P&S; Medical Review: Spring 1998, Vol.5, No.1

The patient is a 70-year-old male who presented to Columbia Presbyterian Medical Center (CPMC) emergency room (ER) complaining of being unsteady on his feet.

The patient's past medical history (PMH) includes hypertension. During his only prior admission (8/94) for chest pain and shortness of breath, he was found to be in atrial fibrillation with electrocardiogram (EKG) evidence of a prior inferior wall myocardial infarction (MI). An echocardiogram showed biatrial enlargement, a dilated left ventricle (LV), depressed ejection fraction (EF), and severe mitral and tricuspid regurgitation. Initially trace guaiac positive, he ruled out for acute MI, his guaiac cleared, and he was sent home on a failure regimen for outpatient gastrointestinal (GI) workup and consideration of chronic anticoagulation. There was concern the patient would fail to follow up after this admission and therefore he was not started on a coumadin regimen. Indeed, the patient never returned to clinic.

After 8/94, the patient was lost to follow up. He reports doing well on a regimen of shark cartilage until the morning of admission, when he awoke feeling nauseated and vomited. He attempted to stand but was unable to balance himself (although he denied vertigo); despite having full use of all four limbs, he found himself falling to the right when attempting to walk.

This patient's PMH and medications are only those listed above. He denies a history of tobacco use and reports only occasional alcohol use.

On exam, the patient appeared well developed, well nourished and in no apparent distress. He had a heart rate of 68 irregular, blood pressure of 186/90, respiratory rate of 16, and temperature of 97.3°. Head, eye, ear, nose and throat exam revealed the pupils to be equal, round, and reactive to light; optic discs sharp; no epistaxis; and a clear oropharynx. Neck exam showed no jugular venous distension, and the carotids were without bruits. Chest exam revealed bibasilar crackles. Heart exam revealed an irregular pulse, no murmurs, rubs, or gallops, although a leftward shifted point of maximum impulse (suggestive of left ventricular dilatation) was noted. The abdomen was soft, nontender, nondistended, without hepatosplenomegaly, and with normal bowel sounds. Extremity exam was benign. Rectal exam was normal and negative for occult blood. On neurological exam the patient was noted to be awake, alert, and attentive. He was found feeding himself with knife and fork when the neurologist entered the room. The patient spoke normally without dysarthria or aphasia. There was no apraxia or neglect; he bisected tape in midline.

There was no visual field deficit and extraocular movements were intact without nystagmus. He had normal facial sensations, facial strength, hearing, palate, and tongue. Also noted were normal symmetrical limb strength, good fingernosefinger and heelshin test results, and normal rapid alternating movements. The patient's gait was ataxic and veered to the right. Peripheral sensations were symmetrically intact to pinprick throughout all dermatomal distributions. Deep tendon reflexes were symmetric and the plantar reflex was downgoing.

Table 1. Blood Chemical and Hematological Values

	On Admission	Nl. Value
Whitecell count (103/µL)	9.2	4.8 10.8
Differential count (%)
neutrophils band cells lymphocytes monocytes	86 11 2 1	5462 35 2535 37
Hemoglobin (g/dL)	14	1418
Hematocrit (%)	41	4252
Platelet count (103/µL)	150	150450
Prothrombin time (sec)	13.2	1214
Partialthromboplastin time (sec)	28	2035
Sodium (mmol/L)	137	136146
Potassium (mmol/L)	4.1	3.55.1
Chloride (mmol/L)	101	96106
Bicarbonate (mmol/L)	23	2329
Blood Urea Nitrogen (mg/dL)	12	718
Creatinine (mg/dL)	1.0	0.71.3
Glucose (mg/dL)	203	70115
Calcium (mg/dL)	9.7	8.410.2
Phosphorus (mg/dL)	3.3	2.74.5
Uric Acid (mg/dL)	4.8	4.58.0
Cholesterol (mg/dL)	181	<200
Total protein (g/dL)	8.5	6.48.3
Total albumin(g/dL)	4.6	3.59.1
Total bilirubin (mg/dL)	0.7	0.21.3
Direct bilirubin (mg/dL)	0.3	0.00.3
Alkaline phosphatase(U/L)	307	39117
Aspartate aminotransferase (U/L)	39	540
Alanine aminotransferase (U/L)	37	756
Lactate Dehydrogenase (U/L)	276	122220
Creatine Kinase (U/L)	82	60320
Magnesium (mg/dL)	1.8	1.32.1

Figure 1: EKG confirming history of old IWMI and presence of atrial fibrillation. Evidence of left ventricular hypertrophy. No evidence of ongoing ischemia.

