Journal of Neuro-Ophthalmology, March 1999, Volume 19, Issue 1

Optic Atrophy and Chronic Acquired Polyneuropathy

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic, multifocal disorder usually defined as limited to the peripheral nervous system. Multifocal motor neuropathy, an acquired demyelinating neuropathy with conduction block affecting motor neurons only, may be a pathogenically distinct syndrome or a predominantly motor variant of chronic inflammatory demyelinating polyneuropathy. Central nervous system demyelination including optic neuropathy has been reported uncommonly previously in these entities. We report two cases and review the literature on the possible association of optic neuropathy and chronic acquired polyneuropathy.

Journal of Neuro- Ophlhalmology 19( 1): 67- 69, 1999. © 1999 Lippincotl Williams & Wilkins, Inc., Philadelphia Optic Atrophy and Chronic Acquired Polyneuropathy Andrew G. Lee, M. D., Steven L. Galetta, M. D., Frederick E. Lepore, M. D., and Stanley H. Appel, M. D. Chronic inflammatory demyelinating polyneuropathy ( CIDP) is a chronic, multifocal disorder usually defined as limited to the peripheral nervous system. Multifocal motor neuropathy, an acquired demyelinating neuropathy with conduction block af­fecting motor neurons only, may be a pathogenically distinct syndrome or a predominantly motor variant of chronic inflam­matory demyelinating polyneuropathy. Central nervous system demyelination including optic neuropathy has been reported uncommonly previously in these entities. We report two cases and review the literature on the possible association of optic neuropathy and chronic acquired polyneuropathy. Key Words: Chronic inflammatory demyelinating polyneurop­athy- Optic neuropathy. Chronic inflammatory demyelinating polyneuropathy ( CIDP) is a chronic, multifocal disorder that has tradi­tionally been defined as limited to the peripheral nervous system. Multifocal motor neuropathy, an acquired demy­elinating neuropathy with conduction block affecting motor neurons only, may be a pathogenically distinct syndrome or a predominantly motor variant of CIDP. Scattered reports of central nervous system ( CNS) de­myelination in patients with CIDP and other chronic ac­quired demyelinating neuropathies have been increas­ingly reported in the literature, and the features may be indistinguishable from those of multiple sclerosis ( 1- 10). In addition, although optic neuropathy has been reported to occur rarely in some patients with CIDP, this finding has not been emphasized in the ophthalmologic literature ( 1- 10). The clinical criteria for the diagnosis of CIDP include a motor or sensory neuropathy affecting two or more Manuscript received April 21, 1998; accepted September 16, 1998. From the Departments of Ophthalmology ( A. G. L.), Neurology ( A. G. L., S. H. A.), and Neurosurgery ( A. G. L.), Baylor College of Medi­cine, Houston, Texas; the Department of Neurosurgery ( A. G. L.), M. D. Anderson Cancer Center, The University of Texas, Houston; the De­partment of Neurology ( S. L. G.), University of Pennsylvania Medical Center, Philadelphia; and the Department of Neurology ( F. E. L.), The University of Medicine and Dentistry, Robert Wood Johnson Medical School, New Brunswick, New Jersey, U. S. A. Address correspondence and reprint requests to Andrew G. Lee, M. D., Department of Ophthalmology, Baylor College of Medicine, 6565 Fannin Street, NC- 205, Houston, TX 77030, U. S. A. limbs that develops over a period of more than 2 months in the absence of toxic, systemic, or genetic causes of neuropathy; neurophysiological criteria of slowed nerve conduction into the demyelinating range, or conduction block; presence of demyelinated nerve fibers without vasculitis, amyloid, or storage disorder; and a normal cerebrospinal fluid cell count with increased protein con­centration. Weakness usually predominates over sensory loss, and cranial nerves are less often involved than in Guillain- Barre syndrome ( 11). We report two cases of acquired polyneuropathy ( one case of CIDP and one case of multifocal motor neurop­athy) associated with optic atrophy and review the lit­erature on the possible association of optic neuropathy and chronic acquired polyneuropathy ( 1- 10). CASE REPORTS Case One A 57- year- old woman was seen in our center in 1996 with bilateral peripheral lower extremity pain and weak­ness of the left foot. Her symptoms progressed over sev­eral months to include bilateral pain and paresthesia in the upper and lower extremities and areflexia. Her medical history was significant for hypothyroid­ism that had been well controlled with replacement therapy for 25 years, hypertension, borderline diabetes, and diverticulosis. Her surgical history was significant for removal of a ganglion cyst, removal of a left benign breast mass, and removal of a fatty benign tumor from her back. She did not drink alcohol or smoke tobacco. Her family history was negative for hereditary motor or sensory neuropathy. Her medications included 40 mg oral prednisone per day alternating with 10 mg per day, levothyroxine, amitriptyline, omeprazole, esterified es­trogen and methyltestosterone, and triamterene/ hydro­chlorothiazide. She had had acute onset of visual loss of the left eye ( LE) in October 1996. In April 1997, exami­nation revealed visual