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Subacute brainstem angioencephalopathy: a case report and review of the literature
Journal of the Neurological Sciences 208 (2003) 101 – 104 www.elsevier.com/locate/jns
Short communication
Subacute brainstem angioencephalopathy: a case report and review of the literature Helmut Rauschka a, Johann Retzl b, Ulf Baumhackl b, Hans Christian Bankl c, Erich Salomonowitz d, Manfred Schmidbauer a,* a
Department of Neurology, Municipal Hospital Lainz, Wolkersbergenstrasse 1, A-1130 Vienna, Austria b Department of Neurology, Municipal Hospital of St. Po¨lten, Austria c Institute of Pathology, Municipal Hospital of St. Po¨lten, Austria d Institute of Radiology, Municipal Hospital of St. Po¨lten, Austria Received 5 April 2002; received in revised form 12 August 2002; accepted 15 October 2002
Abstract A previously healthy 69-year-old man developed a progressive neurological illness with bulbar signs and ataxic paraparesis. Repeated MRI examinations revealed a large space occupying lesion in the lower brain stem with patchy contrast enhancement. MRI angiography was unremarkable and CSF had normal cell count but raised protein content. A brainstem tumor was suspected and a course of intravenous glucocorticosteroids was started. No improvement occurred and the patient died of pneumonia 11 weeks after onset. Neuropathology revealed confluent areas of complete or incomplete necrosis with marked edema in the lower brainstem. Predominantly venous meningeal vessels of the brainstem showed extensive fibromuscular thickening of all layers with luminal narrowing. In addition, intramural mononuclear infiltration was found. With the exception of localisation, this case exhibits all pathologic features of subacute diencephalic angioencephalopathy (SDAE), a rare fatal disease of unknown aetiology. In addition, the clinical features of typical age, male sex, disease duration and raised CSF proteins are shared. A common disease entity is suggested and the pathogenetic relevance of inflammation and venous outflow obstruction is discussed. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Angioencephalopathy; Brainstem; Pathology; Vasculitis; Veins
1. Introduction
2. Case report
Subacute diencephalic angioencephalopathy (SDAE) is a rare fatal disease of unknown aetiology characterised by an obliterating angiopathy and complete or incomplete parenchymal necrosis. In the five reported cases [1– 4], progressive intellectual, behavioural, motor and vegetative impairment in male individuals led to death within 7 to 24 weeks. CSF had a normal cell count with increased protein content, indicating a disturbed blood brain barrier. We present here a case of obliterating brainstem angiopathy which shows all histopathological features and important clinical aspects of SDAE, suggesting a common aetiology and pathogenesis.
A previously healthy 69-year-old man developed a progressive neurological illness which led to death in 11 weeks. Starting 2 weeks prior to admission, the patient developed a progressive gait disturbance and a slurred speech. Initial neurological examination revealed a Horner’s sign, palatal weakness and a paresis of the XII cranial nerve on the left side. The speech of the patient was dysarthric without swallowing difficulties. A profound gait disturbance was due to an ataxic paraparesis with extensor plantar signs. Urinary bladder function and defecation were unaffected. CSF analysis revealed a normal cell count with an increased protein content of 0.81 g/l. Serum investigations including electrophoresis, antiphospholipid antibodies, ANAs, anti-DNA antibodies and ANCAs as well as tests for HIV and Treponema pallidum (VDRL and TPHA) were unremarkable. Repeated MRI examinations showed a
* Corresponding author. Tel.: +43-1-80110-3559; fax: +43-1-801103685. E-mail address: [email protected] (M. Schmidbauer).