Blood chemistries were essentially normal and non-specific with respect to electrolytes, cell counts and coagulation times. The only finding of note was a high glucose; the patient had no history of glucose intolerance (Table 1). An EKG confirmed the history of an old inferior wall MI (IWMI), the presence of atrial fibrillation, as well as left ventricular hypertrophy (Figure 1). However, there was no evidence of active ongoing ischemia. Chest X-ray showed a mildly enlarged heart and a splaying upward of the left mainstem bronchus suggestive of left atrial enlargement. There was no evidence of infiltrate (Fig. 2). Head CT scan was significant for an old right frontal infarct and the possibility of an old right occipital infarct; there was a question of slight lucency of left cerebellum (Fig. 3a and 3b).

Figure 2: CXR showing mildly enlarged heart with a suggestion of left atrial enlargement, as evidenced by a splaying upward of the left mainstem bronchus. No evidence of infiltrate.

Assessment: Head CT suggested cerebrovascular ischemic disease for this patient, leading the team evaluating himto believe that he had suffered from a stroke.

Ischemic stroke affects nearly 500,000 people in the United States each year.¹ Approximately 400,000 stroke patients are discharged from acute care centers annually, 75% after their first stroke. Because there is currently no clear way to prevent stroke or reduce the morbidity of this disease, medicine has been witness to a rigorous study of the etiology and pathogenesis of stroke in recent history.

The Framingham Study included 5070 women and men between the ages of 30 and 62, without evidence of cardiovascular disease at the start of the study.² The study followed these patients for 36 years between 1950 and 1986, during which time there were 693 cases of acute stroke. These were classified as atherothrombotic (large or small vessel occlusive), cerebral embolism, transient ischemic attack (TIA), subarachnoid hemorrhage (SAH), intracerebral hemorrhage, or other. The plurality, 43.6% (among women) and 44.3% (among men) were of the atherothrombotic type. From the study data there were no significant differences in the types of strokes between men and women. The annual incidence of stroke increased with age, doubling with each consecutive decade over age 30. In any given decade, men were at higher risk than women.

Risk factors for stroke were defined by the Framingham Study through multivariate statistical analysis, a statistical tool used to separate the influence of one risk factor from another. These data allowed the investigators to conclude that hypertension is the strongest independent contributor to stroke risk. The significance of the independent contribution of hypertension goes down with age as it does for most risk factors for stroke, but remains significant even into the ninth decade. There is no threshold blood pressure below which the stroke risk flattens. Every increase of 7.5 mm Hg of diastolic blood pressure is associated with a 46% increase overall in risk of stroke and for every decrease of 5.8 mm Hg mean blood pressure (through therapeutic intervention) there is a 42% reduced risk of stroke. Isolated systolic hypertension, the prevalence of which is 20% in men and 30% in women over 75 years of age, is also an independent risk factor.

Heart disease is another strong predictor of stroke. Coronary artery disease or MI increased the stroke risk 3fold, independent of hypertension and tobacco use. Congestive heart failure (CHF) increased the risk by 5fold. Left ventricular hypertrophy was associated with a 4fold increase in stroke risk and was independent of age and blood pressure at the time of the stroke.

Atrial fibrillation (AF) incidence in the Framingham study ranged from 0.2/1000 in people in their fourth decade to 39/1000 among those in their ninth decade of life. AF was associated with a 5fold increased risk of stroke independent of other cardiovascular disorders. It represented the only stroke risk factor that increased with age: 6.7% of strokes in people in their sixth decade were attributed to atrial fibrillation; 36.2% of strokes in those in their ninth decade. In addition, the risk of recurrence within six months of first stroke was more than 2fold greater in patients with atrial fibrillation. (These patients were not anticoagulated).

Other risk factors with less strong stroke associations included cholesterol level, history of diabetes, and tobacco use. Total and low-density lipoprotein levels correlated with the degree of extracranial carotid stenosis, but not with incidence of stroke. Total cholesterol below 160 was an independent risk factor for intraparenchymal hemorrhage (this is an interesting bimodal risk). The history of stroke in patients with diabetes was estimated to be 34 times more common than in people with normal glucose tolerance. In the Framingham Study, diabetes was a significant independent risk factor only in women over the age of 65 years. Tobacco was associated with a 2fold increased risk of stroke at 2 packs per day. Of note, the risk remains greater in nonsmokers for up to five years after cessation. Other risk factors may include: hematocrit, fibrinogen, homocysteine level, and obesity.

