This monograph is the result of one of the satellite conferences of the 1992 Annual Congress of the European Association of Nuclear Medicine. About half the book is devoted to brief reviews of the fundamental principles of functional brain imaging, specifically single photon emission computed tomography (SPECT), with some brief discussion given to positron emission tomography (PET). There is an introductory discussion of cerebral blood flow and metabolism, blood-brain barrier, and neurotransmission. One chapter is devoted to the application of techniques for the study of neuroreceptors and neurotransmission. There is a detailed study of the mathematical basis and guidelines for instrumentation for brain SPECT and the radiopharmaceuticals used in brain imaging. The second half of the book is devoted to the clinical application of these techniques, particularly brain SPECT, discussions of the types of results that can be obtained in a variety of clinical conditions, including stroke, epilepsy, and dementias

This is a review of extant concepts of transient ischemic attacks (TIAs), their definitions, prognostic significance, pathogenesis, physiology, and management. The natural history of TIAs depends upon the risk factors of the population group studied, so that therapeutic trials should be controlled and randomized and not dependent upon published natural history data. A strong association between TIAs and coronary artery disease has now been established. It may be difficult to establish the cause or pathogenesis of TIAs in any given patient in view of the relatively poor correlation between the patient's symptoms and location of arterial plaques. Recent studies have suggested mechanisms aside from impaired perfusion or embolization from carotid plaques or vertebral basilar disease. There are no proven indications for carotid endarterectomy, a procedure which has been excessively used in the United States, but presently ongoing prospective, randomized, controlled multi-center studies will likely resolve this important issue. Neither is there scientific validation for the use of long-term anticoagulants, but data support the efficacy of ASA in reducing the incidence of stroke and myocardial infarction in patients with TIAs.

This is a review of therapeutic modalities that have been utilized in the treatment of stroke. Each is based upon data obtained from the study of the biologic events that occur during experimentally induced cerebral ischemia in animals. The type of information obtained from these studies could not have been obtained in any other manner. Despite the apparent effectiveness of some of these modalities in modifying stroke in animals, their application to humans with stroke has been disappointingly ineffectual. The delay between onset of stroke symptoms and initiation of treatment is usually several hours or more, which may be too late to rescue ischemic neurons. In order to be effective, treatment will have to be initiated as early as possible (preferably within 1 hour) to take advantage of the biologic window of opportunity. There is evidence that this can be accomplished by proper planning and training of personnel.

We studied the degree of edema resulting from focal brain compression in rats raised on vitamin E-deficient, -normal, or -supplemented diets. After release of 24 hours of epidural compression, edema developed ipsilaterally and was characterized by extravasation of serum protein, increased water and sodium content, and little change in potassium. The degree of swelling and increase of sodium in the previously compressed area were most pronounced in the vitamin E-deficient group and mildest in the vitamin E-supplemented group. Degradative processes of biomembranes seem to participate in the pathogenesis of brain edema; vitamin E may stabilize membranes by physicochemical interactions between the phytyl side chain and polyunsaturated phospholipids, or vitamin E may disrupt chains of free radical reactions.

Publisher Summary This chapter presents an approach to the assessment and management of the patient with acute stroke. It discusses the differential diagnosis, medical complications, stroke in progression, and available therapeutic modalities. The chapter also describes the physiologic objectives of therapy along with the types of edema seen in cerebral infarction. The management of acute stroke is often a difficult problem. There are several basic principles that govern the initial assessment and treatment of the patient with an acute stroke. First, the etiology of the underlying disorder must be established. Second, the primary medical problems or their complications must be identified and treated. Particular emphasis must be placed on the prevention of pulmonary aspiration. Third, the progression of the neurological deficit must be determined. Therapeutic intervention with pharmacological agents must be initiated when indicated.

The mechanisms whereby CO 2 affects cerebral vessels are not as simple as once thought, 1, 2 and are probably both directly on cerebral vascular walls 3, 4 and indirectly by action on brain stem neurones. 5 Furthermore, cerebral vascular reactivity to CO 2 has been reported to be altered by a number of physiological and pathological circumstances. The capacity to dilate to increased Pa CO CO2 is decreased in cerebral vascular lesions, 6-8 and is affected by changes in cerebral perfusion pressure. 9 Cervical sympathectomy is said to increase CBF response to Pa CO CO2 changes, whereas sympathetic nerve stimulation abolishes reactivity to CO 2 . 10 Deep anesthesia, hypothermia, or trauma to brain reduces reactivity to cerebral vessels to CO 2 , the one common denominator for these states being reduced cerebral metabolism. This report demonstrates that the capacity of cerebral vessels to dilate or constrict in response to changes in Pa CO CO2 is influenced by cerebral oxygen consumption.

The local effects of hypoxia induced by inhalation of 6% oxygen-nitrogen gas mixture on cortical blood flow of dogs, measured by heat clearance, are variable, whereas the ratio of cerebral venous pressure to mean arterial pressure as an indication of cerebral vascular conductance, uniformly increased. Local cortical flow decreased in one third of animals during hypoxia, but all showed an increased local flow in all areas studied to hypercapnia. The mechanism for a vasoconstrictive response to hypoxia in local cortical regions is not understood.