0022-510X/02/$ - see front matter D 2002 Elsevier Science B.V. All rights reserved. doi:10.1016/S0022-510X(02)00395-7
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Fig. 1. Sagittal (A) and axial (B) T2 weighted MRI of the brain showing asymmetric high signal in the brainstem. Axial T1 weighted (C) MRI showing contrast enhancement.
large space occupying lesion in the lower brain stem with patchy contrast enhancement (Fig. 1A – C). The lesion did not follow the territories of arterial supply and, in addition, MRI angiography was normal. A brainstem tumor was suspected and a trial of intravenous glucocorticosteroids was started. Further deterioration occurred, the patient got immobile, developed dysphagia and died of pneumonia. At autopsy, pneumonia on both sides, pulmonary edema and dilated left and right cardiac ventricles were found. In addition, coronary sclerosis, renal angiosclerosis and general arteriosclerosis of moderate degree were present.
3. Neuropathology 3.1. Macroscopical investigations The outer surface of the brain was unremarkable. Brain weight after formalin fixation was 1397 g. The arterial vessels at the base of the scull were free of arteriosclerosis. Coronal sections of the telencephalon were unremarkable, whereas sections of the brainstem showed a patchy grey discoloration in the lower pons and upper medulla oblongata, predominantly on the left side. 3.2. Histopathology Formalin-fixed and paraffin-embedded sections were examined by routine staining methods (haematoxylin-eosin, Luxol fast blue, Bielschowsky’s axonal silver impregnation, Van Gieson Elastin, Ziehl Neelson, Gram, Grocott, WarthinStarry) and by immunocytochemistry for leucocyte and viral
antigens (CMV, EBV, HSV 1 and 2, VZV, European TickBorne Encephalitis) as well as for elastin and smooth muscle actin. Parenchymal lesions: Confluent areas of complete but predominantly incomplete necrosis with marked edema, tissue-degrading macrophages, astrogliosis and some small haemorrhages were found in the lower pons and the upper parts of the medulla oblongata (Fig. 2A). The lesion had its greatest extension at the level of the upper medulla oblongata, involving the whole left side and the right pyramidal tract. In the striatum and pallidum, loss of neurons and sparse astroglial proliferation was found. Special stains and immunocytochemistry for various bacterial and viral antigens as well as a PCR for Borrelia burgdorferi were negative. Vascular pathology: Large and moderately sized meningeal vessels of the brainstem showed extensive fibrous thickening of all layers and proliferation of smooth muscle fibres with considerable narrowing of the lumen, but without thrombotic occlusions (Fig. 2B). This vascular pathology could be found bilaterally, although there was a left side predominance. In these, as well as in vessels with mild or moderate obliterative changes, an internal elastic membrane was completely absent and the muscle fibres of the media did not show any orderly layering, suggesting a venous origin. Focal and diffuse intramural mononuclear infiltration of mild to moderate degree was found in a part of these thickened vessels, but inflammation could also be found in some veins with sparse or no fibrous thickening (Fig. 2C and D). Some vessels with very severe fibrous changes were free of inflammation. Immunocytochemistry revealed the infiltrates to be composed of B- and T-lymphocytes and a smaller proportion of macrophages. Small intraparenchymal veins of the brainstem were surrounded by vasogenic edema
H. Rauschka et al. / Journal of the Neurological Sciences 208 (2003) 101–104
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Fig. 2. Brain stem section showing complete and incomplete necrosis, edema and haemorrhages (A); large meningeal vessel with extensive fibromuscular wall thickening and luminal narrowing (B); small meningeal vein with inflammatory infiltration and moderate fibrosis (C – D); small intramedullary veins with rufflike adventitial fibrosis (E) and plasma extravasation (F); stainings: Luxol fast blue: (A), Van Gieson elastin: (B, C, E), common leucocyte antigenimmunohistochemistry: (D); H and E: (F).
or showed marked thickening of the wall due to fibroblastic proliferation in the adventitia (Fig. 2E and F). With the exception of mild to moderate fibrous intima proliferation, meningeal and parenchymal arteries were free of pathology. In the basal ganglia, small and moderately sized arteries showed mural lipohyalinosis, indicative of hypertensive small vessel disease.
