We have used the technique of antibody mediated cell dependent immune lysis to examine paired samples of serum and CSF for antibody to herpes simplex virus. The 40 patients studied had no inflammatory disease of the nervous system, yet 20 of the CSF specimens did have antiviral antibody. This is an extremely sensitive technique for the detection of at least one type of antiviral antibody and “in vitro” is a very effective way of killing virus infected cells. There is no correlation between the level of antiviral antibody in the CSF with the total protein content, but the high CSF: serum antibody ratio in some subjects who are particularly susceptible to recurrent herpes infection raises the possibility that local stimulation and production of this antibody may occur.

Ten patients with multiple sclerosis were found to have lived in close proximity in a Nova Scotia farming community of 150 people. All had drunk unpasteurized milk as children, were teetotallers, ate a high animal fat diet, and were well educated. Of greater interest was the observation that six of the ten cases were related in two family groups.

The only time all patients lived in the community at the same time was in 1951 and 1952 during a polio outbreak. The relationship of polio to multiple sclerosis bears further study.

The average age of the patients when they had measles was 11.8 years. Evidence suggests a link between risk of multiple sclerosis and both late onset of measles and pubertal age. Late onset of measles may be important in this cluster. Further epidemiological studies are needed to examine the age of onset of measles in M.S. cases.

Recent evidence indicates that Wall (1970) may have been premature in concluding that dorsal column lesions produce no discernable sensory defects. Much of the negative evidence Wall presented to support this view is inconclusive. In addition several studies have reported significant sensory deficits in animals with severed dorsal columns. On the other hand, the literature strongly supports Wall's view that dorsal column lesions cause motor disturbances. A review of the anatomical and electrophysiological literature reveals growing evidence for the dissociation of two major subsystems relaying in the dorsal column nuclei. The possible functions of these two systems are discussed.

It is proposed that the basic mechanism of vasospasm which sometimes follows subarachnoid hemorrhage is dependent on increased free intracellular calcium ion produced by spasmogens from closely applied extravasated blood. Relaxation of this spasm occurs when the intracellular cyclic AMP levels are raised, resulting in sequestration of calcium ion by the vascular smooth muscle cell sarcoplasmic reticulum.

Forty-eight surgically removed pituitary adenomas have been investigated hy electron microscopy. Distinct differences in fine structural appearances permitted their separation into 5 classes: 1) Growth hormone, (GH)-cell tumors; 2) Prolactin cell tumors; 3) Mixed adenomas composed of GH and prolactin cell's; 4) Adrenocorticotrophic-Melanocyte stimulating hormone (ACTH-MSH) cell tumors; 5) Undifferentiated cell adenomas. Densely and sparsely granulated tumors were distinguished within forms appeared to represent well defined entities, they may be variants of the same tumor differing only in pace of hormone production and/or release. Number and size of secretory granules varied considerably among tumors composed of the same cell type indicating that pituitary tumor classification cannot be based solely on granule morphology. This classification takes into account morphogenesis with emphasis on clinical features and structure-function relationship.

The post-mortem examination of the nervous system of a patient with Shy-Drager syndrome successfully treated with levodopa (Sharpe et al, 1972) revealed features of striato-nigral degeneration and amyotrophic lateral sclerosis, a cerebellar system degeneration and a loss of approximately 75% of sympathetic preganglionic neurons. Lewy bodies were not present and no detectable changes were observed in the sympathetic prevertebral ganglia.

While the limited and transient beneficial effect of levodopa on the bradykinesia in our case is possibly due to the progressive loss of striatal dopaminergic receptors seen in striatonigral degeneration, we propose that in Shy-Drager syndrome, levodopa therapy benefits orthostatic hypotension because of a suppression of the central depressor action of this drug. This suppression is attributable to functional disconnection of sympathetic ganglia secondary to the loss of preganglionic neurons or to degeneration of central autonomic catechoiaminergic systems.

This review evaluates the long-term results of Levodopa therapy in Parkinson's disease upon quality of life, prolongation of survival and excess mortality. It also focuses on recent and new therapeutic approaches: Levodopa in comhindation with a Dopa-decarboxylase inhibitor or MAO-B inhibitor, dopamine agonists and an active tripeptide: L-prolyl-L-leucylglycine amide (M1F-I). It ends by looking at new avenues of etiological research in Parkinson's disease which may indicate specific accelerated ageing of catecholaminergic (pigmented) neuronal systems.

The clinical and biochemical findings are presented of two brothers suffering from McArdle's Disease (Myophosphorylase Deficiency). Tissue enzyme estimations and lactate levels were done in affected and non-affected members of the family. Affected members showed absence of phosphorylase enzyme by histochemical and quantitative estimation. No quantitative abnormalities were found in other enzyme systems of glycolytic pathways in the family investigated. Various other aspects of clinical features, biochemical abnormalities and inheritance are discussed.

