The Diagnosis and Treatment of Otitic Meningitis

Medical Clinics of North America September, 1937. Baltimore Number

CLINIC OF DR. lAMES

G.

ARNOLD, JR.

FROM THE DEPARTMENTS OF NEUROSURGERY AND NEUROLOGY, UNIVERSITY OF MARYLAND MEDICAL SCHOOL

THE DIAGNOSIS AND TREATMENT OF OTITIC MENINGITIS

THE most common cause of meningitis, excluding the meningococcic and tuberculous forms, is otitic infections. Otitis media is, therefore, a serious infection, primarily because of its complications. Prevention is the best treatment, and careful, understanding observation of every middle ear infection will lead to earlier recognition of the serious sequelae. The onset of an intracranial complication following a middle ear infection may develop almost immediately after the appearance of the otitis, or it may run a subacute course with relatively few symptoms other than draining ear, and a complication will become manifest at the time the patient is thought to be out of danger. In infants, the ear infection may easily be overlooked until after meningeal invasion has occurred. The course which a middle ear infection may take depends UpGjl the organism, its virulence, and the route of infection which it follows in the temporal bone. The infection may involve the labyrinth, the pneumatized mastoid cells, or the petrous pyramid. From these foci the infection may extend along thrombosed and infected vessels in the bone into the subarachnoid space and brain, and by direct invasion of the leptomeninges from the labyrinth. If the mastoid cells or petrous pyramid become infected, there may be a gradual necrosis of bone and dura, with extension of the infection into the subarachnoid space, brain, or lateral sinus. Therefore, the intracranial infection may be rapid when it travels by way of the labyrinth or infected vessels, and more deliberate when extension occurs through bone and dura. When the mode of exVOL. 2I-83

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JAMES G. ARNOLD, JR.

tension is retrograde through the vessels, there may be a rapid intracranial complication without any warning signal. Infections in the labyrinth produce signs of labyrin"thine irritation such as vertigo, vomiting, and nystagmus. When the infection takes a more deliberate route directly through bone, the patient usually shows evidence of definite mastoid infection, with pain and swelling of the ear and skin over the mastoid process and persistent discharge from the ear. However, this external evidence may be lacking in some mastoid infections and usually when the petrous pyramid is infected. Once an infection is thought to be present in the temporal bone, procrastination concerning operation may be the cause of an intracranial complication. The intracranial complications which may follow middle ear infection are meningitis, brain abscess, infective sinus thrombosis, epidural abscess, involvement of cranial nerves by local meningeal reaction, such as described by Gradenigo,I and nonsuppurative encephalitis. Occasionally the facial nerve may be paralyzed by necrosis of bone in the region of the facial canal. DIAGNOSIS

Any inflammatory reaction of the meninges may be termed a meningitis, but the fundamental differential is whether the meningeal reaction is sterile or whether it is due to the actual presence of bacteria in the subarachnoid space. A patient 81ay have all the clinical signs of meningitis with a pessimistic outlook only to find that the patient makes an uneventful recovery. The appearance of symptoms indicating meningeal invasion in a patient with an ear infection should be recognized as early as possible. Headache and mild rigidity of the neck, together with some degree of febrile rise are the earliest symptoms. It is during this period that eradication of the focus may be possible by operative procedure on the mastoid bone. If a mastoid operation has already been done the symptoms may indicate that a walled-off focus was not exposed in the original operation. The impression that the patient is doomed because of these early symptoms is entirely unwarranted, because it i~ often at this stage that the patient has a cellular reaction

