Cerebellar Infarction A

Clinicopathological Study

George

W.

Sypert, MD, Ellsworth C. Alvord, Jr.,

The clinical and

pathological features

of 28 fatal cases of acute uncomplicated massive cerebellar infarction are reviewed. Although infarcts may involve any portion of the cerebellum, they predominantly involve the posteroinferior half of one cerebellar hemisphere. The frequency of acute uncomplicated fatal cerebellar infarction is much greater than previously appreciated, approximating that of acute fatal cerebellar hemorrhage. All patients were past middle age. Atherosclerosis and acute vertebral artery occlusion were the most common etiological factors. The onset was sudden in most cases, with vomiting, dizziness, vertigo, and cerebellar dysfunction. All patients died with progressive brain stem dysfunction and medullary respiratory failure secondary to compression by a swollen cerebellum. Death usually occurred between the third and sixth days following the onset of symptoms, but only six to 30 hours after the onset of obtundation; therefore, decompressive therapy must be instituted

promptly. (Arch Neurol 32:357-363, 1975) Accepted

for publication Oct 29, 1974. From the departments of neurological surgery and pathology (Laboratory of Neuropathology), University of Washington, Seattle. Dr. Sypert is now with the Division of Neurological Surgery, University of Florida School of Medicine, Gainesville, Fla.

Reprint requests to Neurological Surgery, University of Florida, Box 725, JHM Health Center, Gainesville, FL 32610 (Dr. Sypert).

MD

À lthough numerous cases of infarcof the cerebellum have been reported at autopsy,19 there have been no extensive clinicopathological studies of these cases. However, re¬ cent clinical case reports have begun to establish a clinical syndrome re¬ lated to massive cerebellar infarction and swelling.1""' The small number of these reports suggests that this po¬ tentially fatal affliction is either rare or remains largely unrecognized clini¬ cally. Furthermore, the reports fail to yield important data regarding the natural history of massive cerebellar il tion

infarction. Recent observation at autopsy of a number of incorrectly diagnosed cases prompted this retrospective, clinicopathological study to delineate the incidence, natural history, and clinical syndrome of massive cerebel¬ lar infarction. INCIDENCE

Cases of infarction of the cere¬ bellum examined by members of the Laboratory of Neuropathology, Uni¬ versity of Washington School of Med¬ icine, Seattle, between 1963 and 1973 have been reviewed. The cases were derived from three University-affili¬ ated general hospitals: University Hospital, Harborview Medical Cen-

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ter, and Seattle Veterans Adminis¬ tration Hospital (VAH). Cases of

small acute hemorrhages or infarc¬ tions (less than 2 cm) were not in¬ cluded. Of 5,494 autopsies in which the adult brain was examined, there were 97 (1.8%), cases of spontaneous acute massive vascular lesions of the cerebellum, 39 cases (0.7%) of acute cerebellar hemorrhage, and 58 cases (1.1%) of acute cerebellar infarction (30 complicated, 28 uncomplicated). Proportion of uncomplicated infarc¬ tions to hemorrhages was 28/39 (74%). The incidence of acute cerebel¬ lar hemorrhages in the present au¬ topsy population is similar to the inci¬ dence found by Rey-Bellet1? and Dinsdale18 in their clinicopathological studies of acute cerebellar hemor¬ rhage. Thus, it would appear that both of the present figures approxi¬ mate the actual incidence of these two diseases in a general hospital if it is assumed that these diseases are uniformly fatal, which, fortunately, is not the situation, as shown by the fol¬

lowing:

Cerebellar hemorrhage Old Acute Cerebellar infarction Old Acute uncomplicated

41 2 39

(5%)

24 28

(46%)

52

Cases of acute cerebellar infarction further classified as either com¬

were

plicated

or

uncomplicated. Compli¬

patients had histories of an acute hemiparesis followed by moderate and ex¬ lier. Two

cellent recoveries.

cated cases associated with other lifethreatening central nervous system

most frequently acute mas¬ sive brain stem infarctions (93%), were not included in the present de¬ tailed analysis. Uncomplicated cases,

lesions,

which form the basis for this study, included some with small associated central nervous system lesions, which usually are not life-threatening. The incidence of uncomplicated acute cerebellar infarctions was approxi¬ mately 1 in 192 adult autopsies, slightly less than that noted for acute cerebellar hemorrhages, a lesion that has received much more attention. CLINICAL DATA Age and Sex The 28 patients with acute uncompli¬ cated cerebellar infarctions ranged in age from 41 to 86 years (mean, 63 years), with almost 80% between 55 to 75. There were 21 men and 7 women, with the predomi¬ nance of men reflecting in part nine pa¬ tients from the VAH.

