Rapid postanoxic calcification of the basal ganglia Gyl Midroni, MD, and Robert Willinsky, MD, FRCP(C)
Article abstract-A 22-year-old male diabetic on hemodialysis suffered a cerebral anoxic event. Serial CT showed the development of basal ganglia calcification over a period of no more than 17 days. It appears that the basal ganglia may develop petechial hemorrhage, necrosis, calcification, or combinations of these following a n anoxic insult. The neuropathologic substrate and mechanism of rapid postanoxic calcification are unknown. NEUROLOGY 1992;42:2144-2146
Calcification of the basal ganglia (BG) occurs in association with a variety of medical conditions including hypoparathyroidism, pseudohypoparathyroidism, radiation therapy, malignancy, infection, post-cerebral anoxia of any etiology (including hypotension, hypoxemia, and carbon monoxide poisoning) and in inherited Conditions.' We report the clinical and radiologic details of an adult who developed postanoxic basal ganglia calcification (PABGC) within 17 days of an anoxic insult. Case report. A 22-year-old man was admitted to hospital after a respiratory arrest due to Haemophilus influenza pneumonia. On the way to the hospital, he had two cardiac arrests with a total pulseless time of 10 minutes. History included 13 years of poorly controlled insulindependent diabetes mellitus, and "crack" cocaine abuse. He was seropositive for HIV but had had no AIDS-defini n g illnesses. He h a d end-stage r e n a l disease t h a t required hemodialysis for the 6 months preceding admission. In the intensive care unit, the patient was unresponsive for 4 days and could do no better than respond to pain with weak limb withdrawal or moaning. Over the next 3 weeks, the patient's condition gradually improved, and a t the end of 1 month, he was able to open eyes, move all limbs to command, and replied appropriately to simple questions in phrases of two or three words. Initial examinations were notable for markedly increased tone in all limbs. This resolved i n 2 weeks. Movements were very slow and fine movements were not performed at all. There was a t least grade 4 (MRC scale) strength in all limbs. Reflexes were present bilaterally except in the ankles, and toes were flexor. Toward the end of the month, as the patient became more alert, evidence of a short-term memory deficit appeared. Thirty days after the onset of his acute illness, the p a t i e n t s u d d e n l y died d u e to r e s p i r a t o r y f a i l u r e . Postmortem was refused.
Laboratory tests were notable for severe metabolic acidosis on admission (pH = 6.89, total CO, = 8 mmol/l), and no gross abnormality of calcium metabolism (phosphate = 1.17 mmolil, calcium = 1.97 mmoL4, albumin = 35 g/l, alkaline phosphatase within normal range). Five CTs of t h e head were performed during t h e patient's time in hospital. These show rapid development of BG calcifications. Noncontrast scans from admission, day 17, and day 27 postadmission are shown in the figure.
Discussion. There are two previous reports of rapid PABGC in adults. Iwasaki et a12 reported a diabetic who developed acute pulmonary edema, prolonged hypoxemia, and two cardiac arrests; CT at 9 days postevent showed diffuse increased signal of the BG bilaterally. Sarwar and Ford3 reported a 29-year-old woman with hemorrhagic pancreatitis who developed bilateral homogenous increased signal of the striatum on CT within 31 days after two cardiac arrests. Both of these patients had a normal CT on admission. The differential diagnosis of acutely developing bilateral diffusely increased signal in the BG, on CT, includes calcification and petechial hemorrhage. Schwartz et al,4 in reporting a patient with chorea after carbon monoxide poisoning, showed a CT with bilateral increased BG density at 10 days following anoxia, which cleared up at 24 days leaving an area of decreased signal. Similarly, in the case of Lodder and Baard,Bthe bilateral increased density of the striatum was no longer present on CT 10 weeks later. A definitive distinction between calcification and petechial hemorrhage on CT can be made by examining the time course of the signal increase. In hemorrhage, the signal can be expected t o fade away over days to weeks, a s with the patients
From the Departments of Neurology (Dr. Midroni) and Neuroradiology (Dr. Willinsky), Toronto Hospital, University of Toronto, Ontario, Canada. Received February 7, 1992. Accepted for publication in final form April 16, 1992. Address correspondence and reprint requests to Dr. Gyl Midroni, 52 Bruce Farm Drive, North York, ON, Canada M2H 1G5. 2144 NEUROLOGY 42 November 1992
Figure. Unenhanced CTs. (A) The day of admission; there is cerebral atrophy. (B) On day 17, there is increased density bilaterally in the basal ganglia, with relative sparing of the internal capsule. There is no mass effect relative to CT on admission. (C) On day 27, there is intensification of the increased density in the basal ganglia. There is slight enlargement of the third and lateral ventricles. (0) Using a window level of 1, the calcification in the basal ganglia, pineal, and choroid plexus (arrows) appears simultaneously at a level of 74 to 80 HU.
