17. Kaye BR Rheumablogicmanif&tiom of infection with human immunodeficiency virus (IITV).Ann Intern Med 1989,111:158-167. 18. Edelman AS, Zolla-PaznerS. AIDS: a syndrome of immune dysregulation, dysfunction, and deficiency. FASEB J 1989;3:22-30. 19. Drew WL. Other virus infections in AIDS. 1. Cytomegalovirus. In: Levy JA, ed. AIDS pathogenesis and treatment. New York: Dekker, 1989:507-533. 20. Mintz L, Drew WL, Miner RC, Braff EH. Cytomegalovirus infections in homosexual men: an epidemiologicalstudy. Ann Intern Med 1983;99:326-329. 21. P e w Ph, Amott G, Fortier B, et aL Syndmme de Guillain et Barre d’evolutionfavorable dans un cas #infection recente par le virus
de l’immunodi?ficience humaine. Rev Neurol (Paris) 1988;14432-35. 22. Lanska MJ, Lanska DJ, SchmidleyJW.Syphilitic polyradiculopathy in an HIV-positive man. Neurology 1988;38:1297-1301. 23. Comblath DFt, McArthur JC. Pdominantly sensory newpathy in patients with AIDS and AIDS-related complex. Neurology 1988;38:794-796. 24. Leger JM, Bouche P, Bolgert F, et al. The spectrum of polyneuropathiesin patients infected with HIV. J Neurol Neurosurg Psychiatry 1989;52:1369-1374. 25. Conlon CP. HIV infection presenting as Guillain-Barrksyndrome in Lusaka, Zambia. Trans R SOCTrop Med Hyg 1989;83:109.
Cerebrovascular complications after orthotopic liver transplantation: A clinicopathologic study Conrado J. Estol, MD; Michael S. Pessin, MD; and A. Julio Martinez, MD Article abstract-We analyzed 55 autopsy cases in 1,357 patients undergoing orthotopic liver transplantation at the University of Pittsburgh and found that 13 (23.6%)patients had intracranial bleeding, and five (9%) had infarcts. Eight patients had bleeding localized to one intracranial compartment: intracerebral hemorrhage (three patients); subarachnoid hemorrhage (three patients); and subdural hematoma (two patients). Five patients had combinations of multiple sites of bleeding: three with subarachnoid hemorrhage-intracerebral hemorrhage, one with subarachnoid hemorrhage-intracerebral hemorrhage-subdural hematoma, and one with subdural hematoma-intracerebral hemorrhage. Coexistent CNS infections (fungal or bacterial) were associated with hemorrhagic infarcts and intracerebral hemorrhage in four patients. Cerebral embolism and hemorrhagic infarction from bacterial endocarditis occurred in one patient. Five patients died of intracranial bleeding. Severe coagulopathy was the major cause of intracranial bleeding and was associated with systemic bleeding in 12 patients. Significant systemic or metabolic complications were present in all patients and masked the focal signs of the intracranial process in more than one half. NEUROLOGY 1991;41:815-819
Neurologic complications are important causes of morbidity and mortality following orthotopic (implantation of the new organ in place of the old) liver transplantations (OLTx).l In previous rep0rts,2>~ we emphasized the high frequency of central pontine myelinolysis (CPM) and seizures after OLTx. We herein report the cerebrovascular complications after OLTx. Methods. From January 1981 to December 1987, 1,357 patients had OLTx at the University Health Center of Pittsburgh (UHCP). Eight hundred sixty-seven were adults. Of those who died, 118 had autopsies but only 55 had complete neuropathologic examinations. Of these 55, 17 (31%) had intracranial bleeding or cerebral infarction. Patients with global cerebral ischemia were excluded. One with intracranial trauma from a motor vehicle accident was also excluded. The 17 patients included nine men and eight women ranging in age from 19 to 55 years (average, 34 years) (table).Eleven patients
had one transplant, five had two, and one had three. The survival time after OLTx ranged from 0 to 80 days: two patients survived 0 to 5 days, six survived 6 to 30 days, seven survived 31 to 60 days, and two survived 60 to 80 days. The etiologies of liver failure in these 17 patients included chronic hepatitis (5), cryptogenic cirrhosis (3), primary biliary cirrhosis (3), sclerosing cholangitis (l), biliary atresia (l), Wilson’s disease (l),Budd-Chiari syndrome (l), angiosarcoma of the liver (l), and alpha-1-antitrypsin deficiency (one). The clinical course and essential laboratory data were reviewed. The neuropathologic assessment involved gross examinations of the brains and spinal cords after fixation in 10% buffered formalin for at least 2 weeks. The cerebral hemispheres and brainstem were sectioned in the coronal plane at 1-cm intervals. The cerebellum was sectioned in the sagittal and parasagittal planes a t about 5-mm intervals. Samples were taken from the frontal, temporal, parietal, and occipital lobes, the corpus striatum and insula, hippocampi, midbrain, brainstem, spinal cord, and pituitary gland. Light microscopic studies were done with hematoxylin-eosin.
