Monoamine metabolism and sympathetic nervous activation following subarachnoid haemorrhage: influence of gender and hydrocephalus

Subarachnoid haemorrhage is a serious condition, often accompanied by cerebral vasospasm and hydrocephalus, which may result in delayed cerebral ischaemia and neurological deterioration. While the mechanisms responsible remain unknown, activation of the sympathetic nervous system, leading to elevated levels of circulating catecholamines is, at least in part, implicated. In this study, we sought to examine the importance of sympathetic nervous activation and its relation to brain monoaminergic neurotransmission in 25 patients following subarachnoid haemorrhage by examining plasma and cerebrospinal fluid levels of the catecholamines noradrenaline, adrenaline and dopamine, and their metabolites. Total body sympathetic activity was concurrently assessed using isotope dilution methodology. In the early phase following subarachnoid haemorrhage patients exhibited markedly elevated rates of spillover of noradrenaline to plasma (9.11 +/- 1.12 vs. 3.39 +/- 0.26 nmol/min, p < 0.01), with rates being higher in those patients in whom hydrocephalus developed (11.15 +/- 1.40 vs. 7.90 +/- 1.41 nmol/min, p = 0.05). The degree of sympathetic nervous activation tended to be higher in females compared with males. Lower cerebral perfusion pressures were observed in those patients in whom cerebrospinal fluid concentrations of noradrenaline and dopamine metabolites were high. A marked sympathetic nervous activation, more pronounced in women and in those with hydrocephalus, occurs following subarachnoid haemorrhage. The diminished cerebral perfusion seen following subarachnoid bleeding may occur as a result of activation of central catecholaminergic neurones.     

Results of early surgical treatment of intracranial aneurysm. Preliminary report

The authors report their preliminary experiences with early (within 72 hours after haemorrhage) operations in cases of intracranial aneurysms. Out of 131 patients operated on from April 1985 to March 1986 in the Department of Neurosurgery, Medical Academy in Warsaw 20 were qualified for surgical intervention immediately after haemorrhage. In 13 cases Nimodipine (Nimotop) was given locally during the operation and in the postoperative period. The schedule of drug administration is shown. In 15 cases (75%) a very good result was noted, in 3 (15%) major signs of focal brain damage were observed within 6 months after the operation. Two patients (20%) died. In 4 cases neurological focal signs developed 4-5 days after subarachnoid haemorrhage due to ischaemia confirmed with CT. The operative conditions during early operations, and the approach to the vessels at the base of the brain were as good as during delayed operations.     

Subarachnoid hemorrhage of unknown etiology

A group of 73 patients is described in whom diagnostic procedures failed to demonstrate the source of haemorrhage. In this group 92% of patients were in good clinical condition after the episode (I and II clinical group). In only one patient with angiographically demonstrated diffuse vasospasm in one cerebral hemisphere signs of focal brain damage developed leading to death. The remaining 95.9% of patients left the hospital in good condition, without focal signs. During follow-up in two (3.2%) out of 62 patients with known condition a recurrence of subarachnoid haemorrhage developed. Most patients were in good condition, fully fit up to 3 years after the haemorrhage. In summary, the authors stress a mild course of subarachnoid haemorrhage of unknown aetiology, good prognosis as to return of full fitness, and relatively low risk of development of focal brain damage or death from haemorrhage.     

Immobilization dystonia

OBJECTIVE: Some studies have examined gender differences in brain function based on cerebral blood flow and cerebral metabolism by using positron emission tomography (PET). However, the findings of these studies are controversial and most of them were analyzed by the regions of interest (ROIs) method. Here, we evaluated gender differences of cerebral glucose metabolism under the resting state in a voxel-based analysis. METHODS: We studied 44 healthy volunteers (22 females, 63.0+/-6.3 years, and 22 males, 63.1+/-8.4 years). Cerebral glucose metabolic images were obtained with (18)F-fluorodeoxyglucose (FDG) and PET. All individual data were transformed to standard brain space and the male and female groups were compared using statistical parametric mapping (SPM). RESULTS: The males had significantly higher glucose metabolism in the right insula, middle temporal gyrus, and medial frontal lobe than the females. Glucose metabolism in the hypothalamus was significantly higher in females than in males. There was a significant correlation between aging and glucose metabolism in the left thalamus in males and in the left caudate nucleus and hypothalamus in females. In males, but not females, there was a significant asymmetry between the bilateral hemispheres. CONCLUSION: We found that there were obvious gender differences in regional cerebral glucose metabolism and this is the first report of higher glucose metabolism in the hypothalamus in females than in males.     

