Journal of
J. Neurol. 216, 227--233 (1977)
Neurology © by Springer-Verlag 1977
Residual Lesions of Cerebral Fat Embolism A. R. von Hochstetter and R. L. Friede Neuropathologische Abteilung des Institutes fOx Pathologie der Universit~t Zoxich, Kantonsspital, Schmelzbergstr. 12, CH-8000 Zoxich, Switzerland
Summary. Necropsy findings of a case which survived for three months after massive cerebral fat embolism are presented. The lesions are charcterized by numerous patchy necroses and areas of demyelination in the white matter of cerebral and cerebellar hemispheres and brain stem, accompanied by atrophy of white matter and ventricular enlargement. Attention is drawn to the significance of these lesions for posttraumatic coma or dementia. Key words: Atrophy of white matter - Cerebral fat embolism - Coma, posttraumatic - Dementia, posttraumatic - Demyelination - Residual lesions of cerebral fat embolism - Ventricular enlargement.
Zusammenfassung. Ein Fall von Sp~itl~isionen nach massiver zerebraler Fettembolie zeigt zahlreiche fleckf~Srmige Nekrosen und Zonen yon Demyelinisierung der weifSen Substanz der GroBhirn- und Kleinhirnhemisph~iren und des Hirnstammes. A u f die Bedeutung dieser L~isionen for die Entstehung eines posttraumatischen C o m a oder posttraumatischen Demenz wird hingewiesen.
Introduction It seems paradoxical that the high frequency of posttraumtic fat embolism should yield so few cases in which late sequelae are observed. In a large series [2] embolicaUy dispersed fat was found in 16.3% of all deaths caused by trauma; other authors [8] quote figures up to 24%. Cerebral fat embolism, however, carries a high mortality rate, especially when associated with coma [15, 10]; patients either succumb within days of injury or recover and are subsequently lost to detailed psychological, neurological or neuropathological follow-up. The present report concerns the necropsy findings in a patient who survived for three months.
228
A.R. von Hochstetter and R. L. Friede
Case Report A woman, aged 48 years, was in an automobile accident on October 9th, 1975; no details concerning the nature of the accident are available. On admission to the Cantonal Hospital Schwyz she complained of severe pain in the lower abdomen and right thigh. There were no external signs of trauma to the head. Blood pressure was 120/95, pulse 100, respirations regular. Neurological examination was within normal limits. X-rays revealed multiple fractures of the pelvic girdle and right femur. Due to a rapidly progressive worsening of the patient's state of consciousness, she was transferred the following day to the Surgical Clinic B of the University Hospital Ziirich. On admission, the patient was unconscious without response to pain. Blood pressure was 110/80, pulse I00, temperature between 38--39°C. A Babinski reflex was easily elicited on the left. The skin of the anterior thorax and shoulders was stippled with multiple petechial hemorrhages. X-rays confirmed fractures of pelvis, femur and right shoulder blade; there were patchy infiltrates in the upper and middle lung fields, thought to be compatible with massive fat emboli. The patient was transferred to the Intensive Care Unit for cardiovascular, respiratory and neurological surveillance and treatment undertaken for fat embolism, incumbent shock and orthopedic problems. Her respiratory insufficiency with low arterial blood gases necessitated mechanical assistance with an Engstrom respirator. The patient subsequently developed severe bilateral pneumonia from which Pseudomonas aeruginosa, staph, aureus and Klebsiella pneumoniae were cultured; there were clinical signs of septic shock and an intermittent bleeding disorder of the lower GI tract with reduced thrombocyte counts and prothrombin times. Gastrostomy, tracheostomy and osteosynthesis of the femoral fractures were performed. By the end of December the patient seemed awake but remained unresponsive. Three EEGs showed bilateral synchronous slowing consistent with a non-specific encephalopathy and brain stem damage, with slow amelioration on successive readings. Respirations were spontaneous and arterial blood gases almost within normal limits. There were periods of tachypnea and bronchial spasm. Kidney function was satisfactory and electrolytes, BUN and creatinine within normal limits. The cardiavascular system seemed relatively stable but failed suddenly, and the patient expired on January 3rd, 1976.
