On a cranial MR imaging examination
Fig. 4. Axial, Tl-weighted MR image (inversion recovery pulse sequence; TRjTQTE, 2800/850/30/ one excitation; slice thickness = 5 mm, matrix= 160 x 224) shows the left frontal lesion to be hypointense (arrow). Similar signal pattern is noted in the lesions at the region of optic radiations (open arrows), which involves a smaller area
Fig. 2. Coronal, T2-weighted MR image shows hyperintense nodular lesions (arrows).
compared to that seen on the TZ-weighted image (see Fig. 3). These could represent the presenceof gliotic tissue in the regions of defective myelination in phenylketonuria.
Gliotic, nodular lesions in phenylketonuria
bilateral lesions were seen in the deep white matter involving the periventricular regions and optic radiations, an expected finding in phenylketonuria. Besides this a number of scattered nodular lesions mimicking those seen in multiple sclerosis were noted. We speculate that these small round lesions, unrelated to multiple sclerosis, possibly represent foci of gliotic tissue, as previous neuropathological studies indicated that the myelin reduction in phenylketonuria results from a reduced myelin synthesis, leading to a dysmyelinating condition, and that these areas of defective myelination may be accompanied by foci of gliosis. REFERENCES 1. Pwx~. K.D.; Gean-Marton, A.D.; Levy, H.L.; Davis, K.R. Phenylketomuia: MR imaging of the - brain with rkical correlation. Radioloav 177:437+lO: 1990. 2. Shaw, D.W.; Mara&, K.R.; We&berger, E.; Garretson, J.; Trahms. C.M.; Scott, C.R. MR imaging in phenylketonuria. AJNR 12:403-406; 1991.
l
R. N. SENER
401
3. Kendall, B.E. Disorders of lysosomes, peroxisomes, and mitochondria. AJNR 13:621-653; 1992. 4. Corselis, J.A.N. The pathological report of a case of phenylpyruvic oligophrenia. J. Neurol. Neurosurg. Psych. 163139-143; 1953. 5. Alford, E.C.; Stevenson, L.D.; Vogel, F.S.; Engle, R.L. Neuropathological findings in phenylpyruvic oligophrenia (phenylketonuria). J. Neurouathol. Exn. Neurol. 9:298-310: 1950. 6. Poser, C.M.; Van Bogaert, L. Neuropathological observations in nhenvlketonuria. Brain 8211-g: 1959. 7. Osborn: A.G. Diagnostic neurdradiology. St Louis: Mosby; 1994: 755-761.
About the Author-R. NURI SENERserves as the Chief of Pediatric Radiology and Neuroradiology Sections, and of the Magnetic Resonance Unit, at the D&artment of Radiology of Ege University, Izmir. Turkey, where he is Professor of Radioloav. He com&ted a Neurorkiology Research Fellowship be&v& 1990 and 1991 at the Neuroradiology Section of the University of Texas, Health Science Center, San Antonio, Texas. His primary field of research is Podiatric Neuroradiology. Dr Sener has served as a Visiting Professor at the Radiology Departments of the Ullevaal Hospital of Oslo University, Oslo, Norway, Royal Alexandra Hospital for Children, Sydney, Australia, and Hospital of !%o Paula University, SBo Paulo, Brazil.