Predictors of cerebral palsy in very preterm infants: the EPIPAGE prospective population‐based cohort study

Aim The aim of this study was to assess the independent role of cerebral lesions on ultrasound scan, and several other neonatal and obstetric factors, as potential predictors of cerebral palsy (CP) in a large population‐based cohort of very preterm infants. Method As part of EPIPAGE, a population‐based prospective cohort study, perinatal data and outcome at 5 years of age were recorded for 1812 infants born before 33 weeks of gestation in nine regions of France in 1997. Results The study group comprised 942 males (52%) and 870 females with a mean gestational age of 30 weeks (SD 2wks; range 24–32wks) and a mean birthweight of 1367g (SD 393g; range 450–2645g). CP was diagnosed at 5 years of age in 159 infants (prevalence 9%; 95% confidence interval [CI] 7–10%), 97 males and 62 females, with a mean gestational age of 29 weeks (SD 2wks; range 24–32wks) and a mean birthweight of 1305g (SD 386g; range 500–2480g). Among this group, 67% walked without aid, 14% walked with aid, and 19% were unable to walk. Spastic, ataxic, and dyskinetic CP accounted for 89%, 7%, and 4% of cases respectively. The prevalence of CP was 61% among infants with cystic periventricular leukomalacia, 50% in infants with intraparenchymal haemorrhage, 8% in infants with grade I intraventricular haemorrhage, and 4% in infants without a detectable cerebral lesion. After controlling for cerebral lesions and obstetric and neonatal factors, only male sex (odds ratio [OR] 1.52; 95% CI 1.03–2.25) and preterm premature rupture of membranes or preterm labour (OR 1.72; 95% CI 0.95–3.14) were predictors of the development of CP in very preterm infants. Interpretation Cerebral lesions were the most important predictor of CP in very preterm infants. In addition, infant sex and preterm premature rupture of membranes or preterm labour were also independent predictors of CP.     

Neuroprotective effects of female gonadal steroids in reproductively senescent female rats

BACKGROUND AND PURPOSE: Young adult female rats sustain smaller infarcts after experimental stroke than age-matched males. This sex difference in ischemic brain injury in young animals disappears after surgical ovariectomy and can be restored by estrogen replacement. We sought to determine whether ischemic brain injury continues to be smaller in middle-aged, reproductively senescent female rats compared with age-matched males and to test the effect of ovarian steroids on brain injury after experimental stroke in females. METHODS: Four groups of 16-month old Wistar rats (males [n=9], untreated females [n=9], and females pretreated with 17beta-estradiol [25-microgram pellets administered subcutaneously for 7 days; n=9] or progesterone [10-mg pellets administered subcutaneously for 7 days; n=9] were subjected to 2 hours of middle cerebral artery occlusion with the intraluminal filament technique, followed by 22 hours of reperfusion. Physiological variables and laser-Doppler cerebral cortical perfusion were monitored throughout ischemia and early reperfusion. In a separate cohort of males (n=3), untreated females (n=3), females pretreated with 17beta-estradiol (n=3), and females pretreated with progesterone (n=3), end-ischemic regional cerebral blood flow was measured by [(14)C]iodoantipyrine autoradiography. RESULTS: As predicted, infarct size was not different between middle-aged male and female rats. Cortical infarcts were 21+/-5% and 31+/-6% of ipsilateral cerebral cortex, and striatal infarcts were 44+/-7% and 43+/-5% of ipsilateral striatum in males and females, respectively. Both estrogen and progesterone reduced cortical infarct in reproductively senescent females (5+/-2% and 16+/-4% in estrogen- and progesterone-treated groups, respectively, compared with 31+/-6% in untreated group). Striatal infarct was smaller in the estrogen- but not in the progesterone-treated group. Relative change in laser-Doppler cerebral cortical perfusion from preischemic baseline and absolute end-ischemic regional cerebral blood flow were not affected by hormonal treatments. CONCLUSIONS: We conclude that the protection against ischemic brain injury found in young adult female rats disappears after reproductive senescence in middle-aged females and that ovarian hormones alleviate stroke injury in reproductively senescent female rats by a blood flow-independent mechanism. These findings support a role for hormone replacement therapy in stroke injury prevention in postmenopausal women.     

