Acute Hemorrhagic Leukoencephalitis

X TE hemor rhag ic l eukoencepha l i t i s has been r ega rded as a ra re and uni f o rmly fa t a l neurologica l c a t a s t ro phe. Class ical ly , the lesions are confined to cerebra l whi te m a t t e r , f r equen t ly un i l a t e ra l b u t occas iona l ly invo lv ing bo th hemispheres , the b ra in s t em or even the cerebel lum. F r o m the t ime of t he or iginal r epo r t of H u r s t 5 in 1941 un t i l t h a t of Kr i s t i an sen et al. 7 in 1956 no cases were d iagnosed pr ior to p o s t m o r t e m examina t ion . I n the l a t t e r r epo r t 7 of 5 surgica l ly explored pa t i en t s , biopsies of the b ra in in the ~ who su rv ived were compa t ib l e wi th th is d iagnosis a l t hough his tologic sect ions were no t shown. Never the less , i t was e m p h a sized t h a t al l cases of acu te hemor rhag ic l eukoencepha l i t i s need no t necessar i ly t e rmi i~ate fa ta l ly , even t hough the specific d iagnosis had un t i l t hen no t been m a d e pr ior to dea th . I t is our pu rpose to r epo r t ~ add i t i ona l cases of acu t e hemor rhag ic l eukoencepha l i t i s , t r e a t e d p r o m p t l y b y in te rna l and ex te rna l surgical decompress ion . I n the second case the b ra in was processed for e lec t ron as well as l ight microscopy .

Examination on admission revealed slight irritability but an otherwise normal mental state.The temperature was 37°C and the pulse 134 beats per minute.Blood pressure was l6Oi 100 mm Hg.The neck was not rigid.A grade 214 systolic ejection murmur was present at the left sternal border.Breath sounds were reduced at the left lung base and axilla.The disc margins were flat, but retinal venous pulsations were absent.The peripheral visual fields were full to confrontation.The pupils were equal and reacted briskly to light and on convergence.Extraocular movements were limited in upward gaze.The left lower side of the face was slightly weak.Function of the other cranial nerves was normal.There was mildly diminished strength and tone in the left arm and leg.Occasional involuntary pincer-like movements of the left thumb and forefinger were observed.The reflexes were hypoactive and symmetrical.The right plantar response was flexor, the left neutral.Reaction to pinprick was impaired over the left side of the trunk and extremities.
While under observation the patient developed a generalized tonic-clonic seizure, greater on the left.The episode lasted five minutes, after which he was obtunded and had more severe left-sided paralysis.
Laboratory findings inc1uded.awhite cell count of 15,500 with 84% neutrophils and 8% band neutrophils.The urine, hemoglobin, erythrocyte sedimentation rate, serum glucose, nonprotein nitrogen, and electrolytes were all normal.Lumbar puncture yielded cloudy cerebrospinal fluid (CSF) under a pressure of 300 mg HZO.The fluid contained 3,143 white cells per cubic millimeter, 95% polymorphonuclear, and no red blood cells; total protein was 160 mgidl, and glucose 66 mgidl.N o organisms were seen on smear, and culture \;as negative.Serum and CSF serology results were negative.An electrocardiogram showed diffuse loss of T-wave voltage and S-T segment sagging.An electroencephalogram was diffusely abnormal with delta activity throughout and rare runs of spike waves and sharp and slow waves in the right central and parietal regions.
A roentgenogram of the chest showed a left perihilar infiltrate.A computerized tomographic (CT) scan performed 18 hours after the onset of neurological symptoms showed a mass effect of the right hemisphere with partial obliteration and shift of the right lateral ventricle and septum pellucidum to the left of midline (Fig 1).Areas of low absorption coefficient involved the white matter of the temporal and parietal regions, more marked on the right, with generalized contrast enhancement of gray matter (Fig 2).
The patient's seizures were treated with intravenous diphenylhydantoin and diazepam, and he received dexamethasone and mannitol for cerebral edema.On the second hospital day he was unresponsive, had decerebrate responses to stimuli, and had blurred disc margins and sluggish pupillary reactions.Intermittent seizure activity of the left leg persisted.A brain biopsy obtained through a right temporal craniotomy contained no inflammation or inclusion bodies.Neurons showed loss of cytoplasmic and nuclear detail, suggesting degeneration.Fluorescent antibody studies and viral cultures for herpes simplex were negative.Adenine arabinoside therapy was begun empirically, but the patient deteriorated with loss of brainstem reflexes and two successive isoelectric electroencephalograms.H e died on the eighth hospital day.

