J Neurol (1991) 238 : 55-56
Journal of
Neurology © Springer-Verlag 1991
Retinal migraine, chorea, and retinal artery thrombosis in a patient with primary antiphospholipid antibody syndrome J. A. Gutrecht 1, N. Kattwinkel 2, and M . J . Stillman 1* 1Department of Neurology and 2Section of Rheumatology, Lahey Clinic Medical Center, 41 Mall Road, Burlington, MA 01805, USA Received July 18, 1990 / Accepted September 3, 1990 Summary. W e report the case of a patient with the unusual c o m b i n a t i o n of migraine, chorea, and retinal arterial thrombosis along with l a b o r a t o r y evidence of autoimmunity. In the absence of systemic lupus e r y t h e m a t o s u s , the clinical manifestations suggest the presence o f the p r i m a r y antiphospholipid a n t i b o d y s y n d r o m e .
Key words: Migraine - C h o r e a - Arterial thrombosis Antiphospholipid antibody
Introduction Primary antiphospholipid antibody ( a P L A b ) s y n d r o m e is characterized by the presence of a P L A b in patients who have evidence for a u t o i m m u n i t y but n o n e of the m a j o r specific clinical or serological features of systemic lupus e r y t h e m a t o s u s ( S L E ) [4]. A n t i n u c l e a r a n t i b o d y ( A N A ) and decreased c o m p l e m e n t levels are sometimes present, but d o u b l e - s t r a n d e d deoxyribonucleic acid ( D N A ) or extractable n u c l e o p r o t e i n a n t i b o d y ( E N A ) is absent. False-positive V D R L , antimitochondrial antibody, rheum a t o i d factor, i m m u n e complexes, cryoglobulinemia, antithyroid antibody, and t h r o m b o c y t o p e n i a m a y be present. This s e r o i m m u n o l o g i c a l picture is strongly assod a t e d with venous or arterial thrombosis, including single or multiple strokes [3, 10, 13]. A c u t e ischemic encephalopathy, migraine, o p h t h a l m o l o g i c a l manifestations, and c h o r e a have also b e e n r e p o r t e d [2, 5, 7 - 9 ] in this syndrome. W e r e p o r t the case of a patient with this s y n d r o m e in w h o m classic retinal migraine [6], h e m i c h o r e a , and thrombosis of the central retinal artery d e v e l o p e d in succession o v e r a 3-year period. *Present address: The Polyclinic, 1145 Broadway, Seattle, WA
98122-4299, USA Offprint requests to: J. A. Gutrecht
Case report A 31-year-old man was investigated because of leukopenia, thrombocytopenia, and migraine. He described having 10-min episodes of tunnel vision surrounded by blurriness, wavy lines, and occasionally scintillating phenomena. His symptoms involved either eye, usually the right, and were sometimes associated with a sharp pain in the frontal area, cold sweating, dizziness, and nausea. These episodes recurred daily and had been present for 5 years. He had bilateral pressure pain of the mastoid process most of the time. Two sisters had tension headaches, and his mother had SLE. Physical examination revealed mild psoriasis and vitiligo. Results of the neurological examination were normal. Laboratory studies showed a white blood cell count of 3,700/gl; platelet count, 120,000/~d; serum creatinine, 1.7mg/dl; C3, 48mg/dl (normal range, 85-160 mg/dl); C4, 7 mg/dl (normal range, 17-45 mg/dl); CHs0, 83 units (normal range, 150-250 units); and ANA, 1:320 in both homogeneous and speckled patterns. Results of antiDNA antibody, immune complexes, urinalysis, hemoglobin, hematocrit, mean corpuscular volume, erythrocyte sedimentation rate, glucose, blood urea nitrogen, creatine kinase, SGOT, alkaline phosphatase, total bilirubin, cholesterol, total protein, albumin, globulin, calcium, phosphorus, uric acid, thyroid function tests, anticentromere antibody, RNP Ab, SM-Ab (ENA), SSA(RO) Ab, SSB (LA) Ab, and computed tomography of the head were negative or normal. The patient was given propranolol with little effect. Five months later, after administration of medication had been stopped, dysarthria and mild right-sided chorea developed. The results of an electroencephalogram were normal, and magnetic resonance imaging of the brain demonstrated three small high-signal areas on the T2-weighted images in the right subcortical white matter. No abnormalities were seen in the basal ganglia. These clinical symptoms subsided in 2 months. The patient's ocular symptoms continued. Severe right frontal headaches developed 14 months later, and after one of these headaches, the patient awoke with blindness in the left eye, which was similar to past transient episodes. The visual loss did not improve, and 2 days later examination disclosed only finger-waving vision in a small area lateral to the fixation point. An abnormality of the afferent pupillary light reflex was noted, and funduscopic examination revealed "milky" perimacular edema. The rest of the neurological examination was normal. Laboratory studies showed a platelet count of 129,000/pl; hemoglobin, 13.2g/dl; hematocrit, 38%; blood urea nitrogen, 30mg/dl; serum creatinine, 1.5mg/dl; activated PTT, 32.6s (normal range, 2232s); C3, 64mg/dl; C4, 9mg/dl; CHs0, 85 units; positive ANA at
56 1 : 640 dilution in a homogeneous pattern and at 1 : 160 dilution in a speckled pattern: and anticardiolipin lgG titer at 1 : 256 dilution. Results of cerebral angiography were normal. Results of other laboratory studies were normal~ including RPR, lupus anticoagulant (LA), and routine urinalysis. The patient was given warfarin sodium.
