D. Denny-Brown

The Cerebral Collateral Circulation 2. Production of Cerebral Infarction by Ischemic Anoxia and its Reversibility in Early Stages

IT IS COMMON clinical experience that a remarkable degree of functional recovery may occur in a neurologic disorder resulting from thrombosis and insufficiency’ of the major cerebral vessels. Indeed, in syndromes due to insufficiency of the basilar and carotid arteries the intermittent nature of the symptoms characterizes the disorder.1-4 For example, we have recently treated an elderly woman suffering from occlusion of the internal carotid artery who has had nine transient episodes of complete hemiplegia and hemianopia of one to one and a half hours duration, with complete recovery on each occasion. The tenth attack lasted for 48 hours and some spastic weakness of the arm has persisted. Both clinical and experimental evidence indicate that, in most types of such transient paralysis, the onset of symptoms is due to a fall in systolic blood pressure reflected in the supply to an area that is already compromised by stenosis or occlusion of its major tributory.’ Under these circumstances recovery from the resulting hemodynamic crisis may reflect only the rapid recovery of adequate systolic blood pressure. In other circumstances recovery of function occurs in spite of continuation of diminished cardiac output for many hours or days. In this case, the collateral circulation may itself have adjusted to the state of insufficiency. A fall of systolic pressure of sufficient duration, for example, that is related to gastrointestinal hemorrhage2 can certainly lead to catastrophic infarction. In embolism the area of infarction is also greatly variable, manifestly due to variations in collateral supply. It is, therefore, desirable to learn more of the dynamic adjustments of collateral vessels in the brain, with a view to better definition of the factors that increase collateral blood flow when a main vessel is occluded. In previous comm~nications5~~ we have reported an experimental analysis of collateral circulation in terms of the fall and recovery of oxygen tension in the relatively ischemic area and in terms of the reactive vasodilation of collateral vessels. The level of systolic pressure, the level of intraluminal pressure, the oxygenation of arterial blood, the vascular resistance of the ischemic area, and, to a less extent, metabolic by-products of anoxia in the ischemic area emerged as important factors. The present study is devoted to a close examination of events in the vessels of the ischemic area, seeking to define the local factors underlying ischemic response, increased vascular resistance, and infarction. An attempt has been made to produce varying degrees of failure of the collateral circulation and to examine the resulting functional impairment in terms of neuronal injury as indicated by the electrocorticogram and steady potential (S.P.) . The validity of these technics has been critically reviewed previously.7 Vascular damage was judged by observations of blood flow in the cortical vessels with a microscope and by photomicrography. In many experiments changes in vascular permeability were studied after the intravenous injection of trypan blue, as used by Broman and others.8-10 Attempts were made in most experiments to improve any functional damage to the cortex or its blood flow by restoration of the blood pressure and by the administration of oxygen or of heparin solution intravenously. Neuronal and vascular damage were also analyzed in terms of any change in local oxygen tension, as determined by the polaroyaphic method,”r and compared to that prouced by prolonged nitrogen breathing for purposes of comparison. In three experiments histologic studies of the brain after removal, fixation, and staining were correlated with the microscopic and polarographic observations made in vivo.

Experimental cerebral concussion.

EXPERIMENTAL concussion is a condition well known from the early investigations of Kocher [1901], Duret [1920], Polis [1894] and, more recently, Miller [1927] to be associated with a cessation of respiration and rise of blood pressure, of duration corresponding to the intensity of the blow. Re-investigation of the phenomenon in cats under nembutal anaesthesia confirms its appearance in severe degree, and ability to result in death, without macroscopic lesions of the brain stem. It is further established that the phenomenon can be elicited in the decerebrate animal, and corresponds with a passing depression of all bulbar reflexes (corneal, pinna reflexes, etc.). The respiratory centre is the most sensitive to percussion. Acceleration in movement resulting from the blow is the essential factor in the stimulus, for if the head is prevented from moving when struck the phenomenon fails to occur. Momentary deformity of the skull, and stimulation of superficial structures, therefore appear to play no part. An instant acceleration of the head from zero to 23 feet per second (or reverse deceleration) is the minimal stimulus for the cat. It is slightly higher for the macaque monkey. Labyrinthine stimulation likewise appears to have slight if any part in the phenomenon, for it is obtained after section of both eighth nerves. Rise of intracranial pressure does not accompany the phenomenon, though it is possible under certain circumstances to reproduce a similar effect by a shock-like rise of intracranial pressure alone. The nervous effect of a blow is thus considered to be due to the physical acceleration directly transmitted to each and every centre.

