- Email: [email protected]
Paraneoplastic downbeat nystagmus
Correspondence recognized (with respect to effectiveness and availability) are automated perimetry in the central 10 degrees and Amsler grid testing. Multifocal ERG and fundus autofluorescence may play an increasing role in centres where testing is available.10 This case demonstrates the importance of regular screening for chloroquine toxicity. With severe toxicity, diffuse ocular involvement and permanent severe vision loss are possible, especially in more susceptible individuals. We recommend investigation for other causes in advanced or atypical cases, to rule out underlying systemic or ocular disease. REFERENCES 1. Bernstein HN. Chloroquine ocular toxicity. Surv Ophthalmol 1967;12:415–47. 2. Finbloom DS, Silver K, Newsome DA, Gunkel R. Comparison of hydroxychloroquine and chloroquine use and the development of retinal toxicity. J Rheumatol 1985;12:692–4. 3. Levy GD, Munz SJ, Paschal J, Cohen HB, Pince KJ, Peterson T. Incidence of hydroxychloroquine retinopathy in 1,207 patients in a large multicenter outpatient practice. Arthritis Rheum 1997;40:1482–6. 4. Marmor MF, Carr RE, Easterbrook M, Farjo AA, Mieler WF. Recommendations on screening for chloroquine and hydroxy-
Paraneoplastic downbeat nystagmus
A
cquired downbeat nystagmus (DBN) is most often associated with a structural lesion at the craniovertebral junction. We describe 2 patients where DBN was the predominant initial clinical sign of a paraneoplastic syndrome. Neuroimaging ruled out pathology at the craniocervical junction, and further investigations ruled out toxic, metabolic, nutritional, and infectious etiologies. Serum paraneoplastic antibodies were subsequently isolated in both patients. A previously healthy 63-year-old woman presented with a 2-week history of progressive vertigo. Her husband also described memory loss and a recent 10-pound weight loss. She had a 40 pack-year history of smoking. There was no history of recent infection, travel, new medication use, alcohol, or street drug use. The initial examination was remarkable for prominent DBN. There was no dysarthria. Mild dysmetria and truncal and gait ataxia were noted. The remainder of the neurological examination was normal. She worsened over the next 2 months. On repeat examination, an obvious vertical head titubation was present and her speech was characterized by a marked scanning dysarthria. There was frequent involuntary eye blinking. Persistent conjugate DBN was observed in primary position, as well as in all directions of gaze. Pupillary response and visual fields were intact and ophthalmoscopy was unremarkable. Smooth pursuit eye movements were unremarkable, but saccades were hypometric. Prominent bilateral upper and lower limb dysmetria, as
5.
6.
7.
8.
9. 10.
chloroquine retinopathy. American Academy of Ophthalmology. Available at: http://www.aao.org. Accessed April 30, 2007. Ingster-Moati I, Bui Quoc E, Crochet M, Orssaud C, Dufier JL, Roche O. Severe chloroquine- and hydroxychloroquineinduced retinopathy. J Fr Ophtalmol 2006;29:642–50. Okun E, Gouras P, Bernstein H, Von Sallmann L. Chloroquine retinopathy: a report of eight cases with ERG and darkadaptation findings. Arch Ophthalmol 1963;69:59–71. Robberecht W, Bednarik J, Bourgeois P, van Hees J, Carton H. Myasthenic syndrome caused by direct effect of chloroquine on neuromuscular junction. Arch Neurol 1989;46:464–8. De Bleecker J, De Reuck J, Quatacker J, Meire F. Persisting chloroquine-induced myasthenia? Acta Clin Belg 1991;46: 401–6. Easterbrook M. Dose relationships in patients with early chloroquine retinopathy. J Rheumatol 1987;14:472–5. Kellner U, Renner AB, Tillack H. Fundus autofluorescence and mfERG for early detection of retinal alterations in patients using chloroquine/hydroxychloroquine. Invest Ophthalmol Vis Sci 2006;47:3531–8.
