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Corticobasal degeneration presenting with progressive conduction aphasia
Journal of the Neurological Sciences 269 (2008) 163 – 168 www.elsevier.com/locate/jns
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Corticobasal degeneration presenting with progressive conduction aphasia Noriyuki Kimura ⁎, Toshihide Kumamoto, Takuya Hanaoka, Yusuke Hazama, Kenichiro Nakamura, Ryuki Arakawa Department of Neurology and Neuromuscular Disorders, Oita University, Faculty of Medicine, Oita, Japan Received 25 July 2007; received in revised form 5 December 2007; accepted 6 December 2007 Available online 29 January 2008
Abstract We report the case of a woman with primary progressive aphasia (PPA) presenting with conduction aphasia. Neurological findings showed bilateral finger tremor and signe de poignet figé in her right hand. Memory, orientation, and activities of daily living were well preserved. Linguistic examination showed severe impairment in repetition, fluent spontaneous speech with phonemic paraphasia, and relatively well preserved comprehension. Limb-kinetic apraxia and parkinsonism were not observed during the course of her illness. T1weighted magnetic resonance imaging revealed severe atrophy of the left temporal lobe and dilatation of the left Sylvian fissure. Neuropathological findings demonstrated the most severe atrophy in the left superior temporal gyrus and Gallyas–Braak-positive or phosphorylated tau-immunoreactive cytoskeletal structures, which were consistent with corticobasal degeneration (CBD). We speculate that the progressive conduction aphasia of our patient might have been caused by left temporal lobe impairment. We suggest that progressive conduction aphasia may be a feature of CBD presenting with PPA. © 2007 Elsevier B.V. All rights reserved. Keywords: Corticobasal degeneration; Primary progressive aphasia; Conduction aphasia; Abnormal cytoskeletal structures; Left superior temporal gyrus
1. Introduction In 1982, Mesulam described six patients who experienced language disorders that progressed slowly over many years [1]; he subsequently named this condition primary progressive aphasia (PPA) [2]. Primary progressive aphasia is a clinical syndrome characterized by slowly progressive loss of speech and language function in the setting of relatively preserved memory and visuospatial skills within the initial two years [2,3]. Recent studies have indicated that PPA is clinically and histopathologically heterogeneous, and several underlying pathologies have been described, such as Alzheimer's disease [4], Pick's disease [5], Pick complex [6], non-specific cortical degeneration with spongiform ⁎ Corresponding author. Department of Neurology and Neuromuscular Disorders, Oita University, Faculty of Medicine, Idaigaoka 1-1, Hasama, Yufu, Oita 879-5593, Japan. Tel.: +81 97 586 5814; fax: +81 97 586 6502. E-mail address: [email protected] (N. Kimura). 0022-510X/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2007.12.017
change or dementia lacking distinct histology [7], Creutzfeldt–Jakob disease [8], corticobasal degeneration (CBD) [9–16], and motor neuron disease with dementia [17]. Here, we reported the rare case of a patient with PPA presenting with conduction aphasia of the fluent type. Although our patient did not show the typical symptoms of CBD at any time during the course of the disease, the postmortem examination confirmed a diagnosis of CBD. Conduction aphasia is characterized by markedly impaired repetition of words and phrases with normal or nearly normal comprehension and was originally proposed to result from a separation of the posterior language comprehension area and the anterior motor speech area of the left hemisphere [18]. Such a disconnection has been attributed to a lesion of the arcuate fasciculus [19]. The neuropathological findings of our patient revealed that cerebral involvement was accentuated in the left superior temporal gyrus and various types of cytoskeletal abnormalities were observed in the cerebral cortex and white matter, mainly in the frontal lobe, as well as
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in the basal ganglia and brainstem. To our knowledge, this is the first report of an autopsy case of CBD with progressive conduction aphasia. In this report, we focus on the relationship between cortical foci of degenerating areas and the clinical expression of CBD.
Limb-kinetic apraxia and Parkinsonian symptoms were not observed during the course of her illness. The follow-up MRI showed that the atrophy of left temporal lobe was slightly progressed. She died of lung cancer at the age of 72 years, 5 years after the onset of symptoms. The clinical diagnosis was PPA.
