Cerebral amyloid angiopathy

lntracerebral hemorrhage (ICH) occurs in about 70%-75% of all strokes, and hypertension and cerebral amyloid angiopathy (CAA) are the main underlying causes. There is often controversy regarding surgical evacuation especially in elderly patients. Follow-up of these patients and regulation of hypertension is important to prevent re-bleeding. The number of recurrent hematomas will increase with time of follow-up. We reviewed 968 patients with an ICH treated in our Department and 48 patients with recurrent hemorrhages (4.9%). The mean interval between the first and the second hemorrhage was three years (one month to W years). Clinical outcome after a second hemorrhage was severe and only 50% of patients were operated on the second hemorrhage compared to 77% (37/48) of patients who were operated on the first hemorrhage. [Neurol Res 2003; 25: 853-856]

Keywords: lntracerebral hemorrhage; recurrence; cerebral amyloid angiopathy; hypertension

INTRODUCTION

Intracerebral hemorrhage (ICH) accounts for 10%-15% of all strokes and is a common neurosurgical emergency and operative procedure. The patients are becoming older and hypertension and CAA are usually the causes for ICH. Recurrence of hemorrhages is a frequent phenomenon. The recurrence rate is between 2.7%1 and 24%2. Hill et al.3 examined 423 patients with ICH and found a risk of recurrence of 2.4% per year. Bailey et al.4 reviewed 10 studies reporting recurrent stroke in survivors of primary ICH. Patients with a primary lobar ICH had a higher rate of recurrent ICH than those with a deep, hemispheric ICH. Burn et al.5 followed 675 patients with a stroke and found that the risk of stroke recurrence did not appear to be related to age. Lobar location of the primary hemorrhage was one predictor of recurrence and increased risk for a second hemorrhage2,3. Regular antihypertensive therapy of the patients after the first hemorrhage is important to prevent a recurrent hemorrhage, which often occurs at a different location from the previous ICH.

MATERIALS AND METHODS

We reviewed the charts of 968 patients with an ICH, who were treated in our Department between January 1991 and May 2002. All concomitant diseases were evaluated, especially blood pressure, results of blood samples, malignant tumors, anticoagulation, diabetes and coronary heart disease. The regular medication of the patient, histological examination and complications of the operation were analyzed. The CT scans and MRI scans of the 48 patients with recurrent ICH were evaluated to compare size and localisation of the different bleedings.

RESULTS

Between January 1991 and June 2002, 1145 patients with an ICH were seen in our Department. Of these, 968 patients were treated as inpatients, the other patients were seen on referrals and not operated on. Of the 1145 patients, 918 had hypertension.

Of the 968 patients, 757 had hypertension, 526 coronary heart disease and 1 79 diabetes mellitus.

Male patients numbered 552, female 416 (1.3:1). Mean age was 63.7 years (four months-94 years). Lobar hemorrhage was found in 494 patients, deep hemispheric bleeding was found in 327 patients. Ventricular hemorrhage occured in 28 patients, bleeding within the cerebellum in 104, and within the brainstem 71 patients.

Of 968 patients 246 died within 30 days after the hemorrhage (25.4%).

CAA was found in 70 patients. Anticoagulation was the reason for the hemorrhage in 139 patients. Tumor hemorrhage was proven histologically in 56 patients, an arteriovenous malformation (AVM) as underlying pathology was found in 32 patients and cavernoma in 20 patients.

Hypertension and CAA were found in 5.9 % (57/968).

Forty-eight patients had recurrent ICH (4.9%). Fortytwo had hypertension and 13 of these had no antihypertensive medical therapy. Thirty-four had coronary heart disease, 10 diabetes mellitus, nine CAA and four were on anticoagulation therapy.

Hypertension and CAA were found in 12.5 % (6/48).

Twenty-nine patients were male, 19 female (1.5:1). The mean age at the time of the first stroke was 65 years (32-84 years). The mean age at the second hemorrhage was 67.8 years (42-84 years).

In 77% (37/48) the first ICH was removed surgically. Eleven patients were treated conservatively. Lobar hemorrhage was found in 27 patients, deep hemispheric bleeding was found in 14 patients. Ventricular hemorrhage occured in three patients, bleeding within the cerebellum in three and within the brainstem in one patient.

