This is the first report of a method of sequential regional cerebral blood flow (rCBF) analysis, called Croma-Memo-Flow. This technique is a computerized modification of the initial slope method of regional cerebral blood flow (rCBF init.), allowing temporal resolution of the flow pattern by calculation of the slopes of sequential segments of the initial 1-2 minutes of the Xenon-133 washout curve. The same theoretical analysis applies to this method as to the rCBF init. method. Each flow calculation is based on the slope of a discrete 16 second segment of the initial washout; and each second the segment is advanced by one second. A new flow calculation is made each second and is displayed as a color coded map on a TV screen. Each map is labelled, indicating the time in seconds following Xenon injection, and sequential rCBF changes during the clearance period can be immediately visualized. This allows for almost instantaneous analysis and display of rapid or transient rCBF responses to activation and deactivation of the cerebral cortices.

The data is stored in a 35 channel memory for deliberate replay, photography, and analysis.

Functional tests may be applied during the initial washout period and both the magnitude and chronological relationships of the evoked regional cerebrovascular responses observed. A clinical study is presented to illustrate the possibilities of applying the technique to assess cortical reactivity.

Sixteen cases of spontaneous dissection of the cervical internal carotid artery (6 verified) are described. The mean age was 45 years. The clinical picture varied from simply headache and a bruit to hemiplegia and aphasia. Eleven patients had transient ischemic attacks. Headache, facial pain, a subjective bruit, oculo-sympathetic palsy and transient monocular blindness were present in various combinations in two-thirds of cases and their presence suggested the correct diagnosis. Examples of suspected dissection of the intracranial internal carotid, middle cerebral, posterior cerebral and extracranial vertebral arteries are also presented. Spontaneous dissection is more common than the literature indicates.

The general principles of bypass surgery as they affect the cerebral circulation are reviewed. The preliminary results of an extracranial intracranial bypass operation performed on a group of 19 patients suffering from cerebral ischemia are presented. The results of the surgery compare favorably with those published in the literature.

The effects of bilateral common carotid artery occlusion en brain metabolism and arterial acid-base balance were studied in normotensive and experimental renovascular hypertensive rats.

One hour after carotid occlusion in hypertensive rats, supratentorial lactate increased to 383% and lactate-pyruvate ratio to 280% of the controls, while adenosine triphosphate (ATP) decreased to 69%. These metabolic changes were thought to be due to cerebral ischemia. Arterial pC02 was lowered and the pH was raised in the hypertensive animals due to cerebral ischemia induced hyperventilation. In the normotensive rats, carotid occlusion had minimal effects on cerebral metabolism and arterial acid-base balance.

These results suggest that hypertensive rats are more susceptible to cerebral ischemia caused by carotid occlusion than normotensive rats. Increased cerebrovascular resistance in hypertension is discussed as a casual factor in cerebral ischemia.

Broken cell preparations derived from rat cerebral cortical grey matter were studied cytochemically to localize adenylate cyclase (AC) activity in subcellular organelle membranes. AC activity was localized by visualizing reaction product in brain particulate fractions by electron microscopy. Activity was found in the endoplasmic reticulum, on the inside of the inner mitochondrial membrane and on both leaflets of the nuclear membrane. Reaction product was found in the postsynaptic density area of most synapses. The reaction product tended to be more prominent in the presence of flouride. A synaptosome-rich fraction was shown to have NE stimulated AC activity which was blocked in vitro by both a α-and an β-blocker and in vivo by propranolol.

The effect of general anesthesia on 42 multiple sclerosis (MS) patients who underwent 88 episodes of general anesthesia was analyzed. One patient experienced a relapse after a procedure under general anesthesia, which is compatible with the natural history of the disease. A literature review revealed little information on this subject or on the use of particular anesthetic agents in MS. Our experience with spinal and local anesthesia is reported. In the evaluation of the former our limited data suggested that spinal anesthesia is less preferable than other alternatives in MS. Local anesthetics had a benign effect on the course of MS.

The microvascular architecture of the subependymal matrix in premature infants was studied with microangiography and benzidine stains. This revealed that the subependymal matrix is the end zone or the border zone between cerebral arteries and the collection zone of the deep cerebral veins. Focal hypoxic changes of this subependymal matrix may occur in hypoxemia and ischemia because of the characteristic architecture.

The vascular permeability of these vessels was studied in rabbits using three different molecular weights of FITC-dextran. Vascular permeability was increased in the subependymal matrix by hypoxia and especially by hypoxia associated with an increased venous pressure. These findings may be related to the pathogenesis of subependymal hemorrhage in prematurity.

A short summary of the state of our knowledge at the start of Phase Two of the Quebec Cooperative Study of Friedreich's ataxia is presented. The main questions raised hy the discoveries made in the Phase One Survey are listed and the plan of our current investigations is outlined.