Pathological Findings G e n e r a l necropsy revealed severe b r o n c h o p n e u m o n i a with p u l m o n a r y edema, n o d u l a r hyperplasia of b o t h a d r e n a l cortices a n d n o d u l a r goiter. The multiple fractures involving the right femur, pelvis a n d right shoulder blade were confirmed. The skull was intact. Brain weight after fixation was 1320 g, of which the supratentorial part was 1150 g. Both hemispheres, cerebellum a n d b r a i n stem were u n r e m a r k a b l e in size a n d shape a n d enveloped b y t r a n s l u c e n t leptomeninges. The m a j o r vessels of the base were n o r m a l in c o n f i g u r a t i o n , free of atherosclerosis a n d patent. No h e r n i a t i o n s or other signs of increased i n t r a c r a n i a l pressure were noted, a n d n o t r a u m a t i c lesions could be indentified. C o r o n a l sections revealed m a r k e d a n d u n i f o r m dilatation of the ventricular system (Fig. 1): the greatest transverse diameter of the lateral ventricles at the level of the f o r a m e n of M o n r o measured 62 m m , that of the third ventricle 12 m m , while the height of the septum pellucidum, from corpus callosum to anterior c o m m i s s u r e , was 20 mm. Cerebral cortex a n d basal ganglia were u n r e m a r k a b l e . The white m a t t e r showed multiple patches of gray discoloration up to several m m in d i m e n s i o n . These were particularly m a r k e d in the periventricular white
Residual Lesions of Cerebral Fat Embolism
229
Fig. 1. Coronal sections revealing discrete areas of gray discoloration and marked ventricular enlargement
matter of the frontal lobes, less in the occipital lobes; larger confluent grayish areas were noted within the corona radiata. The tectum and tegmentum of the brain stem were diffusely discolored, the lesions being most marked in the pontine tegmenturn and sharply demarcated from the pontine base. More caudally, the discoloration was again more patchy, affecting the lateral subependymal regions within the medulla oblongata in particular. No pathological findings were noted within the lower oblongata or cerebellum. Microscopic examination revealed an abundance of foci of demyelination with or without necrosis, scattered thoughout the white matter of the cerebrum, cerebellum and brain stem. In some instances the lesions were perivascular, but for some no relation between focus and vessels was evident. Most perivascular lesions were filled with lipid-laden gitter cells (Fig. 2), while others presented as microscopic scars containing astrocytes and some microglial
230
A.R. von Hochstetter and R. L. Friede
Fig. 2. Typical focus of necrosis in cerebral white matter with gitter cells and glial reaction. HE, 160x
Fig. 3. Patchy areas of demyelination in cerebral white matter; myelin stain 25 ×
Residual Lesions of Cerebral Fat Embolism
231
cells. Occasionally minute clusters of hemosiderin-laden macrophages were noted. Elsewhere multiple demyelinated foci (Fig. 3) in no obvious vicinity to vessels displayed various degrees of myelin disruption, interstitial vacuolation and accumulation of gitter cells with proportional damage to axis cylinders. Only few blunted ends of disrupted nerve fibers or retraction balls were noted. In addition there were widely distributed ill-defined zones of diminished myelin staining that corresponded to the gray discoloration seen on gross inspection. At the level of the pyramids the corticospinal tracts showed widespread early myelin fragmentation. The cortical architecture was generally well preserved; one evidently recent cortical focus consisted of perivascular and interstitial infiltration by polymorphonuclear leukocytes. Ammon's horn was unremarkable. A slit-like microinfarct in the head of one caudate nucleus displayed cavitation, gitter cells and glial proliferation. Findings in blood vessels were diappointing. Sudanophilic droplets or granules were at times suspected within capillary endothelial cells, but their precise location could not be established. A few intra and parafocal vessels associated with the more recent lesions exhibited a moderate endothelial reaction, but no intraluminal fat could be demonstrated. Some of the lenticulostriate arterioles had granular calcium deposits within their walls.
