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Pseudotumor Cerebri Syndrome*
MECHANISM OF WATER-DRINKING TEST be similar, the inability to administer large doses of water militates against a specific conclusion. 7 The findings of this study help explain the variability of the water provocative test in humans. W a t e r absorption from the stomach is a variable and complex process. Though the range of reduction in blood osmolality is relatively constant, a moderate variability in the absolute value occurs. Since only a small change in blood osmolality is necessary to induce water transfer sufficient to increase intraocular pressure in the glaucomatous eye,
60S
the incidence of a positive test in this popula tion is quite high. In the normal population, and particularly in that group where the in traocular pressure level is suspicious of glau coma, a false-positive response is obtainable if an unusually large reduction in blood os molality occurs. Conversely, a rather small reduction in tonicity may lead to a negative test. The use of 6.0 mm. H g as a clinical level would have far more validity if one could measure osmole changes concomitantly. 525 East 68th Street
(21).
REFERENCES
1. Galin, M. A., Aizawa, F., and McLean, J. M.: Evaluation of the water provocative test. Am. J. Ophth., 51:451 (Mar.; 1961. 2. Kronfeld, P. C : Glaucoma: A Symposium. Springfield, Thomas, 1955, p. 234. 3. Sugar, H. S.: The provocative tests in the diagnosis of the glaucomas. Am. J. Ophth., 31:1193, 1948. 4. Leydhecker, W.: The water drinking test. Brit. J. Ophth., 34:457, 1950. 5. McLean, J. M., and Galin, M. A.: The effect of reduced blood osmolality on intraocular pressure. Tr. Am. Ophth. Soc, 58:118, 1960. 6. Galin, M. A., Aizawa, F., and McLean, J. M.: Urea as an osmotic ocular hypotensive agent in glaucoma. AM A Arch. Ophth., 62:347, 1959. 7. : The effect of various volumes of water on intraocular pressure. In preparation.
PSEUDOTUMOR CEREBRI
SYNDROME*
F O L L O W I N G UNILATERAL RADICAL N E C K DISSECTION WILLIAM
G.
M A R R , M.D.,
A N D ROBERT G.
CHAMBERS,
M.D.
Baltimore, Maryland It is not generally known that following unilateral radical neck dissection there may develop a symptom-complex suggesting pseudotumor cerebri. It is the purpose of this paper to report two such cases. T h e so-called "radical neck dissection" has become standardized as to technique, indica tions for operation and possible complica tions. T h e operation as described by Crile 1 almost 40 years ago has been refined only slightly to include en bloc resection of the primary tumor, as well as the lymphatic tis sues of the neck. T h e operation is designed to remove all possible lymphatic tissue en cased between recognized fascial planes, the * From the Wilmer Ophthalmological Institute of The Johns Hopkins University and Hospital.
superficial and deep cervical fascia. T h e boundaries of the dissection are rigidly fixed and, unless encroached upon by malignant disease, adhered to. The superior border of the excision is the horizontal ramus of the mandible, that por tion of the parotid gland inferior to the main trunk of the facial nerve, the roof of the jugular fossa and the mastoid bone. The posterior border is the trapezius muscle and the inferior boundary is the clavicle. A n teriorly, the dissection includes the submental space and follows the midline of the neck to the sternum. T h e anterior excision may or may not include resection of the strap mus cles and thyroid lobe, depending upon the extent of the disease. Deep margins of the dissection extend to the scalene, erector
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WILLIAM G. MARR AND ROBERT G. CHAMBERS
spinae and levator scapulae muscles and superiorly to the mylohyoid muscles. The block of tissue so removed includes the major lymphatic tissues of the neck, in ternal and external jugular veins, spinal ac cessory and cervical sensory nerves, carotid sheath, the submaxillary salivary gland and a portion of the parotid. Excised also are the sternocleidomastoid and omohyoid mus cles and, at times, the digastric and stylohyoid muscles. The dissection proceeds in an orderly manner from the periphery and usu ally commences in the region of the clavicle. Care is taken to preserve vital structures if they are not involved with tumor. Every attempt is made to protect the pleura, vagus, phrenic, hypoglossal and lingual nerves, the common and internal carotid arteries, and the brachial plexus. The possible complications of neck dis section are legion, some serious and others relatively mild. Those usually mentioned are: cosmetic appearance, facial paralysis, injury to the brachial plexus and other vital nerves, muscular disability, air embolism, pneumothorax, leakage of chyle, injury to major ar teries, postoperative infection and salivary fistula. The extent of the disease will at times dictate the subsequent appearance of some of these complications. Vascular complications attributed to neck dissection are principally arterial injury and hemorrhage. Interruption of major venous drainage has long been considered innocuous other than for the rare occurrence of air embolism. Most head and neck surgeons seem confident that venous structures of the neck can be ligated unilaterally or bilaterally with impunity. However, reports are present in the literature of complications following bilat eral and rarely unilateral resection of the in ternal jugular vein. Sugarbaker and Wiley2 described five pa tients who had a unilateral radical neck dis section followed at a later date by a dissec tion on the opposite side. All five developed congestion of the face or chemosis of the con junctiva immediately after the second in
ternal jugular vein was ligated and concomitantly there was marked elevation of the spinal fluid pressure. The optic fundi of two of the patients were examined and engorgement of the retinal veins was found. In these five patients the facial congestion lasted from one day to three weeks. These authors also presented another patient whose face became darkly cyanotic and swollen fol lowing ligation of the left internal jugular vein only and the spinal fluid pressure went up to 750 mm. H 2 0 . The vital signs and spinal fluid pressure returned to normal after 150 cc. of spinal fluid were removed. On the seventh postoperative day the patient died of aspiration pneumonia and an autopsy showed no abnormalities in the venous-sinus system of the skull but the opposite side of the neck was not dissected out to determine whether any occlusion of the right internal jugular was present. Anlyan, Browning, Black, Clifton and Janzen, 3 described a patient who had a left radical neck dissection. When the left in ternal jugular vein was cut, the breathing be came labored and the face purple. Six hours later a right hemiplegia developed and per sisted until his death two months later. At autopsy the left parietal and occipital regions of the brain were softened and necrotic, al though the arteries supplying these regions were patent. On dissecting the dural sinsuses, the right transverse sinus was found to have only a pinpoint lumen. They concluded that the predominant venous drainage was to the left and, therefore, after the left jugular vein was resected, the patient suffered a sud den block of venous outflow from his brain. Jones,4 in 1951, published a paper on in creased intracranial pressure following radi cal neck surgery. He measured the spinal fluid pressure in 11 patients who underwent radical neck dissection, preoperative and postoperatively from two hours to 12 days after operation. All patients had a spinal fluid pressure well within normal limits prior to neck surgery and all had definitely elevated pressures two hours postoperatively.
