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Aids In Neurological Diagnosis
Aids In Neurological Diagnosis FRANK A. ELLIOTT, M.B., F.R.C.P. Professor of Clinical Neurology, University of Pennsylvania School of M edicine; Neurologist to Pennsylvania Hospital, Philadelphia
modern laboratory techniques have contributed much to the diagnosis of neurological disease, they are apt to be less conclusive and more ambiguous than in other systems of the body. A normal x-ray of the chest excludes the presence of any considerable tumor of the lung, whereas a comparatively massive tumor of the brain may be present despite negative x-rays, and even arteriography and ventriculography may fail to disclose it. Similarly, a normal electroencephalogram means far less than a normal electrocardiogram. This paper seeks to outline some of the more important practical facts and fallacies relevant to the investigation of a neurological case.
ALTHOUGH
X-RAYS OF THE SKULL
In the interests of speed and economy, it is desirable when ordering x-rays to inform the department as to the precise nature of the problem involved so that correct views may be taken at the outset. For routine work it is necessary to ask for five views of the skull: right and left laterals, postero-anterior, antero-posterior and axial or submento-vertical. If views of the optic foramen, the pituitary fossa or the internal auditory meatus are wanted, this should be stated. Stereoscopic pictures are often valuable, but generally speaking, they should be reserved for the elucidation of abnormalities seen in routine pictures. There is no need to stress the importance, both forensic and medical, of x-raying the skull after injury, nor to emphasize that severe brain damage can occur in the absence of any fracture, nor to recall that fractures of the base may be radiologically invisible. A fracture line across the middle meningeal groove alerts the physician to the possibility of hemorrhage from middle meningeal vessels. Fractures involving the posterior wall of the frontal sinus and the petrous portion of the temporal bone serve warning that infection may thereafter reach the subarachnoid space, from the nose and ear respectively. Displacement of a calcified pineal gland is a valuable lateralizing sign in the diagnosis of subdural
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and epidural hemorrhage and other space-occupying lesions. The value of x-rays of the skull in patients who have been subjected to explosions or blast injuries is underlined by the fact that a foreign body can enter the brain through a barely visible laceration of the scalp without causing unconsciousness at the time of impact. In space-occupying lesions of the brain, straight x-rays of the skull are normal more often than not. The most important positive signs are five in number: calcification in or around a mass, erosion or sclerosis of bone in an area related to the disease, erosion of the clinoid processes by raised intracranial pressure, displacement of the pineal to one side or downward, and, in children, widening of the sutures in the presence of raised intracranial pressure. X-rays of the skull sometimes shed light on systemic conditions, notably, Paget's disease of bone, syphilis, osteitis fibrosa cystic a, multiple myelomatosis, secondary neoplasms, rickets and xanthomatosis. Similarly, x-ray pictures of the lungs frequently throw light on intracranial symptoms. In view of the high incidence of cerebral metastases from bronchial carcinoma, an x-ray of the lungs is obligatory in every case of suspected cerebral tumor; at the same time, it must be recognized that massive intracranial secondaries may occur at the stage when the primary in the lung is radiographic ally invisible. Similarly, radiological evidence of tuberculosis of the lungs may give the first hint as to the possible nature of a subacute meningitis, and both Fallot's tetralogy and bronchiectasis are important precursors of cerebral abscess. Sarcoidosis is yet another condition which may be present both in the lungs and in the meninges.
Special X-Ray Studies The techniques of ventriculography, pneumoencephalography and angiography fall outside the scope of this paper, but their relative value in the diagnosis of neurological disease deserves mention. Pneumoencephalography is reserved for patients with normal intracranial pressure. Its greatest value is in the demonstration of cerebral atrophy in the presenile dementias and in the identification of porencephalic cysts, either developmental in origin or due to birth injury. In the case of an intracranial space-occupying lesion unassociated with a rise in intracranial pressure, pneumoencephalography can be of localizing value but, in general, the results are inconclusive and unsatisfactory. Ventriculography is more accurate, but it should never be carried out unless facilities for immediate neurosurgical intervention are available. On the whole, it is superior to angiography for the demonstration of hydrocephalus and tumors in the midline of the cerebral hemispheres. Angiography, on the other hand, can be carried out for diagnostic purposes in the absence of neurosurgical facilities and provides information which is not available through ventriculography. It is of value in demonstrating stenosis or occlusion of the carotid, the vertebral and the basilar arteries or their
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main branches, and it is obviously the method of choice in locating aneurysms and angiomatous malformations. Displacement of the visualized arterial and venous tree can be seen in the presence of some tumors, in subdural hematomas and in abscesses. Moreover, vascular tumorsglioblastomas and some meningiomas-take up the contrast medium and thereby disclose not only their presence but the nature of the mass. On the other hand, a small mass may not be disclosed by either angiography or ventriculography, so that a completely negative neuroradiological examination will not, in such a case, rule out the presence of a space-occupying lesion. This is particularly true of saccular aneurysms; a negative arteriogram may be obtained in from 10 to 30 per cent of these cases. X-RAYS OF THE SPINE
For most purposes, antero-posterior and lateral views suffice, but for the upper thoracic region a stereoscopic film in the antero-posterior position is necessary because it is almost impossible to get a satisfactory view of this region in any other way. Oblique views are required to demonstrate the intervertebral foramina if, for instance, it is necessary to determine whether a root pain is caused by a tumor (which may enlarge the foramen) or a disc protrusion (which will narrow it). Recent herniations of the nucleus pulposus are not radiopaque; any clearly visualized calcified spur in the intervertebral foramen or elsewhere on the circumference of a disc has been present for months or years and is not necessarily the cause of the patient's symptoms. Indeed, since protrusion of one or more discs, with or without spur formation, is virtually universal in the cervical and lumbar regions after the age of 40, the chief function of x-rays in relation to root pains is not the identification of a protruded disc, but the exclusion of conditions such as tuberculous caries, spondylolisthesis and new growths which can simulate the disc syndrome. It is often impossible to detect bone changes in the early stages of destructive lesions of the spine, and re-examination at a later date is desirable in any case in which this possibility exists. Although the identification of the root or roots involved by a prolapsed disc or protruded annulus fibrosus can usually be made by analysis of the symptoms and signs, myelography with a radiopaque contrast medium greatly adds to the accuracy of diagnosis. However, even the myelogram may be negative in the presence of pain due to a large protruded disc which lies far out in the intervertebral foramen. Contrast myelography is also extremely valuable in the identification of spaceoccupying lesions within the spinal canal. It is a safe procedure in experienced hands and modern contrast media cause little irritation, if any, especially if the medium is removed after the myelogram is completed. Rarely, when a spinal tumor is present, myelography is followed by a
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rapid worsening of symptoms, necessitating immediate laminectomy; for this reason it should not be carried out in tumor suspects unless neurosurgical facilities are available. Congenital malformations of the spine are common (indeed, in the lumbosacral region they occur in some 80 per cent of all otherwise normal adults as judged by anatomical dissection), but they are so often asymptomatie that it is prudent to avoid aseribing symptoms to sueh malformations unless or until every other possibility has been exeluded. This applies with speeial foree to spina bifida occulta and to cervical ribs. For instanee, of ten recent personal cases of cervical ribs in which symptoms were present in the upper limbs, four patients were suffering from the effects of cervical spondylosis, two from prolapsed disc, three from the earpal tunnel syndrome and one from a demonstrable traumatie neuroma of the ulnar nerve at the elbow. Even spondylolisthesis in the lumbar region need not necessarily cause any symptoms at all, though low baek pain is not uncommon and, in exceptional cases, compression of the cauda equina can occur.