Discussion
In a comprehensive study of systemic fat embolism, Sevitt [10] distinguishes three clinical patterns: the fulminating course has rapid onset of cerebral symptoms leading to early coma and death; the posttraumatic period is so short that it may never be witnessed. The complete or classical course displays an asymptomatic interval, followed typically within 48 h [1] by symptoms of cerebral dysfunction, mostly stupor or coma with or without neurological deficits, respiratory distress and a petechial rash, characteristic in appearance and distribution. In addition, tachycardia and pyrexia are usual. The third course comprises incomplete or partial syndromes in which one or more of the typical manifestations may be absent. Of undisputed importance is the symptom-free interval between injury and cerebral signs [15, 5, 10]. Hence on clinical grounds there is littel doubt that our p a t i e n t manifested the complete or classical syndrome of systemic fat embolism. A recurrent problem in the interpretation of fat embolism is the difficulty in correlating the clincial syndrome of pulmonary a n d / o r cerebral dysfunction with the patho-anatomic entity of fat globules within the vascular lumen. Indeed, as the survival time of fat emboli is in the order of a few weeks [3, 14] the demonstration of intraluminal fat droplets in the protracted case remains fruitless. Hence, clinicopathological correlation must rely on the interpretation of clinical data and morphological features of lesions. The mental and neurological changes in our patient could have been brought on by a variety of other cerebral and extracerebral conditions, particularly
232
A.R. von Hochstetter and R. L. Friede
hypotensive shock or a hypoxic crisis. Indeed hypotensive shock may occur within a few hours of injury and may compound the severity of fat embolism [2, 4, 13] although the two entities are certainly distinct [7, 13]. However, there were no significant lesions in the gray matter, particularly no evidence of anoxic encephalopathy. In addition, other causes of multifocal cerebral ischemia or anoxic lesions should be considered. Among them, hypertensive encephalopathy, widespread small vessel occlusion of hypercoagulable states, or specific anglopathies may create micronecrotic lesions. However, these do not show predilection for white matter, and such diseases may readily be eliminated on clinical grounds. Septic embolization or disseminated colonization during bouts of bacteremia should have left residual lesions in other organs, and the brain typically shows larger infarcts as well as abscesses. Our patient did have a bleeding disorder but the absence of larger residual hematomas and of appreciable accumulations of cerebral perivascular hemosiderin make the possibility of disseminated intravascular coagulation unlikely. Areas of demyelination following trauma have been described by Strich [11, 12] who incriminates stretching and tearing of nerve fibers and blood vessels throughout the brain as a consequence of shearing strains and distortions in head injuries accompanied by rotation. In all her cases the physical damage to the nervous system produced permanent abnormal neurological signs upon or almost immediately after injury. The typical morphological alteration consisted of widespread and diffuse degeneration of white matter in cerebral hemispheres and brain stem. Our case differs in two respects: delayed onset of mental or neurological signs and multifocal disposition of the lesions. In view of the patient's clinical history and the pattern of her lesions congruent with the one seen in acute cases of fat embolism, there is little doubt then that the multifocal demyelination was the result of showers of fat emboli disseminated subsequent to her accident. Sequelae of embolically dispersed fat are probably much more fequent than reported [ 10]. However, detailed psychological and neurological follow-up is rare and there is little neuropathological information on the residual lesions. A case described by Sarbo [9] focuses on the peculiar clinical evolution over ten months, characterized by the picture of general paresis. The patient's subsequent recovery, however, withdrew him from neuropathological scrutiny. Sevitt cites Silverstein's case of choreoathetoid movements following a fracture of the hip in a 65 year old w o m a n who survived five months. Necropsy revealed selective bilateral demyelination with necrosis of the globus pallidus also involving the substantia nigra. Fat globules were reportedly present in cortical vessels but not in the softened areas. However, the distinction between intraluminal and intraendothelial fat could not be made, and there was the question whether the patient did not suffer intraoperative cerebral anoxia. In a survivor of thirty-four days Koenig [5] found few remaining intraluminal fat emboli, but many perivascular foci in various degenerative, resorptive and reparative stages, particularly in the white matter. McTaggert and Neubuerger [6] describe the case of a 52 year old male who sustained fractures of extremities, pelvis and vertebrae accompanied by an initial period of hypovolemic shock. After 18 h he developed clinical signs of cerebral fat emboli and slid into coma from which he recovered slowly. Four months