PSEUDOTUMOR CEREBRI
The ophthalmoscopic findings consisted of retinal venous engorgement and blurring of the disc edges but no overt papilledema was observed in any instance. After 12 days, two patients were dead, two again had a normal spinal fluid pressure, and seven patients still had an elevated pressure. The cases described thus far were more acute in their onset than the three cases we are reporting. CASE REPORTS CASE 1
After unilateral radical neck dissection patient had brief "black-out" spells, developed bilateral papilledema with flame-shaped hemorrhages and increased cerebrospinal fluid pressure. Metastasis was suspected. Within five months all evidences of increased intracranial pressure had disappeared. G. F., a 44-year-old white man, in May, 1958, had a right radical neck dissection for a squamouscell carcinoma of the right side of the tongue. His immediate postoperative course was entirely un eventful and he was discharged eight days after operation. About three weeks after his discharge he occasionally noticed an unsteady feeling while walking. H e had two "black-outs" which lasted only a few seconds. H e was not troubled by head aches either immediately after operation or later. Two months after operation he visited an ophthal mologist because his vision seemed distorted. The examiner found blurring of the right disc nasally with some flame-shaped hemorrhages nasally and two diopters of papilledema on the left with sur rounding flame-shaped hemorrhages. The peripheral field in each eye was normal to a one-degree white test object. Because of the possibility of an intracranial metastasis or of an unrelated intracranial lesion, the patient was readmitted to The Johns Hopkins Hospital on August 21, 1958. Except for scars from the operation and bilateral papilledema, the general physical examination was normal. The blood pressure was 130/90 mm. Hg. On lumbar puncture the cerebrospinal fluid pressure was 290 mm. H 2 0 . On right jugular compression the pressure was 290 mm. H 2 0 while on left jugular compression the pressure was 360 mm. H2O and on bilateral jugular compression the pressure was 360 mm. H2O with a prompt fall on release. There were no cells in the cerebrospinal fluid and the protein content was within normal limits. A right cerebral arteriogram showed no abnormalities. X-ray films of the skull showed evidence of a large right transverse sinus and no transverse sinus could be seen on the left. A scanogram was negative. Ventriculography was not performed. The patient was discharged on , August 28th. His eyes were examined again in November, 1958. He had not had difficulty with his vision for about
SYNDROME
607
three months. On ophthalmoscopy all of the flameshaped hemorrhages had disappeared. The right disc was still blurred nasally and the left disc was elevated one diopter. H e was last seen in September, 1959, at which time both discs were normal. CASE 2
After unilateral radical dissection of neck for carcinoma of thyroid, this patient suffered black outs and developed diplopia. She also exhibited bi lateral papilledema and retinal hemorrhages. After 11 weeks, the diplopia disappeared. The papilledema had entirely disappeared after six months. P . P., a 26-year-old white woman, had a right radical neck dissection in August, 1958, for car cinoma of the thyroid. Her blood pressure on ad mission was 110/70 mm. Hg. For two weeks after operation she had some brief blackouts when she sat up quickly and for about a month her head would hurt when she would lie down; this was relieved by getting up. Ten days postoperatively she developed diplopia due to a paresis of the right external rectus muscle. Five weeks after operation she had 20/30 vision in each eye with a slight myopic correction and each eye showed three diopters of papilledema with a few surrounding flame-shaped hemorrhages. Visual fields were normal except for slight generalized constric tion and marked enlargement of the blindspot. The diplopia gradually improved and after 11 weeks she no longer had to wear an occluder over one eye. The papilledema did not increase but, after a month, hard exudates appeared in a radial pattern between the disc and macula in each eye. After three months the vision was at 20/40 corrected and the papilledema and exudates were unchanged but the flame-shaped hemorrhages had absorbed. The papilledema began to subside four months after it was first noticed and it had disappeared entirely two months later. She was last seen in September, 1959, when she was in good health and at which time the best cor rected vision was: R. E., 20/40; L. E., 20/30. The hard exudates had disappeared but in each eye the macula appeared slightly atrophic. This was thought to be secondary to the prolonged retinal edema as sociated with the papilledema. The peripheral fields were normal and there was some enlargement of the blindspot in each eye. An X-ray film of the occipital region showed the transverse sinus on the right side to be well outlined and of good size while no transverse sinus could be outlined on the left. CASE 3
K. S., a 48-year-old white man, in April, 1960, had a right radical neck dissection. His postoperative course was uneventful for approximately one month; then he began to notice double vision in the evening when he was tired. Examination six weeks after operation showed bilateral papilledema and a paresis of the right superior oblique muscle. The diplopia disappeared one month after it commenced and both discs had returned to normal five months after the
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W I L L I A M U M A R K A N D R O B E R T G. C H A M B E R S
papilledema was discovered. X-ray films of the skull showed the right lateral sinus to be well de fined, while the left was either absent or rudi mentary. His eyes were normal when he was last examined almost one year after his neck operation. DISCUSSION
The symptomatology of the two patients whose case studies have been given resembles that of pseudotumor cerebri in which con dition there is increased intracranial pressure without an intracranial neoplasm. Wagener 5 said the typical cerebral pseudotumor syn drome was characterized by bilateral papil ledema, a normal or smaller than normal ven tricular system and a cerebrospinal fluid normal except for increase in pressure. Patients in whom pseudotumor cerebri de velops often are under 30 years of age6 and appear in good health, with a clear mental state. Headache is the most common present ing complaint and Smith7 found this symp tom in 64 percent of his series. Nausea and vomiting are not uncommon. Paralysis of one or both abducens nerves may occur. The amount of papilledema varies and up to 11 diopters of papilledema has been reported.8 Visual acuity may be affected if the papill edema is severe or is of long duration. Constriction of the peripheral fields and enlargement of the blindspots may occur. After recovery visual acuity may return to normal or may be permanently reduced from secondary optic atrophy or macular changes secondary to prolonged macular edema. Re covery from pseudotumor cerebri often oc curs spontaneously. Therapy varies widely. In The Johns Hop kins Hospital it has been either no treatment, believing that recovery would ultimately oc cur, or subtemporal decompression when the severity of the papilledema threatens vision. Elsewhere repeated spinal fluid drainage has been advocated. Restriction of fluids, reduc tion of salt intake and the administration of Diamox or one of the newer carbonic anhydrase inhibitors have also been suggested. The etiology of pseudotumor cerebri is in many cases obscure and the subject further