Etiological Factors A history of prior atherosclerotic cardio¬

vascular disease was the most important predisposing factor (19 patients, 68%). General autopsy studies showed evidence of moderate to substantial atherosclerotic cardiovascular changes in 24 of 28 pa¬ tients. Old myocardial infarcts were pres¬ ent in four patients. The heart was en¬ larged in 22 of the 28 patients, weighing from 380 to 790 gm (average 460 gm). In six patients (22%), embolism to the verte¬ bral artery secondary to a recent myocar¬ dial infarction (three patients) or atrial fibrillation (three patients) was found at

autopsy. Hypertension (blood pressure greater than 140/95 mm Hg) usually of five years

or more duration was also an important predisposing factor (12 patients, 43%). Pre¬ existing diabetes mellitus was noted in five patients (18%).

Previous Neurological Disease

patients (25%) had a history sug¬ gestive of previous neurological distur¬ Seven

bances.

Vertebrobasilar artery insuffi¬

ciency was diagnosed in two patients, and a compatible history was present in two other patients. One patient had suffered a lateral medullary infarction two years ear-

Symptoms Two a

at Onset

patients appeared at the hospital in a medical history

comatose state without

and for this reason were excluded from this portion of the analysis. In the remain¬ ing 26 patients, the onset was usually sud¬ den without any immediately premonitory symptoms or precipitating factors. In most of the patients, the initial symptom was a fall (11), with the inability to stand and ataxia of gait (19). Vomiting (15), dizziness or vertigo (13), dysarthria (12), and ataxia of the extremities (ten) also were common symptoms at onset/ Transient loss of con¬ sciousness occurred in four patients and confusion with clouding of consciousness in six. Five patients complained of a hemi¬ paresis, but review of the charts does not clarify whether this symptom may have been confused with ataxia. Headache was

infrequent (four). Other symptoms oc¬ curred in seven patients. A history of intermittent symptoms prior to the onset of this final illness was elicited in four patients. These consisted of intermittent dizziness or vertigo, ataxia of gait or extremities, dysarthria, confusion, and blurred vision, which occurred during the preceding days or weeks. The 12-hour interval immediately fol¬ lowing the onset of symptoms was charac¬ terized by a lack of progression or change in the symptoms. However, the subsequent 12- to 96-hour interval was invariably asso¬ ciated with an increase in severity and number of symptoms. Of the 15 patients who came to the hospital within 12 to 96 hours following the onset of symptoms, three had already developed coma, six ob¬ tundation, and two dysarthria and dysphagia.

Signs

on

Admission

Twenty-one patients were admitted to neurology services at each hospital and two patients to the neurosurgery services. The four remaining patients were ad¬ the

mitted to the internal medicine services where two patients were seen by consul¬ tant neurologists. The major clinical signs elicited on ad¬ mission to the hospital are shown below: Mental Status Comatose Obtunded Confused Respiratory disturbance Central hyperventilation Ataxic respirations Pupillary abnormalities

(64%) 5 7 6

(18%) 3 2

(14%)

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Pinpoint and sluggish Asymmetrical Ocular movement abnormality Ipsilateral gaze paresis Ipsilateral abducens paresis Oculovestibular abnormalities

Upward gaze paresis Skew deviation Other cranial nerve abnormalities V VII

, XII Cerebellar signs (21 able to cooperate)

Dysarthria Nystagmus Extremity dysmetria

Gait/trunkal ataxia Motor disturbances Flaccid quadriparesis Flaccid hemiparesis

Spastic quadriparesis Spastic hemiparesis Decerebration Babinski sign Bilateral Unilateral

3 1

(47%) 8 3 9 1 1

(57%) 8 10 8 2

(81%) 14 13 12 15

(42%) 1 2 4 5 3

(42%) 7 5

Most patients exhibited various combi¬ nations of impairment of consciousness, cerebellar signs, ocular movement abnor¬ malities and other cranial nerve distur¬ bances, and motor system involvement. A few patients exhibited some degree of res¬ piratory disturbance, pupillary abnormal¬ ities, and sensory system involvement. One patient had normal neurological examina¬ tion results on admission. Mental Status.—When seen for the first time, five patients were in coma, and 13 were obtunded or confused; ten patients were fully alert with normal mental status. Coma or an obtunded state usually oc¬ curred between 48 and 96 hours following the onset of symptoms. Eventually, all pa¬ tients lapsed into coma and remained in this condition until death. Fluctuations in the level of consciousness were not ob¬ served. Death occurred less than 12 hours after the onset of coma in 15 patients, 12 to 24 hours in seven, 24 to 48 hours in three, and 2 to 12 days in three (Figure). Respiration.—Disturbances of respiration occurred late in the course of the disease and were invariably associated with severe obtundation or coma. Ataxic breathing de¬ veloped in most patients just prior to death. A Cheyne-Stokes pattern was noted in seven patients and central hyperventilation in 11 patients for variable periods prior to the onset of the terminal ataxic pattern. In many patients, there was a clear indication of the respiratory nature