Toni et al. (1995) looked at a series of 152 consecutive patients with their first ischemic event, who received medical attention within 5 hours of onset.³ All were evaluated against a fixed neurological scale and by CT on admission, with neurological evaluation repeated daily and CT repeated at 57 days. They stratified participants by course: progressing or nonprogressing. The course classification was based on sequential decrement of their neurological score. Age did not differ significantly between the progressing and nonprogressing groups. In addition, Canadian Neurological Score at presentation did not significantly predict outcome. However, the delay in being seen by the M.D. was significantly higher in people who did worse i.e., those who progressed (this may or may not reflect the way in which these people are treated). Blood pressure was not a significant predictor, but serum glucose level on admission was a significant predictor. Those who progressed had a documented elevation of serum glucose on admission. Other parameters examined included atrial fibrillation, various cardiopathies, diabetes, hypertension, previous TIA's, and smoking. None of these parameters were significant predictors of outcome. The importance of serum glucose levels is interesting our patient was admitted with a glucose of 203, with no history of diabetes.

The patient was admitted to the hospital and given a 5,000 unit bolus of heparin and begun on a heparin drip. A neurological consult was requested and the following recommendations were made: no more heparin boluses, keep PTT on the high side of normal (1.5x control), stop heparin immediately if there is any worsening of the neurological exam, monitor blood pressure with "gentle control" acutely, and work up stroke etiology with doppler studies, echocardiogram, erythrocyte sedimentation rate (ESR), and thyroid function tests (TFT's).

The neurological exam remained stable for the first 48 hours on the floor, HR 7090, BP 140/80 (off medication); hematocrit stable, PTT 62 (2.5x control). In the evening of day 2, crosscoverage was called for elevated blood pressure 190/110. Neurological exam was stable: flat discs, absence of retinal changes. A BUN/Cr of 15/.9 was noted. The decision was made to intervene for increased blood pressure and a test dose of 6.25 mg captopril was given.

This decision raises the question of what to do with blood pressure control after ischemic stroke. Strandgaard (1973) examined cerebral blood flow in humans over a range of systemic perfusion pressures and described an autoregulatory role of the cerebral arteries.⁴ Over a wide range of pressures in humans, (60 150 mm Hg) flow is held constant at approximately 50cc/100 g of tissue/ minute. It is only at very low and very high pressures that autoregulation is unable to compensate and flow varies from normal. In ischemic tissues, however, the autoregulatory function of the cerebral arteries is impaired; thus blood flow becomes much more dependent on perfusion pressure. At a flow of 2025 cc/100g/ minute electrical activity in the brain is lost; at 12 cc membrane integrity (and thus membrane potential) is lost.

Britton et al. (1990) did a retrospective study of 388 consecutive stroke patients admitted to a Stockholm hospital.⁵ Patients with a high blood pressure (>200/115) were compared with controls for outcome. No treatment intervention was given. The "high pressure" (HP) group consisted of 27 out of the 388 patients. The control group consisted of the remaining 361 patients. The authors did note a significant age difference between "high pressure" and control groups and therefore created an "age matched" control group by choosing for each member of the HP group two members of the control group who matched the HP member within 1 year of age. Other significant differences between the two groups were history of hypertension (more frequent in the HP group) and evidence of left ventricular hypertrophy (also more frequent in the HP group). There was no significant difference between HP and controls in terms of condition on presentation (e.g., alert vs. coma), or whether symptoms progressed or not. Overall "poor outcome," defined as death or discharge to a chronic care facility due to loss of independence, did not differ significantly between members of the HP group and either control group.

These studies and others led the American Heart Association Stroke Council to recommend in September of 1994 that blood pressure reduction "may be warranted if high blood pressure accompanies hemorrhagic transformation, MI, renal failure secondary to hypertension, or dissection. In general (in the absence of these signs), antihypertensive drugs should be withheld unless the calculated mean blood pressure [(systolic + 2 x the diastolic) / 3] is greater than 130 mmHg or the systolic blood pressure is greater than 220 mmHg."⁶ Agents recommended by the AHA are noted to have minimal intrinsic effect on cerebral vasculature and include: intravenous enalapril and labetolol and per orum captopril and nicardipine.

