s57 Clinical Neurology and Neurosurgery, 94 (Suppl.) (1992) SS7-S60 0 1992 Elsevier Science Publishers B.V. All rights reserved 0303~8467/92/$05.00 CNN 00108
Follow-up magnetic resonance imaging in Hallervorden-Spatz
disease
O.F. Brouwerl, P.M. Laboyrie’, A.C.B. Peters’ and G.J. Vielvoye2 1Department of Neurology, Division of Child Neurology, and 2 Depament
Key words:
Hallervorden-Spatz
disease; Magnetic
resonance
of Radiology, University Hospital, Leiden (The Netherlands)
imaging, brain; Diseases,
central
nervous
system; Diseases,
iron Summary Bilateral high signal emitting areas in the globus pallidus surrounded by low signal emitting areas have been described as a typical MRI finding in Hallervorden-Spatz disease (HSD). We made a diagnosis of HSD in an Il-year-old girl with progressive dystonia of 4 years duration who showed these typical MRI abnormalities. An initial MRI at the age of 9 was normal. Pathological confirmation of these typical MRI findings has not yet been described, but earlier reports as well as our case suggest that MRI may be helpful in making a clinical diagnosis of HSD. This case further shows that MRI may be normal in an early stage of the disease.
Introduction Hallervorden-Spatz disease (HSD) is a neurodegenerative disorder with an autosomal recessive mode of inheritance. The main clinical features are (a) occurrence at a young age, generally between the age of 2 and 15 years; (b) motor disorder, mainly of extrapyramidal type (dystonic postures, muscular rigidity, involuntary movements, choreoathetosis or tremor), and signs of corticospinal system involvement; (c) dementia; and (d) relentlessly progressive course. In addition ataxia, seizures, optic atrophy and retinitis pigmentosa have been described [l]. It seldom makes its presentation after the age of 20 and in these late-onset cases a Parkinsonian syndrome may be the predominant clinical manifestation [2]. Although the clinical features and course may suggest HSD, diagnosis is still based on pathologic findings, especially the unique combination of pallidonigral hyperpigmentation [3], widespread axonal spheroids, and excessive amounts of iron in the globus pallidus and substantia nigra [4]. Abnormalities in the kinetics of radioactively labeled iron [5-71, and ultrastructural abnormalities in skin, lymphocytes and bone-marrow have been reported [6,8], but these findings are not consistent. Computerized tomography (CT) of the brain is usually normal [9], or may Correspondence to: O.F. Brouwer, Department of Neurology, Division of Child Neurology, University IIospital, P.O. Box 9600,230O RC kiden, The Netherlands. Tel.: (71) 263920; Fax: (71) 154537.
show symmetrical areas of increased density in the basal ganglia [lo]. Magnetic resonance imaging (MRI) of the brain has been reported to show abnormalities in HSD with high signal emission areas in the medial part of the globus pallidus surrounded by low signal emission areas on T, weighted images [ll-131. Because of the typical appearance, the MRI abnormality has been called “eye-of-thetiger” sign [13]. Sequential MRI has shown evolution of abnormalities in one patient in a 3-year follow-up period [14]. In other patients with HSD, MRI was normal [9]. We report an 11-year-old girl with progressive dystonia, who initially had a normal MRI. Only two years later MRI showed the typical abnormalities as have been described in HSD. Case report This 11-year-old girl was the first of two children from non-consanguineous parents. Psychomotor devclopmcnt was normal until the age of 7 years when she developed dystonic posturing of her left hand. One year later, dystonia of the left arm and bilateral hyperreflexia were noticed. Her motor performance progressively deteriorated in the following years. Dystonia of both arms and a spastic paraparesis caused severe disability. Dysarthria and dysphagia developed gradually and communication became difficult. Neuropsychological testing revealed no impairment of cognitive function. Family history was negative.
Fig. 1. Tz-weighted (TR 2500; TE 100 ms; 0.5 T) images. a: first MRI study (9-year-old patient) shows no abnormalities. b: second MN study (11-year-old patient) shows bilateral high signal emitting areas in the globus pallidus, surrounded by low signal emission, giving a target-like appearance (eye-of-the-tiger sign).
