The clinico-pathological features of five patients with vascular amyloid restricted to the central nervous system are presented.

In three normotensive patients, intracerebral hemorrhage was the dramatic manifestation of amyloid angiopathy. In two other cases, one of amyloid in an arteriovenous malformation, the other of amyloid following therapeutic radiation, amyloid deposition was asymptomatic.

Clinically, amyloid angiopathy must be considered in the different diagnosis of intracerebral hemorrhage, independent of the presence of dementia. Pathologically, a factor common to the syndrome of cerebrovascular amyloid appears to be locally increased vascular permeability resulting from a variety of previous tissue injuries.

This paper is a review of the causes of intermittent monocular blindness. The nature of cholesterol and platelet retinal emboli is discussed. Their sources, the frequency with which they may cause transient or fixed blindness and the association between these emboli and pathology of the major cerebral vessels and other organs is discussed.

Consideration is given to the equally important abnormalities of platelet behavior and to some of the physiology of retinal blood flow and non-embolic blindness.

The current treatment of this symptom may be anticoagulation, surgical correction of a stenotic artery or both. The effect of treatment is unpredictable and in some situations the rationale is suspect.

This review may provide a summary on which to base future studies of the effectiveness of various therapeutic agents.

This review describes the recent advances in slow infections of the nervous system emphasizing the pathogenetic aspects of these diseases. A theoretical model for the pathogenesis of subacute sclerosing panencephalitis (SSPE) is proposed, illustrating the factors that may affect host response to the measles virus and allow it to persist and produce the panencephalitis. The isolation of an oncogenic virus from progressive multifocal leukoencephalopathy (PML) has implications in the consideration of a viral etiology for some brain tumors. The agent responsible for the transmissibility of kuru and Creutzfeldt-Jakob disease (CJD) remains uncharacterized despite recent interest in viroids and abnormalities in replication of cell membranes. The epidemiological data on multiple sclerosis suggests an exposure to an infectious agent at an early age of life modified by the host response. No specific agent has been consistently associated with multiple sclerosis. Amyotrophic lateral sclerosis (ALS), Parkinson’s disease, Mollare’s meningitis and Behcet’s disease are other examples where a virus is suspect but unproven. The ability of viruses to persist in the host for months to years has linked many chronic neurologic diseases to an infectious agent, enlarging the spectrum of disease caused by viruses.

On the basis of the information presented in this review, it is difficult to reach any firm decision regarding the role of cyclic AMP (or cyclic GMP) in synaptic transmission in the brain. While it is clear that cyclic nucleotide levels can be altered by the exposure of neural tissues to various neurotransmitters, it would be premature to claim that these nucleotides are, or are not, essential to the transmission process in the pre- or postsynaptic components of the synapse. In future experiments with cyclic AMP it will be necessary to consider more critically whether the extracellularly applied nucleotide merely provides a source of adenosine and is thus activating an extracellularly located adenosine receptor, or whether it is actually reaching the hypothetical sites at which it might act as a second messenger. The application of cyclic AMP by intracellular injection techniques should minimize this particular problem, although possibly at the expense of new difficulties. Prior blockade of the adenosine receptor with agents such as theophylline or adenine xylofuranoside may also assist in the categorization of responses to extracellularly applied cyclic AMP as being a result either of activation of the adenosine receptor or of some other mechanism. Ultimately, the development of highly specific inhibitors for adenylate cyclase should provide a firm basis from which to draw conclusions about the role of cyclic AMP in synaptic transmission. Similar considerations apply to the actions of cyclic GMP and the role of its synthesizing enzyme, guanylale cyclase.

The use of phosphodiesterase inhibitors in studies on cyclic nucleotides must also be approached with caution. The diverse actions of many of these compounds, which include calcium mobilization and block of adenosine uptake, could account for many of the results that have been reported in the literature.

Gray and white matter were obtained during neurosurgical therapy of focal epilepsy from 17 patients. In 10 patients, receiving only phenobarbital, the drug was uniformly distributed between gray and white matter. Phenytoin concentrations averaged 1.4-fold greater in white matter than in gray matter when expressed per gram wet weight of tissue. The gray matter/plasma ratio of phenytoin was approximately 2-fold greater than that of phenobarbital. Carbamazepine levels were also slightly greater in white matter The data revealed wide differences between drugs in the relative concentrations in gray and white matter, which must be taken into account in any quantitative studies of anticonvulsant drug levels in the brain.

Examination of the effects of primary site kindling upon the development of secondary site amygdaloid kindling in cats showed that the former exerts powerful positive as well as negative after effects upon the latter. The positive after effect appears to be directed towards establishing a linkage between the secondary site and the Stage 6 generalized convulsive mechanism. The negative after effects were strikingly similar to those observed in animals with forebrain bisection subjected to amygdaloid kindling, suggesting that it is primarily directed towards functional accessibility of the cerebral structures interconnected by the forebrain commissure. The similarity of the findings in animals with anterior neocortical lesions supports such an assumption. The transient nature of the negative after effects was indicated by the development of a ‘normal’ clinical ictal pattern from the secondary site when it occurred spontaneously. Secondary site kindling exerted similar but less prominent negative after effects when the primary site was re-tested. Stage 6 seizure was elicited upon the first trial, however.

