The Japanese Journal of Psychiatry and Neurology, Vol. 46, No. 3, 1992
An Autopsied Case of Dentatorubropallidoluysian Atrophy with Atypical Pathological Features Katsuyoshi Mizukami, M.D., Megumi Sasaki, M.D., Hiroyasu Shiraishi, M.D., Junzo Koizumi, M.D., Takesaburo Ogata, M.D.* and Kenji Kosaka** Department of Psychiatry, Institute of Clinical Medicine, University of Tsukuba, Tsukuba *Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba **Department of Psychiatry and Neurology, Yokohama City University, School of Medicine, Yokohama
Abstract: This is a report of an autopsied case of dentatorubropallidoluysian atrophy (DRPLA) with atypical neuropathological Andings. The patients was a 31-year-old female. Her clinical symptoms were epileptic seizures, cerebellar ataxia, choreoathetosis and dementia. A neuropathological examination revealed the Abrillary gliosis in various areas of the CNS and severe degeneration in the cerebellar cortex and nucleus fwiculi dorsalis in addition to a marked degeneration of the dentatorubropallidoluysiansystems. The present case is diagnosed neuropathologically as DRPLA associated with the flndings of chronic diphenylhydantoin intoxication and epileptic brain damage. Key Words ; DRPLA, cerebellar lesion, degeneration of nucleus fasciculi dorsalis, chronic diphenylhydantoin intoxication Jpn J Psychiatr Neurol46: 749-754,1992
INTRODUCTION
Dentatorubropallidoluysian atrophy (DRPLA) is a rare heredo-degenerative disease. The main clinical features are cerebellar ataxia, choreoathetosis, myoclonus, epileptic seizures and mental disorders such as personality changes and dementia. Neuropathologically, both the dentatorubral and pallidoluysian systems are selectively afReceived for publication on Feb. 3, 1992. Mailing address: Katsuyoshi Mizukami, M.D., Department of Psychiatry, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305,Japan.
fected.l 3-5
9 10 12-15
In this paper we present an atypical case of DRPLA with fibrillary gliosis in various areas of the CNS and severe degeneration in the cerebellar cortex and nucleus fasciculi dorsalis. CASE REPORT
A mildly mentally retarded female had a grand ma1 convulsive attack at the age of 20. After that, similar attacks recurred once in half a year. Unsteady gait began at the age of 23. Two years later, dysarthria and choreiform movements developed and progressed gradually. She was admitted with dementia
K. Mizukami et al.
750
and urinary incontinence to the psychiatric ward, The University of Tsukuba Hospital at age 26. On admission, her cerebellar ataxia, choreoathetotic movements, epileptic seizures, personality changes and dementia were noticed. The family history revealed 12 similar patients in four successive generations (Fig. 1). It means an autosomal dominant heredity. CT showed a mild atrophy of the cerebrum and brainstem with a moderate dilatation of the lateral, third and fourth ventricles. The patient was diagnosed clinically as DRPLA from the findings of clinical symptoms and CT. Neurological and mental deterioration progressed steadily. At age 29, she became bedridden, almost apathetic and mute and her choreoathetotic movements gradually decreased. Status epilepticus occurred twice at her terminal stage, but neither myoclonus nor disturbance of ocular movement was observed. She suffered recurrently from pneumonia and died at age 3 1. The total duration of the disease was 11 years. Anticonvulsant drugs (diphenylhydantoin 150-375 mg, phenobarbital 48-200 mg, sodium valproate 8001,200 mg/day) had been administered since the age of 20. Neuropathological findings. The brain weight was 770 grams and a severe diffuse brain atrophy was observed. The cerebellum was also atrophic. Coronal sections of the brain revealed the atrophy of the caudate nucleus, lateral pallidal segment and sub-
thalamic nucleus with brownish discoloration of the latter two nuclei. The superior cerebellar peduncle, dentate hilus and pontine tegmentum were also obviously atrophic (Fig. 2). Microscopically, no obvious neuronal loss was observed in the cerebral cortex, except for “Ammon’s horn sclerosis,” although the severe brain atrophy was present. Moderate fibrillary gliosis was present in the whole cerebral white matter, internal and external capsules and optic tract. In the lateral segment of the globus pallidus remarkable neuronal loss with dense fibrillary gliosis was found (Fig. 3). The subthalamic nucleus had mild neuronal loss with dense fibrillary gliosis. In the red nucleus mild neuronal loss with moderate fibrillary gliosis was present. In the cerebellum, Purkinje cells were severely decreased in number and Bergmann’s glia proliferated (Fig. 4). These changes were more pronounced in the ventral parts of the cerebellum, especially of the cerebellar hemispheres. The superior cerebellar peduncle was demyelinated and gliotic. In the dentate nucleus, apparent neuronal loss with astrocytosis was recognized. Otherwise, fibrillary gliosis was observed in the striatum, thalamus,
0
I .