4. Discussion Since the first description of SDAE in 1974 [1], four further cases have been reported [2 –4]. Each case showed lesions in a symmetrical centrencephalic distribution with typical histopathological features: (1) fibrous thickening of vessels with sparse or absent mononuclear intramural infiltrates and narrowing of the lumen without thrombotic occlusions; (2) fibroblastic adventitial proliferation of small intraparenchymal vessels and plasma extravasation; (3) confluent, partly haemorrhagic, complete and incomplete parenchymal necrosis. With the exception of lesion localisation, our case shows all pathological features of SDAE and shares the clinical features of typical age, male sex, disease duration and raised CSF proteins. This strongly suggests that SDAE and the present case belong to the same disease entity.
Whereas a cause and effect relationship between angiopathy and parenchymal damage is accepted [2,3], the mechanisms are unclear. Although in the original description vessel wall pathology is assigned to veins and arteries [1], in the further reports, vessels are either identified as veins or cannot be classified because of the severity of fibrotic changes [2– 4]. In the present case, histopathological investigations including immunocytochemistry for elastin and actin suggest a predominantly venous process. An arterial origin of the obliterated vessels, whereby disintegration of an orderly muscle fibre layering and complete loss of the internal elastic membrane are due to the severity of mural changes, cannot be ruled out completely. The occurrence of incipient obliterative changes in vessels clearly identifiable as veins, but not in arteries, as well as the type of parenchymal damage, which is predominantly incomplete necrotic and congestive, argue against the latter possibility. Venous hypertension due to outflow obstruction is sufficient to explain the subacute progressive course and the kind of parenchymal damage. Disturbed arteriovenous blood flow and venous hypertension are the pathogenetic hallmarks of spinal Foix –Alajouanine disease (FAD) and angiodysgenetic necrotizing encephalopathy (ANE) [5– 8], which share subacute disease course, clinical features, CSF findings and neuropathological changes with SDAE, as has been emphasized recently [3]. In addition, the regions of parenchymal
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damage in SDAE match with the drainage areas of the deep cerebral venous system but not with the areas of arterial supply [2,9]. In FAD and ANE, disturbed outflow is caused by vascular malformations, and the fibroblastic thickening of veins is regarded to be a secondary change, as has also been reported in telencephalic dural arteriovenous malformation [10]. In contrast, SDAE and the present case lack angiodysgenetic (malformative) features, which could explain the vessel pathology as secondary. Sparse mononuclear infiltration of unknown significance is present within the vessel walls in most cases of SDAE [1– 3], but has not been described in FAD and ANE [5 –8]. In the present case, inflammation was also present in veins with sparse or no fibrotic changes, whereas a part of severely fibrosed and thickened vessels was free of mononuclear infiltration. These findings suggest a cause and effect relationship between inflammation and fibrotic-obliterating changes and argue against a mere ‘‘bystander inflammation’’, although inflammatory vessel pathology in SDAE and in the present case neither resembles any known noninfectious vasculitis [11], nor could any bacterial, fungal or viral agent be identified. In addition to demonstrating that the characteristic pathological changes of SDAE can also occur in another brain region, this case points to the pathogenetic relevance of inflammation and venous outflow obstruction in this characteristic disease entity.
Acknowledgements The authors wish to thank Mrs. E. Katztensteiner, Mrs. S. Bariszlovits, Mrs. M. Leisser and Mrs. H. Flicker for excellent technical assistance.