confounded by the many different names given to the syndrome. Quincke9 may have been the first to describe some such cases under the eponym, serous meningitis. Nonne10 was the originator of the term, pseu dotumor cerebri, in 1904, and, interestingly enough, among the cases he reported was one in which the cause of the increased intra cranial pressure was found to be a throm bosis of the left transverse sinus in a patient who two years previously had had a left otitis media. Symonds11 reported similar cases as otitic hydrocephalus and McAlpine12 preferred the term, toxic hydrocephalus. Dandy13 referred to the syndrome as intra cranial pressure without brain tumor. In 1931, Symonds11 used the term, otitic hydrocephalus, to describe cases which usu ally occur in children who have had a recent aural infection, develop a squint, usually due to a sixth nerve paralysis, and complain of headache. On f unduscopic examination papil ledema is found and a lumbar puncture in the fully developed state shows the cerebro spinal fluid to be under increased pressure but clear and containing no excess of cells or protein. Symonds at first thought the affection was the result of an excessive se cretion from the choroid plexus or defective absorption through the arachnoid villi. In a later article,14 he agreed that, since the ven tricles were normal or smaller than normal, otitic hydrocephalus was a misnomer. After discussing confirmatory evidence, he con cluded that dural sinus thrombosis might be responsible for the symptom-complex. He studied several post-mortem cases and found that thrombosis of one lateral sinus alone could produce otitic hydrocephalus, but he was uncertain whether there might have been a contributory anatomic factor, such a s ' a smaller opposite lateral sinus. In three other autopsies he found obstruction to the venous outflow from the level of the torcular. Symonds has pointed out that thrombosis of the inferior petrosal sinus probably explains many cases of sixth nerve paralysis. McAlpine12 described cases similar to those
PSEUDOTUMOR CEREBRI SYNDROME reported by Symonds but they followed a nasopharyngeal infection as well as otitis media and he felt, therefore, that the adjec tive otitic was better replaced by the word "toxic" which carried a less specific impli cation as to the causative factor. Dandy13 reported 22 cases of what is here termed pseudotumor cerebri under the title "Intracranial pressure without brain tumor." All the patients he put into this category had elevated intracranial pressure, papilledema, normal or smaller than normal ventricles, and sixth nerve palsies were frequently present. In 1954, Zuidema and Cohen15 published a follow-up report on 12 of Dandy's cases. Ten individuals were living and well while two had died of causes not related to increased intracranial pressure. Ersner and Myers,16 in 1936, published a paper suggesting that the etiology of otitic hydrocephalus might be connected with ob literation of a lateral sinus. They briefly de scribed two cases in which signs of increased intracranial pressure developed following obliteration of the right lateral sinus. The symptoms were ameliorated by the use of magnesium sulfate, glucose intravenously and lumbar puncture. They also presented three other cases in detail; X-ray films re vealed one large lateral sinus with the op posite sinus much smaller in two of the cases. In the third case the X-ray film of the lateral sinuses was not mentioned. The three pa tients recovered following spinal drainage and removal of the irritative focus in the mastoid. Woodhall17 described the embryology and anatomic variations of the lateral sinuses and contiguous structures and reported the clinical symptomatology of thrombosis of one or more of the venous channels. One of the patients was a 46-year-old man with the his tory of right otitis media and mastoiditis three months previously. On admission the only neurologic finding was papilledema. Be cause of increased intracranial pressure a right subtemporal decompression was per formed. This was followed by pneumococcus
609
meningitis and death occurred within a week. An autopsy showed the superior longitudinal sinus and the right lateral sinus into which it emptied to contain a partly organized thrombus. The left lateral sinus was patent but in size was less than half the diameter of the right sinus. Evidence that it is not unusual for the right transverse sinus to be the larger has been supplied by Woodhall.18 He studied variations of the cranial venous sinuses in the region of the torcular herophili in 100 consecutive autopsies in which the structures had not been damaged. He reported a rightsided predominance, with the larger volume of the superior sagittal sinus directed toward the right transverse sinus and the lesser vol ume of the straight sinus directed toward the left transverse sinus, in 39 percent of the cases. Left-sided predominance in which the larger superior sagittal sinus emptied into the left transverse sinus and the smaller straight sinus discharged into the right trans verse sinus was found in 13 percent. He also found a major disproportion between the transverse sinuses in 24 percent and the absence of one transverse sinus in four per cent. Woodhall19 later observed that roentgenograms of the occipital region demonstrated relative differences and variations in the size of the bony marking of the transverse sinuses which closely corresponded to his previous anatomic observations. In other words anteroposterior roentgenograms of the occipital bone showed markings due to the transverse sinuses from which it could be determined that the right transverse sinus was the larger with presumed right-sided predominance and that there existed a major disproportion between the sinuses in ap proximately the same percentages as he found in his autopsy studies. Ray and Dunbar,20 by sagittal sinus venography, were able to confirm that thrombosis of one or more of the dural venous sinuses could produce the symptom-complex of pseu dotumor cerebri.
