- Email: [email protected]
Acute Sensorimotor Polyneuropathy With Tonic Pupils and an Abduction Deficit
SURVEY OF OPHTHALMOLOGY VOLUME 43 • NUMBER 4 • JANUARY–FEBRUARY 1999
AFTERIMAGES JONATHAN WIRTSCHAFTER, EDITOR
Acute Sensorimotor Polyneuropathy With Tonic Pupils and an Abduction Deficit: An Unusual Presentation of Polyarteritis Nodosa JEFFREY L. BENNETT, MD, PHD,1 VICTORIA A. PELAK, MD,1 ZISSIMOS MOURELATOS, MD,2 SHAWN BIRD, MD,1 AND STEVEN L. GALETTA, MD1 Departments of 1Neurology and 2Pathology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA Abstract. A tonic pupil may occur in isolation or as part of a systemic disorder. We report a patient who developed tonic pupils and an abduction deficit in the setting of polyarteritis nodosa. The combination of a tonic pupil and an abduction deficit should suggest the possibility of a vasculopathic disorder, because the ciliary ganglion and lateral rectus muscle are both supplied by the lateral muscular artery. Widespread small artery and arteriolar narrowing and occlusion are the hallmarks of polyarteritis nodosa. Unusual ischemic syndromes may occur, such as this rare combination of neuro-ophthalmic signs, by involvement of both the nutrient artery and its collaterals. We are unaware of other reports of neuropathic tonic pupils in association with polyarteritis nodosa. (Surv Ophthalmol 43:341–344, 1999. © 1999 by Elsevier Science Inc. All rights reserved.) Key words. abducens palsy • Guillain-Barré syndrome • Miller–Fisher syndrome • peripheral neuropathy • polyarteritis nodosa • tonic pupils • vasculitis
fore admission, he noted the acute onset of distal right arm weakness that was soon followed by left arm weakness. Several days later, he noted a transient erythematous rash over his arms, face, and trunk. Two days before admission, the patient experienced the onset of bilateral lower extremity weakness and the acute onset of mild arthralgias and myalgias. At the time of presentation, he was unable to walk without assistance. He denied any recent illnesses, fever, unusual workplace exposures, or illicit substance use. His medical history was significant for an episode of Guillain-Barré syndrome (GBS) 15 years earlier after an immunization. During his illness, he required mechanical ventilatory support;
Neuro-ophthalmologic signs and symptoms commonly accompany inflammatory and noninflammatory neuromuscular disorders. The tempo and character of these neuro-ophthalmologic problems may often provide invaluable clinical information to direct future diagnostic studies. Here, we report a case of acute peripheral neuropathy in which the subsequent development of an abduction deficit and neuropathic tonic pupils directed the appropriate diagnostic tissue biopsies for vasculitis.
Case Report A 47-year-old man was admitted to the hospital because of progressive limb weakness. Two weeks be341 © 1999 by Elsevier Science Inc. All rights reserved.
0039-6257/99/$19.00 PII S0039-6257(98)00047-2
342
Surv Ophthalmol 43 (4) January–February 1999
his recovery was complete over a 1- to 2-year period. There were no pupillary abnormalities noted at that time. On examination, blood pressure was normotensive and pulse was regular. There was a mild diffuse livedoid rash on his back and chest. Acuity at near was J1 OD and J11 OS. Visual fields were full, pupils were sluggishly reactive to light, and ocular ductions were full. Nondilated funduscopic examination was normal. He had a mild facial diplegia, and he had severe bilateral upper extremity weakness (1-3/5) and moderate bilateral lower extremity weakness (3-4/5), worse distally. Reflexes were absent and there was diminished sensation to pinprick and temperature to the level of the knees and forearms, bilaterally. The gait was wide-based. A comprehensive chemistry panel was remarkable only for an alanine aminotransferase level of 112 U/L (normal, 0-40 U/L), aspartate aminotransferase level of 54 U/L (normal, 0-36 U/L), and gamma glutamyltransferase level of 303 U/L (normal, 8-78 U/L). Urine heavy metal screen was negative, and urine collection was negative for porphyrins. Lumbar puncture revealed a glucose level of 59 mg/dL, protein level of 39 mg/dL, and one white blood cell. Nerve conduction studies (NCSs) on the second hospital day showed a severe sensorimotor polyneuropathy with axonal loss and no demyelinating