Journal of Neuro-Ophthalmology, September 1998, Volume 18, Issue 3

Pachymeningitis with Mulitple Cranial Neuropathies and Unilateral Optic Neuropathy Secondary to Pseudomonas aeruginosa

Hypertrophic cranial pachymeningitis is a rare disorder that frequently presents with multiple cranial neuropathies. This disorder, which is characterized by thickening and infiltration of the cranial dura, can result from a variety of inflammatory and infectious conditions. A patient with hypertrophic cranial pachymeningitis is described in whom meningeal biopsy and bacterial cultures of the biopsy specimen revealed Pseudomonas aeruginosa. The authors believe this to be the first documented case of pachymeningitis secondary to this organism.

Joiinitil of Nnm>-(> iihlhtilnmhK\ I HIM: I'M 2( 1( 1. IVVH. (:> 1W8 l. ippinmll Williams A Wilkins. Philadelphia Pachymeningitis With Multiple Cranial Neuropathies and Unilateral Optic Neuropathy Secondary to Pseudomonas aeruginosa Case Report and Review Christopher A. Girkin, M. n., Julian D. Perry, M. D., Neil R. Miller, M. D., and Stephen G. Reieh, M. D. Hypertrophic cranial pachymeningitis is a rare disorder that frequently presents with multiple cranial neuropathies. This disorder, which is characterized by thickening and infiltration of the cranial dura, can result from a variety of inflammatory and infectious conditions. A patient with hypertrophic cranial pachymeningitis is described in whom meningeal biopsy and bacterial cultures of the biopsy specimen revealed I'seuclanio-nas aeruginosa. The authors believe this to be the first docu­mented case of pachymeningitis secondary to this organism. Key Words: Pachymeningitis- Cranial nerve palsy- Pseu-domas aeruginosa-- Optic neuropathy. Hypertrophic cranial pachymeningitis is a rare disor­der characterized by diffuse or local thickening and in­flammation of the dura that often presents with multiple cranial neuropathies. Although several causal agents have been identified, most cases arc idiopathic ( 1). We describe a patient with multiple cranial neuropathies caused by chronic progressive pachymeningitis second­ary to Pseudonioiuts aeruginosa. To our knowledge, this is the first case of pachymeningitis caused by this organ­ism. CASK REPORT A 60- year- old man with a prior history of gastritis and peptic ulcer disease, who had undergone treatment for suspected tuberculosis in 1988, was healthy until Febru­ary 1995. when he began to have difficulty walking, which resulted in several falls, and gradually increasing hoarseness associated with progressive hearing loss. Manuscript received October 1997; accepted february 1998. from the Departments of Ophthalmology ( C. A. C. .1.1). P.. N. R. M.) and Neurology ( N. R. M. S. Ci. k.). The Johns Hopkins Medical Institu­tions. Baltimore. Maryland. U. S. A. Address correspondence and reprint requests to Neil R. Miller. M. D.. The Johns Hopkins Hospital. Maumenee B- 109. 600 North Wolle Street. Baltimore. Maryland 2 12X7- 9204. U. S. A. Presented in part at the 2Xth annual frank B. Walsh meeting. Salt fake City, Utah, february 10 I I. 1996. Over the next month, the patient began to experience difficulty swallowing that progressed until he could not cat solid foods. Me was examined by an otolaryngologist who found left vocal cord paralysis and bilateral hearing loss. He w; ts referred to an internist and admitted for a neurologic workup in March 1995, when he was found to have a left esotropia with limited abduction of the left eye, diffuse facial weakness, bilateral hearing loss, bilat­eral biceps and deltoid weakness, and deviation of the tongue to the left. Magnetic resonance imaging of the head and neck showed diffuse atrophic changes of the brain and areas of low density in the while matter. In addition, there was severe cervical spondylosis with ste­nosis extending from C- 4 to T- l. A lumbar puncture revealed a normal opening pressure, with a glucose of 67 mg/ dl, protein of 57 mg/ dl, two white cells, a negative cryploeoccus antigen, and negative cultures for bacteria including Mycobacterium litberculo. sis. The patient was evaluated by a neurosurgeon who did not recommend spinal decompression, and the patient received it percu­taneous gastrostomy for his dysphagia. He was also started on a trial of pyridostigmine bromide ( Mestinon, Roche