Showing papers in "Neurology in 1965"

Lacunes: Small, deep cerebral infarcts

Abstract: Neurology 1965;15:774-784 Lacunes may be defined as ischemic infarcts of restricted size in the deeper parts of the brain. Absent from the cerebral and cerebellar cortex, they are best known in the chronic healed stage when they form irregular cavities, 0.5 to 15 mm. in diameter, principally in the basal ganglia and basis pontis (Figs. 1, 2, 3, 4, and 5). Although outnumbering all the other varieties of cerebrovascular lesion combined,1 lacunes are not as well known to the neurologist as they deserve to be. The present paper is a survey of the pathological findings in a series of patients with lacunes autopsied at a general hospital. While it was possible to correlate lacunes with the occurrence of cerebral atherosclerosis and arterial hypertension, the clinical details in the cases were so deficient that a good clinicopathologic correlation could not be made. Fig. 1. Section showing lacunes in putamen and head of caudate nucleus Fig. 2. Lacunes in thalamus and opposite putamen Fig. 3. Lacune in basis pontis Fig. 4. Lacune in frontal white matter Fig. 5. Lacunes in deep parietal white matter The term lacune can be traced back to Durand-Fardel2 who in his treatise on softening of the brain described the pathological findings in his case No. 78 as follows: "The striatum on each side showed a certain number of small lacunes with no associated alteration of color or consistency from whose surface there extended a fine meshwork containing very small vessels." Elsewhere in the same monograph the author described for the first time etat crible (riddled with shot or sievelike) consisting of numerous canals or small round holes in the cerebral tissue from each of which a small vessel projected and which were located in the striatum, thalamus, and cerebral white matter. That he was not …

Cerebral vasomotor paralysis produced by intracranial hypertension.

Abstract: THE SIGNS and symptoms of increased intracranial pressure and cerebral compression have occupied the interest of numerous investigators since earliest times. Although changes in vital signs in response to alterations in intracranial dynamics have long been recognized, the importance of these changes in the diagnosis and management of patients with expanding intracranial lesions has been questioned. In particular, the arterial hypertension which is readily produced experimentally by increased intracranial pressure has been considered to be of limited clinical significance because it has been assumed that blood pressure does not increase until the intracranial pressure approaches the diastolic pressure and that this rarely occurs. This conclusion was based primarily on periodic recording of the lumbar subarachnoid pressnre and thus requires the additional assumption that the spinal fluid pressure at all times approximates the intracranial pressure. In a previous report we presented experimental evidence that obstruction at the tentorial incisura during expansion of a supratentorial mass prevents communication of pressure to the posterior fossa and spinal cana1.l Also, as the pressure gradient across the incisura increases, the vasopressor threshold decreases, and arterial hypertension may then occur, with absolute intracranial pressures far below the diastolic pressure.? The first purpose of the present experiments was to extend these observations in an attempt to determine the sequence of events which ultimately lead to neurological deterioration and death during gradual expansion of an intracranial mass lesion. The history of the investigation of cerebral compression before 1900 was reviewed by

Further notes on disability evaluation in multiple sclerosis, with scale modifications.

Abstract: IN 1955 a disability status scale for multiple sclerosis was published that delineated 10 progressive steps or grades of overall neurologic dysfunction attributable to this disease.1 This was later elaborated233 to include a complementary system of grades within 8 “functional systems” of involvement: pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, mental, and other. Since these scales have attained a modest popularityl-7 it seemed advisable to record certain changes suggested by further experience.

Tortuosity, coiling, and kinking of the internal carotid artery. i. etiology and radiographic anatomy.

Abstract: ALTHOUGH in recent years considerable attention has been directed to the study of tortuosity and kinking of the internal carotid artery, the etiology and significance of these conditions are still matters of controversy. Arteriographic studies of the internal carotid artery suggest 3 different types of abnormality, namely, tortuosity, coiling, and kinking, each having its own morphological characteristics. Otolaryngologists were the first clinicians to be concerned with sigmoid tortuosity of the internaI carotid artery. Fatal hemorrhagic complication, as a result of injury to a tortuous segment of the artery close to the lateral or posterior wall of the pharynx, occasionally followed tonsillectomy or removal of adenoid vegetations.'-5 To avoid such complication, it was recommended that visual and digital examination for arterial pulsation always be carried out before operating in the pharynx. Prominent and pulsating internal carotid arteries in thc lateral and posterior walls of the pharynx have been studied by Wood6 and Kelly.? They found that this condition, caused by sigmoid tortuosity of the internal carotid artery, occurred unilaterally or bilaterally in young as well as in older persons. Demme, quoted by Skillern,5 found pulsation in the pharyngeal wall in 2% of 10,000 patients examined over a period of ten years. Most of the recently published reports on tortuosity and kinking of the internal carotid artery have been concerned with angiographic studies in geriatric patients, chiefly those with cerebrovascular disorders. Very few such studies have been made in young adults and none in children under 10 years of age. We have undertaken this review in order to obtain further information regarding the etiology and clinical significance of pathological alterations and anatomic variations in the length and course of the internal carotid artery in patients of a11 age groups. Anatomic studies carried out in the dissecting room early in this century demonstratecl that the internal carotid artery in some individuals has a course and configuration markedly different from that usually described in textbooks of normal anatomy. Edingtons reported ' 1 case of a 34-year-old male with bilateral tortuosity of the internal carotid arterv at the level of the superior margin of the thyroid cartilage. Cameron,\" Moorhead,l\" and Smith,l* each in 1902, found that this condition was nolt dn infrequent occurrence. The tortuosity was usually located about 3 cm. above the bifurcation of the common carotid artery. in some cases bilaterally but more frequently unilaterally, particularly on the left side. Most of these abnormalities were found in elderly persons, but a few were discovered in young people as well. Rowlands and Swan\" reported a case of a 94-year-old female in whom the internal carotid was S-shaped and peculiarly symmetrical on both sides, with the tortuosity occurring 5 cm. from the bifurcation of the common carotid artery. SmithT1 reperted another with a complete circular coil 3 cm. above the bifurcation of the left common carotid artery. Fisher2 also reported 2 patients in whom there was an S-shaped curve in both internal carotid arteries at the level of the tonsillar fossa. Cairneyl3 dissected the head and neck of

