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January 1976, Vol 33, No. 1 >
Article | January 1976

Hypoxic-Ischemic Leukoencephalopathy in Man

Myron D. Ginsberg, MD; E. Tessa Hedley-Whyte, MD; Edward P. Richardson, Jr, MD
[+] Author Affiliations

Accepted for publication Jan 14, 1975.

Reprint requests to Department of Neurology, Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104 (Dr Ginsberg).


Arch Neurol. 1976;33(1):5-14. doi:10.1001/archneur.1976.00500010007002
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References
Comments

• Three cases of hypoxic-ischemic leukoencephalopathy were studied. In two patients, the neurologic disorder followed drug overdosage; in the third, the apparent precipitating event was a postoperative myocardial infarction complicated by circulatory insufficiency. All patients were deeply unresponsive, with varying reflex patterns. In all three cases, the brain showed extensive symmetrical necrotic lesions of the central white matter, with minimal damage to gray matter structures. The lesions in case 3 showed, in addition, vascular necrosis and ring hemorrhages. Common to all cases was a prolonged period of hypoxemia, hypotension, and elevated venous pressure. Acidosis occurred in two. These observations and analysis of previous reports of similar cases suggest that leukoencephalopathy tends to occur when the hypoxemia is prolonged and is associated with periods of hypotension and metabolic imbalance.

REFERENCES

1 +
Meyer A:  Intoxications , in Blackwood W, McMenemey WH, Meyer A, et al (eds): Greenfield's Neuropathology . Baltimore, Williams & Wilkins, 1967;.
2 +
Grinker RR:  Über einen Fall von Leuchtgasvergiftung mit doppelseitiger Pallidumerweichung und schwerer Degeneration des tieferen Grosshirnmarklagers . Z Gesamte Neurol Psychiat 98:433-456, 1925;.
3 +
Hsý YK, Ch'eng YL:  Cerebral subcortical myelinopathy in carbon monoxide poisoning . Brain 61:384-392, 1938;.
4 +
Schwedenberg TH:  Leukoencephalopathy following carbon monoxide asphyxia . J Neuropathol Exper Neurol 18:597-608, 1959;.
5 +
Lapresle J, Fardeau M:  Les leuco-encéphalopathies de l'intoxication oxycarbonée . Acta Neuropathol 6:327-348, 1966;.
6 +
Lapresle J, Fardeau M:  The central nervous system and carbon monoxide poisoning: II. Anatomical study of brain lesions following intoxication with carbon monoxide (22 cases) . Prog Brain Res 24:31-74, 1967;.
7 +
Brucher JM:  Neuropathological problems posed by carbon monoxide poisoning and anoxia . Prog Brain Res 24:75-100, 1967;.
8 +
Bodechtel G:  Gehirnveränderungen bei Herzkrankheiten . Z Gesamte Neurol Psychiat 140:657-709, 1932;.
9 +
Globus JH, Bender MB:  Disseminated toxic degenerative encephalopathy (disseminated sclerosing demyelination) secondary to extensive and severe burns . J Nerv Ment Dis 83:518-529, 1936;.
10 +
Baker AB:  Cerebral lesions in hypoglycemia: II. Some possibilities of irrevocable damage from insulin shock . Arch Pathol 26:765-776, 1938;.
11 +
O'Brien JD, Steegmann AT:  Severe degeneration of the brain following nitrous oxide-oxygen anesthesia . Ann Surg 107:486-491, 1938;.
12 +
Jervis GA, Kindwall JA:  Schilder's disease in ergotamine intoxication . Am J Psychiatry 98:650-655, 1941-2;.
13 +
Malamud N, Haymaker W:  Cranial trauma and extrapyramidal involvement: Cerebral changes simulating those of anoxia . J Neuropathol Exp Neurol 6:217-226, 1947;.
14 +
Jervis GA, Joyce FT:  Barbiturate-opiate intoxication with necrosis of the basal ganglions of the brain . Arch Pathol 45:319-326, 1948;.