610
WILLIAM G. MARR AND ROBERT G. CHAMBERS
The method of dural sinus venography consists of the injection of 35-percent Diodrast into the anterior portion of the superior sagittal sinus via a catheter introduced into the sinus through a small midline burr hole, with appropriate roentgenograms. In the nor mal, the contrast medium passes backward through the superior sagittal sinus to the torcular herophili and thence through both transverse sinuses into the internal jugular veins. The cerebral veins and other dural sinuses do not fill unless there is some ob struction in the superior sagittal or trans verse sinuses. One of the patients described by Ray and Dunbar20 was a man who had an earache and purulent discharge from the right ear canal for two weeks. On the day of admission he had developed a high fever ( 4 0 ° C ) . Blood culture was positive ■ for Proteus vulgaris. Roentgenograms showed evidence of acute right mastoiditis. A right mastoidectomy was performed and the transverse venous sinus was found to contain an infected thrombus which was not removed. On antibiotic ther apy there was rapid improvement of the pa tient's condition but within a few days he began to experience blurred vision and gen eralized mild headache. There were about two diopters of papilledema bilaterally and a few small retinal hemorrhages. The neuro logic examination was otherwise normal. The spinal fluid pressure was 400 mm. H 2 0 and the fluid was clear, colorless and accellular. A sagittal sinus venogram showed complete obstruction of the right transverse sinus just lateral to the torcular herophili and a small left transverse sinus. The patient improved gradually and the headache, blurred vision and papilledema subsided steadily and had disappeared after two months. It was shown that the thrombus was limited to the right transverse sinus while the superior sagittal and the other small trans verse sinus were both patent. The develop ment of increased intracranial pressure points to the inadequacy of the remaining small left transverse sinus to compensate for
the obstruction of the opposite larger trans verse sinus. The subsidence of the signs and symptoms of elevated intracranial pressure were assumed to be due to the development of collateral circulation. This case resembles the otitic hydrocephalus cases described by Symonds ex cept that the state of good health, excluding the signs of increased intracranial pressure, occurred spontaneously in Symonds' cases while in Ray and Dunbar's case the rapid improvement in the patient's condition before papilledema developed was presumably due to the antibiotic treatment. Although Ray and Dunbar expressed the hope that sinus venography would show the majority of cases of pseudotumor cerebri to be due to thrombosis of one or more of the dural venous sinuses, additional studies did not support their original supposition. Ray,21 in 1955, reported that in less than half of the cases could obstruction of venous channels be demonstrated. There still remains a large group for which full explanation is lacking. An unusual and unexplained occurrence of pseudotumor cerebri has been seen in women in association with generalized edema appear ing at the menstrual period. Thomas22 de scribed two such cases and McCullagh23 re ported one. Both authors attributed the im provement in their patients to hormonal ther apy, which suggests an endocrine basis for the disorder. CONCLUSIONS
Following unilateral radical neck dissec tion for malignancy three patients developed signs and symptoms of increased intracranial pressure and other essential feautures which characterize pseudotumor cerebri. Because a malignant tumor had been excised, the pos sibility of intracranial metastasis was con sidered. Spontaneous clearing of the signs eliminated this probability. Since in our pa tients here reported major venous drainage channels had been obstructed, it seems ap parent that this accounted for the develop ment of a picture of pseudotumor cerebri.
PSEUDOTUMOR CEREBRI SYNDROME This concept is in agreement with studies made by Symonds, E r s n e r and Myers, Woodhall, and Ray and Dunbar. O u r patients had a large transverse sinus according to X-ray films and the internal jugular vein of the same side was ligated. T h e opposite transverse sinus could not be identified and may well have been small or absent. These
611
case reports supply additional evidence that the interruption of dominant dural sinus drainage may produce the picture of^pseudotumor cerebri. The Johns Hopkins Hospital (5), ACKNOWLEDGMENT
,,, ., ^ . , t „ ~ . „ We wish to express our gratitude to Dr. frank B. Walsh for help in preparation of this manuscript:
REFERENCES
1. Crile, G. W.: Carcinoma of the jaws, tongue, cheek and lips. Surg. Gynec. & Obstet., 36:159, 1923. 2. Sugarbaker, E. D., and Wiley, H. M.: Intracranial-pressure studies incident to resection of the in ternal jugular veins. Cancer, 4:242, 1951. 3. Anlyan, A. J., Browning, H. C, Black, S. P. W., Clifton, E. E., and Janzen, A. H.: Dural sinus studies in relation to radical operations of the neck. Surg. Forum, 1951, p. 300. 4. Jones, R. K.: Increased intracranial pressure following radical neck surgery. Arch. Surg., 63:599, 1951. 5. Wagener, H. P.: Pseudotumor cerebri. Am. J. Med. Sc, 227:214, 1954. 6. Dunn, J., Baker, G. S., and Wagener, H. P.: Pseudotumor cerebri: A review and report of four cases. Proc. Staff Meet., Mayo Clin., 30:505, 1955. 7. Smith, J. L.: Pseudotumor cerebri. Tr. Am. Acad. Ophth., 62:432, 1958. 8. Frazier, C. H.: Cerebral pseudotumors. Arch. Neur. & Psychiat., 24:1117, 1930. 9. Quincke, H.: Ueber meningitis serosa. Samml. Klin. Vort., N. F. Nr., 67 (Inn. Med. Nr. 23):655, 1893. 10. Nonne, M.: Ueber Falle vom Symptomenkomplex "Tumor cerebri" mit Ausgang in Heilung (Pseudotumor cerebri): Uber letal verlaufene Falle von "Pseudotumor cerebri" mit Sektionsbefund. Deutsche Ztschr. f. Nervenh., 27:169, 1904. 11. Symonds, C. P.: Otitic hydrocephalus. Brain, 54:55, 1931. 12. McAlpine, D.: Toxic hydrocephalus. Brain, 60:180, 1937. 13. Dandy, W. E.: Intracranial pressure without brain tumor. Ann. Surg., 106:492, 1937. 14. Symonds, C. P.: Otitic hydrocephalus. Neurology, 6:681, 1956. 15. Zuidema, G. D., and Cohen, S. J.: Pseudotumor cerebri. J. Neurosurg., 11:433, 1954. 16. Ersner, M. S., and Myers, D.: Otitic hydrocephalus with a suggestion as to etiology. Ann. Otol., Rhin. & Laryng., 45:553, 1936. 17. Woodhall, B.: Anatomy of the cranial blood sinuses with particular reference to the lateral. Laryngoscope, 49:966, 1939. 18. Woodhall, B.: Variations of the cranial venous sinuses in the region of the torcular herophili. Arch. Surg., 33:297, 1936. 19. Woodhall, B., and Seeds, A. E.: Cranial venous sinuses. Arch. Surg., 33:867, 1936. 20. Ray, B. S., and Dunbar, H. S.: Thrombosis of the dural venous sinuses as a cause of "pseudotumor cerebri." Ann. Surg., 134:376, 1951. 21. Ray, B. S.: Benign intracranial hypertension. In Cecil and Loeb: A Textbook of Medicine. Phila delphia, Saunders, 1959, ed. 10. 22. Thomas, W. A.: Generalized edema occurring only at the menstrual period. J.A.M.A., 101:1126, 1933. 23. McCullagh, E. P.: Menstrual edema with intracranial hypertension (pseudotumor cerebri). Clev. Clin. Quart., 8:202, 1941.