Gastrointestinal disturbances in stroke

The study includes analysis of 498 post-mortems of stroke patients treated in the Department of Vascular Diseases of the CNS Warsaw, in the years 1974-1985. In that group, gastrointestinal complications were found in 120 cases (24.09%) which included 82 cases of ischaemic focus in the brain and 38 cases of haemorrhagic focus due to cerebral haemorrhage. Of the 120 patients with gastrointestinal complications 75 (63.5%) had massive haemorrhage into the lumen of the alimentary tract; in half, gastrointestinal haemorrhage had occurred within 7 days of the stroke. No statistically significant correlation was observed between the type of mucosal lesion and the site of ischaemic or haemorrhagic lesion in the brain.     

Changes in prodynorphin and POMC gene expression in several brain regions of rat fetuses prenatally exposed to Delta(9)-tetrahydrocannabinol

Recently, we demonstrated that prenatal Delta(9)-tetrahydrocannabinol (Delta(9)-THC) exposure alters proenkephalin mRNA levels in several brain regions of rat fetuses. In the present study, we analyzed mRNA levels of the two other opioid peptide precursors, prodynorphin and pro-opiomelanocortin (POMC), in several brain nuclei of rat fetuses which were exposed daily to Delta(9)-THC from day 5 of gestation. Prenatal Delta(9)-THC exposure altered POMC and prodynorphin mRNA levels in most of the brain areas studied at different fetal ages, but the effects were sex-dependent. Thus, POMC mRNA levels increased in Delta(9)-THC-exposed females, but decreased in Delta(9)-THC-exposed males at GD21 in the arcuate nucleus, cerebral cortex and habenular nuclei. POMC mRNA levels also increased in the arcuate nucleus and cerebral cortex of Delta(9)-THC-exposed fetuses at GD18. Prodynorphin mRNA levels were not altered by the prenatal Delta(9)-THC exposure in the striatum, cerebral cortex, hippocampus and hypothalamic structures of fetuses at GD16 and GD18, but a sexually dimorphic response was observed at GD21. Thus, prodynorphin mRNA levels increased in the cerebral cortex, hippocampus and paraventricular hypothalamic nucleus of Delta(9)-THC-exposed females, whereas no changes were observed in Delta(9)-THC-exposed males. In summary, Delta(9)-THC exposure altered the prenatal development of POMC and prodynorphin mRNA levels in several brain structures. Changes in POMC were similar to those reported previously for proenkephalin, increases in females but decreases in males, whereas changes in prodynorphin were only observed in females.     

A study on the cerebral sizes of Koreans in their 20S and 40S

The purpose of this study was to measure the cerebral sizes of Korean adults in their third (20s) and fifth decades (40s) of life using Talairach-Nowinski reference points to determine the effect of sex and age on cerebral size and asymmetry. Magnetic resonance images of the brain of 94 adults between 20 and 29 years of age (43 males and 51 females) and 99 adults between 40 and 49 years of age (38 males and 61 females) were measured. The distance between reference points and cerebral size of males was greater than those of females. Cerebral width and the size of the left cerebrum of those in their 40s decreased more than those in their 20s. The effect of age on left cerebral atrophy of males was greater than that of females. Left cerebral size was greater than right cerebral size. There was no difference in cerebral asymmetry between the genders. Cerebral asymmetry of those in their 40s was smaller than of those in their 20s and the decrease of cerebral asymmetry of males due to age was greater than that of females. A positive relationship existed between cerebral height, and body height and weight for males in their 20s.     

