Print ISSN: 0039-2499. Online ISSN: 1524-4628 Copyright 1983 American Heart Association, Inc. All rights reserved. is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Stroke doi: 10.1161/01.STR.14.4.501 1983;14:501-505 Stroke. http://stroke.ahajournals.org/content/14/4/501 on the World Wide Web at: The online version of this article, along with updated information and services, is located
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The frequency of secondary brain stem hemorrhage was found to be 45 % in cerebral hemorrhage, 15 % in cerebral infarction, and 36% in ruptured aneurysms. In the majority of cases the secondary brain stem hemorrhage occurred a few days after the onset of cerebral hemorrhage or infarction. Ruptured aneurysms showed a more widespread temporal distribution of secondary brain stem hemorrhage. The median survival time was 2 days in cases of cerebral hemorrhage, 4 days in ruptured aneurysm and 4 days in cerebral infarction. The frequency of secondary brain stem hemorrhage was significantly lower in patients younger than 20 years. No significant difference was found in its distribution between the sexes. Secondary occipital lobe infarction was present in 3.5% of the patients. It is concluded that secondary brain stem hemorrhage is a common major contribution to the cause of death in stroke. Stroke, Vol 14, No 4, 1983 TRANSTENTORIAL HERNIATION is a well known complication of expanding supratentorial lesions with resulting clinical impairment of consciousness and brain stem functions, and often culminating in death. I_5 Expanding supratentorial lesions are frequently fol- lowed by secondary brain stem hemorrhage. 6 The risk of secondary brain stem hemorrhage has been regarded as a function of the growth velocity of the primary space occupying lesion, as well as of the volume which the lesion ultimately achieves. 7,10 It is assumed that a quickly expanding lesion, such as cerebral hemor- rhage, will produce a more rapid caudal displacement of the brain stem causing secondary brain stem hemor- rhage, than a slower growing lesion such as infarction with concomitant edema. 6 In early death following acute cerebrovascular lesions, symptoms of cerebral herniation are seen, and it is generally accepted that herniation often is a significant factor contributing to death. The aim of the present study was to evaluate these aspects by the analysis of a large autopsy materi- al with recent cerebral hemorrhage, infarction or rup- tured aneurysm and to assess the lesions frequency, time of occurrence, and age and sex distribution. Material and Methods Among all patients who had brain autopsy at Rigs- hospitalet from January 1971 through August 1982, 435 had recent cerebral hemorrhage, infarction or rup- tured aneurysm in the carotid artery distribution and were selected for the present study. Patients who were subjected to surgery were excluded from the study. Only cases in which the death occurred within 100 days of onset of symptoms were considered. The patho-anatomical diagnosis has been made by the same neuropathologist (LK) in all cases. Spontaneous cere- bral hemorrhage or infarction were clinically denned as an event which was sudden in onset and unassociat- From the Department of Neurology, Rigshospitalet, Copenhagen, Denmark, and the Institute of Neuropathology, University of Copenha- gen, Denmark. Address correspondence to: Maiken Nedergaard, B.M., Institute of Neuropathology, University of Copenhagen, 11 Frederik V's Vej, DK- 2100 Copenhagen O, Denmark. Received December 1, 1982; revision accepted February 21, 1983. ed with apparent trauma, neoplasm or vascular malfor- mation. The brains were fixed in formalin for at least 14 days and selected areas were embedded in paraffin for mi- croscopic examination. Sections from pons and mes- encephalon were prepared in all cases. Secondary brain stem hemorrhage was defined as perivascular bleeding in pons or mesencephalon with- out edema, glial proliferation or perivascular leucotyte infiltration. Most bleedings were a few mm in size. The intracranial vessels were carefully examined for thrombosis. Unfotunately the extracranial arteries were not routinely dissected in the general autopsy department. The autopsy rate was 86-89%, and did not differ according to age and sex. The significance of difference was tested by a chi- square test. Results Frequency of Secondary Brain Stem Hemorrhage The frequency of secondary brain stem hemorrhage varied considerably according to the character of the precipitating supratentorial lesion (table 1). In cerebral hemorrhage, the