Hearing loss in carcinomatous meningitis By MELVIN C. ALBERTS and

CHRISTOPHER F. TERRENCF

(Pittsburgh, Pennsylvania) Introduction IN 1900, Saenger was the first to report deafness as a consequence of carcinomatous meningitis, with infiltration of the acoustic nerve in the subarachnoid space by metastatic tumour. Since this early report, there have been a number of clinical and pathologic reports noting hearing loss in carcinomatous meningitis, but except for the series of Oshiro and Perlman (1965), which dealt mainly with deafness due to meningcal infiltration from primary glial tumours, no report has stressed hearing loss as a presenting complaint in carcinomatous meningitis. In this communication, we will report on the clinical features of five patients who presented with hearing loss as the first manifestation of cytologically proven leptomeningeal carcinomatosis. Two cases are presented in detail and all the cases are briefly summarized in Table I. Case reports Case 1. A 48-year-old man was admitted to the hospital complaining of hearing loss and unsteadiness when walking. He had been in good health until 2i months prior to admission when he gradually developed fairly constant pain in the right hip radiating into the leg unrelieved by analgesics. Approximately two weeks prior to admission, he developed a loud buzzing sound in his right ear associated with a constant periauricular headache. He rapidly developed rightsided hearing loss which over the next two days became bilateral. One week prior to hospitalization he developed hoarseness of his voice and also began to complain of dysphagia for both solids and liquids. He also noted recent onset of numbness over the right face, drooping of the right corner of the mouth and inability to close the right eye. Past history revealed that he had been a heavy drinker for several years, consuming up to a fifth of whiskey daily and had also smoked 1J packs of cigarettes daily for 30 years. The patient admitted to a 20 lb weight loss over the past two months and recent onset of shortness of breath. General physical examination revealed dullness to percussion and decreased breath sounds over the right mid-thorax. He also had clubbing of the fingernails but the remainder of the general examination was unremarkable. Neurologic testing revealed a right peripheral facial weakness, bilateral deafness, droop of the soft palate on the right with preservation of the gag reflex, and profound dysarthria. He had bilateral atrophy of the tongue, greater on the left, with deviation to the left on protrusion. He was unable to swallow solid foods due to inability to propel food into the posterior pharynx and attempts to swallow liquids caused nasal regurgitation. He also had weakness of muscles innervated 233

Bilateral deafness

Bilateral hearing loss

Bilateral hearing loss and tinnitus

Bilateral hearing loss and tinnitus

74/M

50/M

62/M

N.P. ••- Not performed.

Deafness on left, high frequency loss on right

Bilateral tinnitus, left-sided hearing loss, occipital headache

64,/F

Otologic testing

Bilateral deafness

Right peripheral VII nerve palsy

Undifferentiated of lung

Primary tumour

Bilateral sensoryneural loss. No response to calorics bilaterally

Unknown

Adenocarcinoma of lung

Unknown

Profound neurosensory Unknown loss on left; high frequency neurosensory loss on right; ENG's bilaterally weak

Right V nerve, bilateral Bilateral neurosensory hearing loss peripheral VII nerve palsies; dysmetria left arm; positive straight leg raising on left

None

Right peripheral VFr N.P. nerve, IX nerve, X nerve, bilateral XII nerve palsies; weakness L6 myotome on right; positive Babinski

Associated neurologic findings

Deafness on left, partial Left peripheral VII N.P. hearing loss on right nerve palsy, hoarseness, dysphagia, absent gag leflex