Rusty J. Ritenour, Alan F. Cruess, Aditya V. Mishra Dalhousie University, Halifax, N.S. Correspondence to Rusty Ritenour, MD: [email protected] Can J Ophthalmol 2008;43:241–3 doi:10.3129/i08-023
well as truncal and gait ataxia, were also noted. The remainder of the neurological examination was normal. Examination of the respiratory, cardiovascular, and abdominal systems was unremarkable. Breast examination was normal and lymph nodes were not palpable. Initial magnetic resonance imaging (MRI) of the brain did not reveal any structural lesions of the craniocervical junction, brainstem, or cerebellum, and there were no encephalitic changes. Further investigations were aimed at ruling out a toxic-metabolic, inflammatory, infectious, or paraneoplastic etiology for the patient’s symptoms (see later discussion). Complete blood count, electrolytes (including calcium, magnesium, and phosphate), renal indices, liver enzymes, vitamin B12 and folate levels, thyroid-stimulating hormone and antithyroid antibodies, VDRL, and Lyme serology were all normal or negative. Cerebrospinal fluid (CSF) analysis revealed a nucleated cell count of 26 ×106 cells/L (94% lymphocytes), protein of 540 mg/L (normal 150–450 mg/L), and glucose of 4.7 mmol/L (normal 2.2–3.9 mmol/L). CSF cytology and angiotensin-converting enzyme levels were normal. Bacterial, viral, and fungal cultures, as well as viral polymerase chain reaction (PCR), were negative. A computed tomography scan of the chest, abdomen, and pelvis revealed a 1.2 cm × 2.3 cm right paratracheal lymph node, and a 1.5 cm × 1.8 cm spiculated right apical lung lesion (Fig. 1) suspicious for malignancy. Mediastinoscopy and biopsy of the paratracheal node was performed. Pathological examination demonstrated a metastatic, poorly differentiated adenocarcinoma. Results CAN J OPHTHALMOL—VOL. 43, NO. 2, 2008
243
Correspondence of a paraneoplastic antibody screen (NeoComplete Paraneoplastic profile, Athena Diagnostics Inc, Worcester, Mass.) eventually demonstrated the presence of serum antiMa1 and anti-Ma2 antibodies. The patient was treated with etoposide/carboplatin chemotherapy, as well as palliative radiotherapy. There was no improvement in her DBN or cerebellar symptoms, and she died approximately 1 year after her presentation. A 57-year-old woman presented with several weeks of fatigue, nausea, and loss of appetite associated with oscillopsia and a sensation of imbalance. Her past medical history was significant for hypertension, hyperlipidemia, and peptic ulcer disease. She had a 20 pack-year history of smoking. There was no history of recent infection, travel, new medication use, alcohol, or street drug use. Initial clinical examination was remarkable primarily for DBN present in primary position and in all directions of gaze (see Video 1, available online). Eye movements were full, although smooth pursuit movements were saccadic. Pupillary response and ophthalmoscopy were normal. Over the following several months, however, the patient developed marked scanning dysarthria and ataxia (Video 1). At the 6-month follow-up, the patient was no longer able to ambulate independently because of severe truncal and gait ataxia. The rest of the neurological examination remained normal. Respiratory, cardiovascular, abdominal, and breast examinations were unremarkable. Complete blood count, electrolytes, vitamin B1, B12, and folate levels, vasculitis screen, and renal, liver, and thyroid indices were all normal or negative. CSF analysis demonstrated a nucleated cell count of 2 ×106 cells/L (87% lymphocytes), protein of 588 mg/L (normal 150–450 mg/L), and glucose of 3.4 mmol/L (normal 2.2–3.9 mmol/L). CSF cytology, cultures, and viral PCR were negative. An MRI of the brain did not reveal any abnormalities of the craniocervical junction, brainstem, or cerebellum and no abnormal enhancement. Chest x-ray, abdominal and pelvic ultrasound, and mammography were negative for malignancy. Screening for paraneoplastic antibodies (NeoComplete Paraneoplastic profile, Athena Diagnostics Inc), however, demonstrated the presence of serum anti-Hu and -CV2 antibodies, highly suggestive of an underlying small cell lung cancer. Persistent investigation, including computed tomography of the chest at the 10-month follow-up, eventually demonstrated the development of subcarinal lym-
Fig. 1—Axial computed tomography of the thorax, demonstrating an enlarged paratracheal lymph node (white arrow on left) and a spiculated apical lung lesion (black arrow on right).