A Study on the Cerebral Sizes of Koreans in Their 20S and 40S

The purpose of this study was to measure the cerebral sizes of Korean adults in their third (20s) and fifth decades (40s) of life using Talairach-Nowinski reference points to determine the effect of sex and age on cerebral size and asymmetry. Magnetic resonance images of the brain of 94 adults between 20 and 29 years of age (43 males and 51 females) and 99 adults between 40 and 49 years of age (38 males and 61 females) were measured. The distance between reference points and cerebral size of males was greater than those of females. Cerebral width and the size of the left cerebrum of those in their 40s decreased more than those in their 20s. The effect of age on left cerebral atrophy of males was greater than that of females. Left cerebral size was greater than right cerebral size. There was no difference in cerebral asymmetry between the genders. Cerebral asymmetry of those in their 40s was smaller than of those in their 20s and the decrease of cerebral asymmetry of males due to age was greater than that of females. A positive relationship existed between cerebral height, and body height and weight for males in their 20s.     

The importance of gender on the beneficial effects of posttraumatic hypothermia

The authors studied the importance of gender on the consequences of mild posttraumatic hypothermia following parasagittal fluid-percussion (F-P) brain injury in rats. After traumatic brain injury (TBI), brain temperature was maintained at normothermia (37 degrees C) or reduced to 33 degrees C for 4 h starting 30 min after the insult followed by a 1.5-h slow rewarming period. Animals (n = 48) were allowed to survive for 3 days before quantitative histopathological and immunocytochemical examination. As previously reported, contusion volume in normothermic animals (37 degrees C) was smaller (P < 0.05) in intact females compared to males. In addition, numbers of NeuN-positive cortical neurons were greater in females versus males after TBI. Posttraumatic hypothermia significantly reduced overall contusion volume in males (P < 0.05), while not significantly reducing contusion volume in females. Likewise, hypothermia protected against the loss of cortical neurons in males but had no effect in females. Ovariectomized females showed contusion volumes and neuronal cell counts comparable to those seen in males as well as a significant reduction in contusion volumes and greater neuronal counts following posttraumatic hypothermia. These data are the first to demonstrate that posttraumatic hypothermia (4 h) does not affect short-term histopathological outcomes in female rats. Potential mechanisms underlying this gender difference are discussed. Finally, these experimental findings may have important implications in terms of clinical trials using therapeutic hypothermia targeting patients with central nervous system (CNS) injury.     

Visual search in school-aged children with unilateral brain lesions

In this preliminary study, visual search for targets within and beyond the initial field of view was investigated in seven school-aged children (five females, two males; mean age at testing 8 years 10 months, SD 1 year 3 months; range 6 to 10 years) with various acquired, postnatal, focal brain injuries (haematoma, haemorrhage, meningioma, neuroblastoma, and cerebral abscess) in anterior or posterior sites of the left or right hemisphere, and seven control children (matched for age and sex) were also studied. All participants attended mainstream primary schools. The children with lesions underwent surgery after diagnosis (mean age at diagnosis 5 years 4 months, SD 2 years 7 months). Group results indicated that for the overall scores on three psychometric tests of visuospatial and fine motor abilities (Southern California Figure Ground Perception Test, Visual Organization Test, and Visual-Motor Integration Test), no difference between the children with left and right lesions was present. However, children with lesions in the right hemisphere, and not in the left hemisphere, took significantly more time than the controls to locate visual targets presented within and beyond the field of view. Examination of individual data suggested that, in accordance with brain imaging research, right-sided anterior cerebral lesions sustained in early childhood might have an enduring detrimental effect on voluntary visual search performance during development. This persistent effect of early brain injury might imply that developmental plasticity of the brain does not apply to certain specific functions of particular areas of the right hemisphere.     

Cases of cavernous hemangioma discovered in patients with post traumatic intracerebral hematoma]

Cavernous haemangioma has various forms. The cases with spontaneous intracerebral haemorrhage are most common, but post-traumatic intracerebral haematoma was not reported. The aim of this report is to present cases of cavernous haemangioma with unusual clinical course. In seven patients with post-traumatic intracerebral haematoma, fragments of histologically confirmed cavernous haemangioma tissue situated in the place of haematoma were found. In one case, delayed intracerebral haematoma twenty four hours after trauma and initial CT-scan was observed. On the initial CT-scan in this patient only traumatic changes in the brain without haematoma or tumour were present. In our cases, cavernous haemangioma was situated most frequently in frontal and temporal region, shown as haematoma usually 24 hours after trauma, mainly in men in age range 30-44 years with disorders of consciousness (GCS 11). As the result of operation, the majority of patients (6 out of 7) were discharged as self-independent. The authors reviewed the literature for cavernous haemangioma. The tumour may be present in any region of the brain including infratentorial region. The lesion is disclosed most frequently in children as spontaneous brain haemorrhage and rarely as seizures or intracranial hypertension. Final diagnosis is based on cerebral angiography or MRI. CT-scans are not typical and before the appearance of haematoma do not suggest the presence of tumour. Surgical removal of haematoma with tumour fragments is the main method of therapy, but radiation is possible in order to diminish the mass. The authors conclude that in each patient with post-traumatic intracerebral haematoma, the presence of cavernous haemangioma is possible.     

