Volumes of brain, grey and white matter and cerebrospinal fluid in schizophrenia in the Northern Finland 1966 Birth Cohort: an epidemiological approach to analysis.

Magnetic resonance imaging (MRI) studies in schizophrenia have seldom involved a general population birth cohort or other epidemiological samples. We studied the Northern Finland 1966 Birth Cohort and identified all people with psychotic disorders. Along with an unaffected age-matched control sample (n = 100) from the cohort, 54 subjects with schizophrenia underwent MRI brain scan at age 33-35 years from which we defined volumes of whole brain, grey and white matter and intracranial cerebrospinal fluid (CSF). Whole brain, grey and white matter volumes were 2-3% smaller in the schizophrenia subjects, who showed a 7% increase in CSF volume. These volume changes were independent of the effects of gender, family history of psychosis, perinatal risks or age at onset of illness. Moreover, there was no evidence that the effects were due to particular subgroups of cases having very low or high values. Rather, there were linear trends in the associations between whole brain and grey matter volume measures and schizophrenia. Our study replicates the previous findings of brain volume differences in schizophrenia on a general population level.

Hypertension and diabetes as predictors of early death after spontaneous intracerebral hemorrhage.

OBJECT: Previous investigators have suggested that a high mean arterial blood pressure (MABP) and an elevated plasma glucose level at admission are associated with a poor outcome after hemorrhagic stroke. It remains unclear, however, whether hypertension and diabetes are responsible for this effect. High admission MABP and plasma glucose levels may also be markers of other factors such as stroke severity. METHODS: The authors retrospectively investigated the role of a high admission MABP and plasma glucose level together with other predictors of early death among 379 nonsurgical patients with spontaneous intracerebral hemorrhages (ICHs) who were admitted to the stroke unit of Oulu University Hospital. RESULTS: The 3-month mortality rate was 28%. The patients who died within 3 months of ICH had significantly higher plasma glucose levels and MABPs at admission (p < 0.001). After adjustments for patient sex, age, size and location of hematoma, Glasgow Coma Scale score at admission, presence of intraventricular hemorrhage, history of cardiac disease, and previous use of warfarin, history of diabetes (relative risk 1.61, 95% CI 1.03-2.53, p < 0.05) and high MABP at admission (relative risk 1.01 per mm Hg, 95% CI 1.00-1.02, p < 0.05) remained independent predictors of death 3 months after ICH. A high admission plasma glucose level and history of hypertension were not independent predictors of death. CONCLUSIONS: A high MABP at admission was found to be an independent predictor of early death in patients with ICH. History of hypertension was not responsible for the effect. Admission hyperglycemia appeared to be a stress response to the severity of the bleeding, whereas diabetes predicted early death.

Impact of ischemic heart disease and atrial fibrillation on survival after spontaneous intracerebral hemorrhage.

OBJECT: The well-known predictors for increased early deaths after spontaneous intracerebral hemorrhage (ICH) include the clinical and radiological severity of bleeding as well as being on a warfarin regimen at the onset of stroke. Ischemic heart disease and atrial fibrillation may also increase early deaths. In the present study the authors aimed to elucidate the role of the last 2 factors. METHODS: The authors assessed the 3-month mortality rate in patients with spontaneous ICH (453 individuals) who were admitted to the stroke unit of Oulu University Hospital within a period of 11 years (1993-2004). RESULTS: The 3-month mortality rate for the 453 patients was 28%. The corresponding mortality rates were 42% for the patients who had ischemic heart disease and 61% for those with atrial fibrillation on admission. The following independent predictors of death emerged after adjustment for sex and the use of warfarin or aspirin at the onset of ICH: 1) ischemic heart disease (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.12-2.48, p < 0.02); 2) atrial fibrillation on admission (HR 1.79, 95% CI 1.12-2.86, p < 0.02); 3) the Glasgow Coma Scale score on admission (HR 0.82 per unit, 95% CI 0.79-0.87, p < 0.01); 4) size of hematoma (HR 1.11 per 10 ml, 95% CI 1.07-1.16, p < 0.01); 5) intraventricular hemorrhage (HR 2.62, 95% CI 1.71-4.02, p < 0.01); 6) age (HR 1.04 per year, 95% CI 1.02-1.06, p < 0.01); and 7) infratentorial location of the hematoma (HR 1.93, 95% CI 1.26-2.97, p < 0.01). CONCLUSIONS: Both ischemic heart disease and atrial fibrillation independently and significantly impaired the 3-month survival of patients with ICH.