ELECTROENCEPHALOGRAPHY The electroencephalogram is influenced by the patient's age and level of consciousness and attention, by raised intracranial pressure, hypoglycemia, hepatic failure, uremia, hypothyroidism, barbiturate medication and other factors. It is therefore desirable that the request form should convey suffieient information as to the elinical condition of the patient to guide in the interpretation of the record. Furthermore, the nature and location of suspeeted neurological disease should be clearly stated in order to assist the technician in electrode selection and choice of activating techniques. Indeed, there is no form of special investigation in which detailed elinical information is more necessary; there would be less disillusionment with the fruits of electroencephalography-at this stage of its development-if this were more widely realized. What ean be expected of an EEG? In the epilepsies and in many types of organic cerebral disease, the record obtained from a patient may vary from day to day; therefore, a negative report based on a single examination can be misleading. Furthermore, the significance to be attached to a single negative report varies according to the thoroughness of the examination; for instance, in the epilepsies, the EEG abnormalities which are not present in the waking record often become apparent in induced sleep. Therefore, a record which remains negative for epilepsy, both in the waking state and during induced sleep, is more significant than one in which a sleep record was not done. Even with the full complement of activation techniques, negative results may be obtained in patients suffering from grand mal. It is not easy to give a statistically accurate account of how many patients suffering from a given malady will have a
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normal EEG, since there are differences of opinion as to what constitutes a normal record. But in both major epilepsy and organic disease of the brain the margin is sufficiently wide to make most experienced neurologists and neurosurgeons dismiss a normal EEG report if the rest of the clinical and laboratory evidence is sufficiently suggestive. It is usually agreed, however, that in the primary psychoses, which are unassociated with structural disease of the brain, there is no significant deviation from the normal range, and the value of the EEG in such cases lies in the elimination of organic disease which, in its early stages, can masquerade as a primary psychosis or neurosis. On the other hand, in children there is a relatively high incidence of EEG abnormalities in the presence of personality disorders. In organic intracranial disease, the findings are variable. The EEG is usually normal in posterior fossa tumors, provided that there is no rise in intracranial pressure, whereas any considerable mass in the cerebral hemispheres is apt to be accompanied by electrical disturbance. Generally speaking, acutely developing organic disease is more likely to produce EEG changes than more chronic lesions, though an exception to this statement is seen in the focal discharges around some slowly developing tumors. Diffuse acute cortical and subcortical processes, notably encephalitis, cerebral contusion and general paresis, are likely to show abnormalities, but the EEG is the least important factor in arriving at a diagnosis. It is in the epilepsies that the EEG is most useful, often providing information that cannot be obtained with certainty from other sources. Not only can it help to distinguish idiopathic epilepsy from seizures due to structural lesions, but it can also help to identify grand mal, petit mal and temporal lobe epilepsy, and may sometimes demonstrate the epileptic basis of episodic disorders of behavior. In petit mal, records done between seizures usually show abnormalities, but in grand mal, particularly when the attacks are infrequent and in people over the age of 40, the percentage of positive results falls sharply. In general, the normal interseizure record means little in the presence of grand mal, whereas if a normal record is obtained in a patient who is suffering from frequent attacks of suspected petit mal, the epileptic basis of these attacks is questionable. In narcolepsy, interseizure records are usually normal, but during an actual attack a typical sleep pattern is found. The EEG can also help in the management of epilepsy. Phenobarbital and Dilantin sodium are the most effective drugs for patients showing the EEG changes characteristic of idiopathic grand mal. Mysoline, either alone or in combination with Dilantin, is also useful. In psychomotor epilepsy Dilantin is the drug of choice. Tridione, paradione, Celontin and Milontin are the only drugs that have any appreciable influence on the frequency of petit mal attacks in children, provided that such attacks are associated with the characteristic spike and wave complexes of this condition. The control of seizures by surgical excision of
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scar tissue or other focal disease depends largely for its success on EEG studies, and the same applies to the rare condition known as temporal lobe or psychomotor epilepsy. These, however, are uncommon problems. In the more pedestrian type of case which arises from day to day in medical practice, the EEG can make a modest contribution to the diagnosis of some cases, and its usefulness in this respect is much enhanced when the clinician is able to help the laboratory by describing the problem in full. EXAMINATION OF THE VISUAL FIELDS
Although instrumental aids are necessary for the accurate mapping of visual field defects, much useful information can be obtained in a minute or two, in the office or at the bedside, by simple clinical techniques. The need for this method of examination is underlined by the fact that most patients with incomplete varieties of hemianopia are quite unaware of having any visual symptoms and do not complain of them. A bilateral contraction of the upper temporal fields is often the earliest objective sign of a pituitary tumor, and a complete or incomplete homonymous hemianopia may be the sole clue to basilar artery stenosis, posterior cerebral infarction or tumor in the temporal, parietal or occipital lobes. There is far less danger of missing the visual defects due to lesions in the central area of the retina or in the optic nerve, because in such instances central or paracentral vision is nearly always involved and the patient is fully aware of his disability. Even in these cases, however, the simple methods outlined below can assist diagnosis. It is possible, for instance, to identify the central scotoma of retrobulbar neuritis, the centrocecal scotoma of glaucoma, the segmental defect of a branch thrombosis in the retina, and the peripheral constriction of vision which occurs when papilledema is giving rise to secondary optic atrophy. The type of test employed must obviously be suited to the patient's level of consciousness and attention. Large objects are more easily seen than small ones, and moving objects than still ones. Colored objects are more easily seen than white objects if the background is white, and conversely if the background is black. The confrontation test is best carried out with the patient sitting up and the light behind him. The examiner should be about three feet away and should take care that any test objects employed should be held midway between the patient and himself. The first test, a relatively coarse one, is carried out with the patient looking fixedly at the bridge of the examiner's nose. The examiner then places his hands well out into the temporal fields, at the level of the patient's eyes, and moves the fingers of both hands very slightly. The patient is asked to say which hand moved. The same test is then applied to the two half fields of each eye separately. The principle of the simul-