Tortuosity, coiling, and kinking of the internal carotid artery: II. Relationship of morphological variation to cerebrovascular insufficiency

Abstract: SEVERAL recent publications have suggested a relationship between cerebrovascular insufficiency and kinking and coiling of the internal carotid artery in its extracranial portion. Riser and associates1 reported a case of coiling and kinking associated with severe attacks of vertigo. After a surgical procedure in which the artery was straightened by attaching it to the sternocleidomastoid muscle, the episodes subsided. Two patients reported by Derrick and Smith2 had not only a loop in the left internal carotid artery but also kinking of the artery on the opposite side. Henly and associates3 reported 7 patients in whom cerebral manifestations were believed to be due to coiling of the internal carotid artery. A review of the symptoms reported in their patients reveals that the cerebral disturbance was on the side of the coiling in only one case and that even in this instance it would appear more likely that the symptoms were due to disease of the small intracranial vessels. There was no evidence of narrowing of the lumen in the coiled segment, nor was there any report that the size of the lumen was altered by the position of the head. In their other 6 patients the symptoms suggested insufficiency in the vertebrobasilar system rather than a disorder related to a unilateral carotid lesion. These patients were not followed over a long enough period of time, and the results are inconclusive.

Pure sensory stroke involving face, arm, and leg.

Abstract: a clinical syndro,me within the field of cerebrovascular. disease is of great value when it permits the accurate diagnosis of both the site and nature of the lesion and assists in decisions concerning the prognosis, the need for arteriography, and th? therapeutic management of the patient. Syndromes such as the carotid, vertebral-basilar, lateral medullary, and pure motor hemiplegia are examples. Another candidate for this group is the pure hemisensory stroke. I n this syndrome the symptomatology is limited to a persistent or transient numbness and mild sensory loss over one entire side of the body, including the face, arm, and leg. The power of the limbs is preserved, and usually there is no vertigo, diplopia, dysarthria, dysphasia, visual field defect, nystagmus, memory loss, or other deficit. Cases with a more limited sensory involvement may represent a partial syndrome, but the remarks below apply, for the most part, to the full syndrome. In the past few years we have examined 26 patients in whom this syndrome, or variations of it, occurred, as follows: sensory stroke only, 10; transient ischemic sensory attacks, 8; sensory stroke after transient ischemic attacks, 3; only arm and leg affected, 3; and atypical, 2.

Neurological manifestations of sarcoidosis

Abstract: ALTHOUGH SARCOIDOSIS involves many organs (commonly lungs, lymph nodes, and liver), it infrequently involves the nervous system. Thus, it is worthwhile to present findings on 28 patients who had nervous system involvement. The patient reported by Boeckl in 1899 had involvement of skin and lymph nodes but no central nervous system involvement. In the 3 patients with neurological complications reported by Heerfordt' in 1909, iridocyclitis was noted in all, facial palsy in 2, optic neuritis in 2, and diabetes insipidus in 1. Two patients were followed and the symptoms and signs, including diabetes insipidus, subsided within one to three months after their appearance. In 1935, Levin3 collected from the literature reports of 66 patients with uveoparotid fever. He noted that 24 had facial palsy and 6 had diabetes insipidus. The cerebrospinal fluid frequently showed an increase in the number of cells, predominantly lymphocytes, and the protein content was occasionally increased. Even though Roos4 found no difference between the neurological manifestations of lymphogranulomatosis benigna of Schaumann and those of uveoparotid fever of Heerfordt, he believed these 2 entities different. Of his 14 patients, 5 had diabetes insipidus and 4 had convulsions. Any part of the nervous system might be affected and produce appropriate manifestations. However, certain manifestations are seen more frequently than others. In a review of 118 patients with neurological involvement, including 3 of his own, Colover5 found that 58 had facial weakness, 29 had dysphagia, 21 had involvement of the peripheral nerves, 20 had diabetes insipidus, and 16 had swelling of the optic disks. Other neurological manifestations were less common in this review. The pathological feature of sarcoidosis consists of isolated or multiple widely infiltrating noncaseous granulomas. Lenartowicz and Rothfeld\" reported diffuse infiltration of the brain in 1 patient, Jefferson' found an isolated granuloma in the right postcentral gyrus of a patient with focal epilepsy, Popper and associates8 found a granuloma in the cerebellum with tonsilar herniation and ventricular obstruction, Aszkanazyg found focal spinal cord involvement, and Wood and Breamlo found localized granulomatous infiltration of the arachnoid. Skeletal muscles are rarely affected clinically and Dyken,ll in 1962, found only 27 patients with sarcoid myopathy described in the literature. It is uncertain if skeletal muscle involvement is associated with a higher incidence of myocardial involvement.12-14 The incidence of neurological manifestations, as given in the literature, varies generally between 2 and 7%.15-18 In 1963, Mayock and associatesls reviewed the findings on 145 of their own patients with sarcoidosis and those on 1,109 patients reported in the literature. They found central nervous system involvement in 16% of their 145 patients and in 5.12 of the 625 patients from the literature on whom sufficient information was available. Central nervous system involvement is also seen in children, and McGovern and Merritt20 reported an incidence of 7% in 113 children. The clinical course of sarcoidosis is variable. Individual manifestations may last only a few months but frequently the course is prolonged and benign. A few patients die from the neurological manifestations while others are left with a permanent. d e f i ~ i t . ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ In the majority of patients, however, neurological symptoms subside or show a tendency toward stabilization or amelioration.2*23,24