From the Department of Neurology (Drs. Estol and Pessin), Tufts University School of Medicine and the New England Medical Center, Boston, MA; end the Pathology Department, Neuropathology Division (Dr. Martinez), Presbyterian University Hospital, University of Pittsburgh, Pittsburgh. PA. Received September 24,1990. Accepted for publication in final form November 26,1990. Addreap correspondence and reprint requests to Dr. Conrado Estol, Department of Neurology. New England Medical Center, 750 Washington Street, Boston, MA 02111.
June 1991 NEUROLOGY 41 816
Table. Clinical and neuroDathologic findings after OLTx
Pt no.
Age/Sex 28F
Neuropathology
L parieto-occipital SDH; CPM; herniation; A2
PT PTT L R SDH CPM 'A2 NA
Platelets PT (cont/patient) PTT (contlpatient)
Clinical course
76,000 11.5114.9 NA
Global cerebral ischemia secondary to hemopneumothorax; POD 2 4 myoclonus, encephalopathy; unresponsive with fixed pupils after a GMsz
35F
Midbrain hemorrhages; focal hemorrhages (cerebellum, white matter, basal ganglia); herniation
103,000 11.1113.8 NA
POD 38: cardiac arrest; resuscitation and szs until death 3 days later
23F
HI (Rfrontal, L parietal, midbrain, cerebellar hemisphere); acute leptomeningitis (suspected Aspergilllls but not proven); CPM; A2; herniation
31,000 12115.4 NA
POD 15: 3 GM szs; remained unresponsive, R pupil dilated and fixed; angiography suggested herniation; sputum positive for Aspergillus; BC grew Enterobacter
21/M
20/M
HI (cerebellum,basal ganglia, cortex) (hyphae in vessel lumen); CPM; A2 SAH (severe); SDH (Lfrontoparietal); focal hemorrhage (L amygdalalcaudate); A2
77,000 1l.l/NA NAl28.3 40,000 11.5115.4 NA
Unresponsive after Tx 2; also ARF, fever, rejection, respiratory failure, sepsis, and systemic aspergillosis POD 3: GM szs; CT showed SAH, no brainstem reflexes, and EEG showed brain death
53F
SAH (severe); L ICH, herniation; A2
27,000 11.5112.6 NA
POD 45: developed encephalopathy and tetraplegia; CT showed SAH; POD 46: death
43/M
Recent infarct (pons, temporal lobe); CPM; cortical laminar necrosis; subacute combined degeneration; A2
76,000 NAl17.2 NA/40
POD 2: left hemiparesis; POD 5: respiratory failure, unresponsiveness, and focal motor szs; POD 6 0 massive rectal bleeding (hemorrhoids) and rejection; POD 66: death
33lM
ICH (R temporal lobe) secondary to Listeria; CPM
113,000 NA118.9 NAl35.2
POD 4: encephalopathy; POD 6: szs and anisocoria (CTILP negative); POD 3 0 coma, BC grew Listeria; rejection, GI hemorrhage, pneumonia, ARDS, ARF, pneumothorax; POD 43: death
Prothrombin time. Partial thromboplastin time.
Left. Right.
Subdural hematoma. Central pontine myelinolysis. Alzheimer type I1 astrocytosis. Not available.
POD Postoperative day. GM Grand mal. SZ Seizure. HI Hemorrhagic infarct. BC Blood cultures. Tx Transplant. ARF Acute renal failure. SAH Subarachnoid hemorrhage.