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taneous presentation of two stimuli is an important one, for in the presence of many parietal and early occipital lesions, the patient will readily identify a single object, but will fail to do so when two objects are presented simultaneously, one in the normal and one in the abnormal visual fields. This "attention" hemianopia is precisely similar to other forms of sensory inattention found in affections of one parietal lobe. In such a case, although hearing is intact in each ear, simultaneous stimuli to the two sides will not be heard on both sides; the patient will recognize only the stimulus on the side of the le8ion. If both hands are lightly touched at the same time, he will feel only the stimulus on the side of the lesion, although single stimuli to either side will be correctly appreciated. The moving finger is, however, a gross stimulus. The same principle can be applied with greater accuracy by using small test objects, such as white- or red-headed pins. The test is repeated in the same way as before, simultaneously confronting the patient with two similar test objects. Lesions of the visual pathways, as opposed to those of the parietal lobe, will usually show some absolute depression of vision in addition to the attention defect. Having established the presence or absence of a peripheral field defect, it is then desirable to bring the test object slowly in toward the fixation point, asking the patient to report whether it disappears from view at any point. The test object is slowly brought in from various points on the circumference of the visual field, and in this way it is possible to detect visual depression in the center of the field. The test object, disappears, for instance, in the presence of a central 8cotoma from retrobulbar neuritis, and the shape and size of the scotoma can be mapped out in this way. The confrontation method has limitations. In particular, early visual defects due to lesions of the optic nerve and chiasma sometimes leave both central and peripheral vision intact, but depress it in the intermediate area of the temporal fields. Thjs situation can be investigated effectively only on the wide angle screen, a sine qua non for the early identification of lesions in this region. Examination on the screen or the perimeter-both of which give precise quantitative information if carried out correctly-is also necessary whenever the progress of a field defect has to be watched, but this does not detract from the fact that the confrontation method provides the internist with a simple, rapid and extremely helpful diagnostic aid. AUSCULTATION IN NEUROLOGICAL PRACTICE
Auscultation of the head and neck is an essential part of any neurological examination. A high-pitched systolic intracranial bruit occurs in most large angiomatous malformations inside the head and should be sought for over the eyes, the temples and the occipital region. The in-
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tensity of the bruit varies from hour to hour and from day to day, and the absence of this sign does not exclude the presence of a malformation. A bruit is seldom, if ever, heard in the presence of an ordinary saccular or berry aneurysm, but it is present in cases of carotid-cavernous fistula, in which it is usually accompanied by a pulsating proptosis and papilledema. Very rarely asystolic bruit is heard over the skull in infants with arterial hypertension. Atherosclerotic narrowing of the carotid artery gives rise to a bruit which, unlike the systolic murmur of aortic stenosis, is loudest in the neck. In severe stenosis or complete occlusion a bruit may be absent. (It is interesting to note that Owen3 has found that stenosis of one renal artery, an occasional cause of hypertension, can be accompanied by a systolic bruit heard two inches above and to one side of the umbilicus.) Auscultation along the spinal column is a new development. Mathews 4 recently found a bruit in two cases of spinal angiomatous malformations. These structures can give rise to spinal subarachnoid hemorrhage and also to cord symptoms of abrupt onset. A theoretical possibility in this connection is that a bruit coming from an angiomatous malformation in the lungs might also be heard along the spine, as well as elsewhere in the chest, but this will be settled by radiological examination of the chest. Contraindications
LUMBAR PUNCTURE
A spinal tap should not be carried out in the presence of cerebrospinal otorrhea or rhinorrhea secondary to head injury, because it can reverse the direction of flow at the site of the leak and so draw microorganisms into the subarachnoid space, leading to meningitis or abscess formation. A spinal tap is also contraindicated when the intracranial pressure is known to be raised by a space-occupying lesion, such as extradural or subdural hematoma, tumor, abscess or massive intracranial hemorrhage. The withdrawal of fluid under these circumstances can give rise to sudden caudal displacement of the brainstem and the production of a rapidly fatal pressure cone. It must be remembered in this connection that if intracranial pressure rises very rapidly there may not be time for papilledema to have developed when the patient is first seen. If a tap is done under these circumstances, and the spinal fluid rapidly rises to the top of the manometer, the needle should be withdrawn at once. Conversely, papilledema sometimes develops in conditions such as meningitis, serous meningitis and sinus thrombosis; in these conditions spinal tap is safe because the withdrawal of fluid causes no significant displacement of brain structure. Procedure
The key to easy spinal tap is correct positioning of the patient. He should lie on his side along the edge of the bed with the spine horizontal, flexed and free from torsion in its long axis. It is unnecessary to flex the