U
0
.
I & m
.
.
0
3
. .
present c ~ s e
Fig. 1 : Pedigree of the family.
aRectd
Fig. 2: The superior cerebellar peduncle, dentate hilus and pontine tegmentum are obviously atrophic. The superior cerebellar peduncles are demyelinated. (Kltiver-Barrera stain, X 1.4).
DRPLA with Atypical Pathological Features
75 1
Fig. 3: The globus pallidus, especially the lateral segment, shows fibrillary gliosis. (Holzer stain, X 15.5).
Fig. 4 : Purkinje cells are severely decreased in number and Bergmann’s glia markedly proliferate. (H.E.stain, X 155).
mamillary body, nucleus basalis of Meynert, hypothalamic region, substantia nigra, central gray matter, superior and inferior colliculi, pontine tegmentum, inferior olivary nucleus and medial lemiscus. The posterior column nuclei, especially the gracile nucleus, showed almost complete loss of neurons with dense fibrillary gliosis and numerous spheroids (Fig. 5 ) . The posterior columns in the upper cervical cord were also degenerative
with demyelination and numerous spheroids (Fig. 6). DISCUSSION
DRPLA is known neuropathologically as a hereditary system degeneration involving both the dentato-rubral and pallido-luysian systems. The first case of DRPLA was reported by Titica and Van Bogaert16in 1946.
752
K. Mizukami et al.
Fig. 5 : The gracile nucleus shows almost complete loss of neurons with tissue rarefaction and numerous ’ spheroids. (H.E.stain, X 78).
Fig. 6: The posterior columns reveal severe demyelination. (KlUver-Barrera stain, X 15.5).
Since then, many autopsied cases have been reported mainly in Japan. From the clinical . ~Iizuka et viewpoints, Hirayama et ~ 1 and al.5 classified DRPLA into three types: ( 1) ataxo-choreoathetoid, (2) pseudo-Huntington, and (3) myoclonic-epileptic types. According to their classification, the present case belongs to the ataxo-choreoathetoid type, because of prominent cerebellar ataxia and choreoathetoid movements. They pointed
out that no marked mental changes were detected but ocular symptoms were characteristic in the ataxo-choreoathetoid type. However, our case had profound dementia and no ocular symptoms. Case 1 of Tanaka et al.” is similar to ours in these clinical features. Hereditary dentatorubral-pallidoluysian atrophy, proposed by Naito and Oyanagi”, is characterized by the following three clinical and pathological features: (1)
DRPLA with Atypical Pathological Features myoclonus epilepsy syndrome with or without cerebellar ataxia and/or choreoathetosis, (2) dentatorubral-pallidoluysianatrophy, and (3) autosomal dominant heredity. Our case does not fit this definition because myoclonus was not recognized clinically. Neuropathologically, the main degenerative lesions in our case were presented in the dentatorubral and pallidoluysian systems. However, some atypical features showed in our case: (1) Our case had an unusually severe brain atrophy. The brain weighted only 770 grams. (2) Widespread fibrillary gliosis was observed. In addition to the dentatorubro pallidoluysian systems, the cerebral white matter, internal and external capsules, optic tract, striatum, thalamus, mamillary body, hypothalamus, nucleus basalis of Meynert, substantia nigra, central