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Background and aim: To update our 1996 review on the incidence of subarachnoid haemorrhage (SAH) and assess the relation of incidence with region, age, gender and time period. Methods: We searched for studies on the incidence of SAH published until October 2005. The overall incidences with corresponding 95% confidence intervals were calculated. We determined the relationship between the incidence of SAH and determinants by means of univariate Poisson regression. Results: We included 51 studies (33 new), describing 58 study populations in 21 countries, observing 45 821 896 person-years. Incidences per 100 000 person-years were 22.7 (95% CI 21.9 to 23.5) in Japan, 19.7 (18.1 to 21.3) in Finland, 4.2 (3.1 to 5.7) in South and Central America, and 9.1 (8.8 to 9.5) in the other regions. With age category 45-55 years as the reference, incidence ratios increased from 0.10 (0.08 to 0.14) for age groups younger than 25 years to 1.61 (1.24 to 2.07) for age groups older than 85 years. The incidence in women was 1.24 (1.09 to 1.42) times higher than in men; this gender difference started at age 55 years and increased thereafter. Between 1950 and 2005, the incidence decreased by 0.6% (1.3% decrease to 0.1% increase) per year. Conclusions: The overall incidence of SAH is approximately 9 per 100 000 person-years. Rates are higher in Japan and Finland and increase with age. The preponderance of women starts only in the sixth decade. The decline in incidence of SAH over the past 45 years is relatively moderate compared with that for stroke in general.

Retrospective surveys of patients with subarachnoid haemorrhage suggest that minor episodes with sudden headache (warning leaks) may precede rupture of an aneurysm, and that early recognition and surgery might lead to improved outcome. We studied 148 patients with sudden and severe headache (possible sentinel headache) seen by 252 general practitioners in a 5-year period in the Netherlands. Subarachnoid haemorrhage was the cause in 37 patients (25%) (proven aneurysm in 21, negative angiogram in 6, no angiogram done in 6, sudden headache followed by death in 4). 103 patients had headache as the only symptom, 12 of whom proved to have subarachnoid haemorrhage (6 with a ruptured aneurysm). Previous bouts of sudden headache had occurred in only 2. Other serious neurological conditions were diagnosed in 18. In the remaining 93, no underlying cause of headache was found; follow-up over 1 year showed no subsequent subarachnoid haemorrhage or sudden death. In this cohort, acute, severe headache in general practice indicated a serious neurological disorder in 37% (95% CI 29-45%), and subarachnoid haemorrhage in 25% (18-32%). 12% (5-18%) of those with headache as the only symptom. The notion of warning leaks as a less serious variant of subarachnoid haemorrhage is not supported by this study. Early recognition of subarachnoid haemorrhage is important but will probably have only limited impact on the outcome in the general population.

Summary: The effect of somatosensory stimulation on the local CBF (LCBF), CMRglu (LCMRglu), tissue pH, and tissue content of AT P, glucose, and lactate was studied in chloralose-anesthetized rats before and after 30 min of near-complete forebrain ischemia. In nonischemic rats LCBF in primary somatosensory cortex increased by 33%, LCMRglu increased by 55%, tissue glucose content decreased by 21%, and lactate increased by 30%. Local AT P and tissue pH did not change. Functional activation of the intact chloralose-anesthetized rat, in consequence, is associated with the stimulation of "aerobic"glycolysis but does not result in disturbances of energy or acid-base homeostasis. After 30-min ischemia and 3-h recircula-The coupling between neuronal activity, blood flow, and glucose utilization is a well-documented phenomenon that has been extensively studied in the past and that provides the basis for the meta bolic mapping of functional activity of the brain (Sokoloff, 1981). The general concept of metabolic coupling is based on the assumption that the activa tion of neuronal circuits is associated with an in crease of energy and transmitter turnover that has to be fueled by an increased supply of glucose and oxygen. Recently, evidence has been provided that a period of transient cerebral ischemia suppresses the stimulation-evoked increase of glucose utiliza tion for up to several days after the ischemic impact (Dietrich et aI., 1986). The responsiveness of blood flow to changes of Pco2, which is thought to con- tribute to the flow-metabolism couple, is also sup pressed for days, if not months, after ischemia even if spontaneous and evoked electrical activity return to normal (Schmidt-Kastner et aI., 1986).If functional activation of the brain after ischemia requires the same amount of energy as in the intact brain, and if neither blood flow nor glucose con sumption is increased during activation, the brain will have to cover the increased energy demands by utilizing its energy stores. This process should lead to measurable alterations in the regional content of energy metabolites. To test this hypothesis we have studied the effect of functional activation before and after global ischemia of rat brain by combining autoradiographic measurements of local CBF (LCBF) and CMRg\u (LCMRglu) with methods for the pictorial evaluation of energy metabolites and of the acid-base state of the brain ("multiparame tric brain imaging") (Hossmann et aI., 1985).The results obtained demonstrate that following a period of severe forebrain ischemia, activation of blood flow or glucose utilization is completely sup pressed although EEG and evoked potentials re cover. Surprisingly, this dissociation does not cause any disturbances of the regional energy state of the brain, which raises the fundamental question of the