244
CAN J OPHTHALMOL—VOL. 43, NO. 2, 2008
phadenopathy. Pathological examination of a transbronchial needle aspirate was consistent with small cell lung cancer. At a 3-month follow-up subsequent to a course of palliative radiotherapy, the patient’s disabling neurological symptoms had stabilized but showed no sign of improvement. Acquired DBN is thought to occur as a result of disrupted connections among the cerebellum, the medulla, and the anterior and posterior semicircular canals.1,2 Its presence is most often associated with a structural lesion of the craniovertebral junction.1–3 Arnold-Chiari malformations are a frequent etiology. Other causative lesions in this location include syringomyelia, platybasia, basilar invagination, and vertebral artery dolichoectasia, as well as local and metastatic neoplastic processes. DBN may also occur with bilateral cerebellar or brainstem dysfunction secondary to stroke, multiple sclerosis, or degenerative disorders (e.g., olivopontocerebellar atrophy, Friedreich’s ataxia, or spinocerebellar ataxia). Toxic-metabolic etiologies include thiamine, B12, or magnesium deficiency or the use of lithium, amiodarone, or antiseizure medications such as carbamazepine, phenytoin, or lamotrigine. Rarely, DBN may occur in association with more diffuse central nervous system involvement secondary to an infectious4–5 or paraneoplastic6–12 encephalitis. We describe 2 patients in whom DBN was the predominant initial clinical sign of a paraneoplastic syndrome. DBN, however, is rarely the sole manifestation of a paraneoplastic syndrome and usually occurs as part of a larger cluster of signs and symptoms. It has been described in the syndromes of paraneoplastic cerebellar degeneration,6,10 paraneoplastic brainstem encephalitis,10 and paraneoplastic optic neuropathy.7,8 The neurological manifestations of these syndromes often precede the diagnosis of a neoplasm by months, or even years. Although the precise pathophysiology has yet to be elucidated, paraneoplastic disorders are thought to occur secondary to immunological mechanisms triggered by neuronal-like proteins expressed by tumors.10 Serum antibodies found in patients with these syndromes react against both the tumor and the nervous system, and in the patients described above, presumably interfere with, or destroy, neuronal networks in the brainstem and (or) cerebellum involved in ocular movement.10 Serum antibodies found in patients with paraneoplastic DBN, along with their most commonly associated malignancies, include anti-Hu (small cell lung), anti-Yo (ovary, breast), anti-Ma (testicular), anti-CV2/CRMP5 (small cell lung, thymoma), anti-Tr (Hodgkin’s lymphoma), anti-Zic1 and anti-Zic4 (small cell lung).6–12 Testing for the majority of paraneoplastic antibodies is not routinely available in most Canadian centres and is expensive, requiring financial approval from provincial health organizations. In patients with DBN of undetermined etiology, despite extensive investigation, testing for paraneoplastic antibodies should be considered in the appropriate clinical context as it may lead to earlier diagnosis and treatment of an underlying neoplasm. Even in
Correspondence the absence of autoantibodies, further investigations should still be performed to rule out a paraneoplastic process. Malignancies found in association with paraneoplastic disorders are more likely to be small or occult, and therefore, missed on initial investigations (and sometimes found only at autopsy). The finding of a specific autoantibody allows focused investigations for specific associated malignancies, potentially discovering an underlying malignancy earlier than it might otherwise have been clinically manifest, as was the case in the 2 patients reported above. The presence of DBN warrants emergent neuroimaging to rule out pathology of the craniocervical junction, cerebellum, or brainstem. In the absence of an obvious structural cause, further investigations for potential toxic, metabolic, nutritional, infectious, and paraneoplastic etiologies should be considered, guided by the clinical history and examination. REFERENCES 1. Böhmer A, Straumann D. Pathomechanism of mammalian downbeat nystagmus due to cerebellar lesion: a simple hypothesis. Neurosci Lett 1998;250:127–30. 2. Pierrot-Deseilligny C, Milea D. Vertical nystagmus: clinical facts and hypotheses. Brain 2005;128:1237–46. 3. Yeow YK, Tjia TL. The localizing value of downbeat nystagmus. Singapore Med J 1989;30:273–6. 4. Prasad S, Brown MJ, Galetta SL. Transient downbeat nystagmus from West Nile virus encephalomyelitis. Neurology 2006;66:1599–600.