15 +
Richardson JE, Russell DS:  Cerebral disease due to functioning islet-cell tumours . Lancet 2:1054-1059, 1952;.
16 +
Courville CB: Contributions to the Study of Cerebral Anoxia . Los Angeles, San Lucas Press, 1953;.
17 +
Denst J:  Pathologic changes in the brain in coma following ether anesthesia . Neurology 3:239-249, 1953;.
18 +
Orthner H:  Methylalkoholvergiftung mit besonders schweren Hirnveränderungen . Virchows Arch Pathol Anat Physiol 323:442-464, 1953;.
19 +
Meriwether LS, Hager H, Scholz W:  Cerebral pathology following serum anaphylaxis . Arch Neurol Psychiatry 73:286-292, 1955;.
20 +
Jacob H:  Strangulation , in Lubarsch O, Henke F, Rössle R (eds): Handbuch der Speziellen Pathologischen Anatomie und Histologie . Berlin, Springer-Verlag, 1957;, vol 13, 1B, pp 1712-1731.
21 +
Erbslöh F:  Das Zentralnervensystem bei Krankheiten der Drýsen mit innerer Sekretion , in Lubarsch O, Henke F, Rössle R (eds): Handbuch der Speziellen Pathologischen Anatomie und Histologie . Berlin, Springer-Verlag, 1958;, vol 13, 2B, pp 1740-1768.
22 +
Pentschew A:  Intoxikationen , in Lubarsch O, Henke F, Rössle R (eds): Handbuch der Speziellen Pathologischen Anatomie und Histologie . Berlin, SÜberger-Verlag, 1958;, pp 1907-2502.
23 +
Ule G:  Über eine tödliche, klinisch intervalläre Natriumnitrat-Vergiftung . Arzneim Wochenschr 13:1038-1040, 1958;.
24 +
Richardson JC, Chambers RA, Heywood PM:  Encephalopathies of anoxia and hypoglycemia . Arch Neurol 1:178-190, 1959;.
25 +
Newman M, McMenemey WH:  Sudanophilic diffuse sclerosis ("Schilder's disease") with ictal onset . Br Med J 1:1461-1464, 1960;.
26 +
Meyer JE:  Hirnveränderungenvom Typ der CO-Vergiftung nach Stickoxydul-äther-Narkose . Arch Psychiat Nervenkr 202:113-125, 1961;.
27 +
Brucher JM, Laterre EC:  Les aspects neuropathologiques de l'encéphalopathie postanesthésique: Étude de deux cas , in Jacob H (ed): IV. Internationaler Kongress für Neuropathologie . Stuttgart, Georg Thieme Verlag, 1962;, vol 3, pp 126-137.
28 +
Jacob H, Mumme C, Solcher H:  Entmarkung bei cerebralen Ödemschäden (Strangulations-myelopathie) . Arch Psychiat Nervenkr 203:311-320, 1962;.
29 +
Plum F, Posner JB, Hain RF:  Delayed neurological deterioration after anoxia . Arch Intern Med 110:18-25, 1962;.
30 +
Lindenberg R:  Patterns of CNS vulnerability in acute hypoxaemia, including anaesthesia accidents , in Schadé JP, McMenemey WH (eds): Selective Vulnerability of the Brain in Hypoxaemia . Philadelphia, FA Davis Co, 1963;, pp 189-209.
31 +
Draganesco S, Nereantiu F, Vuia O:  Encéphalopathie hypoxique prolongée . Acta Neuropathol 3:387-391, 1964;.
32 +
Mani KS, McMenemey WH, Cumings JN:  Ischemic leucoencephalopathy: A case presenting with presenile dementia . Confinia Neurol 24:404-416, 1964;.
33 +
Payan H, Toga M, Tommasi M:  Les lésions du systéme nerveux central au cours de l'anoxie . Rev Lyon Méd 13:609-638, 1964;.
34 +
Courville CB:  Studies on the pathogenesis of multiple sclerosis: III. Disseminated infarctions of the cerebral centrum . Bull Los Angeles Neurol Soc 30:85-94, 1965;.