Blood amino acids, lactate, arylsulfatase A, galactocerebrosidase, very long chain fatty acids, copper and ceruloplasmin were all normal. Visual, somatosensory, and brainstem auditory evoked potentials as well as electroen~ph~o~aphy showed no abnormalities. Motor conduction velocities of peripheral nerves were within normal limits. Ophthalmologic examination was normal. Electron microscopic examination of lymphocytes, skin and sural nerve disclosed no abnormalities. Cerebrospinal fluid (CSF) cell count, protein content and lactate were normal. Cerebral CT and NRI (Fig. la) at the age of 9 years showed no abnormalities. On the MRI at the age of 11 years, a circumscribed high signal emitting area was found in the medial part of both globi pallidi on T, weighted images surrounded by a low signal emitting area (Fig. lb).
Discussion This 11-year-old girl presented with a progressive extrapyramidal and pyramidal syndrome of 4 years duration, without cognitive impairment. Wdson disease, mitochondrial encephalopathy and metachromatic leukodystrophy were ruled out. Dystonia musculorum deformans was unlikely because of the presence of bipyramidal signs. The negative family history and the absence of rigidity and tremor made Huntington’s or Parkinson’s disease unlikely. The absence of spheroids in sural nerve biopsy argues against infantile neuroaxonal dystrophy. Therefore a diagnosis of HSD was adopted. Only two years later abnormalities in the globus pallidus were seen on MRI as have been described in HSD [ll-131. Combined clinical and MRI findings have been described in 8 patients with a clinical diagnosis of HSD (Table 1). In one of them postmortem examination con-
s59
S60 firmed the diagnosis, but in this patient the MRI was normal. The other patients are still alive. To our knowledge, abnormalities on MRI preceded by a normal MRI have not been reported before in HSD. Sequential MRI has been reported in one HSD patient during a follow-up period of 3 years [14]. The first MRI was performed 5 years after the onset of symptoms and showed bilateral increase of signal intensity in the pallidi. Three years later, rings of decreased signal intensity surrounding hyperintense areas were seen in the globi pallidi. From a pathological point of view, in HSD, two types of abnormalities are found, both capable of interfering with the T,-weighted signal intensity. These abnormalities are iron deposit and formation of axonal spheroids. The excessive iron deposition is scanty or absent in the early stage and it progressively increases during the evolution of the pathology [14]. The neuroaxonal degeneration, with consequent spheroid production, probably is the basis of the pathology, and the pallidonigral pigmentation is a subsequent phenomenon, deriving from auto-oxidation of an increased rate of lipopigments, normally occurring in these areas [14,15]. MRI may therefore be capable of showing specific abnormalities in HSD consistent with gradual increase of iron concentration in the globus pallidus surrounding a hyperintense focus in the medial part of the globus pallidus, which may be assumed to be due to cellular degeneration [ll-131. The development of low signal emission on MRI in our patient within a period of two years supports the hypothesis of gradual accumulation of iron in the globus pallidus. Except for the pathognomonic MRI features in HSD, unilateral or bilateral putaminal and/or pallidal high signal-intensity areas have also been found in Leigh’s disease, post-infarct and post-infectious dystonia, and metabolic glutaric aciduria [12]. Low signal-intensity neostriatal areas have been described in hereditary spastic dystonia [16], mitochondrial disorders [16], and Wilson’s disease [12,17].