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neck and it is undesirable to flex the thighs to more than a right angle, especially with fat people. Such enforced and excessive flexion can be uncomfortable and can cause a spurious rise in intracranial pressure. Torsion of the spine is avoided by keeping the back, from shoulders to sacrum, in a vertical plane; if the mattress sags in the middle, a pillow placed between the knees will help to prevent torsion. Gloves are unnecessary provided that the physician's hands are carefully scrubbed beforehand. Dry-sterilized needles (gauge 20) are desirable. The skin of the lower lumbar area is cleaned with antiseptic solution and the space between the 4th and 5th lumbar spines is identified; it usually lies in the line drawn between the iliac crests. Three or four drops of procaine are injected into the skin in the midline; injection to a greater depth is not necessary and may cause pain afterwards. The needle should be introduced at right angles to the skin, but in cases of extreme lumbar lordosis, a slightly upward inclination is required. A distinct click is felt by the operator when the needle pierces the ligamentum subflavum, and again when it pierces the dura. The stylet is then withdrawn and if fluid fails to appear, suction should be applied by a syringe in case the pressure is subnormal. If suction fails, the needle should be pushed farther in. If the patient experiences pain down the leg, the needle should be almost completely withdrawn and then pushed in at a suitably corrected angle. Pressure readings should always be taken. If spinal compression is in question, both jugular veins should be firmly compressed. The extent and speed of the rise of cerebrospinal fluid pressure should be noted. Failure to rise or an incomplete and slow elevation usually means that spinal block is present, hut it should be noted that in cases of spinal arachnoiditis, in which cystic collections of spinal fluid compress the cord, the rise of pressure induced by jugular compression may he transmitted to the lumbar sac. Contrast myelography is the only really reliable method of identifying the presence, site and extent of spinal block. Following the Queckenstedt maneuver, 3 cc. of fluid should be collected in each of two tubes. The pressure is again read and the needle is then withdrawn. It is usually advisable for the patient to lie flat, using only one pillow, for two hours after the test. A low-pressure headache, which is aggravated by sitting up and relieved by lying flat, occurs in a small number of cases and can usually be stopped by injecting intrathecally a volume of sterile saline equivalent to the amount of fluid withdrawn, or more slowly by giving a pint and a half of intravenous saline, or more slowly still by making the patient drink large quantities of fluid while keeping him at rest. Pressure Readings
In a normal subject, lying horizontally, the height of the pressure as determined by lumbar puncture ranges from 30 mm. to 150 mm., de-
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pending largely on the height of the subject's uppermost lateral ventricle above the site of the needle in the lumbar theca. Abnormally low pressures are seen in the presence of spinal block, occasionally after closed head injuries and sometimes in the presence of a pressure cone which, by pushing the medulla and cerebellar tonsils into the foramen magnum, cuts off the spinal subarachnoid space from the intracranial cavity. Rarely, low pressure headaches occur as an intermittent phenomenon in patients without other signs of intracranial disease. This syndrome usually occurs in middle-aged men, but is not confined to them, and usually clears up after some months. The cause is unknown. Pressure readings between 150 and 250 mm. are difficult to assess. They can occur if the patient is not suitably relaxed or in obese subjects if the knees are drawn up too high. Pressures over 250 mm. are usually pathological, especially if they persist after the patient has been made to take a few deep breaths. Color and Contents
Normal fluid is gin-clear. Yellowish coloration may be due to oxyhemoglobin, bilirubin and-exceptionally-methemoglobin; these can be identified by spectrophotometry and by chemical tests.! Lysis of blood in the subarachnoid space produces oxyhemoglobin, which can be detected in about two hours after the onset of hemorrhage; bilirubin does not begin to appear before about two days, a fact which can be used to distinguish between xanthochromia due to traumatic spinal tap done within 48 hours and a subarachnoid hemorrhage at an earlier date. Xanthochromia occurs in jaundice, spinal block and severe "infective" polyneuritis. Xanthochromia may decrease or disappear if the specimen is left standing in sunlight. The specimen should be examined for its cellular content within a few hours, hecause cells lyse fairly rapidly. Normal cerebrospinal fluid obtained from the lumbar sac contains not more than four lymphocytes per Cll. mm. (there are no cells in normal ventricular fluid). Polymorphs, plasma cells and compound granular corpuscles are always due to disease. In general, a cellular increase means that active disease is present in the meninges, or in the brain or spinal cord. However, the count may he unaltered when foci of acute disease are buried deep in the substance of the brain, away from the subarachnoid and ventricular surfaces. A polymorph response is seen in coccal meningitis and may also appear along with lymphocytes in the early stages of tuberculous meningitis, cerebral abscess and poliomyelitis. A lymphocytosis is seen in many virus infections, in active neurosyphilis and in tumors or infarcts which are situated adjacent to the subarachnoid or ventricular surfaces. The protein content of fluid withdrawn from the lateral ventricles varies from 5 to 15 mg. per 100 m!. and that from the lumbar sac from 15 to 40 mg. per 100 m!. Nevertheless, it is not uncommon to find an
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elevation up to 60 mg. per 100 ml., especially in elderly people without obvious signs of neurological disease; too much significance should not be attached to such findings in the absence of other signs. A rise in protein usually involves both the albumin and globulin fractions, but in neurosyphilis there may be a disproportionate rise in the latter. In multiple sclerosis, there is usually a significant rise in gamma globulin, even if the total protein is within normal limits, and it is this which sometimes produces an abnormal colloidal gold curve in this disease. The presence of a so-called paretic curve in an otherwise normal fluid, with negative tests for syphilis, is virtually diagnostic of multiple sclerosis. The glucose content follows the blood level in diabetes and is diminished in coccal meningitis. It is usually normal in tuberculous meningitis and in virus infections. A reduction of chlorides (normal, 720 to 750 mg. per 100 cc.) occurs in most forms of acute meningitis, but the fall is earliest and most conspicuous in tuberculosis of the meninges. The chlorides may rise in uremia. Restrictions of space preclude a more detailed treatment of this subject, but a description of the changes in the spinal fluid in some 88 neurological diseases is available elsewhere. 2 REFERENCES 1. Barrows, L. J., Hunter, F. T. and Banker, B. Q.: The Nature and Clinical Significance of Pigments in the Cerebrospinal Fluid. Brain 78: I, 59-80, 1955. 2. Elliott, F. A.: In Douthwaite, A. TT. (ed.): French's Index of Differential Diagnosis. 7th ed. Bristol, John Wri\!;ht & Sons, Ltd., 1954, p. 875. 3. Owen, K.: Renal Artery Stenosis. Proc. Roy. Soc. Med. 58: 32, 1960. 4. Mathews, W. B.: The Spinal Bruit. Lancet 2: 117,1959. 5. Strauss, H., Ostow, M. and Greenstein, L.: Diagnostic Electroenccphalography. New York, Grune & Stratton, 1\)52.