features. Electromyography (EMG) showed evidence of very acute neurogenic changes in all weak muscles studied. There was a predominance of normal motor unit potentials (MUPs) recruited in discrete patterns with rapid firing rates. Mild, chronic denervation was seen in a few distal leg muscles. The patient was started on intravenous immunoglobulins at 2 g/kg over 5 days for presumed GBS. On hospital day 10, lumbar puncture, NCSs, and EMG were repeated. The cerebrospinal fluid was acellular with a protein level of 73 mg/dL; NCSs and EMG studies were unchanged. On hospital day 24, the patient complained of worsening upper extremity weakness, back pain, and difficulty urinating. He was noted to have lost 5 to 6 pounds since admission. Neurologic examination showed 0 to 2/5 strength in the left arm and 1 to 3/5 strength in the right arm. Leg strength was unchanged. The right pupil was now noted to be unreactive. Magnetic resonance imaging of the cervical spine and brain were unremarkable. Repeat NCSs showed evidence of severe sensory and motor axonal loss, without demyelinating features. In the arm muscles studied, there was the appearance of markedly polyphasic MUPs of increased duration, consistent with new collateral sprouting. Laboratory studies revealed an erythrocyte sedimentation rate of 56 mm/ hr (normal, 0-15 mm/hr); rheumatoid factor, nega-
BENNETT ET AL
tive; cryoglobulins, negative; antinuclear antibody 1: 160 (normal, , 1:160); antineutrophil cytoplasmic antibody, , 1:8 (normal, , 1:8); C3/C4 complements, normal; rapid plasma reagin, negative; and hepatitis B surface antibody, positive. The patient continued to lose weight (a total of 10-15 pounds over 6 weeks), and on hospital day 40, he complained of increasing weakness and diplopia in lateral gaze. Neuro-ophthalmologic examination revealed 5-mm pupils, which were unreactive to light with a tonic near response (Figs. 1A and 1B). Administration of 0.125% pilocarpine induced pupillary constriction in both eyes (Fig. 1C). Abduction was limited in the right eye. He was orthophoric in left gaze. By Maddox rod testing, he had a 4-prism diopter (D) esotropia in primary gaze that increased to 8 D in right gaze. Vertical eye movements were normal. Funduscopic examination was normal. With concern for a vasculitic cause, nerve (sural) and muscle (gastrocnemius) biopsies were performed. Both specimens revealed evidence of vasculitis with chronic inflammatory cells and polymorphonuclear cells surrounding vessels and within vessel walls (Fig. 2). In the muscle biopsy specimen, there was evidence of vessel wall destruction. The nerve showed marked axonal degeneration on paraffin and teased fiber preparations. Residual muscle fibers were severely atrophied and necrotic debris was abundant (Fig. 2). The clinical history and histologic features of the biopsy specimens established the diagnosis of polyarteritis nodosa (PAN). Therapy was initiated with intravenous methylprednisolone (1 g/day for 5 days) followed by oral prednisone (1 g/kg) and monthly intravenous cyclophosphamide (800 mg/m2). The patient’s strength improved moderately during the subsequent 30 days. The patient’s double vision resolved within 2 weeks, but his tonic pupils persisted. Repeat Maddox rod testing revealed a 2-D exophoria at distance.
Discussion Polyarteritis nodosa is a necrotizing arteritis that affects medium and small arteries.12 Because of the variable location of the affected vessels, the clinical manifestations of PAN are quite diverse. Multiple organ systems may be involved, including the nervous system, kidneys, skin, digestive tract, heart, and eyes. Systemic symptoms are frequently reported at the onset of disease; however, they may be absent when the illness is restricted to the nervous system,8 skin,29 muscle,29 or eye.27,32 There are no diagnostic tests for PAN, although a large proportion of patients are hepatitis B virus-positive and 80% of those with microscopic artery involvement are antineutrophil cytoplasmic antibody-positive.18,26 Diagnosis is ulti-
ACUTE SENSORIMOTOR POLYNEUROPATHY
343
Fig. 1. Neuropathic tonic pupils in a patient with a sensorimotor neuropathy. A: The pupils were unreactive to light stimulation. B: The pupils responded tonically to a near stimulus. C: On instillation of dilute 0.125% pilocarpine, the pupils showed marked constriction.