In conclusion, we suggest that MRI may bc helpful in the diagnosis of HSD, but it may be normal early in the course of the disease. When a diagnosis of HSD is considered on clinical grounds, follow-up MRI studies may be necessary to show the specific abnormalities. References 1 Dooling EC, Shoene WC, Richardson 2 3 4 5 6 7 8 9 10 11 12
13 14 15 16 17 18 19 20
EP. Arch Neurol 1974; 30: 70-83. Jankovic J, Jirpatrick JB, Blomquist KA, Langlais PJ, Bird ED. Neurology 198.5; 3.5: 227-234. Dreese MJ, Netsky MG. In Minckler J (ed.), Pathology of the Nervous System. New York: McGraw-Hill, 1968: 1199-1202. Perry TL, Norman MG, Yang VW, et al. Ann Neural 1985: 18: 482289. Vakili S, Drew AL, Schuching van S, et al. Arch Neural 1977; 34: 729-738. Swaiman KF, Smith SA, Track GL, et al. Neurology 1983; 33: 301-305. Szanto J, Gallyas F. Arch Nemo1 1966; 14: 438442. Stover ML, Zimmerman AW, Donaldson JO. Neurology 1981; 31: 93. Alberta R, Rafel E, Chinchon I, Vadillo J, Navarro A. J Neural Neurosurg Psychiat 1987; SO: 1665-1668. Tennison MB, Bouldin TW, Whaley RA. Neurology 1988; 38: 15415.5. Schaffert DA, Johnsen SD, Johnson PC, Drayer BP. Neurology 1989; 39: 440-444. Rutledge JN, Hilal SK Silver AJ, et al. In Fahn S, et al (eds.), Advances in Neurology: Dystonia 2. New York: Raven Press, 1988: 265-275. Sethi KD, Adams RI, Loring DW, et al. Ann Neural 1988; 24: 692-694. Gallucci M, Cardona F, Arachi M, Slendiani A, Bozzao A, Passaricllo II. J Comput Assist Tomogr 1989; 14: 118-120. Seitclberger F, Gross II. Dtsch Z Nervenheilk 1957; 176: 104-125. Bruyn GW, Vielvoye GJ, Went LN. J Neural Sci 1991; 103: 195-202. Lukes SA, Aminoff MJ, Crooks L, Kaufman L, Mills C, Newton TII. Ann Neural 1983; 13: 690-691. Littrup PJ, Gebarski SS. J Comput Assist Tomogr 1985; 9: 491-493. Tanfani G, Mascalchi M, Dal Pozzo GC, Tavemi N, Saia A, Trevisan C. J Comput Assist Tomogr 1987; 11: 1057-1058. Mutoh K, Gkuno T, Masatoshi I, Nakano S, Mikawa H, Fujisawa I, Asato R. J Comput Assist Tomogr 1988; 12: 851-853.
Follow-up magnetic resonance imaging in Hallervorden-Spatz
disease
O.F. Brouwerl, P.M. Laboyrie’, A.C.B. Peters’ and G.J. Vielvoye2 1Department of Neurology, Division of Child Neurology, and 2 Depament
Key words:
Hallervorden-Spatz
disease; Magnetic
resonance
of Radiology, University Hospital, Leiden (The Netherlands)
imaging, brain; Diseases,
central
nervous
system; Diseases,
iron Summary Bilateral high signal emitting areas in the globus pallidus surrounded by low signal emitting areas have been described as a typical MRI finding in Hallervorden-Spatz disease (HSD). We made a diagnosis of HSD in an Il-year-old girl with progressive dystonia of 4 years duration who showed these typical MRI abnormalities. An initial MRI at the age of 9 was normal. Pathological confirmation of these typical MRI findings has not yet been described, but earlier reports as well as our case suggest that MRI may be helpful in making a clinical diagnosis of HSD. This case further shows that MRI may be normal in an early stage of the disease.
Introduction Hallervorden-Spatz disease (HSD) is a neurodegenerative disorder with an autosomal recessive mode of inheritance. The main clinical features are (a) occurrence at a young age, generally between the age of 2 and 15 years; (b) motor disorder, mainly of extrapyramidal type (dystonic postures, muscular rigidity, involuntary movements, choreoathetosis or tremor), and signs of corticospinal system involvement; (c) dementia; and (d) relentlessly progressive course. In addition ataxia, seizures, optic atrophy and retinitis pigmentosa have been described [l]. It seldom makes its presentation after the age of 20 and in these late-onset cases a Parkinsonian syndrome may be the predominant clinical manifestation [2]. Although the clinical features and course may suggest HSD, diagnosis is still based on pathologic findings, especially the unique combination of pallidonigral hyperpigmentation [3], widespread axonal spheroids, and excessive amounts of iron in the globus pallidus and substantia nigra [4]. Abnormalities in the kinetics of radioactively labeled iron [5-71, and ultrastructural abnormalities in skin, lymphocytes and bone-marrow have been reported [6,8], but these findings are not consistent. Computerized tomography (CT) of the brain is usually normal [9], or may Correspondence to: O.F. Brouwer, Department of Neurology, Division of Child Neurology, University IIospital, P.O. Box 9600,230O RC kiden, The Netherlands. Tel.: (71) 263920; Fax: (71) 154537.