Bilateral deafness

Right tinnitus, bilateral hearing loss, right periauricular headache

48/M

Otologic findings

1

Presenting complaint

Age/Sex

Patient

SUMMARY OF CASES

TABLE I

O

m

o

d

>

as m 7*

n

a

to

HEARING LOSS IN CARCINOMATOUS MENINGITIS

235

by the fifth lumbar root on the right and straight leg raising was positive at 45°. There was a positive Babinski sign noted on the right and the remainder of the examination was unremarkable. Admission chest X-ray revealed a right hilar mass and tissue obtained from bronchoscopy was interpreted as undifferentiated carcinoma. Lumbar puncture revealed 21 white blood cells, 6 polymorphonuclear leukocytes, and 15 lymphocytes with protein of 109 and glucose of 49. Simultaneous blood sugar was 99 and cytology was negative. A repeat lumbar puncture was positive for malignant cells and he was begun on intrathecal methotrexate and irradiation to the brain and lumbar subarachnoid space. No definite improvement in neurologic symptoms was noted and he was later discharged to his home. He subsequently was readmitted with bilateral aspiration pneumonitis and died the following day. A post mortem examination was unfortunately refused by the family. Case 2. A 64-year-old woman was admitted to the hospital with a history of decreased hearing in the left ear. She had been in good general health until four months prior to admission when she developed gradual onset of decreased auditory acuity on the left. She also complained of a dull constant occipital headache for the three months prior to hospitahzation and two weeks before admission developed tinnitus in the right ear. The general physical examination revealed no abnormalities. Neurological examination revealed essentially no hearing on the left. Rinne was positive on the right and the Weber test lateralized to the right. The remainder of the examination was unremarkable. Admission laboratory studies including chest X-ray and skull films with tomograms of the petrous bone were unremarkable. During the first four days of hospitalization, her hearing on the right decreased and by the time of audiogram she had a high frequency neurosensory loss on the right and a profound neurosensory loss on the left. Electronystagmography revealed bilaterally weak responses. Posterior fossa myelogram revealed no filling of the internal auditory canal on the left and it was felt that exploration was indicated. A transcortical labyrinthectomy was performed and the internal auditory canal explored. It was filled with a large tumour mass which, when traced laterally, was felt to be oedematous eighth nerve. This was partially decompressed in its vertical position and petrous end. Neurology consultation following surgery suggested the diagnosis of carcinomatous meningitis and numerous lumbar punctures were performed. The results are summarized in Table II and, although cytologies were suspicious for malignancy, it was felt that the cerebrospinal fluid (CSF) pleocytosis could be secondary to surgery. A search was made for a primary tumour site with a chest X-ray, upper and lower gastrointestinal series, intravenous pyelogram, proctoscopy, and mammography but no malignancy was found. She was discharged to be followed by her private physician. Two months later she was readmitted and was found to have bilateral deafness, right peripheral facial paresis, right hemiparesis and right homonymous hemianopia. A lumbar puncture at this time revealed pleocytosis, hypoglycorrachia, and cytology positive for malignant cells. She was begun on steroid therapy and a marked improvement was noted in her hemiparesis. The patient received a total of 30 mg of intrathecal methotrexate without obvious benefit and the family declined radiation therapy.

4 5

3

5P.I7L 4P.16L 4P.24L

120 80

N.R.

0

N.R.

160 145 160

1P.10L 6P,35L 4P.40L 10P.140L 2P.28L 5P.45L

22L

N.R. N.R. N.R. N.R.

165

6P,15L 2P,40L

Cell count

N.R.

N.R. = Not recorded. N.P. — Not performed. P = Polymorphonuclear leukocytes. L — lymphocytes.

9/27/76 10/13/76 10/18/76 11/9/74 11/17/74 11/21/74 1/6/75 2/2/73 2/8/73 7/26/73 8/7/73 8/11/73 10/10/73

1

2

Date

Patient

Opening pressure (mm CSF)

TABLE II

— — — — — — — — — — — —

Culture (bacterial, fungal, AFB) 109 109 124 45 40 47 56 172 188 206 37 33 96

Protein

SPINAL FLUID RESULTS

49 50 53 65 60 62 33 61 51 70 72 74 90

Glucose

110 136

N.P. N.P.

127

N.P.

126

N.P. N.P. N.P.

99 97 100

Simultaneous blood glucose

— — —

+ Adenocarcinoma -1- Adenocarcinoma

t —

N.P. Suspicious Suspicious

+

+ Adenocarcinoma

Cytology

m

>o m

p

O

g . ALB

HEARING LOSS IN CARCINOMATOUS MENINGITIS

237

Review of cases

Five cases of carcinomatous meningitis presented to the University of Pittsburgh Health Center during the period 1971-1976 as progressive hearing loss. Although all cases initially began unilaterally, a rapid progression to bilateral deafness occurred in all but Case 2. Tinnitus was noted in four offivecases, but headache, felt to be the most common initial symptom by Olson et al. (1974), was present in only two cases and was localized to the occipital or periauricular region rather than being diffuse. None of our patients demonstrated nuchal rigidity although Case 1 had limitation of straight leg raising indicating lumbar root irritation. All patients demonstrated a peripheral facial palsy at some point in their illness presumably due to the close proximity of cranial nerves VII and VIII during their course through the subarachnoid space. In all cases where they were obtained, caloric responses demonstrated bilateral ear weakness and audiometry revealed severe neurosensory loss. Review of the cerebrospinal fluid studies in Table II indicate that a pieocytosis is common with cell counts usually below 100 and consisting predominantly of lymphocytes. The initial cytology was not always diagnostic of malignancy as evidenced by Case 2 who had three lumbar punctures negative for malignant cells. However, neoplastic cells were finally found on her second admission. This is in agreement with Olson et al. (1974) who stated that over 90 per cent of their patients required two or more lumbar punctures and only 37 of 50 had positive cytology even after multiple lumbar punctures. The positive cytological specimen obtained from the CSF of Case 1 is shown in Figure 1. Hypoglycorrachia (less than 60 per cent of blood glucose) was present in three of five cases. CSF protein elevation was variable with a range of 37 to 206 although it tended to be elevated in direct proportion to the severity and duration of the disease. Elevated opening pressure (200 mm CSF or above) was not noted in any of our cases. Discussion