death, the pulse continuing for a short period after the last visible respiratory ef¬ of

fort. Cranial Nerves.—Pupillary abnormalities not frequent until the later stages of the illness, and these were usually associ¬ ated with a severe deterioration in the level of consciousness. Small, sluggish or nonreactive pupils represented the most were

frequent abnormality

noted. Pupillary unilateral dilated pupil, usually ipsilateral to the site of cerebellar infarction, was noted at some point in the course in five patients. Papilledema was found in four patients and hypertensive retinopathy in ten. Subhyaloid hemorrhages and exophthalmos were not noted in any patients. Disorders of ocular movements and oculovestibular reflexes were frequent findings, usually developing after 48 hours from onset. Conjugate deviation of the eyes contralateral to the site of infarction (secondary to an ipsilateral gaze paresis) was noted in 12 patients. In four, an ipsi¬ lateral abducens palsy was observed. Ocu¬ lar bobbing developed in three patients with the onset of coma. Upward gaze pa¬ resis and skew deviation were noted in in¬ dividual patients. Oculovestibular abnor¬ malities were observed eventually in 17 patients, the most frequent disturbance consisting of a loss of the ipsilateral caloric response to ice water. An ipsilateral facial paresis was com¬ mon, eventually developing in 14 patients. Fifth cranial nerve dysfunction, consisting of an ipsilateral loss of facial pain and

asymmetry with

a

temperature sensibility, was definitely shown in six patients. Furthermore, eight

patients showed an ipsilateral depression of the corneal reflex. Lower cranial nerve (IX and X) dysfunctions occurred in nine patients ipsilateral to the site of cerebellar infarction. Ipsilateral paresis of the tongue was found in two patients. Find¬ ings consistent with a classical lateral medullary

Wallenburg syndrome were present in five patients. Cerebellar Signs.—Cerebellar signs were the most frequent early signs and, retro¬ spectively, should have been of great di¬ agnostic value. Seventeen of the 21 pa¬ tients who were able to cooperate for the neurological examination showed evidence of cerebellar dysfunction on admission. Ataxia of gait, extremity dysmetria, dys¬ arthria, and nystagmus were frequent findings. With progression, two additional patients developed evidence of cerebellar dysfunction. Motor System Signs.—Motor system dys¬ function usually appeared late, closely as¬ or

sociated with a marked deterioration in the level of consciousness. With the onset

of coma, most patients developed a spastic quadriparesis and decerebration, followed by flaccidity just prior to death. In alert patients, hemiparesis was noted only four times and quadriparesis once. Babinski sign was closely correlated with the devel¬ opment of motor system dysfunction. Sensory System Signs.—A disturbance of sensation was demonstrated in only five patients, consisting of a contralateral de¬ crease in pain and temperature sensibility. There was a question of homonymous hemianopsia in two patients. Vital Signs.-Although only 46% of the patients had a history of hypertension, 71%

found to have blood pressure greater than 150/100 mm Hg at the time of their final admission. There was a tendency for the blood pressure to rise in association with a deterioration in the patient's level of consciousness. A fall in blood pressure was noted preterminally. The pulse rate was normal on admission, except for the two patients who were comatose and had slow pulse rate. In most patients, the pulse rate fell below 60 beats/min with the onset of coma. Only four patients were admitted with mild fevers of 37.7 to 38.8 C (100 to 102 F), and two of these had evidence of pneu¬ monia and one, severe aspiration. Two were

patients developed temperatures greater than 39.4 C (103 F), with no obvious cause being found outside the central nervous system.

Laboratory

Data

Lumbar puncture was performed in 11 patients; seven had an elevated pressure. One patient had grossly bloody spinal fluid, and four others had from 24 to 860 RBC/cu mm. An elevation in spinal fluid protein to 280 mg/100 ml was found in five and a leukocytosis (460 WBC/cu mm) in six. Only three patients had nuchal rigidity prior to the lumbar puncture, a finding that became more common in the later stages of the illness. One patient, who was alert prior to the lumbar puncture, sud¬ denly deteriorated and died within one hour of the procedure. His spinal fluid pressure was substantially elevated at the time of the lumbar puncture. An electroencephalogram was performed on six patients and showed bifrontal slow wave activity in four and mild nonspecific abnormalities in two. In the three patients in whom a ventriculogram was performed, hydrocephalus and aqueductal occlusion were found. Ventricular filling could not be accomplished in the one patient who un¬ derwent pneumoencephalography. The single carotid arteriogram was consistent with hydrocephalus and showed elevation of the posterior cerebral arteries. The

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single retrograde arteriogram performed showed occlusion of the left vertebral ar¬ tery without other abnormalities noted. Twist drill needle biopsy of the cerebellum showed necrotic cerebellar tissue in two patients and normal tissue in one. Other systemic laboratory examinations were not helpful for the diagnosis.