Discussion
This patient had some serological but no clinical features of SLE. D e p r e s s e d c o m p l e m e n t levels were impressive but i m m u n e complexes were not detected. H o w e v e r , the patient's s y m p t o m s fulfilled the p r o p o s e d criteria for the diagnosis of primary a P L A b s y n d r o m e [4]. The developm e n t of retinal migraine headaches was followed a year later by transient c h o r e a and by central retinal artery thrombosis a year after that. A l t h o u g h the prevalence of migraine in patients with p r i m a r y a P L A b s y n d r o m e is not k n o w n , m a n y cases of this association have b e e n reported. For example, complicated migraine is m o r e c o m m o n than uncomplicated migraine and often is the first manifestation [3, 8, 12]. C h o r e a has also been r e p o r t e d [2, 3] with this s y n d r o m e but has not b e e n confirmed by others [1]. The developm e n t of c h o r e a in this patient supports the suggestion that it m a y be yet a n o t h e r manifestation of the s y n d r o m e r a t h e r than a chance occurrence. The association of arterial thrombosis and the a P L A b s y n d r o m e is the strongest and best recognized [1, 3-5]. W h e t h e r the presence of migraine, chorea, and arterial thrombosis is a strong e n o u g h association to m a k e a clinical diagnosis of p r i m a r y a P L A b s y n d r o m e cannot be a n s w e r e d at this time. H o w e v e r , the possibility of this s y n d r o m e must be entertained early on because migraine is often the first manifestation [8]. Men with migraine h e a d a c h e s and no family history for t h e m should be suspect. W h e n a second manifestation, such as chorea or transverse myelitis [6], occurs, the w o r k - u p should include A N A titer, V D R L , and activated PTT. W h e n the s y n d r o m e is strongly suspected, L A and cardiolipin antib o d y must be o b t a i n e d because results of the P T T m a y still be n o r m a l or minimally prolonged. Finally, a P L A b m a y be present in the absence of L A . D e p r e s s e d comp l e m e n t c o m p o n e n t s have b e e n described in primary a P L A b s y n d r o m e and m a y indicate a congenital deficiency rather than c o n s u m p t i o n c o m p l e m e n t depression [4]. T h e a p p r o p r i a t e t r e a t m e n t of patients with this synd r o m e is not k n o w n . Aspirin has been prescribed for c h o r e a [7] and migraine [8]. Patients with high a P L A b titers m a y experience a greater n u m b e r of neurological
complications, such as acute ischemic e n c e p h a l o p a t h y , cerebral infarction, retinal infarction, or ischemic optic n e u r o p a t h y [5], and the illness m a y be m o r e severe. These patients may require anticoagulation therapy. Lastly, immunosuppressive therapy and plasmapheresis have been used in patients with involvement that is severe and even life threatening [5]. The natural history of this s y n d r o m e is not known, and stricter guidelines for treatment await further study [11]. References