807 Spruce Street Philadelphia 7, Pennsylvania
modern laboratory techniques have contributed much to the diagnosis of neurological disease, they are apt to be less conclusive and more ambiguous than in other systems of the body. A normal x-ray of the chest excludes the presence of any considerable tumor of the lung, whereas a comparatively massive tumor of the brain may be present despite negative x-rays, and even arteriography and ventriculography may fail to disclose it. Similarly, a normal electroencephalogram means far less than a normal electrocardiogram. This paper seeks to outline some of the more important practical facts and fallacies relevant to the investigation of a neurological case.
ALTHOUGH
X-RAYS OF THE SKULL
In the interests of speed and economy, it is desirable when ordering x-rays to inform the department as to the precise nature of the problem involved so that correct views may be taken at the outset. For routine work it is necessary to ask for five views of the skull: right and left laterals, postero-anterior, antero-posterior and axial or submento-vertical. If views of the optic foramen, the pituitary fossa or the internal auditory meatus are wanted, this should be stated. Stereoscopic pictures are often valuable, but generally speaking, they should be reserved for the elucidation of abnormalities seen in routine pictures. There is no need to stress the importance, both forensic and medical, of x-raying the skull after injury, nor to emphasize that severe brain damage can occur in the absence of any fracture, nor to recall that fractures of the base may be radiologically invisible. A fracture line across the middle meningeal groove alerts the physician to the possibility of hemorrhage from middle meningeal vessels. Fractures involving the posterior wall of the frontal sinus and the petrous portion of the temporal bone serve warning that infection may thereafter reach the subarachnoid space, from the nose and ear respectively. Displacement of a calcified pineal gland is a valuable lateralizing sign in the diagnosis of subdural
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and epidural hemorrhage and other space-occupying lesions. The value of x-rays of the skull in patients who have been subjected to explosions or blast injuries is underlined by the fact that a foreign body can enter the brain through a barely visible laceration of the scalp without causing unconsciousness at the time of impact. In space-occupying lesions of the brain, straight x-rays of the skull are normal more often than not. The most important positive signs are five in number: calcification in or around a mass, erosion or sclerosis of bone in an area related to the disease, erosion of the clinoid processes by raised intracranial pressure, displacement of the pineal to one side or downward, and, in children, widening of the sutures in the presence of raised intracranial pressure. X-rays of the skull sometimes shed light on systemic conditions, notably, Paget's disease of bone, syphilis, osteitis fibrosa cystic a, multiple myelomatosis, secondary neoplasms, rickets and xanthomatosis. Similarly, x-ray pictures of the lungs frequently throw light on intracranial symptoms. In view of the high incidence of cerebral metastases from bronchial carcinoma, an x-ray of the lungs is obligatory in every case of suspected cerebral tumor; at the same time, it must be recognized that massive intracranial secondaries may occur at the stage when the primary in the lung is radiographic ally invisible. Similarly, radiological evidence of tuberculosis of the lungs may give the first hint as to the possible nature of a subacute meningitis, and both Fallot's tetralogy and bronchiectasis are important precursors of cerebral abscess. Sarcoidosis is yet another condition which may be present both in the lungs and in the meninges.
Special X-Ray Studies The techniques of ventriculography, pneumoencephalography and angiography fall outside the scope of this paper, but their relative value in the diagnosis of neurological disease deserves mention. Pneumoencephalography is reserved for patients with normal intracranial pressure. Its greatest value is in the demonstration of cerebral atrophy in the presenile dementias and in the identification of porencephalic cysts, either developmental in origin or due to birth injury. In the case of an intracranial space-occupying lesion unassociated with a rise in intracranial pressure, pneumoencephalography can be of localizing value but, in general, the results are inconclusive and unsatisfactory. Ventriculography is more accurate, but it should never be carried out unless facilities for immediate neurosurgical intervention are available. On the whole, it is superior to angiography for the demonstration of hydrocephalus and tumors in the midline of the cerebral hemispheres. Angiography, on the other hand, can be carried out for diagnostic purposes in the absence of neurosurgical facilities and provides information which is not available through ventriculography. It is of value in demonstrating stenosis or occlusion of the carotid, the vertebral and the basilar arteries or their
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main branches, and it is obviously the method of choice in locating aneurysms and angiomatous malformations. Displacement of the visualized arterial and venous tree can be seen in the presence of some tumors, in subdural hematomas and in abscesses. Moreover, vascular tumorsglioblastomas and some meningiomas-take up the contrast medium and thereby disclose not only their presence but the nature of the mass. On the other hand, a small mass may not be disclosed by either angiography or ventriculography, so that a completely negative neuroradiological examination will not, in such a case, rule out the presence of a space-occupying lesion. This is particularly true of saccular aneurysms; a negative arteriogram may be obtained in from 10 to 30 per cent of these cases. X-RAYS OF THE SPINE
For most purposes, antero-posterior and lateral views suffice, but for the upper thoracic region a stereoscopic film in the antero-posterior position is necessary because it is almost impossible to get a satisfactory view of this region in any other way. Oblique views are required to demonstrate the intervertebral foramina if, for instance, it is necessary to determine whether a root pain is caused by a tumor (which may enlarge the foramen) or a disc protrusion (which will narrow it). Recent herniations of the nucleus pulposus are not radiopaque; any clearly visualized calcified spur in the intervertebral foramen or elsewhere on the circumference of a disc has been present for months or years and is not necessarily the cause of the patient's symptoms. Indeed, since protrusion of one or more discs, with or without spur formation, is virtually universal in the cervical and lumbar regions after the age of 40, the chief function of x-rays in relation to root pains is not the identification of a protruded disc, but the exclusion of conditions such as tuberculous caries, spondylolisthesis and new growths which can simulate the disc syndrome. It is often impossible to detect bone changes in the early stages of destructive lesions of the spine, and re-examination at a later date is desirable in any case in which this possibility exists. Although the identification of the root or roots involved by a prolapsed disc or protruded annulus fibrosus can usually be made by analysis of the symptoms and signs, myelography with a radiopaque contrast medium greatly adds to the accuracy of diagnosis. However, even the myelogram may be negative in the presence of pain due to a large protruded disc which lies far out in the intervertebral foramen. Contrast myelography is also extremely valuable in the identification of spaceoccupying lesions within the spinal canal. It is a safe procedure in experienced hands and modern contrast media cause little irritation, if any, especially if the medium is removed after the myelogram is completed. Rarely, when a spinal tumor is present, myelography is followed by a
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rapid worsening of symptoms, necessitating immediate laminectomy; for this reason it should not be carried out in tumor suspects unless neurosurgical facilities are available. Congenital malformations of the spine are common (indeed, in the lumbosacral region they occur in some 80 per cent of all otherwise normal adults as judged by anatomical dissection), but they are so often asymptomatie that it is prudent to avoid aseribing symptoms to sueh malformations unless or until every other possibility has been exeluded. This applies with speeial foree to spina bifida occulta and to cervical ribs. For instanee, of ten recent personal cases of cervical ribs in which symptoms were present in the upper limbs, four patients were suffering from the effects of cervical spondylosis, two from prolapsed disc, three from the earpal tunnel syndrome and one from a demonstrable traumatie neuroma of the ulnar nerve at the elbow. Even spondylolisthesis in the lumbar region need not necessarily cause any symptoms at all, though low baek pain is not uncommon and, in exceptional cases, compression of the cauda equina can occur.
