Korean Journal of Cerebrovascular Surgery 2008;10(3):429-436.
Published online September 1, 2008.
Clinical Analysis of Spontaneous Intracerebral Hemorrhage in Young People.
Lee, Hyun Woo , Chang, In Bok , Choi, Hyun Chul , Rim, Dae Cheol , Song, Joon Ho , Ahn, Sung Ki
Department of Neurosurgery, College of Medicine, Hallym University, Anyang, Korea. askns@hallym.ac.kr
Abstract
OBJECTIVE
Spontaneous intracerebral hemorrhage (sICH) is a leading cause of morbidity and mortality, especially in Asian countries. Nevertheless, few reports of sICH in young people have been published. This study investigates the clinical features of sICH in young people. METHODS: Between February 1999 and December 2007, we retrospectively reviewed the medical records of patients aged 45 years diagnosed with sICH at our institute. We analyzed the causes, locations, risk factors, and final outcomes of sICH in these patients. RESULTS: Twenty-one patients (14.5%) were younger than 25 years, while 27 patients (18.6%) were 25~34 years old. Ninety-seven patients (66.9%) were between the ages of 35~45. The most common cause of sICH was hypertension (57.9%). The most common location of sICH was in the lobar region (35.2%). Vascular anomaly was the main cause in both the <25 age group (76.2%) and the 25~34 age group (70.4%). The diagnostic rate of angiography was 75% for the under 25 age group and 80% in the 25~34 age group. CONCLUSIONS: Hypertension is the most common cause of sICH in people between 35 and 45, and vascular anomaly is the main cause in people under 35 years of age. Thus, angiography should be mandatory for people under 35 with sICH, and for people with lobar hemorrhage. For young people, early diagnosis of hypertension and strict blood pressure control is recommended.
Key Words: Intracerebral hemorrhage, Risk factors, Young people

Introduction


  
Spontaneous intracerebral hemorrhage (sICH) is a disorder that causes a high rate of morbidity and mortality worldwide. In western countries, sICH accounts for 10% of all stroke cases. However, in Asia, the incidence is higher with sICH accounting for 25.8% of stroke cases in Japan, and for 22
~35% of cases in Taiwan.18) In South Korea, more than 30% of stroke patients suffered a sICH, showing very high incidence. Despite various developments and improvements in treatment, there still appears to be a high rate of morbidity and mortality among the South Koreans.3)15) In 1990 alone, the World Health Organization estimated that there were 2.1 million people who died of sICH in Asia.23) 
   Although there might be slightly different results among researchers, the incidence of sICH in young people varies from 3.7
~40% of strokes.1)17)18) sICH is usually caused by hypertension and appears mainly in the basal ganglia, cerebellum, and brain stem. However, only 50~60% of sICH cases occurring in the lobar region were found to be caused by hypertension.5)23) There are only few studies on sICH in young people and fewer studies published in South Korea. In this study, we analyze the causes, locations, risk factors, and prognosis of sICH in young people and compare these characteristics with other studies to help prevent, diagnose, and judge the prognosis for sICH. 