Analysis of angiographical findings in patients with severe brain disorders progressing to brain death

In the present study, the authors analysed the serial angiographical findings progressing to brain death and their relation to the intracranial pressure (ICP) and the cerebral perfusion pressure (CPP). Seventy two patients, from four to eighty four years old (fourty six males and twenty six females) admitted in the Department of Emergency Medicine, University of Tokyo Hospital during the period from January, 1981 to April, 1986, were studied. Their underlying diseases were supratentorial primary brain lesions except two cases with asphyxias which progressed to brain death. ICP was continuously measured and CPP was calculated as the pressure gradient between the mean arterial blood pressure (MAP) and ICP. The direct carotid angiography was performed to follow the cerebral circulation. Fourty five patients were subjected to barbiturate (pentobarbital sodium) therapy. The degree of the intracranial filling staged as "Non-filling", "Siphon-filling", "Partial-filling", "Delayed-filling", "All-filling" correlated significantly with ICP and CPP. These relationships, however, disappeared once ICP exceeded MAP. When "Non-filling" angiogram was obtained, clinical signs had already showed brain death. On the other hand, minimal flow ("Siphon-filling", "Partial-filling", "Delayed-filling") were still demonstrated in six brain death cases while ICP was approaching its "peak" value. This study showed that clinical diagnosis of brain death preceded the Non-filling phenomenon, suggesting that, for the demonstration of the cerebral circulatory arrest, the angiograms should be performed after the clinical diagnosis of brain death was established and CPP became zero. The evaluation of the extremely slow and minimal filling is still a matter of discussion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuropathological complications of infective endocarditis : study of autopsy material

78 autopsy proven cases of infective endocarditis (IE) seen during 1983 to 1995 were retrospectively reviewed. The brain was available for examination in 44 cases. In the remaining cases, brain was not examined because examination of it was not requested due to lack of neurological findings. Brain lesions were observed in 35 out of 44 cases of IE. Assuming remaining 34 cases to be without brain lesions, the brain involvement in IE would be 44.87% (35 out of 78 cases). Mean age of all cases of IE and those with brain lesions was similar i.e. 26.5+/-16.6 years and 26.6+/-13.06 years respectively. Largest number of cases with neuropathological lesions were associated with normal valve IE (48.57%). Mitral valve was most commonly involved in cases with CNS complications (57.14%) (p<0.05). The various types of brain lesions were infarction (68.57%), haemorrhage (57.14%), cerebral micro-abscess (31.42%) and focal meningitis (14.28%). More than one type of lesion was observed in 19 cases, indicating complicated nature of brain lesions in fatal cases of IE. Left sided middle cerebral artery (MCA) territory was the commonest site of infarction and haemorrhage. Staphylococcus aureus appeared to be the most common organism in fatal cases of IE. Normal valve IE with or without CNS complications constitutes a significant group in India and is different from the west as far as the predisposing conditions are concerned.     

Associations among right minus left brain weight, right- and left-brain weight and the degree of paw preference in right- and left-preferent male and female cats.

The relation of right and left brain weight to right minus left (R-L) brain weight and the relation of R-L paw use to brain weight were studied in adults cats. The R-L brain weight was significantly larger than zero in right-pawed (RH) male and left-pawed (LH) females. The R-L brain weight was significantly smaller than zero in LH males, not significantly different from zero in RH females. The R-L brain weight was negatively linearly correlated with the left-brain weight in RH and LH males (no significant correlations in females). The R-L paw use showed a significant positive linear correlation with the R-L brain weight in RH male and females. There was a significant negative linear correlation between R-L paw use and R-L brain weight especially in LH males. Total brain weight showed a significant negative linear correlation with R-L paw use in RH males, and a positive linear correlation in LH males (no correlations in female cats). These results indicated that intermanual difference in paw use is associated with interhemispheric weight difference and total brain weight, especially in male cats; the left brain seems to be of importance in cerebral lateralization.     