Treatment All

patients

received

general supportive

Two patients were treated with¬ out success with external ventriculostomy drainage to relieve the hydrocephalus noted at ventriculography. Only one pa¬ tient underwent surgery with evacuation of the necrotic cerebellar tissue. Unfortu¬ nately, that patient was comatose at the time of surgery and failed to recover in the measures.

postoperative period. Course of the illness is shown in the Figure. Except for the two patients in coma, without histories, there was a time interval of 30 hours or more between the onset of symptoms and death. Excluding these two patients, the mortality for the initial 48 hours was 15%, which differs markedly from the high mortality reported for cerebellar hemorrhage during the same time interval."·18 The time interval of 60 to 120 hours prior to death included the onset of symptoms in the majority of patients (65%). This incidence would have been greater if intensive life-support measures (artificial respiration) had not been insti¬ tuted in the three patients whose life was prolonged in a vegetative state for the 8 to 15 days in the Figure. Two further important observations were made. First, in the majority of pa¬ tients, an interval of approximately six hours between the onset of obtundation or stupor and the onset of coma was noted. A similar interval was noted between the on¬ set of coma and death. Second, once the pa¬ tient's level of consciousness began to de¬ teriorate, there was a relatively short time in which to treat the disease aggressively if one were to salvage any of the patients. The final clinical diagnosis was brain stem (pontine) infarction in seven pa¬ tients, cerebral vascular accident in six, ce¬ rebral hemorrhage in five, pontine hemor¬ rhage in two, subarachnoid hemorrhage in one, and multiple sclerosis in one. Cerebel¬ lar infarction, hemorrhage, and tumor were the clinical diagnoses in single pa¬ tients. In three patients, diagnosis of pri¬ mary respiratory failure, pneumonia, and myocardial infarction were made without a suspicion of central nervous system le¬ sions. In no case was the correct diagnosis made early, as Dinsdale18 and Rey-Bellet17 The

course

also noted in 83

cases

with cerebellar hem¬

50

orrhage. NEUROPATHOLOGICAL DATA Locations of cerebellar infarctions shown below.

Superior left Bilateral Posterior Superior Total

14 9 1

Left vertebral Bilateral vertebral Left posterior inferior cerebellar Right posterior inferior cerebellar Left superior cerebellar Left posterior cerebral

^20·

3 1 28

The most common site was the posteroinferior half of a cerebellar hemisphere. This site represents that portion of the cerebellum that is predominantly supplied directly from the ipsilateral vertebral ar¬ tery via the posterior inferior cerebellar artery. The sites of recent arterial occlu¬ sions are as follows:

Right vertebral

1 30-

Predominantly

unilateral Posterior left Posterior right

40-

,

are

10 7 1 5

5 1 2

In only four cases was the infarction bi¬ lateral with extensive destruction of major portions of both cerebellar hemispheres. The size of the predominantly unilateral infarction was always extensive, involving greater than a third of the affected hemi¬ sphere in all cases and up to one half to two thirds in the majority of cases. The in¬ farction was of the hemorrhagic type in seven of the 28 cases. In all cases, the microscopical appear¬ ance was that of infarction (necrosis), is¬ chemie or hemorrhagic, varying from 48 hours to two weeks in duration. The major¬ ity of cases showed microscopic changes consistent with an infarction of three to six days duration with substantial pallor and edema, loss of neurons, ischemie neuronal change, invasion of polymorphonuclear and mononuclear cells, astrocytic swelling, and the early appearance of gitter cells. Marked molding with compression of the medulla was present in all cases (28) and was the probable cause of death in these patients. Obliteration or shift, or both, of the fourth ventricle was observed in 27 of the 28 specimens. Secondary obstructive

hydrocephalus was a frequent accom¬ paniment. The majority of specimens (24)

showed herniation of necrotic cerebellar tonsils through the foramen magnum. Of

::: -1-

24

"

48

72

*\, .\/SL·

-1-1-/ — —[— — 12 15 9 120 6 96

Hours Days INTERVAL TO DEATH onset of symptoms (squares, thin lines, shaded), of obtunda¬

Duration to death from tion (circles, heavy line), and of

coma

(dots).