Neurological sequelae following dilantin overdose in a patient and in experimental animals.

Abstract: W E RECENTLY OBSERVED a young woman who received large doses of diphenylhydantoin ( DilantinB) in combination with other anticonvulsant drugs. She developed nystagmus and ataxia which persisted after withdrawal of the drug, suggesting that Dilantin@ had caused permanent neurological dysfunction. The first part of the paper gives the details of this patient and presents studies of her metabolism of Dilantina. The second part of the paper attempts to clarify the pathogenesis of her disorder and reports the DilantinB dosage, duration, and blood and tissue levels that have produced cerebellar damage in experimental animals.

Cerebral blood flow with intracranial hypertension.

Abstract: IN A PREVIOUS REPORT we advanced the hypothesis that a progressive rise in intracranial pressure ultimately causes vasomotor paralysis and brain swelling, the latter due primarily to an increase in cerebral blood volume.1 This process was termed cerebrovascular decompensation and was divided into 4 successive stages. The development of this hypothesis was, in part, dependent on the demonstration of the relationship of increased pressure to volume within the intracranial space. We confirmed previous observations that spatial compensation for an expanding mass occurs by expression of fluid from the intracranial space, and a rise in pressure occurs only when the volume added exceeds the volume of fluid displaced. However, when displaceable fluid has been eliminated, a slight further increase in the volume of the mass causes a great rise in intracranial pressure, due to the fact that the skull approaches a closed, rigid container. Thus, during the period of spatial compensation (stage 1) the volume-pressure curve is essentially horizontal, with volume on the abscissa and pressure on the ordinant, then rises abruptly, nearly vertical to the abscissa, after displaceable volume has been eliminated. Indirect evidence also was presented that increased intracranial pressure, produced by expansion of an extradural balloon, causes cerebral vasodilation and an increase in intracranial blood volume, which is further augmented by a rise in systemic arterial pressure when the intracranial pressure reaches the vasopressor threshold. The most likely cause of the initial cerebra1 vasodilation is anoxia and carbon dioxide retention due to diminished blood flow. If this secondary rise in intracranial volume and tension is sufficient to cause additional elevation of the arterial pressure, both pressures rise together as a pressure wave, often to an intracranial pressure in excess of 100 mm. Hg (stage 2) . After repeated pressure waves the vasopressor response begins to fail, and, as the intracranial pressure approaches the arterial pressure, severe cerebral ischemia ensues. This leads to further vascular dilation due to ischemic vasomotor paralysis, and progressive brain swelling develops as cerebral blood volume increases (stage 3) . Ultimately the vasomotor paralysis is complete, and when the mass is suddenly evacuated the intracranial pressure falls and then rebounds quickly to the level of the arterial pressure. Pressure is equal everywhere now within the intracranial space, the decompensation process is complete and irreversible, and we postulated that at this time cerebral blood flow has ceased (stage 4). In the present experiments changes in cerebral blood flow have been measured continuously during the stages of cerebrovascular decompensation, and the results support the concept that vasomotor paralysis is the essential feature of the decompensation process.

Central nervous system manifestations of periarteritis nodosa.

Abstract: PERIARTERITIS or polyarteritis nodosa is a disease of unknown etiology characterized by focal disseminated inflammatory lesions involving the medium-size and small arteries. A great variety of clinical features results from the variable distribution of these arterial lesions. Neurological manifestations are common; peripheral neuropathy, in particular, has been well known.l.2 However, relatively little attention has been paid to the central nervous system manifestations of the disease. The frequency and type of involvement of the central nervous system in periarteritis nodosa have varied among different According to Arkin,j central nervous system manifestations occur in 8% of cases. Malamud and Foster6 reviewed 300 reported cases and found that central nervous system involvement occurred in 20%. Parker and Kernohan? reported 16 necropsy-proved cases of periarteritis nodosa, in which 7 of the patients (44%) had had prominent and early clinical manifestations of central nervous system involvement, and an additional 4 (25%) had had such involvement late or terminally. Specimens from these 11 patients showed appropriate microscopic changes in the cerebral arteries. Clinical evidence of central nervous system involvement was noted by Griffith and Vurals in 5 of 17 cases and by Rose9 in 9 of 24 cases of periarteritis nodosa. Drachmanlo reviewed 104 reported cases of Wegener’s granulomatosis and found involvement of the central nervous system or cranial structures in 30 (29%). The differences in the percentages of reported central nervous system manifestations are probably related, in part, to the manner of the selection of cases for inclusion in the review; that is, cases based on necropsy

Focal seizures as a manifestation of hyperglycemia without ketoacidosis. a report of seven cases with review of the literature.

