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Bilateral Intracavernous Carotid Artery Occlusion Caused by Invasive Lymphocytic Hypophysitis
Case Report
Bilateral Intracavernous Carotid Artery Occlusion Caused by Invasive Lymphocytic Hypophysitis Luca Peruzzotti-Jametti, MD,* Davide Strambo, MD,* Francesca Sangalli, MD,* Annamaria De Bellis, MD,† Giancarlo Comi, MD,* and Maria Sessa, MD*
Lymphocytic hypophysitis is a rarely recognized disease that is characterized by inflammatory infiltration and destruction of the pituitary gland. The etiology of lymphocytic hypophysitis is still unclear, but an autoimmune pathogenesis has been advocated. In fact, histopathologic specimens reveal a diffuse infiltration of the hypophysis by CD31CD41 T cells and CD201 plasma cells, and antipituitary antibodies are usually found in sera of affected patients. Although previous cases were found to be correlated only to pregnancy and the postpartum period, recent reports in men and women (without association with pregnancy) suggest a possibly higher prevalence of disease. We present the case of a 55-year-old woman affected by an unusually aggressive form of lymphocytic hypophysitis that infiltrated both cavernous sinuses causing bilateral internal carotid artery occlusion and acute ischemic stroke. Diagnosis was achieved with both a biopsy specimen of the pituitary gland and the detection of antipituitary antibodies. The prompt administration of steroid therapy was effective to obtain regression and stabilization of the disease, but both carotid arteries remained permanently occluded. The natural history of lymphocytic hypophysitis is unpredictable. It usually has a benign evolution, but in exceptional cases the inflammatory process may extend beyond the pituitary gland and infiltrate the surrounding structures. These extremely serious consequences highlight the importance of early diagnosis and treatment of this otherwise curable disease. Key Words: Bilateral carotid artery occlusion—ischemic stroke— lymphocytic hypophysitis. Ó 2012 by National Stroke Association
From the *Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Stroke Unit-Department of Neurology and Neurophysiology, Milan; and †‘‘F. Magrassi, A. Lanzara,’’ Second University of Naples, Department of Clinical and Experimental Medicine and Surgery, Naples, Italy. Received March 19, 2012; revision received May 13, 2012; accepted June 4, 2012. Drs. Peruzzotti-Jametti and Strambo contributed equally to this manuscript. Address correspondence to Luca Peruzzotti-Jametti, MD, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Stroke Unit-Department of Neurology and Neurophysiology, Via Olgettina 58, I-20132 Milano, Italy. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2012 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2012.06.003
A 55-year-old woman with a previously unremarkable clinical history developed recurring episodes of headache and nausea. After 3 months, a magnetic resonance imaging (MRI) scan of the brain was performed. The examination revealed a 1-cm wide pituitary lesion that was initially interpreted as a pituitary adenoma (Fig 1A). At 3 months of follow-up, a second MRI revealed an extension of the pituitary lesion to the right cavernous sinus, causing asymptomatic occlusion of the right internal carotid artery (ICA; Fig 1B). At that time, no treatment was introduced and a wait and watch approach was adopted. Four months later, the patient suddenly developed slurred speech and right-sided
Journal of Stroke and Cerebrovascular Diseases, Vol. 21, No. 8 (November), 2012: pp 918.e9-918.e11
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Figure 1. (A) T2-weighted fluid-attenuated inversion recovery (FLAIR) magnetic resonance images of the initial pituitary lesion (arrow), (B) infiltration of the right cavernous sinus causing right internal carotid artery (ICA) occlusion (arrow) after 3 months, and (C) bilateral intracavernous ICA occlusion (arrows) at stroke onset (D). (E) Hematoxylin and eosin–stained photomicrographs showing diffuse infiltration of the pituitary gland: immunohistochemistry showing CD31 lymphocytes (upper right insert) and CD201 plasma cell infiltrates (lower right insert). Scale bar: 20 mm. (F) Magnetic resonance angiography at follow-up showing complete thrombosis of both internal carotid arteries to their origin (arrows), with the intracranial circulation depending on the vertebrobasilar axis.
hemiparesis. She was brought to our attention on the following day. MRI and magnetic resonance angiography scans of the brain revealed a dramatic expansion of the pituitary lesion to both cavernous sinuses, causing bilateral intracavernous ICA occlusion and concomitant acute left frontoparietal ischemic stroke (Figs 1C and 1D). Cerebrospinal fluid was normal, except for positive intrathecal immunoglobulin G synthesis. Blood examinations revealed hallmarks of autoimmunity, with positivity for antinuclear and anticardiolipin immunoglobulin M antibodies. A trans-sphenoidal biopsy specimen of the pituitary lesion revealed necrotic and inflammatory material with a small lymphocytic infiltrate, which is suggestive of lymphocytic hypophysitis (LYH; Fig 1E). To confirm our diagnosis, antipituitary gland antibodies (APAs) were dosed and found to be positive at high titers. Steroid therapy was introduced with reduction of the pituitary mass, but at follow-up both internal carotid arteries remained permanently occluded (Fig 1F).