Management of Coats disease with bevacizumab in 2 patients
5. Hirst LW, Clark AW, Wolinsky JS, et al. Downbeat nystagmus. A case report of herpetic brain stem encephalitis. J Clin Neuroophthalmol 1983;3:245–9. 6. Hammack J, Kotanides H, Rosenblum MK, Posner JB. Paraneoplastic cerebellar degeneration. II. Clinical and immunologic findings in 21 patients with Hodgkin’s disease. Neurology 1992;42:1938–43. 7. Malik S, Furlan AJ, Sweeney PJ, Kosmorsky GS, Wong M. Optic neuropathy: a rare paraneoplastic syndrome. J Clin Neuroophthalmol 1992;12:137–41. 8. Calvert PC. A CR(I)MP in the optic nerve: recognition and implications of paraneoplastic optic neuropathy. J Neuroophthalmol 2006;26:165–7. 9. Dalmau J, Graus F, Villarejo A, et al. Clinical analysis of antiMa2-associated encephalitis. Brain 2004;127:1831–44. 10. Bataller L, Dalmau J. Neuro-ophthalmology and paraneoplastic syndromes. Curr Opin Neurol 2004;17:3–8. 11. Rosenfeld MR, Eichen JG, Wade DF, Posner JB, Dalmau J. Molecular and clinical diversity in paraneoplastic immunity to Ma proteins. Ann Neurol 2001;50:339–48. 12. Wong AM, Musallam S, Tomlinson RD, Shannon P, Sharpe JA. Opsoclonus in three dimensions: oculographic, neuropathologic and modelling correlates. J Neurol Sci 2001;189:71–81.
Miguel Bussière, Amal Al-Khotani, Jamie L. Steckley, Michael Nicolle, David Nicolle University of Western Ontario, London, Ont. Correspondence to Miguel Bussière, MD: [email protected] Can J Ophthalmol 2008;43:243–5 doi:10.3129/i08-026
first patient had no change in visual acuity (hand movement) and persistent macular edema, the second patient had vision improvement from hand movement to 20/800 and a
C
oats disease, first described by George Coats in 1907, is characterized by telangiectatic and aneurysmal blood vessels associated with intraretinal and subretinal exudation, and progresses to exudative retinal detachment and rubeosis iridis with painful secondary glaucoma, if left untreated.1 Even after various treatments, the visual prognosis is dismal because of persistent foveal subretinal fluid, exudation, and (or) fibrosis.2 Elevated vascular endothelial growth factor (VEGF) levels in Coats disease, and rapid response to pegaptanib sodium, have been reported recently by Sun et al.3 However, the more commonly used anti-VEGF agent, bevacizumab (Avastin, Genentech Inc, San Francisco, Calif.), has not been studied in this retinal vascular disease. We report the results of intravitreal bevacizumab in 2 cases of Coats disease. Two girls (14 and 16 years old) presented with unilateral Coats disease with macular edema and exudates of more than 6 months’ duration. A complete evaluation was done, including best-corrected visual acuity, slit-lamp biomicroscopy, fundus fluorescein angiography (FFA), and optical coherence tomography (OCT). After taking informed consent, intravitreal bevacizumab (1.25 mg/0.05 mL) was injected as primary treatment in both patients. While the