Results. The clinical and neuropathologic features are presented in the table. The major neuropathologic findings were intracranial bleeding in 13 patients and infarcts in five. The intracranial bleeding included eight patients with intracerebral hemorrhage (ICH) (five hemispheric, two brainstem, and one hemispheric and brainstem), seven with subarachnoid hemorrhage (SAH), and four with subdural hematoma (SDH). Five patients had infarcts (three hemorrhagic [HI] and two ischemic). No congenital or mycotic aneurysms were found. One patient had an arteriovenous malformation (AVM) but no evi816 NEUROLOGY 41 June 1991
CT ICH LP GI ARDS AVR CyA
CATscan. Intracerebral hemorrhage. Lumbar puncture. Gastrointestinal. Adult respiratory distress syndrome Aortic valve replacement. Cyclosporine.
dence of intracranial bleeding or infarction. Eight patients had a single type of hemorrhagic lesion. In five patients bleeding occurred at more than one site: SAH with ICH in three patients; SAH, ICH, and SDH in one; and SDH and ICH in one. Five patients had multiple lesions of the same hemorrhagic type. CNS infections were an etiologic factor of the cerebrovascular complications in five patients. One patient with CNS aspergillosis had multiple abscesses with necrosis and ICH in the right frontal and parietal lobes and left cerebellum. Another patient with acute lep-
table continued
Pt no.
Platelets
PT (cont/patient) PTT (contlpatient)
Age/Sex
Neuropathology
9
55m
SAH (R frontotemporal); SAH (spinal cord); acute pituitary hemorrhage; leptomeningitis (purulent); bacterial endocarditis
64,000 NAl12.4 NAl26.7
POD 5 of Tx 3: ARF’, hypotension, death
10
19F
S A H ICH (cerebral, cerebellar); A2
22,000 11.8118.2 NA
POD 3 0 rejection, BC grew Candida, respiratory failure, hypotension; POD 36: death
11
53m
SDH (L); brainstem hemorrhage; herniation
91,000 11.8/19.8 NA
POD 13: nausea, headache, purpura, coma, L hemiparesis, decerebrate posture, and anisocoria; C T SDH, POD 14: death
12
22FI
SAH (small); cerebral edema; A2
191,000 NA/51 NAl70.7
Global cerebral ischemia during Tx 2, then hypotensive, pulmonary and GI hemorrhage, generalized petechiae; POD 1: death
13
40/M
SAH (R occipital, L parietal); HI (L parieto-occipital)
28,000 NAl16.4 NAl36.9
POD 1 0 BC grew Staphylococcus aureus; POD 2 0 lethargic, L gaze preference, R facial palsy; echo: vegetations; POD 30: AVR refractory hypotension; POD 31: death
14
37F
SDH (L occipital); leptomeningitis with panangiitis (Ctyptococcus); herpes encephalitis
203,000 NAl14.4 NAl28.7
POD 7 8 lethargic with fever; CT: small SDH, C S F 465 WBCs, glucose
de l’immunodi?ficience humaine. Rev Neurol (Paris) 1988;14432-35. 22. Lanska MJ, Lanska DJ, SchmidleyJW.Syphilitic polyradiculopathy in an HIV-positive man. Neurology 1988;38:1297-1301. 23. Comblath DFt, McArthur JC. Pdominantly sensory newpathy in patients with AIDS and AIDS-related complex. Neurology 1988;38:794-796. 24. Leger JM, Bouche P, Bolgert F, et al. The spectrum of polyneuropathiesin patients infected with HIV. J Neurol Neurosurg Psychiatry 1989;52:1369-1374. 25. Conlon CP. HIV infection presenting as Guillain-Barrksyndrome in Lusaka, Zambia. Trans R SOCTrop Med Hyg 1989;83:109.