frequency was 45%, in ruptured con- genital aneurysm 36%, and in cerebral infarction only 15%. However, the frequency of secondary brain stem hemorrhage was 29% in those cases which showed thrombosis and infarction in the internal carotid artery and its branches. In cases of infarction without demon- strated thrombosis in these vessels the frequency was only 1.2%. Length of Survival Hemorrhage The median survival time was 2 days (fig. 1). The frequency of secondary brain stem hemorrhage was significantly higher during the first 2 days than during the following days (p = 0.0021). Complications of either subarachnoidal bleeding or intraventricular bleeding, or both, did not increase the risk of secon- dary brain stem hemorrhage. Ruptured Aneurysms The median survival time was 4 days (fig. 2). Un- like cerebral hemorrhage and infarction there was no by guest on June 2, 2014 http://stroke.ahajournals.org/ Downloaded from 502 STROKE VOL 14, No 4, JULY-AUGUST 1983 TABLE 1 Secondary Brain Stem Hemorrhage in Stroke Frequency No. with of secon- secondary dary brain No. of brain stem stem cases hemorrhage hemorrhage Cerebral hemorrhage 139 63 0.45 Ruptured congenital aneurysm 134 48 0.36 Cerebral infarct, all cases 162 24 0.15 Cerebral infarct with- out thrombosis in the internal carotid artery system 82 1 0.01 Cerebral infarct with thrombosis in the in- ternal carotid artery system 80 23 0.29 tendency towards an early secondary brain stem hem- orrhage. The greater part of the ruptured aneurysms were localised on the middle cerebral arteries but their exact localisation did not affect frequency of the secon- dary brain stem hemorrhage. Infarction The median survival time was 4 days (fig. 3). The frequency of secondary brain stem hemorrhage was significantly higher during the first 4 days than during the following days (p = 0.0001). Up to day 30, the Cerebral hemorrhage Ruptured aneurysm Number of cases 40- 1 m n a i i i i 15 20 25 30 Survival in days 4 31-100 FIGURE 1. Frequency distribution of all deaths according to numbers of days after cerebral hemorrhage. Striped areas rep- resent the finding of secondary brain stem hemorrhage. Number of cases 40- 35 30-L 25- 20 15-1 10 5- d VVt 5 t 10 m mM pjfl A i // n 25 30 31-100 15 20 Survival in days FIGURE 2. Frequency distribution of all deaths according to numbers of days after ruptured aneurysm. Striped areas repre- sent the finding of secondary brain stem hemorrhage. survival time in cases of infarction with demonstrated thrombosis in the intracranial vessels was identical with the distribution in those without thrombosis. After day 31, there was a higher frequency of death in cases of infarction without demonstrated thrombosis (fig. 3). Relation Between Secondary Brain Stem Hemorrhage, Sex and Age Table 2 shows a slight tendency towards a higher frequency of secondary brain stem hemorrhage in women, a difference which is statistically non-signifi- cant. No instances of secondary brain stem hemorrhage were encountered in 11 patients who were younger than 20 years (table 3). In all other age groups secon- dary brain stem hemorrhage occurred with the same frequency, although there was a tendency to a some- what higher frequency in the age groups between 40 and 70 years. The difference between the patients un- der 20 years and those belonging to other age groups was statistically significant (p = 0.042). Secondary Occipital Infarcts Secondary occipital infarcts were found in 15 pa- tients (3, 5%) who died relatively late (table 4). Six had cerebral hemorrhage, 7 had ruptured aneurysm, and only 2 had cerebral infarction. No correlation was found between occipital lobe infarction and secondary brain hemorrhage. by guest on June 2, 2014 http://stroke.ahajournals.org/ Downloaded from SECONDARY BRAIN STEM HEMORRHAGE IN STROKE/Nedergaard et al. 503 Cerebral infarction without intracranial thrombosis TABLE 3 Age Distribution of Secondary Brain Stem Hemorrhage r 20- 15- 10- 5- vlumber o cases 2.I.: ..ZltHnJ. lfln Cerebral infarction with intracranial thrombosis 10- - f e l LiiiiL T B M i 1 r 10 15 20 Survival in days 11 m n 25 -9- //- m 30 31-100 FIGURE 3. Distribution of all deaths according to number of days after cerebral infarction. Striped areas represent secon- dary brain stem hemorrhage. Discussion Supratentorial space occupying lesions may cause transtentorial caudal herniation with downward dis- placement through the tentorial notch of parts of the hemispheres, which compress the diencephalon and the adjoining midbrain. 