Nezlropathological Findings
The whole brain weighed 1,3 10 gm, including 185 gm of the brainstem and cerebellum after fixation.The leptomeninges were normal.The cerebral arteries showed no atherosclerosis.There was caudal herniation of cerebellar tonsils, which were necrotic and friable.The cerebrum was dusky and mildly friable because of autolysis.It was sectioned in a fresh state, so the cut surfaces were irregularly shrunken and brain slices were distorted.The degree of transtentorial herniation could not be evaluated.Coronal sections of the cerebral hemispheres revealed flattening of convexities and obliteration of sulci.The third and lateral ventricles appeared to be displaced to the left but were normal in size.There was diffuse swelling with softening, gray discoloration, and numerous petechial hemorrhages of the right frontoparietal white matter (Fig 3).This lesion was relatively sharply demarcated from the overlying cerebral cortex, but the ventral border was poorly defined.The arcuate or U fibers were grossly preserved (Fig 4 ) .The cerebral cortex was congested, with focal gray discoloration in the depth of the sulci.The brainstem and cerebellum showed diffuse swelling with obliteration of the aqueduct and fourth ventricle.The spinai cord was not studied.
Microscopically, the lesion in the right frontoparietal white matter showed diffuse edema and marked demyelination with focal necrosis and numerous ring-and-ball hemorrhages.Nerve fibers were well preserved except in foci of necrosis.Blood vessels showed thickened walls.Vascular necrosis and perivenous fibrinous exudates were also present.A small number of lymphocytes were found in the wall of some blood vessels, but inflammatory exudates were inconspicuous.On the other hand, microglia cells were abundant and had a tendency to cluster around blood vessels but also infiltrated diffusely into the parenchyma in a patchy fashion.Necrosis and demyelinatiori were more pronounced in the subcortical re- gions and became less marked in deeper white matrer.The subcortical arcuate fibers were unstained with myelin stain but were free of necrosis, gitter cell infiltration, and edema.The cerebral cortex over the lesion was well preserved except for occasional small foci of ischemic neuronal changes and edema.No lesions except for edema and autolytic changes were found in other parts of the brain.
Though this brain showed a moderate degree of autolysis because the patient had been placed on a respirator for six days, both the macroscopic and microscopic findings are characteristic of AHL.

Discussion
Acute hemorrhagic leukoencephalitis is a hyperacute disease of cerebral white matter characterized by progressive coma, pyramidal signs, seizures, and usually death {3].The CT scans in this patient mirrored the violent effects of the disease on the brain and demonstrated the presence of a low absorption coefficient and mass effect resulting from edema and necrosis of the centrum semiovale.The presence of contrast enhancement reflected abnormal permeability of contrast from damaged blood vessels.
One previous case report described CT

Fig
Fig I .CT Scan obtained 18 hours after onset of neurologicaf symptom.r,area of decreased density in the right hemisphere jJ cawir2g lateral f,entrjclr and &ift of midline structures from right to 14.There ;.F coyitrajt enha,tc-ement of peripheral gray matter.

F i g 2 .
Brain substance near the vertex is decreased in density bilaterah).u i t h more extensi&e invohement on the righi side and lhqt of midline from right toDi//use contrart enhancement 0fgra.ymatter is again seen.

Fig 3 .
Fig 3. Coronal section through the puhinav.There is difluse swelling ojthe right cerebral hemzsphere with peteshial hemorrhage.r,gray discoloration, and necrosir of the superior parietal white matter.

Fig 4 .
Fig 4. Magnified view of the lesion, disclosing widespread petechial hemorrhage and necrosis in the white matter sparing the cortex and U-Jzbers.
AHL and HSE.In HSE, the CT is usually normal in the early stages [I}.Subsequently, the predominant finding is an area of decreased attenuation in the temporal lobes that may involve the insular cortex but spares the lenticular nucleus El, 4 , 71.These changes were rarely present sooner than five days after the onset of neurological symptoms [l, S], and early in the course CT often failed to reflect the full extent of the disease process {S].Mass effect, when present, increased with time and paralleled the increasing size of the low-density lesion {2).Bilateral mass effect was an early finding in two patients who eventually developed low-absorption abnormalities 111.The <IT changes in HSE conform to the development of angiographic and technetium brain scan alterations, in which patients examined five days after the onset of neurological symptoms had abnormal findings [ S ] .The presence of a mass effect or increased absorption coefficient on CT within the first three days after the onset of hyperacute encephalitis suggests AHL, and may permit diagnosis during life.