Safety of low-dose subcutaneous enoxaparin for the prevention of venous thromboembolism after primary intracerebral haemorrhage.

BACKGROUND: The risks and benefits of low molecular weight heparins (LMWH) for the prevention of deep-vein thrombosis (DVT) and pulmonary embolism (PE) after intracerebral haemorrhage (ICH) have not been assessed. The few studies on this subject have revealed conflicting results. METHODS: We retrospectively evaluated whether subcutaneous enoxaparin (20 mg daily) reduced symptomatic venous complications or caused increased 3-month death rate. We included 407 patients who were admitted to a stroke unit and survived the first two days after onset of ICH. There were 232 patients who received anticoagulant treatment for the prevention of DVT and PE and 175 who did not. RESULTS: Despite the fact that the treated patients were in worse clinical condition at the start of the treatment, 3-month death rate was 19% among them compared to 21% among those not receiving anticoagulant therapy. Low-dose subcutaneous enoxaparin (20 mg once daily) induced a significant plasma anti-factor Xa activity 2-3 hours after administration (p=0.018). Haematoma enlargements (33%) occurred in 9% and 7% of the treated and untreated patients, whereas symptomatic venous thromboembolic complications were observed in 3% and 2%, respectively. CONCLUSIONS: We did not observe any increased mortality among ICH patients who survived the first 2 days after the onset of ICH and were thereafter treated with enoxaparin 20 mg daily relative to patients remaining untreated. A randomized trial of the effect of LMWH with a higher dose in prevention of venous thromboembolic complications would be indicated.

Regular aspirin-use preceding the onset of primary intracerebral hemorrhage is an independent predictor for death.

BACKGROUND AND PURPOSE: Hematoma volume and impaired level of consciousness are the most potent predictors of outcome after spontaneous intracerebral hemorrhage (ICH). The effect of preceding aspirin-use on outcome after ICH is poorly investigated. We investigated short-term mortality and hematoma enlargement in subjects with ICH to find the predictors for these outcomes. METHODS: This population-based study included all subjects with ICH during a period of 33 months in the population of Northern Ostrobothnia, Finland. The subjects were identified, and their clinical characteristics and outcomes were checked from hospital records or death records. RESULTS: Three-month mortality of the 208 identified subjects with ICH was 33%. The independent risk factors for death were regular aspirin-use at the onset of ICH (relative risks [RR], 2.5; 95% CI, 1.3 to 4.6; P=0.004), warfarin-use at the onset of ICH (RR, 3.2; 95% CI, 1.6 to 6.1; P=0.001), and ICH score higher than 2 on admission (RR, 13.8; 95% CI, 6.0 to 31.4; P<0.001). Regular aspirin-use preceding the onset of ICH associated significantly with hematoma enlargement during the first week after ICH (P=0.006). CONCLUSIONS: We observed poor short-term outcomes and increased mortality, probably attributable to rapid enlargement of hematomas, in the subjects with ICH who had been taking regularly moderate doses of aspirin (median 250 mg) immediately before the onset of the stroke.

Hippocampus and amygdala volumes in schizophrenia and other psychoses in the Northern Finland 1966 birth cohort.

Structural brain differences have been reported in many studies with schizophrenia, but few have involved a general population birth cohort. We investigated differences in volume, shape and laterality of hippocampus and amygdala in patients with schizophrenia, all psychoses and comparison subjects within a large general birth cohort sample, and explored effects of family history of psychosis, perinatal risk and age-at-onset of illness. All subjects with psychosis from the Northern Finland 1966 birth cohort were invited to a survey including MRI scan of the brain, conducted in 1999-2001. Comparison subjects not known to have psychosis were randomly selected from the same cohort. Volumes of hippocampus and amygdala were measured in 56 subjects with DSM-III-R schizophrenia, 26 patients with other psychoses and 104 comparison subjects. Small hippocampal volume reductions in schizophrenia (2%) and all psychoses (3%) were not significant when adjusted for total brain volume. The shape of hippocampus in schizophrenia did not differ significantly from comparison subjects. Right hippocampus and amygdala were significantly larger than the left in all groups. Mean amygdala volume in schizophrenia or all psychoses did not differ from comparison subjects. Patients with family history of psychosis had larger hippocampus than patients without. Neither perinatal risk nor age-at-onset of illness had any effect on hippocampal or amygdala volumes. Small hippocampal volume reduction in schizophrenia and all psychoses was not disproportionate to reduced whole brain volume in this population-based sample. Perinatal events that have been suggested as of etiological importance in structural pathology of psychosis had no effect.

