Abnormal cerebrospinal fluid-blood flow dynamics. Implications in diagnosis, treatment, and prognosis in normal pressure hydrocephalus.

Increased cerebral blood flow (CBF) has been proposed as responsible for the clinical improvement after cerebrospinal fluid (CSF) shunting in patients with normal pressure hydrocephalus (NPH). In order to determine any abnormal CSF-CBF pressure-flow relationships in NPH, measurements of regional cerebral blood flow (rCBF) and regional cerebral blood volume (rCBV) were made before and after lowering CSF pressure (CSFP) in 15 patients with NPH, and in ten patients with presumed hydrocephalus ex vacuo. Maximal reduction of rCBF and rCBV occurred in the territory of the anterior cerebral artery in NPH but no in dementia due to brain atrophy. Both CBF and rCBV increased after lowering the CSFP by lumbar puncture in patients with NPH. Patients with higher preoperative rCBF and maximal increases in rCBR and rCBV after lowering CSFP showed the most consistent clinical improvement after CSF shunting. Evidence is offered that CBF autoregulation is impaired in NPH. The CBF test assists in both diagnosis and selection of patients for CSF shunting.

Increased cerebral blood volume in benign intracranial hypertension.

In two patients with benign intracranial hypertension, the regional cerebral blood volume was markedly elevated (mean of 85 percent) while regional cerebral blood flow was slightly reduced (mean of 10 percent). Reduction of cerebrospinal fluid pressure by removal of cerebrospinal fluid reduced the mean values of regional cerebral blood volume by 13 percent without significant change in regional cerebral blood flow. The abnormal regional volume and regional flow returned to normal concurrent with the clinical improvement. Vinous engorgement and increased intracranial blood volume appear to play an important part in the pathophysiology of increased intracranial pressure in benign intracranial hypertension. A unified concept of the pathogenesis of benign intracranial hypertension is proposed.

PIP: 2 women complaining of headaches were found to have benign intracranial hypertension with increased rCBV (regional cerebral blood volume) of 85% and reduced rCBF (regional cerebral blood flow) of 10%. A lumbar puncture was done showing a small rCBV reduction of 13% but no significant change in rCBF. The patients were also administered 1.5 gm/kilogram body weight of glycerol 3 times a day. After 18 weeks of glycerol treatment, headaches and papilledema disappeared, rCBV and rCBF returned to normal levels, and cerebrospinal fluid pressure was reduced. It is believed that all 3 intracranial compartments may be involved in producing intracranial pressure in benign intracranial hypertension patients although it is difficult to determine the varying degrees to which each factor may be involved. The intracranial pressure may be increased due to venous engorgement and increased CBV. Because of undesirable side effects after long term use of deramethasone and diuretics like furosemide, oral glycerol therapy is used for prolonged therapy without adverse reactions.

Neurogenic control of cerebral blood flow in the baboon.

Cerebral chemical vasomotor reactivity and autoregulation were tested in normal baboons before and after the intravenous or intravertebral infusion of atropine sulfate (0.02 mg/kg). Atropine did not appreciably effect autoregulatory response, but intravertebral injection suppressed the increase of cerebral blood flow (CBF) by inhalation of 5% CO2 and enhanced the decrease of CEF induced by hyperventilation. These changes produced by intravertebral injection of atropine were not observed after intravenous injection. Since the vertebrobasilar arterial system supplies the brain stem and diencephalon, this suggests that a central vasodilator tonus of the cerebral vessels is maintained by the innervation of the cerebral vessels by cholinegic neurons which have their central origin in the brain sterm and diencephalic area.

Central cholinergic control of cerebral blood flow in the baboon. Effect of cholinesterase inhibition with neostigmine on autoregulation and CO2 responsiveness.