Abstract: A SYNDROME consisting of severe hyperglycemia and stupor or coma without ketoacidosis has recently been defined in the literature.1-13 This syndrome occurs in diabetics, and the majority have been elderly. In some cases, the patients were not known to have been diabetic, and stupor accompanied by severe hyperglycemia without ketoacidosis was the first manifestation of the disease. Dehydration, with consequent hemoconcentration, rise in blood urea, and, if excessive, hypovolemic shock, is another clinical feature of this syndrome. Response to insulin and fluid therapy is usually good but on occasion the metabolic disturbances have been irreversible, and deaths have been reported. Autopsy findings have revealed little beyond changes often seen in diabetes. Nineteen cases of nonketoacidotic hyperglycemia reported since 1956 and one additional case which, in our opinion, represents an example of this entity14 are summarized in table 1.1-ls In addition to marked hyperglycemia 8 of the cases presented with hypernatremia. The urines were consistently free of acetone, and the carbon dioxide content of the sera was within normal range. Shock was a frequent admission finding. In spite of the absence of ketoacidosis most of the patients p r e sented with polypnea. Depression of consciousness was present in all cases and varied in severity from stupor to deep coma. Further neurological dysfunction included in one case (No. 12) a bilateral Babinski sign, in another hyperthermia of central type (No. 7), and seizures in 2 others (Nos. 18 and 20). The patient of Azerad and Lubetzki13 had a left focal seizure half an hour after admission. Serial electroencephalographic tracings showed bilateral paroxysmal features accentuated on the right shortly after the seizure which disappeared after the metabolic imbalance had been controlled with insulin and rehydration. The patient remained seizure free without

Diphenylhydantoin activated seizures.

Abstract: EXCESSIVE intake of many common anticonvulsant drugs may result in symptoms of central nervous system intoxication. It is the premise of this paper that such toxic states may provoke convulsions as are encountered in other types of drug encephalopathy. Overdose of diphenylhydantoin ( DilantinB) , in 3 cases to be discussed, is considered to have resulted in increased numbers of seizures. The clinical and eIectroencephalographic picture in this syndrome is sufficiently uniform to be readily recognized and to alert the physician to the need to decrease or stop DilantinB.

Congenital nonprogressive myopathy: Central core disease and nemaline myopathy in one family

Abstract: CENTRAL CORE DISEASE was first described in 1956 by Shy and Mageel and called “a new congenital nonprogressive myopathy.” Five members of 3 generations of one family were affected. The pedigree suggested an autosoma1 dominant pattern of inheritance with incomplete penetrance. The case reported by Bethlem and Meyjes2 seemed to be isolated and nonfamilial. The father of the patient reported by Engel and associates,3 although clinically normal, had some histological and biochemical alterations in the muscle which suggested that he may be a carrier of the trait. Details of 4 additional cases are not available.4 The clinical findings of the reported cases were similar. They had generalized hypotonia in infancy with delayed motor development but walked before the age of 5 years. All were able to go to school or to work. All had proximal muscle weakness, but even the most severely affected muscles could be moved against gravity. Muscles innervated by cranial nerves were affected in some cases. Muscle wasting was not prominent. The deep tendon reflexes were normal or decreased. There were no other abnormal neurological findings, and the intelligence of all affected individuals was normal. Slight improvement was noted in some cases and none progressed. The electromyograms were essentially normal. Serum creatinine, glucose, calcium, inorganic phosphorus, alkaline phosphatase, blood urea nitrogen, serum proteins, protein-bound iodine, and spinal fluid examinations were normal. Serum enzyme studies were not reported.

Intracranial collateral circulation via leptomeningeal and rete mirabile anastomoses.

Abstract: EMBOLIC OR THROMBOTIC occlusions of intracranial arteries are followed by adjustments in the distribution of blood through the circle of Willis, external-internal carotid communication by way of the opthalmic artery, leptomeningeal arterial anastomosis, and, occasionally, the rete mirable. Angiographic analyses of changes in flow through the circle of Willis as a result of intracranial arterial occlusive disease are well known. The purpose of this report is to discuss our technique of angiographic demonstration of leptomeningeal and rete mirabile arterial anastomosis with illustrative cases. Angiographic criteria for the diagnosis of intracranial arterial occlusion will be illustrated and discussed. The demonstration of these occlusions requires special radiological equipment, and the technique of selective carotid angiography simplifies the procedure. Selective internal carotid angiography by the catheter technique offers certain advantages in the diagnosis of intracranial arterial occlusions in the visualization of collateral circulation. Occlusions of large intracranial arteries rarely present any diagnostic problems, but, when a small branch is occluded, the diagnosis may be difficult. In these cases, overlapping branches of the external carotid may be very confusing, and, if complete filling of the peripheral branches of the intracranial arteries is not obtained, collateral circulation via leptomeningeal arteries may not be seen. Leptomeningeal arteries. There is an extensive arteriolar network over the surface of the cerebral cortex which is, in effect, a mantle in the pia mater supplied by the internal carotid and vertebral arteries. The conducting arteries connect with one another through this extensive arteriolar network via anastomotic vessels called leptomeningeal arteries. Heubner,l in 1874, first demonstrated these anastomotic vessels. Fay,z in 1925, injected metallic mercury via a cannula in the middle cerebral artery at autopsy and demonstrated anastoniotic arteries on stereoscopic roentgenograms. Cobb,3 in 1931, reported his studies of the anatomy of the cerebral circulation and stated that there are no end arteries in the brain. Vander Eecken and A d a r n ~ , ~ in 1935, described the anatomy of the meningeal arterial anastomoses in adults and children and discussed their functional significance. The leptomeningeal arteries lie in the depths of the sulci of the brain and vary from 180 to 610 p in diameter. Some of the arteries form loops to anastomose with others, while some may have oblique or branched configurations.4 Collateral circulation via these vessels has been demonstrated angiographically by a number of authors.5-7 Rete mirahle. The rete mirabile, or “wonderful net,” refers to anastomotic vessels joining the meningeal arteries from the external carotid artery with the leptomeningeal arteries on the surface of the brain.s-lo

Human rabies encephalitis. A study of forty-nine fatal cases with a review of the literature.