2 Neuropathological examina- tion of such cases shows cerebral grooving in the vicin- ity of the tentorial notch resulting from compression against the free edge of the tentorium cerebelli. However, grooves are often found in the uncus of Cerebral hemorrhage 0-19 20-39 40-59 60-79 80-99 Total Ruptured aneurysm 0-19 20-39 40-59 60-79 80-99 Total Cerebral infarction 0-19 20-39 40-59 60-79 80-99 Total No. of cases 3 10 45 58 23 139 8 20 76 39 1 134 0 2 29 71 52 162 No. with secondary brain stem hemorrhage 0 3 23 28 9 63 0 8 30 10 0 48 0 0 6 12 6 24 Frequency of secon- dary brain stem hemorrhage 0 0.33 0.51 0.48 0.39 0.45 0 0.35 0.40 0.26 0 0.36 0 0 0.21 0.17 0.12 0.15 brains free from overt disease," and the range of nor- mal variation is not defined." Secondary brain stem hemorrhage always represents a pathological condi- tion, indicating advanced transtentorial herniation, but some degree of transtentorial herniation may be pres- ent without the occurrence of such hemorrhage as indi- TABLE 4 Occipital Lobe Infarction Secondary to Transtentorial Caudal Herniation TABLE 2 Sex Distribution Cerebral hemorrhage women men total Ruptured aneurysm women men total Cerebral infarction women men total of Secondary Brain Stem No. with No. of cases 66 73 139 52 82 134 79 83 162 secondary brain stem Hemorrhage Frequency of secon- dary brain stem hemorrhage hemorrhage 33 30 63 21 27 48 13 11 24 0.50 0.41 0.45 0.41 0.33 0.36 0.17 0.13 0.15 Survival for patients with secondary brain stem hemorrhage Survival for patients without secondary brain stem hemorrhage Cerebral hemorrhage N = 6 2 days 3 10 days 6 days 12 13 days Ruptured aneurysm N = 7 2 days 4 9 10 15 15 days 13 days Cerebral infarction N = 2 12 days 20 days by guest on June 2, 2014 http://stroke.ahajournals.org/ Downloaded from 504 STROKE VOL 14, No 4, JULY- AUGUST 1983 cated by our own cases with secondary occipital lobe infarction without brain stem hemorrhage. It has been postulated that either the displacement of the brain tissue per se, 2< ll_l3 ' 15 occlusion of veins at the level of the tentorial notch, 4 ' 15,16 or lengthening and angulation of the penetrating arteries caused by caudal displacement of the brain stem, 17,18 are the reasons for the appearance of secondary brain stem hemorrhages. It is contended that secondary brain stem hemorrhage occurs only in the presence of active circulation in the damaged blood vessels of the displaced rostral brain stem." There is some variation in the incidence of secon- dary brain stem hemorrhage reported by different au- thors. Our finding that 45% of the patients with lethal cerebral hemorrhages had secondary brain stem hem- orrhage, is comparable to 57% reported by Cohen, 6 but higher than the frequency of 14% and 31 % reported by Poppen 15 and Klintworth, 19 respectively. Most patients died within 48 hours, which may indi- cate that in hemorrhage it is the expanding lesion and not reactive edema which is the primary cause of sec- ondary brain stem hemorrhage. In cases of ruptured aneurysm a frequency of 36% of secondary brain stem hemorrhages was found, which is a higher value than the frequency of 21 % reported by Cohen. 6 Secondary brain stem hemorrhage was ob- served with equal frequency in early and late death in patients with ruptured aneurysm. Most patients died shortly after either the acute episode or after a rebleed- ing from the aneurysm. The frequency of secondary brain stem hemorrhage in cases of infarction was 15%, which is comparable to 9% reported by Cohen 6 and 11.6% reported by Klintworth. 19 The finding that secondary brain stem hemorrhage had the highest frequency from day 1 to 5, with the maximum at day 4, is consistent with the prevailing clinical concept 20,21 and recent CT find- ings 22 indicating that cerebral edema becomes maximal at 2 to 7 days after infarction. Our results do not con- firm results of Bounds, 23 who found that in 100 cases of recent cerebral infarction 31% of the deaths were caused by transtentorial herniation with maximum at 1 to 2 days. The neuropathology of transtentorial herni- ation was, however, not described in their study. The great difference observed in the present study between cases of secondary brain stem hemorrhage in cerebral infarction with thrombosis in comparison with those without thrombosis, can only partly be ex- plained. As the extracranial arteries were not routinely dissected we have undoubtedly missed some of the thrombosis. The time of death after the acute attack in cases with demonstrated intracranial thrombosis ver- sus those without is broadly similar and it can hardly explain the difference. Impaired general circulation, including