mately made by biopsy in conjunction with clinical history.21 Neurologic symptoms, particularly peripheral neuropathy, are common in PAN and may dominate the clinical picture.11,24,29 Ocular symptoms, however, are much rarer (10–20% of cases), although they may occur in isolation early in the course of the disease.16,32 Ophthalmologic and neuro-ophthalmic manifestations of PAN are protean and include chorioretinitis, neuroretinitis, optic neuropathy, chiasmal arachnoiditis, ocular motor palsies, uveitis, episcleritis, and corneal ulcers.10,16 The most common ophthalmoscopic finding in PAN is retinopathy
Fig. 2. Gastrocnemius muscle biopsy (hematoxylin and eosin, 3 200). Microscopic examination shows a dense perivascular inflammatory infiltrate with effacement of the arterial wall. Arrows indicate neutrophils that have marginated and infiltrated the vessel wall. In the periphery of the specimen, fat replacement of atrophic muscle is present.
secondary to renal hypertension4; the choroidal vessels are most frequently involved on pathologic examination.14 Sluggish pupils have been reported in association with PAN, but no documentation was made of light-near dissociation in that case.4 A critical juncture in our patient’s course was the development of an abduction deficit and neuropathic tonic pupils. Tonic pupils are defined by the presence of three characteristic findings: poor or absent contraction to light, full contraction to near response with slow and delayed redilation, and constriction in response to conjunctival instillation of a dilute solution of pilocarpine (0.125%).22 Tonic pupils may result from either injury to postsynaptic cholinergic neurons in the ciliary ganglion, their projections to the ciliary body and iris, or their preganglionic innervation.17,22 Independent of the exact localization of the lesion, the final common insult entails denervation of the ciliary body and iris because of degeneration of second-order parasympathetic neurons in the ciliary ganglion.23 Because of the varied localization of the lesion, the causes of tonic pupils are myriad. When conjoined with a peripheral neuropathy, however, the list is more limited: GBS and its Miller-Fisher variant,19,31 vasculitides,1,6,7,15,30 infection,3 paraneoplastic neuropathy,2 and certain degenerative and hereditary sensorimotor and autonomic neuropathies.13,28,33 Therefore, although our patient’s tonic pupils and abduction deficit were consistent with the preliminary diagnosis of GBS, the relative rarity of these findings in the GBS, the stepwise progression of his deficits, the persistent axonal pathology on electrophysiologic studies,5,20 and the modest elevation in the sedimentation rate pointed to an alternative vasculopathic cause. Given the thrombotic mechanism of PAN, we concluded that the likely cause of our patient’s tonic pupils was ischemia to the ciliary ganglion or short ciliary nerves. In this regard, it is interesting that our pa-
344
Surv Ophthalmol 43 (4) January–February 1999
tient had a concomitant abduction deficit because both the ciliary ganglion and the lateral rectus muscle receive a portion of their blood supply from the trunk of the lateral muscular artery.9 Currie and Lessell6 proposed a similar mechanism for tonic pupils associated with temporal arteritis. Definitive diagnosis in our case was made only after nerve and muscle biopsy. Said et al25 examined retrospectively the value of nerve and muscle biopsy in corroborating the diagnosis of PAN and found that independent of the presence of multisystem disease, muscle biopsy in combination with nerve biopsy significantly improved diagnostic sensitivity from roughly 60% to 80%. Similarly, in our case, although both tissue samples revealed signs of vascular inflammation, only muscle tissue showed arteries with focal destruction of the vessel wall. Therefore, despite a clinical presentation limited to peripheral neuropathy, the muscle biopsy proved invaluable in the diagnostic evaluation.