Laboratories, Nutley, New Jersey) for presumed myasthenia gravis, despite a negative acetylcholine an­tibody test, and was discharged from the hospital. The patient's condition worsened, and he was referred to a neurologist at The Johns Hopkins Hospital in June 1995. At this point he had a " large" esotropia with limitation of abduction of the left eye, bilateral facial weakness, bilateral hearing loss, and a decreased gag reflex: he could barely speak above a whisper. He had no visual complaints other than diplopia. He had normal acuity, lull visual fields, no relative afferent pupillary defect, and normal- appearing ocular fundi. His upper ex­tremity weakness had slowly worsened and was now associated with fasciculations. The patient continued to lose weight despite regular tube feedings, and his dysphagia, dysphonia, and hearing progressively worsened. In kite August 1995, the patient noticed drooping of his right eyelid that progressed to complete ptosis over several days. When he raised the lid. he could not see from the right eye. He contacted his neurologist and was admitted for further workup. 196 PACHYMENINGITIS FROM PSEUDOMONAS AERUGINOSA 197 The patient was examined in the Neuro- Ophthal-mology Unit of The Johns Hopkins Hospital on Septem­ber 9, 1995. At that time, he had no light perception in the right eye, and visual acuity of 20/ 30 in the left. Color vision was 8.5/ 10 by Hardy- Rand- Rittler plates on the left, and the visual field of the left eye was full by kinetic perimetry. The right pupil was 5 mm and nonreactive to direct light stimulation, and the left pupil was 3 mm and briskly reactive to light. There was a marked relative afferent pupillary defect in the right eye, complete ptosis of the right eyelid, and a slight esotropia. The right eye was completely immobile; the left eye exhibited marked reduction in abduction, moving only slightly past the midline, but had full elevation, depression, and adduc­tion. Corneal and cutaneous sensation was diminished in the V1 and V2 distributions on the right side. Hertel measurements were 22 on the right and 20 on the left with a base of 99. The patient had bilateral facial weak­ness and profound hearing loss such that he could barely hear shouted speech. Slit- lamp biomicroscopy revealed early cataracts and normal optic disks, maculae, and pe­ripheral retina in both eyes. The patient was thought to have a cranial polyneuropathy consisting of a complete right 3rd nerve palsy; a right 4th nerve palsy; bilateral 6th nerve palsies; a partial right 5th nerve palsy; bilateral 8th, 9th, and 10th cranial nerve palsies; a left 12th nerve palsy, and a right optic neuropathy presumed secondary to an orbital apex syndrome. Repeat magnetic resonance imaging of the brain re­vealed dural thickening around the right sphenoid ridge, petrous apex, and clivus, with enhancement after gado­linium infusion, and marked bony destruction of the cli-noids and petrous bone ( Fig. 1). A soft- tissue density, which enhanced after gadolinium infusion, was infiltrat­ing the right cavernous sinus and the right orbital apex ( Fig. 2). A lumbar puncture yielded clear cerebrospinal fluid with one monocyte. Cerebrospinal fluid glucose was 90 mg/ dl and protein was 37 mg/ dl. The fluid was negative for cryptococcus antigen and Borrelia burgdor­feri. Bacterial and fungal cultures were negative. A pu­rified protein derivative was placed and was negative. Lyme titers and syphilis serology were both negative as was human immunodeficiency virus ( HIV) testing. An angiotensin- converting enzyme level was obtained and was normal. Computed tomography of the chest and ab­domen were both normal. The patient was empirically placed on corticosteroids at 60 mg/ d with no improve­ment. The patient underwent a right frontotemporal craniot­omy and a meningeal biopsy of the right subfrontal dura, which was thick and red. Pathologic examination of the biopsy specimen disclosed acute and chronic nongranu­lomatous inflammation associated with gram- negative intracellular bacteria. The morphology of the bacteria was consistent with a Pseudomonas species ( Fig. 3), and cultures of the tissue grew P. aeruginosa. A computed tomography scan of the skull and temporal bones was performed to localize a route of entry for this organism. This showed bilateral mastoid