Cerebral autoregulation and vastomotor responsiveness to carbon dioxide (CO2) were measured quantitatively by the use of the autoregulation index and chemical index, respectively, in normal baboons before and after intravertebral and intracarotid infusion of the anticholinesterase agent, neostigmine methylsufate (Prostigmin). Continuous measurements were made of cerebral blood flow (measured as bilateral internal jugular venous outflow), arterial and cerebral venous pO2 and pCO2, cerebral arteriovenous oxygen differences, and endotracheal CO2. The effect of intravertebral infusion of neostigmine (12.5 mug/kg body weight) was compared to intravertebral infusion of neostigmine (25 mug/kg body weight) for assessment of any specific action of the drug on a hypothetical cholinergic vasomotor center, presumed to be located in the territory of the vertebrobasilar supply. No significant or persistent changes in cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) followed either intravertebral or intracarotid infusion of neostigmine. Cerebral vascular resistance (CVR) and cerebral perfusion pressure (CPP), however, decreased significantly after intravertebral infusion. Cerebral autoregulatory vasoconstriction during increases of CCP was significantly reduced following both intravertebral and intracarotid infusion. Cerebral autoregulatory vasodilatation was not altered as CPP was lowered. Cerebral vasodilatory reactivity to CO2 inhalation was significantly enhanced following intravertebral neostigime but not following intracarotid neostigmine. Cerebral vasoconstrictive response to hyperventilation was not influenced by neostigmine. These results support the view that central cholinergic cerebrovascular influences exist, and are vasodilatory in nature.

[Double cholinergic and adrenergic regulation of cerebral blood flow]. / Dvoinaia--kholinérgicheskaia i adrenergicheskaia reguliatsiia mozgovogo krovotoka

Cerebral vascular tonus was measurably influenced by both alpha or beta adrenergic blockade and by inhibition of cerebrovascular acetylcholine or acetylcholinesterase. Cerebral autoregulatory response was significantly affected by intravenous injection of PBZ, intravertabral and intravenous injection of PPL and intravertebral and intracarotid injection of neostigmine. Cerebral vasomotor reactivity to changes in aPCO2 was altered significantly by intravertebral injection of PPL, atropine, and neostigmine. The doses of intravenous PBZ injections were large (1.5 mg/kg) so that PBZ not only blocked peripheral alpha adrenergic receptor sites in the cerebrovascular system but probably also those possibly located in the brain stem (vertebrobasilar territory). The functional significance of a double cholinergic and adrenergic neuronal system located in the brain stem influencing CBF appears to have been established.

Relationship between disturbed rheological properties and cerebral hemodynamics in recent cerebral infarction.

In 75 patients with neurological symptoms due to RCI serum fibrinogen, whole blood viscosity and platelet aggregability have been determined before treatment was started. In addition, in 24 of the patients also HBF has been measured. In patients with RCI viscosity was significantly increased. Serum fibrinogen was higher at increased viscosity levels and when enhanced platelet aggregation was evident. At low shear rates increased blood viscosity correlated significantly with serum fibrinogen as well as with reduction of HBF.

Disordered cholinergic neurotransmission and dysautoregulation after acute cerebral infarction.

The possible role of displaced neurotransmitter acetylcholine (ACHh) in dysautoregulation was examined after experimental regional cerebral infarction was produced by occluding the middle cerebral artery (MCA) in babons. Regional cerebral blood flow (rCBF) was measured after intracarotid injection of 133Xenon using the gamma camera. Autoregulation was tested with metaraminol or angiotensin infusion and the autoregulation index (A.I.) was calculated. Acetylcholinesterase (ACHhE) was measured in brain tissue of noninfarcted and infarcted hemispheres. Cerebral arteriovenous (A-V) differences for cholinesterase (ChE) were also measured. Regional dysautoregulation was found in infarcted gray matter and correlated with increased AChE levels in the same zones of cortex and basal ganglia. The time course of onset of dysautoregulation correlated with increased ChE uptake by the brain. Intravenous infusion of the cholinergic neurotransmitter blocker, scopolamine, restored autoregulation to the ischemic zones. Autoregulation appears to be a myogenic reflex, influenced by neurogenic and metabolic mechanisms.