References 1. Bachmeyer C, Zuber M, Dupont S, et al: Adie syndrome as the initial sign of primary Sjögren syndrome. Am J Ophthalmol 123:691–692, 1997 2. Bell TAG: Adie’s tonic pupil in a patient with carcinomatous neuromyopathy. Arch Ophthalmol 104:331–332, 1986 3. Bennett JL, Mahalingam R, Wellish MC, Gilden DH: Epstein Barr virus associated acute autonomic neuropathy. Ann Neurol 40:453–455, 1996 4. Boeck J: Ocular changes in periarteritis nodosa. Am J Ophthalmol 42:567–577, 1956 5. Bouche P, Leger JM, Travers MA, Cathala HP, Castaigne P: Peripheral neuropathy in systemic vasculitis: clinical and electrophysiologic study of 22 patients. Neurology 36:1598– 1602, 1986 6. Currie J, Lessell S: Tonic pupil with giant cell arteritis. Br J Ophthalmol 68:135–138, 1984 7. Davis RH, Daroff RB, Hoyt WF: Tonic pupil after temporal arteritis. Lancet 1:822, 1968 8. Dyck PJ, Benstead TJ, Conn DL, et al: Nonsystemic vasculitic neuropathy. Brain 110:843–853, 1987 9. Eliskova M: Blood vessels of the ciliary ganglion in man. Br J Ophthalmol 57:766–772, 1973 10. Galetta SL: Vasculitis, in Newman NA, Miller NR (eds): Walsh and Hoyt’s Clinical Neuro-Ophthalmology, ed V, vol 3. Baltimore, Williams & Wilkins, 1998, pp 3744–3752 11. Guillevin L, Le Thi Huong D, Godeau P, Jais P, Wechsler B: Clinical findings and prognosis of polyarteritis nodosa and Churg-Strauss angiitis: a study in 165 patients. Br J Rheumatol 27:258–264, 1988 12. Guillevin L, Lhote F, Gherardi R: Polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: clinical spects, neurologic manifestations, and treatment. Neurol Clin 15:865–886, 1997 13. Hedges TR, Gerner EW: Ross’ syndrome (tonic pupil plus). Br J Ophthalmol 59:387–391, 1975
BENNETT ET AL 14. Henkind P, Gold DH: Ocular manifestations of rheumatic disorders: Natural and iatrogenic. Rheumatology 4:13–59, 1973 15. Hoyle C, Ewing DJ, Parker AC: Acute autonomic neuropathy in association with systemic lupus erythematosus. Ann Rheum Dis 44:420–424, 1985 16. Jabs DA: The rheumatic diseases, in Ryan J, Schachat AP, Murphy RP (eds): Retina, vol 2. St Louis, CV Mosby, 1994, pp 1421–1444 17. Jacobson DM: Pupillary responses to dilute pilocarpine in preganglionic 3rd nerve disorders. Neurology 40:804–808, 1990 18. Jennette JC, Wilkman AS, Falk RJ: Anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and vasculitis. Am J Pathol 135:921–930, 1989 19. Keane JR: Tonic pupils with acute ophthalmoplegic polyneuritis. Ann Neurol 2:393–396, 1977 20. Kissel JT, Slivka AP, Warmolts JR, Mendell JR: The clinical spectrum of necrotizing angiopathy of the peripheral nervous system. Ann Neurol 18:251–257, 1985 21. Lightfoot RW Jr, Michel BA, Bloch DA, et al: The American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Arth Rheum 33:1088–1093, 1990 22. Loewenfeld IE, Thompson HS: The tonic pupil: a re-evaluation. Am J Ophthalmol 63:46–87, 1967 23. Loewenfeld IE, Thompson HS: Mechanism of tonic pupil. Ann Neurol 10:275–276, 1981 24. Moore PM, Fauci AS: Neurologic manifestations of systemic vasculitis: A retrospective and prospective study of the clinicopathologic features and responses to therapy in 25 patients. Am J Med 71:517–524, 1981 25. Said G, Lacroix-Ciaudo C, Fujimura H, Bas C, Faux N: The peripheral neuropathy of necrotizing arteritis: a clinicopathological study. Ann Neurol 23:461–465, 1988 26. Sergent JS, Lockshin MD, Christian CL, Gocke DJ: Vasculitis with hepatitis B antigenemia: long-term observation in nine patients. Medicine 55:1–18, 1976 27. Stillerman ML: Ocular manifestations of diffuse collagen disease. Arch Ophthalmol 41:239, 1951 28. Takase Y, Takahashi K, Takada K, Tatsumi H, Tabuchi Y: Hereditary motor and sensory neuropathy type 1 (HMSN1) associated with cranial neuropathy: an autopsy case report. Acta Neurol Scand 82:368–373, 1990 29. Tervaert JWC, Kallenberg C: Neurologic manifestations of systemic vasculitides. Rheum Dis Clin North Am 19:913–940, 1993 30. Victor DI, Green WR, Stark WJ, Walsh FB: A non-permanent tonic pupil in rheumatoid arteritis. Can J Neurol Sci 4:209– 212, 1977 31. Williams D, Brust JC, Abrams G, Challenor Y, Devereaux M: Landry-Guillain-Barré syndrome with abnormal pupils and normal eye movements: a case report. Neurology 29:1033– 1040, 1979 32. Wise GN: Ocular periarteritis nodosa: report of two cases. Arch Ophthalmol 48:1–11, 1952 33. Young RR, Asbury AK, Corbett JL, Adams RD: Pure pan-dysautonomia with recovery: description and discussion of diagnostic criteria. Brain 98:613–636, 1975
Reprint address: Steven L. Galetta, MD, Hospital of the University of Pennsylvania, Department of Neurology, 3400 Spruce St, Philadelphia, PA 19104.