Thromboxane and prostacyclin biosynthesis in patients with acute spontaneous intracerebral hemorrhage.

OBJECTIVE: Elevated levels of 11-dehydrothromboxane B2 (11-dehydro-TXB2) excreted in urine have been observed in acute ischemic stroke. This marker of platelet activation has not been investigated in patients with acute spontaneous intracerebral hemorrhage (ICH). METHODS: We examined 43 patients with spontaneous ICH and 23 controls. Urinary excretion rates of 11-dehydro-TXB2, 2,3-dinor-thromboxane B2 (2,3 dinor-TXB2) and 2,3-dinor-6-ketoprostaglandin F(1alpha) (2,3-dinor-PGF(1alpha)) during the first week and at 3 months after ICH were compared between patients who had or had not used aspirin and controls. RESULTS: On admission, ICH patients without aspirin use had significantly higher urinary levels of 11-dehydro-TXB2 (p<0.001), 2,3-dinor-TXB2 (p<0.001) and 2,3-dinor-PGF(1alpha) (p=0.019) than controls. Aspirin users had significantly lower urinary levels of these metabolites than nonusers. The metabolite levels of aspirin users on admission did not significantly differ from those of controls. The differences between aspirin users and nonusers leveled off during the following 3-5 days, however, as the blocking effect of aspirin on the production of TXA2 and PGI2 ceased. Three months after ICH, the metabolite excretion levels in all the patients were similar to those in nonusers of aspirin on admission. On admission, aspirin users had longer bleeding times (p=0.032) than nonusers, but aspirin use did not associate with impaired recovery or hematoma enlargement. CONCLUSIONS: Urinary excretion levels of 11-dehydro-TXB2, 2,3-dinor-TXB2 and 2,3-dinor-PGF1alpha were higher in patients with acute ICH than in controls. The levels in aspirin users were equally low as in controls but rose to the levels of the other patients within a few days. The metabolite levels remained high 3 months after ICH in all patients. Prior use of aspirin did not seem to cause hematoma enlargement.

Cardiovascular regulation and hippocampal sclerosis.

PURPOSE: Cardiovascular dysregulation has been detected in patients with temporal lobe epilepsy (TLE) by using cardiovascular reflex tests and analysis of heart rate variability (HRV). The two methods have not previously been used in the same study to compare them in the assessment of cardioregulatory function. Magnetic resonance imaging (MRI) is considered the best method to reveal structural changes such as hippocampal sclerosis associated with TLE. It is not known whether these structural changes modify cardioregulatory function in patients with TLE. METHODS: Standard cardiovascular reflex tests and analysis of spectral and dynamic measures from 24-h electrocardiogram (ECG) recordings were performed for eight patients with and 31 patients without hippocampal sclerosis and for 72 control subjects. MRI also was performed in each patient to reveal hippocampal sclerosis. RESULTS: Various measures of cardiovascular reflexes and HRV were diminished in patients with TLE compared with the control subjects. No significant differences were found in the measures obtained from the cardiovascular reflex tests or analysis of HRV between those with and without hippocampal sclerosis, although a nonsignificant trend toward reduced values was seen among those with hippocampal sclerosis. The values of cardiovascular reflexes and spectral analysis of HRV correlated with each other. CONCLUSIONS: These results suggest that functional rather than structural changes related to TLE are involved mainly as a mechanism of altered cardioregulatory function. The cardiovascular reflex test and analysis of HRV both appear to be useful in studying cardioregulation in patients with TLE.

Effects of head and extracranial injuries on serum protein S100B levels in trauma patients.