2. Case report The patient was a right-handed woman who had graduated from high school. There was no family history of neurological problems. At the age of 67 years, she became aware of a speech disturbance, specifically phonemic paraphasia in her spontaneous speech. Although she could perform household activities and her daily routine by herself, and her personality did not change, her language abilities gradually deteriorated. At the age of 69 years, she visited our hospital with language problems. On neurological examination, she appeared alert and oriented. There were no abnormalities of the cranial nerves, muscle strength, deep tendon reflexes, or sensory system, except for mild upward gaze limitation. She showed bilateral hand-finger tremor and signe de poignet figé in her right hand, but neither bradykinesia, gait disturbance, nor Myerson's sign. On neuropsychological study, the Mini-Mental State Examination (MMSE) was within the normal range, at 23 points. The Wechsler Adult Intelligence Scale-Revised (WAIS-R) was abnormal, at 61 points, because the verbal intelligence quotient (60) was low for aphasia, despite a normal performance intelligence quotient (82). Apraxia, agnosia, and dyscalculia were absent. The standard language test of aphasia revealed that spontaneous speech was fluent, but phonemic and verbal paraphasia were obvious on naming, reading aloud, and repetition. She was unable to repeat short sentences. She recognized her own errors and tried hard to correct them by herself. Impairment of repetition was the most prominent of the linguistic abnormalities. Her writing was slightly disturbed in both kana and kanji. By contrast, her auditory comprehension was normal. The profile of her language impairment was consistent with that of conduction aphasia. Her routine blood tests, electrocardiography, and electroencephalography were normal. Cranial T1-weighted magnetic resonance images (MRI) revealed severe atrophy of the left temporal lobe and dilatation of the left Sylvian fissure (Fig. 1a, b). Tc-99m-hexamethylpropyleneamine oxine single photon emission computed tomography (SPECT; GCA9300A/HG, Toshiba, Tokyo, Japan) showed mild hypoperfusion in the left temporal and parietal lobes (Fig. 1c). Three years after the onset of this condition, memory, orientation, and activities of daily living were well preserved, but linguistic disturbance had progressed. Neuropsychological reevaluation demonstrated that language fluency, auditory comprehension, writing, and reading were mild impaired, in contrast to a severe disturbance in repetition.
Fig. 1. T1-weighted MRI and 123I-IMP-SPECT images. T1-weighted MRI revealed severe atrophy of the left temporal lobe and dilation of the left Sylvian fissure (a, b). Hypoperfusion was noted in the left perisylvian area (c). The right side is shown on the left-hand side of each figure.
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2.1. Post-mortem examination The brain weight was 1170 g after fixation. Macroscopic examination revealed slight atrophy in the frontal and temporal lobes, more accentuated on the left side. The most severe atrophy was found in the left superior temporal gyrus, especially the anterior portion (Fig. 2a). The left Sylvian fissure was moderately dilated. The parietal and occipital lobes showed normal convolutions. Coronal slices disclosed moderate to mild atrophy of the caudate nucleus, putamen, and globus pallidus, slightly accentuated on the left side (Fig. 2b). The substantia nigra was pale (Fig. 2c).
Fig. 3. In the superior temporal cortex, all layers show neuronal loss and gliosis (a). Ballooned neurons are seen in the frontal cortex (b). Moderate neuronal loss and extraneuronal pigment are present in the substantia nigra (c). Hematoxylin and eosin stain. Scale bars 100 µm.
Fig. 2. Lateral view of the left cerebrum exhibits atrophy of the superior temporal gyrus and slight enlargement of the left Sylvian fissure (a). Coronal section of the brain at the mammillary body level shows marked atrophy of the left superior temporal gyrus and slight atrophy of the caudate, putamen, globus pallidus, and thalamus on the left side (b). Transverse section of the midbrain shows marked depigmentation of the substantia nigra (c).
Histological examination demonstrated moderate neuronal loss with gliosis (Fig. 3a) and a spongy appearance throughout all layers of the left superior temporal gyrus. The frontal, parietal, and occipital lobes and the remainder of the temporal lobe were relatively well preserved. Numerous ballooned neurons were seen in the frontal cortex and occasionally in the temporal, parietal, and occipital cortices