The indication for removal of the recurrent hematoma is difficult and dependent on the clinical condition of the patient. The second bleeding was operated on in only 50% (24/48) and the other 24 patients were observed. Ten patients (20.8%) died after the second hemorrhage. The Glasgow Outcome Score was GOS1 in 10 patients, GOS2 in two, GOS3 in 28, GOS4 in seven and GOS5 in one patient.

Thirty-one patients received anti-hypertensive therapy (64.6%). Seventeen did not receive anti-hypertensive medication at the time of the second stroke (35.4%).

The mean interval between the first and the second hemorrhage was three years (1 month-10 years). The localisation of the second hemorrhage was the same in 16 patients (33.3%) and different to the first one in 32 patients (66.6%).

DISCUSSION

Primary ICH remains a stroke subtype associated with a high mortality rate and for which the level of consciousness on admission is the strongest predictor of fatal outcome both at 30 days and during the first year after bleeding. A pre-ictal history of heart disease increased the 30-day mortality rate6. The outcome after a second recurrent hemorrhage is even worse1,2,7,8.

Chen el al.7 examined 47/892 (5.3%) patients with recurrent hypertensive ICH. There were 25 men and 22 women. The mean age was 59 years at the first bleed and 62 years at the second bleed. The median interval between two hemorrhages was two years and four months. Of the hemorrhages, 46/47 occurred at a different site from the previous hemorrhage. The outcome of the recurrent bleeding was severe. Twenty-six percent died and 51% were totally dependent or vegetative. Arakawa et al.9 analyzed 74 patients with hypertensive brain hemorrhage. Eight patients (11%) had recurrent hematomas and the overall recurrence rate was 2.0% per patient-year. The interval between first and second hemorrhage ranged between 1.3 to 12.3 years. They found that the diastolic blood pressure was significantly higher in the recurrence group than in the nonrecurrence group. No patients with diastolic blood pressure

The risk of recurrent hemorrhage significantly increased in the patients who had anti-hypertensive therapy of less than three months after the initial attack compared to those with further long-term therapy. The risk of recurrent hemorrhage was not significantly associated with factors such as age, sex and medical histories. Lee et al.1 reported 14 patients with recurrent intracerebral hemorrhage due to hypertension. Thirteen were women. The mean interval between the attacks was 13.1 months. None of the patients had received regular anti-hypertensive therapy. The site of the recurrent hemorrhage was different from the initial site in 13 patients. Lee et al.1 think that the hypertensive changes of the cerebral arteries are considered to be the major cause of these recurrent hemorrhages. Neau et al.8 found 24/375 (6.4%) patients with a recurrent ICH. Seventy-one percent of the patients were hypertensive. The recurrent hemorrhage occurred at a different location from the previous ICH. The outcome after the recurrent hemorrhage was usually poor. They found lobar hematoma and younger age as risk factors for recurrences whereas gender and previous hypertension were not.

Our experience was that anti-hypertensive therapy was inadequate in most of the patients and that this increased the risk of recurrent bleeding. Also the clinical condition of the patients after a second hemorrhage was worse and the indication for an operation was not as aggressive as for the first hemorrhage. In the 48 patients who had a recurrent hemorrhage 37 patients were operated at the time of the first hemorrhage while only 24 were operated on the second hemorrhage.

The relation between female and male patients is nearly 1 :17,10. In our patient group we had 29 male and 19 female patients (1.5:1). Only Lee et al.1 described recurrent hemorrhage in 13 female patients out of 14 patients.

Apart from hypertension, patients with CAA are at risk for a recurrent hemorrhage. Tyler et al.11 described a 63year-old man with four ICHs due to CAA. They noted that the occipital and temporal vessels are most commonly affected. Important also is the fact that the second hemorrhage often occurs at a different site2,5,8,9,12. We also found a new localisation of the recurrent hemorrhage in 66% (32/48) of the patients.