Regional cerebral blood flow changes after bilateral external carotid artery ligation in acute experimental infarction.

Regional cerebral blood flow (rCBF) was measured in baboons by intracarotid injection of 133Xe and a gamma camera after acute cerebral infarction was induced by occlusion of the middle cerebral artery (MCA). A steady state of rCBF was measured four hour after MCA occlusion and was followed by bilateral ligation of the external cartoid arteries (ECA). Subsequent rCBF measurements were obtained at 30, 60, and 120 minutes. After bilateral ECA ligation, flow in ischaemic and non-ischaemic areas was greatly enhanced and flow in the hyperaemic areas significantly reduced, presumably since they had provided collateral circulation to the ischaemic zone with a favourable redistribution.

Circulatory and metabolic effects of glycerol infusion in patients with recent cerebral infarction.

The effect of intravenous infusion of 10 per cent glycerol on regional cerebral blood flow (using hydrogen bolus and Xenon-133 (133Xe) clearance methods) and metabolism was investigated in 57 patients with recent cerebral infarction. Hemispheric blood flow (HBF) increased, together with increase in regional cerebral blood flow (rCBF) and cerebral blood volume (rCBV), in foci of brain ischemia. Hemispheric oxygen consumption (HMIO2) decreased together with hemispheric respiratory quotient. Systemic blood levels of glucose, lactate, pyruvate, and triglycerides also increased after glycerol while free fatty acids (FFA) and inorganic phosphate (Pi) decreased. Hemispheric glucose consumption was unaltered after glycerol so that hemispheric glucose to oxygen ratio tended to rise. Pyruvate and lactate production by brain was unchanged. Glycerol moved across the blood brain barrier into brain and cerebrospinal fluid (CSF). Release of FFA and Pi from infarcted brain was reversed by glycerol. Total phosphate balance was maintained actoss brain both before and after glycerol infusion. Triglycerides increased in CSF after glycerol, originating either from cerebral blood or as a result of lipogenesis in cerebral tissue. The EEG Recording and neurological status of the patients improved despite decreased brain oxygen consumption. Results of this study suggest that after intravenous infusion of 10 per cent glycerol in patients with recent cerebral infarction, glycerol rapidly enters the CSF and brain compartments and favorably affects the stroke process in two ways: first, by redistribution of cerebral blood flow with increase in rCBF and rCBV in ischemic brain secondary to reduction in focal cerebral edema; and second glycerol may become an alternative source of energy either by being directly metabolized by the brain, or indirectly, by enhancing lipogenesis, or by both processes. Involvement of glycerol in lipogenesis with esterification to accumulated FFA might lead to improved coupling of oxidative phosphorylation, a hypothesis that fits the finding of improved neuronal function despite further decrease in cerebral hemispheric oxygen consumption.

Regional cerebral blood flow measured by the gamma camera after direct injection of 133Xe into the distal stump of the occluded middle cerebral artery.

Regional cerebral blood flow (rCBF) was measured after intracarotid injection of 133Xe concurrently with measurements of local cerebral blood flow (LCBF) after injection of 133Xe directly into the distal stump of the occluded middle cerebral artery (MCA) by the use of the gamma camera after producing experimental ischemia in baboons by occluding the MCA. Regional MCA stump pressure (rMCAP) was also measured. Regions of ischemia assessed by intracarotid injection of 133Xe correlated well with the territory of infarct defined by injection of 133Xe into the distal MCA stump. Flow values in ischemic regions obtained by direct injection of 133Xe into the MCA were 15% to 20% lower than those obtained by intracarotid injection of 133Xe. Possible explanations for these differences are discussed. During induced hypertension autoregulation in ischemic areas was abolished and paradoxical responses of LCBF and rMCAP to changes in arterial carbon dioxide tension (PaCO2) were confirmed.