ELECTROENCEPHALOGRAPHY The electroencephalogram is influenced by the patient's age and level of consciousness and attention, by raised intracranial pressure, hypoglycemia, hepatic failure, uremia, hypothyroidism, barbiturate medication and other factors. It is therefore desirable that the request form should convey suffieient information as to the elinical condition of the patient to guide in the interpretation of the record. Furthermore, the nature and location of suspeeted neurological disease should be clearly stated in order to assist the technician in electrode selection and choice of activating techniques. Indeed, there is no form of special investigation in which detailed elinical information is more necessary; there would be less disillusionment with the fruits of electroencephalography-at this stage of its development-if this were more widely realized. What ean be expected of an EEG? In the epilepsies and in many types of organic cerebral disease, the record obtained from a patient may vary from day to day; therefore, a negative report based on a single examination can be misleading. Furthermore, the significance to be attached to a single negative report varies according to the thoroughness of the examination; for instance, in the epilepsies, the EEG abnormalities which are not present in the waking record often become apparent in induced sleep. Therefore, a record which remains negative for epilepsy, both in the waking state and during induced sleep, is more significant than one in which a sleep record was not done. Even with the full complement of activation techniques, negative results may be obtained in patients suffering from grand mal. It is not easy to give a statistically accurate account of how many patients suffering from a given malady will have a
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normal EEG, since there are differences of opinion as to what constitutes a normal record. But in both major epilepsy and organic disease of the brain the margin is sufficiently wide to make most experienced neurologists and neurosurgeons dismiss a normal EEG report if the rest of the clinical and laboratory evidence is sufficiently suggestive. It is usually agreed, however, that in the primary psychoses, which are unassociated with structural disease of the brain, there is no significant deviation from the normal range, and the value of the EEG in such cases lies in the elimination of organic disease which, in its early stages, can masquerade as a primary psychosis or neurosis. On the other hand, in children there is a relatively high incidence of EEG abnormalities in the presence of personality disorders. In organic intracranial disease, the findings are variable. The EEG is usually normal in posterior fossa tumors, provided that there is no rise in intracranial pressure, whereas any considerable mass in the cerebral hemispheres is apt to be accompanied by electrical disturbance. Generally speaking, acutely developing organic disease is more likely to produce EEG changes than more chronic lesions, though an exception to this statement is seen in the focal discharges around some slowly developing tumors. Diffuse acute cortical and subcortical processes, notably encephalitis, cerebral contusion and general paresis, are likely to show abnormalities, but the EEG is the least important factor in arriving at a diagnosis. It is in the epilepsies that the EEG is most useful, often providing information that cannot be obtained with certainty from other sources. Not only can it help to distinguish idiopathic epilepsy from seizures due to structural lesions, but it can also help to identify grand mal, petit mal and temporal lobe epilepsy, and may sometimes demonstrate the epileptic basis of episodic disorders of behavior. In petit mal, records done between seizures usually show abnormalities, but in grand mal, particularly when the attacks are infrequent and in people over the age of 40, the percentage of positive results falls sharply. In general, the normal interseizure record means little in the presence of grand mal, whereas if a normal record is obtained in a patient who is suffering from frequent attacks of suspected petit mal, the epileptic basis of these attacks is questionable. In narcolepsy, interseizure records are usually normal, but during an actual attack a typical sleep pattern is found. The EEG can also help in the management of epilepsy. Phenobarbital and Dilantin sodium are the most effective drugs for patients showing the EEG changes characteristic of idiopathic grand mal. Mysoline, either alone or in combination with Dilantin, is also useful. In psychomotor epilepsy Dilantin is the drug of choice. Tridione, paradione, Celontin and Milontin are the only drugs that have any appreciable influence on the frequency of petit mal attacks in children, provided that such attacks are associated with the characteristic spike and wave complexes of this condition. The control of seizures by surgical excision of
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scar tissue or other focal disease depends largely for its success on EEG studies, and the same applies to the rare condition known as temporal lobe or psychomotor epilepsy. These, however, are uncommon problems. In the more pedestrian type of case which arises from day to day in medical practice, the EEG can make a modest contribution to the diagnosis of some cases, and its usefulness in this respect is much enhanced when the clinician is able to help the laboratory by describing the problem in full. EXAMINATION OF THE VISUAL FIELDS
Although instrumental aids are necessary for the accurate mapping of visual field defects, much useful information can be obtained in a minute or two, in the office or at the bedside, by simple clinical techniques. The need for this method of examination is underlined by the fact that most patients with incomplete varieties of hemianopia are quite unaware of having any visual symptoms and do not complain of them. A bilateral contraction of the upper temporal fields is often the earliest objective sign of a pituitary tumor, and a complete or incomplete homonymous hemianopia may be the sole clue to basilar artery stenosis, posterior cerebral infarction or tumor in the temporal, parietal or occipital lobes. There is far less danger of missing the visual defects due to lesions in the central area of the retina or in the optic nerve, because in such instances central or paracentral vision is nearly always involved and the patient is fully aware of his disability. Even in these cases, however, the simple methods outlined below can assist diagnosis. It is possible, for instance, to identify the central scotoma of retrobulbar neuritis, the centrocecal scotoma of glaucoma, the segmental defect of a branch thrombosis in the retina, and the peripheral constriction of vision which occurs when papilledema is giving rise to secondary optic atrophy. The type of test employed must obviously be suited to the patient's level of consciousness and attention. Large objects are more easily seen than small ones, and moving objects than still ones. Colored objects are more easily seen than white objects if the background is white, and conversely if the background is black. The confrontation test is best carried out with the patient sitting up and the light behind him. The examiner should be about three feet away and should take care that any test objects employed should be held midway between the patient and himself. The first test, a relatively coarse one, is carried out with the patient looking fixedly at the bridge of the examiner's nose. The examiner then places his hands well out into the temporal fields, at the level of the patient's eyes, and moves the fingers of both hands very slightly. The patient is asked to say which hand moved. The same test is then applied to the two half fields of each eye separately. The principle of the simul-