DIAGNOSIS AND TREATMENT OF OTITIC MENINGITIS

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in the meninges without actual invasion by bacteria. As the infection spreads through bone to the epidural surface, there is a reactive process in the dura which attempts to wall off the infection with the formation of an epidural collection of pus. If this is not drained, the inner wall of the dura becomes involved in the extension and again inflammatory reaction is thrown out in advance of bacterial invasion, producing a sterile localized reaction of the leptomeninges. If the spinal fluid is examined at this stage, the cerebrospinal fluid pressure may be slightly increased and microscopic examination will show the presence of a few up to several thousand cells per cubic millimeter. The fluid should be cultured immediately and after culture the fluid centrifuged and smears made to determine the presence of bacteria. In this early stage of sterile meningeal reaction, no time should be lost in. attempting to find and eliminate the focus of infection. If operation has previously been done, a second exploration should be considered in the hope of finding a walled-off focus which was not removed at the first operation. Within twenty-four to forty-eight hours after the initial symptoms of headache and mild rigidity of the neck, the temperature begins to rise rapidly to a level around 104° F. to 105° F., the pulse becomes rapid, the <;ervical rigidity becomes increased, headache is severe, the patient becomes very restless with later development of delirium, there is a generalized hyperesthesia over the entire body, the Kernig sign is positive, and there may be cranial nerve palsies secondary to the meningeal reaction. At this stage, examination of the spinal fluid gives every indication of the actual presence of organisms in the subarachnoid space. The cell count ranges, as a rule, from 1000 to 5000, and in some instances may reach 35,000 to 40,000. The globulin is increased, the total protein ranges from 75 to 150 mg. per cent, and there is marked reduction or absence of spinal fluid sugar, and decrease in spinal fluid chlorides. The spinal fluid pressure usually ranges from 200 to 400 mm. of water. The cytology of the spinal fluid shows a predominance of polymorphonuclear leukocytes and smears show the presence of organisms. In a report by Neal, Jackson, and Applebaum2 on 231 cases of meningitis following otitis media and sinusitis, 121 were

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JAMES G. ARNOLD, JR.

due to streptococci, 75 to pneumococci, 20 to the influenza bacillus, and the remaining 15 to staphylococci, streptothrix, Bacillus coli, B. friedlanderi, and torula. TREATMENT

The treatment and prognosis depend upon whether the' meningitis is sterile or infective, and on the organism. Cultures should be taken from the ear at the time of paracentesis and from every mastoid operation so that if meningitis subsequently develops, the organism causing the ear infection will be known in case the spinal fluid is sterile. In all cases of sterile meningitis, the mastoid should be operated upon immediately, so that drainage may be instituted at the source of the infection. Spinal drainage should be done once or twice daily until clinical improvement occurs and the spinal fluid approaches normal. Hypotonic glucose, 0.45 per cent, from 500 to 1000 cc., given an hour before drainage will increase the flow of cerebrospinal fluid. By early recognition of the preinfective or sterile stage of meningitis, infective meningitis can often be prevented. Recoveries from infective otitis meningitis have been reported from time to tiVle, but this is accepted as a rarity. Dwyer 3 states that he has seen 367 cases of meningitis, with 18 recoveries. In a series of 623 cases of meningitis, excluding meningococcic and tuberculous types, Neal, Jackson, and Applebaum 2 state that 16 patients recovered. Of these, 121 cases were streptococcic infections due to otitis media, mastoiditis, and sinusitis, with 9 recoveries. The recent use of para-amino-benzene-sulfonamide in the treatment of streptococcic infections 4 , 5, 6, 7 is most encouraging. Approximately 50 per cent of all otitic meningitis is due to hemolytic streptococci, and if treatment is instituted early, recovery may be expected in this type in the majority of cases. Too few cases have been treated with the drug to arrive at definite conclusions, but in a series of 6 cases of hemolytic streptococcic meningitis and 2 cases of sterile meningitis secondary to streptococcic mastoiditis,s all recovered except 1. The following case illustrates the course and treatment of an ontic hemolytic streptococcic meningitis with recovery.