fluid collections with no bony erosion or middle ear involvement, although the clivus showed evidence of destruction ( Fig. 4). The pa­tient was examined by an otolaryngologist who found no abnormalities other than hearing loss and bilateral vocal cord paralysis. Tobramycin ( 100 mg every 8 hours) and ceftazidime ( 3 g every 8 hours) were started for pre­sumed Pseudomonas pachymeningitis, and the patient improved markedly during a 4- week course of antibiot­ics. His dysphagia completely resolved, and he was able to eat solid food. His gait, although still slightly ataxic, was greatly improved to the point that he used his cane only occasionally. His dysphonia improved partially, his right third and sixth nerve palsies completely resolved, . etiYK/ i- Qcp FIG. 1. Magnetic resonance imaging of the brain and skull base. A: Axial, unenhanced, T1 - weighted image demonstrates destruction of the petrous area ( asterisks). B: Axial, gadolinium- enhanced, T1- weighted image shows enhancement and thickening of the basilar dura ( arrowheads). J Neum- Oplillmliiml, Vol. 18. No. 3, 1998 198 C. A. GIRK/ N ET AL. FIG. 2. Magnetic resonance imaging of the right orbit. A: Axial, gadolinium- enhanced, T1- weighted image shows enhancing material in the posterior orbit ( arrowheads). Note that the right optic canal is diffusely thickened and that abnormal enhancing material surrounds the optic nerve and extends into the posterior ethmoid and sphenoid sinuses ( asterisks). B: Coronal, T1- weighted, gadolinium- enhanced image shows diffuse enhancement of the posterior right orbit ( asterisk), as well as enhancement of the right subfrontal dura ( arrowhead). and his vision improved to hand motions in the right eye. However, he still could not abduct the left eye past the midline, and his hearing loss progressed to complete deafness. DISCUSSION Pachymeningitis refers to a well- circumscribed area of chronic inflammatory dural thickening. The term is somewhat misleading in that the arachnoid and pia are also involved in the inflammatory response, and all three meningeal layers become fused by dense fibrotic mem­branes. Patients usually present, as ours did, with mul­tiple progressive cranial neuropathies ( 1). The optic nerves and orbital apex are occasionally involved, de­pending on the location of the lesion ( 2). Generally, with optic nerve involvement, the visual prognosis is poor, but there has been one case report of visual recovery after surgical decompression of the optic nerve in idiopathic pachymeningitis ( 3). Magnetic resonance imaging typically reveals well-circumscribed hyperintense laminar thickening of the dura with enhancement after intravenous infusion of gad-olinium- diethylenetriamine- pentaacetic acid or a similar paramagnetic agent ( 4). This appearance is often similar to meningioma en plaque, and when the systemic workup is nondiagnostic, craniotomy with meningeal biopsy is required to differentiate the various causes of pachymen­ingitis from meningioma and meningeal carcinomatosis. The first case of pachymeningitis was reported by Charcot and Joffroy in 1869 and was attributed to syphi­lis ( 5). Since that time, several cases have been reported secondary to a variety of traumatic ( 6), infectious, au­toimmune, and toxic causes ( see Table 1). However, FIG. 3. Meningeal biopsy. A: Low- power view shows thickening and inflammatory infiltration. B: At higher magnification, many gram-negative rods are evident ( arrowheads). .1 Ni'iim- Ophlliaimcil, Vol. 18. No. .1. 1998 I'A CI I) MliNINC UTIS I- ROM PSPAUX) MONAS A ERUCINOSA 199 FIG. 4. Unenhanced, axial, computed tomography scan, bone-window density, shows bilateral fluid collections in the mastoid air cells ( asterisks), as well as extensive destruction of the clivus ( arrowheads). most cases remain idiopathic ( I ). Infectious causes in­clude syphilis ( 7), tuberculosis ( 8), and fungi such as Aspergillus Jhivus (*•)). I'eiriellidium hovtlii ( 10). Pseudtillescheria hoxdii ( 11). and Candida iropieidis ( 12). Bacterial causes of pachymeningitis have included one reported case caused h\ Propionihaelerium a< ne\ ( 13) and diffuse eraniocervical pachymeningitis associated with an epidural empyema secondary to /'. aerui'inosa ( 14). The condition has occasionally been associated \\ ith bacterial sphenoid and ethmoid