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the incidence of a positive test in this popula tion is quite high. In the normal population, and particularly in that group where the in traocular pressure level is suspicious of glau coma, a false-positive response is obtainable if an unusually large reduction in blood os molality occurs. Conversely, a rather small reduction in tonicity may lead to a negative test. The use of 6.0 mm. H g as a clinical level would have far more validity if one could measure osmole changes concomitantly. 525 East 68th Street
(21).
REFERENCES
1. Galin, M. A., Aizawa, F., and McLean, J. M.: Evaluation of the water provocative test. Am. J. Ophth., 51:451 (Mar.; 1961. 2. Kronfeld, P. C : Glaucoma: A Symposium. Springfield, Thomas, 1955, p. 234. 3. Sugar, H. S.: The provocative tests in the diagnosis of the glaucomas. Am. J. Ophth., 31:1193, 1948. 4. Leydhecker, W.: The water drinking test. Brit. J. Ophth., 34:457, 1950. 5. McLean, J. M., and Galin, M. A.: The effect of reduced blood osmolality on intraocular pressure. Tr. Am. Ophth. Soc, 58:118, 1960. 6. Galin, M. A., Aizawa, F., and McLean, J. M.: Urea as an osmotic ocular hypotensive agent in glaucoma. AM A Arch. Ophth., 62:347, 1959. 7. : The effect of various volumes of water on intraocular pressure. In preparation.
PSEUDOTUMOR CEREBRI
SYNDROME*
F O L L O W I N G UNILATERAL RADICAL N E C K DISSECTION WILLIAM
G.
M A R R , M.D.,
A N D ROBERT G.
CHAMBERS,
M.D.
Baltimore, Maryland It is not generally known that following unilateral radical neck dissection there may develop a symptom-complex suggesting pseudotumor cerebri. It is the purpose of this paper to report two such cases. T h e so-called "radical neck dissection" has become standardized as to technique, indica tions for operation and possible complica tions. T h e operation as described by Crile 1 almost 40 years ago has been refined only slightly to include en bloc resection of the primary tumor, as well as the lymphatic tis sues of the neck. T h e operation is designed to remove all possible lymphatic tissue en cased between recognized fascial planes, the * From the Wilmer Ophthalmological Institute of The Johns Hopkins University and Hospital.
superficial and deep cervical fascia. T h e boundaries of the dissection are rigidly fixed and, unless encroached upon by malignant disease, adhered to. The superior border of the excision is the horizontal ramus of the mandible, that por tion of the parotid gland inferior to the main trunk of the facial nerve, the roof of the jugular fossa and the mastoid bone. The posterior border is the trapezius muscle and the inferior boundary is the clavicle. A n teriorly, the dissection includes the submental space and follows the midline of the neck to the sternum. T h e anterior excision may or may not include resection of the strap mus cles and thyroid lobe, depending upon the extent of the disease. Deep margins of the dissection extend to the scalene, erector
606
WILLIAM G. MARR AND ROBERT G. CHAMBERS
spinae and levator scapulae muscles and superiorly to the mylohyoid muscles. The block of tissue so removed includes the major lymphatic tissues of the neck, in ternal and external jugular veins, spinal ac cessory and cervical sensory nerves, carotid sheath, the submaxillary salivary gland and a portion of the parotid. Excised also are the sternocleidomastoid and omohyoid mus cles and, at times, the digastric and stylohyoid muscles. The dissection proceeds in an orderly manner from the periphery and usu ally commences in the region of the clavicle. Care is taken to preserve vital structures if they are not involved with tumor. Every attempt is made to protect the pleura, vagus, phrenic, hypoglossal and lingual nerves, the common and internal carotid arteries, and the brachial plexus. The possible complications of neck dis section are legion, some serious and others relatively mild. Those usually mentioned are: cosmetic appearance, facial paralysis, injury to the brachial plexus and other vital nerves, muscular disability, air embolism, pneumothorax, leakage of chyle, injury to major ar teries, postoperative infection and salivary fistula. The extent of the disease will at times dictate the subsequent appearance of some of these complications. Vascular complications attributed to neck dissection are principally arterial injury and hemorrhage. Interruption of major venous drainage has long been considered innocuous other than for the rare occurrence of air embolism. Most head and neck surgeons seem confident that venous structures of the neck can be ligated unilaterally or bilaterally with impunity. However, reports are present in the literature of complications following bilat eral and rarely unilateral resection of the in ternal jugular vein. Sugarbaker and Wiley2 described five pa tients who had a unilateral radical neck dis section followed at a later date by a dissec tion on the opposite side. All five developed congestion of the face or chemosis of the con junctiva immediately after the second in
ternal jugular vein was ligated and concomitantly there was marked elevation of the spinal fluid pressure. The optic fundi of two of the patients were examined and engorgement of the retinal veins was found. In these five patients the facial congestion lasted from one day to three weeks. These authors also presented another patient whose face became darkly cyanotic and swollen fol lowing ligation of the left internal jugular vein only and the spinal fluid pressure went up to 750 mm. H 2 0 . The vital signs and spinal fluid pressure returned to normal after 150 cc. of spinal fluid were removed. On the seventh postoperative day the patient died of aspiration pneumonia and an autopsy showed no abnormalities in the venous-sinus system of the skull but the opposite side of the neck was not dissected out to determine whether any occlusion of the right internal jugular was present. Anlyan, Browning, Black, Clifton and Janzen, 3 described a patient who had a left radical neck dissection. When the left in ternal jugular vein was cut, the breathing be came labored and the face purple. Six hours later a right hemiplegia developed and per sisted until his death two months later. At autopsy the left parietal and occipital regions of the brain were softened and necrotic, al though the arteries supplying these regions were patent. On dissecting the dural sinsuses, the right transverse sinus was found to have only a pinpoint lumen. They concluded that the predominant venous drainage was to the left and, therefore, after the left jugular vein was resected, the patient suffered a sud den block of venous outflow from his brain. Jones,4 in 1951, published a paper on in creased intracranial pressure following radi cal neck surgery. He measured the spinal fluid pressure in 11 patients who underwent radical neck dissection, preoperative and postoperatively from two hours to 12 days after operation. All patients had a spinal fluid pressure well within normal limits prior to neck surgery and all had definitely elevated pressures two hours postoperatively.