References [1] DeGirolami U, Haas ML, Richardson Jr RP. Subacute diencephalic angioencephalopathy: a clinicopathological case study. J Neurol Sci 1974;22:197 – 210. [2] Kinney H, Burger PC, Vogel FS. Subacute diencephalic angioencephalopathy: report of an additional case. J Neurol Sci 1980;45:73 – 81. [3] Schmidbauer M, Lassmann J, Pilz P, Vass Sr K, Budka H. Subacute diencephalic angioencephalopathy: an entity similar to angiodysgenetic necrotizing encephalopathy and Foix – Alajouanine disease. J Neurol 1992;239:379 – 81. [4] Tihan T, Burger PC, Pomper M, Sanchez O, Ramzan M, Eberhart CG, et al. Subacute diencephalic angioencephalopathy: biopsy diagnosis and radiological features of a rare entity. Clin Neurol Neurosurg 2001; 103:160 – 7. [5] Foix C, Alajouanine T. La mye´lite ne´crotique subaigue. Mye´lite central angio-hypertrophique a` e´volution progressive. Paraple´gie amyotrophique lentement ascendate, d’abord spasmodique, puis flasque, s’accompagnant de dissociation albumono-cytologique. Rev Neurol (Paris) 1926;33:1 – 42. [6] Jellinger K, Minauf M, Garzuly F, Neumayer E. Angiodysgenetische nekrotisierende Myelopathie (Bericht u¨ber 7 Fa¨lle). Arch Psychiatr Nervenkr 1968;211:377 – 404. [7] Hurst R, Kenyon L, Lavi E, Raps E, Marcotte P. Spinal dural arteriovenous fistulas: the pathology of venous hypertensive myelopathy. Neurology 1995;45:1309 – 13. [8] Schmitt HP, Bersch W, Carls C. ‘‘Angiodysgenetic necrotizing encephalopathy’’ and its different manifestations. Acta Neuropathol (Berl) 1988;75:621 – 6. [9] Hassler O. Deep cerebral venous system in man. a microangiopathic study on its areas of drainage and its anastomoses with the superficial cerebral veins. Neurology (Minneap) 1966;16:505 – 11. [10] Hurst RW, Bagley LJ, Galetta S, Glosser G, Liebermann AP, Trojanowski J, et al. Dementia resulting from dural arteriovenous fistulas: the pathologic findings of venous hypertensive encephalopathy. Am J Neuroradiol 1988;19:1267 – 73. [11] Kalima H, Kaste M, Haltia M. Non-infectious vasculitides. In: Graham DI, Lantos PL, editors. Greenfield’s neuropathology. London: Arnold; 1997. p. 332 – 6.
Short communication
Subacute brainstem angioencephalopathy: a case report and review of the literature Helmut Rauschka a, Johann Retzl b, Ulf Baumhackl b, Hans Christian Bankl c, Erich Salomonowitz d, Manfred Schmidbauer a,* a
Department of Neurology, Municipal Hospital Lainz, Wolkersbergenstrasse 1, A-1130 Vienna, Austria b Department of Neurology, Municipal Hospital of St. Po¨lten, Austria c Institute of Pathology, Municipal Hospital of St. Po¨lten, Austria d Institute of Radiology, Municipal Hospital of St. Po¨lten, Austria Received 5 April 2002; received in revised form 12 August 2002; accepted 15 October 2002
Abstract A previously healthy 69-year-old man developed a progressive neurological illness with bulbar signs and ataxic paraparesis. Repeated MRI examinations revealed a large space occupying lesion in the lower brain stem with patchy contrast enhancement. MRI angiography was unremarkable and CSF had normal cell count but raised protein content. A brainstem tumor was suspected and a course of intravenous glucocorticosteroids was started. No improvement occurred and the patient died of pneumonia 11 weeks after onset. Neuropathology revealed confluent areas of complete or incomplete necrosis with marked edema in the lower brainstem. Predominantly venous meningeal vessels of the brainstem showed extensive fibromuscular thickening of all layers with luminal narrowing. In addition, intramural mononuclear infiltration was found. With the exception of localisation, this case exhibits all pathologic features of subacute diencephalic angioencephalopathy (SDAE), a rare fatal disease of unknown aetiology. In addition, the clinical features of typical age, male sex, disease duration and raised CSF proteins are shared. A common disease entity is suggested and the pathogenetic relevance of inflammation and venous outflow obstruction is discussed. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Angioencephalopathy; Brainstem; Pathology; Vasculitis; Veins
1. Introduction
2. Case report
Subacute diencephalic angioencephalopathy (SDAE) is a rare fatal disease of unknown aetiology characterised by an obliterating angiopathy and complete or incomplete parenchymal necrosis. In the five reported cases [1– 4], progressive intellectual, behavioural, motor and vegetative impairment in male individuals led to death within 7 to 24 weeks. CSF had a normal cell count with increased protein content, indicating a disturbed blood brain barrier. We present here a case of obliterating brainstem angiopathy which shows all histopathological features and important clinical aspects of SDAE, suggesting a common aetiology and pathogenesis.