Materials and Methods 

   One hundred forty five patients under the age of 45 were diagnosed with sICH, either by means of brain computerized tomography (CT) or Magnetic Resonance Imaging (MRI), and admitted to Hallym University Sacred Heart Hospital between February 1999 and December 2007. We retrospectively analyzed the medical records and the radiologic data of those patients. Cases that were accompanied with a traumatic hemorrhage or subarachnoid hemorrhage were excluded, and cases that had medical records in which the risk factors, clinical features, and prognosis were hard to determine were also excluded from this study. 
   Out of the 145 patients, three groups were categorized according to their age: those under 25, those between 25 and 34, and those between 35 and 45. An analysis was done on the etiologies, risk factors, clinical features, and prognoses for all patients in each category. 
   The etiologies of sICH were based on clinical features, radiological findings, and the results of surgical pathology. These etiologies were categorized into hypertension (HTN), vascular anomaly, brain tumor, coagulopathy, and cryptogenic. Based on cerebral angiographic results or surgically proven pathologic findings, vascular anomaly was defined as arteriovenous malformation, cerebral aneurysm, or as Moyamoya disease and other vascular anomalies. A sICH caused by brain tumor was included only when it was confirmed as a brain tumor in pathologies after surgically evacuating the hematoma. Coagulopathy was defined for patients diagnosed with hemophilia, or patients with a platelet count of less than 50000 /ul, or patients with a prolonged prothrombin time (PT) and activated partial thrombin time (aPTT), and without other etiologies.3)18) 
   Classification of each hematoma location was based on the location of the epicenter of the hematoma. These included the basal ganglia, thalamus, brain stem, lobar, or multiple locations. 
   Risk factors that were investigated are as follows: HTN, diabetes mellitus (DM), alcohol abuse, smoking, total serum cholesterol, coagulopathy (PT>14.6 seconds or aPTT>44.5 seconds), thrombocytopenia (platelet <130,000/ul), and a family history of HTN, DM or strokes. Hypertension was confined to those patients who had been pre-diagnosed by a clinician or whose systolic pressure was over 160 mmHg and whose diastolic pressure was over 100 mmHg twice after the acute stroke.12)18) The total serum cholesterol was tested during fasting and categorized into cases with lower than 160 mg/dl, cases between 160
~220 mg/dl, and cases higher than 220 mg/dl. When the serum cholesterol level was <160 mg/dl, the morbidity and mortality rates of sICH were high, confirming the research of Yano et al. and Iso et al.6)25)
   MRI and cerebral angiography were conducted when patients had no history of HTN, no high blood pressures when hospitalized, and a hemorrhage in the lobar region, if the patients were adapted to perform the test. 
   The surgical methods were distinguished into decompressive craniectomy or craniotomy with removal of hematoma, stereotactic aspiration, extraventricular drainage, and others (coil embolization when diagnosed with aneurysm through cerebral angiography). We considered the practice of surgical treatments in cases where the patients exceeded 20cc of hemorrhage. In cases where the patients had intraventricular hemorrhages, extraventricular drainage was performed accordingly. Stereotactic aspiration was performed in patients with a hematoma volume of <30cc or brain stem hemorrhages. 
   The prognosis was assessed by the clinical chart records according to the Glasgow outcome scale (GOS) at last follow up. A 'Good' GOS score was defined as 4 or 5, a 'Poor' GOS score as 2 or 3. 'Death' was ascribed to a GOS score of 1. 

Statistical analysis 
   The causes, location of hemorrhage, risk factors, and prognosis underwent a Chi-square test and a Fisher's exact test to identify the implications of each variable. Moreover, to examine the mortality rate and the prognosis factors, a logistic regression analysis was performed on factors which conveyed a sense of significance in the factor analysis. All statistical analyses were performed using SAS 9.1, with a statistical significance of 0.05. 