PSEUDOTUMOR CEREBRI
The ophthalmoscopic findings consisted of retinal venous engorgement and blurring of the disc edges but no overt papilledema was observed in any instance. After 12 days, two patients were dead, two again had a normal spinal fluid pressure, and seven patients still had an elevated pressure. The cases described thus far were more acute in their onset than the three cases we are reporting. CASE REPORTS CASE 1
After unilateral radical neck dissection patient had brief "black-out" spells, developed bilateral papilledema with flame-shaped hemorrhages and increased cerebrospinal fluid pressure. Metastasis was suspected. Within five months all evidences of increased intracranial pressure had disappeared. G. F., a 44-year-old white man, in May, 1958, had a right radical neck dissection for a squamouscell carcinoma of the right side of the tongue. His immediate postoperative course was entirely un eventful and he was discharged eight days after operation. About three weeks after his discharge he occasionally noticed an unsteady feeling while walking. H e had two "black-outs" which lasted only a few seconds. H e was not troubled by head aches either immediately after operation or later. Two months after operation he visited an ophthal mologist because his vision seemed distorted. The examiner found blurring of the right disc nasally with some flame-shaped hemorrhages nasally and two diopters of papilledema on the left with sur rounding flame-shaped hemorrhages. The peripheral field in each eye was normal to a one-degree white test object. Because of the possibility of an intracranial metastasis or of an unrelated intracranial lesion, the patient was readmitted to The Johns Hopkins Hospital on August 21, 1958. Except for scars from the operation and bilateral papilledema, the general physical examination was normal. The blood pressure was 130/90 mm. Hg. On lumbar puncture the cerebrospinal fluid pressure was 290 mm. H 2 0 . On right jugular compression the pressure was 290 mm. H 2 0 while on left jugular compression the pressure was 360 mm. H2O and on bilateral jugular compression the pressure was 360 mm. H2O with a prompt fall on release. There were no cells in the cerebrospinal fluid and the protein content was within normal limits. A right cerebral arteriogram showed no abnormalities. X-ray films of the skull showed evidence of a large right transverse sinus and no transverse sinus could be seen on the left. A scanogram was negative. Ventriculography was not performed. The patient was discharged on , August 28th. His eyes were examined again in November, 1958. He had not had difficulty with his vision for about
SYNDROME
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three months. On ophthalmoscopy all of the flameshaped hemorrhages had disappeared. The right disc was still blurred nasally and the left disc was elevated one diopter. H e was last seen in September, 1959, at which time both discs were normal. CASE 2
After unilateral radical dissection of neck for carcinoma of thyroid, this patient suffered black outs and developed diplopia. She also exhibited bi lateral papilledema and retinal hemorrhages. After 11 weeks, the diplopia disappeared. The papilledema had entirely disappeared after six months. P . P., a 26-year-old white woman, had a right radical neck dissection in August, 1958, for car cinoma of the thyroid. Her blood pressure on ad mission was 110/70 mm. Hg. For two weeks after operation she had some brief blackouts when she sat up quickly and for about a month her head would hurt when she would lie down; this was relieved by getting up. Ten days postoperatively she developed diplopia due to a paresis of the right external rectus muscle. Five weeks after operation she had 20/30 vision in each eye with a slight myopic correction and each eye showed three diopters of papilledema with a few surrounding flame-shaped hemorrhages. Visual fields were normal except for slight generalized constric tion and marked enlargement of the blindspot. The diplopia gradually improved and after 11 weeks she no longer had to wear an occluder over one eye. The papilledema did not increase but, after a month, hard exudates appeared in a radial pattern between the disc and macula in each eye. After three months the vision was at 20/40 corrected and the papilledema and exudates were unchanged but the flame-shaped hemorrhages had absorbed. The papilledema began to subside four months after it was first noticed and it had disappeared entirely two months later. She was last seen in September, 1959, when she was in good health and at which time the best cor rected vision was: R. E., 20/40; L. E., 20/30. The hard exudates had disappeared but in each eye the macula appeared slightly atrophic. This was thought to be secondary to the prolonged retinal edema as sociated with the papilledema. The peripheral fields were normal and there was some enlargement of the blindspot in each eye. An X-ray film of the occipital region showed the transverse sinus on the right side to be well outlined and of good size while no transverse sinus could be outlined on the left. CASE 3
K. S., a 48-year-old white man, in April, 1960, had a right radical neck dissection. His postoperative course was uneventful for approximately one month; then he began to notice double vision in the evening when he was tired. Examination six weeks after operation showed bilateral papilledema and a paresis of the right superior oblique muscle. The diplopia disappeared one month after it commenced and both discs had returned to normal five months after the
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W I L L I A M U M A R K A N D R O B E R T G. C H A M B E R S
papilledema was discovered. X-ray films of the skull showed the right lateral sinus to be well de fined, while the left was either absent or rudi mentary. His eyes were normal when he was last examined almost one year after his neck operation. DISCUSSION
The symptomatology of the two patients whose case studies have been given resembles that of pseudotumor cerebri in which con dition there is increased intracranial pressure without an intracranial neoplasm. Wagener 5 said the typical cerebral pseudotumor syn drome was characterized by bilateral papil ledema, a normal or smaller than normal ven tricular system and a cerebrospinal fluid normal except for increase in pressure. Patients in whom pseudotumor cerebri de velops often are under 30 years of age6 and appear in good health, with a clear mental state. Headache is the most common present ing complaint and Smith7 found this symp tom in 64 percent of his series. Nausea and vomiting are not uncommon. Paralysis of one or both abducens nerves may occur. The amount of papilledema varies and up to 11 diopters of papilledema has been reported.8 Visual acuity may be affected if the papill edema is severe or is of long duration. Constriction of the peripheral fields and enlargement of the blindspots may occur. After recovery visual acuity may return to normal or may be permanently reduced from secondary optic atrophy or macular changes secondary to prolonged macular edema. Re covery from pseudotumor cerebri often oc curs spontaneously. Therapy varies widely. In The Johns Hop kins Hospital it has been either no treatment, believing that recovery would ultimately oc cur, or subtemporal decompression when the severity of the papilledema threatens vision. Elsewhere repeated spinal fluid drainage has been advocated. Restriction of fluids, reduc tion of salt intake and the administration of Diamox or one of the newer carbonic anhydrase inhibitors have also been suggested. The etiology of pseudotumor cerebri is in many cases obscure and the subject further