Clinical and angiographic findings in migraine are briefly reviewed in relation to cerebral hemodynamic changes shown by regional cerebral blood flow (rCBF) studies. Three cases of migraine studied by the intracarotid xenon 133 method during attacks are reported.

In classic migraine, with typical prodromal symptoms, a decrease in cerebral blood flow has been demonstrated during the aura. Occasionally, this flow decrease persists during the headache phase. In common migraine, where such prodr.omata are not seen, a flow decrease has not been demonstrated.

During the headache phase of both types of migraine, rCBF has usually been found to be normal or in the high range of normal values. The high values may represent postischemic hyperemia, but are probably more frequently secondary to arousal caused by pain.

Thus, during the headache phase rCBF may be subnormal, normal or high. These findings do not exclude the possibility of distension of the larger intracranial arteries during migraine headache, but the angiographic evidence, however limited, does not support this speculation.

Determination of lipoprotein patterns and of major plasma lipids was carried out in 171 patients with strokes. Of these, 22 had hyperlipoproteinemia (HLIPR) by paper electrophoresis and by elevation of principal plasma lipids (either cholesterol over 300 mg/100 ml or triglycerides over 200 mg/100 ml or both these components). More than two-thirds of the patients had at least one close relative with elevated blood lipids. Using criteria of the World Health Organization, these patients were classified as follows: 5 had HLIPR type IIa, 8 had HLIPR type IIb, 3 had HLIPR type III and 6 had HLIPR type IV. Phospholipids showed relatively little change from the values of normal controls. The numerical distribution of patients with stroke and HLIPR into the four different types corresponds quite well with the approximate frequency of these types of HLIPR in the general population. Thus, this study does not indicate that the patients with a particular type of HLIPR are at a greater risk to have a stroke than those belonging to other types.

This presentation includes six cases of chronic bilateral pure motor hemiplegia, one of these with pathological findings; one clinical case of chronic pure motor quadriplegia and one pathologically-studied case of chronic pure motor paraplegia. These cases may illustrate a spectrum of pure corticospinal disorders that heretofore has not been fully recognized.

Haloperidol (0.25 mglkg i.m.) was injected daily for 6 months in six normal monkeys. Over a 24 hour period, the following symptoms could he observed: akathisia, circling, akinesia, choreoathetoid and dystonic movements, oro-facial dyskinesias and postural tremor with or without harmaline. Six months after cessation of haloperidol, harmaline-induced postural tremor could still be observed in all animals and oro-facial abnormal movements, in one monkey. The neuropathologic study of the experimental material did not disclose any alteration of the central nervous system.

The treatment of high blood pressure prevents death from congestive heart failure, hypertensive nephropathy, and encephalopathy, and strokes from cerebral arteriolar disease (lacunes, hemorrhage from micro-aneurysms). However, atherosclerosis, manifested as coronary artery disease, is just as frequent a cause of death in well-controlled hypertensives as in poorly-controlled patients. Increasing evidence suggests that increased blood velocity, by causing turbulence and high shear rates at the endothelial surface of arteries, may be important in the pathogenesis of atherosclerosis. Turbulence has been observed in cerebral berry aneurysms. In order to measure the effects of antihypertensive agents on blood velocity, a new method of analysing Doppler ultrasound velocity recordings has been developed. Studies in Rhesus monkeys show the following: In doses which reduce diastolic pressure by 13-28%, propranolol decreased mean blood velocity (MV) by 17%, clonidine decreased MV by 14%, while methyldopa increased MV 12%, and hydralazine increased MV by 52%. (p < .00001). It is hypothesized that enlargement of berry aneurysms, the progression of cerebral atherosclerosis, and embolism from carotid lesions might all be decreased by the selection of antihypertensive agents which decrease blood velocity.

Fifty-six patients with 63 aneurysms were selected from a larger group of patients because they had at least one angiographic and one CT scan study. A total of 102 CT scans and 136 angiograms were analyzed. In five patients the aneurysm was visualized on the CT scan. There was a tendency for the location of the subarachnoid hemorrhage and intracerebral hematomas visualized on the CT scans to correlate with the site of the aneurysm as seen on the angiogram. The CT scan was useful in demonstrating the evolution of hydrocephalus and in differentiating hematoma from edema. The patients with normal CT scans were more likely to have good neurological grades. No single angiographic or CT scan feature correlated significantly with survival at lower than the 5 percent level.

Two patients had lumbosacral radiculopathy following radiation treatment of cancer. Twenty previously reported cases were similar. The clinical picture is one of progressive motor and sensory loss in the legs, usually appearing within a year after radiation, but sometimes delayed up to several years. Experimental studies quoted indicate greater vulnerability of peripheral nerves to ionizing radiation than has been previously recognized. Lumbo-sacral radiculopathy is readily produced in the experimental animal (rat) and affords an experimental model closely resembling the human cases reported.