35 +
Girard PF, Tommasi M, Rochet M, et al:  Leuco-encéphalopathie avec cavitations massives, bilatérales et symétriques: Syndrome de décortication post-traumatique . Presse Méd 76:163-166, 1968;.
36 +
Buchan GC, Alvord EC Jr:  Diffuse necrosis of subcortical white matter associated with bacterial meningitis . Neurology 19:1-9, 1969;.
37 +
Lindenberg R:  Systemic oxygen deficiencies , in Minckler J (ed): Pathology of the Nervous System . New York, McGraw-Hill Book Co Inc, 1971;, vol 3, pp 1583-1617.
38 +
Feigin I, Budzilovich G, Weinberg S, et al:  Degeneration of white matter in hypoxia, acidosis and edema . J Neuropathol Exp Neurol 32:125-143, 1973;.
39 +
Strich SJ:  Diffuse degeneration of the cerebral white matter in severe dementia following head injury . J Neurol Neurosurg Psychiatry 19:163-185, 1956;.
40 +
Strich SJ:  Shearing of nerve fibres as a cause of brain damage due to head injury . Lancet 2:443-448, 1961;.
41 +
Lumsden CE:  Pathogenetic mechanisms in the leucoencephalopathies in anoxicischemic processes, in disorders of the blood and in intoxications , in Vinken PJ, Bruyn GW (eds): Handbook of Clinical Neurology , Amsterdam, North Holland Publishing Co, 1970;, vol 9, pp 572-663.
42 +
Korenke HD, Pribilla O:  Suicid durch einmalige Inhalation von Tetrachlorkohlenstoff (CCl4) mit Leukoencephalopathie . Arch Toxikol 25:109-126, 1969;.
43 +
Jennett B, Plum F:  Persistent vegetative state after brain damage . Lancet 1:734-737, 1972;.
44 +
Gross H, Rupprecht A, Seitelberger F:  Anatomische Befunde bei Spättod nach Lachgasnarkose . Wien Z Nervenheilkd 10:397-405, 1955;.
45 +
Hurst EW:  Acute haemorrhagic leucoencephalitis: A previously undefined entity . Med J Aust 2:1-6, 1941;.
46 +
Adams RD, Cammermeyer J, Denny-Brown D:  Acute necrotizing hemorrhagic encephalopathy . J Neuropathol Exp Neurol 8:1-29, 1949;.
47 +
Symmers W StC:  Thrombotic microangiopathy (thrombotic thrombocytopenic purpura) associated with acute haemorrhagic leucoencephalitis and sensitivity to oxophenarsine . Brain 79:511-521, 1966;.
48 +
Adams JH, Brierley JB, Connor RCR, et al:  The effects of systemic hypotension upon the human brain: Clinical and neuropathological observations in 11 cases . Brain 89:235-268, 1966;.
49 +
Brierley JB, Brown AW, Excell BJ, et al:  Brain damage in the rhesus monkey resulting from profound arterial hypotension: I. Its nature, distribution and general physiological correlates . Brain Res 13:68-100, 1969;.
50 +
Meldrum BS, Horton RW, Brierley JB:  Insulin-induced hypoglycaemia in the primate: Relationship between physiological changes and neuropathology , in Brierley JB, Meldrum BS (eds): Brain Hypoxia . London, William Heinemann Ltd, 1971;, pp 207-224.
51 +
Ginsberg MD, Myers RE:  Experimental carbon monoxide encephalopathy in the primate: I. Physiological and metabolic aspects . Arch Neurol 30:202-208, 1974;.
52 +
Ginsberg MD, Myers RE, McDonagh BF:  Experimental carbon monoxide encephalopathy in the primate: II. Clinical aspects, neuropathology and physiological correlation . Arch Neurol 30:209-216, 1974;.
53 +
Brierley JB: The influence of brain swelling, age and hypotension upon the pattern of cerebral damage in hypoxia, in Lýthy F, Bischoff A (eds): Proceedings of the Fifth International Congress of Neuropathology. Amsterdam, Excerpta Medica Foundation, 1966, pp 21-28.