A previously healthy 69-year-old man developed a progressive neurological illness which led to death in 11 weeks. Starting 2 weeks prior to admission, the patient developed a progressive gait disturbance and a slurred speech. Initial neurological examination revealed a Horner’s sign, palatal weakness and a paresis of the XII cranial nerve on the left side. The speech of the patient was dysarthric without swallowing difficulties. A profound gait disturbance was due to an ataxic paraparesis with extensor plantar signs. Urinary bladder function and defecation were unaffected. CSF analysis revealed a normal cell count with an increased protein content of 0.81 g/l. Serum investigations including electrophoresis, antiphospholipid antibodies, ANAs, anti-DNA antibodies and ANCAs as well as tests for HIV and Treponema pallidum (VDRL and TPHA) were unremarkable. Repeated MRI examinations showed a
* Corresponding author. Tel.: +43-1-80110-3559; fax: +43-1-801103685. E-mail address: [email protected] (M. Schmidbauer).
0022-510X/02/$ - see front matter D 2002 Elsevier Science B.V. All rights reserved. doi:10.1016/S0022-510X(02)00395-7
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H. Rauschka et al. / Journal of the Neurological Sciences 208 (2003) 101–104
Fig. 1. Sagittal (A) and axial (B) T2 weighted MRI of the brain showing asymmetric high signal in the brainstem. Axial T1 weighted (C) MRI showing contrast enhancement.
large space occupying lesion in the lower brain stem with patchy contrast enhancement (Fig. 1A – C). The lesion did not follow the territories of arterial supply and, in addition, MRI angiography was normal. A brainstem tumor was suspected and a trial of intravenous glucocorticosteroids was started. Further deterioration occurred, the patient got immobile, developed dysphagia and died of pneumonia. At autopsy, pneumonia on both sides, pulmonary edema and dilated left and right cardiac ventricles were found. In addition, coronary sclerosis, renal angiosclerosis and general arteriosclerosis of moderate degree were present.
3. Neuropathology 3.1. Macroscopical investigations The outer surface of the brain was unremarkable. Brain weight after formalin fixation was 1397 g. The arterial vessels at the base of the scull were free of arteriosclerosis. Coronal sections of the telencephalon were unremarkable, whereas sections of the brainstem showed a patchy grey discoloration in the lower pons and upper medulla oblongata, predominantly on the left side. 3.2. Histopathology Formalin-fixed and paraffin-embedded sections were examined by routine staining methods (haematoxylin-eosin, Luxol fast blue, Bielschowsky’s axonal silver impregnation, Van Gieson Elastin, Ziehl Neelson, Gram, Grocott, WarthinStarry) and by immunocytochemistry for leucocyte and viral
antigens (CMV, EBV, HSV 1 and 2, VZV, European TickBorne Encephalitis) as well as for elastin and smooth muscle actin. Parenchymal lesions: Confluent areas of complete but predominantly incomplete necrosis with marked edema, tissue-degrading macrophages, astrogliosis and some small haemorrhages were found in the lower pons and the upper parts of the medulla oblongata (Fig. 2A). The lesion had its greatest extension at the level of the upper medulla oblongata, involving the whole left side and the right pyramidal tract. In the striatum and pallidum, loss of neurons and sparse astroglial proliferation was found. Special stains and immunocytochemistry for various bacterial and viral antigens as well as a PCR for Borrelia burgdorferi were negative. Vascular pathology: Large and moderately sized meningeal vessels of the brainstem showed extensive fibrous thickening of all layers and proliferation of smooth muscle fibres with considerable narrowing of the lumen, but without thrombotic occlusions (Fig. 2B). This vascular pathology could be found bilaterally, although there was a left side predominance. In these, as well as in vessels with mild or moderate obliterative changes, an internal elastic membrane was completely absent and the muscle fibres of the media did not show any orderly layering, suggesting a venous origin. Focal and diffuse intramural mononuclear infiltration of mild to moderate degree was found in a part of these thickened vessels, but inflammation could also be found in some veins with sparse or no fibrous thickening (Fig. 2C and D). Some vessels with very severe fibrous changes were free of inflammation. Immunocytochemistry revealed the infiltrates to be composed of B- and T-lymphocytes and a smaller proportion of macrophages. Small intraparenchymal veins of the brainstem were surrounded by vasogenic edema
H. Rauschka et al. / Journal of the Neurological Sciences 208 (2003) 101–104
103