Residual Lesions of Cerebral Fat Embolism
233
following the i n j u r y he was m o r e alert b u t u n a b l e to talk; three years l a t e r he was able to w a l k with little assitance b u t c o u l d n o t dress himself. H e was d y s a r t h r i c , distractible a n d d i s o r i e n t a t e d a n d p r o d u c e d a v e r b a l I Q o f 63. H e d i e d o f u n r e l a t e d causes seven y e a r s after his injury. N e u r o p a t h o l o g i c a l e x a m i n a t i o n r e v e a l e d i r r e g u l a r foci a n d p a t c h e s o f d e m y e l i n a t i o n o f v a r i o u s degrees in b o t h central a n d c o n v o l u t i o n a l white m a t t e r with a m i n i m a l astroglial a n d m i c r o g l i a l p r o l i f e r a t i o n . F i b r o t i c changes in small vessels were a s c r i b e d to o l d d a m a g e to t h e i r wails, p o s s i b l y b y fat e m b o l i . R e s i d u a l lesions o f g r a y m a t t e r c o u l d n o t be d e m o n s t r a t e d c o n v i n c i n g l y a n d the a u t h o r s surmise t h a t "chances o f survival a r e b e t t e r if the lesions are m o r e o r less limited to the white m a t t e r " . It is o f interest t h a t the e v o l u t i o n o f m e n t a l f u n c t i o n in the cases r e p o r t e d b y M c T a g g e r t a n d N e u b u e r g e r , Strich, as well as in the p r e s e n t one, p r o g r e s s e d t o w a r d d e m e n t i a r a t h e r t h a n p r o l o n g e d c o m a . I n time such p a t i e n t s m a y manifest a clear difference b e t w e e n the w a k i n g a n d the sleeping states, a n d chewing, swallowing a n d even b l i n k i n g in r e s p o n s e to m e n a c e m a y be p r e s e r v e d [11]. K o e n i g [5] also s p e a k s o f r e d u c e d p e r s o n a l i t y . T h e a n a t o m i c a l s u b s t r a t e in all o f these p a t i e n t s was n o t c o r t i c a l d a m a g e b u t a severe, either focal o r diffuse d e m y e l i n a t i o n o f white m a t t e r .
References 1. Alldred, A. J.: Fat embolism with a report of 9 cases. Brit. J. Surg. 41, 82--87 (1953) 2. Fuchsig, P., Brucke, P., Blumel, G., Gottlob, R.: A new clinical and experimentalconcept on fat embolism. N. Engl. J. Med. 276, 1192--1193 (1967) 3. Halasz, N. A., Marasco, J. P.: Experimental study of fat embolism. Surgery 41, 921--929 (1957) 4. Harman, J. W., Ragaz, F. J.: Pathogenesis of experimental fat embolism. Amer. J. Path. 26, 551--563 (1950) 5. Koenig, P.-A.: Beitrag zur protrahierten Fettembolie. Mschr. Unfallheilk. 59, 289--294 (1956) 6. McTaggert, D. M., Neubuerger, K. T.: Cerebral fat embolism: Pathologic changes in the brain after survival of 7 years. Acta Neuropath. (Bed.) 15, 183--187 (1970) 7. Morton, K. S., Murjar, M. P.: Hemorrhagic shock and fat embolism: A clinical and experimental study. J. Trauma 4, 687--691 (1964) 8. Saldeen, T.: Fat embolism and signs of intravascular coagulation in a posttraumatic autopsy material. J. Trauma 10, 273--286 (1970) 9. Sarbo, A. v.: Ein geheilter Fall yon Fettembolie des Gehirns nach Unterschenkelbruch, im Bilde der progressiven Paralyse verlaufend. Klin. Wschr. 4, 1918--1920 (1925) 10. Sevitt, S.: Fat Embolism. London: Butterworths 1962 11. Strich, S. J.: Shearing of nerve fibers as a cause of brain damage due to head injury: A pathologic study of 20 cases. Lancet 1961 II, 443 448 12. Strich, S. J.: Lesions in the cerebral hemispheres after blunt head injury. J. Clin. Path. 23, Suppl. (Roy. Coll. Path.), 4, 166---171 (1970) 13. Tedeschi, C. G., Walter, C. E., Tedeschi, L. G.: Shock and fat embolism: An appraisal. Surg. Clin. N. Amer. 48, 431--453 (1968) 14. Whiteley, H. J.: Relationship between tissue injury and the manifestations of pulmonary fat embolism. J. Path. Bact. 67, 521--530 (1954) 15. Winkelman, N. W.: Cerebral fat embolism: A clinico-pathologic study of 2 cases. Arch. Neurol. Psychiat. 47, 57--76 (1942) Received February 15, 1977
J. Neurol. 216, 227--233 (1977)
Neurology © by Springer-Verlag 1977
Residual Lesions of Cerebral Fat Embolism A. R. von Hochstetter and R. L. Friede Neuropathologische Abteilung des Institutes fOx Pathologie der Universit~t Zoxich, Kantonsspital, Schmelzbergstr. 12, CH-8000 Zoxich, Switzerland
Summary. Necropsy findings of a case which survived for three months after massive cerebral fat embolism are presented. The lesions are charcterized by numerous patchy necroses and areas of demyelination in the white matter of cerebral and cerebellar hemispheres and brain stem, accompanied by atrophy of white matter and ventricular enlargement. Attention is drawn to the significance of these lesions for posttraumatic coma or dementia. Key words: Atrophy of white matter - Cerebral fat embolism - Coma, posttraumatic - Dementia, posttraumatic - Demyelination - Residual lesions of cerebral fat embolism - Ventricular enlargement.