Involvement of the leptomeninges by metastatic carcinoma has been described numerous times since the initial description by Oppenheim and Bettleheur in 1888. The clinical features of carcinomatous meningitis have been divided into four major syndromes by Jacobs and Richland (1951) on the basis of whether the involvement of the meninges is focal or diffuse. These clinical manifestations are: (1) meningeal irritation, (2) increased intracranial pressure, (3) multiple cranial nerve palsies, and (4) organic mental syndromes. They attribute the first two to diffuse involvement of the leptomeninges, the third to infiltration of the meninges at the base of the skull and the organic mental syndrome to parenchymal invasion along perivascular channels. Olson et al. (1974) feel that the majority of patients with cerebral symptoms are suffering from communicating hydrocephalus rather than direct parenchymal invasion although other factors such as

238

M. C. ALBERTS AND C. F. TERRENCE

FIG. 1 Clusters of malignant ceils with abundant vacuolated cytoplasm and some with prominent nucleuli (Papanicolau's stain, mag. about x 1800).

electrolyte abnormalities or ischemic neuronal damage may play a role. The diagnosis of leptomeningeal carcinomatosis is usually first entertained when the patient develops cranial nerve palsies as the other manifestations are often neither specific nor dramatic. Although most authors have commented upon cranial neuropathy, Rubinstein's (1969) series records only one case with hearing loss. In the largest series to date (Olson et ah, 1974), only three of fifty cases presented with hearing loss; Jacobs and Richland (1951) report one of four cases with eighth nerve involvement. In our series approximately ten per cent of patients with carcinomatous meningitis seen at the University of Pittsburgh Health Center over a fiveyear period presented with progressive hearing loss. The clinical features of our cases may be summarized as follows: (1) hearing loss is initially unilateral and associated with tinnitus; (2) unilateral hearing loss rapidly progresses to severe bilateral involvement; (3) audiometric and caloric studies reveal severe eighth nerve impairment; (4) facial nerve palsy is commonly noted at the time of hearing loss. In contrast, hearing loss due to cerebellopontine angle tumours is slowly progressive and, with the exception of neurofibromatosis, is usually unilateral. Bilateral deafness and

HEARING LOSS IN CARCINOMATOUS MENINGITIS

239

CSF protein elevation may be seen in Refsum's disease and the neuropathy of Dejerine-Sottas but again slow progression and the presence of associated neuropathy should aid in diagnosis. Granulomatous meningitis may present with cranial neuropathy but hearing loss is unusual except in sarcoidosis (Wiederholt and Siekert, 1965) and spinal fluid cytology and culture should establish the aetiology of the basilar inflammatory reaction. Spread of nasopharyngeal carcinoma through basilar foramina may cause cranial neuropathy but hearing loss is uncommon, Cytologic examination of the CSF is the single most important aid in establishing the diagnosis of leptomeningeal carcmomatosis. The need for multiple lumbar punctures has been stressed by several authors and an initial negative cytology does not rule out the diagnosis. Other findings on CSF examination in order of frequency are: (1) elevated protein, (2) mild cellular pleocytosis, predominantly lymphocytic, (3) hypoglycorrhachia, (4) elevated opening pressure (Olson et a!., 1974). This pattern of CSF abnormalities is similar to our series, and at no time did any patient have a completely normal lumbar puncture. Several mechanisms have been advanced to explain the invasion of the leptomeninges by carcinoma: (1) haematogenous metastases to the choroid plexus and secondarily to the leptomeninges, (2) primary haematogenous metastases through leptomeningeal vessels, (3) spread via Batson's venous plexus, (4) retrograde dissemination of tumour along perineural lymphatics and sheaths, (5) centripetal extension along perivascular lymphatics, (6) secondary spread from epidural or parenchymal metastases. Recently Gonzalez-Vitale and Garcia-Bunucl (1976) have demonstrated extensive tumour infiltration of endoneural, perineural, and perivascular lymphatics and sheaths up to the intervertebral foramina in all cases in which lumbosacral plexuses and peri vertebral soft tissues were examined. They also demonstrated tumour in ten of eleven choroid plexuses examined but felt this was secondary to meningeal infiltration. Direct spread of tumour from leptomeningeal vessels has been well demonstrated in leukaemia (Price and Johnson, 1973), but probably plays less of a role in carcinomatous infiltration. Meningeal spread of tumour from parenchymal metastases does not fit the criteria of leptomeningeal carcinomatosis agreed upon by most authors. Oshiro and Perlman (1965) have reported on the mechanism of involvement of the labyrinth from subarachnoid tumour infiltrates. Of their five cases, three were primary glial tumours, one was a lymphosarcoma and one a renal adenocarcinoma. They noted the tumour infiltrates filling the internal auditory canal, infiltrating the facial nerve to the geniculate ganglion where the subarachnoid space ends. The middle ear and mastoids were free of tumour. The characteristic rapid hearing loss can be explained by tumour infiltration of the nerve until vascular compromise occurs in the rigid internal auditory canal. Similar findings were noted by Grabscheid in an earlier report published in 1949. 5A