AFTERIMAGES JONATHAN WIRTSCHAFTER, EDITOR
Acute Sensorimotor Polyneuropathy With Tonic Pupils and an Abduction Deficit: An Unusual Presentation of Polyarteritis Nodosa JEFFREY L. BENNETT, MD, PHD,1 VICTORIA A. PELAK, MD,1 ZISSIMOS MOURELATOS, MD,2 SHAWN BIRD, MD,1 AND STEVEN L. GALETTA, MD1 Departments of 1Neurology and 2Pathology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA Abstract. A tonic pupil may occur in isolation or as part of a systemic disorder. We report a patient who developed tonic pupils and an abduction deficit in the setting of polyarteritis nodosa. The combination of a tonic pupil and an abduction deficit should suggest the possibility of a vasculopathic disorder, because the ciliary ganglion and lateral rectus muscle are both supplied by the lateral muscular artery. Widespread small artery and arteriolar narrowing and occlusion are the hallmarks of polyarteritis nodosa. Unusual ischemic syndromes may occur, such as this rare combination of neuro-ophthalmic signs, by involvement of both the nutrient artery and its collaterals. We are unaware of other reports of neuropathic tonic pupils in association with polyarteritis nodosa. (Surv Ophthalmol 43:341–344, 1999. © 1999 by Elsevier Science Inc. All rights reserved.) Key words. abducens palsy • Guillain-Barré syndrome • Miller–Fisher syndrome • peripheral neuropathy • polyarteritis nodosa • tonic pupils • vasculitis
fore admission, he noted the acute onset of distal right arm weakness that was soon followed by left arm weakness. Several days later, he noted a transient erythematous rash over his arms, face, and trunk. Two days before admission, the patient experienced the onset of bilateral lower extremity weakness and the acute onset of mild arthralgias and myalgias. At the time of presentation, he was unable to walk without assistance. He denied any recent illnesses, fever, unusual workplace exposures, or illicit substance use. His medical history was significant for an episode of Guillain-Barré syndrome (GBS) 15 years earlier after an immunization. During his illness, he required mechanical ventilatory support;
Neuro-ophthalmologic signs and symptoms commonly accompany inflammatory and noninflammatory neuromuscular disorders. The tempo and character of these neuro-ophthalmologic problems may often provide invaluable clinical information to direct future diagnostic studies. Here, we report a case of acute peripheral neuropathy in which the subsequent development of an abduction deficit and neuropathic tonic pupils directed the appropriate diagnostic tissue biopsies for vasculitis.
Case Report A 47-year-old man was admitted to the hospital because of progressive limb weakness. Two weeks be341 © 1999 by Elsevier Science Inc. All rights reserved.
0039-6257/99/$19.00 PII S0039-6257(98)00047-2
342
Surv Ophthalmol 43 (4) January–February 1999
his recovery was complete over a 1- to 2-year period. There were no pupillary abnormalities noted at that time. On examination, blood pressure was normotensive and pulse was regular. There was a mild diffuse livedoid rash on his back and chest. Acuity at near was J1 OD and J11 OS. Visual fields were full, pupils were sluggishly reactive to light, and ocular ductions were full. Nondilated funduscopic examination was normal. He had a mild facial diplegia, and he had severe bilateral upper extremity weakness (1-3/5) and moderate bilateral lower extremity weakness (3-4/5), worse distally. Reflexes were absent and there was diminished sensation to pinprick and temperature to the level of the knees and forearms, bilaterally. The gait was wide-based. A comprehensive chemistry panel was remarkable only for an alanine aminotransferase level of 112 U/L (normal, 0-40 U/L), aspartate aminotransferase level of 54 U/L (normal, 0-36 U/L), and gamma glutamyltransferase level of 303 U/L (normal, 8-78 U/L). Urine heavy metal screen was negative, and urine collection was negative for porphyrins. Lumbar puncture revealed a glucose level of 59 mg/dL, protein level of 39 mg/dL, and one white blood cell. Nerve conduction studies (NCSs) on the second hospital day showed a severe sensorimotor polyneuropathy with axonal loss and no demyelinating features. Electromyography (EMG) showed evidence of very acute neurogenic changes