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(Fig. 3b). Diffuse fibrillary gliosis was observed in the white matter with a distribution corresponding to cortical degeneration. Neuronal loss and gliosis were moderate in the substantia nigra and mild in the striatum and globus pallidus. There were no Lewy bodies in the cerebrum and brainstem. With modified Bielschowsky staining, Pick bodies and senile plaques were not seen in the cerebral cortex or hippocampus. A few neurofibrillary tangles were present in the CA1 region of the hippocampus. Grumose degeneration was also present in the dentate nucleus. The modified Gallyas–Braak staining and anti-phosphorylated tau immunostaining revealed massive argyrophilic and anti-phosphorylated tau-positive threads, scattered coiled bodies, pretangles, and astrocytic plaques in the neurons and glial cells (Fig. 4a–c). Pretangles and astrocytic plaques were found mainly in the frontal cortex, in spite of mild neuronal loss and gliosis. However, these cytoskeletal abnormalities were observed less frequently in the severely affected left superior temporal gyrus. The argyrophilic threads were most prominent in the affected cortical region, but they were also observed in the relatively well preserved cortex, basal ganglia, and brainstem. In addition, numerous argyrophilic threads and coiled bodies were also seen in the white matter of the cerebrum, cerebellum, and brainstem. 3. Discussion We described a case of CBD with slowly progressive language disorder without dementia, parkinsonism, and pyramidal signs. The patient was able to manage her household during the course of her illness and was clinically deemed to have typical PPA. The clinical representations of PPA are sub-divided into fluent and non-fluent forms [20]. Fluent forms are characterized by impairment of auditory comprehension and empty, circumlocutory speech. Nonfluent forms are associated with stuttering or dysprosodic speech, articulatory disturbances, and agrammatism. In the present case, linguistic examination showed severe impairment of repetition, fluent spontaneous speech with phonemic paraphasia, and relatively well preserved comprehension. Conduction aphasia is characterized by fluency and paraphasia in spontaneous speech, with normal or nearly normal comprehension of spoken language but markedly impaired repetition of words and phrases [18]. The patient's condition was therefore diagnosed as PPA presenting with conduction aphasia. Although the clinical symptoms of our patient were unusual, post-mortem examination showed pathological features of CBD. Corticobasal degeneration has been recognized as one type of disorder presenting with PPA [9–16]. Clinically, CBD is characterized by an asymmetric, akinetic, rigid syndrome with prominent apraxia, myoclonus, cortical sensory loss, and sometimes alien limb behavior [21]. The occurrence of aphasia and dementia has not been recognized in CBD for a long time; however, autopsyconfirmed cases of CBD have revealed that cognitive im-
Fig. 4. Phosphorylated tau immunohistochemistry showed diffuse or granular staining of neurons (pretangles) and threads throughout the frontal cortex (a). An astrocytic plaque is seen in the cortex (b). A phosphorylated tau-positive inclusion in a glial cell in the white matter. (c). Phosphorylated tau immunohistochemistry. Scale bars 100 µm.
pairment and speech problems are prominent clinical features of the disease. Graham et al. reported that 34% of patients with pathological confirmation were noted to be aphasic [22]. Neuropathologically, CBD is characterized by asymmetric atrophy of the frontal and parietal lobes, swollen achromatic neurons, and degeneration of the substantia nigra. Recent neuropathological criteria emphasize Gallyas– Braak-positive or tau-immunoreactive lesions such as pretangles, astrocytic plaques, coiled bodies, and argyrophilic threads in neurons and glia [23]. Neuropathological examination of our patient revealed marked atrophy with neuronal loss and gliosis in the left superior temporal gyrus and substantia nigra, and to a lesser extent, the striatum, globus pallidus, and brainstem. Gallyas–Braak-positive or
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tau-immunoreactive cytoskeletal structures were observed in the cortical and sub-cortical regions, mainly in the frontal lobe. These neuropathological findings were consistent with the recent neuropathological criteria of CBD [24]. Only eight pathologically confirmed cases of CBD with PPA have been reported (Table 1) [9–16]. According to these reports, non-fluent aphasia was observed in five cases, whereas three cases showed the fluent form. All cases with non-fluent aphasia revealed a marked atrophy in the left superior or inferior frontal gyrus, while two of three cases with fluent aphasia showed marked atrophy in the left superior temporal gyrus. The present case with fluent aphasia also showed the most severe atrophy in the left superior temporal gyrus. We suggest that the fluent type of PPA may be caused by a lesion of the left superior temporal gyrus. The cardinal symptoms of conduction aphasia are significant impairments in word repetition with preserved comprehension, naming, and reading. Wernicke postulated that any lesion disrupting the arcuate fasciculus should result in conduction aphasia. The arcuate fasciculus is a white matter tract from the site of auditory language comprehension to the site of motor expression of speech [19]. By contrast, Goldstein attributed conduction aphasia to a disturbance of a localized cortical center [25]. He suggested that the linguistic mechanisms of conduction aphasia were due to a disturbance of verbal short-term memory and phonological output. The lesions might be in the inferior parietal lobe, especially the supramarginal gyrus, and the superior temporal gyrus [26–28]. These results suggest that conduction aphasia may be a heterogeneous syndrome anatomically and linguistically. We speculate that the progressive conduction aphasia of our patient might have been caused by a disturbance of short-term memory due to a Table 1 Aphasic form and most severely affected site in eight previously reported cases and the present case of corticobasal degeneration with primary progressive aphasia Author (year) Age at onset