Cerebrovascular complications after orthotopic liver transplantation: A clinicopathologic study Conrado J. Estol, MD; Michael S. Pessin, MD; and A. Julio Martinez, MD Article abstract-We analyzed 55 autopsy cases in 1,357 patients undergoing orthotopic liver transplantation at the University of Pittsburgh and found that 13 (23.6%)patients had intracranial bleeding, and five (9%) had infarcts. Eight patients had bleeding localized to one intracranial compartment: intracerebral hemorrhage (three patients); subarachnoid hemorrhage (three patients); and subdural hematoma (two patients). Five patients had combinations of multiple sites of bleeding: three with subarachnoid hemorrhage-intracerebral hemorrhage, one with subarachnoid hemorrhage-intracerebral hemorrhage-subdural hematoma, and one with subdural hematoma-intracerebral hemorrhage. Coexistent CNS infections (fungal or bacterial) were associated with hemorrhagic infarcts and intracerebral hemorrhage in four patients. Cerebral embolism and hemorrhagic infarction from bacterial endocarditis occurred in one patient. Five patients died of intracranial bleeding. Severe coagulopathy was the major cause of intracranial bleeding and was associated with systemic bleeding in 12 patients. Significant systemic or metabolic complications were present in all patients and masked the focal signs of the intracranial process in more than one half. NEUROLOGY 1991;41:815-819
Neurologic complications are important causes of morbidity and mortality following orthotopic (implantation of the new organ in place of the old) liver transplantations (OLTx).l In previous rep0rts,2>~ we emphasized the high frequency of central pontine myelinolysis (CPM) and seizures after OLTx. We herein report the cerebrovascular complications after OLTx. Methods. From January 1981 to December 1987, 1,357 patients had OLTx at the University Health Center of Pittsburgh (UHCP). Eight hundred sixty-seven were adults. Of those who died, 118 had autopsies but only 55 had complete neuropathologic examinations. Of these 55, 17 (31%) had intracranial bleeding or cerebral infarction. Patients with global cerebral ischemia were excluded. One with intracranial trauma from a motor vehicle accident was also excluded. The 17 patients included nine men and eight women ranging in age from 19 to 55 years (average, 34 years) (table).Eleven patients
had one transplant, five had two, and one had three. The survival time after OLTx ranged from 0 to 80 days: two patients survived 0 to 5 days, six survived 6 to 30 days, seven survived 31 to 60 days, and two survived 60 to 80 days. The etiologies of liver failure in these 17 patients included chronic hepatitis (5), cryptogenic cirrhosis (3), primary biliary cirrhosis (3), sclerosing cholangitis (l), biliary atresia (l), Wilson’s disease (l),Budd-Chiari syndrome (l), angiosarcoma of the liver (l), and alpha-1-antitrypsin deficiency (one). The clinical course and essential laboratory data were reviewed. The neuropathologic assessment involved gross examinations of the brains and spinal cords after fixation in 10% buffered formalin for at least 2 weeks. The cerebral hemispheres and brainstem were sectioned in the coronal plane at 1-cm intervals. The cerebellum was sectioned in the sagittal and parasagittal planes a t about 5-mm intervals. Samples were taken from the frontal, temporal, parietal, and occipital lobes, the corpus striatum and insula, hippocampi, midbrain, brainstem, spinal cord, and pituitary gland. Light microscopic studies were done with hematoxylin-eosin.
From the Department of Neurology (Drs. Estol and Pessin), Tufts University School of Medicine and the New England Medical Center, Boston, MA; end the Pathology Department, Neuropathology Division (Dr. Martinez), Presbyterian University Hospital, University of Pittsburgh, Pittsburgh. PA. Received September 24,1990. Accepted for publication in final form November 26,1990. Addreap correspondence and reprint requests to Dr. Conrado Estol, Department of Neurology. New England Medical Center, 750 Washington Street, Boston, MA 02111.
June 1991 NEUROLOGY 41 816
Table. Clinical and neuroDathologic findings after OLTx
Pt no.
Age/Sex 28F
Neuropathology
L parieto-occipital SDH; CPM; herniation; A2
PT PTT L R SDH CPM 'A2 NA
Platelets PT (cont/patient) PTT (contlpatient)
Clinical course
76,000 11.5114.9 NA
Global cerebral ischemia secondary to hemopneumothorax; POD 2 4 myoclonus, encephalopathy; unresponsive with fixed pupils after a GMsz
35F
Midbrain hemorrhages; focal hemorrhages (cerebellum, white matter, basal ganglia); herniation
103,000 11.1113.8 NA
POD 38: cardiac arrest; resuscitation and szs until death 3 days later
23F
HI (Rfrontal, L parietal, midbrain, cerebellar hemisphere); acute leptomeningitis (suspected Aspergilllls but not proven); CPM; A2; herniation
31,000 12115.4 NA
POD 15: 3 GM szs; remained unresponsive, R pupil dilated and fixed; angiography suggested herniation; sputum positive for Aspergillus; BC grew Enterobacter
21/M
20/M
HI (cerebellum,basal ganglia, cortex) (hyphae in vessel lumen); CPM; A2 SAH (severe); SDH (Lfrontoparietal); focal hemorrhage (L amygdalalcaudate); A2
77,000 1l.l/NA NAl28.3 40,000 11.5115.4 NA
Unresponsive after Tx 2; also ARF, fever, rejection, respiratory failure, sepsis, and systemic aspergillosis POD 3: GM szs; CT showed SAH, no brainstem reflexes, and EEG showed brain death
53F
SAH (severe); L ICH, herniation; A2
27,000 11.5112.6 NA
POD 45: developed encephalopathy and tetraplegia; CT showed SAH; POD 46: death
43/M
Recent infarct (pons, temporal lobe); CPM; cortical laminar necrosis; subacute combined degeneration; A2
76,000 NAl17.2 NA/40
POD 2: left hemiparesis; POD 5: respiratory failure, unresponsiveness, and focal motor szs; POD 6 0 massive rectal bleeding (hemorrhoids) and rejection; POD 66: death
33lM
ICH (R temporal lobe) secondary to Listeria; CPM
113,000 NA118.9 NAl35.2
POD 4: encephalopathy; POD 6: szs and anisocoria (CTILP negative); POD 3 0 coma, BC grew Listeria; rejection, GI hemorrhage, pneumonia, ARDS, ARF, pneumothorax; POD 43: death
Prothrombin time. Partial thromboplastin time.