reported by Schwartz et a14and Lodder and Baard.5 The prior reports of rapid PABGC do not allow this d i s t i n c t i ~ n .In ~ ?Iwasaki ~ et al’s case,2 the interval of 9 days between anoxia and CT is insufficient to exclude a petechial hemorrhage. In the case of Sarwar and the interval between the anoxic event and the CT study is not given. Our report, however, shows that increased signal on a noncont r a s t CT w a s definitely p r e s e n t a t 17 days postevent, and further intensified, rather than faded, by 27 days; this proves that the increased signal is calcium. Tissue density, measured in Hounsfield units (HU), was found t o be 80 units for the area of increased signal i n t h e BG (figure, C ) . Measurements of choroid plexus and pineal calcification in the same scan gave values of, respectively, 74 HU and 79 HU (figure, D). An intracerebral hematoma can give a value in this range in the acute phase, but the typical time course is a decline in density over a period of a few days6 A petechial hemorrhage, with blood interspersed between brain tissue, would not be expected to produce an attenuation equivalent to that of dense clotted blood. In soft tissue calcification, the calcium deposits are interspersed with soft tissue components, and such deposition cannot be expected to produce attenuation equivalent to pure bone (HU as high as 1,000 or more). There is little data on rapid PABGC in adults. In a recent autopsy study of cerebral calcification in 20 consecutive brain^,^ of four patients who had bilateral globus pallidus calcifications, two had survived an anoxic insult for more than 5 days and were noted to have “hypoxic brain damage on CT.” The authors presumed that these calcifications had been present prior to t h e illness. Muenter and Whisnants reviewed a number of autopsy cases of
basal ganglionic calcification, one of which was found at 1month post-carbon monoxide poisoning. Rapid PABGC has been documented in children. Voit and Lemburgg reported an infant who had an anoxic insult at birth, died at 14 days, and showed progressive changes i n the BG on serial ultrasounds that were pathologically proven to be calcification. On autopsy, Hastrup and Reske-Nielson’O documented symmetric basal calcification in two infants who suffered from perinatal anoxia, one of whom lived for 1month. Not all patients who suffer anoxic BG damage have calcification. More often, decreased signal on CT or necrosis on autopsy has been described.”J2 It is not known why some cases show necrosis and others show calcification. There is no neuropathologic data available about the histologic correlates of rapid PABGC in adults. Review of pathologic information from cases of neonatal rapid PABGC,SJOfrom autopsies on adult patients with BG calcification of all causes,B and from a series of autopsies with cerebral calcification7 reveals a lack of agreement regarding the severity of neuronal loss (from no loss to severe loss) and the location of the calcium (perivascular deposits, deposits i n necrotic a r e a s , calcium “encrusted” neurons, and intraneuronal calcium spherules). None of these series specifically deals with postanoxic calcification in adults. The mechanism of early postanoxic calcification is also unknown. Mitochondria1 accumulation of calcium appears to underly initiation of the process of t i s s u e calcification following anoxia. l 3 , I 4 However, studies of this process have been restricted to the first few hours or days following acute ischemia in a variety of organ systems, and to the formation of bony tissues. No information is available about the processes through which calcium November 1992 NEUROLOGY 42 2145
deposits form over a period of a several days t o weeks following anoxic injury to soft tissue. We recognize that another issue in this patient is his renal disease, as soft tissue calcinosis is a recognized feature of chronic renal failure. This patient’s calcium balance indices showed no gross abnormality, but the possibility that a1tered calcium metabolism contributed to rapid PABGC cannot be excluded.