Aphasic form
Most affected cortical region
Lippa et al. (1990) Lippa et al. (1991) Arima et al. (1994) Sakurai et al. (1996) Ikeda et al. (1996) Mimura et al. (2001) Sánchez et al. (2006) Takao et al. (2006) Present case (2007)
72/M
Non-fluent
Left parasylvian
68/M
72/M
Transcortical motor Left superior frontal (non-fluent) gyrus Amnesic (fluent) Left superior temporal gyrus Amnesic (fluent) Right frontal
67/F
Sensory (fluent)
73/M
65/F 57/F 67/F 67/F
Left superior temporal gyrus Transcortical motor Left inferior frontal (non-fluent) gyrus Non-fluent Left frontal operculmus and pre-motor area Non-fluent Left inferior frontal gyrus Conduction (fluent) Left superior temporal gyrus
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lesion in the left superior temporal gyrus. In addition, a previous report of a case of PPA presenting with conduction aphasia revealed atrophy of the left superior temporal gyrus, although this was not pathologically confirmed [29]. Thus, the present case suggests that conduction aphasia might be caused by an impairment of the left superior temporal gyrus in the present case. Further studies are needed to clarify the correlation between pathological lesions and the aphasic form of CBD with progressive conduction aphasia. In summary, we reported the first case of CBD with progressive conduction aphasia. The neuropathological findings of our case showed severe atrophy of the left superior temporal gyrus. This case is important for understanding the clinical heterogeneity and clinicopathological correlation of CBD with progressive conduction aphasia. References [1] Mesulam MM. Slowly progressive aphasia without generalized dementia. Ann Neurol 1982;11:592–8. [2] Mesulam MM. Primary progressive aphasia. Ann Neurol 2001;49:425–32. [3] Kertesz A, Hudson L, Mackenzie IR, Munoz DG. The pathology and nosology of primary progressive aphasia. Neurology 1994;44:2065–72. [4] Greene JD, Hodges JR, Ironside JW, Warlow CP. Alzheimer disease and nonfluent progressive aphasia. Arch Neurol 1996;53:1072–8. [5] Graff-Radford NR, Damasio AR, Hyman BT, Hart MN, Tranel D, Damasio H, et al. Progressive aphasia in a patient with Pick's disease: a neuropsychological, radiologic, and anatomic study. Neurology 1990;40:620–6. [6] Kertesz A, Munoz DG. Primary progressive aphasia. Clin Neurosci 1997;4:95–102. [7] Kirshner HS, Tanridag O, Thurman L, Whetsell Jr WO. Progressive aphasia without dementia: two cases with focal spongiform degeneration. Ann Neurol 1987;22:527–32. [8] Mandell AM, Alexander MP, Carpenter S. Creutzfeldt–Jakob disease presenting as isolated aphasia. Neurology 1989;39:55–8. [9] Ikeda K, Akiyama H, Iritani S, Kase K, Arai T, Niizato K, et al. Corticobasal degeneration with primary progressive aphasia and accentuated cortical lesion in superior temporal gyrus: case report and review. Acta Neuropathol 1996;92:534–9. [10] Takao M, Tsuchiya K, Mimura M, Momoshima S, Kondo H, Akiyama H, et al. Corticobasal degeneration as cause of progressive non-fluent aphasia: clinical, radiological and pathological study of an autopsy case. Neuropathology 2006;26:569–78. [11] Sanchez-Valle R, Forman MS, Miller BL, Gorno-Tempini ML. From progressive nonfluent aphasia to corticobasal syndrome: a case report of corticobasal degeneration. Neurocase 2006;12:355–9. [12] Mimura M, Oda T, Tsuchiya K, Kato M, Ikeda K, Hori K, et al. Corticobasal degeneration presenting with nonfluent primary progressive aphasia: a clinicopathological study. J Neurol Sci 2001;183:19–26. [13] Sakurai Y, Hashida H, Uesugi H, Arima K, Murayama S, Bando M, et al. A clinical profile of corticobasal degeneration presenting as primary progressive aphasia. Eur Neurol 1996;36:134–7. [14] Lippa CF, Smith TW, Fontneau N. Corticonigral degeneration with neuronal achromasia. A clinicopathologic study of two cases. J Neurol Sci 1990;98:301–10. [15] Lippa CF, Cohen R, Smith TW, Drachman DA. Primary progressive aphasia with focal neuronal achromasia. Neurology 1991;41:882–6. [16] Arima K, Uesugi H, Fujita I, Sakurai Y, Oyanagi S, Andoh S, et al. Corticonigral degeneration with neuronal achromasia presenting with primary progressive aphasia: ultrastructural and immunocytochemical studies. J Neurol Sci 1994 20;127:186–97.
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[17] Mitsuyama Y. Presenile dementia with motor neuron disease in Japan: clinico-pathological review of 26 cases. J Neurol Neurosurg Psychiatry 1984;47:953–9. [18] Bartha L, Benke T. Acute conduction aphasia: an analysis of 20 cases. Brain and Lang 2003;85(1):93–108. [19] Damasio H, Damasio AR. The anatomical basis of conduction aphasia. Brain 1980;103:337–50. [20] Rosen HJ, Kramer JH, Gorno-Tempini ML, Schuff N, Weiner M, Miller BL. Patterns of cerebral atrophy in primary progressive aphasia. Am J Geriatr Psychiatry 2002;10:89–97. [21] Rebeiz JJ, Kolodny EH, Richardson Jr EP. Corticodentatonigral degeneration with neuronal achromasia. Arch Neurol 1968;18:20–33. [22] Graham NL, Bak TH, Hodges JR. Corticobasal degeneration as a cognitive disorder. Mov Disord 2003;18:1224–32. [23] Ferrer I, Hernandez I, Boada M, Llorente A, Rey MJ, Cardozo A, et al. Primary progressive aphasia as the initial manifestation of corticobasal degeneration and unusual tauopathies. Acta Neuropathol 2003;106:419–35.