in all weak muscles studied. There was a predominance of normal motor unit potentials (MUPs) recruited in discrete patterns with rapid firing rates. Mild, chronic denervation was seen in a few distal leg muscles. The patient was started on intravenous immunoglobulins at 2 g/kg over 5 days for presumed GBS. On hospital day 10, lumbar puncture, NCSs, and EMG were repeated. The cerebrospinal fluid was acellular with a protein level of 73 mg/dL; NCSs and EMG studies were unchanged. On hospital day 24, the patient complained of worsening upper extremity weakness, back pain, and difficulty urinating. He was noted to have lost 5 to 6 pounds since admission. Neurologic examination showed 0 to 2/5 strength in the left arm and 1 to 3/5 strength in the right arm. Leg strength was unchanged. The right pupil was now noted to be unreactive. Magnetic resonance imaging of the cervical spine and brain were unremarkable. Repeat NCSs showed evidence of severe sensory and motor axonal loss, without demyelinating features. In the arm muscles studied, there was the appearance of markedly polyphasic MUPs of increased duration, consistent with new collateral sprouting. Laboratory studies revealed an erythrocyte sedimentation rate of 56 mm/ hr (normal, 0-15 mm/hr); rheumatoid factor, nega-
BENNETT ET AL
tive; cryoglobulins, negative; antinuclear antibody 1: 160 (normal, , 1:160); antineutrophil cytoplasmic antibody, , 1:8 (normal, , 1:8); C3/C4 complements, normal; rapid plasma reagin, negative; and hepatitis B surface antibody, positive. The patient continued to lose weight (a total of 10-15 pounds over 6 weeks), and on hospital day 40, he complained of increasing weakness and diplopia in lateral gaze. Neuro-ophthalmologic examination revealed 5-mm pupils, which were unreactive to light with a tonic near response (Figs. 1A and 1B). Administration of 0.125% pilocarpine induced pupillary constriction in both eyes (Fig. 1C). Abduction was limited in the right eye. He was orthophoric in left gaze. By Maddox rod testing, he had a 4-prism diopter (D) esotropia in primary gaze that increased to 8 D in right gaze. Vertical eye movements were normal. Funduscopic examination was normal. With concern for a vasculitic cause, nerve (sural) and muscle (gastrocnemius) biopsies were performed. Both specimens revealed evidence of vasculitis with chronic inflammatory cells and polymorphonuclear cells surrounding vessels and within vessel walls (Fig. 2). In the muscle biopsy specimen, there was evidence of vessel wall destruction. The nerve showed marked axonal degeneration on paraffin and teased fiber preparations. Residual muscle fibers were severely atrophied and necrotic debris was abundant (Fig. 2). The clinical history and histologic features of the biopsy specimens established the diagnosis of polyarteritis nodosa (PAN). Therapy was initiated with intravenous methylprednisolone (1 g/day for 5 days) followed by oral prednisone (1 g/kg) and monthly intravenous cyclophosphamide (800 mg/m2). The patient’s strength improved moderately during the subsequent 30 days. The patient’s double vision resolved within 2 weeks, but his tonic pupils persisted. Repeat Maddox rod testing revealed a 2-D exophoria at distance.
Discussion Polyarteritis nodosa is a necrotizing arteritis that affects medium and small arteries.12 Because of the variable location of the affected vessels, the clinical manifestations of PAN are quite diverse. Multiple organ systems may be involved, including the nervous system, kidneys, skin, digestive tract, heart, and eyes. Systemic symptoms are frequently reported at the onset of disease; however, they may be absent when the illness is restricted to the nervous system,8 skin,29 muscle,29 or eye.27,32 There are no diagnostic tests for PAN, although a large proportion of patients are hepatitis B virus-positive and 80% of those with microscopic artery involvement are antineutrophil cytoplasmic antibody-positive.18,26 Diagnosis is ulti-
ACUTE SENSORIMOTOR POLYNEUROPATHY
343
Fig. 1. Neuropathic tonic pupils in a patient with a sensorimotor neuropathy. A: The pupils were unreactive to light stimulation. B: The pupils responded tonically to a near stimulus. C: On instillation of dilute 0.125% pilocarpine, the pupils showed marked constriction.