Our patient had a pressure of 190/110, with a mean pressure of 136 mmHg. In this case, the intervention taken by the crosscovering team was well justified.

There are three principal arteries that supply the cerebellum. The superior cerebellar artery (SCA), the anterior-inferior cerebellar artery (AICA) and the posterior-inferior cerbellar artery (PICA). Both inferior cerebellar arteries serve the inferior surface of the cerebellum, CN V and VIII, the descending sympathetics and the spinothalamic tracts. The symptoms common to strokes of these areas include: limb and gait ataxia, facial hypesthesia, vertigo, nystagmus, Horner's syndrome and limb/trunk hypesthesia. What distinguishes these two clinically is that AICA supplies the cochlear aspect of the eighth cranial nerve and occlusion of this artery is therefore associated with deafness and tinnitus. The SCA serves the superior surface of the cerebellum (lesions to which would also yield ataxia), but also supplies territories higher in the brainstem. As a result, occlusion of this artery classically yields ischemia of CN IV leading to a CN IV palsy. Another distinguishing feature of this type of infarct is choreiform dyskinesia associated with infarct of the brachium conjunctiva.

A PICA infarct is the most common cerebellar infarct. Typically it begins with headache, vertigo, nystagmus, and ataxia. PICA infarct is frequently associated with lateral medullary infarction (Wallenberg's syndrome): vertigo, nystagmus, ataxia, ipsilateral facial numbness, dysphonia, dysphagia, Horner's syndrome, hiccup, and possible loss of taste. The mechanism of PICA infarction is embolic in approximately 50% of cases and local thrombotic in the other 50%.

With SCA infarction, the "classic" syndrome is actually uncommon in clinical practice and includes ipsilateral limb and gait ataxia, Horner's syndrome, choreiform movements, and CN IV palsy. Commonly, however, it presents as ipsilateral gait ataxia and headache with or without vertigo. The mechanism is most commonly embolic. A SCA infarct is slightly less common than PICA infarction.

An AICA infarct is the rarest of the three accidents. The most common signs are vertigo, tinnitus, ipsilateral hearing loss, dysarthria and facial palsy, and may present with or without Horner's syndrome. Nearly 100% of these infarcts are locally thrombotic.

Frequently, cerebellar infarction is a benign condition with complete resolution of neurological findings. Resolution is less likely with brainstem involvement. These infarctions become life threatening, especially if they are large, when edema develops causing a mass effect in the posterior fossa and concomitant brainstem compression. Most severe cases follow PICA infarction because the PICA serves the largest volume of the cerebellum. Clinically, infarction followed by edema and mass effect results in progressive lethargy with bilateral Babinski's sign at about 48 hours postinfarction. With increasing posterior fossa pressure there follows obstruction of the fourth ventricle with hydrocephalus and compression of the anterior pons causing CN VI palsy, corneal areflexia, facial palsy, coma and decerebrate rigidity. Herniation either superiorly (supratentorially) or inferiorly through the foramen magnum may occur. This same syndrome may be caused by a postinfarction large cerebellar hemorrhage.

C.S. Kase (1994) suggested a plan for the management of cerebellar infarction.⁷ CT or magnetic resonance imaging (MRI) should be used to determine the size, extent, and location of the infarct. If small or partial, the author recommends workup for a cardiac source of embolism or posterior circulation disease. If it is a large, bilateral or multiple infarct it is suggested to monitor the patient in the ICU for 48 hours. Following this monitoring, if the patient is stable, further care can be provided in a less intensively monitored setting. If, in the first 48 hours, the patient shows progressive loss of consciousness, ipsilateral gaze palsy or other signs of impending herniation, an emergency CT or MRI should be pursued. If hydrocephalus is seen, ventriculostomy should be performed. If there is improvement following ventriculostomy no further surgical therapy is recommended. However, with further neurological deterioration, posterior fossa decompressive craniotomy should be performed.

On Day 3, vital signs were stable and the patient's neurological exam remained unchanged. The echocardiogram was essentially unchanged from the one done on prior admission. It confirmed a mildly dilated hypertrophic LV with inferior akinesis, mildly depressed ejection fraction, biatrial enlargement with mitral and tricuspid regurgitation. No clots were visualized. TFT's were within normal limits (WNL), ESR 12, Hct stable, and PTT 66. The patient was sent to Milstein Hospital from the Allen Pavilion for a MRI of the head in the afternoon. He tolerated the test well and the results remained pending on his arrival back at the Allen.