[24] Dickson DW, Bergeron C, Chin SS, Duyckaerts C, Horoupian D, Ikeda K, et al. Office of Rare Diseases of the National Institutes of Health. Office of Rare Diseases neuropathologic criteria for corticobasal degeneration. J Neuropathol Exp Neurol 2002;61:935–46. [25] Goldstein K. Language and language disturbance. New York: Grune & Stratton Inc.; 1948. [26] Axer H, von Keyserlingk AG, Berks G, von Keyserlingk DG. Supraand infrasylvian conduction aphasia. Brain Lang 2001;76:317–31. [27] Quigg M, Fountain NB. Conduction aphasia elicited by stimulation of the left posterior superior temporal gyrus. J Neurol Neurosurg Psychiatry 1999;66:393–6. [28] Anderson JM, Gilmore R, Roper S, Crosson B, Bauer RM, Nadeau S, et al. Conduction aphasia and the arcuate fasciculus: A reexamination of the Wernicke–Geschwind model. Brain Lang 1999;70:1–12. [29] Hachisuka K, Uchida M, Nozaki Y, Hashiguchi S, Sasaki M. Primary progressive aphasia presenting as conduction aphasia. J Neurol Sci 1999;167:137–41.
Short communication
Corticobasal degeneration presenting with progressive conduction aphasia Noriyuki Kimura ⁎, Toshihide Kumamoto, Takuya Hanaoka, Yusuke Hazama, Kenichiro Nakamura, Ryuki Arakawa Department of Neurology and Neuromuscular Disorders, Oita University, Faculty of Medicine, Oita, Japan Received 25 July 2007; received in revised form 5 December 2007; accepted 6 December 2007 Available online 29 January 2008
Abstract We report the case of a woman with primary progressive aphasia (PPA) presenting with conduction aphasia. Neurological findings showed bilateral finger tremor and signe de poignet figé in her right hand. Memory, orientation, and activities of daily living were well preserved. Linguistic examination showed severe impairment in repetition, fluent spontaneous speech with phonemic paraphasia, and relatively well preserved comprehension. Limb-kinetic apraxia and parkinsonism were not observed during the course of her illness. T1weighted magnetic resonance imaging revealed severe atrophy of the left temporal lobe and dilatation of the left Sylvian fissure. Neuropathological findings demonstrated the most severe atrophy in the left superior temporal gyrus and Gallyas–Braak-positive or phosphorylated tau-immunoreactive cytoskeletal structures, which were consistent with corticobasal degeneration (CBD). We speculate that the progressive conduction aphasia of our patient might have been caused by left temporal lobe impairment. We suggest that progressive conduction aphasia may be a feature of CBD presenting with PPA. © 2007 Elsevier B.V. All rights reserved. Keywords: Corticobasal degeneration; Primary progressive aphasia; Conduction aphasia; Abnormal cytoskeletal structures; Left superior temporal gyrus
1. Introduction In 1982, Mesulam described six patients who experienced language disorders that progressed slowly over many years [1]; he subsequently named this condition primary progressive aphasia (PPA) [2]. Primary progressive aphasia is a clinical syndrome characterized by slowly progressive loss of speech and language function in the setting of relatively preserved memory and visuospatial skills within the initial two years [2,3]. Recent studies have indicated that PPA is clinically and histopathologically heterogeneous, and several underlying pathologies have been described, such as Alzheimer's disease [4], Pick's disease [5], Pick complex [6], non-specific cortical degeneration with spongiform ⁎ Corresponding author. Department of Neurology and Neuromuscular Disorders, Oita University, Faculty of Medicine, Idaigaoka 1-1, Hasama, Yufu, Oita 879-5593, Japan. Tel.: +81 97 586 5814; fax: +81 97 586 6502. E-mail address: [email protected] (N. Kimura). 0022-510X/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2007.12.017
change or dementia lacking distinct histology [7], Creutzfeldt–Jakob disease [8], corticobasal degeneration (CBD) [9–16], and motor neuron disease with dementia [17]. Here, we reported the rare case of a patient with PPA presenting with conduction aphasia of the fluent type. Although our patient did not show the typical symptoms of CBD at any time during the course of the disease, the postmortem examination confirmed a diagnosis of CBD. Conduction aphasia is characterized by markedly impaired repetition of words and phrases with normal or nearly normal comprehension and was originally proposed to result from a separation of the posterior language comprehension area and the anterior motor speech area of the left hemisphere [18]. Such a disconnection has been attributed to a lesion of the arcuate fasciculus [19]. The neuropathological findings of our patient revealed that cerebral involvement was accentuated in the left superior temporal gyrus and various types of cytoskeletal abnormalities were observed in the cerebral cortex and white matter, mainly in the frontal lobe, as well as
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in the basal ganglia and brainstem. To our knowledge, this is the first report of an autopsy case of CBD with progressive conduction aphasia. In this report, we focus on the relationship between cortical foci of degenerating areas and the clinical expression of CBD.