BACKGROUND: Serum protein S100B determinations have been recently suggested as markers of traumatic brain injury. However, little is known about the effects of extracranial injuries on S100B levels in trauma patients. METHODS: We studied 224 patients with head trauma (54 of whom also had extracranial injuries), 155 patients with various types of extracranial injuries, and 8 healthy pilots exposed to high Gz forces. The head trauma patients had either no brain injury (n = 35), mild brain injury (n = 165), or moderate to severe brain injury (n = 24). The extracranial injuries were divided into small and large injuries. Serum protein S100B levels were determined from samples taken within 6 hours after the trauma event. RESULTS: The head trauma patients had a significantly higher median S100B (0.17 microg/L) than the patients with extracranial injuries (0.07 microg/L) (p < 0.001). Serum S100B levels also correlated with the severity of brain injury (p < 0.001), the highest values occurring in the patients with moderate to severe brain injury (1.27 microg/L). However, large extracranial injuries also elevated S100B levels (0.35 microg/L), whereas small extracranial injuries in the absence of head trauma did not significantly affect S100B levels (0.07 microg/L). Above the cutoff level of 0.13 microg/L, there were 61% of the head trauma patients and 26% of those with extracranial injuries (Pearson chi test, p < 0.001). However, only 4% of the patients with purely extracranial injuries had a concentration of S100B above the cutoff level of 0.50 microg/L, whereas the head trauma patients with moderate to severe brain injury exceeded this cutoff in 67% of the cases. Exposure to high Gz forces did not influence serum S100B levels in healthy individuals. CONCLUSION: We conclude that serum S100B is a sensitive marker of brain injury, which correlates with the severity of the injury. Large extracranial injuries also elevate S100B levels. However, S100B has a high negative predictive power, and the finding of a normal S100B value shortly after trauma should thus exclude significant brain injury with a high accuracy.

Neurological diseases and accidental falls of the aged.

OBJECTIVE: To assess the influence of central and peripheral neurological diseases on the incidence of accidental falls of the aged. DESIGN: 1. Case-control study with cross-section at two years and 2. prospective study in a follow-up up to seven years thereafter. SETTING: Sample of a population study including all 589 inhabitants older than 70 years in three rural communities. PARTICIPANTS: 44 subjects with recurrent falls during two years' follow-up and 41 age and sex matched controls. MEASURES: Neurological diseases and evaluation, other diseases, and incidence of falls during the seven years' follow-up after the cross-section. RESULTS: Compared with the controls the fallers had more often multiple vascular lesions of the brain, extrapyramidal symptoms and signs as well as lumbar nerve root lesions. In the follow-up, cerebrovascular disease, especially with multiple lesions and residual signs of pyramidal tract lesion, Parkinson's disease, rigidity and hypokinesia were associated with increases risk of falling. In multivariate analysis signs of pyramidal tract lesion, rigidity and prior falls were predictors of falls. An increase in the incidence of falls was also associated with vascular lesion of the cerebellum, cerebral white matter hypodensity and cortical atrophy visible on CT. CONCLUSIONS: High incidence of falls was associated with chronic central nervous system diseases. Lumbar root lesions were more common among the fallers but did not increase the incidence of falls in the follow-up. Neurological diseases and evaluation, other diseases, and incidence of falls during the seven years' follow-up after the cross-section. Compared with the controls the fallers had more often multiple vascular lesions of the brain, extrapyramidal symptoms and signs as well as lumbar nerve root lesions. In the follow-up, cerebrovascular disease, especially with multiple lesions and residual signs of pyramidal tract lesion, Parkinson's disease, rigidity and hypokinesia were associated with increased risk of falling. In multivariate analysis signs of pyramidal tract lesion, rigidity, and prior falls were predictors of falls. An increase in the incidence of falls was also associated with vascular lesion of the cerebellum, cerebral white matter hypodensity and cortical atrophy visible on CT.

Perfusion MRI and SPECT of brain after treatment for childhood acute lymphoblastic leukemia.