54 +
Seitelberger F, Jellinger K:  Zur Frage der "CO-Leukoencephalopathie." Wien Klin Wochenschr 72:422-429, 1960;.
55 +
Preziosi TJ, Lindenberg R, Levy D, et al:  An experimental investigation in animals of the functional and morphologic effects of single and repeated exposures to high and low concentrations of carbon monoxide . Ann NY Acad Sci 174:369-384, 1970;.
56 +
Salamon G: Atlas de la Vascularisation Arterielle chez l'Homme . Paris, Sandoz Editions, 1971;.
57 +
De Reuck J:  The human periventricular arterial blood supply and the anatomy of cerebral infarctions . Eur Neurol 5:321-334, 1971;.

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1 +
Meyer A:  Intoxications , in Blackwood W, McMenemey WH, Meyer A, et al (eds): Greenfield's Neuropathology . Baltimore, Williams & Wilkins, 1967;.
2 +
Grinker RR:  Über einen Fall von Leuchtgasvergiftung mit doppelseitiger Pallidumerweichung und schwerer Degeneration des tieferen Grosshirnmarklagers . Z Gesamte Neurol Psychiat 98:433-456, 1925;.
3 +
Hsý YK, Ch'eng YL:  Cerebral subcortical myelinopathy in carbon monoxide poisoning . Brain 61:384-392, 1938;.
4 +
Schwedenberg TH:  Leukoencephalopathy following carbon monoxide asphyxia . J Neuropathol Exper Neurol 18:597-608, 1959;.
5 +
Lapresle J, Fardeau M:  Les leuco-encéphalopathies de l'intoxication oxycarbonée . Acta Neuropathol 6:327-348, 1966;.
6 +
Lapresle J, Fardeau M:  The central nervous system and carbon monoxide poisoning: II. Anatomical study of brain lesions following intoxication with carbon monoxide (22 cases) . Prog Brain Res 24:31-74, 1967;.
7 +
Brucher JM:  Neuropathological problems posed by carbon monoxide poisoning and anoxia . Prog Brain Res 24:75-100, 1967;.
8 +
Bodechtel G:  Gehirnveränderungen bei Herzkrankheiten . Z Gesamte Neurol Psychiat 140:657-709, 1932;.
9 +
Globus JH, Bender MB:  Disseminated toxic degenerative encephalopathy (disseminated sclerosing demyelination) secondary to extensive and severe burns . J Nerv Ment Dis 83:518-529, 1936;.
10 +
Baker AB:  Cerebral lesions in hypoglycemia: II. Some possibilities of irrevocable damage from insulin shock . Arch Pathol 26:765-776, 1938;.
11 +
O'Brien JD, Steegmann AT:  Severe degeneration of the brain following nitrous oxide-oxygen anesthesia . Ann Surg 107:486-491, 1938;.
12 +
Jervis GA, Kindwall JA:  Schilder's disease in ergotamine intoxication . Am J Psychiatry 98:650-655, 1941-2;.
13 +
Malamud N, Haymaker W:  Cranial trauma and extrapyramidal involvement: Cerebral changes simulating those of anoxia . J Neuropathol Exp Neurol 6:217-226, 1947;.
14 +
Jervis GA, Joyce FT:  Barbiturate-opiate intoxication with necrosis of the basal ganglions of the brain . Arch Pathol 45:319-326, 1948;.
15 +
Richardson JE, Russell DS:  Cerebral disease due to functioning islet-cell tumours . Lancet 2:1054-1059, 1952;.
16 +
Courville CB: Contributions to the Study of Cerebral Anoxia . Los Angeles, San Lucas Press, 1953;.
17 +
Denst J:  Pathologic changes in the brain in coma following ether anesthesia . Neurology 3:239-249, 1953;.
18 +
Orthner H:  Methylalkoholvergiftung mit besonders schweren Hirnveränderungen . Virchows Arch Pathol Anat Physiol 323:442-464, 1953;.
19 +
Meriwether LS, Hager H, Scholz W:  Cerebral pathology following serum anaphylaxis . Arch Neurol Psychiatry 73:286-292, 1955;.