Limb-kinetic apraxia and Parkinsonian symptoms were not observed during the course of her illness. The follow-up MRI showed that the atrophy of left temporal lobe was slightly progressed. She died of lung cancer at the age of 72 years, 5 years after the onset of symptoms. The clinical diagnosis was PPA.
2. Case report The patient was a right-handed woman who had graduated from high school. There was no family history of neurological problems. At the age of 67 years, she became aware of a speech disturbance, specifically phonemic paraphasia in her spontaneous speech. Although she could perform household activities and her daily routine by herself, and her personality did not change, her language abilities gradually deteriorated. At the age of 69 years, she visited our hospital with language problems. On neurological examination, she appeared alert and oriented. There were no abnormalities of the cranial nerves, muscle strength, deep tendon reflexes, or sensory system, except for mild upward gaze limitation. She showed bilateral hand-finger tremor and signe de poignet figé in her right hand, but neither bradykinesia, gait disturbance, nor Myerson's sign. On neuropsychological study, the Mini-Mental State Examination (MMSE) was within the normal range, at 23 points. The Wechsler Adult Intelligence Scale-Revised (WAIS-R) was abnormal, at 61 points, because the verbal intelligence quotient (60) was low for aphasia, despite a normal performance intelligence quotient (82). Apraxia, agnosia, and dyscalculia were absent. The standard language test of aphasia revealed that spontaneous speech was fluent, but phonemic and verbal paraphasia were obvious on naming, reading aloud, and repetition. She was unable to repeat short sentences. She recognized her own errors and tried hard to correct them by herself. Impairment of repetition was the most prominent of the linguistic abnormalities. Her writing was slightly disturbed in both kana and kanji. By contrast, her auditory comprehension was normal. The profile of her language impairment was consistent with that of conduction aphasia. Her routine blood tests, electrocardiography, and electroencephalography were normal. Cranial T1-weighted magnetic resonance images (MRI) revealed severe atrophy of the left temporal lobe and dilatation of the left Sylvian fissure (Fig. 1a, b). Tc-99m-hexamethylpropyleneamine oxine single photon emission computed tomography (SPECT; GCA9300A/HG, Toshiba, Tokyo, Japan) showed mild hypoperfusion in the left temporal and parietal lobes (Fig. 1c). Three years after the onset of this condition, memory, orientation, and activities of daily living were well preserved, but linguistic disturbance had progressed. Neuropsychological reevaluation demonstrated that language fluency, auditory comprehension, writing, and reading were mild impaired, in contrast to a severe disturbance in repetition.
Fig. 1. T1-weighted MRI and 123I-IMP-SPECT images. T1-weighted MRI revealed severe atrophy of the left temporal lobe and dilation of the left Sylvian fissure (a, b). Hypoperfusion was noted in the left perisylvian area (c). The right side is shown on the left-hand side of each figure.
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2.1. Post-mortem examination The brain weight was 1170 g after fixation. Macroscopic examination revealed slight atrophy in the frontal and temporal lobes, more accentuated on the left side. The most severe atrophy was found in the left superior temporal gyrus, especially the anterior portion (Fig. 2a). The left Sylvian fissure was moderately dilated. The parietal and occipital lobes showed normal convolutions. Coronal slices disclosed moderate to mild atrophy of the caudate nucleus, putamen, and globus pallidus, slightly accentuated on the left side (Fig. 2b). The substantia nigra was pale (Fig. 2c).
Fig. 3. In the superior temporal cortex, all layers show neuronal loss and gliosis (a). Ballooned neurons are seen in the frontal cortex (b). Moderate neuronal loss and extraneuronal pigment are present in the substantia nigra (c). Hematoxylin and eosin stain. Scale bars 100 µm.
Fig. 2. Lateral view of the left cerebrum exhibits atrophy of the superior temporal gyrus and slight enlargement of the left Sylvian fissure (a). Coronal section of the brain at the mammillary body level shows marked atrophy of the left superior temporal gyrus and slight atrophy of the caudate, putamen, globus pallidus, and thalamus on the left side (b). Transverse section of the midbrain shows marked depigmentation of the substantia nigra (c).