Discussion Bilateral carotid artery occlusion is a rare clinical finding.1 In the vast majority of cases, the occlusion is located at the extracranial portion of the carotid arteries and is caused by severe atherosclerotic disease.2 The involvement of both carotid arteries at the intracranial level is less frequent and, to our knowledge, only 1 other case of permanent bilateral intracavernous occlusion has been described.3 Interestingly, both cases were triggered by an aggressive form of LYH. LYH is a rarely recognized disease that should not be forgotten in the differential diagnosis of the most relevant causes of pituitary lesions with cavernous sinus involvement (eg, granulomatous processes and tumors).4 However, because the criterion standard for the diagnosis of LYH remains trans-sphenoidal pituitary biopsy, more feasible tools are needed to identify this disease at early time points.5 Remarkably, positivity for APAs is emerging as a reliable marker for autoimmune hypophysitis.6 In our case, in fact, early testing could have prevented the
LYMPHOCYTIC HYPOPHYSITIS AND BILATERAL ICA OCCLUSION
bilateral occlusion of the ICAs, stroke, and subsequent disability.
References 1. Mead G, Wardlaw J, Lewis S, et al. No evidence that severity of stroke in internal carotid occlusion is related to collateral arteries. J Neurol Neurosurg Psychiatry 2006;77:729-733. 2. Persoon S, Klijn C, Algra A, et al. Bilateral carotid artery occlusion with transient or moderately disabling ischaemic stroke: Clinical features and long-term outcome. J Neurol 2009;256:1728-1735.
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3. Melgar MA, Mariwalla N, Gloss DS, et al. Recurrent lymphocytic hypophysitis and bilateral intracavernous carotid artery occlusion. An observation and review of the literature. Neurol Res 2006;28:177-183. 4. Caturegli P, Newschaffer C, Olivi A, et al. Autoimmune hypophysitis. Endocr Rev 2005;26:599-614. 5. Rumana M, Kirmani A, Khursheed A, et al. Lymphocytic hypophysitis with normal pituitary function mimicking a pituitary adenoma: A case report and review of literature. Clin Neuropathol 2010;29:26-31. 6. De Bellis A, Bizzarro A, Bellastella A. Pituitary antibodies and lymphocytic hypophysitis. Best Pract Res Clin Endocrinol Metab 2005;19:67-84.
Bilateral Intracavernous Carotid Artery Occlusion Caused by Invasive Lymphocytic Hypophysitis Luca Peruzzotti-Jametti, MD,* Davide Strambo, MD,* Francesca Sangalli, MD,* Annamaria De Bellis, MD,† Giancarlo Comi, MD,* and Maria Sessa, MD*
Lymphocytic hypophysitis is a rarely recognized disease that is characterized by inflammatory infiltration and destruction of the pituitary gland. The etiology of lymphocytic hypophysitis is still unclear, but an autoimmune pathogenesis has been advocated. In fact, histopathologic specimens reveal a diffuse infiltration of the hypophysis by CD31CD41 T cells and CD201 plasma cells, and antipituitary antibodies are usually found in sera of affected patients. Although previous cases were found to be correlated only to pregnancy and the postpartum period, recent reports in men and women (without association with pregnancy) suggest a possibly higher prevalence of disease. We present the case of a 55-year-old woman affected by an unusually aggressive form of lymphocytic hypophysitis that infiltrated both cavernous sinuses causing bilateral internal carotid artery occlusion and acute ischemic stroke. Diagnosis was achieved with both a biopsy specimen of the pituitary gland and the detection of antipituitary antibodies. The prompt administration of steroid therapy was effective to obtain regression and stabilization of the disease, but both carotid arteries remained permanently occluded. The natural history of lymphocytic hypophysitis is unpredictable. It usually has a benign evolution, but in exceptional cases the inflammatory process may extend beyond the pituitary gland and infiltrate the surrounding structures. These extremely serious consequences highlight the importance of early diagnosis and treatment of this otherwise curable disease. Key Words: Bilateral carotid artery occlusion—ischemic stroke— lymphocytic hypophysitis. Ó 2012 by National Stroke Association