20 +
Jacob H:  Strangulation , in Lubarsch O, Henke F, Rössle R (eds): Handbuch der Speziellen Pathologischen Anatomie und Histologie . Berlin, Springer-Verlag, 1957;, vol 13, 1B, pp 1712-1731.
21 +
Erbslöh F:  Das Zentralnervensystem bei Krankheiten der Drýsen mit innerer Sekretion , in Lubarsch O, Henke F, Rössle R (eds): Handbuch der Speziellen Pathologischen Anatomie und Histologie . Berlin, Springer-Verlag, 1958;, vol 13, 2B, pp 1740-1768.
22 +
Pentschew A:  Intoxikationen , in Lubarsch O, Henke F, Rössle R (eds): Handbuch der Speziellen Pathologischen Anatomie und Histologie . Berlin, SÜberger-Verlag, 1958;, pp 1907-2502.
23 +
Ule G:  Über eine tödliche, klinisch intervalläre Natriumnitrat-Vergiftung . Arzneim Wochenschr 13:1038-1040, 1958;.
24 +
Richardson JC, Chambers RA, Heywood PM:  Encephalopathies of anoxia and hypoglycemia . Arch Neurol 1:178-190, 1959;.
25 +
Newman M, McMenemey WH:  Sudanophilic diffuse sclerosis ("Schilder's disease") with ictal onset . Br Med J 1:1461-1464, 1960;.
26 +
Meyer JE:  Hirnveränderungenvom Typ der CO-Vergiftung nach Stickoxydul-äther-Narkose . Arch Psychiat Nervenkr 202:113-125, 1961;.
27 +
Brucher JM, Laterre EC:  Les aspects neuropathologiques de l'encéphalopathie postanesthésique: Étude de deux cas , in Jacob H (ed): IV. Internationaler Kongress für Neuropathologie . Stuttgart, Georg Thieme Verlag, 1962;, vol 3, pp 126-137.
28 +
Jacob H, Mumme C, Solcher H:  Entmarkung bei cerebralen Ödemschäden (Strangulations-myelopathie) . Arch Psychiat Nervenkr 203:311-320, 1962;.
29 +
Plum F, Posner JB, Hain RF:  Delayed neurological deterioration after anoxia . Arch Intern Med 110:18-25, 1962;.
30 +
Lindenberg R:  Patterns of CNS vulnerability in acute hypoxaemia, including anaesthesia accidents , in Schadé JP, McMenemey WH (eds): Selective Vulnerability of the Brain in Hypoxaemia . Philadelphia, FA Davis Co, 1963;, pp 189-209.
31 +
Draganesco S, Nereantiu F, Vuia O:  Encéphalopathie hypoxique prolongée . Acta Neuropathol 3:387-391, 1964;.
32 +
Mani KS, McMenemey WH, Cumings JN:  Ischemic leucoencephalopathy: A case presenting with presenile dementia . Confinia Neurol 24:404-416, 1964;.
33 +
Payan H, Toga M, Tommasi M:  Les lésions du systéme nerveux central au cours de l'anoxie . Rev Lyon Méd 13:609-638, 1964;.
34 +
Courville CB:  Studies on the pathogenesis of multiple sclerosis: III. Disseminated infarctions of the cerebral centrum . Bull Los Angeles Neurol Soc 30:85-94, 1965;.
35 +
Girard PF, Tommasi M, Rochet M, et al:  Leuco-encéphalopathie avec cavitations massives, bilatérales et symétriques: Syndrome de décortication post-traumatique . Presse Méd 76:163-166, 1968;.
36 +
Buchan GC, Alvord EC Jr:  Diffuse necrosis of subcortical white matter associated with bacterial meningitis . Neurology 19:1-9, 1969;.
37 +
Lindenberg R:  Systemic oxygen deficiencies , in Minckler J (ed): Pathology of the Nervous System . New York, McGraw-Hill Book Co Inc, 1971;, vol 3, pp 1583-1617.