Results 

   A total number of 145 cases were subjected to this research. Ninety-one were male, and 54 were female with a ratio of 6.3:3.7. Table 1 shows the distribution of causes, locations, and risk factors across various age groups. Those patients between 35
~45 totaled 97 (66.9%) showing the highest results, while 27 people (18.6%) were aged between 25 and 34 and 21 people (14.5%) were aged under 25. The most common location of sICH was in the lobar region occurring in 51 patients (35.2%), followed by 47 in the basal ganglia (32.4%), 18 in the brain stem (12.4%), 15 in the thalamus (10.3%), 12 in the cerebellum (8.3%), and two with sICH across multiple locations (1.4%). In the case of lobar hemorrhages, 39.2% were located mainly in the frontal lobe. There was no difference in location with regard to gender. In the under 25 group and 25~34 group, a sICH in the lobar region occurred in 10 patients (47.6%) and 17 patients (63%), respectively, showing the highest rate of incidence. In the 35~45 age group, 38 people (39.2%) had a sICH in the basal ganglia. This indicates that the younger the patient, the higher the likelihood of a sICH occurring in the lobar region (P=0.0031). 
   The most common cause for a sICH was HTN, occurring in 84 patients (57.9%). A vascular anomaly was the second most common cause, occurring in 50 patients (34.5%). A vascular anomaly was also the most common cause for a sICH in both the under 25 group (76.2%) and the 25
~34 age group (70.4%). Moreover, with regard to vascular anomaies, 27 cases of arteriovenous malformation, nine cases of Moyamoya disease, and two cases of venous thrombosis were diagnosed. This implies that arteriovenous malformation was the main cause for a sICH due to vascular anomalies. Finally, there were two cases of sICH diagnosed with a brain tumor from a pathologic finding, three cases of coagulopathy, and six cases with no supportive reasons. 
   Table 2 shows the relationship between the locations and the causes. Of the sICH caused by hypertension, 48.8% were found in the basal ganglia, while 66% of the sICH caused by a vascular anomaly were mainly found in the lobar region. 
   Table 1 shows the risk factors, indicating that 58 out of 145 patients were smokers. Seven patients had a history of DM and six of them were 35
~45 years old. Regarding total serum cholesterol, 51 patients out of 125 were under 160mg/dl, 62 were between 160 and 220mg/dl and 12 were over 220mg/dl. Among them, 13 patients (86.7%) who were under the age of 25 and 14 patients (58.4%) between the ages of 25 and 34 were below 160mg/dl, whereas only 24 patients (27.9%) between the ages of 35 and 45 were below 160 mg/dl. Regarding their etiologies, 22 patients (29.3%) who were included in the HTN group were below 160 mg/dl and 27 patients (65.9%) who were included in the vascular anomaly group were below 160 mg/dl.(Table 3
   Prognosis of the sICH is indicated in Table 4. Thirty-seven patients died, 88 patients were diagnosed as 'Good', and 20 of them as 'Poor'. A prognosis of 'Good' was most likely in patients with a high GCS score on admission (P<0.05), a smaller hematoma volume (P<0.05), and no intraventricular hemorrhages (P<0.05). There were no statistical connections between prognosis and age, gender, locations, causes, thrombocytopenia, total serum cholesterol, alcohol, smoking, or family history. 
   Thirty-seven patients (25.5%) died within 30 days of their stroke, 72.2% of the patients died when the volume of hemorrhage went above 50cc and 49.2% died when they had an intraventricular hemorrhage. Of patients with less than nine GCS score on admission, 60.7% died. The relevant variables from the Chi-Square test were put into a logistic regression analysis. The analysis indicated noticeable differences in mortality rate, according to the cases where the mental status was in semicoma (P=0.0187), where an IVH accompanied (P=0.0132), and where the amount of hemorrhage was over 20cc (P=0.0286). The mortality rates were higher in the cases accompanied with an IVH (odd ratio:5.59), in cases with a 20
~50cc of hematoma size (odd ratio:4.95), in cases with ≥50cc of hematoma size (odd ratio:7.55), and in cases where the mental status was less than semicoma (odd ratio:5.5). 
   The results of MRI performed on 38 patients showed 28 cases (73.7%) of no abnormal findings, seven cases (18.4%) of arteriovenous malformation, two cases (5.3%) of cerebral aneurysms, and one case (2.6%) of Moyamoya disease. Among the patients who underwent an MRI, 27.3% had abnormal findings. Five cases in the group under the age of 25, eight cases in the group between 25 and 34, and 25 cases in the group between 35 and 45 underwent an MRI. 
   Sixty-one patients (42.1%) underwent a cerebral angiography, including 16 patients from the group under the age of 25, 20 patients from the 25
~34 group, and 25 patients from the 35~45 group. In the under 25 group, the cerebral angiography results showed eight cases of arteriovenous malformation, two cases of Moyamoya disease, two cases of cerebral aneurysm, and four cases without abnormal findings, resulting in a 75% of diagnostic rate. In the 25~34 group, a cerebral angiography was performed on 20 patients. The results showed 11 cases of arteriovenous malformation, one case of Moyamoya disease, one case of an aneurysm, one case of venous thrombosis, and four cases of no abnormal finding, resulting in 80% of diagnostic rate. Among the 35~45 group, 16 cases reported no abnormal finding, while four cases reported cerebral aneurysms, four cases arteriovenous malformation, and one case Moyamoya disease. The overall diagnostic rate was 36%.(Table 5