Fig. 2. Brain stem section showing complete and incomplete necrosis, edema and haemorrhages (A); large meningeal vessel with extensive fibromuscular wall thickening and luminal narrowing (B); small meningeal vein with inflammatory infiltration and moderate fibrosis (C – D); small intramedullary veins with rufflike adventitial fibrosis (E) and plasma extravasation (F); stainings: Luxol fast blue: (A), Van Gieson elastin: (B, C, E), common leucocyte antigenimmunohistochemistry: (D); H and E: (F).
or showed marked thickening of the wall due to fibroblastic proliferation in the adventitia (Fig. 2E and F). With the exception of mild to moderate fibrous intima proliferation, meningeal and parenchymal arteries were free of pathology. In the basal ganglia, small and moderately sized arteries showed mural lipohyalinosis, indicative of hypertensive small vessel disease.
4. Discussion Since the first description of SDAE in 1974 [1], four further cases have been reported [2 –4]. Each case showed lesions in a symmetrical centrencephalic distribution with typical histopathological features: (1) fibrous thickening of vessels with sparse or absent mononuclear intramural infiltrates and narrowing of the lumen without thrombotic occlusions; (2) fibroblastic adventitial proliferation of small intraparenchymal vessels and plasma extravasation; (3) confluent, partly haemorrhagic, complete and incomplete parenchymal necrosis. With the exception of lesion localisation, our case shows all pathological features of SDAE and shares the clinical features of typical age, male sex, disease duration and raised CSF proteins. This strongly suggests that SDAE and the present case belong to the same disease entity.
Whereas a cause and effect relationship between angiopathy and parenchymal damage is accepted [2,3], the mechanisms are unclear. Although in the original description vessel wall pathology is assigned to veins and arteries [1], in the further reports, vessels are either identified as veins or cannot be classified because of the severity of fibrotic changes [2– 4]. In the present case, histopathological investigations including immunocytochemistry for elastin and actin suggest a predominantly venous process. An arterial origin of the obliterated vessels, whereby disintegration of an orderly muscle fibre layering and complete loss of the internal elastic membrane are due to the severity of mural changes, cannot be ruled out completely. The occurrence of incipient obliterative changes in vessels clearly identifiable as veins, but not in arteries, as well as the type of parenchymal damage, which is predominantly incomplete necrotic and congestive, argue against the latter possibility. Venous hypertension due to outflow obstruction is sufficient to explain the subacute progressive course and the kind of parenchymal damage. Disturbed arteriovenous blood flow and venous hypertension are the pathogenetic hallmarks of spinal Foix –Alajouanine disease (FAD) and angiodysgenetic necrotizing encephalopathy (ANE) [5– 8], which share subacute disease course, clinical features, CSF findings and neuropathological changes with SDAE, as has been emphasized recently [3]. In addition, the regions of parenchymal
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H. Rauschka et al. / Journal of the Neurological Sciences 208 (2003) 101–104
damage in SDAE match with the drainage areas of the deep cerebral venous system but not with the areas of arterial supply [2,9]. In FAD and ANE, disturbed outflow is caused by vascular malformations, and the fibroblastic thickening of veins is regarded to be a secondary change, as has also been reported in telencephalic dural arteriovenous malformation [10]. In contrast, SDAE and the present case lack angiodysgenetic (malformative) features, which could explain the vessel pathology as secondary. Sparse mononuclear infiltration of unknown significance is present within the vessel walls in most cases of SDAE [1– 3], but has not been described in FAD and ANE [5 –8]. In the present case, inflammation was also present in veins with sparse or no fibrotic changes, whereas a part of severely fibrosed and thickened vessels was free of mononuclear infiltration. These findings suggest a cause and effect relationship between inflammation and fibrotic-obliterating changes and argue against a mere ‘‘bystander inflammation’’, although inflammatory vessel pathology in SDAE and in the present case neither resembles any known noninfectious vasculitis [11], nor could any bacterial, fungal or viral agent be identified. In addition to demonstrating that the characteristic pathological changes of SDAE can also occur in another brain region, this case points to the pathogenetic relevance of inflammation and venous outflow obstruction in this characteristic disease entity.