IN a previous report1we demonstrated that carbon dioxide (CO2) may increase cerebral blood flow (CBF) when supplied to the brain via the subarachnoid space (SAS) while the arterial carbon dioxide tension (Paco2) is kept at a low level, suggesting that the effect of CO2on CBF may not necessarily be mediated by its effect on the smooth muscle of the cerebral arterial wall, but perhaps by another mechanism, such as mediation through a chemoreceptor reflex mechanism. Reviewing previous pertinent work, it was somewhat surprising to discover that no direct demonstration of the effect of CO2on the smooth muscle of the cerebral arterial wall had been described. The only direct investigation, frequently quoted in various reviews dealing with this subject, is the work of Cow2in 1911 who observed that isolated segments of the carotid artery dilate when CO2is added

THE PURPOSE of this study was to explore the lactate and pyruvate levels of arterial and cerebral venous blood in normal resting persons and in ill hospitalized patients, with methods and conditions routinely used in our laboratory. These control results would be preliminary to a study of cerebral anoxia or hypoxia. Evaluation of excess lactate production, as described by Huckabee 1,2 is possible by calculations from such data. Excretion of lactate by the resting brain might indicate that some of the glucose taken up by brain is not metabolized beyond the end reaction of anaerobic glycolysis. It has been known from results obtained in several laboratories that the ratio of glucose to oxygen utilization by brain in vivo is not stoichiometric; approximately 6.0 vol% O 2 and 10 mg% glucose are representative average values for cerebral oxygen and glucose extraction respectively. The difference between the glucose taken up and

The traditional measurement of cerebral blood flow (CBF) by the nitrous oxide method of Kety and Schmidt1has the two important limitations that flow rates reflect only the average rate over a ten-minute equilibratory period and that the values reflect rates per unit weight of perfused cerebral tissue. The first limitation prevents obtaining quantitative data concerning brain blood flow and metabolism under short-acting stresses and rapidly changing states, while the second may prevent recognition of changes in the total mass of perfused brain. Wechsler2and Lewis et al3have recently employed Kr79as the inert gas in CBF determinations, and by virtue of the ability to monitor continuously the brain content of γ-emitting Kr79by external head scintillation detectors were able to measure minute by minute values of CBF over approximately five minutes of a ten-minute period of Kr79inhalation. This valuable advance in

While patients receiving adrenocorticotrophic hormone (ACTH) often show an increased sense of well-being and mild euphoria, a small number become psychotic. Electroencephalographic (EEG) changes (1) have been reported in patients receiving ACTH who become psychotic, but the changes have been inconsistently present. In one instance (2) the EEG changes appeared to be related to a decrease in serum potassium level. These observations led to a study of cerebral blood flow and metabolism in patients receiving ACTH. Concurrent investigation of the EEG (3) and of the clinical and metabolic responses of these subjects will be reported elsewhere (4). METHOD A total of 44 observations on 14 patients was made; 15 before, 23 during, and six following ACTH treatment. ACTH was administered intramuscularly to adults in full therapeutic doses (60-100 mgs. Armour ACTH or 30 to 40 mgs. Wilson's Corticotropin daily).3 One 12 year old child received 33 mgs. Armour ACTH daily. There was no significant difference noted in the clinical response to the two brands of ACTH at these doses. Measurements were made at least once during therapy and as often as four times at intervals varying from seven to 56 days. In all patients, except one studied at seven days, at least one of the repeat studies was made between the second and third week on therapy. Several disease states are represented, including five patients with active rheumatoid arthritis, three with disseminated lupus ery-thematosis, and one each with subacute glomerulonephritis with edema, chronic glomerulonephritis, primary systemic amyloidosis, myasthenia gravis, chronic pulmonary fibro-sis, and chronic exfoliative dermatitis. All patients showed increased appetite and sense of well-being and supplies of ACTH for these studies. most developed the facial fullness and redness suggestive of Cushing's syndrome. All of the patients were studied under similar laboratory conditions in the fasting state. The nitrous oxide method originally described by Kety and Schmidt (5) and modified by Scheinberg and Stead (6) was used. The gas mixture used in the determination consisted of approximately 15% N20, 64% N2, and 21% 0. Arterial blood pressure was measured by the auscultatory method with the arm held at heart level. Mean arterial blood pressures were calculated from these readings by adding one third of the pulse pressure to the diastolic pressure. Blood samples for determination of oxygen and glucose contents were drawn just before and following each cerebral blood flow. The A-V oxygen difference was determined by the method described …

1. Cerebral blood flow and metabolism were measured in 16 patients with pernicious anemia. Seven of the patients were restudied in various stages of therapy. 2. The patients fell into two equal groups, those with severe anemia and those with moderate or no anemia. In the first group, cerebral blood flow was increased and cerebral vascular resistance decreased; in the second group, cerebal blood flow was decreased and vascular resistance increased. In both groups, cerebral oxygen and glucose consumption was decreased, as was cerebral venous oxygen tension . 3. There was a good correlation between the mental status defects and cerebral oxygen consumption and between severity of neurologic involvement and cerebral oxygen consumption. There was no correlation between cerebro-vascular resistance and cerebral oxygen consumption, nor between degree of anemia and cerebral oxygen consumption. 4. Specific therapy resulted in a moderate increase in cerebral oxygen consumption and cerebro-vascular resistance. In no instance did cerebral oxygen consumption become normal. 5. The disparity between the functional ability of the patients and the low values for cerebral metabolism is discussed. 6. It is concluded that pernicious anemia results in specific nervous system involvement not related to the anemia, and that this damage is at least partially irreversible in many patients.

Measurement of cerebral blood flow by the nitrous oxide method before and during intravenous administration of nicotinic acid indicates that cerebral vessels do not respond to this drug. Evidence that contamination of cerebral by extracerebral blood occurs in about 20 per cent of subjects is adduced from the effects of nicotinic acid on the measured cerebral blood flows; studies making use of the intravascular catheter technic to sample internal jugular blood tend to confirm this hypothesis.