Abstract: WITH THE INTRODUCTION of better and better public health measures, fatal human rabies is becoming a rarity in the western hemisphere.1 Yet, the disease is ubiquitous and large wildlife reservoirs may precipitate an outbreak whenever stringent control is relaxed.2 For this reason, rabies* has continued to challenge the neuropathologist. In recent years, studies on human rabies from the western hemisphere have been scarce, in spite of the fact that our knowledge as well as understanding of the disease and its pathology remain incomplete.3 As far back as 1925, Schukri and Spatz4 complained: “The literature concerning the anatomic-pathology of rabies is voluminous. Most descriptions, however, have been done on animal material. Fatal human rabies especially in recent years are becoming rare.” The following is a clinicopathological review of the fifty-nine fatal cases coded as human rabies in the files of the Armed Forces Institute of Pathology between 1930 and 1965. It is hoped that this study, together with a systematic review of the older literature, may serve to fill in gaps in our present knowledge, raise new questions in need of examination, exhume old ones which should never have been buried, and stimulate worthwhile research into this fascinating entity.

Effects of anoxia on cerebral metabolism and electrolytes in man.

Abstract: THE OXYGEN tension (PO,) of brain tissue obeys the law of supply and demand. Supply is influenced by arterial oxygen content, cerebral blood flow, and cerebral blood pH (by the Bohr effect), and demand depends soleIy on the functional state of brain metabolism. If the oxygen tension of the blood is reduced (for example, by anoxic anoxia of nitrogen inhalation), presumably a value will be reached below which capillary PO, is insufficient to maintain oxygen diffusion into brain tissue; functional impairment with signs of cerebral anoxia will result. Such thresholds for oxygen tension have been determined for brain preparations; below these cerebral oxygen consumption became decreased and thresholds for cerebral venous PO,-at which electroencephalographic slowing and decreased cerebral metabolism occurred-have also been estimated in animals by several investigators.1-5 There is as yet no comparable data available in man except a few determinations of the levels of oxygen saturation in the internal jugular vein at which loss of consciousness occurred during nitrogen breathing and postural hypotension.6 It has been reported in animals that when tissue or capillary venous pOz fell below threshold during induced anoxia the extracellular sodium ions of the brain decreased and there was an increase of extracellular potassium. This ionic change was said to correlate with electroencephalographic slowing.5,7rs Such data support the notion that anoxic symptoms and signs are due to failure of the mechanism for active sodium transport in brain, which is apparently dependent on cerebral energy metabolism. The present study reports for the first time in man similar observations concerning the threshold for cerebral venous oxygen tension

See-saw nystagmus.

Abstract: SEE-SAW NYSTAGMUS is a n unusual bu t distinctive phenomenon initially described by Maddox in 1914.l Just twelve additional cases have been reported subsequently.”-lO The characteristic feature of the nystagmus is that one eye rises while the other eye falls, resembling the action of a see-saw. Actually, as originally noted by Maddox,l and in most other cases in which it is carefully described, the nystagmus is basically rotary (torsional) with the eyes moving conjugately clockwise and then counterclockwise. During the torsional movements, the intorting eye elevates while the opposite eye, which is extorting, falls (see figure). Most cases have been reported in association with large parasellar or pituitary tumors which have extended into the third ventricle. One of the two patients to be described had such a lesion. The other probably had cerebrovascular disease involving the brainstem.

Neurological complications of dialysis, transplantation, and other forms of treatment in chronic uremia.

Abstract: THE FORMER therapeutic negativism of the physician dealing with chronic renal failure has been replaced by an interest in procedures and approaches which are capable of greatly prolonging the lives of these patients. The major future goals in keeping the patient with renal failure alive are rehabilitation to productive status and, if possible, eventually, transplantation of a normal or nearly normal functioning kidney. Though many problems still lay ahead, remarkable progress has been made in this field

An investigation of complicated migraine.

Abstract: THE CLASSICAL CASE of migraine with paroxvsmal unilateral headache preceded by visual and sensory phenomena and accompanied by nausea and vomiting is easy to recognize, particularly when a close relative is or has been similarly affected. Diagnostic difficulty and confusion arise, however, in cases of so-called complicated migraine. By this term is implied the development of a persistent hemiparesis, facial paresis, retinal arterial occlusion, or omlar nerve palsv in association with the attack of migraine. These cases of hemiplegic, facioplegic, retinal, and ophthalmoplegic migraine are relatively uncommon, and several authorities have advised that their occurrence should lead to the serious consideration of the presence of an intracranial vascular lesion.’-j Most physicians are also familiar with patients who give a long history of typical migrainous attacks and present catastrophically with a severe headache of sudden onset, associated with Fhotophobia, neck rigidity, and profuse vomiting. Such patients are reasonably suspected of having wffered a subarachnoid hemorrhage and are appropriately investigated. Basilar artery migraine4 may also manifest alarming features which suggest a structural lesion of the brainstem. Despite the dramatic nature of these complications of migraine, recent work has indicated that investigation of such cases rarely reveals a demonstrable vascular lesion. Thus, Lees,; studying this problem concluded that “investigation of a patient with headache is unlikely to reveal an angioma of the brain unless the headache and aura are persistently one-sided or unless the interval examination reveals abnormal neurological signs or a cranial ‘bruit.’ ” In a study of 18 patients with migraine com-

The relationship between intelligence and birth weight in twins.