One third of patients with aneurysmal subarachnoid haemorrhage (ASAH) present with headache only. A prompt diagnosis is crucial, but these patients must be distinguished from patients with non-haemorrhagic benign thunderclap headache (BTH). The headache characteristics and associated features at onset in subarachnoid haemorrhage and benign thunderclap headache were studied to delineate the range of early features in these conditions. In this prospective study, one of two observers interviewed 102 patients with acute severe headache by means of a standard questionnaire. The patients were alert on admission and had no focal deficits. ASAH was subsequently diagnosed in 42 patients, non-aneurysmal perimesencephalic haemorrhage (PMH) in 23 patients, and BTH in 37 patients. Headache developed almost instantaneously in 50% of patients with ASAH, 35% of patients with PMH, and 68% of patients with BTH and within 1 to 5 minutes in 19%, 35%, and 19%, respectively. Loss of consciousness was reported in 26% of patients with ASAH, 4% of patients with PMH and 16% of patients with BTH, and transient focal symptoms in 33%, 9%, and 22% respectively. Seizures and double vision had occurred only in ASAH. Vomiting and physical exertion preceding the onset of headache were more frequent in patients with ASAH (69% and 50%) and those with PMH (83% and 39%) than in those with BTH (43% and 22%). Headache developed almost instantaneously in only half the patients with aneurysmal rupture and in two thirds of patients with benign thunderclap headache. In patients with acute severe headache, female sex, the presence of seizures, a history of loss of consciousness or focal symptoms, vomiting, or exertion increases the probability of ASAH, but these characteristics are of limited value in distinguishing ASAH from BTH. Aneurysmal rupture should be considered even if focal signs are absent and the headache starts within minutes. (J Neurol Neurosurg Psychiatry 1998;65:791-793)

Brain tissue pH and lactate content were measured in rats under three different experimental conditions, namely: during complete global cerebral ischemia; after reversible near-complete cerebral ischemia; and in experimental brain tumors. At the end of the experiments brains were frozen with liquid nitrogen. A series of 20-microns thick coronal sections was prepared in a cryostat and then used for the regional determination of tissue pH (umbelliferone technique) and tissue lactate (bioluminescent technique). In addition, tissue samples were taken for the quantitative measurement of brain lactate (enzymatic fluorometric technique). The relationship between lactate content and tissue pH was different for each of the three experimental models studied: only after short-term global cerebral ischemia did an increase in the lactate content correlate with a decrease in tissue pH (r = 0.94; p less than 0.001). A highly significant increase in the lactate content (p less than 0.001) was accompanied by physiological pH values (6.96 +/- 0.08 in comparison to 6.97 +/- 0.04 in controls) during recirculation after transient cerebral ischemia and in brain tumors even by an alkaline pH shift. In view of these observations the term "lactacidosis" should not be used without measuring both the lactate content and the pH. The observed dissociation between pH and lactate is due to the fact that both parameters are regulated independently. During anaerobiosis the main source of proton production is ATP hydrolysis rather than glycolysis. It is, therefore, suggested that the terms "acidosis" and "lactosis" should be used instead of "lactacidosis."

The actual incidence of SAH has remained stable over the last three decades; the apparent decline in incidence is entirely explained by the greater proportion of patients investigated with CT. The incidence of SAH in Finland is almost three times as high as in other parts of the world.

Exclusive monotherapy with zinc in symptomatic Wilson disease is controversial. Seventeen symptomatic patients with Wilson disease were treated with zinc only. The mean age at diagnosis and start of treatment was 18 years (range 13-26) with approximately half presenting as adolescents. Presentation was exclusively hepatic, exclusively neurologic, and combined in seven, five, and five patients, respectively. The median follow-up was 14 years (range 2-30). At baseline, two of the 12 patients with hepatic disease exhibited decompensated cirrhosis, five exhibited compensated cirrhosis, and five had less severe disease. Both patients with decompensated cirrhosis improved to a compensated state after initiation of therapy. Two of the five patients with initial compensated cirrhosis progressed to decompensated state, and three remain stable. Three of the five patients with moderate or mild liver disease remain stable and two improved. Apart from decreasing bilirubin levels, no significant changes occurred in the liver biochemistry or function during long-term follow-up. Nine of 10 neurologic patients improved markedly and one deteriorated. Two patients with exclusively neurologic presentation developed liver disease during zinc treatment. Two patients with exclusively hepatic presentation developed mild neurologic symptoms. According to 24-hour urinary copper excretions (213 ؎ 38 versus 91 ؎ 23 g: P ‫؍‬ 0.01) and serum non-ceruloplasmin-bound copper concentrations (11 ؎ 2 versus 7 ؎ 1 g/dL: P ‫؍‬ 0.1) at the end of follow-up, the efficacy of decoppering was less in the exclusively hepatic than in the neurologic group. The prescribed zinc dose and 24-hour urinary zinc excretions tended to be less in the exclusively hepatic group. Conclusion: The outcome of exclusive zinc therapy is generally good in cases of neurologic disease. A less satisfactory outcome in hepatic disease may relate to less efficient decoppering.