acuity of 20/ 20 right eye ( RE) and 20/ 25 LE. There was a dense nasal arcuate defect LE and a normal visual field RE. Visual evoked potential ( VEP) showed reduced amplitude and a delayed PI00 wave form LE and was normal RE. Findings in a magnetic 67 68 A. G. LEE ET AL. resonance ( MR) scan of the head were normal. Electro­myography ( EMG) and nerve conduction study results were consistent with moderate distal and proximal de­nervation of the legs and arms bilaterally with no fas-ciculations. There was abnormal sensory conduction in the lower extremities. There was mild proximal slowing in motor conduction in the arms and slightly slow sen­sory conduction. In May 1997, a sural nerve biopsy was performed, and analysis revealed severe depopulation of myelinated nerve fibers. The clinical diagnosis of CIDP was made. Analysis of cerebrospinal fluid obtained by lumbar puncture showed elevated protein of 66 mg/ dl, white blood cells 6/ mm3, increased 7- globulin, and two bands of immunoglobulin-' Y on high- resolution electrophoresis. The remainder of the cerebrospinal fluid was unremark­able. In July 1997, the patient was treated with intrave­nous immunoglobulin. In August 1997, visual acuity was 20/ 25 RE and 20/ 50 LE. A diagnosis of optic neuritis was made, and she was treated with intravenous steroid therapy followed by an oral taper. On examination on September 16, 1997, visual acuity was 20/ 25 RE and 20/ 30 LE. The pupils were equal, with a slightly dimin­ished light reaction in both eyes and a left relative affer­ent pupillary defect. Motility was normal. Slit lamp biomicroscopy produced normal findings. Intraocular pressure measurements by applanation were 26 mm Hg in each eye. Visual field testing by kinetic Goldmann perimetry revealed generalized constriction, a superior arcuate defect, and several paracentral scotomas RE. Vi­sual field testing of the LE revealed a superior paracen­tral defect and an inferior nasal defect extending into central fixation. Ophthalmoscopy revealed a cup- to- disc ratio 0.6 RE and 0.8 LE and pallor in the remaining neuroretinal rim of each optic nerve. A neurologic examination showed mildly increased tone throughout. Motor examination indicated mild weakness ( 4+/ 5) of the right deltoid and the muscles of the left arm, mild weakness ( 4+/ 5) of the iliopsoas bilat­erally, and moderate weakness of the ankle flexors and ankle extensors ( 3+/ 5). Sensory examination revealed decreased response to pinprick, temperature, light touch, and vibration and decreased proprioception in the ex­tremities below the elbows and midthighs. Magnetic resonance scan of the head revealed mucosal thickening in the right ethmoid and sphenoid sinuses, consistent with sinusitis and a sphenoethmoidal muco­cele. There was mild enhancement of the right optic nerve after gadolinium contrast administration. A diag­nosis of bilateral optic neuropathy with superimposed glaucomatous disc cupping was made. Topical glaucoma drops applied twice daily was prescribed. In October 1997, the patient underwent functional endoscopic sinus surgery with drainage of a sphenoethmoidal mucocele. On October 13, 1997, she underwent intravenous immu­noglobulin therapy ( 66 g for 2 days). On last examination in February 1998, the patient's condition remained un­changed with stable visual acuity, visual field defects, and ophthalmologic examination. Case Two A 52- year- old woman was well until 1990 when weakness developed in her left upper extremity. Her medical history was significant for removal of a chon-droid hamartoma from the right lung. Her medications were estrogen and progesterone replacement therapy. She did not drink alcohol or smoke cigarettes, and she was not exposed to any known toxins. Her family history was negative for hereditary neuropathy. Analysis of a specimen obtained in a left biceps muscle biopsy in December 1993 revealed neurogenic atrophy. In February 1994, a lumbar puncture yielded normal findings, except for cerebrospinal fluid protein of 65 mg/ dl. Bone marrow examination showed mild ery-throid hyperplasia. In May 1994, nerve conduction and EMG showed motor neuropathy with multifocal conduc­tion block consistent with multifocal motor neuropathy. Erythrocyte sedimentation rate and vitamin B] 2 level were normal. In August 1995, the patient experienced the acute onset of visual loss RE associated with pain during eye movement. Visual acuity was 20/ 80 RE and 20/ 30 LE. An MR scan of the head revealed mild enhancement of the right optic nerve after the administration of gad-olinium- diethylenetriamine pentaacetic acid ( DTPA). A diagnosis of optic neuritis RE was made. The patient declined treatment with intravenous steroids. Vision in the RE worsened over the next several months to counting fingers on September 19, 1995. A right afferent pupillary defect was present. Ophthalmos­copy revealed optic atrophy RE and a normal optic disc LE. On October 3, 1995, further visual loss developed LE associated with eye pain. Visual acuity was 20/ 60 RE and 20/ 400 LE. Goldmann kinetic perimetry revealed a central field loss in the LE greater than that in the RE. The diagnosis of acute optic neuritis LE was made, but the patient declined therapy. Her vision LE gradually improved. On November 21, 1995, visual acuity was 20/ 30 RE and 2/ 200 LE; on December 5, 