sinusitis ( 4. \ 5). and in one case it was associated with otitis media thai re­sponded to antibiotics ( 16). In addition, two cases of pachymeningitis were reported in patients with periph­eral lymphocytosis with an increase in helper/ inducer T- cells. elevated anlihuman T- ccll lymphocyte virus- 1 ( HT1. V- I) antibody tilers, and increased loads of proviral i III A I 1)\ A with no other underlying infectious or autoimmune disease ( 17). Pachymeningcal inflammation can be caused by a va­riety of noninfectious inflammatory autoimmune disor­ders, including sarcoidosis ( 18). rheumatoid arthritis ( 19), Wegener's granulomatosis ( 20). temporal arteritis ( 21). periarteritis nodosa ( 22). and mixed connective tis­sue disease ( 23). In addition, many authors suggest that idiopathic hypertrophic inlcrcranial pachymeningitis, like fibrosing pseudotumor and the Tolosa- I lunl syn­drome, mav be a manifestation of multifocal librosclc-rotic disease ( 24). finally, pachymeningitis has been re­ported alter intraspinal injection of methylprcdnisolone acetate ( 25). Our case of hypertrophic cranial pachymeningitis was caused by P. aeruginosa, which was identified in the biopsy specimen and cultured from tissue samples. No clear- cut route of entry for the organism was apparent. and an extensive evaluation both radiographically and clinically was negative for a contiguous source. There was no evidence of systemic immunosuppression, in­cluding IIIV infection. Pseudouumas aeruginosa is a rare cause of meningitis that accounts for (•>'/< to \ 2'/< of all gram- negative bacte­rial meningitis ( 2d). It is most frequently seen in patients who arc immunosuppressed. or who have undergone neurosurgical procedures and have ventricular shunt, drains, or reservoirs ( 27). Pseudomonas meningitis also occurs in patients with chronic otitis media, after exten­sive head and neck surgery, and after spinal anesthesia ( 28). Malignant external otitis media, caused bv Pseudomo­nas anil progressing to osteomyelitis of the temporal bone, has been described both clinically and pathologi­cally ( 2(), 30). Although no obvious route of entry was identified in our patient, we believe it likely that his infection originated from a previous episode of untreated otilis media that progressed to osteomyelitis of the skull base with secondary pachymeningitis. This is consistent with the bilateral mastoid fluid collections and destruc­tion of the clivus that were noted on neuroimaging. This would also explain why hearing was affected initially (. luring the course of the disease. Our patient's cranial nerve function showed marked improvement over the 4- weck course of antibiotics. This, along with ( he meningeal biopsy results, helped confirm that Pseudomonas was the cause of his pachymeningitis and was not simply an associated colonization. To our knowledge, this is the first reported case of pachymen­ingitis secondary to /'. aeruginosa. As previously nicn- TABI. h I. ('{> iiili! ion\ ( issti( iiilcil with i> i! rh\ nn'nin^ ius I. I'raunialic II. Infectious A liacienal I . Pn> i> ionthti< U'riuni < u lies . V Psnulallitmtis cicrn^ ititKsti C Trcpoiinuti pallidum I. A/ vioh, i< I, mini luhi i, if/ nvA H I- IIIUMI I. .\ s/> cri! ilhi\ flnviis 1. Prlrii'lliuiii bovilii . v I'scihlullc-,, In- iiu hti\, lii •\ Caihlhhi li'npicalis ( ' . Viral I. Hamuli ' I ' lymphotropic virus type 1 III. Inflammatory V khcumaioid animus H. Naicoidosis ( ' . Sinusilis/ Oiilis media 1). Wegener's j. Miinulnnialusis I' fpidural cmp\ cum Is Temporal ailcruis ( i . I'criarlcrilis nodosa II. Mixed conncclive tissue disease I. Multifocal hhrosclcrolic disease 1 ( libit, il pseudoiumoi . V I'olosa- l lunl syndrome IV. Toxic A. Intraspinal injection ol' nielh) Iprednisolone acelaie V. Idiopathic / V ; . . , . Oplilhulni. ii 1',./ IS. \,, <. IWS 200 C. A. GIRKIN ET AL. tioned, Uemura et al. ( 14) reported a case of diffuse cranial pachymeningitis associated with an empyema due to the same organism; however, the meningeal in­flammation in their case was reactive and secondary to a localized infection, not to diffuse infiltration of the me­ninges. Our case emphasizes that the primary concern in the evaluation of a patient with pachymeningitis is searching diligently for an underlying cause. 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