1. Alarcdn-Segovia D, Delez6 M, Oria CV, Sgmchez-Guerrero J, Gdmez-Pacheco L, Cabiedes J, Fernfindez L, Ponce de Le6n S (1989) Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus: a prospective analysis of 500 consecutive patients. Medicine (Baltimore) 68 : 353365 2. Asherson RA, Hughes GR (1988) Antiphospholipid antibodies and chorea (Letter). J Rheumatol 15:377-379 3. Asherson RA, Khamashta MA, Gil A, Vazquez J J, Chan O, Baguley E, Hughes GR (1989) Cerebrovascular disease and antiphospholipid antibodies in systemic lupus erythematosus, lupus-like disease, and the primary antiphospholipid syndrome. Am J Med 86 : 391-399 4. Asherson RA, Khamashta MA, Ordi-Ros J, Derksen RHWM, Machin SJ, Barquinero J, Outt HH, Harris EN, Vilardell-Torres M, Hughes GRV (1989) The "primary" antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore) 68 : 366-374 5. Briley DP, Coull BM, Goodnight SH Jr (1989) Neurological disease associated with antiphospholipid antibodies. Ann Neurol 25:221-227 6. Headache Classification Committee of the International Headache Society (1988) Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 8 [Suppl 7] : 1-96 7. Hodges JR (1987) Chorea and the lupus anticoagulant (Letter). J Neurol Neurosurg Psychiatry 50 : 368-369 8. Hogan MJ, Brunet DG, Ford PM, Lillicrap D (1988) Lupus anticoagulant, antiphospholipid antibodies and migraine. Can J Neurol Sci 15:420-425 9. Jonas J, K0tble K, VOlcker HE, Kalden JR (1986) Central retinal artery occlusion in Sneddon's disease associated with antiphospholipid antibodies. Am J Ophthalmol 102 : 37-40 10. Levine SR, Welch KM (1987) Cerebrovascular ischemia associated with lupus anticoagulant. Stroke 18 : 257-263 11. Levine SR, Welch KMA (1989) Antiphospholipid antibodies. Ann Neurol 26 : 386-389 12. Levine SR, Joseph R, D'Andrea G, Welch KM (1987) Migraine and the lupus anticoagulant: case reports and review of the literature. Cephalalgia 7:93-99 13. Meyer O, Piette JC, Bourgeois P, Fallas P, Bletry O, Jungers P, Kahn MF, Godeau P, Ryckewaert A (1987) Antiphospholipid antibodies: a disease marker in 25 patients with antinuclear antibody negative systemic lupus erythematosus (SLE): comparison with a group of 91 patients with antinuclear antibody positive SLE. J Rheumatol 14:502-506
Journal of
Neurology © Springer-Verlag 1991
Retinal migraine, chorea, and retinal artery thrombosis in a patient with primary antiphospholipid antibody syndrome J. A. Gutrecht 1, N. Kattwinkel 2, and M . J . Stillman 1* 1Department of Neurology and 2Section of Rheumatology, Lahey Clinic Medical Center, 41 Mall Road, Burlington, MA 01805, USA Received July 18, 1990 / Accepted September 3, 1990 Summary. W e report the case of a patient with the unusual c o m b i n a t i o n of migraine, chorea, and retinal arterial thrombosis along with l a b o r a t o r y evidence of autoimmunity. In the absence of systemic lupus e r y t h e m a t o s u s , the clinical manifestations suggest the presence o f the p r i m a r y antiphospholipid a n t i b o d y s y n d r o m e .
Key words: Migraine - C h o r e a - Arterial thrombosis Antiphospholipid antibody
Introduction Primary antiphospholipid antibody ( a P L A b ) s y n d r o m e is characterized by the presence of a P L A b in patients who have evidence for a u t o i m m u n i t y but n o n e of the m a j o r specific clinical or serological features of systemic lupus e r y t h e m a t o s u s ( S L E ) [4]. A n t i n u c l e a r a n t i b o d y ( A N A ) and decreased c o m p l e m e n t levels are sometimes present, but d o u b l e - s t r a n d e d deoxyribonucleic acid ( D N A ) or extractable n u c l e o p r o t e i n a n t i b o d y ( E N A ) is absent. False-positive V D R L , antimitochondrial antibody, rheum a t o i d factor, i m m u n e complexes, cryoglobulinemia, antithyroid antibody, and t h r o m b o c y t o p e n i a m a y be present. This s e r o i m m u n o l o g i c a l picture is strongly assod a t e d with venous or arterial thrombosis, including single or multiple strokes [3, 10, 13]. A c u t e ischemic encephalopathy, migraine, o p h t h a l m o l o g i c a l manifestations, and c h o r e a have also b e e n r e p o r t e d [2, 5, 7 - 9 ] in this syndrome. W e r e p o r t the case of a patient with this s y n d r o m e in w h o m classic retinal migraine [6], h e m i c h o r e a , and thrombosis of the central retinal artery d e v e l o p e d in succession o v e r a 3-year period. *Present address: The Polyclinic, 1145 Broadway, Seattle, WA