1996, 20/ 30 RE and 20/ 70 LE; and in February 1997, 20/ 50 RE and 20/ 70 LE. The pupils were sluggish bilaterally to light stimu­lus, and there was a left afferent pupillary defect. Visual field testing revealed a bilateral central scotoma. Results of an extraocular motility examination were normal. Ophthalmoscopy revealed bilateral optic atrophy. Motor examination showed normal strength bilaterally in the extremities. Sensory examination was normal to primary modality testing. Results of coordination and reflex test­ing were normal. On May 13, 1997, visual acuity was 20/ 60 RE and 7/ 200 LE. Visual field testing revealed a small absolute central scotoma RE and a large absolute central scotoma LE. Results in the remainder of the ex­amination were unchanged. In May 1997, analysis of cerebrospinal fluid obtained in a lumbar puncture showed protein of 84 mg/ dl, no pleocytosis; the remainder of the findings were normal. The patient was treated with 1 g per day intravenous methylprednisolone for 4 days. In August 1997, visual acuity was 20/ 60 RE and 6/ 200 LE. Visual field testing revealed improvement in the previous central scotomas bilaterally. ./ Neuro- Ophthaimol, Vol. 19, No. 1, 1999 OPTIC ATROPHY IN CHRONIC POLYNEUROPATHY 69 DISCUSSION Although CIDP has traditionally been described as affecting the peripheral nervous system ( 11), there is increasing evidence of CNS involvement in this disorder ( 1- 10). Ophthalmoplegia is well described in Guillain- Barre syndrome ( 12), and some reports have described cranial nerve involvement in CIDP. Optic nerve involve­ment, however, is uncommon in CIDP ( 1- 10). In addi­tion, patients with Guillain- Barre syndrome may expe­rience optic neuritis, which may be evidence of CNS involvement in acquired inflammatory polyneuropathy ( 12). Rubin et al. ( 8) in 1987 reviewed five reports from the literature and reported two additional cases of com­bined centra] and peripheral myelinopathy. In these seven eases, three patients had evidence of optic neurop­athy. Lewis et al. ( 4) reported five patients with multi­focal demyelinating neuropathy with persistent conduc­tion block, two of whom had subacute visual loss, central scotomas, optic atrophy, and prolonged VEPs. Pakalnis et al. ( 7) reported 18 patients with CIDP who had undergone visual and brain stem- evoked potentials and MR imaging of the brain to assess for evidence of CNS demyelination ( 7). Nine ( 50%) of these 18 patients had an abnormal evoked potential, 5 patients ( 28%) had demyelination on MR scan of the brain, and 3 patients ( 17%) had clinical evidence of optic neuritis. Uncini et al. ( 9) reported evoked potentials and MR scan results in eight patients. The VEP was abnormal in six of these patients ( 75%). One of these six patients had bilateral optic neuritis followed 4 weeks later by Guillain- Barre syndrome and a second relapse several years later. Oph­thalmoscopy in two patients revealed bilateral optic at­rophy, and two additional patients had enlargement of the blind spot detected in visual field testing. Two pa­tients had demyelinating lesions on MR scan. Feasby et al. ( 1) reported one abnormal VEP in eight patients with CIDP, but that patient had no clinical evidence of optic neuropathy. Mendell et al. ( 5) reported 6 of 16 patients with clini­cal features of CIDP and multiple sclerosis, some of whom had presumed demyelinating lesions on MR scan. They reported periventricular, subcortical, and brainstem white matter lesions indistinguishable from those seen in multiple sclerosis in 6 of 16 patients with CIDP. Three of these patients had a prolonged VEPs and a history of optic neuritis. Ormerod et al. ( 6) reported MR abnormali­ties consistent with CNS demyelination in 14 of 28 pa­tients with CIDP. Gigli et al. ( 2) reported four patients ( seven eyes) with an abnormal VEP. Bilateral optic at­rophy was noted in one of these four patients ( 2). Both our patients had enhancement of the optic nerve on MR scan, supporting an inflammatory cause of optic nerve dysfunction. To date, neither patient has shown evidence of a more widespread CNS demyelinating pro­cess. It is not clear whether immunosuppressive therapy had any beneficial effect on their visual function. In our patients, extensive evaluations for other causes of optic neuropathy and polyneuropathy were performed and were negative. Toxic ( e. g., heavy metal), systemic inflammatory ( e. g., sarcoidosis or polyarteritis nodosa), or hereditary diseases may affect the optic and peripheral nerves. Clinicians should screen patients appropriately for these alternative causes before making the diagnosis of optic neuropathy associated with chronic acquired polyneuropathy. In most instances, the clinical history and the electromyographic findings should be sufficient to allow the diagnosis of the previously mentioned alter­native causes of optic atrophy and polyneuropathy. In summary, we report two cases of acquired polyneu­ropathy ( one case with criteria of CIDP and one case of multifocal motor neuropathy) associated with optic atro­phy. Although the condition is uncommon, clinicians should be aware of the possible association of optic neu­ropathy and these chronic acquired polyneuropathies ( I - 10). REFERENCES 1. Feasby TE, Hahn AF, Koopman WJ, cl al. 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