mately made by biopsy in conjunction with clinical history.21 Neurologic symptoms, particularly peripheral neuropathy, are common in PAN and may dominate the clinical picture.11,24,29 Ocular symptoms, however, are much rarer (10–20% of cases), although they may occur in isolation early in the course of the disease.16,32 Ophthalmologic and neuro-ophthalmic manifestations of PAN are protean and include chorioretinitis, neuroretinitis, optic neuropathy, chiasmal arachnoiditis, ocular motor palsies, uveitis, episcleritis, and corneal ulcers.10,16 The most common ophthalmoscopic finding in PAN is retinopathy
Fig. 2. Gastrocnemius muscle biopsy (hematoxylin and eosin, 3 200). Microscopic examination shows a dense perivascular inflammatory infiltrate with effacement of the arterial wall. Arrows indicate neutrophils that have marginated and infiltrated the vessel wall. In the periphery of the specimen, fat replacement of atrophic muscle is present.
secondary to renal hypertension4; the choroidal vessels are most frequently involved on pathologic examination.14 Sluggish pupils have been reported in association with PAN, but no documentation was made of light-near dissociation in that case.4 A critical juncture in our patient’s course was the development of an abduction deficit and neuropathic tonic pupils. Tonic pupils are defined by the presence of three characteristic findings: poor or absent contraction to light, full contraction to near response with slow and delayed redilation, and constriction in response to conjunctival instillation of a dilute solution of pilocarpine (0.125%).22 Tonic pupils may result from either injury to postsynaptic cholinergic neurons in the ciliary ganglion, their projections to the ciliary body and iris, or their preganglionic innervation.17,22 Independent of the exact localization of the lesion, the final common insult entails denervation of the ciliary body and iris because of degeneration of second-order parasympathetic neurons in the ciliary ganglion.23 Because of the varied localization of the lesion, the causes of tonic pupils are myriad. When conjoined with a peripheral neuropathy, however, the list is more limited: GBS and its Miller-Fisher variant,19,31 vasculitides,1,6,7,15,30 infection,3 paraneoplastic neuropathy,2 and certain degenerative and hereditary sensorimotor and autonomic neuropathies.13,28,33 Therefore, although our patient’s tonic pupils and abduction deficit were consistent with the preliminary diagnosis of GBS, the relative rarity of these findings in the GBS, the stepwise progression of his deficits, the persistent axonal pathology on electrophysiologic studies,5,20 and the modest elevation in the sedimentation rate pointed to an alternative vasculopathic cause. Given the thrombotic mechanism of PAN, we concluded that the likely cause of our patient’s tonic pupils was ischemia to the ciliary ganglion or short ciliary nerves. In this regard, it is interesting that our pa-
344
Surv Ophthalmol 43 (4) January–February 1999
tient had a concomitant abduction deficit because both the ciliary ganglion and the lateral rectus muscle receive a portion of their blood supply from the trunk of the lateral muscular artery.9 Currie and Lessell6 proposed a similar mechanism for tonic pupils associated with temporal arteritis. Definitive diagnosis in our case was made only after nerve and muscle biopsy. Said et al25 examined retrospectively the value of nerve and muscle biopsy in corroborating the diagnosis of PAN and found that independent of the presence of multisystem disease, muscle biopsy in combination with nerve biopsy significantly improved diagnostic sensitivity from roughly 60% to 80%. Similarly, in our case, although both tissue samples revealed signs of vascular inflammation, only muscle tissue showed arteries with focal destruction of the vessel wall. Therefore, despite a clinical presentation limited to peripheral neuropathy, the muscle biopsy proved invaluable in the diagnostic evaluation.