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taneous presentation of two stimuli is an important one, for in the presence of many parietal and early occipital lesions, the patient will readily identify a single object, but will fail to do so when two objects are presented simultaneously, one in the normal and one in the abnormal visual fields. This "attention" hemianopia is precisely similar to other forms of sensory inattention found in affections of one parietal lobe. In such a case, although hearing is intact in each ear, simultaneous stimuli to the two sides will not be heard on both sides; the patient will recognize only the stimulus on the side of the le8ion. If both hands are lightly touched at the same time, he will feel only the stimulus on the side of the lesion, although single stimuli to either side will be correctly appreciated. The moving finger is, however, a gross stimulus. The same principle can be applied with greater accuracy by using small test objects, such as white- or red-headed pins. The test is repeated in the same way as before, simultaneously confronting the patient with two similar test objects. Lesions of the visual pathways, as opposed to those of the parietal lobe, will usually show some absolute depression of vision in addition to the attention defect. Having established the presence or absence of a peripheral field defect, it is then desirable to bring the test object slowly in toward the fixation point, asking the patient to report whether it disappears from view at any point. The test object is slowly brought in from various points on the circumference of the visual field, and in this way it is possible to detect visual depression in the center of the field. The test object, disappears, for instance, in the presence of a central 8cotoma from retrobulbar neuritis, and the shape and size of the scotoma can be mapped out in this way. The confrontation method has limitations. In particular, early visual defects due to lesions of the optic nerve and chiasma sometimes leave both central and peripheral vision intact, but depress it in the intermediate area of the temporal fields. Thjs situation can be investigated effectively only on the wide angle screen, a sine qua non for the early identification of lesions in this region. Examination on the screen or the perimeter-both of which give precise quantitative information if carried out correctly-is also necessary whenever the progress of a field defect has to be watched, but this does not detract from the fact that the confrontation method provides the internist with a simple, rapid and extremely helpful diagnostic aid. AUSCULTATION IN NEUROLOGICAL PRACTICE
Auscultation of the head and neck is an essential part of any neurological examination. A high-pitched systolic intracranial bruit occurs in most large angiomatous malformations inside the head and should be sought for over the eyes, the temples and the occipital region. The in-
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tensity of the bruit varies from hour to hour and from day to day, and the absence of this sign does not exclude the presence of a malformation. A bruit is seldom, if ever, heard in the presence of an ordinary saccular or berry aneurysm, but it is present in cases of carotid-cavernous fistula, in which it is usually accompanied by a pulsating proptosis and papilledema. Very rarely asystolic bruit is heard over the skull in infants with arterial hypertension. Atherosclerotic narrowing of the carotid artery gives rise to a bruit which, unlike the systolic murmur of aortic stenosis, is loudest in the neck. In severe stenosis or complete occlusion a bruit may be absent. (It is interesting to note that Owen3 has found that stenosis of one renal artery, an occasional cause of hypertension, can be accompanied by a systolic bruit heard two inches above and to one side of the umbilicus.) Auscultation along the spinal column is a new development. Mathews 4 recently found a bruit in two cases of spinal angiomatous malformations. These structures can give rise to spinal subarachnoid hemorrhage and also to cord symptoms of abrupt onset. A theoretical possibility in this connection is that a bruit coming from an angiomatous malformation in the lungs might also be heard along the spine, as well as elsewhere in the chest, but this will be settled by radiological examination of the chest. Contraindications
LUMBAR PUNCTURE
A spinal tap should not be carried out in the presence of cerebrospinal otorrhea or rhinorrhea secondary to head injury, because it can reverse the direction of flow at the site of the leak and so draw microorganisms into the subarachnoid space, leading to meningitis or abscess formation. A spinal tap is also contraindicated when the intracranial pressure is known to be raised by a space-occupying lesion, such as extradural or subdural hematoma, tumor, abscess or massive intracranial hemorrhage. The withdrawal of fluid under these circumstances can give rise to sudden caudal displacement of the brainstem and the production of a rapidly fatal pressure cone. It must be remembered in this connection that if intracranial pressure rises very rapidly there may not be time for papilledema to have developed when the patient is first seen. If a tap is done under these circumstances, and the spinal fluid rapidly rises to the top of the manometer, the needle should be withdrawn at once. Conversely, papilledema sometimes develops in conditions such as meningitis, serous meningitis and sinus thrombosis; in these conditions spinal tap is safe because the withdrawal of fluid causes no significant displacement of brain structure. Procedure
The key to easy spinal tap is correct positioning of the patient. He should lie on his side along the edge of the bed with the spine horizontal, flexed and free from torsion in its long axis. It is unnecessary to flex the