Familial cerebral amyloid angiopathy presenting as recurrent cerebral haemorrhage

Eleven patients belonging to two generations of a Dutch family with cerebral and cerebellar haemorrhage, haemorrhagic infarction and infarction are described. Their ages varied from 44 to 58 years. The principal clinical characteristic was recurring cerebral haemorrhages, sometimes preceded by a history of migrainous headaches or mental changes.In 4 of the 6 autopsied cases, old and new multiple cerebral haemorrhagic infarcts and infarcts were found, in one case a single cerebral haemorrhage and in another a cerebellar haemorrhage. In 5 cases this resulted in secondary subarachnoid haemorrhage. In one case the infarcts were only slightly haemorrhagic and did not result in subarachnoid haemorrhage. This patient presented as dementia.Microscopically, in these 6 cases and in one biopsy specimen hyaline thickening of the walls of cortical arterioles was found. The arteries of the arachnoid showed marked tortuosity, concentric proliferation, and focal hyalinization of the walls. Amyloid was found in the hyalinized vessels in 5 cases, but not outside the central nervous system.We believe that we are dealing with an inherited disorder with an autosomal dominant mode of inheritance, in which microangiopathy leads to cerebral haemorrhage and (haemorrhagic) infarction. It seems likely that amyloidosis underlies the angiopathy, and that this family suffers from a condition similar to the one described by Gudmundsson in 1972.     

Contributions of the right and left brains to manual asymmetry in hand skill in right-handed normal subjects.

The relation of intermanual difference in hand skill to cerebral lateralization was studied in right-handed male and female subjects. Hand preference was assessed by the Edinburgh Handedness Inventory. Hand skill was measured by the peg moving task. In subjects with familial sinistrality (FS+), the mean right hand peg moving times (PMTs) were found to be significantly and negatively linearly correlated with the mean left minus right (L - R) hand PMTs in females (no correlation in males). Contrarily, there was a direct relationship between the mean L - R hand PMTs and the mean left hand PMTs in FS+ males (no correlation in FS+ females). Similar results were obtained with the FS- subjects. The correlations were modified by eye and foot preferences. The overall results suggested that generally the right brain in males and the left brain in females are of importance in determining the intermanual difference in hand skill; an insufficient right brain (a slower left hand) in males and a sufficient left brain (a faster right hand) in females would create a more asymmetrical organization in skill between hands.     

The risk of complications of cerebral angiography in patients with cerebral aneurysms in relation to the time of its use

The authors analysed the effect of cerebral angiography on the condition of the patients after haemorrhage from an intracranial aneurysm. The studied material comprised 242 patients in whom cerebral angiography was carried out at various times after the haemorrhage by the method of direct percutaneous needle insertion into the carotid artery. Complications of angiography included: worsening of the general condition or neurological condition during the angiography and within 24 hours after it. Such complications were found in 14 patients (5.8%). In only 3 cases they appeared during the angiography. No cases of repeated haemorrhage from the aneurysm were observed. The greatest risk of complications was after 7-9 days from the haemorrhage which was connected with the greatest intensity of arteriospasm at that time. All carotid angiographies were done using a contrast medium hypersmolar and hypertonic in relation to the blood and cerebrospinal fluid (Uropolinum-Polfa 60%).     

Amyloid angiopathy and lobar cerebral haemorrhage.

Seven cases of lobar cerebral haemorrhage due to amyloid angiopathy were found among 60 necropsy cases of intracerebral haemorrhage. Clinically five patients were demented and two had hypertension. Immediately after the onset of stroke there was a high incidence of headache and vomiting, followed by nuchal rigidity. Amyloid angiopathy was most prominent in the cerebral cortex and the leptomeninges. Senile plaques were noted in all cases. One should suspect that a haemorrhage may be due to amyloid angiopathy, when lobar cerebral haemorrhage occurs in an aged, normotensive patient with or without dementia. Surgical evacuation of the haematoma is inadvisable, because of the diffuse nature of amyloid angiopathy, high recurrence rate and less tendency to cause brain stem compression.