show symmetrical areas of increased density in the basal ganglia [lo]. Magnetic resonance imaging (MRI) of the brain has been reported to show abnormalities in HSD with high signal emission areas in the medial part of the globus pallidus surrounded by low signal emission areas on T, weighted images [ll-131. Because of the typical appearance, the MRI abnormality has been called “eye-of-thetiger” sign [13]. Sequential MRI has shown evolution of abnormalities in one patient in a 3-year follow-up period [14]. In other patients with HSD, MRI was normal [9]. We report an 11-year-old girl with progressive dystonia, who initially had a normal MRI. Only two years later MRI showed the typical abnormalities as have been described in HSD. Case report This 11-year-old girl was the first of two children from non-consanguineous parents. Psychomotor devclopmcnt was normal until the age of 7 years when she developed dystonic posturing of her left hand. One year later, dystonia of the left arm and bilateral hyperreflexia were noticed. Her motor performance progressively deteriorated in the following years. Dystonia of both arms and a spastic paraparesis caused severe disability. Dysarthria and dysphagia developed gradually and communication became difficult. Neuropsychological testing revealed no impairment of cognitive function. Family history was negative.
Fig. 1. Tz-weighted (TR 2500; TE 100 ms; 0.5 T) images. a: first MRI study (9-year-old patient) shows no abnormalities. b: second MN study (11-year-old patient) shows bilateral high signal emitting areas in the globus pallidus, surrounded by low signal emission, giving a target-like appearance (eye-of-the-tiger sign).
Blood amino acids, lactate, arylsulfatase A, galactocerebrosidase, very long chain fatty acids, copper and ceruloplasmin were all normal. Visual, somatosensory, and brainstem auditory evoked potentials as well as electroen~ph~o~aphy showed no abnormalities. Motor conduction velocities of peripheral nerves were within normal limits. Ophthalmologic examination was normal. Electron microscopic examination of lymphocytes, skin and sural nerve disclosed no abnormalities. Cerebrospinal fluid (CSF) cell count, protein content and lactate were normal. Cerebral CT and NRI (Fig. la) at the age of 9 years showed no abnormalities. On the MRI at the age of 11 years, a circumscribed high signal emitting area was found in the medial part of both globi pallidi on T, weighted images surrounded by a low signal emitting area (Fig. lb).
Discussion This 11-year-old girl presented with a progressive extrapyramidal and pyramidal syndrome of 4 years duration, without cognitive impairment. Wdson disease, mitochondrial encephalopathy and metachromatic leukodystrophy were ruled out. Dystonia musculorum deformans was unlikely because of the presence of bipyramidal signs. The negative family history and the absence of rigidity and tremor made Huntington’s or Parkinson’s disease unlikely. The absence of spheroids in sural nerve biopsy argues against infantile neuroaxonal dystrophy. Therefore a diagnosis of HSD was adopted. Only two years later abnormalities in the globus pallidus were seen on MRI as have been described in HSD [ll-131. Combined clinical and MRI findings have been described in 8 patients with a clinical diagnosis of HSD (Table 1). In one of them postmortem examination con-
s59