BACKGROUND: Treatment of childhood leukemia may cause perfusion defects in the brain observed by SPECT. Perfusion MRI is a novel method to study brain perfusion which has not been used previously in this setting. This study was performed to compare SPECT with perfusion MRI in patients with acute lymphoblastic leukemia (ALL) after treatment. PROCEDURE: Nineteen children or young adults underwent perfusion MRI at the cessation of treatment (n = 9) or 4-8 years after the treatment (n = 10). Seventeen of them also underwent SPECT at the time of MRI (within 0-3 days, n = 14) or a couple of months later (1.5-6 months, n = 3). SPECT images and relative cerebral blood volume (CBV) and cerebral blood flow (CBF) maps from perfusion MRI were analyzed visually. Relative CBV ratios of gray matter to white matter and thalamus to white matter were also calculated from the perfusion MRI. RESULTS: Perfusion MRI did not show any focal perfusion defects, while small defects were observed by SPECT in five of 17 children (29%) in the basal, frontal or temporal areas on the left. No significant differences were observed by perfusion MRI in the relative CBV ratios in the different treatment groups. Time since treatment, age at diagnosis, brain irradiation, or findings in conventional MRI or SPECT did not have any effect on the relative perfusion values either. CONCLUSIONS: SPECT may show small perfusion defects after treatment for childhood leukemia which are not visible by perfusion MRI. The clinical significance or prognosis of these defects is not known.

MR abnormalities of the lateral pterygoid muscle in patients with nonreducing disk displacement of the TMJ.

The aim of this study was to investigate the pathological changes of the lateral pterygoid muscle (LPM) using magnetic resonance imaging (MRI) in patients with anterior disk displacement with nonreduction (ADDnr) of the temporomandibular joint (TMJ) and to compare the abnormal findings of the LPM with the clinical symptoms and other pathological MRI alterations of the TMJ. Bilateral or unilateral ADDnr was demonstrated in 142 patents by MRI (176 TMJs; 106 females; 36 males; range 19 to 72 years; mean 43.9 years). In 123 TMJs, the LPMs were clearly observed in MRIs and analyzed in this study. Pathological changes of the LPM were found in 92 TMJs (74.8%) in MRI. Hypertrophy, atrophy and/or contracture were detected in the superior belly of the LPM (SBLPM) (35.8%, 44/123) or in the inferior belly of the LPM (IBLPM) (9.8%, 12/123) or in both bellies (29.3%, 36/123). The pathological changes of the LPM in MRI presented a significant association with the main clinical symptoms of TMJs with ADDnr, i.e. pain on jaw movement (P<0.01), pain in the LPM (P<0.01), pain in TMJ (P<0.05) and restricted jaw opening (P<0.05). The proportion of the abnormalities in LPM was significantly lower in TMJs with condylar limitation (63.6%) than in TMJs with condylar hypermobility (83.3%) and normal motion (88.9%)(P=0.008). Osteoarthritis was found to be correlated with condylar limitation (P<0.01). The results of this study indicate that the pathological changes of the LPM in TMJs with ADDnr could be detected by MRI and have a significant association with the main clinical symptoms of the patients. When condylar limitation happened, on the contrary, the pathological changes of the LPM in MRI were reduced. The alteration of the clinical symptoms in the patents with ADDnr might be associated with the pathological situations and symptoms of the LPM.

MR perfusion, diffusion and BOLD imaging of methotrexate-exposed swine brain.

PURPOSE: To evaluate the methotrexate (MTX)-exposed swine brain, functional magnetic resonance imaging (MRI), including perfusion, diffusion, and blood-oxygen-level-dependent (BOLD) contrast imaging, was used. MATERIAL AND METHODS: Juvenile pigs received either 2 x 5 g/m(2), or 5 x 2 g/m(2) MTX intravenously within one month. MRI was performed (sedative: propofol) before (14-17 kg, N = 6) and after (21-27 kg, N = 4) the MTX exposure. Also, age-matched controls (22-27 kg, N = 4) were imaged. RESULTS: After the MTX exposure, reduced (from 2%-4% to 0%-1%) or negative (-2% to -3%) BOLD responses were detected; apparent diffusion coefficient (ADC) or relative perfusion values did not change. CONCLUSION: This study suggests that MTX-related changes in the brain may be detected as changes in flow-metabolism coupling as reduced or negative response (for somatosensory activation) in the BOLD contrast MRI. The contrast agent perfusion MRI, without absolute quantification, may not show global damage in brain perfusion related to the MTX exposure in the swine model used. ADC (in one direction) may not indicate MTX-related changes in the brain.