Fig. 1—Fundus photographs and fluorescein angiograms at baseline (A, C, E) and 6 weeks after intravitreal bevacizumab (B, D, F) show a decrease in exudation and leakage at the macula and inferotemporal peripheral retina. CAN J OPHTHALMOL—VOL. 43, NO. 2, 2008
245
Paraneoplastic downbeat nystagmus
A
cquired downbeat nystagmus (DBN) is most often associated with a structural lesion at the craniovertebral junction. We describe 2 patients where DBN was the predominant initial clinical sign of a paraneoplastic syndrome. Neuroimaging ruled out pathology at the craniocervical junction, and further investigations ruled out toxic, metabolic, nutritional, and infectious etiologies. Serum paraneoplastic antibodies were subsequently isolated in both patients. A previously healthy 63-year-old woman presented with a 2-week history of progressive vertigo. Her husband also described memory loss and a recent 10-pound weight loss. She had a 40 pack-year history of smoking. There was no history of recent infection, travel, new medication use, alcohol, or street drug use. The initial examination was remarkable for prominent DBN. There was no dysarthria. Mild dysmetria and truncal and gait ataxia were noted. The remainder of the neurological examination was normal. She worsened over the next 2 months. On repeat examination, an obvious vertical head titubation was present and her speech was characterized by a marked scanning dysarthria. There was frequent involuntary eye blinking. Persistent conjugate DBN was observed in primary position, as well as in all directions of gaze. Pupillary response and visual fields were intact and ophthalmoscopy was unremarkable. Smooth pursuit eye movements were unremarkable, but saccades were hypometric. Prominent bilateral upper and lower limb dysmetria, as
5.
6.
7.
8.
9. 10.
chloroquine retinopathy. American Academy of Ophthalmology. Available at: http://www.aao.org. Accessed April 30, 2007. Ingster-Moati I, Bui Quoc E, Crochet M, Orssaud C, Dufier JL, Roche O. Severe chloroquine- and hydroxychloroquineinduced retinopathy. J Fr Ophtalmol 2006;29:642–50. Okun E, Gouras P, Bernstein H, Von Sallmann L. Chloroquine retinopathy: a report of eight cases with ERG and darkadaptation findings. Arch Ophthalmol 1963;69:59–71. Robberecht W, Bednarik J, Bourgeois P, van Hees J, Carton H. Myasthenic syndrome caused by direct effect of chloroquine on neuromuscular junction. Arch Neurol 1989;46:464–8. De Bleecker J, De Reuck J, Quatacker J, Meire F. Persisting chloroquine-induced myasthenia? Acta Clin Belg 1991;46: 401–6. Easterbrook M. Dose relationships in patients with early chloroquine retinopathy. J Rheumatol 1987;14:472–5. Kellner U, Renner AB, Tillack H. Fundus autofluorescence and mfERG for early detection of retinal alterations in patients using chloroquine/hydroxychloroquine. Invest Ophthalmol Vis Sci 2006;47:3531–8.