DIAGNOSIS AND TREATMENT OF OTITIC MENINGITIS

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S. B., white male, age seven, was admitted to the South Baltimore General Hospital on March 2, 1937. On February 25, 1937, the child had earache on the left side, with purulent discharge from the ear on the following day. Later in the afternoon the drainage from the ear ceased and a paracentesis was done. The child was sluggish, complained of headache, and was feverish. On March 2 he was very drowsy and was found to have marked cervical rigidity. The examination on admission showed mild delirium and marked rigidity of the neck. The skin was flushed and hot. A purulent discharge was present in the left external auditory meatus. There was some swelling over the mastoid tip with tenderness. The deep reflexes were present and active. The Kernig sign was positive. The patient was seen by Dr. Nathan Snyder and the diagnosis of mastoiditis with meningeal irritation was made. A left simple mastoidectomy was done and the mastoid cells were found to be necrotic and filled with a thin purulent exudate. The following morning a spinal fluid examination was done by Dr. Louis McIIhany, and the fluid was found to be cloudy, contained 13,760 cells, was under a pressure of 380 mm. of water, smear showed gram-positive cocci, and after culture a hemolytic streptococcus was identified. The patient was seen by Dr. Richard G. Coblentz and treatment was begun with sulfanilamide (para-amino-benzene-sulfonamide). The temperature course is shown in Fig. 87 and the treatment and laboratory findings are shown in Fig. 88. The patient showed an immediate improvement in the spinal fluid findings, but his clinical course was very stormy. On the fourth day after treatment was. begun he was definitely improved, showed less rigidity of the neck, and was more alert. On March 13 his temperature rose to 105 0 F., the mastoid incision was widened for better drainage, the patient appeared very toxic, and his neck was still quite rigid. On March 13 and 16 small transfusions were given. From this point on there was slow but gradual improvement with a gradual decline of the temperature by lysis, and after April 1 the temperature did not exceed 100 0 F. rectally. The drainage from the mastoid incision and ear gradually decreased and when he left the hospital on April 18 the wound was healed and the discharge from the ear had ceased entirely. Three weeks following discharge from the hospital, he was again examined and was found to be in excellent health, was gaining weight, and had no complaints.

From Fig. 88 it will be seen that in the treatment the drug was administered by the oral, subcutaneous, and intrathecal routes. At the beginning of treatment in meningitis, the oral administration cannot, as a rule, be relied upon because of the uncooperative state of the patient. The calculated daily dose should be given in two infusions of 1 per cent solution in normal saline, eight to twelve hours apart. In preparing the solution, the saIt solution should be brought to the boiling point and after cooling a few degrees, the powdered sulfanilamide added slowly. No further sterilization is necessary. The

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solution should be cooled to body temperature and given. The drug can be given by mouth in divided doses as soon as the patient is cooperative. In infants, the parenteral route will have to be employed.

13 20

JAMES G. ARNOLD, JR.

Concerning the intrathecal administration, the exact requirements have not yet been determined. In 7 of the 8 cases of streptococcic meningitis treated by me, the drug was given intrathecally once a day in a dose ranging from 25 to 50 cc. of a 1 per cent solution. This was continued until at least 3 negative spinal fluid cultures were obtained. In the case just described, 5 injections were given after the spinal fluid became negative, because of the stormy course. However, in 1 case of the series, only 1 intrathecal injection was given and the patient made a prompt recovery. In computing the dose, an average of 1 Gm. per 20 pounds of body weight every twenty-four hours has been advocated by Long. 6 Children will tolerate much larger doses, but whether this is necessary has not yet been determined. In two children weighing 50 pounds, 6 Gm. a day were well tolerated. The majority of patients receiving the drug will develop varying degrees of cyanosis, but this clears up rapidly after administration is stopped. A moderate anemia may develop after prolonged use, and in patients who have an idiosyncrasy to the drug, an occasional severe hemolytic anemia may occur, as shown by the excretion of urine of port-wine color. If acidosis occurs, alkalis should be administered. Therefore, during the treatment the hemoglobin, red count, carbon dioxide combining power, and urine should be carefully watched. As previously stated, the treatment of otitic meningitis depends Upon whether it is sterile or infective and the causative organism. The preliminary work on streptococcic meningitis indicates that a fair percentage of recoveries can be expected when treated by sulfanilamide, so that if the original otitis media or mastoiditis is known to be due to hemolytic streptococci, this drug should be employed. If the causative organism in the original infection is not known and the spinal fluid shows the absence of organisms, it would seem worth while to use sulfanilamide because of the high percentage of streptococcic infections in otitic meningitis. In dealing with streptococcic meningitis wheresulfanilamide therapy is used, the advisability of doing a mastoidectomy is an open one. The first case I treated had a severe mastoid infection, but the operation was deferred until after the spinal fluid cultures were ~gative. In another case, the mastoid was not operated upon