confounded by the many different names given to the syndrome. Quincke9 may have been the first to describe some such cases under the eponym, serous meningitis. Nonne10 was the originator of the term, pseu dotumor cerebri, in 1904, and, interestingly enough, among the cases he reported was one in which the cause of the increased intra cranial pressure was found to be a throm bosis of the left transverse sinus in a patient who two years previously had had a left otitis media. Symonds11 reported similar cases as otitic hydrocephalus and McAlpine12 preferred the term, toxic hydrocephalus. Dandy13 referred to the syndrome as intra cranial pressure without brain tumor. In 1931, Symonds11 used the term, otitic hydrocephalus, to describe cases which usu ally occur in children who have had a recent aural infection, develop a squint, usually due to a sixth nerve paralysis, and complain of headache. On f unduscopic examination papil ledema is found and a lumbar puncture in the fully developed state shows the cerebro spinal fluid to be under increased pressure but clear and containing no excess of cells or protein. Symonds at first thought the affection was the result of an excessive se cretion from the choroid plexus or defective absorption through the arachnoid villi. In a later article,14 he agreed that, since the ven tricles were normal or smaller than normal, otitic hydrocephalus was a misnomer. After discussing confirmatory evidence, he con cluded that dural sinus thrombosis might be responsible for the symptom-complex. He studied several post-mortem cases and found that thrombosis of one lateral sinus alone could produce otitic hydrocephalus, but he was uncertain whether there might have been a contributory anatomic factor, such a s ' a smaller opposite lateral sinus. In three other autopsies he found obstruction to the venous outflow from the level of the torcular. Symonds has pointed out that thrombosis of the inferior petrosal sinus probably explains many cases of sixth nerve paralysis. McAlpine12 described cases similar to those
PSEUDOTUMOR CEREBRI SYNDROME reported by Symonds but they followed a nasopharyngeal infection as well as otitis media and he felt, therefore, that the adjec tive otitic was better replaced by the word "toxic" which carried a less specific impli cation as to the causative factor. Dandy13 reported 22 cases of what is here termed pseudotumor cerebri under the title "Intracranial pressure without brain tumor." All the patients he put into this category had elevated intracranial pressure, papilledema, normal or smaller than normal ventricles, and sixth nerve palsies were frequently present. In 1954, Zuidema and Cohen15 published a follow-up report on 12 of Dandy's cases. Ten individuals were living and well while two had died of causes not related to increased intracranial pressure. Ersner and Myers,16 in 1936, published a paper suggesting that the etiology of otitic hydrocephalus might be connected with ob literation of a lateral sinus. They briefly de scribed two cases in which signs of increased intracranial pressure developed following obliteration of the right lateral sinus. The symptoms were ameliorated by the use of magnesium sulfate, glucose intravenously and lumbar puncture. They also presented three other cases in detail; X-ray films re vealed one large lateral sinus with the op posite sinus much smaller in two of the cases. In the third case the X-ray film of the lateral sinuses was not mentioned. The three pa tients recovered following spinal drainage and removal of the irritative focus in the mastoid. Woodhall17 described the embryology and anatomic variations of the lateral sinuses and contiguous structures and reported the clinical symptomatology of thrombosis of one or more of the venous channels. One of the patients was a 46-year-old man with the his tory of right otitis media and mastoiditis three months previously. On admission the only neurologic finding was papilledema. Be cause of increased intracranial pressure a right subtemporal decompression was per formed. This was followed by pneumococcus
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meningitis and death occurred within a week. An autopsy showed the superior longitudinal sinus and the right lateral sinus into which it emptied to contain a partly organized thrombus. The left lateral sinus was patent but in size was less than half the diameter of the right sinus. Evidence that it is not unusual for the right transverse sinus to be the larger has been supplied by Woodhall.18 He studied variations of the cranial venous sinuses in the region of the torcular herophili in 100 consecutive autopsies in which the structures had not been damaged. He reported a rightsided predominance, with the larger volume of the superior sagittal sinus directed toward the right transverse sinus and the lesser vol ume of the straight sinus directed toward the left transverse sinus, in 39 percent of the cases. Left-sided predominance in which the larger superior sagittal sinus emptied into the left transverse sinus and the smaller straight sinus discharged into the right trans verse sinus was found in 13 percent. He also found a major disproportion between the transverse sinuses in 24 percent and the absence of one transverse sinus in four per cent. Woodhall19 later observed that roentgenograms of the occipital region demonstrated relative differences and variations in the size of the bony marking of the transverse sinuses which closely corresponded to his previous anatomic observations. In other words anteroposterior roentgenograms of the occipital bone showed markings due to the transverse sinuses from which it could be determined that the right transverse sinus was the larger with presumed right-sided predominance and that there existed a major disproportion between the sinuses in ap proximately the same percentages as he found in his autopsy studies. Ray and Dunbar,20 by sagittal sinus venography, were able to confirm that thrombosis of one or more of the dural venous sinuses could produce the symptom-complex of pseu dotumor cerebri.