240

M. C. ALBERTS AND C. F. TERRENCE

The treatment of leptomeningeal carcinomatosis must be different from that for intracerebral metastases since the entire neuraxis is involved by tumour. Posner (1977) has advocated local radiation therapy to the site of neurologic symptoms accompanied by intrathecal administration of methotrexate and/or cytosine arabinoside. An Ommaya reservoir is recommended over lumbar puncture as the preferred route of drug instillation as this allows more uniform drug dispersal and does not have the 5-10 per cent failure rate of lumbar injection. Bramlet et a!. (1976) have advocated oral l-(2-chlorethyl)-3-cyclohexyl-l-nitrosourea (CCNU) as an adjunct to methotrexate therapy as this drug, when administered systemically, crosses the blood brain barrier due to its high degree of lipid solubility. Several authors have reported striking improvement in patients following therapy although the rule is insidious progression (Domasch et ctL, 1976; Little et ai, 1974; Moberg and Reis, 1961). Since untreated patients usually succumb within six weeks of diagnosis, a trial of therapy is certainly justified. In our experience, the presentation of a patient with the rapid progression of bilateral hearing loss with associated cranial nerve palsies, particularly peripheral facial palsy, is characteristic of carcinomatous meningitis. Although other basilar meningitidies may mimic this presentation, examination of the cerebrospinal fluid with special attention to cytology should aid in diagnosis. Since a negative cytologic examination does not exclude leptomeningeal carcinomatosis, repeated lumbar punctures must be performed until a diagnosis is established. Treatment must be begun immediately since mildly affected patients tend to respond better than those more severely affected. Hearing loss, when complete, will probably not improve as the nerve has already been destroyed by neurovascular compression. Summary

Although the syndrome of carcinomatous meningitis presenting as multiple cranial neuropathies is well known, hearing loss as a presenting complaint has not been previously stressed. Five cases of carcinomatous meningitis beginning as hearing loss are presented and the clinical and laboratory features discussed. A thorough review of the literature summarizes the pathology, pathogenesis and recommended modes of therapy of this disease and the importance of early diagnosis and treatment is stressed. Acknowledgement

We wish to thank Dr. G. R. Rao for the preparation and interpretation of the cytology in Case 1. REFERENCES BRAMLET, D . , GILIBERTI, J,, and BENDER, J. (1976) Neurology, 26, 287.

DOMASCH, D., PRZUNTEK, H., GRUNGER, W., arid MERTENS, H. G. (1976) European Neurology,

14, 178. GONZALEZ-VITALE, J. C , and GARCIA-BUNUEL, R. (1976) Cancer, 37, 2906.

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GRABSCHEID, E. (1949) Archives of Otolaryngology, 49, 547. JACOBS, L. L., and RICHLAND, K. J. (1951) Bulletin of The Los Angeles Neurological Society, 16, 335. LITTLE, J. R., DALE, A. J., and OKAZAKI, H. (1974) Archives of Neurology, 30, 138.

MOBERG, A., and REIS, G. V. (1961) Acta Medica Scandinavica, 170, 747. OLSON, M. E., CHERNIK, N. L., and POSNLR, J. B. (1974) Archives of Neurology, 30, 124. OPPENHEIM, and BETTLEMIUK (1888) Charite-Armalen, 13, 339.

OSHIRO, H., and PKRLMAN, H. B. (1965) Archives of Otolaryngology, 81, 328. POSNER, J. B. (1977) Seminars in Oncology, 4, 81. PRICE, R. A. and JOHNSON, W. W. (1973) Cancer, 31, 520.

RUBINSTEIN, M. K. (1969) Annals of Internal Medicine, 70, 49. SAENGER, A. (1900) Munehener Medizinische Wochenschrift 47, 341. WIEDERHOLT, W, C , and SibKLRT, R. G. (1965) Neurology, 15, 1147. M. C. Alberts, Neurology Service, Veterans Administration Hospital, University Drive C, Pittsburgh, PA 15240, U.S.A.

Hearing loss in carcinomatous meningitis.

Hearing loss in carcinomatous meningitis By MELVIN C. ALBERTS and CHRISTOPHER F. TERRENCF (Pittsburgh, Pennsylvania) Introduction IN 1900, Saenger w...
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