interest were two specimens with upward transtentorial herniation of the anterior cerebellum following massive superior cerebellar infarctions. Two specimens showed no herniation. The brain stem was examined micro¬ scopically in all cases. The gross and micro¬ scopical examination of the brain stem in 18 of the 28 cases failed to show any sub¬ stantial abnormality. A lateral medullary infarction of duration consistent with the associated cerebellar infarction was noted in five specimens. An old lateral medullary infarction was found in one case. Small acute pontine infarctions were noted in two cases, one in the basis and the other in the tegmentum. Old healed small pontine infarctions were evident in two additional cases. None of these pontine infarcts ap¬

peared large enough or appropriately enough located to have contributed much to clinical misdiagnosis. Other than hydrocephalus and cerebral edema in 23 cases, examination of the cere¬ brum failed to show substantial acute pathological changes except in three cases: recent posterior temporo-occipital infarcts in two and a recent small hemorrhagic thalamic infarcì in one. In addition, pre¬ existing cerebral lesions were found in nine cases: old infarcts in seven cases (two with middle cerebral artery infarcts, two with posterior cerebral artery infarcts, two with basal ganglia infarcts, and one with an internal capsule infarcì and état lacu¬ naire). An incidental olfactory groove meningioma was found in one case and an old temporal lobe contusion in another. A severe degree of atherosclerosis in all the vessels at the base was seen in 16 cases, specifically including the vertebro-

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basilar system. In eight cases, the ath¬ erosclerosis was moderate and in four slight. Old occlusions of the vertebral ar¬ tery were noted in two cases, and an old oc¬ clusion of the internal carotid artery was noted in an additional case. These recent arterial occlusions were found in 21 of the 28 cases; in seven cases, a site of occlusion was not shown. The most frequent site of occlusion associated with massive cerebel¬ lar infarction was one vertebral artery. In each case, the side of vertebral artery oc¬ clusion determined the cerebellar hemi¬ sphere involved. An isolated occlusion of a posterior inferior cerebellar artery was found in one case.

OLD CEREBELLAR INFARCTIONS

Large old areas of cystic necrosis of the cerebellum were found in 24 of the 5,494 adult brains examined. These 24 lesions were grossly and microscopically consist¬ ent with old healed massive cerebellar in¬ farcts and measured 2x2x0.5 cm or greater in size. The posteroinferior half of one cerebellar hemisphere was involved in 18 cases and the superior half of one cere¬ bellar hemisphere in six cases. An old ver¬ tebral artery occlusion was found in 11 cases and an old superior cerebellar artery occlusion in five cases. An associated old lateral medullary infarction was noted in three cases and old pontine infarction in two additional cases. Moderate hydro¬ cephalus was found in 13 cases. An intensive review of these patients' past medical histories from the hospital records failed to show evidence of a past symptomatic episode or a hospital admis¬ sion that could be correlated with these old cerebellar infarctions in 12 of the 24 cases.

A past hospital admission for a cerebro¬ vascular accident was elicited from three patients, but the specific details could not be found. All of the remaining nine pa¬ tients had been admitted to a hospital three months to 14 years prior to their ter¬ minal illness with an acute central nervous system illness that could, retrospectively, be attributed to an acute cerebellar infarc¬ tion. In seven patients, symptoms and signs of cerebellar dysfunction had been noted; three of these developed some de¬ gree of obtundation, and one became comatose for five days. They all subse¬ quently recovered without a substantial neurological deficit. The remaining two pa¬ tients had been admitted for progressive obtundation without focal neurological signs. One deteriorated to a comatose state lasting three days, but both patients recov¬ ered without a substantial residual neuro¬ logical deficit. Of the six patients who de¬ veloped a marked deterioration in their level of consciousness, four proved to have had superior cerebellar infarctions; these four patients included the two who devel¬ oped coma and subsequently recovered. The correct clinical diagnosis was not recorded in any of these patients. Further¬ more, there were no characteristic features in the symptoms, signs, or course that could have differentiated these patients from those who died acutely of massive cerebellar infarction. Another observation of interest is re¬ lated to the patients with old cerebellar in¬ farcts who also had hydrocephalus at au¬ topsy. Of 13 such patients, seven had a substantial unexplained dementia. Only two of the remaining 11 patients without hydrocephalus had been demented.

COMMENT The reason why acute cerebellar in¬ farction is considered clinically a rare disease is evident from the present review: the correct premortem diag¬ nosis was made in only one patient and then only just before death. Acute cerebellar infarction appearing as an enlarging posterior fossa mass is considered an even rarer dis¬ ease.1015 Indeed, only isolated case re¬ ports are available of the correct diagnosis being made during life. However, our data indicate that its frequency is greater than is generally thought even when one considers only those cases uncomplicated by massive brain stem or cerebral infarctions. The incidence of such massive un¬ complicated cerebellar infarctions ap¬ proximates that of acute spontaneous