References 1. Jellinger K. Exogenous lesions of the pallidum. In: Vinken PJ, Bruyn GW, Klawans HL, eds. Handbook of neurology. Amsterdam: Elsevier Science, 1986:465-491. 2. Iwasaki Y, Kinoshita M, Kiyoshi T. Rapid development of basal ganglia calcification caused by anoxia. J Neurol Neurosurg Psychiatry 1988;51:449-450. 3. Sanvar M, Ford K. Rapid development of basal ganglia calcification. AJNR 1981;2:103-104. 4. Schwartz A, Hennerici M, Wegener OH. Delayed choreoathetosis following acute carbon monoxide poisoning. Neurology 1985;35:98-99. 5. Lodder J, Baard WC. Paraballism caused by bilateral hemor-
2146 NEUROLOGY 42 November 1992
rhagic infarction in basal ganglia. Neurology 1981;31:484-486. 6. Bergstrom M, Ericson K, Levander B, Svendsen P, Larsson S. Variation with time of the attenuation values of intracranial hematomas. J Comput Assist Tomogr 1977;1:57-63. 7. Arnold MM, Kreel L. Asymptomatic cerebral calcification-a previously unrecognized f e a t u r e . P o s t g r a d Med J 1991;67:147-153. 8. Muenter MD, Whisnant J P . Basal ganglia calcification, hypoparathyroidism, and extrapyramidal motor manifestations. Neurology 1968;18:1075-1083. 9. Voit T, Lemburg P. Damage of thalamus and basal ganglia i n a s p h y x i a t e d f u l l - t e r m neonates. Neuropediatrics 1987;18:176-181. 10. Hastrup H, Reske-Nielson E. Symmetrical brain calcifications in infants. Acta Neurol Scand 1965;41(suppl 13):637643. 11. Hawker K, Lang AE. Hypoxic-ischemic damage of the basal ganglia: case reports and a review of the literature. Mov Disord 1990;5:219-224. 12. Adams JH, Brierley JB, Connor RCR, Treip CS. The effects of systemic hypotension upon the human brain. Clinical and neuropathological o b s e r v a t i o n s i n 11 cases. B r a i n 1966;89:235-268. 13. Buja LM, Hagler HK, Willerson JT. Altered calcium homeostasis in t h e pathogenesis of myocardial ischemic and hypoxic injury. Cell Calcium 1988;9:205-217. 14. Anderson HC. Mechanisms of pathologic calcification. Rheum Dis Clin North Am 1988;14:303-319.
Rapid postanoxic calcification of the basai ganglia Gyl Midroni and Robert Willinsky Neurology 1992;42;2144 DOI 10.1212/WNL.42.11.2144 This information is current as of November 1, 1992 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/42/11/2144.full.html
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Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 1992 by the American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
Article abstract-A 22-year-old male diabetic on hemodialysis suffered a cerebral anoxic event. Serial CT showed the development of basal ganglia calcification over a period of no more than 17 days. It appears that the basal ganglia may develop petechial hemorrhage, necrosis, calcification, or combinations of these following a n anoxic insult. The neuropathologic substrate and mechanism of rapid postanoxic calcification are unknown. NEUROLOGY 1992;42:2144-2146
Calcification of the basal ganglia (BG) occurs in association with a variety of medical conditions including hypoparathyroidism, pseudohypoparathyroidism, radiation therapy, malignancy, infection, post-cerebral anoxia of any etiology (including hypotension, hypoxemia, and carbon monoxide poisoning) and in inherited Conditions.' We report the clinical and radiologic details of an adult who developed postanoxic basal ganglia calcification (PABGC) within 17 days of an anoxic insult. Case report. A 22-year-old man was admitted to hospital after a respiratory arrest due to Haemophilus influenza pneumonia. On the way to the hospital, he had two cardiac arrests with a total pulseless time of 10 minutes. History included 13 years of poorly controlled insulindependent diabetes mellitus, and "crack" cocaine abuse. He was seropositive for HIV but had had no AIDS-defini n g illnesses. He h a d end-stage r e n a l disease t h a t required hemodialysis for the 6 months preceding admission. In the intensive care unit, the patient was unresponsive for 4 days and could do no better than respond to pain with weak limb withdrawal or moaning. Over the next 3 weeks, the patient's condition gradually improved, and a t the end of 1 month, he was able to open eyes, move all limbs to command, and replied appropriately to simple questions in phrases of two or three words. Initial examinations were notable for markedly increased tone in all limbs. This resolved i n 2 weeks. Movements were very slow and fine movements were not performed at all. There was a t least grade 4 (MRC scale) strength in all limbs. Reflexes were present bilaterally except in the ankles, and toes were flexor. Toward the end of the month, as the patient became more alert, evidence of a short-term memory deficit appeared. Thirty days after the onset of his acute illness, the p a t i e n t s u d d e n l y died d u e to r e s p i r a t o r y f a i l u r e . Postmortem was refused.