38 +
Feigin I, Budzilovich G, Weinberg S, et al:  Degeneration of white matter in hypoxia, acidosis and edema . J Neuropathol Exp Neurol 32:125-143, 1973;.
39 +
Strich SJ:  Diffuse degeneration of the cerebral white matter in severe dementia following head injury . J Neurol Neurosurg Psychiatry 19:163-185, 1956;.
40 +
Strich SJ:  Shearing of nerve fibres as a cause of brain damage due to head injury . Lancet 2:443-448, 1961;.
41 +
Lumsden CE:  Pathogenetic mechanisms in the leucoencephalopathies in anoxicischemic processes, in disorders of the blood and in intoxications , in Vinken PJ, Bruyn GW (eds): Handbook of Clinical Neurology , Amsterdam, North Holland Publishing Co, 1970;, vol 9, pp 572-663.
42 +
Korenke HD, Pribilla O:  Suicid durch einmalige Inhalation von Tetrachlorkohlenstoff (CCl4) mit Leukoencephalopathie . Arch Toxikol 25:109-126, 1969;.
43 +
Jennett B, Plum F:  Persistent vegetative state after brain damage . Lancet 1:734-737, 1972;.
44 +
Gross H, Rupprecht A, Seitelberger F:  Anatomische Befunde bei Spättod nach Lachgasnarkose . Wien Z Nervenheilkd 10:397-405, 1955;.
45 +
Hurst EW:  Acute haemorrhagic leucoencephalitis: A previously undefined entity . Med J Aust 2:1-6, 1941;.
46 +
Adams RD, Cammermeyer J, Denny-Brown D:  Acute necrotizing hemorrhagic encephalopathy . J Neuropathol Exp Neurol 8:1-29, 1949;.
47 +
Symmers W StC:  Thrombotic microangiopathy (thrombotic thrombocytopenic purpura) associated with acute haemorrhagic leucoencephalitis and sensitivity to oxophenarsine . Brain 79:511-521, 1966;.
48 +
Adams JH, Brierley JB, Connor RCR, et al:  The effects of systemic hypotension upon the human brain: Clinical and neuropathological observations in 11 cases . Brain 89:235-268, 1966;.
49 +
Brierley JB, Brown AW, Excell BJ, et al:  Brain damage in the rhesus monkey resulting from profound arterial hypotension: I. Its nature, distribution and general physiological correlates . Brain Res 13:68-100, 1969;.
50 +
Meldrum BS, Horton RW, Brierley JB:  Insulin-induced hypoglycaemia in the primate: Relationship between physiological changes and neuropathology , in Brierley JB, Meldrum BS (eds): Brain Hypoxia . London, William Heinemann Ltd, 1971;, pp 207-224.
51 +
Ginsberg MD, Myers RE:  Experimental carbon monoxide encephalopathy in the primate: I. Physiological and metabolic aspects . Arch Neurol 30:202-208, 1974;.
52 +
Ginsberg MD, Myers RE, McDonagh BF:  Experimental carbon monoxide encephalopathy in the primate: II. Clinical aspects, neuropathology and physiological correlation . Arch Neurol 30:209-216, 1974;.
53 +
Brierley JB: The influence of brain swelling, age and hypotension upon the pattern of cerebral damage in hypoxia, in Lýthy F, Bischoff A (eds): Proceedings of the Fifth International Congress of Neuropathology. Amsterdam, Excerpta Medica Foundation, 1966, pp 21-28.
54 +
Seitelberger F, Jellinger K:  Zur Frage der "CO-Leukoencephalopathie." Wien Klin Wochenschr 72:422-429, 1960;.
55 +
Preziosi TJ, Lindenberg R, Levy D, et al:  An experimental investigation in animals of the functional and morphologic effects of single and repeated exposures to high and low concentrations of carbon monoxide . Ann NY Acad Sci 174:369-384, 1970;.
56 +
Salamon G: Atlas de la Vascularisation Arterielle chez l'Homme . Paris, Sandoz Editions, 1971;.
57 +
De Reuck J:  The human periventricular arterial blood supply and the anatomy of cerebral infarctions . Eur Neurol 5:321-334, 1971;.

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