cerebellar hemorrhage, a disease that recently has been recognized as a rea¬ sonably common and treatable prob¬ lem.1417·19 As with most occlusive cerebro¬ vascular diseases, acute cerebellar in¬ farction is a disease of later life with a predominance in men. A close asso¬ ciation exists between acute cerebel¬ lar infarction and generalized cardio¬ vascular disease, hypertension, and diabetes mellitus. The importance of acute massive cerebellar infarction is emphasized by its high mortality. Exactly how high is difficult to estimate since the cor¬ rect clinical diagnosis was rarely made, so that the denominator (total number of cases of cerebellar infarc¬ tion) is unknown. However, from the fact that we could find 24 examples of old cerebellar infarcts (comparable to the 28 examples of "uncomplicated" acute infarcts) in the adults autopsied, it would appear that the mor¬ tality may approach or exceed 50%. The mortality rises further for those patients who require hospital ad¬ mission and develop evidence of pro¬ gressive brain stem dysfunction. Evidence for such brain stem dys¬ function was elicited in only six cases of old cerebellar infarctions. Thus, the mortality for patients developing signs of progressive brain stem dys¬ function may exceed 80%. It is obvious that one of the princi¬ pal obstacles to the development of a successful management or therapeu¬ tic program for this disease is the failure to make the diagnosis clini¬ cally, particularly in the early stages of the illness. However, consideration of the clinical appearance of acute un¬ complicated cerebellar infarctions in our series shows a sufficiently com¬ mon constellation of symptoms, signs, and course to be of diagnostic value. Most of the early symptoms and signs can be explained on the basis of destruction of cerebellar tissue. Ap¬ proximately 80% of these patients had such symptoms and signs as vom¬ iting, dizziness or vertigo, ataxia of gait, extremity dysmetria, dys¬ arthria, and nystagmus. An associ¬ ated lateral medullary syndrome was exhibited by 21% of the patients at the time of admission. The subse-

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course was characterized by a latent interval of 24 to 96 hours fol¬ lowed by progressive neurological de¬ terioration, including seventh cranial nerve palsy, gaze paresis, small poorly reactive pupils, impairment of con¬ sciousness, and motor (pyramidal type) dysfunction. Once these symp¬ toms and signs appeared, a relentless

quent

progression

to

quadriplegia,

coma,

and death over a few hours or days was the usual course of events (Fig¬ ure). Death was due to a sudden ar¬ rest of cardiorespiratory function following a brief period of ataxic res¬ pirations. The orderly and predictable pattern of respiratory failure usually seen in transtentorial herniation was rarely observed in these patients. All of the later symptoms and signs and the clinical progression point directly to brain stem dysfunction. Since no anatomical changes were found in the medulla, pons, or mid¬ brain on gross and microscopical ex¬ amination, it is reasonable to postu¬ late that the progressive brain stem dysfunction was due to mechanical compression by the massive cerebel¬ lar swelling that was found at au¬ topsy. The time course of the develop¬ ment of maximal symptoms, signs, and death also lends support to such a model. Medullary failure and death occurred in the majority of patients three to five days following the onset of symptoms. This time interval is of the same'order as that noted for max¬ imal swelling following sudden, mas¬ sive cerebral encephalomalacia due to occlusion of a major supratentorial artery.20-21 Thus, each acutely fatal case of massive cerebellar infarction

appeared clinically as an expanding posterior fossa mass with progressive mechanical compression of the brain stem.

Although vertebral artery occlusion frequently asymptomatic, the most common cause for these large cerebel¬ lar infarctions was a recent ipsilater¬ is

al vertebral artery occlusion (65%). A similar incidence of vertebral artery occlusion has been shown in patients with the lateral medullary syn¬ drome.21 Furthermore, large asympto¬ matic cerebellar infarctions are fre¬ quently associated with ipsilateral vertebral artery occlusion. One expia-

nation for cerebellar infarction being less common than brain stem infarc¬ tion is that the cerebellum has a rich collateral circulation.22 However, re¬ cent angiographie studies of the vertebrobasilar arterial system have shown a high incidence of anatomical variations of arterial supply23 and leave in doubt the status of the cere¬ bellar collateral circulation. These variations in the arterial supply to the cerebellum may have been of paramount importance in our pa¬ tients with massive cerebellar infarc¬ tion. Unfortunately, our retrospective pathological data are not adequate to confirm either this point or many other clinicopathological questions of

importance. The

pathogenesis

of the massive

swelling that accompanies large cere¬

bellar infarctions is unknown. Cur¬ evidence, although partly infer¬ ential and incomplete, suggests that the initial abnormality leading to the swelling is an ischemie defect in the capillary or ischemie derangement of glial cell metabolism or both, which result in progressive intracellular and extracellular fluid accumulation.21 The size of the infarcì is important since massive cerebellar swelling has not been observed with infarcts affecting less than one third of a cerebellar hemisphere. Other factors remain to be resolved, such as the role of embo¬ lization to the vertebrobasilar system. One fourth of the infarcts were hem¬ orrhagic, and vertebral system embo¬ lization was verified at autopsy in six of these cases. Thus, embolization oc¬ curs with a high incidence in these acute cases (at least 25%). This high incidence may be a reflection of the sudden occlusion associated with an embolus, which does not permit time for collateral formation or induces spasm in the collaterals already pres¬ ent and therefore results in large symptomatic cerebellar infarctions. When the cerebellar swelling is symptomatic, as in our acutely fatal cases, the cerebellar mass appears to exert its effect predominantly by di¬ rect compression of the brain stem, although in a few patients upward transtentorial and downward tonsillar herniations may be of importance. The effect of such compression or herrent