Electroencephalographic Study of Insufficiency of the Basilar and Carotid Arteries in Man

CLINICAL OBSERVATIONS concerning syndromes due to occlusion of the internal carotid and basilar arteries1 have led to the hypothesis that recurrent symptoms were due to hemodynamic crises resulting in failure of the cerebral collateral circulation in a compromised vascular territory, rather than due to a varying degree of “vasospasm” of the affected artery. In these clinical studies, falls in systolic blood pressure were found to be a frequent cause of failure or impairment of the collateral supply. At necropsy there is frequently a large discrepancy between the severity of the clinical signs and the relative smallness and patchy distribution of infar~t ion.~,~ We, therefore, introduced a physiologic concept of widespread reversible ischemia associated with the hemodynamic crises of these states, determined by the variable efficiency of the extensive anastomoses of the circle of Willis.lc Arteriography in patients with occlusion of the major cerebral vessels and anatomic studies at necropsy have demonstrated the frequency of small arterial anastomoses providing the basis for additional adjustments in the collateral circulation beyond those provided by the circle of W i l l i ~ . ’ ~ ~ ~ ~ In experimental studies in monkeys4 we have been able to demonstrate slow, independent adjustments of cortical vessels to stress on their capacity as collaterals and the crucial role of systolic blood pressure in this phenomenon, It was, therefore, to be anticipated that localized ischemia might be pro-

The Changing Pattern of Neurologic Medicine

GEORGE CHEYNE SHATTUCK (1784–1854), for whom this lecture was named, adorns that period of medicine that boasts Richard Bright, Thomas Addison, Thomas Hodgkin and Robert Graves. His special attribu...

The Localization of Hemispheric Mechanisms of Visually Directed Reaching and Grasping

KENNARD (1936) first drew attention to the remarkable potential of the infant macaque monkey for recovery of motor function following removal of the motor cortex from both hemispheres. In later work she found that additional removal of both frontal lobes resulted in greater spasticity, comparable to that produced by removal of motor cortex in the adult monkey. Additional removal of post-central parietal cortex also resulted in the appearance of a spastic overadducted gait. It was concluded that in the very young animal the management of motor function was largely subcortical, and that towards the end of the first year the frontal and parietal lobes had developed some ability to compensate for loss of such cortical motor function as had developed at that age (KENNARD, 1938, 1942; KENNARD and FULTON, 1942).

Studies of the mechanism of stimulus-sensitive myoclonus in man.

Abstract Clinical and graphic observations of movement, muscular contraction and cerebral electrical activity in relation to a variety of stimuli in a patient with myoclonus-epilepsy are reported. The condition was myoclonus-epilepsy of the Unverricht-Lundborg type due to diffuse neuronal lipoidosis (cerebromacular degeneration). A stimulus evoked appropriately localized cerebral electrical disturbances and a localized myoclonus. With repetition of stimulus these spread progressively to produce the myoclonic convulsion. The clinical course and cerebral electrical concomitants of the transition from myoclonus to seizure are described. Both in response to a single stimulus and in the development of widespread myoclonus resulting from repetitive stimuli the slow wave component of the evoked cortical potential played a prominent part. The cortical spikes in receptor areas were not directly associated with the myoclonic muscular twitch. Diffuse cortical sharp spikes appeared late in the development of a seizure and were then directly related to muscular contractions. This final stage in the seizure is identical with other types of cortical tonic-clonic epileptic discharge, and was preceded by a build-up of the slow wave component of the earlier myoclonic phase. It is postulated that a breakdown in synaptic resistance due to diffuse neuronal disease, particularly in subcortical structures, is responsible for the phenomenon of myoclonus.

Multiple sclerosis—The clinical problem

Abstract Although multiple sclerosis has pathologic and probably etiologic affiliations with a whole group of demyelinating diseases, its intermittent and asymmetrical clinical symptomatology is highly characteristic. The natural tendency to remission is very considerable and disability may be long deferred. Patients with a fair prognosis are too often discouraged, lose employment and led to try expensive and heroic cures, at the same time disregarding simple measures of known value. The psychiatric symptoms are sometimes mistakenly treated, particularly when they are early and prominent. In the acute stage of onset or relapse harm can be done by too energetic measures. Promotion of general health is more important than specific therapy. A better understanding by internists of the problems of the disease, particularly in relation to the presence or absence of recent relapse, and in the recognition of favorable and unfavorable prognosis, would avoid much unnecessary therapy. When diagnosis is unavoidably uncertain, the possible presence of other disease must continually be borne in mind.

POST-CONCUSSION SYNDROME—A CRITIQUE

Excerpt Though head injuries are usually considered to be the province of the surgeon, the physician, as Richard Bright1remarked over a century ago, is so commonly called upon to alleviate their af...

The extrapyramidal system and postural mechanisms

Extrapyramidal disorders, which include a wide range of disturbances involving loss of ability of movement, and muscle stiffness of either the plastic or springy type, are distinguished from those of “spastic paralysis” due to lesions of some part of the corticospinal tract. The most obvious features of the former are disturbances of postural attitude. Other features‐tremor, rigidities, exaggerated deep reflexes, and resistance to stretch‐are discussed in terms of the mechanisms (facilitatory and inhibitory) involved. Data from classical experiments, ahlation and stimulation of the supplementary area and other cortical extrapyramidal postural regions, are reviewed, interpreted, and related to the clinical manifestations of spasticity and dystonias. Current experimental evidence (decorticate monkey) reveals the interdependence between proiected types of motor reactions served hy the pyramidal system and the more elementary reactions such as the grasp reflex and traction reactions, and points to the involvement also of mechanisms at the cortical level in dysionias, previously descrihed as symptoms of basal ganglia diseases.

Neurologic Aspects of Vertigo

VERTIGO is a sensation, a symptom without any essential objective sign, and is therefore subject to all the limitations imposed by the descriptive powers and capacity for observation possessed by t...