Routine neuropathological examination could not explain the dramatic improvement exhibited by one patient with “normal pressure” hydrocephalus after shunting. The improved patient contrasted remarkably with the unchanged condition of four others also shunted successfully. The five brains were analysed by quantitative morphometry to determine the degree of neurofibrillary tangle formation in mesial temporal neurons. The density of tangle-bearing nerve cells in the four unimproved cases was markedly greater than in age-matched control brains from nineteen normal subjects, and fell in the same range as that of eight dements with neuropathologically confirmed Alzheimer's disease. The density of the one who recovered was within normal limits.

The duration of dementia before shunting, and the total duration of dementia in these five patients rank in the same order as their degree of neurofibrillary formation. Furthermore, a positive linear correlation exists between the Tangle Indices and the total duration of dementia. The data suggest that early diagnosis may improve the chances of reversing the dementia of normal pressure hydrocephalus before histological alterations prove too severe.

In order to determine which of two general models (“tapped delay line” or “integrator”) provides a more accurate description of mammalian Purkinje cell (P-cell) activation by natural stimulation, the spatial and temporal characteristics of a population of neurons in cerebellar cortex responsive to small controlled stretches of forelimb muscles were examined in awake, locally anesthetized cats. Stretch of a single wrist muscle excited P-cells over a distance of about 1 mm in the long axis of a folium, a span which is at most half the length of parallel fibers. Both granule cells and molecular layer interneurons were excited over a wider zone than P-cells.

Furthermore, P-cells across a response zone all fired on the average at the same time, as determined by computing peristimulus cross-interval histograms from pairs of simultaneously recorded neurons. Consistent delays could only be demonstrated in the minimal response latencies as measured from peristimulus time histograms. These delays, however, were longer than could be ascribed to parallel fiber conduction velocity.

No evidence, therefore, was found in cat cerebellum to support the “tapped delay line” model, which postulates the successive activation of P-cells as an excitatory volley travels along a parallel fiber beam. Instead, an integrative mode of operation seems to predominate: a relatively wide substratum of activated granule cells simultaneously activates a narrower focus of P-cells centrally situated with respect to the granule cell population. The role of inhibitory interneurons in promoting the “integrator” model is discussed.

Ultrastructural changes in the zone of clamping of the middle cerebral artery of the squirrel monkey are described after application of a surgical clip. The experimental model utilized has been widely applied to the study of cerebral ischemia and possibly has relevance to clamps applied to the cerebral vessels during neurosurgical treatment of patients with cerebrovascular disorders.

The earliest changes within the arterial wall were found in the smooth muscle (media) and accompanying fasciculi of nerves. Changes within the nerve bundles were sufficiently advanced following 4 hours of vascular clipping to suggest temporary or permanent impairment of neurogenic innervation of the cerebral vessels distal to the trunk of the vessel clipped.

A consistent feature in dementia is an overall intellectual deterioration. The present study investigated the intellectual performance of patients with Alzeheimer's disease (AD) and multi-infarct dementia (MID) using the Wechsler Adult Intelligence Scale (WAIS). For reliability and generality purposes two independent samples of patients were collected. Significant differences in Education Level (EDU) and Performance IQ (PIQ) were obtained for the first sample, with the AD group having a significantly higher EDU level. The MID group obtained a higher PIQ. No significant differences were found in the second sample, but EDU level approached significance with the AD group again having a higher EDU level. A discriminant function analysis classified 81% of the patients in the first sample and 100% diagnostic accuracy was obtained for the second sample using the II predictor variables. A maximum R stepwise regression was performed in order to detect the “best” model of variables discriminating between the diagnostic groups. For the first sample the “best” model was the two variable model, including EDU and Full Scale IQ, accounting for 40% of the variance. The simplest model for the second sample was the one variable model including EDU, accounting for 20% of the variance. Quantitative, differences were found between the AD samples. Time since onset of the disease was offered as a possible influence in the quantitative differences in the AD samples. Sampling biases in the behavioral study of dementia are discussed. Successful replication was obtained.

Twenty-four patients with multiple sclerosis were evaluated and classified according to their clinical state. Specific migration inhibition studies were carried out on blood samples from each using myelin basic protein, an acid soluble protein fraction isolated from normal human CNS white matter, and multiple sclerosis myelin basic protein isolated from patients who had the disease, as the antigenic material. This test system employed selected media. Results were compared with those of normal controls and patients with other neurological disease states. Antigen concentration of 500 μ glml in serum free medium combined to produce the greatest inhibiting effect on leukocytes in patients with apparent multiple sclerosis and differentiated these patients from those in the other groups tested.

Leukocytes in patients who had probable multiple sclerosis with partial impairment, signifying possible current activity of the disease, were especially inhibited as compared to the leukocytes from other groups tested against myelin antigen. Cerebrospinal fluid from affected patients when used as a media enhanced the test.

This study suggests that migration inhibition of peripheral leukocytes using myelin protein may be useful in the diagnosis of patients with multiple sclerosis. There is additional evidence that the degree of leukocyte migration inhibition may reflect activity of the disease with its consequent implications on treatment and prognosis.

This paper presents the results of neurophysiological studies of the effects of cerebellar stimulation on H reflexes, late reflexes, blink reflexes, evoked potentials and EEG patterns in 18 human subjects (Male 13, Female 5, Age 25.8 ±10.0, Epileptic 9, Cerebral Palsy 9).