Early the following day (Day 4), the night float intern was called to see the patient for a blood pressure of 250/150 with a question of slurred speech. Because of two simultaneous emergent calls and impending arrival of the day team, the patient was next seen by the dayteam intern at 7 a.m. At this time the patient was unresponsive and BP was 250/140. Neurological exam showed withdrawal to deep pain only, constricted and poorly reactive pupils, absent L corneal reflex, and flaccid, areflexic limbs.

A head CT was ordered which showed a left cerebellar infarct with hemorrhagic transformation and edema; blood in third and lateral ventricles with compression of fourth ventricle and obstructive hydrocephalus; edema seen to have a mass effect on brainstem (Figure 4). The heparin was immediately stopped and the patient was transferred to the ICU, started on a Nipride drip, intubated to institute hyperventilation, and given mannitol and decadron. The MRI of the head done at the Milstein Hospital 14 hours prior to deterioration showed a left cerebellar infarct with hemorrhagic transformation into vermis .

The role of heparin in the treatment of stroke is widely debated. Sandercock et. al. (1992) published a large metaanalysis of randomized heparin trials in acute stroke.⁸ The studies varied with route and bolus of administration (IV vs. SQ).

The natural history of embolic stroke is that approximately 1215% of patients will have a second embolism within 2 weeks of the first event. The Cerebral Embolism Study Group (1984) performed a small, randomized placebo controlled trial of heparin anticoagulation after first embolic stroke.⁹ Intra-venous heparin begun 48 hours after onset of stroke was used to achieve PTT 1.52.5x control for ten days. Two patients were excluded for having hemorrhage on presentation. Other exclusion factors included pregnancy, BP >180/115, recent peptic ulcer disease, creatinine >4, Hct <27, decreased platelets, age >78 or < 18. Of the remaining 45 candidates, 24 received immediate heparin and 21 received placebo. The groups had a similar size distribution of the infarcts as determined by imaging. Outcome in this study was not statistically significant. However, there was a trend toward reduction of embolic risk. Notably there were no hemorrhagic transformations among those treated with heparin. Subsequent studies have shown that the risk of an embolic event following the first embolic event is reduced by 80% on heparin; this constitutes a clear indication for giving heparin in the case of embolic stroke.

Chamorro, et al. (1995) looked at the safety of giving heparin in a retrospective study of 171 consecutive patients receiving medical attention within 72 hours of ischemic stroke.¹⁰ The exclusion criteria were delayed medical attention (>72 hours), loss of consciousness, size, blood pressure >200/120, and history of bleeding disorders. The remaining 83 patients received heparin for 10 days to maintain a PTT 1.5-2x control. This study sought to identify characteristics at presentation which were predictive of increased risk for hemorrhagic transformation. Routine followup CT scans performed on all subjects after seven days revealed that of the 83, 20 underwent hemorrhagic transformations on heparin (as defined purely by imaging studies). Of those 20, only seven had clinical neurologic worsening associated with the transformation. Statistically significant predictors of hemorrhagic transformation included older age, greater volume of initially infarcted tissue (as calculated from scans), and PTT over 2x control. The only statistically significant predictor among those with clinically important hemorrhagic transformation was PTT: the mean PTT among those with clinical worsening was 3x control, compared to 1.6x in the control group.

Kay, et al. (1995) did a double-blind, randomized placebo controlled trial of the efficacy of lowmolecularweight heparin (LMWH) given early (within 6 hours) after acute stroke.¹¹ Exclusion criteria were hemorrhage on CT, > 48 hours to treatment, age, > 80 years of age, TIA, blood pressure >180/120, recent surgery, bleeding disorders, and moribund status. Patients were randomized to one of three groups: low dose LMWH (12,500 U/day), high dose LMWH (25,000 U/day) or placebo. Outcomes were evaluated at 10 days, 3 months, and 6 months. At the earliest evaluation, there was no significant difference in outcomes between the three groups. At 3 months and 6 months patients were evaluated for "poor outcome" which included death or loss of independence with activities of daily living. At the 3 month evaluation, while not statistically significant, there was a trend toward fewer poor outcomes among those receiving LMWH than among controls. At the 6 month evaluation, this trend reached statistical significance (p= .005), and a dose-response correlation emerged: significantly fewer poor outcomes among the high dose group than the low dose group.