98122-4299, USA Offprint requests to: J. A. Gutrecht
Case report A 31-year-old man was investigated because of leukopenia, thrombocytopenia, and migraine. He described having 10-min episodes of tunnel vision surrounded by blurriness, wavy lines, and occasionally scintillating phenomena. His symptoms involved either eye, usually the right, and were sometimes associated with a sharp pain in the frontal area, cold sweating, dizziness, and nausea. These episodes recurred daily and had been present for 5 years. He had bilateral pressure pain of the mastoid process most of the time. Two sisters had tension headaches, and his mother had SLE. Physical examination revealed mild psoriasis and vitiligo. Results of the neurological examination were normal. Laboratory studies showed a white blood cell count of 3,700/gl; platelet count, 120,000/~d; serum creatinine, 1.7mg/dl; C3, 48mg/dl (normal range, 85-160 mg/dl); C4, 7 mg/dl (normal range, 17-45 mg/dl); CHs0, 83 units (normal range, 150-250 units); and ANA, 1:320 in both homogeneous and speckled patterns. Results of antiDNA antibody, immune complexes, urinalysis, hemoglobin, hematocrit, mean corpuscular volume, erythrocyte sedimentation rate, glucose, blood urea nitrogen, creatine kinase, SGOT, alkaline phosphatase, total bilirubin, cholesterol, total protein, albumin, globulin, calcium, phosphorus, uric acid, thyroid function tests, anticentromere antibody, RNP Ab, SM-Ab (ENA), SSA(RO) Ab, SSB (LA) Ab, and computed tomography of the head were negative or normal. The patient was given propranolol with little effect. Five months later, after administration of medication had been stopped, dysarthria and mild right-sided chorea developed. The results of an electroencephalogram were normal, and magnetic resonance imaging of the brain demonstrated three small high-signal areas on the T2-weighted images in the right subcortical white matter. No abnormalities were seen in the basal ganglia. These clinical symptoms subsided in 2 months. The patient's ocular symptoms continued. Severe right frontal headaches developed 14 months later, and after one of these headaches, the patient awoke with blindness in the left eye, which was similar to past transient episodes. The visual loss did not improve, and 2 days later examination disclosed only finger-waving vision in a small area lateral to the fixation point. An abnormality of the afferent pupillary light reflex was noted, and funduscopic examination revealed "milky" perimacular edema. The rest of the neurological examination was normal. Laboratory studies showed a platelet count of 129,000/pl; hemoglobin, 13.2g/dl; hematocrit, 38%; blood urea nitrogen, 30mg/dl; serum creatinine, 1.5mg/dl; activated PTT, 32.6s (normal range, 2232s); C3, 64mg/dl; C4, 9mg/dl; CHs0, 85 units; positive ANA at
56 1 : 640 dilution in a homogeneous pattern and at 1 : 160 dilution in a speckled pattern: and anticardiolipin lgG titer at 1 : 256 dilution. Results of cerebral angiography were normal. Results of other laboratory studies were normal~ including RPR, lupus anticoagulant (LA), and routine urinalysis. The patient was given warfarin sodium.