Histological examination demonstrated moderate neuronal loss with gliosis (Fig. 3a) and a spongy appearance throughout all layers of the left superior temporal gyrus. The frontal, parietal, and occipital lobes and the remainder of the temporal lobe were relatively well preserved. Numerous ballooned neurons were seen in the frontal cortex and occasionally in the temporal, parietal, and occipital cortices
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(Fig. 3b). Diffuse fibrillary gliosis was observed in the white matter with a distribution corresponding to cortical degeneration. Neuronal loss and gliosis were moderate in the substantia nigra and mild in the striatum and globus pallidus. There were no Lewy bodies in the cerebrum and brainstem. With modified Bielschowsky staining, Pick bodies and senile plaques were not seen in the cerebral cortex or hippocampus. A few neurofibrillary tangles were present in the CA1 region of the hippocampus. Grumose degeneration was also present in the dentate nucleus. The modified Gallyas–Braak staining and anti-phosphorylated tau immunostaining revealed massive argyrophilic and anti-phosphorylated tau-positive threads, scattered coiled bodies, pretangles, and astrocytic plaques in the neurons and glial cells (Fig. 4a–c). Pretangles and astrocytic plaques were found mainly in the frontal cortex, in spite of mild neuronal loss and gliosis. However, these cytoskeletal abnormalities were observed less frequently in the severely affected left superior temporal gyrus. The argyrophilic threads were most prominent in the affected cortical region, but they were also observed in the relatively well preserved cortex, basal ganglia, and brainstem. In addition, numerous argyrophilic threads and coiled bodies were also seen in the white matter of the cerebrum, cerebellum, and brainstem. 3. Discussion We described a case of CBD with slowly progressive language disorder without dementia, parkinsonism, and pyramidal signs. The patient was able to manage her household during the course of her illness and was clinically deemed to have typical PPA. The clinical representations of PPA are sub-divided into fluent and non-fluent forms [20]. Fluent forms are characterized by impairment of auditory comprehension and empty, circumlocutory speech. Nonfluent forms are associated with stuttering or dysprosodic speech, articulatory disturbances, and agrammatism. In the present case, linguistic examination showed severe impairment of repetition, fluent spontaneous speech with phonemic paraphasia, and relatively well preserved comprehension. Conduction aphasia is characterized by fluency and paraphasia in spontaneous speech, with normal or nearly normal comprehension of spoken language but markedly impaired repetition of words and phrases [18]. The patient's condition was therefore diagnosed as PPA presenting with conduction aphasia. Although the clinical symptoms of our patient were unusual, post-mortem examination showed pathological features of CBD. Corticobasal degeneration has been recognized as one type of disorder presenting with PPA [9–16]. Clinically, CBD is characterized by an asymmetric, akinetic, rigid syndrome with prominent apraxia, myoclonus, cortical sensory loss, and sometimes alien limb behavior [21]. The occurrence of aphasia and dementia has not been recognized in CBD for a long time; however, autopsyconfirmed cases of CBD have revealed that cognitive im-
Fig. 4. Phosphorylated tau immunohistochemistry showed diffuse or granular staining of neurons (pretangles) and threads throughout the frontal cortex (a). An astrocytic plaque is seen in the cortex (b). A phosphorylated tau-positive inclusion in a glial cell in the white matter. (c). Phosphorylated tau immunohistochemistry. Scale bars 100 µm.
pairment and speech problems are prominent clinical features of the disease. Graham et al. reported that 34% of patients with pathological confirmation were noted to be aphasic [22]. Neuropathologically, CBD is characterized by asymmetric atrophy of the frontal and parietal lobes, swollen achromatic neurons, and degeneration of the substantia nigra. Recent neuropathological criteria emphasize Gallyas– Braak-positive or tau-immunoreactive lesions such as pretangles, astrocytic plaques, coiled bodies, and argyrophilic threads in neurons and glia [23]. Neuropathological examination of our patient revealed marked atrophy with neuronal loss and gliosis in the left superior temporal gyrus and substantia nigra, and to a lesser extent, the striatum, globus pallidus, and brainstem. Gallyas–Braak-positive or
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tau-immunoreactive cytoskeletal structures were observed in the cortical and sub-cortical regions, mainly in the frontal lobe. These neuropathological findings were consistent with the recent neuropathological criteria of CBD [24]. Only eight pathologically confirmed cases of CBD with PPA have been reported (Table 1) [9–16]. According to these reports, non-fluent aphasia was observed in five cases, whereas three cases showed the fluent form. All cases with non-fluent aphasia revealed a marked atrophy in the left superior or inferior frontal gyrus, while two of three cases with fluent aphasia showed marked atrophy in the left superior temporal gyrus. The present case with fluent aphasia also showed the most severe atrophy in the left superior temporal gyrus. We suggest that the fluent type of PPA may be caused by a lesion of the left superior temporal gyrus. The