Acknowledgements The authors wish to thank Mrs. E. Katztensteiner, Mrs. S. Bariszlovits, Mrs. M. Leisser and Mrs. H. Flicker for excellent technical assistance.
References [1] DeGirolami U, Haas ML, Richardson Jr RP. Subacute diencephalic angioencephalopathy: a clinicopathological case study. J Neurol Sci 1974;22:197 – 210. [2] Kinney H, Burger PC, Vogel FS. Subacute diencephalic angioencephalopathy: report of an additional case. J Neurol Sci 1980;45:73 – 81. [3] Schmidbauer M, Lassmann J, Pilz P, Vass Sr K, Budka H. Subacute diencephalic angioencephalopathy: an entity similar to angiodysgenetic necrotizing encephalopathy and Foix – Alajouanine disease. J Neurol 1992;239:379 – 81. [4] Tihan T, Burger PC, Pomper M, Sanchez O, Ramzan M, Eberhart CG, et al. Subacute diencephalic angioencephalopathy: biopsy diagnosis and radiological features of a rare entity. Clin Neurol Neurosurg 2001; 103:160 – 7. [5] Foix C, Alajouanine T. La mye´lite ne´crotique subaigue. Mye´lite central angio-hypertrophique a` e´volution progressive. Paraple´gie amyotrophique lentement ascendate, d’abord spasmodique, puis flasque, s’accompagnant de dissociation albumono-cytologique. Rev Neurol (Paris) 1926;33:1 – 42. [6] Jellinger K, Minauf M, Garzuly F, Neumayer E. Angiodysgenetische nekrotisierende Myelopathie (Bericht u¨ber 7 Fa¨lle). Arch Psychiatr Nervenkr 1968;211:377 – 404. [7] Hurst R, Kenyon L, Lavi E, Raps E, Marcotte P. Spinal dural arteriovenous fistulas: the pathology of venous hypertensive myelopathy. Neurology 1995;45:1309 – 13. [8] Schmitt HP, Bersch W, Carls C. ‘‘Angiodysgenetic necrotizing encephalopathy’’ and its different manifestations. Acta Neuropathol (Berl) 1988;75:621 – 6. [9] Hassler O. Deep cerebral venous system in man. a microangiopathic study on its areas of drainage and its anastomoses with the superficial cerebral veins. Neurology (Minneap) 1966;16:505 – 11. [10] Hurst RW, Bagley LJ, Galetta S, Glosser G, Liebermann AP, Trojanowski J, et al. Dementia resulting from dural arteriovenous fistulas: the pathologic findings of venous hypertensive encephalopathy. Am J Neuroradiol 1988;19:1267 – 73. [11] Kalima H, Kaste M, Haltia M. Non-infectious vasculitides. In: Graham DI, Lantos PL, editors. Greenfield’s neuropathology. London: Arnold; 1997. p. 332 – 6.