circulation within the brain stem, precluding development of sec- ondary brain stem hemorrhages in cases of infarction without thrombosis in the cerebral vessels might con- tribute to the difference, but in this material we have no evidence of such impairment of the general circula- tion. A possible explanation might be that the acute lesion has been larger in patients with proven arterial occlu- sion resulting in the development of more marked ede- ma and thus in a "larger space occupying lesion" and more pronounced transtentorial caudal herniation. Sex-related differences in the occurrence of secon- dary brain stem hemorrhages are a debated matter. Some authors reported higher frequency in men 4,7> 24 and one author in women. 6 The present study does not demonstrate a significant difference between the two sexes. Our results indicate paucity of secondary brain stem hemorrhage in very young persons, a finding which is in agreement with earlier investigations 6,7 - 25 The diminished frequency of secondary brain stem hemorrhages in young persons may be caused by a higher elasticity of the tissues. The tendency towards slightly decreased frequency of secondary brain stem hemorrhage in the very elderly (not significant) may be caused by cerebral tissue atrophy resulting in increased extracerebral space. Occipital lobe infarction is a well defined pathologi- cal entity, 25,26 secondary to increased supratentorial pressure. The condition results from a displacement of the posterior cerebral artery and the hippocampal gyrus through the tentorial notch following stretching and compression of the cortical branches of that artery against the tentorial edge. 24 The observed frequency (3.5%) of such cases is surprisingly high and has not been reported previously. No correlation was found between occipital lobe infarction and secondary brain stem hemorrhage. The main finding of the present study was that secondary brain stem hemorrhages were frequent in all three groups investigated. They are strongly correlated to transtentorial herniation and in- dicate major disturbances of the brain stem. It can be assumed that they have contributed significantly to the death of the patients. The present material does not allow to draw conclusions on differences in the cause of death among patients with and without secondary brain stem hemorrhage. References 1. Johnson RT, Yates PO: Clinicopathological aspects of pressure changes at the tentorium. Acta Radiol 46: 242-249, 1956 2. Scheinker IM: Transtentorial herniation of the brain stem: A char- acteristic clinicopathologic syndrome: Pathogenesis of hemor- rhages in brain stem. Arch Neurol Psychiat 53: 289-298, 1945 3. Schwarz GA, Rosner AA: Displacement and herniation of the hippocampal gyrus through the incisura tentorii. Arch Neurol Psy- chiat 46: 297-321 4. Cannon BW: Acute vascular lesions of the brain stem. Arch Neurol Psychiat 66: 687-696, 1951 5. Plum F, Posner JB: The diagnosis of stupor and coma. F. A. Davis Company, Philadelphia, 1982 6. Cohen SI, Aronson SM: Secondary brain stem hemorrhages. Arch Neurol 19: 257-263, 1968 7. Attwater HL: Pontine hemorrhages. Guy Hosp Rep 65: 339-389, 1911 8. Fields WS, Halpert B: Pontine hemorrhages in intracranial hyper- tension. Am J Pathol 29: 677-687, 1953 9. Lindenberg R: Compression of brain arteries as pathogenetic factor for tissue necroses and their areas of predilection. J Neuropath Exp Neurol 14: 223-243, 1955 10. Wolman L: Ischaemic lesions in the brain stem associated with raised supratentorial pressure. Brain 76: 364-377, 1955 11. Klintworth KG: Paratentorial grooving of human brains with par- by guest on June 2, 2014 http://stroke.ahajournals.org/ Downloaded from SECONDARY BRAIN STEM HEMORRHAGE IN STROKE/Nedergaard et al. 505 ticular reference to transtentorial herniation and the pathogenesis of secondary brain-stem hemorrhages. Am J Pathol S3: 391-399, 1968 12. Vincent C, David M, Thiebaut F: Le cone de pression temporal dans les tumeurs des hemispheres cerebraux. Sa symptomatolofie, sa gravite, les traitement qu'il convient du lui opposer. Rev Neurol (Paris) 65: 536-545, 1936 13. Van Gehuchten P: Le mechanisme de la mort dans certains cas de tumeur cerSbrale. Encephale 2: 113-127, 1937 14. Jefferson G: Tentorial pressure cone. Arch Neurol Psychiat (Chica- go) 40: 857-876, 1938 15. Poppen JL, Kendrick JFJR, Hicks SF: Brain stem hemorrhages secondary to supratentorial space-taking lesions. J Neuropath Exp Neurol 11: 267-279, 1952 16. Evans JP, Scheinker IM: Histologic studies of the brain following head trauma. Arch Neurol Psychiat (Chicago) 50: 258-278, 1943 17. Blackwood W, Corsellis JAN. Greenfield's Neuropathology. 