gray matter, superior and inferior colliculi, pontine tegmentum, cerebral peduncle, cerebellar white matter, inferior olivary nucleus and medical lemiscus were involved. This widespread gliosis in these areas might be due to hypoxia induced by status epilepticus and recurrent pneumonia in the terminal stage. (3) The third atypical pathological feature was a severe degeneration of the Purkinje cell layer. A similar severe degeneration of the Purkinje cell layer has been described only in three DRPLA cases reported by Leeuwen et aL7, Oyanagi et al.” and Takahashi et al.I4. In the case reported by Takahashi et in which no anticonvulsant drugs had been administered, a marked loss of Purkinje cells was more pronounced in the superior parts of the vermis and hemisphere. The cerebellar degeneration in our case was much more extensive than in their case. In addition, the degeneration in our case showed a quite different distribution, namely, it was more marked in the hemisphere than in the vermis and also more marked ventrally than dorsally. This cerebellar cortical degeneration is similar to the chronic diphenylhydantoin intoxication.’ A severe degeneration with numerous spheroids in the nuclei fasciculi dorsalis
753
may support the explanation that our case had been affected by chronic diphenylhydantoin intoxication*. Although the degeneration in those nuclei has been reported in DRPLA3 5-7 I ’ I’ the severe degeneration showing in our case has never been reported previously yet. In addition, our case showed “Ammon’s horn sclerosis.” This finding is thought to be due to epileptic brain damage.’ In summary, the present case is diagnosed as DRPLA associated with the neuropathological findings of chronic diphenylhydantoin intoxication and epileptic brain damage. REFERENCES 1. Akashi, T., Ando, S.,Inose, T., Uemura, H. and Mizushima, S.: Dentato-rubropallidoluysian atrophy: A clinico-neuropathological 2.
3.
4.
5.
6.
7.
study. Rinsho Seishinigaku 16 1163-1 172, 1987 (in Japanese). Ando, S. and Mizushima, S.: Five autopsied cases of chronic diphenylhydantoin intoxication-With special reference to the distribution of cerebellar degeneration and marked degeneration of nucleus fasciculi dorsalis. Seishin Shinkeigaku Zasshi 82: 423-443, 1980 (in Japanese). Goto, I., Tobimatsu, S.,Hosokawa, S., Shibasaki, H. and Kuroiwa, Y.:Dentatorubropallidoluysian degeneration: Clinical, neuroophthalmologic, biochemical, and pathologic studies on autosomal dominant form. Neurology 32: 1395-1399, 1982. Hirayama, K., Iizuka, R., Maehara, K. and Watanabe, T.: Clinicopathological study of dentatorubropallidoluysian atrophy. Part 1Its clinical form and analysis of symptomatology. Shinkei Kenkyu no Shinpo 2 5 725-736, 1981 (in Japanese). Iizuka, R., Hirayama, K. and Maehara, K.: Dentato-rubro-pallido-luysianatrophy. J Neurol Neurosurg Psychiatry 47: 1288-1298, 1984. Kobayashi, H., Kosaka, K., Hoshino, T., Shibayama,H. and Iwase, S.:An autopsy case of the characteristic degeneration of the dentato nucleus with choreic movement and psychiatric symptoms. Rinsho Shinkeigaku 15: 724-730, 1975 (in Japanese). Leeuen, M.A. and Van Bogaert, L.: Heredi-
754
8.
9.
10.
11.
12.