S60 firmed the diagnosis, but in this patient the MRI was normal. The other patients are still alive. To our knowledge, abnormalities on MRI preceded by a normal MRI have not been reported before in HSD. Sequential MRI has been reported in one HSD patient during a follow-up period of 3 years [14]. The first MRI was performed 5 years after the onset of symptoms and showed bilateral increase of signal intensity in the pallidi. Three years later, rings of decreased signal intensity surrounding hyperintense areas were seen in the globi pallidi. From a pathological point of view, in HSD, two types of abnormalities are found, both capable of interfering with the T,-weighted signal intensity. These abnormalities are iron deposit and formation of axonal spheroids. The excessive iron deposition is scanty or absent in the early stage and it progressively increases during the evolution of the pathology [14]. The neuroaxonal degeneration, with consequent spheroid production, probably is the basis of the pathology, and the pallidonigral pigmentation is a subsequent phenomenon, deriving from auto-oxidation of an increased rate of lipopigments, normally occurring in these areas [14,15]. MRI may therefore be capable of showing specific abnormalities in HSD consistent with gradual increase of iron concentration in the globus pallidus surrounding a hyperintense focus in the medial part of the globus pallidus, which may be assumed to be due to cellular degeneration [ll-131. The development of low signal emission on MRI in our patient within a period of two years supports the hypothesis of gradual accumulation of iron in the globus pallidus. Except for the pathognomonic MRI features in HSD, unilateral or bilateral putaminal and/or pallidal high signal-intensity areas have also been found in Leigh’s disease, post-infarct and post-infectious dystonia, and metabolic glutaric aciduria [12]. Low signal-intensity neostriatal areas have been described in hereditary spastic dystonia [16], mitochondrial disorders [16], and Wilson’s disease [12,17].
In conclusion, we suggest that MRI may bc helpful in the diagnosis of HSD, but it may be normal early in the course of the disease. When a diagnosis of HSD is considered on clinical grounds, follow-up MRI studies may be necessary to show the specific abnormalities. References 1 Dooling EC, Shoene WC, Richardson 2 3 4 5 6 7 8 9 10 11 12
13 14 15 16 17 18 19 20
EP. Arch Neurol 1974; 30: 70-83. Jankovic J, Jirpatrick JB, Blomquist KA, Langlais PJ, Bird ED. Neurology 198.5; 3.5: 227-234. Dreese MJ, Netsky MG. In Minckler J (ed.), Pathology of the Nervous System. New York: McGraw-Hill, 1968: 1199-1202. Perry TL, Norman MG, Yang VW, et al. Ann Neural 1985: 18: 482289. Vakili S, Drew AL, Schuching van S, et al. Arch Neural 1977; 34: 729-738. Swaiman KF, Smith SA, Track GL, et al. Neurology 1983; 33: 301-305. Szanto J, Gallyas F. Arch Nemo1 1966; 14: 438442. Stover ML, Zimmerman AW, Donaldson JO. Neurology 1981; 31: 93. Alberta R, Rafel E, Chinchon I, Vadillo J, Navarro A. J Neural Neurosurg Psychiat 1987; SO: 1665-1668. Tennison MB, Bouldin TW, Whaley RA. Neurology 1988; 38: 15415.5. Schaffert DA, Johnsen SD, Johnson PC, Drayer BP. Neurology 1989; 39: 440-444. Rutledge JN, Hilal SK Silver AJ, et al. In Fahn S, et al (eds.), Advances in Neurology: Dystonia 2. New York: Raven Press, 1988: 265-275. Sethi KD, Adams RI, Loring DW, et al. Ann Neural 1988; 24: 692-694. Gallucci M, Cardona F, Arachi M, Slendiani A, Bozzao A, Passaricllo II. J Comput Assist Tomogr 1989; 14: 118-120. Seitclberger F, Gross II. Dtsch Z Nervenheilk 1957; 176: 104-125. Bruyn GW, Vielvoye GJ, Went LN. J Neural Sci 1991; 103: 195-202. Lukes SA, Aminoff MJ, Crooks L, Kaufman L, Mills C, Newton TII. Ann Neural 1983; 13: 690-691. Littrup PJ, Gebarski SS. J Comput Assist Tomogr 1985; 9: 491-493. Tanfani G, Mascalchi M, Dal Pozzo GC, Tavemi N, Saia A, Trevisan C. J Comput Assist Tomogr 1987; 11: 1057-1058. Mutoh K, Gkuno T, Masatoshi I, Nakano S, Mikawa H, Fujisawa I, Asato R. J Comput Assist Tomogr 1988; 12: 851-853.