DIAGNOSIS AND TREATMENT OF OTITIC MENINGITIS

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and the prompt cessation of discharge from the ear and the recovery of the patient suggest that mastoidectomy may be unnecessary in hemolytic streptococcic infections. CIIARr SHOWING LAIlORATORY FINDINGS AND RECORD OF TRE~-·-----DATE (1~~7)

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If the original otitic infection is due to an organism other than hemolytic streptococci and the meningitis is still in the sterile stage, mastoidectomy should be done as early as possible. By so doing, the entrance of organisms into the subarachnoid space may be prevented.

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JAMES G. ARNOLD, JR.

If the meningitis is of pneumococcic etiology, sulfanilamide may be tried, but my experience in 2 cases is discouraging. Both of these patients showed a clinical course modified from the usual untreated pneumococcic meningitis, but death occurred in both cases. Patients with pneumococcic meningitis may recover occasionally with specific antipneumococcic serum and it may be worth while to combine serum and sulfanilamide. However, no satisfactory treatment for pneumococcic meningitis has yet been devised. Approximately 20 per cent of all otitic meningitis is due to organisms other than streptococci and pneumococci. Since there is no specific treatment, daily spinal drainage and general supportive treatment should be employed. BIBLIOGRAPHY 1. Gradenigo, G.: "Ober circumscripte Leptomeningitis mit spinalen Symptomen und iiber Paralyse des N. abducens otitischen Ursprungs, Arch. f. Ohrenh., 62: 255, 1904. 2. Neal, J. B., Jackson, H. W., and Applebaum,W.: A Comprehensive Study of Meningitis Secondary to Otitic or Sinus Infection, Ann. Otol., Rhin. and Laryngol., 43: 658, 1934. 3. Dwyer, J. G.: The Present Status of Otitic Meningitis, Laryngoscope, 46: 245, 1936. 4. Schwentker, F. F., Clason, F. P., Morgan, W. A., Lindsay, J. V., and Long, P. H.: Use of Para-amino-benzene-suIfonamide in the Treatment of Beta-Hemolytic Streptococcic Meningitis, Bull. Johns Hopkins Hosp., 60: 297, 1937. 5. Arnold, J. G., Jr.: Treatment of Hemolytic Streptococcic Meningitis with Para-amino-benzene-suIfonamide; Report of a Case, with Recovery, Ann. Int. Med., 10: 1198, 1937. 6. Long, P. H., and Bliss, E. A.: Para-amino-benzene-suIfonamide and Its Derivatives; Experimental and Clinical Observations on Their Use in the Treatment of Beta-Hemolytic Streptococcic Infection: a Preliminary Report, Jour. Amer. Med. Assoc., 108: 32, 1937. 7. Marshall, E. K., Jr., Emerson, K., Jr., and Cutting, W. C.: ParaaminobenzenesuIfonamide; Absorption and Excretion: Method of Determination in Urine and Blood, Jour. Amer. Med. Assoc., 108: 953, 1937. 8. Arnold, J. G., Jr.: Unpublished.