K. Mizukami et al. tary ataxia with optic atrophy of the retrobulbar neuritis type, and latent pallido-luysian degeneration. Brain 72: 340-363, 1949. Meldrum. B.S. and Corsellis, J.A.N.: Epilepsy. In: Adams, J.H., Corsellis, J.A.N. and Duchen, L.W. (Eds.), Greenfield's neuropathology, fourth edition. Edward Arnold Publisher, London, pp 921-950, 1984. Morioka, E., Nakatsu, T., Kuroda, S., Yamamoto, M., Hosokawa, K. and Otsuki, S.: An autopsy case of dentatorubro-pallidoluysian atrophy showing marked atrophy of the brain stem. Brain Nerve 3 9 769-773, 1987 (in Japanese). Naito, H. and Oyanagi, S.: Familial myoclonus epilepsy and choreoathetosis: Hereditary dentatorubral-pallidoluysian atrophy. Neurology 32: 798-807, 1982. Neuman, M.A.: Combined degeneration of globus pallidus and dentate nucleus and their projection. Neurology 9: 430-438, 1959. Oyanagi, S., Tanaka, M., Naito, H., Shirakawa, K., Saito, K., Nakamura, N. and Ohama, E.: A neuropathological study of 8 autopsy cases of degenerative type of
myoclonus epilepsy: With special reference to latent combination of degeneration of the pallido-luysian system. Shinkei Kenkyu no Shinpo 2 0 410-424, 1976 (in Japanese). 13. Smith, J.K.: Dentatorubropallidoluysianatrophy. In: Vinken, P.J. and Bruyn, G.W. (Eds.), Handbook of clinical neurology Vol. 27. North Holland Publisher, Amsterdam, pp 519-534, 1975. 14. Takahashi, H., Ohama, E., Naito, H., Takeda, S., Nakashima, S., Makifuchi, T. and Ikuta,
F.: Hereditary dentatorubral-pallidoluysian atrophy: Clinical and pathologic variants in a family. Neurology 3 8 1065-1070, 1988. 15. Tanaka, Y., Murofushi, K., Ando, S., Suwa, K. and Hayashi, M.: Combined degeneration of the globus pallidus and the cerebellar nuclei and their efferent systems in two siblings of one family: Primary system degeneration of the globus pallidus and cerebellar nuclei. Brain Nerve 2 9 95-103, 1977 (in Japanese). 16. Titica, J., Van Bogaert, L.: Heredo-degenerative hemiballisumus. A contribution to the question of primary atrophy of the corpus Luysii. Brain 69 251-263, 1946.
An Autopsied Case of Dentatorubropallidoluysian Atrophy with Atypical Pathological Features Katsuyoshi Mizukami, M.D., Megumi Sasaki, M.D., Hiroyasu Shiraishi, M.D., Junzo Koizumi, M.D., Takesaburo Ogata, M.D.* and Kenji Kosaka** Department of Psychiatry, Institute of Clinical Medicine, University of Tsukuba, Tsukuba *Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba **Department of Psychiatry and Neurology, Yokohama City University, School of Medicine, Yokohama
Abstract: This is a report of an autopsied case of dentatorubropallidoluysian atrophy (DRPLA) with atypical neuropathological Andings. The patients was a 31-year-old female. Her clinical symptoms were epileptic seizures, cerebellar ataxia, choreoathetosis and dementia. A neuropathological examination revealed the Abrillary gliosis in various areas of the CNS and severe degeneration in the cerebellar cortex and nucleus fwiculi dorsalis in addition to a marked degeneration of the dentatorubropallidoluysiansystems. The present case is diagnosed neuropathologically as DRPLA associated with the flndings of chronic diphenylhydantoin intoxication and epileptic brain damage. Key Words ; DRPLA, cerebellar lesion, degeneration of nucleus fasciculi dorsalis, chronic diphenylhydantoin intoxication Jpn J Psychiatr Neurol46: 749-754,1992
INTRODUCTION
Dentatorubropallidoluysian atrophy (DRPLA) is a rare heredo-degenerative disease. The main clinical features are cerebellar ataxia, choreoathetosis, myoclonus, epileptic seizures and mental disorders such as personality changes and dementia. Neuropathologically, both the dentatorubral and pallidoluysian systems are selectively afReceived for publication on Feb. 3, 1992. Mailing address: Katsuyoshi Mizukami, M.D., Department of Psychiatry, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305,Japan.