Discussion 

   In this study, 84 patients (55.4%) suffered a hypertensive intracerebral hemorrhage, with the majority occurring in the 35
~45 age group (77 patients, 81.9%). Hypertension is notably known to be the major risk factor.1)5)9)17) In addition, both Eastern Stroke and Coronary Heart Collaborative Research Group and Lawes et al. have claimed that the correlation between hypertension and sICH is much higher in Asia than in the western countries.4)13) Based on the results of research done by the Korea Medical Insurance Corporation, Kim et al. reported in research that if a patient had stage 3 hypertension, the risk of sICH increases 26.8 times in men, and 63.27 times in women. Recent research conducted by the Asia Pacific Cohort Studies Collaboration suggests that if the systolic pressure is lowered by 10mmHg, 40% of incidences of sICH in men and 38% of incidence in women can be lowered. It was also found that the lower the age of the patients, the steeper the relationship, implying the necessity of an early diagnosis of hypertension and blood pressure control in young people.13)19) 
   Several prospective studies have concluded that hemorrhagic strokes occur more frequently in individuals with a low total serum cholesterol than in those with higher concentrations.5)18)20)24)25) Iso et al. conducted a survey with 350,977 American men between the ages of 35 and 57 and revealed that the mortality rate, due to sICH for patients with a total serum cholesterol lower than 4.14 mmol/L (160 mg/dl) was three times higher.6) Yano et al. performed a cohort study for 18 years on 7,850 Japanese-American men in Hawaii and announced that the incidence of sICH was 2.55 times higher when the total serum cholesterol was lower than 189mg/dl. They further stated that the incidence rate reached its highest when the total serum cholesterol was below 160mg/dl.21)25) According to another cohort study done in Japan and China, the incidence rate of sICH increased as the total serum cholesterol was lower.4) The mechanism underlying this relationship is unclear.2)7)18) Some researchers have suggested that a low total serum cholesterol weakens the endothelium of the intracerebral arteries and that high diastolic blood pressure forms microaneurysms in the intracerebral arteries, resulting in a sICH as these microaneurysms are ruptured.2)18) However, in research that analyzed the Korea Medical Insurance Corporation Study and that studied 114,793 Korean men between the age of 34 and 59, Suh I et al. reported that low total serum cholesterol is not an independent risk factor for sICH and that hypertension elevates the incidence of sICH in Korean men.21) 
   Among the 125 patients who performed the cholesterol test for this study, 51 patients were below 160 mg/dl. There were significant statistical differences in age groups (P=0.002). Thirteen patients (86.7%) below the age of 25, 14 patients (58.4%) between the ages of 25 and 34, and 24 patients (27.9%) between the ages of 35 and 45 were below 160mg/dl, indicating that younger patients had a lower total serum cholesterol. However, the major cause of sICH among younger groups was vascular anomaly. Considering the fact that a hypertension-caused sICH was found mostly in the 35
~45 age group, and the fact that total serum cholesterol increased as people got older, it could be considered as a change due to the aging process. Furthermore, after the analysis of the causes for sICH, only 28.9% with hypertensive sICH had <160 mg/dl total serum cholesterol. For this reason, for patients with hypertension, low total serum cholesterol could not be proven to be an independent risk factor for sICH. Therefore, there needs to be more study on the relationship between the total serum cholesterol and intracerebral hemorrhages. 
   Other risk factors known to cause sICH are smoking and alcohol abuse.8)10)11)16) Smoking is known as a definite risk factor for cerebral infarction and subarachnoid hemorrhages. Nevertheless, its connection to the spontaneous intracerebral hemorrhage is still in question.5)10)11)14)21) Kurth et al. reported that smoking cigarettes is not only a risk factor for cerebral infarction but also for sICH.10)11) Lawlor et al., however, did a research on 648,346 Korean men based on the Korean National Health System and confirmed that although smoking does cause cerebral infarction and subarachnoid hemorrhages, there is no statistical relevance which indicates that smoking causes spontaneous intracerebral hemorrhages.14) 
   Alcohol abuse is also suggested as a risk factor for spontaneous intracerebral hemorrhages in many studies.1)5)16)18) Monforte et al. suggested that alcohol abuse provokes sICH. This is because as chronic alcoholics stop drinking, the serum catecholamine increases, thereby increasing the regional cerebral blood flow, aggravating the damage to the cerebral arteries, and eventually causing a spontaneous cerebral hemorrhage. Monforte et al. also indicated that alcohol abuse should be considered as an important risk factor for sICH.16) Nonetheless, more researches needs to be conducted as there are differences in results depending on race and the region.5)21) 
   The results of the study by Sandoval et al. showed that sICH in young people occurred mainly in the lobar region. Moreover, Sandoval et al. showed that a vascular anomaly was found to be the main cause of sICH in young people (49%) and that hypertension only constituted by 11% of cases in young people. Lai et al. stated that sICH in young people was mainly found in the basal ganglia area with 46.6% being caused by hypertension and 18.2% caused by vascular anomaly. Similar to the research results of Lai et al. and Sandoval et al., this study also indicates that the location of sICH is mainly in the lobar region (35.2%). Moreover, this study reveals that hypertension caused spontaneous intracerebral hemorrhages in 57.9% of cases and a vascular anomaly in 34.5% of cases. In patients under 35 years of age, cases of sICH caused by vascular anomaly were higher and most likely to occur in the lobar region. In the 35
~45 age group, sICH due to hypertension were more prevalent and were mainly observed in the basal ganglia area (P<0.05). Finally, s



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