Greenberg et al.1 used serial gradient-echo MRIs in 24 patients with previous lobar hemorrhage 1.5 years after the initial hemorrhage and demonstrated additional hemorrhages at follow-up in 38%. Their results suggest a role for gradient-echo MRI in assessing disease progression in CAA. O'Donnell et al.13 performed a prospective study of elderly patients who survived a lobar ICH. Recurrent hemorrhages were found in 19/71 (27%). The apolipoprotein E genotype was significantly associated with the risk of recurrence. The epsilon2 and the epsilon4 alleles of apolipoprotein E appear to be associated with the severity of CAA. Diabetes was associated with recurrent ICH by univariate analysis.

Passera et al.2 followed 112 survivors of a first primary ICH for a mean period of 84.1 months and found one or more re-bleedings in 24% (27/112) of these patients, and 70% died as a consequence of their second or third hemorrhage.

More than 67% of the patients had arterial hypertension. Re-bleeding occured in the same site as the first hemorrhage in 33% and in a different site in 67% (Figure 1).

Many cases with recurrent hemorrhage exhibited a 'lobar-lobar' type recurrence, which is suggestive of the presence of CAA8,13. This is similar to our case (Figure 2), where lobar hemorrhage occured at a different localisation four months after the first hemorrhage and histological examination revealed CAA. The combination of hypertension and CAA increases the risk of rebleeding.

REFERENCES

1 Lee KS, Bae HG, Yun IG. Recurrent intracerebral hemorrhage due to hypertension. Neurosurgery 1990; 26: 586-590

2 Passero S, Burgalassi L, D'Andrea P, Battistini N. Recurrence of bleeding in patients with primary intracerebral hemorrhage. Stroke 1995; 26: 1189-1192

3 Hill M, Silver F, Austin P, Tu J. Rate of stroke recurrence in patients with primary intracerebral hemorrhage. Stroke 2000; 31: 123-127

4 Bailey RD, Hart RG, Benavente O, Pearce LA. Recurrent brain hemorrhage is more frequent than ischemic stroke after intracranial hemorrhage. Neurology 2001; 56: 773-777

5 Burn J, Dennis M, Bamford J, Sandercock P, Wade D, Warlow C. Long-term risk of recurrent stroke after a first-ever stroke: The Oxfordshire community stroke project. Stroke 1994; 25: 333-337

6 Nilsson OG, Lindgren A, Brandt L, Saveland H. Prediction of death in patients with primary intracerebral hemorrhage: A prospective study of a defined population. J Neurosurg 2002; 97: 531-536

7 Chen ST, Chiang CY, Hsu CY, Lee TH, Tang LM. Recurrent hypertensive intracerebral hemorrhage. Acta Neurol Scand 1995; 91: 128-132

8 Neau JP, Ingrand P, Couderq C, Rosier MP, Bailbe M, Dumas P, Vandermarcq P, Gil R. Recurrent intracerebral hemorrhage. Neurology 1997; 49: 1 06-11 3

9 Arakawa S, Saku Y, lbayashi S, Nagao T, Fujishima M. Blood pressure control and recurrence of hypertensive brain hemorrhage. Stroke 1998; 29: 1 806-1 809

10 Bae HG, Jeong DS, Doh JW, Lee KS, Yun IG, Byun BJ. Recurrence of bleeding in patients with hypertensive intracerebral hemorrhage. Cerebrovasc Dis 1999; 9: 102-108

11 Tyler KL, Poletti CE, Heros RC. Cerebral amyloid angiopathy with multiple intracerebral hemorrhages. J Neurosurg 1982; 57: 286-289

12 Greenberg SM, O'Donnell HC, Schaefer PW, Kraft E. MRI detection of new hemorrhages: Potential marker of progression in cerebral amyloid angiopathy. Neurology 1999; 53: 1135-1138

13. O'Donnell HC, Rosand J, Knudsen KA, Furie KL, Segal AZ, Chiu RI, Ikeda D, Greenberg SM. Apolipoprotein E Genotype and the risk of recurrent lobar intracerebral hemorrhage. N Engl J Med 2000; 342: 240-245

Ralf Buhl, Harald Barth and Hubertus M. Mehdorn

Department of Neurosurgery, University of Kiel, Germany

Correspondence and reprint requests to: Ralf Buhl, MD, Department of Neurosurgery, University of Kiel, Weimarer Str. 8, 24106 Kiel, Germany, [buhlr@nch.uni-kiel.de] Accepted for publication July 2003.

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