Returning to the metaanalysis of Sandercock et al (1992), the potential benefit of heparin on a number of specific clinical outcomes for stroke patients was examined. With respect to deep vein thrombosis, there was a statistically significant 79% risk reduction for all heparin therapies using either I¹²⁵fibrinogen leg scan or venographic detection methods. Although one might expect the same result for pulmonary embolism, there have been few studies that have looked at this outcome and those that have are relatively small. Although there appeared to be a trend for a 58% risk reduction in pulmonary embolism, the results of this analysis were not statistically significant. Heparin's effect on death rate was examined, showing a trend toward survival benefit with heparin but this did not reach significance. (The study of Kay, et al. (1995) was not included in this metaanalysis.) With respect to complications of stroke and hemorrhagic transformation, there were a number of studies that looked at standard heparin and low molecular-weight heparin therapy. Essentially, the variance is so large in these studies we gain nothing significant. (Again Kay, et al. (1995) was not included).

The patient was transferred to the neurological intensive care unit in the Allen Pavilion. On arrival, the patient persisted in coma and was found to have fixed pupils, extensor posturing, and positive Babinski's. A ventricular drain was placed into the right anterior frontal horn in the event that the neurologic deficit might be partially reversible if hydrocephalus was relieved. The patient did not respond to this treatment and was maintained on supportive care for three days during which time he was made DNR and expired.

The conclusions to be drawn from this case and review of the literature are several. The sheer number of studies on the use of heparin in acute ischemic stroke is testimony to the lack of clarity on this particular subject. Examination of outcomes following anticoagulation or thrombolysis after acute myocardial infarction have clearly shown a benefit to intervention within a few hours (4-6) of the event. However, most studies of heparin use in stroke have focused on anticoagulation only within 48 to 72 hours after the acute event, potentially missing a critical therapeutic window. Work in this field is only now moving toward anticoagulation within hours of the event, and it is clear that large randomized controlled studies will be required to yield definitive evidence (one such study ongoing at CPMC presently is the TOAST study). The potential use of thrombolytics (eg tissue plasminogen activator) after acute stroke have also come under study and show promise in reducing long term sequelae of ischemic stroke.

The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study Group has demonstrated the therapeutic benefit of rt-PA in ischemic stroke.¹² Historically, this therapy has been controversial since intracerebral hemorrhage was a complication in early trials of thrombolytic therapy.¹³ Although fewer than 5% of patients met the entry requirements of the NINDS study (largely due to delay in treatment), they report that I.V. administration of rt-PA within 3 hours of stroke onset compared to placebo allowed patients a 30% better likelihood of minimal or no disability at three months. Patients were assessed using four independent scales for outcome. These results have led other investigators to suggest the need for multimodal therapies designed to attack multiple sites of the ischemic cascade, and the use of novel neuroimaging technologies that allow a rapid determination of occlusion sites as well as ischemic versus infarcted tissue.¹⁴

In summary, acknowledging that additional benefit may be derived from earlier initiation of heparin, even within the 48 hour window, there are some clear indications for its use. There is a significant reduction in embolic stroke recurrence following anticoagulation, as well as a significant risk reduction for deep vein thrombosis, and a reduction (though not statistically significant) in risk of pulmonary embolism. Although there does appear to be a 5 20% increased risk of hemorrhagic transformation on heparin (depending on which study one reads), the risk of clinically significant hemorrhagic transformation appears much lower, and indeed does not represent an absolute contraindication to heparin use after stroke. In evaluating the pros and cons of heparin use after acute stroke, the potential for clinical significance of hemorrhagic transformation must be considered. The cerebellum lies within a relatively enclosed bony fossa in the cranium and abuts a critical neurologic structure - the brainstem. Consequently, the risk of a hemorrhage in this site becoming clinically relevant may well be greater than in the cerebral hemispheres. Anticoagulation undertaken after a cerebellar infarct therefore merits careful consideration of the potential benefits and risks and careful monitoring to minimize risk of hemorrhagic transformation. Heparinization should be initiated without the IV bolus commonly given to patients with cardiac ischemia, and the goal should be a PTT lower than that recommended for cardiac patients (only 1.51.6 times control). Finally, vigilance is required to identify signs or symptoms of transformation. Early detection will allow cessation of anticoagulation and early intensive monitoring, with potential therapeutic intervention (intraventricular drainage, posterior craniotomy) prior to irreversible neurologic damage.

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