niation or both is to directly damage the neural tissues and distort the ves¬ sels of the brain stem, ultimately re¬ sulting in necrosis of both neural and vascular elements. The reason why the incidence of symptomatic brain stem compression is greater with large cerebellar infarcts (75%) than with large supratentorial infarcts (25%)21 is probably related to the smaller size of the posterior fossa with less ability of the neural ele¬ ments, cerebrospinal fluid, and blood vessels to compensate for the rapidly

expanding mass lesion. The diagnosis of acute

massive cerebellar infarction can be made if one has a high index of suspicion and an accurate clinical evaluation. Es¬ sentially, the patient has evidence of an expanding posterior fossa mass le¬ sion resembling acute cerebellar hem¬ orrhage."19 Posterior fossa subdural and epidural hematoma or rapidly ex¬

panding cerebellar neoplasms may also present similar clinical pictures; the diagnosis of these conditions may be aided by the presence of an occipi¬ tal skull fracture and history of trauma or the presence of a primary neoplasm. However, the initial differ¬

entiation of these various clinical en¬ tities may not be imperative since they all represent treatable, expand¬ ing posterior fossa mass lesions. Fisher et al19·24 and others21·22 have amply described the differentiating features of the other various stroke syndromes, and in most cases, these should not offer difficulties with the differential diagnosis. Certain cases of complicated cerebellar infarction and progressive brain stem infarction will remain difficult diagnostic prob¬ lems. Furthermore, the diagnosis will remain especially difficult in those pa¬ tients who have no accurate history and are in a stuporous state, so that the clinical examination is limited. From our data and those of oth¬ ers1019 regarding acute cerebellar in¬ farction and hemorrhage, it now ap¬ pears imperative that clinicians immediately and accurately identify treatable posterior fossa mass lesions from brain stem infarction. A delay in a patient exhibiting progressive brain stem dysfunction will in most cases result in irreversible brain

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damage and death. A lumbar puncture may be hazardous, need¬ lessly delaying and frequently con¬ fusing. In contrast to the more fulminating course of cerebellar hem¬ orrhage, the syndrome of cerebellar stem

infarction evolves more slowly, and in most of these patients, there is sufficient time to permit technically skillful neuroradiological studies. The

of choice appears to be combined carotid and vertebral angi¬ ography. This approach implies that angiography will be performed on some patients whose primary lesion is a brain stem infarction; however, the risks of modern contrast media and neuroradiological techniques are suf¬ ficiently low to be justified.25 Further¬ more, vertebral angiography may

procedure

In patients with acute massive cerebellar infarc¬ tion, vertebral angiography should show an avascular cerebellar mass and, in two thirds of the cases, an oc¬ cluded vertebral artery. Carotid angi¬ ography should show some degree of hydrocephalus in the majority. Having determined the presence of an acutely expanding cerebellar mass, the clinician must distinguish between the various posterior fossa mass lesions. The most difficult dif¬ ferential diagnosis will be between acute cerebellar hemorrhage and in¬ farction, but the treatment should be the same in most cases, and no time should be lost. Acute cerebellar hem¬ orrhage is for all practical purposes uniformly fatal without surgical de¬ compression, whereas acute cerebellar infarction with progressive brain stem dysfunction has a mortality that approaches 80%. Since approximately 20% of patients with massive cerebel¬ lar infarctions who have evidence of progressive brain stem dysfunction will recover spontaneously without substantial neurological deficits, it would be ideal to develop a formula to predict which patients would recover. Unfortunately, our data do not yield such a formula. When the diagnosis of acute cere¬ bellar infarction with progressive brain stem dysfunction is reached from the clinical and angiographie evaluation, the initial mode of man¬ agement could include an intensive

yield a specific diagnosis.