Discussion
This patient had some serological but no clinical features of SLE. D e p r e s s e d c o m p l e m e n t levels were impressive but i m m u n e complexes were not detected. H o w e v e r , the patient's s y m p t o m s fulfilled the p r o p o s e d criteria for the diagnosis of primary a P L A b s y n d r o m e [4]. The developm e n t of retinal migraine headaches was followed a year later by transient c h o r e a and by central retinal artery thrombosis a year after that. A l t h o u g h the prevalence of migraine in patients with p r i m a r y a P L A b s y n d r o m e is not k n o w n , m a n y cases of this association have b e e n reported. For example, complicated migraine is m o r e c o m m o n than uncomplicated migraine and often is the first manifestation [3, 8, 12]. C h o r e a has also been r e p o r t e d [2, 3] with this s y n d r o m e but has not b e e n confirmed by others [1]. The developm e n t of c h o r e a in this patient supports the suggestion that it m a y be yet a n o t h e r manifestation of the s y n d r o m e r a t h e r than a chance occurrence. The association of arterial thrombosis and the a P L A b s y n d r o m e is the strongest and best recognized [1, 3-5]. W h e t h e r the presence of migraine, chorea, and arterial thrombosis is a strong e n o u g h association to m a k e a clinical diagnosis of p r i m a r y a P L A b s y n d r o m e cannot be a n s w e r e d at this time. H o w e v e r , the possibility of this s y n d r o m e must be entertained early on because migraine is often the first manifestation [8]. Men with migraine h e a d a c h e s and no family history for t h e m should be suspect. W h e n a second manifestation, such as chorea or transverse myelitis [6], occurs, the w o r k - u p should include A N A titer, V D R L , and activated PTT. W h e n the s y n d r o m e is strongly suspected, L A and cardiolipin antib o d y must be o b t a i n e d because results of the P T T m a y still be n o r m a l or minimally prolonged. Finally, a P L A b m a y be present in the absence of L A . D e p r e s s e d comp l e m e n t c o m p o n e n t s have b e e n described in primary a P L A b s y n d r o m e and m a y indicate a congenital deficiency rather than c o n s u m p t i o n c o m p l e m e n t depression [4]. T h e a p p r o p r i a t e t r e a t m e n t of patients with this synd r o m e is not k n o w n . Aspirin has been prescribed for c h o r e a [7] and migraine [8]. Patients with high a P L A b titers m a y experience a greater n u m b e r of neurological
complications, such as acute ischemic e n c e p h a l o p a t h y , cerebral infarction, retinal infarction, or ischemic optic n e u r o p a t h y [5], and the illness m a y be m o r e severe. These patients may require anticoagulation therapy. Lastly, immunosuppressive therapy and plasmapheresis have been used in patients with involvement that is severe and even life threatening [5]. The natural history of this s y n d r o m e is not known, and stricter guidelines for treatment await further study [11]. References
1. Alarcdn-Segovia D, Delez6 M, Oria CV, Sgmchez-Guerrero J, Gdmez-Pacheco L, Cabiedes J, Fernfindez L, Ponce de Le6n S (1989) Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus: a prospective analysis of 500 consecutive patients. Medicine (Baltimore) 68 : 353365 2. Asherson RA, Hughes GR (1988) Antiphospholipid antibodies and chorea (Letter). J Rheumatol 15:377-379 3. Asherson RA, Khamashta MA, Gil A, Vazquez J J, Chan O, Baguley E, Hughes GR (1989) Cerebrovascular disease and antiphospholipid antibodies in systemic lupus erythematosus, lupus-like disease, and the primary antiphospholipid syndrome. Am J Med 86 : 391-399 4. Asherson RA, Khamashta MA, Ordi-Ros J, Derksen RHWM, Machin SJ, Barquinero J, Outt HH, Harris EN, Vilardell-Torres M, Hughes GRV (1989) The "primary" antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore) 68 : 366-374 5. Briley DP, Coull BM, Goodnight SH Jr (1989) Neurological disease associated with antiphospholipid antibodies. Ann Neurol 25:221-227 6. Headache Classification Committee of the International Headache Society (1988) Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 8 [Suppl 7] : 1-96 7. Hodges JR (1987) Chorea and the lupus anticoagulant (Letter). J Neurol Neurosurg Psychiatry 50 : 368-369 8. Hogan MJ, Brunet DG, Ford PM, Lillicrap D (1988) Lupus anticoagulant, antiphospholipid antibodies and migraine. Can J Neurol Sci 15:420-425 9. Jonas J, K0tble K, VOlcker HE, Kalden JR (1986) Central retinal artery occlusion in Sneddon's disease associated with antiphospholipid antibodies. Am J Ophthalmol 102 : 37-40 10. Levine SR, Welch KM (1987) Cerebrovascular ischemia associated with lupus anticoagulant. Stroke 18 : 257-263 11. Levine SR, Welch KMA (1989) Antiphospholipid antibodies. Ann Neurol 26 : 386-389 12. Levine SR, Joseph R, D'Andrea G, Welch KM (1987) Migraine and the lupus anticoagulant: case reports and review of the literature. Cephalalgia 7:93-99 13. Meyer O, Piette JC, Bourgeois P, Fallas P, Bletry O, Jungers P, Kahn MF, Godeau P, Ryckewaert A (1987) Antiphospholipid antibodies: a disease marker in 25 patients with antinuclear antibody negative systemic lupus erythematosus (SLE): comparison with a group of 91 patients with antinuclear antibody positive SLE. J Rheumatol 14:502-506