Rusty J. Ritenour, Alan F. Cruess, Aditya V. Mishra Dalhousie University, Halifax, N.S. Correspondence to Rusty Ritenour, MD: [email protected] Can J Ophthalmol 2008;43:241–3 doi:10.3129/i08-023
well as truncal and gait ataxia, were also noted. The remainder of the neurological examination was normal. Examination of the respiratory, cardiovascular, and abdominal systems was unremarkable. Breast examination was normal and lymph nodes were not palpable. Initial magnetic resonance imaging (MRI) of the brain did not reveal any structural lesions of the craniocervical junction, brainstem, or cerebellum, and there were no encephalitic changes. Further investigations were aimed at ruling out a toxic-metabolic, inflammatory, infectious, or paraneoplastic etiology for the patient’s symptoms (see later discussion). Complete blood count, electrolytes (including calcium, magnesium, and phosphate), renal indices, liver enzymes, vitamin B12 and folate levels, thyroid-stimulating hormone and antithyroid antibodies, VDRL, and Lyme serology were all normal or negative. Cerebrospinal fluid (CSF) analysis revealed a nucleated cell count of 26 ×106 cells/L (94% lymphocytes), protein of 540 mg/L (normal 150–450 mg/L), and glucose of 4.7 mmol/L (normal 2.2–3.9 mmol/L). CSF cytology and angiotensin-converting enzyme levels were normal. Bacterial, viral, and fungal cultures, as well as viral polymerase chain reaction (PCR), were negative. A computed tomography scan of the chest, abdomen, and pelvis revealed a 1.2 cm × 2.3 cm right paratracheal lymph node, and a 1.5 cm × 1.8 cm spiculated right apical lung lesion (Fig. 1) suspicious for malignancy. Mediastinoscopy and biopsy of the paratracheal node was performed. Pathological examination demonstrated a metastatic, poorly differentiated adenocarcinoma. Results CAN J OPHTHALMOL—VOL. 43, NO. 2, 2008
243
Correspondence of a paraneoplastic antibody screen (NeoComplete Paraneoplastic profile, Athena Diagnostics Inc, Worcester, Mass.) eventually demonstrated the presence of serum antiMa1 and anti-Ma2 antibodies. The patient was treated with etoposide/carboplatin chemotherapy, as well as palliative radiotherapy. There was no improvement in her DBN or cerebellar symptoms, and she died approximately 1 year after her presentation. A 57-year-old woman presented with several weeks of fatigue, nausea, and loss of appetite associated with oscillopsia and a sensation of imbalance. Her past medical history was significant for hypertension, hyperlipidemia, and peptic ulcer disease. She had a 20 pack-year history of smoking. There was no history of recent infection, travel, new medication use, alcohol, or street drug use. Initial clinical examination was remarkable primarily for DBN present in primary position and in all directions of gaze (see Video 1, available online). Eye movements were full, although smooth pursuit movements were saccadic. Pupillary response and ophthalmoscopy were normal. Over the following several months, however, the patient developed marked scanning dysarthria and ataxia (Video 1). At the 6-month follow-up, the patient was no longer able to ambulate independently because of severe truncal and gait ataxia. The rest of the neurological examination remained normal. Respiratory, cardiovascular, abdominal, and breast examinations were unremarkable. Complete blood count, electrolytes, vitamin B1, B12, and folate levels, vasculitis screen, and renal, liver, and thyroid indices were all normal or negative. CSF analysis demonstrated a nucleated cell count of 2 ×106 cells/L (87% lymphocytes), protein of 588 mg/L (normal 150–450 mg/L), and glucose of 3.4 mmol/L (normal 2.2–3.9 mmol/L). CSF cytology, cultures, and viral PCR were negative. An MRI of the brain did not reveal any abnormalities of the craniocervical junction, brainstem, or cerebellum and no abnormal enhancement. Chest x-ray, abdominal and pelvic ultrasound, and mammography were negative for malignancy. Screening for paraneoplastic antibodies (NeoComplete Paraneoplastic profile, Athena Diagnostics Inc), however, demonstrated the presence of serum anti-Hu and -CV2 antibodies, highly suggestive of an underlying small cell lung cancer. Persistent investigation, including computed tomography of the chest at the 10-month follow-up, eventually demonstrated the development of subcarinal lym-
Fig. 1—Axial computed tomography of the thorax, demonstrating an enlarged paratracheal lymph node (white arrow on left) and a spiculated apical lung lesion (black arrow on right).