fected.l 3-5
9 10 12-15
In this paper we present an atypical case of DRPLA with fibrillary gliosis in various areas of the CNS and severe degeneration in the cerebellar cortex and nucleus fasciculi dorsalis. CASE REPORT
A mildly mentally retarded female had a grand ma1 convulsive attack at the age of 20. After that, similar attacks recurred once in half a year. Unsteady gait began at the age of 23. Two years later, dysarthria and choreiform movements developed and progressed gradually. She was admitted with dementia
K. Mizukami et al.
750
and urinary incontinence to the psychiatric ward, The University of Tsukuba Hospital at age 26. On admission, her cerebellar ataxia, choreoathetotic movements, epileptic seizures, personality changes and dementia were noticed. The family history revealed 12 similar patients in four successive generations (Fig. 1). It means an autosomal dominant heredity. CT showed a mild atrophy of the cerebrum and brainstem with a moderate dilatation of the lateral, third and fourth ventricles. The patient was diagnosed clinically as DRPLA from the findings of clinical symptoms and CT. Neurological and mental deterioration progressed steadily. At age 29, she became bedridden, almost apathetic and mute and her choreoathetotic movements gradually decreased. Status epilepticus occurred twice at her terminal stage, but neither myoclonus nor disturbance of ocular movement was observed. She suffered recurrently from pneumonia and died at age 3 1. The total duration of the disease was 11 years. Anticonvulsant drugs (diphenylhydantoin 150-375 mg, phenobarbital 48-200 mg, sodium valproate 8001,200 mg/day) had been administered since the age of 20. Neuropathological findings. The brain weight was 770 grams and a severe diffuse brain atrophy was observed. The cerebellum was also atrophic. Coronal sections of the brain revealed the atrophy of the caudate nucleus, lateral pallidal segment and sub-
thalamic nucleus with brownish discoloration of the latter two nuclei. The superior cerebellar peduncle, dentate hilus and pontine tegmentum were also obviously atrophic (Fig. 2). Microscopically, no obvious neuronal loss was observed in the cerebral cortex, except for “Ammon’s horn sclerosis,” although the severe brain atrophy was present. Moderate fibrillary gliosis was present in the whole cerebral white matter, internal and external capsules and optic tract. In the lateral segment of the globus pallidus remarkable neuronal loss with dense fibrillary gliosis was found (Fig. 3). The subthalamic nucleus had mild neuronal loss with dense fibrillary gliosis. In the red nucleus mild neuronal loss with moderate fibrillary gliosis was present. In the cerebellum, Purkinje cells were severely decreased in number and Bergmann’s glia proliferated (Fig. 4). These changes were more pronounced in the ventral parts of the cerebellum, especially of the cerebellar hemispheres. The superior cerebellar peduncle was demyelinated and gliotic. In the dentate nucleus, apparent neuronal loss with astrocytosis was recognized. Otherwise, fibrillary gliosis was observed in the striatum, thalamus,
0
I .
U
0
.
I & m
.
.
0
3
. .
present c ~ s e
Fig. 1 : Pedigree of the family.
aRectd
Fig. 2: The superior cerebellar peduncle, dentate hilus and pontine tegmentum are obviously atrophic. The superior cerebellar peduncles are demyelinated. (Kltiver-Barrera stain, X 1.4).
DRPLA with Atypical Pathological Features
75 1
Fig. 3: The globus pallidus, especially the lateral segment, shows fibrillary gliosis. (Holzer stain, X 15.5).
Fig. 4 : Purkinje cells are severely decreased in number and Bergmann’s glia markedly proliferate. (H.E.stain, X 155).
mamillary body, nucleus basalis of Meynert, hypothalamic region, substantia nigra, central gray matter, superior and inferior colliculi, pontine tegmentum, inferior olivary nucleus and medial lemiscus. The posterior column nuclei, especially the gracile nucleus, showed almost complete loss of neurons with dense fibrillary gliosis and numerous spheroids (Fig. 5 ) . The posterior columns in the upper cervical cord were also degenerative
with demyelination and numerous spheroids (Fig. 6). DISCUSSION
DRPLA is known neuropathologically as a hereditary system degeneration involving both the dentato-rubral and pallido-luysian systems. The first case of DRPLA was reported by Titica and Van Bogaert16in 1946.