Abstract: AN ASSOCIATION between mental retardation and low birth weight has been described by numerous investigators,ls2 the interpretation given to the findings generally being that prematurity is an important cause of mental retardation.3-1s However, not all observations support this interpretation. Douglas and Baird observed that paradoxically the most severely retarded cases in their series were the least prernature.l9@ Duyzing, considering premaurity in terms of gestational age rather than birth weight, found no appreciable relationship between prematurity and mental retardation.21 The present writer also has found that retardates tend to have low birth weights, but in these studies detailed inquiry has revealed that most retardates with birth weights below 2,500 gm. were born at term.22 Similar observations have been made in cases described by Warkany and assmiates.23 There was reason, then, to suspect that a significant proportion of the mentally retarded population was composed of full-term individuals of low birth weight who heretofore would have been called premature. On the basis of these observations, the author has formulated an hypothesis of “intrauterine impoverishment,” in which it is proposed that during some pregnancies deficiencies of nutritional ingredients, circulation, gas exchange, or waste removal occurs which result in small, full-term babies whose brain development has been interfered with and who are likely to be retarded. Until recently the author’s evidence for the existence of full-term retardates of low birth weight rested on statements about gestational age recalled by mothers of the patients some years after birth. Whether warranted or not, there is general skepticism about the validity of such retrospectively collected data, and it must be admitted that the precise timing of gestational age in humans is difficult. Yet, proof for the existence of “intrauterine impoverishment” in the etiology of mental retardation demands a demonstration that IQ can vary with birth weight independently of gestational age. To investigate this problem, the author designed a study of twins, gestational age obviously being equal within sets, proposing the specific hypothesis that, within pairs, the twin with the lower birth weight would, when tested during grade-school years, be found to have the lower IQ. One might reasonably expect that twin gestation in the human would severely tax maternal resources and often result in “intrauterine impoverishment,” wherein both fetuses are deprived, but possibly one more than the other. In fact, twins are often small at birth even when they are carried to term, and the incidence of twins among retardates is high.24925 Gestational age is equal within twin pairs, and genetic factors are similar in monozygous twins. These factors being controlled, birth weight differences within twin pairs would be expected to reflect an unequal sharing of nutrients between the twins. That the placental circulation is not shared equally between identical twins has been clearly demonstrated.26 In addition to intrauterine factors, there are other environmental differences between twins at the time of birth. Such would

Posterior fossa aneurysms.

Abstract: POSTERIOR FOSSA ANEURYSMS are often said to represent about 15% of intracranial aneurysms. They comprised about 21% of the 1,023 cases collected by McDonald and Korbl in their review of the literature from 1756 to 1939. However, a considerable number of the vertebral and basilar aneurysms referenced in their bibliographic survey are not true aneurysms but diffuse ectasias involving the entire vertebral or basilar artery. Twenty-one or 16% of Dandy’s2 series of 133 intracranial aneurysms were located in the posterior fossa, but 11 were in fact diffuse ectasias which he had encountered in the course of a large number of suboccipital craniectomies performed for the treatment of trigeminal neuralgia or MeniBre’s syndrome.3 An example illustrated in his pioneering monograph shows a dilated vertebral artery which together with a tortuous and dilated basilar artery formed a wide S shaped curve. Whatever the clinical and pathological significance of such ectatic vessels may be, it is certainly quite different from that of saccular or berry aneurysm which by definition represents a dilation of a short segment of a vessel. There would seem to be little justification for confounding the two lesions. Probably the best estimate of the relative incidence of posterior fossa aneurysm may be obtained from the several comprehensive postmortem studies of intracranial aneurysm reported over the past decade (Table 1 ) . These indicate that approximately 8% of intracranial aneurysms occur in the posterior fossa. With improvements in technique, arteriographic study of the vertebral-basilar arterial tree has become an established diagnostic procedure in the past decade.10 Indeed, in many centers, it has become routine to visualize these vessels in cases of subarachnoid hemorrhage particularly when carotid arteriosgraphy does not show a lesion. Consequently, posterior fossa aneurysms, which previously were identified only at autopsy or encountered unexpectedly at operation for suspected tumor, are now regularly recognized during life. An increasing clinical awareness and a growing accumulation of operative cases have recently focused attention on aneurysms in this location. However, infratentorial aneurysms are relatively infrequent, and few clinicians have had experience with more than a random case or two. Moreover, the bulk of the literature is based on autopsy material. The recent review by Hook and associates of 28 cases representing all the posterior fossa aneurysms seen over a period of nearly thirty years in two Swedish clinicsll is the first sizable collection of unselected cases reported to date. With a view to obtaining further data on which to base a general picture of the clinical manifestations and natural history of posterior fossa aneurysms, we collected all the cases of infratentorial saccular aneurysms which had been identified at the Columbia-Presbyterian Medical Center since its opening in 1931. Only true saccular aneurysms or dilations of short segments of the involved artery were reviewed; fusiform enlargements or diffuse ectasias involving long segments or the entire vertebral or basilar artery were excluded. A total of 27 cases were available for study. The first 6 cases were found at autopsy in the ears 1931 to 1953. The first antemortem diagnosis was made by pneumoencephalography in 1955 (case 7) and was confirmed subsequently by autopsy. Subarachnoid hemorrhage in case 8 was ascribed to a supratentorial vascular anomaly; a ruptured basilar artery aneurysm was an unexpected finding at autopsy. Vertebral arteriography has been regularly