244
CAN J OPHTHALMOL—VOL. 43, NO. 2, 2008
phadenopathy. Pathological examination of a transbronchial needle aspirate was consistent with small cell lung cancer. At a 3-month follow-up subsequent to a course of palliative radiotherapy, the patient’s disabling neurological symptoms had stabilized but showed no sign of improvement. Acquired DBN is thought to occur as a result of disrupted connections among the cerebellum, the medulla, and the anterior and posterior semicircular canals.1,2 Its presence is most often associated with a structural lesion of the craniovertebral junction.1–3 Arnold-Chiari malformations are a frequent etiology. Other causative lesions in this location include syringomyelia, platybasia, basilar invagination, and vertebral artery dolichoectasia, as well as local and metastatic neoplastic processes. DBN may also occur with bilateral cerebellar or brainstem dysfunction secondary to stroke, multiple sclerosis, or degenerative disorders (e.g., olivopontocerebellar atrophy, Friedreich’s ataxia, or spinocerebellar ataxia). Toxic-metabolic etiologies include thiamine, B12, or magnesium deficiency or the use of lithium, amiodarone, or antiseizure medications such as carbamazepine, phenytoin, or lamotrigine. Rarely, DBN may occur in association with more diffuse central nervous system involvement secondary to an infectious4–5 or paraneoplastic6–12 encephalitis. We describe 2 patients in whom DBN was the predominant initial clinical sign of a paraneoplastic syndrome. DBN, however, is rarely the sole manifestation of a paraneoplastic syndrome and usually occurs as part of a larger cluster of signs and symptoms. It has been described in the syndromes of paraneoplastic cerebellar degeneration,6,10 paraneoplastic brainstem encephalitis,10 and paraneoplastic optic neuropathy.7,8 The neurological manifestations of these syndromes often precede the diagnosis of a neoplasm by months, or even years. Although the precise pathophysiology has yet to be elucidated, paraneoplastic disorders are thought to occur secondary to immunological mechanisms triggered by neuronal-like proteins expressed by tumors.10 Serum antibodies found in patients with these syndromes react against both the tumor and the nervous system, and in the patients described above, presumably interfere with, or destroy, neuronal networks in the brainstem and (or) cerebellum involved in ocular movement.10 Serum antibodies found in patients with paraneoplastic DBN, along with their most commonly associated malignancies, include anti-Hu (small cell lung), anti-Yo (ovary, breast), anti-Ma (testicular), anti-CV2/CRMP5 (small cell lung, thymoma), anti-Tr (Hodgkin’s lymphoma), anti-Zic1 and anti-Zic4 (small cell lung).6–12 Testing for the majority of paraneoplastic antibodies is not routinely available in most Canadian centres and is expensive, requiring financial approval from provincial health organizations. In patients with DBN of undetermined etiology, despite extensive investigation, testing for paraneoplastic antibodies should be considered in the appropriate clinical context as it may lead to earlier diagnosis and treatment of an underlying neoplasm. Even in
Correspondence the absence of autoantibodies, further investigations should still be performed to rule out a paraneoplastic process. Malignancies found in association with paraneoplastic disorders are more likely to be small or occult, and therefore, missed on initial investigations (and sometimes found only at autopsy). The finding of a specific autoantibody allows focused investigations for specific associated malignancies, potentially discovering an underlying malignancy earlier than it might otherwise have been clinically manifest, as was the case in the 2 patients reported above. The presence of DBN warrants emergent neuroimaging to rule out pathology of the craniocervical junction, cerebellum, or brainstem. In the absence of an obvious structural cause, further investigations for potential toxic, metabolic, nutritional, infectious, and paraneoplastic etiologies should be considered, guided by the clinical history and examination. REFERENCES 1. Böhmer A, Straumann D. Pathomechanism of mammalian downbeat nystagmus due to cerebellar lesion: a simple hypothesis. Neurosci Lett 1998;250:127–30. 2. Pierrot-Deseilligny C, Milea D. Vertical nystagmus: clinical facts and hypotheses. Brain 2005;128:1237–46. 3. Yeow YK, Tjia TL. The localizing value of downbeat nystagmus. Singapore Med J 1989;30:273–6. 4. Prasad S, Brown MJ, Galetta SL. Transient downbeat nystagmus from West Nile virus encephalomyelitis. Neurology 2006;66:1599–600.