In addition to the effects of cerebellar stimulation on the H reflex studies on salens we assessed V1 and V2, “late” responses (Upton et al., 1971), cortical somatosensory evoked potentials (SSEP) after median nerve stimulation, and visual evoked responses (VER) after flash stimulation. Experiments were extended to assess recovery curves of all the potentials and we examined the effects of changes on the rate or voltage of cerebellar stimulation.

Cerebellar stimulation was inhibitory to all the responses except the visual evoked potentials. Serial studies in five patients produced consistent results. Preoperative and postoperative results were compared in two patients with no significant difference in the results in the absence of cerebellar stimulation.

Ipsilateral cerebellar stimulation (CS) had the greatest inhibitory effects on H, V1 and V2 responses in the arm and leg whereas contralateral CS produced the greatest effects on cortical SSEPs. There was a greater bilateral effect on SSEPs and reflex responses after right CS than left CS and this may be the first indication of “dominance” in the cerebellar hemispheres. Cerebellar stimulation in patients on diphenylhydantoin produced minimal effects on SSEP“s and this observation has led to further studies in patients taking diphenylhydantoin.

Recovery of amplitude of the reflex and cortical responses took eight to 30 minutes after one minute of cerebellar stimulation. Serial CS of one minute on and one minute off produced increasing inhibition of SSEP's and reflexes for up to five stimulations. Recovery after cessation of cerebellar stimullion was associated with rebound excitation in six patients, the rebound being noted in the amplitude of H reflexes and SSEP's as well as in the frequency of paroxysmal spike and wave discharges in the EEG.

The correlation of the results of such quantitative neurophysiological tests with clinical improvement may allow prediction of clinical results after cerebellar stimulation. These techniques have already been used to measure the threshold of stimulation and may allow optimal stimulation characteristics to be assessed. The prolonged neurophysiological effects of stimulation may allow the use of maximum effective intervals between optimal epochs of stimulation so that any cerebellar damage can be minimized.

A patient with Von Hippel-Lindau's disease was followed from the time of diagnosis to the time of his death 13 years later. He was asymptomatic when the diagnosis was made, although a hemangioblastoma of the medulla was found on angiography. The patient's course and autopsy are described and the features of this disease are reviewed.

The responses of canine middle cerebral arteries to changes in pCO2 and pO2 were tested in vitro. It was found that there was no response to changes in pCO2 from 38.1 mm. Hg to 26.6 mm. Hg. but there was some constriction of the vessels with lowering of the pCO2 below 26.6 mm. Hg and there was minimal dilatation of the vessels when the pCO2 was increased from 38.1 nan. Hg to 87.2 mm. Hg. There was no reresponse to changes in pO2 from more than 500 mm. Hg to 59.6 mm. Hg, but when pO2 was lowered below 50 mm. Hg there was a sudden, massive constriction of the arteries tested. It is postulated that this constriction is due to build-up of a substance (substances) during a period of hypoxia (pO2 < 50 mm. Hg). The significance of the results obtained are discussed.

The first description of the placing reaction (PR) in 12 human adult cases is given. The optimum position for eliciting the placing reaction (PR) is the dangling leg posture, i.e. the same as for the forward groping of the foot. There are three forms of PR quite similar to those noticed in animal physiology, i.e. the visual-PR, the dorsum-PR and the sole-PR. The term contact placing is preferred for the last two forms. The PR is encountered only in patients displaying a forward and medial groping of the foot as well as a groping of the hand on the same side. The PR is usually ipsilateral to the main cerebral lesion but there was no single case with a well limited unilateral lesion. An involvement of retrorolandic areas seems to be necessary for the occurrence of PR. It is concluded that both groping phenomena and the PR are highly coordinated reflexes subserving self-preservation and belonging to antigravity mechanisms, i.e. the standing posture.

The object of this study was to determine if traumatic brain edema (BE) and increased intracranial pressure (ICP) reduce cerebral blood flow (CBF). Two groups of patients were studied, one with slight BE and ICP less than 20 mm Hg., the other with pronounced BE and ICP over 20 mm Hg. Although ICP was higher and cerebral perfusion pressure lower in pro-nounced edema there was only a small and non-significant reduction in CBF and no difference in cerebro-vascular resistance. Since traumatic BE does not increase resistance to blood flow through the brain, cerebral perfusion can be maintained if an adequate perfusion pressure is established. This in turn, demands the monitoring and control of ICP.

Three types of papovaviruses (JC, BK, and SV40) have been isolated from man. All three are oncogenic in hamsters, cause frequent infection of man, and share a common T antigen. Augmentation of the expression of T antigen by in vitro cultivation of SV40-induced tumors of hamsters suggested that growing human brain tumors in vitro might provide an effective screening technique for the SV40 virus. In a series of human brain tumors examined in cryostat sections and in tissue culture, T antigen could not be demonstrated, suggesting that by this immunofluorescent technique SV40 was not implicated in the etiology of these tumors.