Zusammenfassung. Ein Fall von Sp~itl~isionen nach massiver zerebraler Fettembolie zeigt zahlreiche fleckf~Srmige Nekrosen und Zonen yon Demyelinisierung der weifSen Substanz der GroBhirn- und Kleinhirnhemisph~iren und des Hirnstammes. A u f die Bedeutung dieser L~isionen for die Entstehung eines posttraumatischen C o m a oder posttraumatischen Demenz wird hingewiesen.
Introduction It seems paradoxical that the high frequency of posttraumtic fat embolism should yield so few cases in which late sequelae are observed. In a large series [2] embolicaUy dispersed fat was found in 16.3% of all deaths caused by trauma; other authors [8] quote figures up to 24%. Cerebral fat embolism, however, carries a high mortality rate, especially when associated with coma [15, 10]; patients either succumb within days of injury or recover and are subsequently lost to detailed psychological, neurological or neuropathological follow-up. The present report concerns the necropsy findings in a patient who survived for three months.
228
A.R. von Hochstetter and R. L. Friede
Case Report A woman, aged 48 years, was in an automobile accident on October 9th, 1975; no details concerning the nature of the accident are available. On admission to the Cantonal Hospital Schwyz she complained of severe pain in the lower abdomen and right thigh. There were no external signs of trauma to the head. Blood pressure was 120/95, pulse 100, respirations regular. Neurological examination was within normal limits. X-rays revealed multiple fractures of the pelvic girdle and right femur. Due to a rapidly progressive worsening of the patient's state of consciousness, she was transferred the following day to the Surgical Clinic B of the University Hospital Ziirich. On admission, the patient was unconscious without response to pain. Blood pressure was 110/80, pulse I00, temperature between 38--39°C. A Babinski reflex was easily elicited on the left. The skin of the anterior thorax and shoulders was stippled with multiple petechial hemorrhages. X-rays confirmed fractures of pelvis, femur and right shoulder blade; there were patchy infiltrates in the upper and middle lung fields, thought to be compatible with massive fat emboli. The patient was transferred to the Intensive Care Unit for cardiovascular, respiratory and neurological surveillance and treatment undertaken for fat embolism, incumbent shock and orthopedic problems. Her respiratory insufficiency with low arterial blood gases necessitated mechanical assistance with an Engstrom respirator. The patient subsequently developed severe bilateral pneumonia from which Pseudomonas aeruginosa, staph, aureus and Klebsiella pneumoniae were cultured; there were clinical signs of septic shock and an intermittent bleeding disorder of the lower GI tract with reduced thrombocyte counts and prothrombin times. Gastrostomy, tracheostomy and osteosynthesis of the femoral fractures were performed. By the end of December the patient seemed awake but remained unresponsive. Three EEGs showed bilateral synchronous slowing consistent with a non-specific encephalopathy and brain stem damage, with slow amelioration on successive readings. Respirations were spontaneous and arterial blood gases almost within normal limits. There were periods of tachypnea and bronchial spasm. Kidney function was satisfactory and electrolytes, BUN and creatinine within normal limits. The cardiavascular system seemed relatively stable but failed suddenly, and the patient expired on January 3rd, 1976.