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neck and it is undesirable to flex the thighs to more than a right angle, especially with fat people. Such enforced and excessive flexion can be uncomfortable and can cause a spurious rise in intracranial pressure. Torsion of the spine is avoided by keeping the back, from shoulders to sacrum, in a vertical plane; if the mattress sags in the middle, a pillow placed between the knees will help to prevent torsion. Gloves are unnecessary provided that the physician's hands are carefully scrubbed beforehand. Dry-sterilized needles (gauge 20) are desirable. The skin of the lower lumbar area is cleaned with antiseptic solution and the space between the 4th and 5th lumbar spines is identified; it usually lies in the line drawn between the iliac crests. Three or four drops of procaine are injected into the skin in the midline; injection to a greater depth is not necessary and may cause pain afterwards. The needle should be introduced at right angles to the skin, but in cases of extreme lumbar lordosis, a slightly upward inclination is required. A distinct click is felt by the operator when the needle pierces the ligamentum subflavum, and again when it pierces the dura. The stylet is then withdrawn and if fluid fails to appear, suction should be applied by a syringe in case the pressure is subnormal. If suction fails, the needle should be pushed farther in. If the patient experiences pain down the leg, the needle should be almost completely withdrawn and then pushed in at a suitably corrected angle. Pressure readings should always be taken. If spinal compression is in question, both jugular veins should be firmly compressed. The extent and speed of the rise of cerebrospinal fluid pressure should be noted. Failure to rise or an incomplete and slow elevation usually means that spinal block is present, hut it should be noted that in cases of spinal arachnoiditis, in which cystic collections of spinal fluid compress the cord, the rise of pressure induced by jugular compression may he transmitted to the lumbar sac. Contrast myelography is the only really reliable method of identifying the presence, site and extent of spinal block. Following the Queckenstedt maneuver, 3 cc. of fluid should be collected in each of two tubes. The pressure is again read and the needle is then withdrawn. It is usually advisable for the patient to lie flat, using only one pillow, for two hours after the test. A low-pressure headache, which is aggravated by sitting up and relieved by lying flat, occurs in a small number of cases and can usually be stopped by injecting intrathecally a volume of sterile saline equivalent to the amount of fluid withdrawn, or more slowly by giving a pint and a half of intravenous saline, or more slowly still by making the patient drink large quantities of fluid while keeping him at rest. Pressure Readings
In a normal subject, lying horizontally, the height of the pressure as determined by lumbar puncture ranges from 30 mm. to 150 mm., de-
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pending largely on the height of the subject's uppermost lateral ventricle above the site of the needle in the lumbar theca. Abnormally low pressures are seen in the presence of spinal block, occasionally after closed head injuries and sometimes in the presence of a pressure cone which, by pushing the medulla and cerebellar tonsils into the foramen magnum, cuts off the spinal subarachnoid space from the intracranial cavity. Rarely, low pressure headaches occur as an intermittent phenomenon in patients without other signs of intracranial disease. This syndrome usually occurs in middle-aged men, but is not confined to them, and usually clears up after some months. The cause is unknown. Pressure readings between 150 and 250 mm. are difficult to assess. They can occur if the patient is not suitably relaxed or in obese subjects if the knees are drawn up too high. Pressures over 250 mm. are usually pathological, especially if they persist after the patient has been made to take a few deep breaths. Color and Contents
Normal fluid is gin-clear. Yellowish coloration may be due to oxyhemoglobin, bilirubin and-exceptionally-methemoglobin; these can be identified by spectrophotometry and by chemical tests.! Lysis of blood in the subarachnoid space produces oxyhemoglobin, which can be detected in about two hours after the onset of hemorrhage; bilirubin does not begin to appear before about two days, a fact which can be used to distinguish between xanthochromia due to traumatic spinal tap done within 48 hours and a subarachnoid hemorrhage at an earlier date. Xanthochromia occurs in jaundice, spinal block and severe "infective" polyneuritis. Xanthochromia may decrease or disappear if the specimen is left standing in sunlight. The specimen should be examined for its cellular content within a few hours, hecause cells lyse fairly rapidly. Normal cerebrospinal fluid obtained from the lumbar sac contains not more than four lymphocytes per Cll. mm. (there are no cells in normal ventricular fluid). Polymorphs, plasma cells and compound granular corpuscles are always due to disease. In general, a cellular increase means that active disease is present in the meninges, or in the brain or spinal cord. However, the count may he unaltered when foci of acute disease are buried deep in the substance of the brain, away from the subarachnoid and ventricular surfaces. A polymorph response is seen in coccal meningitis and may also appear along with lymphocytes in the early stages of tuberculous meningitis, cerebral abscess and poliomyelitis. A lymphocytosis is seen in many virus infections, in active neurosyphilis and in tumors or infarcts which are situated adjacent to the subarachnoid or ventricular surfaces. The protein content of fluid withdrawn from the lateral ventricles varies from 5 to 15 mg. per 100 m!. and that from the lumbar sac from 15 to 40 mg. per 100 m!. Nevertheless, it is not uncommon to find an
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elevation up to 60 mg. per 100 ml., especially in elderly people without obvious signs of neurological disease; too much significance should not be attached to such findings in the absence of other signs. A rise in protein usually involves both the albumin and globulin fractions, but in neurosyphilis there may be a disproportionate rise in the latter. In multiple sclerosis, there is usually a significant rise in gamma globulin, even if the total protein is within normal limits, and it is this which sometimes produces an abnormal colloidal gold curve in this disease. The presence of a so-called paretic curve in an otherwise normal fluid, with negative tests for syphilis, is virtually diagnostic of multiple sclerosis. The glucose content follows the blood level in diabetes and is diminished in coccal meningitis. It is usually normal in tuberculous meningitis and in virus infections. A reduction of chlorides (normal, 720 to 750 mg. per 100 cc.) occurs in most forms of acute meningitis, but the fall is earliest and most conspicuous in tuberculosis of the meninges. The chlorides may rise in uremia. Restrictions of space preclude a more detailed treatment of this subject, but a description of the changes in the spinal fluid in some 88 neurological diseases is available elsewhere. 2 REFERENCES 1. Barrows, L. J., Hunter, F. T. and Banker, B. Q.: The Nature and Clinical Significance of Pigments in the Cerebrospinal Fluid. Brain 78: I, 59-80, 1955. 2. Elliott, F. A.: In Douthwaite, A. TT. (ed.): French's Index of Differential Diagnosis. 7th ed. Bristol, John Wri\!;ht & Sons, Ltd., 1954, p. 875. 3. Owen, K.: Renal Artery Stenosis. Proc. Roy. Soc. Med. 58: 32, 1960. 4. Mathews, W. B.: The Spinal Bruit. Lancet 2: 117,1959. 5. Strauss, H., Ostow, M. and Greenstein, L.: Diagnostic Electroenccphalography. New York, Grune & Stratton, 1\)52.
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