752
K. Mizukami et al.
Fig. 5 : The gracile nucleus shows almost complete loss of neurons with tissue rarefaction and numerous ’ spheroids. (H.E.stain, X 78).
Fig. 6: The posterior columns reveal severe demyelination. (KlUver-Barrera stain, X 15.5).
Since then, many autopsied cases have been reported mainly in Japan. From the clinical . ~Iizuka et viewpoints, Hirayama et ~ 1 and al.5 classified DRPLA into three types: ( 1) ataxo-choreoathetoid, (2) pseudo-Huntington, and (3) myoclonic-epileptic types. According to their classification, the present case belongs to the ataxo-choreoathetoid type, because of prominent cerebellar ataxia and choreoathetoid movements. They pointed
out that no marked mental changes were detected but ocular symptoms were characteristic in the ataxo-choreoathetoid type. However, our case had profound dementia and no ocular symptoms. Case 1 of Tanaka et al.” is similar to ours in these clinical features. Hereditary dentatorubral-pallidoluysian atrophy, proposed by Naito and Oyanagi”, is characterized by the following three clinical and pathological features: (1)
DRPLA with Atypical Pathological Features myoclonus epilepsy syndrome with or without cerebellar ataxia and/or choreoathetosis, (2) dentatorubral-pallidoluysianatrophy, and (3) autosomal dominant heredity. Our case does not fit this definition because myoclonus was not recognized clinically. Neuropathologically, the main degenerative lesions in our case were presented in the dentatorubral and pallidoluysian systems. However, some atypical features showed in our case: (1) Our case had an unusually severe brain atrophy. The brain weighted only 770 grams. (2) Widespread fibrillary gliosis was observed. In addition to the dentatorubro pallidoluysian systems, the cerebral white matter, internal and external capsules, optic tract, striatum, thalamus, mamillary body, hypothalamus, nucleus basalis of Meynert, substantia nigra, central gray matter, superior and inferior colliculi, pontine tegmentum, cerebral peduncle, cerebellar white matter, inferior olivary nucleus and medical lemiscus were involved. This widespread gliosis in these areas might be due to hypoxia induced by status epilepticus and recurrent pneumonia in the terminal stage. (3) The third atypical pathological feature was a severe degeneration of the Purkinje cell layer. A similar severe degeneration of the Purkinje cell layer has been described only in three DRPLA cases reported by Leeuwen et aL7, Oyanagi et al.” and Takahashi et al.I4. In the case reported by Takahashi et in which no anticonvulsant drugs had been administered, a marked loss of Purkinje cells was more pronounced in the superior parts of the vermis and hemisphere. The cerebellar degeneration in our case was much more extensive than in their case. In addition, the degeneration in our case showed a quite different distribution, namely, it was more marked in the hemisphere than in the vermis and also more marked ventrally than dorsally. This cerebellar cortical degeneration is similar to the chronic diphenylhydantoin intoxication.’ A severe degeneration with numerous spheroids in the nuclei fasciculi dorsalis
753
may support the explanation that our case had been affected by chronic diphenylhydantoin intoxication*. Although the degeneration in those nuclei has been reported in DRPLA3 5-7 I ’ I’ the severe degeneration showing in our case has never been reported previously yet. In addition, our case showed “Ammon’s horn sclerosis.” This finding is thought to be due to epileptic brain damage.’ In summary, the present case is diagnosed as DRPLA associated with the neuropathological findings of chronic diphenylhydantoin intoxication and epileptic brain damage. REFERENCES 1. Akashi, T., Ando, S.,Inose, T., Uemura, H. and Mizushima, S.: Dentato-rubropallidoluysian atrophy: A clinico-neuropathological 2.
3.
4.
5.
6.