Resuscitation of the brain following total circulatory arrest may be impeded by difficulty in establishing cerebral tissue perfusion, a post-ischemic “low-flow” state. We have confirmed this hypothesis in a rat model of total cerebral ischemia and have demonstrated marked improvement in post-ischemic brain tissue perfusion following epinephrine injection. This is mainly due to the systemic vascular effects of epinephrine, resulting in improved central aortic pressure and cerebral perfusion pressure. Hyperkalemic induced vasoconstriction has also been postulated as a cause of the “low-flow”. We have, therefore, investigated the in vitro effects of increasing potassium ion concentration on cerebrovascular smooth muscle strips. Large arteries constrict, while small arteries dilate in response to hyperkalemia. The net effect on cerebral blood flow remains unsettled. Our research to date suggests that resuscitation of the totally ischemic brain, in animal models at least, is enhanced by epinephrine, mainly via its effects on central aortic pressure.

Morphological speech zone asymmetry in man cannot be due to environmental or developmental factors after birth. The functional implication of such a finding is not yet clear. Morphological asymmetry of the human brain is paralleled by electrophysiological evidence of cerebral hemispheric asymmetries. The results of our analysis of 50 infants suggest that clear occipital-temporal coherency asymmetry similar, but not identical to the adult pattern, also exists at or near birth. These asymmetries are generated by stimuli with no verbal content and in infants who presumably have no or an undeveloped capability for language. It is suggested that language is only a part of much more fundamental asymmetries which include the processing of auditory and visual information. Our results, and those of others, are consistent with the assumption that the left hemisphere is more able to relate stimuli to past experience, either short or long-term, while the right hemisphere is more able to process stimuli which are not easily identifiable or referable. These capabilities would not be based on language, and hence would be expected to develop independently and possibly before speech. The demonstration that reversing electrophysiological asymmetries can be generated with non-speech stimuli in the visual and auditory modalities, and in neonates, supports such an assumption.

Bilateral anteromesial or orbital cortical lesions do not affect sequential pattern of amygdaloid seizure development. However, orbital cortex lesions appear to significantly participate in the elaboration of a Stage 6 seizure pattern.

Amygdaloid kindling ipsilateral to the side of anterodorsal cortical lesion or in animals with the same bilateral lesion appears to predispose them for the development of spontaneous, non-convulsive (partial complex) seizures. It also significantly modifies clinical ictal patterns with practical omission of Stages 2, 3 and 5, and largely lateralizes AD propagation to the stimulated hemisphere.

The latter two features are strikingly reminiscent of the electroclinical manifestations of secondary site AM kindling in intact animals or AM kindling in animals with forebrain commissure bisection.

Nonconvulsive (partial complex) status epilepticus was readily arrested by placement of electrolytic lesions ipsilateral to the AM stimulation, suggesting that MRF is essential for the perpetuation of the recurrent spontaneous seizure.

Finally, the presence and absence of positive and negative aftereffects respectively, in animals with anterodorsal cortical lesion is consistent with the view that transfer and interference effects are mediated through the brain stem and forebrain commissures respectively.

A 76-year-old male with a severely deforming rheumatoid arthritis, eosinophilic!, polymyositis, and episcleritis developed a transient tonic pupil. The episcleritis, and a muscle biopsy revealing an occlusive arteritis with eosinophilia, suggest that a widespread rheumatoid arteritis caused a reversible ischemic insult to the ciliary ganglion and thus created a transient denervation of the pupil.

A study of 200 patients referred to a community neurologist showed that 87.5% of the patients were seen in the office and only 12.5% in hospital. Neurological signs were present in 52% and 28.5% had neurological signs which materially affected the diagnosis. A questionnaire sent to several teaching centers showed that only one center sent students and residents to community neurologists' offices at all and in most centers the resident spent just 10 to 20% of his time seeing out-patients. It was felt that the balance of in-patient/out-patient teaching for students and residents was wrong, and that more emphasis should be placed on the neurological history than on the examination. Proposals are made to involve the community neurologist as well as the academic neurologist in the training of students and residents which would benefit all four groups.

The autoradiographic findings using tritiated leucine are described in muscle biopsy material from five patients with progressive muscular dystrophy (P.M.D.), three with motor neuron disease (M.N.D.) and four with Charcot-Marie-Tooth disease (C.M.T.). In progressive muscular dystrophy there is a marked increase in uptake of leucine into cytoplasmic proteins and precursors, and reduced incorporation into structural protein. In Charcot-Marie Tooth disease muscle there is a significantly increased uptake into cytoplasmic elements and a normal uptake into structural protein. In motor neuron disease the uptake into cytoplasmic elements appears normal but is reduced into structural proteins.

The abnormal uptake in C.M.T. could be explained as a product of regenerative efforts associated with reinnervation. However, the abnormal uptake may represent the primary effects of gene action in the muscle, as seems probable in progressive muscular dystrophy.