cardinal symptoms of conduction aphasia are significant impairments in word repetition with preserved comprehension, naming, and reading. Wernicke postulated that any lesion disrupting the arcuate fasciculus should result in conduction aphasia. The arcuate fasciculus is a white matter tract from the site of auditory language comprehension to the site of motor expression of speech [19]. By contrast, Goldstein attributed conduction aphasia to a disturbance of a localized cortical center [25]. He suggested that the linguistic mechanisms of conduction aphasia were due to a disturbance of verbal short-term memory and phonological output. The lesions might be in the inferior parietal lobe, especially the supramarginal gyrus, and the superior temporal gyrus [26–28]. These results suggest that conduction aphasia may be a heterogeneous syndrome anatomically and linguistically. We speculate that the progressive conduction aphasia of our patient might have been caused by a disturbance of short-term memory due to a Table 1 Aphasic form and most severely affected site in eight previously reported cases and the present case of corticobasal degeneration with primary progressive aphasia Author (year) Age at onset
Aphasic form
Most affected cortical region
Lippa et al. (1990) Lippa et al. (1991) Arima et al. (1994) Sakurai et al. (1996) Ikeda et al. (1996) Mimura et al. (2001) Sánchez et al. (2006) Takao et al. (2006) Present case (2007)
72/M
Non-fluent
Left parasylvian
68/M
72/M
Transcortical motor Left superior frontal (non-fluent) gyrus Amnesic (fluent) Left superior temporal gyrus Amnesic (fluent) Right frontal
67/F
Sensory (fluent)
73/M
65/F 57/F 67/F 67/F
Left superior temporal gyrus Transcortical motor Left inferior frontal (non-fluent) gyrus Non-fluent Left frontal operculmus and pre-motor area Non-fluent Left inferior frontal gyrus Conduction (fluent) Left superior temporal gyrus
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lesion in the left superior temporal gyrus. In addition, a previous report of a case of PPA presenting with conduction aphasia revealed atrophy of the left superior temporal gyrus, although this was not pathologically confirmed [29]. Thus, the present case suggests that conduction aphasia might be caused by an impairment of the left superior temporal gyrus in the present case. Further studies are needed to clarify the correlation between pathological lesions and the aphasic form of CBD with progressive conduction aphasia. In summary, we reported the first case of CBD with progressive conduction aphasia. The neuropathological findings of our case showed severe atrophy of the left superior temporal gyrus. This case is important for understanding the clinical heterogeneity and clinicopathological correlation of CBD with progressive conduction aphasia. References [1] Mesulam MM. Slowly progressive aphasia without generalized dementia. Ann Neurol 1982;11:592–8. [2] Mesulam MM. Primary progressive aphasia. Ann Neurol 2001;49:425–32. [3] Kertesz A, Hudson L, Mackenzie IR, Munoz DG. The pathology and nosology of primary progressive aphasia. Neurology 1994;44:2065–72. [4] Greene JD, Hodges JR, Ironside JW, Warlow CP. Alzheimer disease and nonfluent progressive aphasia. Arch Neurol 1996;53:1072–8. [5] Graff-Radford NR, Damasio AR, Hyman BT, Hart MN, Tranel D, Damasio H, et al. Progressive aphasia in a patient with Pick's disease: a neuropsychological, radiologic, and anatomic study. Neurology 1990;40:620–6. [6] Kertesz A, Munoz DG. Primary progressive aphasia. Clin Neurosci 1997;4:95–102. [7] Kirshner HS, Tanridag O, Thurman L, Whetsell Jr WO. Progressive aphasia without dementia: two cases with focal spongiform degeneration. Ann Neurol 1987;22:527–32. [8] Mandell AM, Alexander MP, Carpenter S. Creutzfeldt–Jakob disease presenting as isolated aphasia. Neurology 1989;39:55–8. [9] Ikeda K, Akiyama H, Iritani S, Kase K, Arai T, Niizato K, et al. Corticobasal degeneration with primary progressive aphasia and accentuated cortical lesion in superior temporal gyrus: case report and review. Acta Neuropathol 1996;92:534–9. [10] Takao M, Tsuchiya K, Mimura M, Momoshima S, Kondo H, Akiyama H, et al. Corticobasal degeneration as cause of progressive non-fluent aphasia: clinical, radiological and pathological study of an autopsy case. Neuropathology 2006;26:569–78. [11] Sanchez-Valle R, Forman MS, Miller BL, Gorno-Tempini ML. From progressive nonfluent aphasia to corticobasal syndrome: a case report of corticobasal degeneration. Neurocase 2006;12:355–9. [12] Mimura M, Oda T, Tsuchiya K, Kato M, Ikeda K, Hori K, et al. Corticobasal degeneration presenting with nonfluent primary progressive aphasia: a clinicopathological study. J Neurol Sci 2001;183:19–26. [13] Sakurai Y, Hashida H, Uesugi H, Arima K, Murayama S, Bando M, et al. A clinical profile of corticobasal degeneration presenting as primary progressive aphasia. Eur Neurol 1996;36:134–7. [14] Lippa CF, Smith TW, Fontneau N. Corticonigral degeneration with neuronal achromasia. A clinicopathologic study of two cases. J Neurol Sci 1990;98:301–10. [15] Lippa CF, Cohen R, Smith TW, Drachman DA. Primary progressive aphasia with focal neuronal achromasia. Neurology 1991;41:882–6. [16] Arima K, Uesugi H, Fujita I, Sakurai Y, Oyanagi S, Andoh S, et al. Corticonigral degeneration with neuronal achromasia presenting with primary progressive aphasia: ultrastructural and immunocytochemical studies. J Neurol Sci 1994 20;127:186–97.
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