3rd ed. London, Arnold, 1976, 121-124 18. Johnson RT, Yates PO: Brain stem haemorrhages in expanding supratentorial conditions. Acta Radiol (Stockholm) 46: 250-256, HEMIPARESIS OR HEMIPLEGIA without sensory, visual or speech deficit (Pure motor hemiparesis, PMH) is the classical presentation for lacunar infarc- tion in the internal capsule or basis pontis. 1 Other re- ported causes of this clinical syndrome include: in- farcts or cortical, 2 pyramidal 1,3 ' 4 or midbrain 5 location, metastases, 23 multiple sclerosis, 2 nocardial abscess, 6 post-craniotomy hemorrhage, 7 and hemorrhages in the basis pontis 8 or internal capsule. 2 ' 910 PMH has not been described in the setting of primary hypertensive putaminal hemorrhage. 11 - 12 This report documents, by detailed neurological evaluation in the acute stage, an instance of a syndrome of PMH in putaminal hem- orrhage. Case Report A 44 year old left-handed hypertensive male noticed right arm weakness and slurred speech after awakening on 8/8/82. He had no headache, nausea, vomiting or gait difficulties. Over the following 2 to 3 hours the right arm paresis worsened and a mild weakness of the From the Department of Neurology, University of South Alabama College of Medicine, Mobile, Alabama. Address correspondence to: Carlos S. Kase, M.D., Department of Neurology, University of South Alabama, 2451 Fillingim Street, Mo- bile, Alabama 36617. Received September 21, 1982: revision accepted December 20, 1982. 1956 19. Klinthworth GK: Evaluation of the role of neurosurgical procedure in the pathogenesis of secondary brain stem haemorrhage. J Neurol Neurosurg Psychiat 29: 423-425, 1966 20. Shaw C-M, Alvard EC Jr, Berry RG: Swelling of the brain follow- ing ischemic infarction with arterial occlusion. Arch Neurol 1: 161-177, 1959 21. Berry RG, Alpers BJ: Occlusion of the carotid circulation: Patho- logic considerations. Neurology (NY) 7: 223-237, 1957 22. Terent A et al.: Ischemic edema in stroke. Stroke 12: 33-39, 1981 23. Bounds JV et al: Mechanisms and timing of deaths from cerebral infarction. Stroke 12: 474-477, 1981 24. Finney LA, Walker AF: Transtentorial herniation. Springfield 111., Charles C Thomas, 1962 25. Sutherland S: The tentorial notch and complications produced by herniations of the brain through that aperture. Brit J Surg 45: 422- 438, 1958 26. Moore M, Stern K: Vascular lesions in the brain stem and occipital lobe occurring in association with brain tumors. Brain 61: 70-98, 1938 right leg developed. When examined 4 hours after the onset, he was alert, oriented, and gave an accurate description of the events leading to admission. His speech was dysarthric but free of dysphasia. The blood pressure was 220/130. Motor examination showed a moderate paresis of shoulder abduction and elbow flexion, with minimal weakness of distal movements. The lower extremity had slight paresis of foot dorsi- flexion, with intact proximal strength. The deep ten- don reflexes were slightly hyperactive in the right arm, and plantar reflexes were flexor. Coordination was intact bilaterally. Sensation was intact for touch and pin-prick in limbs, trunk and face. The slightest stimulation of indi- vidual hairs on the right limbs was felt normally and symmetrically. He did not extinguish to double simul- taneous tactile stimulation. Joint position and vibra- tory sense were intact. Stereognosis, barognosis and graphesthesia were normal and symmetric. Cranial nerve testing showed a marked right inferior facial palsy. Otherwise the examination showed full visual fields to single and double simultaneous stimuli, normal extraocular movements without gaze prefer- ence or nystagmus, reactive pupils of 2 mm diameter, intact facial sensation, preserved palate and tongue movements, and absence of bucco-lingual dyspraxia. CT scan on admission showed a small area of high attenuation (96 Hounsfield units) at the level of the left Hypertensive Putaminal Hemorrhage Presenting as Pure Motor Hemiparesis JORGE F. TAPIA, M.D., CARLOS S. KASE, M.D., RICHARD H. SAWYER, M.D. AND J. P. MOHR, M.D. SUMMARY A 44 year old hypertensive man presented with a pure motor hemiparesis, and CT scan showed a putaminal hemorrhage. The clinical course was characterized by rapid resolution of the deficits. This case illustrates a variety of putaminal hemorrhage of good functional and vital prognosis, and stresses the value of CT scanning as a tool for diagnosis and prognosis. Stroke, Vol 14, No 4, 1983 by guest on June 2, 2014 http://stroke.ahajournals.org/ Downloaded from