trial of hyperosmotic agents and glucocorticoids in an attempt to re¬

lieve the acute brain stem compres¬ sion from cerebellar swelling. If there is either no prompt improvement in brain stem function or evidence of further deterioration, we recommend immediate surgical decompression of the necrotic, swollen cerebellum to prevent permanent brain stem dam¬ age and death. Definitive conclusions regarding the natural history of acute massive uncomplicated cerebellar infarction cannot be made from any retrospec¬ tive study. However, the present data suggest the following: Massive cere¬ bellar infarction carries a high mor¬

tality, 50%

to

80%,

not

quite

so

great

that associated with spontaneous cerebellar hemorrhage. Although some patients survive without sub¬ stantial neurological morbidity in spite of the development of what must have been severe brain stem dysfunction, occult hydrocephalus is a common residual. All available evidence suggests that patients who develop brain stem dysfunction should benefit from an immediate decompression of the in¬ farcted, swollen cerebellar hemi¬ sphere. For this to be accomplished, a as

high index of suspicion diagnosis are required.

and

an

early

study was supported in part by training grants in neuropathology (NS 05231-15) and neurosurgery (NS 05211-13) from the National Institute of Neurological Diseases and Stroke. This

References 1. Schwartz E: \l=U"\berden anatomischen und klinischen Befund bei Verschluss der Arteria cerebelli posterior inferior. Monatsschr Psychiatr Neurol 32:132-159, 1912. 2. Schaffer K: \l=U"\bereinige Bahnen des menschlichen Rhombencephalons. Z Neurol Psychiatr 46:60-94, 1919. 3. Goodhart SP, Davison C: Syndrome of the posterior inferior and anterior inferior cerebellar arteries and their branches. Arch Neurol Psychiatr 35:501-524, 1936. 4. Germain A, Morran A: Ramollissement c\l=e'\rebelleuxpseudotumoral. Bull Soc Med Hop Paris 54:1695-1700, 1938. 5. Adams RD: Occlusion of the anterior inferior cerebellar artery. Arch Neurol Psychiatr 49:765-770, 1943. 6. Kubik CS, Adams RD: Occlusion of the basilar artery: A clinical and pathological study. Brain 69:6-121, 1946. 7. Fattovich G: Sui rammolliment cerebellari. Cervello 26:48-64, 1950. 8. Fang HCH, Palmer JJ: Vascular phenomena involving brain stem structures: A clinical and pathological correlation study. Neurology 6:402-419, 1956. 9. Fisher CM, Karnes WE, Kubik CS: Lateral medullary infarction: The pattern of vascular occlusion. J Neuropathol Exp Neurol 20:323-379, 1961. 10. Fairburn

B, Oliver LC: Cerebellar softA surgical emergency. Br Med J 1:1335\x=req-\ 1336, 1956. 11. Lindgren SO: Infarctions simulating brain

ening:

Downloaded From: http://archneur.jamanetwork.com/ by a University of Iowa User on 05/24/2015

tumors in the

posterior

fossa. J

Neurosurg

13:575-581, 1956. 12. Pomm\l=e'\ B, et al: Le ramollissement

pseudotumoral du cervelet: A propos de deux observations. Sem Hop Paris 35:791-793, 1959. 13. Wood MW, Murphey F: Obstructive hydrocephalus due to infarction of a cerebellar hemisphere. J Neurosurg 30:260-263, 1969. 14. Norris JW, Eisen AA, Branch CL: Problems in cerebellar hemorrhage and infarction. Neurology 19:1043-1050, 1969. 15. Lehrich JR, Winkler GF, Ojemann RG: Cerebellar infarction with brain stem compression: Diagnosis and surgical treatment. Arch Neurol 22:490-498, 1970. 16. Plum F, Posner JB: Diagnosis of Stupor and Coma, ed 2. Philadelphia, FA Davis Co, 1972, pp 136-137. 17. Rey-Bellet J: Cerebellar hemorrhage: A

clinicopathologic study. Neurology 10:217-222,

1960. 18. Dinsdale HB: Spontaneous hemorrhage in the posterior fossa. Arch Neurol 10:98-115,1964. 19. Fisher CM, Picard EM, Polack A, et al: Acute hypertensive cerebellar hemorrhage. J Nerv Ment Dis 140:38-57, 1965. 20. Shaw CM, Alvord EC Jr, Berry RG: Swelling of the brain following ischemic infarction with arterial occlusion. Arch Neurol 1:161-177, 1959. 21. Plum F: Brain swelling and edema in cerebral vascular diseases. Res Publ Assoc Res Nerv Ment Dis 41:318-348, 1966. 22. Loeb C, Meyer JS: Strokes Due to Vertebro\x=req-\ Basilar Disease. Springfield, Ill, Charles C Thomas, 1965, pp 98-102. 23. Takahashi M, Wilson G, Hanafee W: Catheter vertebral angiography: A review of 300 examinations. J Neurosurg 30:722-731, 1969. 24. Fisher CM: Some neuro-ophthalmological observations. J Neurol Neurosurg Psychiatr 30:383-392, 1967. 25. Takahashi M: Atlas of Vertebral Angiography. Baltimore, University Park Press, 1974, pp 11-12.