Left. Right.
Subdural hematoma. Central pontine myelinolysis. Alzheimer type I1 astrocytosis. Not available.
POD Postoperative day. GM Grand mal. SZ Seizure. HI Hemorrhagic infarct. BC Blood cultures. Tx Transplant. ARF Acute renal failure. SAH Subarachnoid hemorrhage.
Results. The clinical and neuropathologic features are presented in the table. The major neuropathologic findings were intracranial bleeding in 13 patients and infarcts in five. The intracranial bleeding included eight patients with intracerebral hemorrhage (ICH) (five hemispheric, two brainstem, and one hemispheric and brainstem), seven with subarachnoid hemorrhage (SAH), and four with subdural hematoma (SDH). Five patients had infarcts (three hemorrhagic [HI] and two ischemic). No congenital or mycotic aneurysms were found. One patient had an arteriovenous malformation (AVM) but no evi816 NEUROLOGY 41 June 1991
CT ICH LP GI ARDS AVR CyA
CATscan. Intracerebral hemorrhage. Lumbar puncture. Gastrointestinal. Adult respiratory distress syndrome Aortic valve replacement. Cyclosporine.
dence of intracranial bleeding or infarction. Eight patients had a single type of hemorrhagic lesion. In five patients bleeding occurred at more than one site: SAH with ICH in three patients; SAH, ICH, and SDH in one; and SDH and ICH in one. Five patients had multiple lesions of the same hemorrhagic type. CNS infections were an etiologic factor of the cerebrovascular complications in five patients. One patient with CNS aspergillosis had multiple abscesses with necrosis and ICH in the right frontal and parietal lobes and left cerebellum. Another patient with acute lep-
table continued
Pt no.
Platelets
PT (cont/patient) PTT (contlpatient)
Age/Sex
Neuropathology
9
55m
SAH (R frontotemporal); SAH (spinal cord); acute pituitary hemorrhage; leptomeningitis (purulent); bacterial endocarditis
64,000 NAl12.4 NAl26.7
POD 5 of Tx 3: ARF’, hypotension, death
10
19F
S A H ICH (cerebral, cerebellar); A2
22,000 11.8118.2 NA
POD 3 0 rejection, BC grew Candida, respiratory failure, hypotension; POD 36: death
11
53m
SDH (L); brainstem hemorrhage; herniation
91,000 11.8/19.8 NA
POD 13: nausea, headache, purpura, coma, L hemiparesis, decerebrate posture, and anisocoria; C T SDH, POD 14: death
12
22FI
SAH (small); cerebral edema; A2
191,000 NA/51 NAl70.7
Global cerebral ischemia during Tx 2, then hypotensive, pulmonary and GI hemorrhage, generalized petechiae; POD 1: death
13
40/M
SAH (R occipital, L parietal); HI (L parieto-occipital)
28,000 NAl16.4 NAl36.9
POD 1 0 BC grew Staphylococcus aureus; POD 2 0 lethargic, L gaze preference, R facial palsy; echo: vegetations; POD 30: AVR refractory hypotension; POD 31: death
14
37F
SDH (L occipital); leptomeningitis with panangiitis (Ctyptococcus); herpes encephalitis
203,000 NAl14.4 NAl28.7
POD 7 8 lethargic with fever; CT: small SDH, C S F 465 WBCs, glucose