Pathological Findings G e n e r a l necropsy revealed severe b r o n c h o p n e u m o n i a with p u l m o n a r y edema, n o d u l a r hyperplasia of b o t h a d r e n a l cortices a n d n o d u l a r goiter. The multiple fractures involving the right femur, pelvis a n d right shoulder blade were confirmed. The skull was intact. Brain weight after fixation was 1320 g, of which the supratentorial part was 1150 g. Both hemispheres, cerebellum a n d b r a i n stem were u n r e m a r k a b l e in size a n d shape a n d enveloped b y t r a n s l u c e n t leptomeninges. The m a j o r vessels of the base were n o r m a l in c o n f i g u r a t i o n , free of atherosclerosis a n d patent. No h e r n i a t i o n s or other signs of increased i n t r a c r a n i a l pressure were noted, a n d n o t r a u m a t i c lesions could be indentified. C o r o n a l sections revealed m a r k e d a n d u n i f o r m dilatation of the ventricular system (Fig. 1): the greatest transverse diameter of the lateral ventricles at the level of the f o r a m e n of M o n r o measured 62 m m , that of the third ventricle 12 m m , while the height of the septum pellucidum, from corpus callosum to anterior c o m m i s s u r e , was 20 mm. Cerebral cortex a n d basal ganglia were u n r e m a r k a b l e . The white m a t t e r showed multiple patches of gray discoloration up to several m m in d i m e n s i o n . These were particularly m a r k e d in the periventricular white
Residual Lesions of Cerebral Fat Embolism
229
Fig. 1. Coronal sections revealing discrete areas of gray discoloration and marked ventricular enlargement
matter of the frontal lobes, less in the occipital lobes; larger confluent grayish areas were noted within the corona radiata. The tectum and tegmentum of the brain stem were diffusely discolored, the lesions being most marked in the pontine tegmenturn and sharply demarcated from the pontine base. More caudally, the discoloration was again more patchy, affecting the lateral subependymal regions within the medulla oblongata in particular. No pathological findings were noted within the lower oblongata or cerebellum. Microscopic examination revealed an abundance of foci of demyelination with or without necrosis, scattered thoughout the white matter of the cerebrum, cerebellum and brain stem. In some instances the lesions were perivascular, but for some no relation between focus and vessels was evident. Most perivascular lesions were filled with lipid-laden gitter cells (Fig. 2), while others presented as microscopic scars containing astrocytes and some microglial
230
A.R. von Hochstetter and R. L. Friede
Fig. 2. Typical focus of necrosis in cerebral white matter with gitter cells and glial reaction. HE, 160x
Fig. 3. Patchy areas of demyelination in cerebral white matter; myelin stain 25 ×
Residual Lesions of Cerebral Fat Embolism
231
cells. Occasionally minute clusters of hemosiderin-laden macrophages were noted. Elsewhere multiple demyelinated foci (Fig. 3) in no obvious vicinity to vessels displayed various degrees of myelin disruption, interstitial vacuolation and accumulation of gitter cells with proportional damage to axis cylinders. Only few blunted ends of disrupted nerve fibers or retraction balls were noted. In addition there were widely distributed ill-defined zones of diminished myelin staining that corresponded to the gray discoloration seen on gross inspection. At the level of the pyramids the corticospinal tracts showed widespread early myelin fragmentation. The cortical architecture was generally well preserved; one evidently recent cortical focus consisted of perivascular and interstitial infiltration by polymorphonuclear leukocytes. Ammon's horn was unremarkable. A slit-like microinfarct in the head of one caudate nucleus displayed cavitation, gitter cells and glial proliferation. Findings in blood vessels were diappointing. Sudanophilic droplets or granules were at times suspected within capillary endothelial cells, but their precise location could not be established. A few intra and parafocal vessels associated with the more recent lesions exhibited a moderate endothelial reaction, but no intraluminal fat could be demonstrated. Some of the lenticulostriate arterioles had granular calcium deposits within their walls.