7.
study. Rinsho Seishinigaku 16 1163-1 172, 1987 (in Japanese). Ando, S. and Mizushima, S.: Five autopsied cases of chronic diphenylhydantoin intoxication-With special reference to the distribution of cerebellar degeneration and marked degeneration of nucleus fasciculi dorsalis. Seishin Shinkeigaku Zasshi 82: 423-443, 1980 (in Japanese). Goto, I., Tobimatsu, S.,Hosokawa, S., Shibasaki, H. and Kuroiwa, Y.:Dentatorubropallidoluysian degeneration: Clinical, neuroophthalmologic, biochemical, and pathologic studies on autosomal dominant form. Neurology 32: 1395-1399, 1982. Hirayama, K., Iizuka, R., Maehara, K. and Watanabe, T.: Clinicopathological study of dentatorubropallidoluysian atrophy. Part 1Its clinical form and analysis of symptomatology. Shinkei Kenkyu no Shinpo 2 5 725-736, 1981 (in Japanese). Iizuka, R., Hirayama, K. and Maehara, K.: Dentato-rubro-pallido-luysianatrophy. J Neurol Neurosurg Psychiatry 47: 1288-1298, 1984. Kobayashi, H., Kosaka, K., Hoshino, T., Shibayama,H. and Iwase, S.:An autopsy case of the characteristic degeneration of the dentato nucleus with choreic movement and psychiatric symptoms. Rinsho Shinkeigaku 15: 724-730, 1975 (in Japanese). Leeuen, M.A. and Van Bogaert, L.: Heredi-
754
8.
9.
10.
11.
12.
K. Mizukami et al. tary ataxia with optic atrophy of the retrobulbar neuritis type, and latent pallido-luysian degeneration. Brain 72: 340-363, 1949. Meldrum. B.S. and Corsellis, J.A.N.: Epilepsy. In: Adams, J.H., Corsellis, J.A.N. and Duchen, L.W. (Eds.), Greenfield's neuropathology, fourth edition. Edward Arnold Publisher, London, pp 921-950, 1984. Morioka, E., Nakatsu, T., Kuroda, S., Yamamoto, M., Hosokawa, K. and Otsuki, S.: An autopsy case of dentatorubro-pallidoluysian atrophy showing marked atrophy of the brain stem. Brain Nerve 3 9 769-773, 1987 (in Japanese). Naito, H. and Oyanagi, S.: Familial myoclonus epilepsy and choreoathetosis: Hereditary dentatorubral-pallidoluysian atrophy. Neurology 32: 798-807, 1982. Neuman, M.A.: Combined degeneration of globus pallidus and dentate nucleus and their projection. Neurology 9: 430-438, 1959. Oyanagi, S., Tanaka, M., Naito, H., Shirakawa, K., Saito, K., Nakamura, N. and Ohama, E.: A neuropathological study of 8 autopsy cases of degenerative type of
myoclonus epilepsy: With special reference to latent combination of degeneration of the pallido-luysian system. Shinkei Kenkyu no Shinpo 2 0 410-424, 1976 (in Japanese). 13. Smith, J.K.: Dentatorubropallidoluysianatrophy. In: Vinken, P.J. and Bruyn, G.W. (Eds.), Handbook of clinical neurology Vol. 27. North Holland Publisher, Amsterdam, pp 519-534, 1975. 14. Takahashi, H., Ohama, E., Naito, H., Takeda, S., Nakashima, S., Makifuchi, T. and Ikuta,
F.: Hereditary dentatorubral-pallidoluysian atrophy: Clinical and pathologic variants in a family. Neurology 3 8 1065-1070, 1988. 15. Tanaka, Y., Murofushi, K., Ando, S., Suwa, K. and Hayashi, M.: Combined degeneration of the globus pallidus and the cerebellar nuclei and their efferent systems in two siblings of one family: Primary system degeneration of the globus pallidus and cerebellar nuclei. Brain Nerve 2 9 95-103, 1977 (in Japanese). 16. Titica, J., Van Bogaert, L.: Heredo-degenerative hemiballisumus. A contribution to the question of primary atrophy of the corpus Luysii. Brain 69 251-263, 1946.