Laboratory tests were notable for severe metabolic acidosis on admission (pH = 6.89, total CO, = 8 mmol/l), and no gross abnormality of calcium metabolism (phosphate = 1.17 mmolil, calcium = 1.97 mmoL4, albumin = 35 g/l, alkaline phosphatase within normal range). Five CTs of t h e head were performed during t h e patient's time in hospital. These show rapid development of BG calcifications. Noncontrast scans from admission, day 17, and day 27 postadmission are shown in the figure.
Discussion. There are two previous reports of rapid PABGC in adults. Iwasaki et a12 reported a diabetic who developed acute pulmonary edema, prolonged hypoxemia, and two cardiac arrests; CT at 9 days postevent showed diffuse increased signal of the BG bilaterally. Sarwar and Ford3 reported a 29-year-old woman with hemorrhagic pancreatitis who developed bilateral homogenous increased signal of the striatum on CT within 31 days after two cardiac arrests. Both of these patients had a normal CT on admission. The differential diagnosis of acutely developing bilateral diffusely increased signal in the BG, on CT, includes calcification and petechial hemorrhage. Schwartz et al,4 in reporting a patient with chorea after carbon monoxide poisoning, showed a CT with bilateral increased BG density at 10 days following anoxia, which cleared up at 24 days leaving an area of decreased signal. Similarly, in the case of Lodder and Baard,Bthe bilateral increased density of the striatum was no longer present on CT 10 weeks later. A definitive distinction between calcification and petechial hemorrhage on CT can be made by examining the time course of the signal increase. In hemorrhage, the signal can be expected t o fade away over days to weeks, a s with the patients
From the Departments of Neurology (Dr. Midroni) and Neuroradiology (Dr. Willinsky), Toronto Hospital, University of Toronto, Ontario, Canada. Received February 7, 1992. Accepted for publication in final form April 16, 1992. Address correspondence and reprint requests to Dr. Gyl Midroni, 52 Bruce Farm Drive, North York, ON, Canada M2H 1G5. 2144 NEUROLOGY 42 November 1992
Figure. Unenhanced CTs. (A) The day of admission; there is cerebral atrophy. (B) On day 17, there is increased density bilaterally in the basal ganglia, with relative sparing of the internal capsule. There is no mass effect relative to CT on admission. (C) On day 27, there is intensification of the increased density in the basal ganglia. There is slight enlargement of the third and lateral ventricles. (0) Using a window level of 1, the calcification in the basal ganglia, pineal, and choroid plexus (arrows) appears simultaneously at a level of 74 to 80 HU.
reported by Schwartz et a14and Lodder and Baard.5 The prior reports of rapid PABGC do not allow this d i s t i n c t i ~ n .In ~ ?Iwasaki ~ et al’s case,2 the interval of 9 days between anoxia and CT is insufficient to exclude a petechial hemorrhage. In the case of Sarwar and the interval between the anoxic event and the CT study is not given. Our report, however, shows that increased signal on a noncont r a s t CT w a s definitely p r e s e n t a t 17 days postevent, and further intensified, rather than faded, by 27 days; this proves that the increased signal is calcium. Tissue density, measured in Hounsfield units (HU), was found t o be 80 units for the area of increased signal i n t h e BG (figure, C ) . Measurements of choroid plexus and pineal calcification in the same scan gave values of, respectively, 74 HU and 79 HU (figure, D). An intracerebral hematoma can give a value in this range in the acute phase, but the typical time course is a decline in density over a period of a few days6 A petechial hemorrhage, with blood interspersed between brain tissue, would not be expected to produce an attenuation equivalent to that of dense clotted blood. In soft tissue calcification, the calcium deposits are interspersed with soft tissue components, and such deposition cannot be expected to produce attenuation equivalent to pure bone (HU as high as 1,000 or more). There is little data on rapid PABGC in adults. In a recent autopsy study of cerebral calcification in 20 consecutive brain^,^ of four patients who had bilateral globus pallidus calcifications, two had survived an anoxic insult for more than 5 days and were noted to have “hypoxic brain damage on CT.” The authors presumed that these calcifications had been present prior to t h e illness. Muenter and Whisnants reviewed a number of autopsy cases of