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WILLIAM G. MARR AND ROBERT G. CHAMBERS
The method of dural sinus venography consists of the injection of 35-percent Diodrast into the anterior portion of the superior sagittal sinus via a catheter introduced into the sinus through a small midline burr hole, with appropriate roentgenograms. In the nor mal, the contrast medium passes backward through the superior sagittal sinus to the torcular herophili and thence through both transverse sinuses into the internal jugular veins. The cerebral veins and other dural sinuses do not fill unless there is some ob struction in the superior sagittal or trans verse sinuses. One of the patients described by Ray and Dunbar20 was a man who had an earache and purulent discharge from the right ear canal for two weeks. On the day of admission he had developed a high fever ( 4 0 ° C ) . Blood culture was positive ■ for Proteus vulgaris. Roentgenograms showed evidence of acute right mastoiditis. A right mastoidectomy was performed and the transverse venous sinus was found to contain an infected thrombus which was not removed. On antibiotic ther apy there was rapid improvement of the pa tient's condition but within a few days he began to experience blurred vision and gen eralized mild headache. There were about two diopters of papilledema bilaterally and a few small retinal hemorrhages. The neuro logic examination was otherwise normal. The spinal fluid pressure was 400 mm. H 2 0 and the fluid was clear, colorless and accellular. A sagittal sinus venogram showed complete obstruction of the right transverse sinus just lateral to the torcular herophili and a small left transverse sinus. The patient improved gradually and the headache, blurred vision and papilledema subsided steadily and had disappeared after two months. It was shown that the thrombus was limited to the right transverse sinus while the superior sagittal and the other small trans verse sinus were both patent. The develop ment of increased intracranial pressure points to the inadequacy of the remaining small left transverse sinus to compensate for
the obstruction of the opposite larger trans verse sinus. The subsidence of the signs and symptoms of elevated intracranial pressure were assumed to be due to the development of collateral circulation. This case resembles the otitic hydrocephalus cases described by Symonds ex cept that the state of good health, excluding the signs of increased intracranial pressure, occurred spontaneously in Symonds' cases while in Ray and Dunbar's case the rapid improvement in the patient's condition before papilledema developed was presumably due to the antibiotic treatment. Although Ray and Dunbar expressed the hope that sinus venography would show the majority of cases of pseudotumor cerebri to be due to thrombosis of one or more of the dural venous sinuses, additional studies did not support their original supposition. Ray,21 in 1955, reported that in less than half of the cases could obstruction of venous channels be demonstrated. There still remains a large group for which full explanation is lacking. An unusual and unexplained occurrence of pseudotumor cerebri has been seen in women in association with generalized edema appear ing at the menstrual period. Thomas22 de scribed two such cases and McCullagh23 re ported one. Both authors attributed the im provement in their patients to hormonal ther apy, which suggests an endocrine basis for the disorder. CONCLUSIONS
Following unilateral radical neck dissec tion for malignancy three patients developed signs and symptoms of increased intracranial pressure and other essential feautures which characterize pseudotumor cerebri. Because a malignant tumor had been excised, the pos sibility of intracranial metastasis was con sidered. Spontaneous clearing of the signs eliminated this probability. Since in our pa tients here reported major venous drainage channels had been obstructed, it seems ap parent that this accounted for the develop ment of a picture of pseudotumor cerebri.
PSEUDOTUMOR CEREBRI SYNDROME This concept is in agreement with studies made by Symonds, E r s n e r and Myers, Woodhall, and Ray and Dunbar. O u r patients had a large transverse sinus according to X-ray films and the internal jugular vein of the same side was ligated. T h e opposite transverse sinus could not be identified and may well have been small or absent. These
611
case reports supply additional evidence that the interruption of dominant dural sinus drainage may produce the picture of^pseudotumor cerebri. The Johns Hopkins Hospital (5), ACKNOWLEDGMENT
,,, ., ^ . , t „ ~ . „ We wish to express our gratitude to Dr. frank B. Walsh for help in preparation of this manuscript:
REFERENCES
1. Crile, G. W.: Carcinoma of the jaws, tongue, cheek and lips. Surg. Gynec. & Obstet., 36:159, 1923. 2. Sugarbaker, E. D., and Wiley, H. M.: Intracranial-pressure studies incident to resection of the in ternal jugular veins. Cancer, 4:242, 1951. 3. Anlyan, A. J., Browning, H. C, Black, S. P. W., Clifton, E. E., and Janzen, A. H.: Dural sinus studies in relation to radical operations of the neck. Surg. Forum, 1951, p. 300. 4. Jones, R. K.: Increased intracranial pressure following radical neck surgery. Arch. Surg., 63:599, 1951. 5. Wagener, H. P.: Pseudotumor cerebri. Am. J. Med. Sc, 227:214, 1954. 6. Dunn, J., Baker, G. S., and Wagener, H. P.: Pseudotumor cerebri: A review and report of four cases. Proc. Staff Meet., Mayo Clin., 30:505, 1955. 7. Smith, J. L.: Pseudotumor cerebri. Tr. Am. Acad. Ophth., 62:432, 1958. 8. Frazier, C. H.: Cerebral pseudotumors. Arch. Neur. & Psychiat., 24:1117, 1930. 9. Quincke, H.: Ueber meningitis serosa. Samml. Klin. Vort., N. F. Nr., 67 (Inn. Med. Nr. 23):655, 1893. 10. Nonne, M.: Ueber Falle vom Symptomenkomplex "Tumor cerebri" mit Ausgang in Heilung (Pseudotumor cerebri): Uber letal verlaufene Falle von "Pseudotumor cerebri" mit Sektionsbefund. Deutsche Ztschr. f. Nervenh., 27:169, 1904. 11. Symonds, C. P.: Otitic hydrocephalus. Brain, 54:55, 1931. 12. McAlpine, D.: Toxic hydrocephalus. Brain, 60:180, 1937. 13. Dandy, W. E.: Intracranial pressure without brain tumor. Ann. Surg., 106:492, 1937. 14. Symonds, C. P.: Otitic hydrocephalus. Neurology, 6:681, 1956. 15. Zuidema, G. D., and Cohen, S. J.: Pseudotumor cerebri. J. Neurosurg., 11:433, 1954. 16. Ersner, M. S., and Myers, D.: Otitic hydrocephalus with a suggestion as to etiology. Ann. Otol., Rhin. & Laryng., 45:553, 1936. 17. Woodhall, B.: Anatomy of the cranial blood sinuses with particular reference to the lateral. Laryngoscope, 49:966, 1939. 18. Woodhall, B.: Variations of the cranial venous sinuses in the region of the torcular herophili. Arch. Surg., 33:297, 1936. 19. Woodhall, B., and Seeds, A. E.: Cranial venous sinuses. Arch. Surg., 33:867, 1936. 20. Ray, B. S., and Dunbar, H. S.: Thrombosis of the dural venous sinuses as a cause of "pseudotumor cerebri." Ann. Surg., 134:376, 1951. 21. Ray, B. S.: Benign intracranial hypertension. In Cecil and Loeb: A Textbook of Medicine. Phila delphia, Saunders, 1959, ed. 10. 22. Thomas, W. A.: Generalized edema occurring only at the menstrual period. J.A.M.A., 101:1126, 1933. 23. McCullagh, E. P.: Menstrual edema with intracranial hypertension (pseudotumor cerebri). Clev. Clin. Quart., 8:202, 1941.