References 1. Bachmeyer C, Zuber M, Dupont S, et al: Adie syndrome as the initial sign of primary Sjögren syndrome. Am J Ophthalmol 123:691–692, 1997 2. Bell TAG: Adie’s tonic pupil in a patient with carcinomatous neuromyopathy. Arch Ophthalmol 104:331–332, 1986 3. Bennett JL, Mahalingam R, Wellish MC, Gilden DH: Epstein Barr virus associated acute autonomic neuropathy. Ann Neurol 40:453–455, 1996 4. Boeck J: Ocular changes in periarteritis nodosa. Am J Ophthalmol 42:567–577, 1956 5. Bouche P, Leger JM, Travers MA, Cathala HP, Castaigne P: Peripheral neuropathy in systemic vasculitis: clinical and electrophysiologic study of 22 patients. Neurology 36:1598– 1602, 1986 6. Currie J, Lessell S: Tonic pupil with giant cell arteritis. Br J Ophthalmol 68:135–138, 1984 7. Davis RH, Daroff RB, Hoyt WF: Tonic pupil after temporal arteritis. Lancet 1:822, 1968 8. Dyck PJ, Benstead TJ, Conn DL, et al: Nonsystemic vasculitic neuropathy. Brain 110:843–853, 1987 9. Eliskova M: Blood vessels of the ciliary ganglion in man. Br J Ophthalmol 57:766–772, 1973 10. Galetta SL: Vasculitis, in Newman NA, Miller NR (eds): Walsh and Hoyt’s Clinical Neuro-Ophthalmology, ed V, vol 3. Baltimore, Williams & Wilkins, 1998, pp 3744–3752 11. Guillevin L, Le Thi Huong D, Godeau P, Jais P, Wechsler B: Clinical findings and prognosis of polyarteritis nodosa and Churg-Strauss angiitis: a study in 165 patients. Br J Rheumatol 27:258–264, 1988 12. Guillevin L, Lhote F, Gherardi R: Polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: clinical spects, neurologic manifestations, and treatment. Neurol Clin 15:865–886, 1997 13. Hedges TR, Gerner EW: Ross’ syndrome (tonic pupil plus). Br J Ophthalmol 59:387–391, 1975
BENNETT ET AL 14. Henkind P, Gold DH: Ocular manifestations of rheumatic disorders: Natural and iatrogenic. Rheumatology 4:13–59, 1973 15. Hoyle C, Ewing DJ, Parker AC: Acute autonomic neuropathy in association with systemic lupus erythematosus. Ann Rheum Dis 44:420–424, 1985 16. Jabs DA: The rheumatic diseases, in Ryan J, Schachat AP, Murphy RP (eds): Retina, vol 2. St Louis, CV Mosby, 1994, pp 1421–1444 17. Jacobson DM: Pupillary responses to dilute pilocarpine in preganglionic 3rd nerve disorders. Neurology 40:804–808, 1990 18. Jennette JC, Wilkman AS, Falk RJ: Anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and vasculitis. Am J Pathol 135:921–930, 1989 19. Keane JR: Tonic pupils with acute ophthalmoplegic polyneuritis. Ann Neurol 2:393–396, 1977 20. Kissel JT, Slivka AP, Warmolts JR, Mendell JR: The clinical spectrum of necrotizing angiopathy of the peripheral nervous system. Ann Neurol 18:251–257, 1985 21. Lightfoot RW Jr, Michel BA, Bloch DA, et al: The American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Arth Rheum 33:1088–1093, 1990 22. Loewenfeld IE, Thompson HS: The tonic pupil: a re-evaluation. Am J Ophthalmol 63:46–87, 1967 23. Loewenfeld IE, Thompson HS: Mechanism of tonic pupil. Ann Neurol 10:275–276, 1981 24. Moore PM, Fauci AS: Neurologic manifestations of systemic vasculitis: A retrospective and prospective study of the clinicopathologic features and responses to therapy in 25 patients. Am J Med 71:517–524, 1981 25. Said G, Lacroix-Ciaudo C, Fujimura H, Bas C, Faux N: The peripheral neuropathy of necrotizing arteritis: a clinicopathological study. Ann Neurol 23:461–465, 1988 26. Sergent JS, Lockshin MD, Christian CL, Gocke DJ: Vasculitis with hepatitis B antigenemia: long-term observation in nine patients. Medicine 55:1–18, 1976 27. Stillerman ML: Ocular manifestations of diffuse collagen disease. Arch Ophthalmol 41:239, 1951 28. Takase Y, Takahashi K, Takada K, Tatsumi H, Tabuchi Y: Hereditary motor and sensory neuropathy type 1 (HMSN1) associated with cranial neuropathy: an autopsy case report. Acta Neurol Scand 82:368–373, 1990 29. Tervaert JWC, Kallenberg C: Neurologic manifestations of systemic vasculitides. Rheum Dis Clin North Am 19:913–940, 1993 30. Victor DI, Green WR, Stark WJ, Walsh FB: A non-permanent tonic pupil in rheumatoid arteritis. Can J Neurol Sci 4:209– 212, 1977 31. Williams D, Brust JC, Abrams G, Challenor Y, Devereaux M: Landry-Guillain-Barré syndrome with abnormal pupils and normal eye movements: a case report. Neurology 29:1033– 1040, 1979 32. Wise GN: Ocular periarteritis nodosa: report of two cases. Arch Ophthalmol 48:1–11, 1952 33. Young RR, Asbury AK, Corbett JL, Adams RD: Pure pan-dysautonomia with recovery: description and discussion of diagnostic criteria. Brain 98:613–636, 1975
Reprint address: Steven L. Galetta, MD, Hospital of the University of Pennsylvania, Department of Neurology, 3400 Spruce St, Philadelphia, PA 19104.