basal ganglionic calcification, one of which was found at 1month post-carbon monoxide poisoning. Rapid PABGC has been documented in children. Voit and Lemburgg reported an infant who had an anoxic insult at birth, died at 14 days, and showed progressive changes i n the BG on serial ultrasounds that were pathologically proven to be calcification. On autopsy, Hastrup and Reske-Nielson’O documented symmetric basal calcification in two infants who suffered from perinatal anoxia, one of whom lived for 1month. Not all patients who suffer anoxic BG damage have calcification. More often, decreased signal on CT or necrosis on autopsy has been described.”J2 It is not known why some cases show necrosis and others show calcification. There is no neuropathologic data available about the histologic correlates of rapid PABGC in adults. Review of pathologic information from cases of neonatal rapid PABGC,SJOfrom autopsies on adult patients with BG calcification of all causes,B and from a series of autopsies with cerebral calcification7 reveals a lack of agreement regarding the severity of neuronal loss (from no loss to severe loss) and the location of the calcium (perivascular deposits, deposits i n necrotic a r e a s , calcium “encrusted” neurons, and intraneuronal calcium spherules). None of these series specifically deals with postanoxic calcification in adults. The mechanism of early postanoxic calcification is also unknown. Mitochondria1 accumulation of calcium appears to underly initiation of the process of t i s s u e calcification following anoxia. l 3 , I 4 However, studies of this process have been restricted to the first few hours or days following acute ischemia in a variety of organ systems, and to the formation of bony tissues. No information is available about the processes through which calcium November 1992 NEUROLOGY 42 2145
deposits form over a period of a several days t o weeks following anoxic injury to soft tissue. We recognize that another issue in this patient is his renal disease, as soft tissue calcinosis is a recognized feature of chronic renal failure. This patient’s calcium balance indices showed no gross abnormality, but the possibility that a1tered calcium metabolism contributed to rapid PABGC cannot be excluded.
References 1. Jellinger K. Exogenous lesions of the pallidum. In: Vinken PJ, Bruyn GW, Klawans HL, eds. Handbook of neurology. Amsterdam: Elsevier Science, 1986:465-491. 2. Iwasaki Y, Kinoshita M, Kiyoshi T. Rapid development of basal ganglia calcification caused by anoxia. J Neurol Neurosurg Psychiatry 1988;51:449-450. 3. Sanvar M, Ford K. Rapid development of basal ganglia calcification. AJNR 1981;2:103-104. 4. Schwartz A, Hennerici M, Wegener OH. Delayed choreoathetosis following acute carbon monoxide poisoning. Neurology 1985;35:98-99. 5. Lodder J, Baard WC. Paraballism caused by bilateral hemor-
2146 NEUROLOGY 42 November 1992
rhagic infarction in basal ganglia. Neurology 1981;31:484-486. 6. Bergstrom M, Ericson K, Levander B, Svendsen P, Larsson S. Variation with time of the attenuation values of intracranial hematomas. J Comput Assist Tomogr 1977;1:57-63. 7. Arnold MM, Kreel L. Asymptomatic cerebral calcification-a previously unrecognized f e a t u r e . P o s t g r a d Med J 1991;67:147-153. 8. Muenter MD, Whisnant J P . Basal ganglia calcification, hypoparathyroidism, and extrapyramidal motor manifestations. Neurology 1968;18:1075-1083. 9. Voit T, Lemburg P. Damage of thalamus and basal ganglia i n a s p h y x i a t e d f u l l - t e r m neonates. Neuropediatrics 1987;18:176-181. 10. Hastrup H, Reske-Nielson E. Symmetrical brain calcifications in infants. Acta Neurol Scand 1965;41(suppl 13):637643. 11. Hawker K, Lang AE. Hypoxic-ischemic damage of the basal ganglia: case reports and a review of the literature. Mov Disord 1990;5:219-224. 12. Adams JH, Brierley JB, Connor RCR, Treip CS. The effects of systemic hypotension upon the human brain. Clinical and neuropathological o b s e r v a t i o n s i n 11 cases. B r a i n 1966;89:235-268. 13. Buja LM, Hagler HK, Willerson JT. Altered calcium homeostasis in t h e pathogenesis of myocardial ischemic and hypoxic injury. Cell Calcium 1988;9:205-217. 14. Anderson HC. Mechanisms of pathologic calcification. Rheum Dis Clin North Am 1988;14:303-319.
Rapid postanoxic calcification of the basai ganglia Gyl Midroni and Robert Willinsky Neurology 1992;42;2144 DOI 10.1212/WNL.42.11.2144 This information is current as of November 1, 1992 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/42/11/2144.full.html
Citations
This article has been cited by 3 HighWire-hosted articles: http://www.neurology.org/content/42/11/2144.full.html##otherarti cles
Permissions & Licensing
Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions
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Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus
Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 1992 by the American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