Management of Coats disease with bevacizumab in 2 patients
5. Hirst LW, Clark AW, Wolinsky JS, et al. Downbeat nystagmus. A case report of herpetic brain stem encephalitis. J Clin Neuroophthalmol 1983;3:245–9. 6. Hammack J, Kotanides H, Rosenblum MK, Posner JB. Paraneoplastic cerebellar degeneration. II. Clinical and immunologic findings in 21 patients with Hodgkin’s disease. Neurology 1992;42:1938–43. 7. Malik S, Furlan AJ, Sweeney PJ, Kosmorsky GS, Wong M. Optic neuropathy: a rare paraneoplastic syndrome. J Clin Neuroophthalmol 1992;12:137–41. 8. Calvert PC. A CR(I)MP in the optic nerve: recognition and implications of paraneoplastic optic neuropathy. J Neuroophthalmol 2006;26:165–7. 9. Dalmau J, Graus F, Villarejo A, et al. Clinical analysis of antiMa2-associated encephalitis. Brain 2004;127:1831–44. 10. Bataller L, Dalmau J. Neuro-ophthalmology and paraneoplastic syndromes. Curr Opin Neurol 2004;17:3–8. 11. Rosenfeld MR, Eichen JG, Wade DF, Posner JB, Dalmau J. Molecular and clinical diversity in paraneoplastic immunity to Ma proteins. Ann Neurol 2001;50:339–48. 12. Wong AM, Musallam S, Tomlinson RD, Shannon P, Sharpe JA. Opsoclonus in three dimensions: oculographic, neuropathologic and modelling correlates. J Neurol Sci 2001;189:71–81.
Miguel Bussière, Amal Al-Khotani, Jamie L. Steckley, Michael Nicolle, David Nicolle University of Western Ontario, London, Ont. Correspondence to Miguel Bussière, MD: [email protected] Can J Ophthalmol 2008;43:243–5 doi:10.3129/i08-026
first patient had no change in visual acuity (hand movement) and persistent macular edema, the second patient had vision improvement from hand movement to 20/800 and a
C
oats disease, first described by George Coats in 1907, is characterized by telangiectatic and aneurysmal blood vessels associated with intraretinal and subretinal exudation, and progresses to exudative retinal detachment and rubeosis iridis with painful secondary glaucoma, if left untreated.1 Even after various treatments, the visual prognosis is dismal because of persistent foveal subretinal fluid, exudation, and (or) fibrosis.2 Elevated vascular endothelial growth factor (VEGF) levels in Coats disease, and rapid response to pegaptanib sodium, have been reported recently by Sun et al.3 However, the more commonly used anti-VEGF agent, bevacizumab (Avastin, Genentech Inc, San Francisco, Calif.), has not been studied in this retinal vascular disease. We report the results of intravitreal bevacizumab in 2 cases of Coats disease. Two girls (14 and 16 years old) presented with unilateral Coats disease with macular edema and exudates of more than 6 months’ duration. A complete evaluation was done, including best-corrected visual acuity, slit-lamp biomicroscopy, fundus fluorescein angiography (FFA), and optical coherence tomography (OCT). After taking informed consent, intravitreal bevacizumab (1.25 mg/0.05 mL) was injected as primary treatment in both patients. While the
Fig. 1—Fundus photographs and fluorescein angiograms at baseline (A, C, E) and 6 weeks after intravitreal bevacizumab (B, D, F) show a decrease in exudation and leakage at the macula and inferotemporal peripheral retina. CAN J OPHTHALMOL—VOL. 43, NO. 2, 2008
245