Studies in multiple sclerosis: I. Normal values for paper electrophoresis of serum and cerebrospinal fluid proteins; description of the method with special reference to a practical concentration technique for cerebrospinal fluid protein

Abstract: SINCE 1948, when Kabat developed his immunochemical technique1 for the estimation of gamma globulin in cerebrospinal fluid (CSF) , numerous investigators have sought simpler, more economical methods which could be carried out in clinical laboratories. With the development of paper electrophoresis for the separation of serum proteins,'-* suitable methods for concentration of CSF proteins were investigated. Techniques for zinc sulfates and acetone precipitation6 of gamma globulin were tried in our laboratory but in our hands were not reproducible. Subsequently we found the concentration of CSF in a colloidion bag to be the most satisfactory method. It does not denature the protein, requires only small amounts of fluid, and is easily adapted for the clinical laboratory. This report records details of the technique of concentration of CSF and paper electrophoresis as used in our laboratory for the past eight years. It is gratifying that basically these details agree with those advocated recently as a standardized method.7 We have compared the paper electrophoretic results for serum and CSF with those obtained by free electrophoresis and have included normal values for serum and CSF as well as tests for the reliability of the technique.

Observations concerning intracerebral vascular occlusions.

Abstract: IT HAS FREQUENTLY been suggested that cerebral emboli are the cause of transient ischemic attacks, but direct proof of such an association has been lacking. Our recent experience with the acute stroke syndrome supports the embolic theory of origin of some transient ischemic attacks. I t also clarifies some of the problems involved in defining the nature of the lesion and in evaluating therapy.

Cerebral toxicity associated with massive intravenous penicillin therapy

Abstract: THE EPILEPTOGENIC POTENTIAL of penicillin is well recognized and has restricted its subarachnoid and intraventricular administration.1-4 This epileptogenic effect has not previously significantly limited its use by other routes of administration. In recent years, however, extremely high doses of penicillin intravenously have been advocated for subacute bacterial endocarditis and for gram-negative bacillary infections.5 In patients with renal tubular dysfunction, this may produce serious neural toxicity. Two patients who developed generalized seizures and other signs of nervous system dysfunction associated with high doses of penicillin have recently been observed. Both had renal tubular malfunction.

Electroencephalographic changes in chronic renal failure

Abstract: RELATIVELY few references have been made to the electroencephalographic changes in renal failure, when this condition is compared with other metabolic derangements. Klinglerl observed slowing of the background activity, “epileptogenic discharges,” and abnormally highvoltage photic evoked responses to slow rates of flashing light in patients with uremia. Watson and associates2 also described abnormal sensitivity to intermittent photic stimulation in uremia. Cadilhac and Ribstein3 gave a brief account of various electroencephalographic changes observed in renal disorders: In acute glomerulonephritis they found “slow hypersynchrony. . . , little affected by sensory stimuli; generalized slow irregular waves, sometimes asymmetrical . . . ; epileptic signs . . . localized or bilateral were found in 25% of cases.” Well-compensated chronic nephropathies without cerebral complication in their experience showed only occasional and minor electroencephalographic disturbances. They observed the most marked ’abnormalities in patients in the terminal period of either acute or chronic renal failure and noted the following changes in the tracing: “Low voltage waves with slowing of the background activity, slow waves in bursts, or irregularly distributed slow waves.” KIinglerl and Cadilhac and Ribsteid were un-

Ocular myopathy with dysphagia

Abstract: PROGRESSIVE dystrophy of the external ocular muscles, or ocular myopathy, is the least common type of muscular dystrophy.l Ocular myopathy, as described by Fuchs' and reviewed by Kiloh and Nevin,\" is characterized clinically by progressive ptosis and external ophthalmoplegia with onset usually before the age of 30 years. Males and females are equally affected. In about 50% of patients the condition is familial. In 25%, other muscles, in addition to the extraocular, are weak. The facial musculature is most frequently involved, but occasionally masticatory, neck, or limb muscles are weak or wasted. Pathological changes in the extraocular muscles in ocular myopathy are ideiiticnl to those found in the affected muscles in other types of muscular dystrophy. Instances of ocular myopathy with onset late in life and associated, in many patients, with dysphngia are reported, h ~ w e v e r . ~ l \" This particular combination of symptoms and signs has been called oculopharyngeal muscular dystrophy.x I t is the purpose of this paper to report 3 patients with late-life onset of ptosis and dysphagia and to determine the incidence of this syndrome aniong the reported cases of ocular myopathy.

Benign intracranial hypertension. vi. obesity.