Discussion
In a comprehensive study of systemic fat embolism, Sevitt [10] distinguishes three clinical patterns: the fulminating course has rapid onset of cerebral symptoms leading to early coma and death; the posttraumatic period is so short that it may never be witnessed. The complete or classical course displays an asymptomatic interval, followed typically within 48 h [1] by symptoms of cerebral dysfunction, mostly stupor or coma with or without neurological deficits, respiratory distress and a petechial rash, characteristic in appearance and distribution. In addition, tachycardia and pyrexia are usual. The third course comprises incomplete or partial syndromes in which one or more of the typical manifestations may be absent. Of undisputed importance is the symptom-free interval between injury and cerebral signs [15, 5, 10]. Hence on clinical grounds there is littel doubt that our p a t i e n t manifested the complete or classical syndrome of systemic fat embolism. A recurrent problem in the interpretation of fat embolism is the difficulty in correlating the clincial syndrome of pulmonary a n d / o r cerebral dysfunction with the patho-anatomic entity of fat globules within the vascular lumen. Indeed, as the survival time of fat emboli is in the order of a few weeks [3, 14] the demonstration of intraluminal fat droplets in the protracted case remains fruitless. Hence, clinicopathological correlation must rely on the interpretation of clinical data and morphological features of lesions. The mental and neurological changes in our patient could have been brought on by a variety of other cerebral and extracerebral conditions, particularly
232
A.R. von Hochstetter and R. L. Friede
hypotensive shock or a hypoxic crisis. Indeed hypotensive shock may occur within a few hours of injury and may compound the severity of fat embolism [2, 4, 13] although the two entities are certainly distinct [7, 13]. However, there were no significant lesions in the gray matter, particularly no evidence of anoxic encephalopathy. In addition, other causes of multifocal cerebral ischemia or anoxic lesions should be considered. Among them, hypertensive encephalopathy, widespread small vessel occlusion of hypercoagulable states, or specific anglopathies may create micronecrotic lesions. However, these do not show predilection for white matter, and such diseases may readily be eliminated on clinical grounds. Septic embolization or disseminated colonization during bouts of bacteremia should have left residual lesions in other organs, and the brain typically shows larger infarcts as well as abscesses. Our patient did have a bleeding disorder but the absence of larger residual hematomas and of appreciable accumulations of cerebral perivascular hemosiderin make the possibility of disseminated intravascular coagulation unlikely. Areas of demyelination following trauma have been described by Strich [11, 12] who incriminates stretching and tearing of nerve fibers and blood vessels throughout the brain as a consequence of shearing strains and distortions in head injuries accompanied by rotation. In all her cases the physical damage to the nervous system produced permanent abnormal neurological signs upon or almost immediately after injury. The typical morphological alteration consisted of widespread and diffuse degeneration of white matter in cerebral hemispheres and brain stem. Our case differs in two respects: delayed onset of mental or neurological signs and multifocal disposition of the lesions. In view of the patient's clinical history and the pattern of her lesions congruent with the one seen in acute cases of fat embolism, there is little doubt then that the multifocal demyelination was the result of showers of fat emboli disseminated subsequent to her accident. Sequelae of embolically dispersed fat are probably much more fequent than reported [ 10]. However, detailed psychological and neurological follow-up is rare and there is little neuropathological information on the residual lesions. A case described by Sarbo [9] focuses on the peculiar clinical evolution over ten months, characterized by the picture of general paresis. The patient's subsequent recovery, however, withdrew him from neuropathological scrutiny. Sevitt cites Silverstein's case of choreoathetoid movements following a fracture of the hip in a 65 year old w o m a n who survived five months. Necropsy revealed selective bilateral demyelination with necrosis of the globus pallidus also involving the substantia nigra. Fat globules were reportedly present in cortical vessels but not in the softened