A new syndrome of autosomal recessive spastic ataxia has been isolated in the Charlevoix-Saguenay region of Quebec. This syndrome is remarkably homogeneous and includes: spasticity, dysarthria, distal muscle wasting, foot deformities, truncal ataxia, absence of sensory evoked potentials in the lower limbs, retinal striation reminiscent of early Leber's atrophy and the frequent presence (57%) of a prolapse of the mitral valve. Biochemically, many cases show impaired pyruvate oxidation, others have hyperbilirubinaemia and some have low serum β-lipoproteins and HDL apoproteins. These features are similar to those found in trypical Friedreich's ataxia.

A thorough investigation of vestibular function has been carried out in 16 patients with typical Friedreich's ataxia. Electronystagmography and caloric tests revealed a number of inconstant abnormalities. Most abnormal findings were related to ocular dysmetria, disorganized pursuit and square waves.

HLA antigen typing was carried out in a family with an autosomal dominant form of spinocerebellar degeneration [possibly olivoponto cerebellar atrophy (O.P.C.A.) — Type 1] . Eleven ataxic patients, three possibly ataxic subjects, two unrelated spouses and 13 clinically normal at risk siblings were typed for ABO and Rh blood groups, HLA-A and HLA-B antigens, C4 component of the complement and a number of other serum proteins (Clq, (β -1A, (β-1C, C5, (β -lipoproteins). No solid evidence for linkage between the ataxia gene and the HLA or C4 loci could be demonstrated in this family. Certain serum proteins, and particularly β -lipoproteins were found to be significantly reduced in some sub-groups of subjects.

Friedreich's ataxia is almost always associated with a cardiomyopathy. The cardiomyopathy and its attendant cardiopulmonary sequelae is the usual cause of death in this disease. The author reviews the known pharmacology of the heart, particularly as it applies to hypertrophic cardiomyopathy. The important role played by calcium and the possible role of taurine is stressed. Therapeutic possibilities are mentioned.

The regulation of cytoplasmic calcium is a key process in nerve tissue. Using a smooth muscle model we have shown that prostaglandine (PG) E2 probably regulates entry from extracellular fluid, whereas the release from intracellular stores depends on the interplay between thromboxane (TX) A2, PGEl and prostacyclin. Hormones and other agents interact with this system in the following ways: vasopressin, angiotensin and inositol mobilize arachidonic acid from membrane phospholipids and increase synthesis of PGE2 and TXA2, Cortisol blocks this action. Prolactin and zinc mobilize dihomo-γ-linolenic acid and increase synthesis of PGEL These effects can be blocked by Cortisol, lithium and taurine, three agents which on their own have no effect on basal PG production. Epileptogenic agents like penicillin and picrotoxin also stimulate PG synthesis, while diphenylhydantoin is a PG antagonist and diazepam is a TXA2 antagonist. The effects of all these agents occur at concentrations which are physiological in the case of the natural ones, and readily attained in human plasma in the case of the drugs. In view of recent evidence that calcium may be important in demyelination and considering the established role it plays in nerve conduction and synaptic transmission, we suggest that these observations may be of significance in understanding Friedreich's ataxia.

The hypothesis that an abnormal oxygen-hemoglobin dissociation curve is a primary or a secondary defect in patients with Friedreich's ataxia was investigated in 12 subjects with this disease. Hemoglobin and P50 were measured and compared with age and sex matched controls. The mean hemoglobin concentration was 14.2 g% and the P50 was 26.25 ton for the patients and 13.8 g% and 26.27 ton in the controls. These results indicate that the oxygen transport system is normal in this disease and likely exclude an abnormal oxygen dissociation curve as a primary or a secondary factor in the pathophysiology of the cardiomyopathy and the neuromyopathy found in this disease.

The combined metabolic stresses of fasting and the intravenous injection of 50 mg nicotinic acid in Friedreich's ataxia resulted in the delineation of two sub-groups of responses. High bilirubin ataxics maintained abnormally elevated levels of bilirubin, while normal bilirubin ataxics behaved like the normal control group. It is postulated that this finding infers the possible linkage of the gene for Friedreich's ataxia and that for Gilbert's disease.

The Pyruvate dehydrogenase multienzyme complex (PDHC) purified from rat brain is phosphorylated in the presence of low concentrations of ATP and MgCl2. The phosphorylated PDHC is incapable of catalyzing the oxidative decarboxylation of pyruvate. In the presence of high concentrations (10 mM) of MgCl2, the phosphorylated (inactive) PDHC is converted back to the dephospho-form of PDHC which is catalytically active.

The dihydrolipoyl dehydrogenase (LAD) component, E3, of PDHC is inactivated by pyridoxal phosphate (PLP) and the PLP-inactivated LAD can be reactivated by an amino acid, taurine. These results indicate the reversible formation of Schiff base between PLP and LAD. They also provide clear evidence for the involvement of LAD (E3) in the previously reported inactivation of PDHC by PLP.

Pyruvate dehydrogenase (PDH), α -keto gluturate dehydrogenase (α -KGDH) and lipoamide dehydrogenase (LAD) were measured in platelets of II patients with typical Friedreich's ataxia and 10 normal control subjects. Serum LAD was also evaluated in the same patients. No statistically significant changes were found in platelets for the group as a whole, although some patients had low values (more than one standard deviation below control mean). Serum LAD was significantly reduced in the patients with Friedreich's ataxia. This was not due to associated diabetes.