Abstract: THE HIGH INCIDENCE of obesity in women suffering from the neurological syndrome benign intracranial hypertension's2 infers a relationship that may be based on endocrine changes which coexist. This interpretation is supported by the frequently seen alterations in menstrual function in obesity3 and impressions derived from the study of this syndrome in females who appeared to be undergoing a state of hormonal imbalance: pregnancy,4 menarche,5 and menstrual dysfbnction.O Clinical study. This study describes the course of 20 obese females who were admitted to the Columbia-Presbyterian Medical Center and the University of Florida Teaching Hospital because of unlocalized increased intracranial pressure, which was unassociated with focal signs of neural impairment, convulsions, mental dysfunction, or cerebrospinal fluid changes. Five were seen personally. Fourteen were Caucasian, and 6 were Negro (see chart). All patients were considered obese on the basis of clinical impression and when compared with standard charts. None were hypertensive, pregnant, or overtly edematous. Although 5 patients acknowledged a recent weight gain (10 to 30 Ib. within six months), 9 others stated their weight was relatively stable during the past year. Irregularities of menstrual function including amenorrhea, intermenstrual bleeding, and prolonged menstruation occurred intermittently in 6 patients. These signs of menstrual dysfunction were not related temporally to recent weight gain or the signs and symptoms of intracranial hypertepsion. Neurological symptoms and signs. Symptoms suggesting increased intracranial pressure were described by all patients for periods of one to ten months. Initially the symptoms were inter-

Latent neuropathy in diabetes and alcoholism: electromyographic and histological study.

Abstract: THE PRACTICE of muscle biopsies has revealed that both contractile and nervous elements of the motor apparatus were very sensitive to various aggressions.1,' This sensitivity is compensated by a remarkable power of regeneration. As far as the motor innervation is eoncerned, this reactive process consists in a collateral sprouting of the spared nerve fibers which results in an increase of the terminal innervation ratio and, therefore, in an extension of the motor unit territory.3!4 Thus, it may be assumed that the clinical manifestations of a neural aggression are the result of a conflict between regressive and regenerative forces. In acute and massive injuries, the degenerative process obviously dominates the cIinical picture and results in a marked reduction of motor power. In diseases leading to chronic and partial involvement of motor neuron or peripheral nerves, the occurrence of muscular weakness can be delayed and partially overcome by the compensatory process of collateral ramification and also by the hypertrophy of the muscle fibers. This is probably the case in motor neuron diseases. It may even happen, provided the disease process is slight enough, that a satisfactory balance between regressive and regenerative changes makes the illness clinically inapparent.* Such a condition may be qualified as subclinical or latent neuropathy. In fact, a good number of biopsies taken in various conditions, including febrile illness of long duration, systemic diseases, malignant tumors, and uremia, have revealed conspicuous changes of the terminal innervation pattern in patients having no symptoms of neural involvement and even in the absence of neurogenic atrophy of the muscle tissue. These changes are a mixture of mild regressive or dystrophic alterations of the terminal arborizations and intramuscular nerve fibers and increased collateral ramification of motor axons. Such a histological picture, giving a clear morphological evidence of the opposite forces acting on the nervous structures, has been considered to represent the very first stage of the latent neuropathies occasionally preceding the fascicular atrophy of the muscle fibers, which itself may precede the clinical evidence of a reduction of the motor power.* The finding of subclinical alterations of intramuscular nerve fibers led us to undertake a systematic investigation of the neuromuscular function in various conditions known to involve the peripheral nervous system, with special interest to the cases in which the symptoms of polyneuropathy were very slight or absent. The purpose of the present study is to describe the histological changes occurring in muscle tissue and terminal motor innervation in diabetic and alcoholic patients and to analyze the evolution of these changes in connection with the clinical picture. The histological features, quantitatively estimated, have been compared with the electromyographic behavior of the neuromuscular territories submitted to a biopsy. It was expected that such a broad approach

Fate of adrenal cortical steroids following intrathecal injection.

Abstract: THIS REPORT has been prompted by the appearance of several publications which have suggested the efficacy of intrathecally administered adrenal cortical steroids in patients with multiple sclerosis and other neurological diseases.1-4 The basis far the recommendation that adrenal steroids be administered intraspinally has been the assumption that adrenal steroids pass the blood-brain and blood-cerebrospinal fluid barriers with great difficulty and that the intraspinal route permits higher concentrations to be achieved in cerebral tissue. A variety of preparations has been used, including cortisol, as well as the “depot” form of methylprednisolone acetate. I t has been recommended that adrenal steroid be injected at intervals as short as several days1 or two weeks3 and as long as three months and longer.’ The importance of the chemical preparation of the injected steroid upon its solubility in body fluids and its ability to cross cellular membranes has not been considered in the published reports. The place of adrenal steroids, if any, in the management of demyelinating disease has not been established. However, if steroid therapy is intended for a nervous system disorder, then it is important to determine whether daily oral or intramuscular administration of hormone is likely to bring about o’ptimal steroidal effects or whether the administration of steroid every two weeks by the intrathecal route has ii mow rational basis. To clarify this question, the bidirectional transfer of steroids b’etween blood and cerebsrospinal fluid has been studied. The importance of the chemical preparation of the drug is also considered in evaluating the magnitudc of the “barriers” to the passage of adrenal steroids. The basis for our conclusion, that

Electroencephalographic abnormalities of children with hyperkinetic behavior.

Abstract: BEHAVIOR DISORDERS in children have long had the attention of pediatricians, psychiatrists, and educators. From their labor has come a concept of the hyperkinetic behavior disorder, encompassing a heterogeneous group of children with excessive undirected motor activity who become disruptive to classroom and home and present special problems of learning and of relating to environment. In the past twenty years the concept of “minimal brain damage” as contributory to this disorder has led to the inclusion of the neurologist in a multidisciplinary approach to the problem. To date, there exists no unanimity of opinion for the cause, manifestations, or treatment of the disorder, although most investigators agree that hyperkinesis is a symptom common to many disorders. Certainly, similar behavior is exhibited by organically impaired children where its onset can be related to trauma or en-