areas. However, the distinction between intraluminal and intraendothelial fat could not be made, and there was the question whether the patient did not suffer intraoperative cerebral anoxia. In a survivor of thirty-four days Koenig [5] found few remaining intraluminal fat emboli, but many perivascular foci in various degenerative, resorptive and reparative stages, particularly in the white matter. McTaggert and Neubuerger [6] describe the case of a 52 year old male who sustained fractures of extremities, pelvis and vertebrae accompanied by an initial period of hypovolemic shock. After 18 h he developed clinical signs of cerebral fat emboli and slid into coma from which he recovered slowly. Four months
Residual Lesions of Cerebral Fat Embolism
233
following the i n j u r y he was m o r e alert b u t u n a b l e to talk; three years l a t e r he was able to w a l k with little assitance b u t c o u l d n o t dress himself. H e was d y s a r t h r i c , distractible a n d d i s o r i e n t a t e d a n d p r o d u c e d a v e r b a l I Q o f 63. H e d i e d o f u n r e l a t e d causes seven y e a r s after his injury. N e u r o p a t h o l o g i c a l e x a m i n a t i o n r e v e a l e d i r r e g u l a r foci a n d p a t c h e s o f d e m y e l i n a t i o n o f v a r i o u s degrees in b o t h central a n d c o n v o l u t i o n a l white m a t t e r with a m i n i m a l astroglial a n d m i c r o g l i a l p r o l i f e r a t i o n . F i b r o t i c changes in small vessels were a s c r i b e d to o l d d a m a g e to t h e i r wails, p o s s i b l y b y fat e m b o l i . R e s i d u a l lesions o f g r a y m a t t e r c o u l d n o t be d e m o n s t r a t e d c o n v i n c i n g l y a n d the a u t h o r s surmise t h a t "chances o f survival a r e b e t t e r if the lesions are m o r e o r less limited to the white m a t t e r " . It is o f interest t h a t the e v o l u t i o n o f m e n t a l f u n c t i o n in the cases r e p o r t e d b y M c T a g g e r t a n d N e u b u e r g e r , Strich, as well as in the p r e s e n t one, p r o g r e s s e d t o w a r d d e m e n t i a r a t h e r t h a n p r o l o n g e d c o m a . I n time such p a t i e n t s m a y manifest a clear difference b e t w e e n the w a k i n g a n d the sleeping states, a n d chewing, swallowing a n d even b l i n k i n g in r e s p o n s e to m e n a c e m a y be p r e s e r v e d [11]. K o e n i g [5] also s p e a k s o f r e d u c e d p e r s o n a l i t y . T h e a n a t o m i c a l s u b s t r a t e in all o f these p a t i e n t s was n o t c o r t i c a l d a m a g e b u t a severe, either focal o r diffuse d e m y e l i n a t i o n o f white m a t t e r .
References 1. Alldred, A. J.: Fat embolism with a report of 9 cases. Brit. J. Surg. 41, 82--87 (1953) 2. Fuchsig, P., Brucke, P., Blumel, G., Gottlob, R.: A new clinical and experimentalconcept on fat embolism. N. Engl. J. Med. 276, 1192--1193 (1967) 3. Halasz, N. A., Marasco, J. P.: Experimental study of fat embolism. Surgery 41, 921--929 (1957) 4. Harman, J. W., Ragaz, F. J.: Pathogenesis of experimental fat embolism. Amer. J. Path. 26, 551--563 (1950) 5. Koenig, P.-A.: Beitrag zur protrahierten Fettembolie. Mschr. Unfallheilk. 59, 289--294 (1956) 6. McTaggert, D. M., Neubuerger, K. T.: Cerebral fat embolism: Pathologic changes in the brain after survival of 7 years. Acta Neuropath. (Bed.) 15, 183--187 (1970) 7. Morton, K. S., Murjar, M. P.: Hemorrhagic shock and fat embolism: A clinical and experimental study. J. Trauma 4, 687--691 (1964) 8. Saldeen, T.: Fat embolism and signs of intravascular coagulation in a posttraumatic autopsy material. J. Trauma 10, 273--286 (1970) 9. Sarbo, A. v.: Ein geheilter Fall yon Fettembolie des Gehirns nach Unterschenkelbruch, im Bilde der progressiven Paralyse verlaufend. Klin. Wschr. 4, 1918--1920 (1925) 10. Sevitt, S.: Fat Embolism. London: Butterworths 1962 11. Strich, S. J.: Shearing of nerve fibers as a cause of brain damage due to head injury: A pathologic study of 20 cases. Lancet 1961 II, 443 448 12. Strich, S. J.: Lesions in the cerebral hemispheres after blunt head injury. J. Clin. Path. 23, Suppl. (Roy. Coll. Path.), 4, 166---171 (1970) 13. Tedeschi, C. G., Walter, C. E., Tedeschi, L. G.: Shock and fat embolism: An appraisal. Surg. Clin. N. Amer. 48, 431--453 (1968) 14. Whiteley, H. J.: Relationship between tissue injury and the manifestations of pulmonary fat embolism. J. Path. Bact. 67, 521--530 (1954) 15. Winkelman, N. W.: Cerebral fat embolism: A clinico-pathologic study of 2 cases. Arch. Neurol. Psychiat. 47, 57--76 (1942) Received February 15, 1977