From the *Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Stroke Unit-Department of Neurology and Neurophysiology, Milan; and †‘‘F. Magrassi, A. Lanzara,’’ Second University of Naples, Department of Clinical and Experimental Medicine and Surgery, Naples, Italy. Received March 19, 2012; revision received May 13, 2012; accepted June 4, 2012. Drs. Peruzzotti-Jametti and Strambo contributed equally to this manuscript. Address correspondence to Luca Peruzzotti-Jametti, MD, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Stroke Unit-Department of Neurology and Neurophysiology, Via Olgettina 58, I-20132 Milano, Italy. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2012 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2012.06.003
A 55-year-old woman with a previously unremarkable clinical history developed recurring episodes of headache and nausea. After 3 months, a magnetic resonance imaging (MRI) scan of the brain was performed. The examination revealed a 1-cm wide pituitary lesion that was initially interpreted as a pituitary adenoma (Fig 1A). At 3 months of follow-up, a second MRI revealed an extension of the pituitary lesion to the right cavernous sinus, causing asymptomatic occlusion of the right internal carotid artery (ICA; Fig 1B). At that time, no treatment was introduced and a wait and watch approach was adopted. Four months later, the patient suddenly developed slurred speech and right-sided
Journal of Stroke and Cerebrovascular Diseases, Vol. 21, No. 8 (November), 2012: pp 918.e9-918.e11
918.e9
L. PERUZZOTTI-JAMETTI ET AL.
918.e10
Figure 1. (A) T2-weighted fluid-attenuated inversion recovery (FLAIR) magnetic resonance images of the initial pituitary lesion (arrow), (B) infiltration of the right cavernous sinus causing right internal carotid artery (ICA) occlusion (arrow) after 3 months, and (C) bilateral intracavernous ICA occlusion (arrows) at stroke onset (D). (E) Hematoxylin and eosin–stained photomicrographs showing diffuse infiltration of the pituitary gland: immunohistochemistry showing CD31 lymphocytes (upper right insert) and CD201 plasma cell infiltrates (lower right insert). Scale bar: 20 mm. (F) Magnetic resonance angiography at follow-up showing complete thrombosis of both internal carotid arteries to their origin (arrows), with the intracranial circulation depending on the vertebrobasilar axis.
hemiparesis. She was brought to our attention on the following day. MRI and magnetic resonance angiography scans of the brain revealed a dramatic expansion of the pituitary lesion to both cavernous sinuses, causing bilateral intracavernous ICA occlusion and concomitant acute left frontoparietal ischemic stroke (Figs 1C and 1D). Cerebrospinal fluid was normal, except for positive intrathecal immunoglobulin G synthesis. Blood examinations revealed hallmarks of autoimmunity, with positivity for antinuclear and anticardiolipin immunoglobulin M antibodies. A trans-sphenoidal biopsy specimen of the pituitary lesion revealed necrotic and inflammatory material with a small lymphocytic infiltrate, which is suggestive of lymphocytic hypophysitis (LYH; Fig 1E). To confirm our diagnosis, antipituitary gland antibodies (APAs) were dosed and found to be positive at high titers. Steroid therapy was introduced with reduction of the pituitary mass, but at follow-up both internal carotid arteries remained permanently occluded (Fig 1F).
Discussion Bilateral carotid artery occlusion is a rare clinical finding.1 In the vast majority of cases, the occlusion is located at the extracranial portion of the carotid arteries and is caused by severe atherosclerotic disease.2 The involvement of both carotid arteries at the intracranial level is less frequent and, to our knowledge, only 1 other case of permanent bilateral intracavernous occlusion has been described.3 Interestingly, both cases were triggered by an aggressive form of LYH. LYH is a rarely recognized disease that should not be forgotten in the differential diagnosis of the most relevant causes of pituitary lesions with cavernous sinus involvement (eg, granulomatous processes and tumors).4 However, because the criterion standard for the diagnosis of LYH remains trans-sphenoidal pituitary biopsy, more feasible tools are needed to identify this disease at early time points.5 Remarkably, positivity for APAs is emerging as a reliable marker for autoimmune hypophysitis.6 In our case, in fact, early testing could have prevented the
LYMPHOCYTIC HYPOPHYSITIS AND BILATERAL ICA OCCLUSION
bilateral occlusion of the ICAs, stroke, and subsequent disability.
References 1. Mead G, Wardlaw J, Lewis S, et al. No evidence that severity of stroke in internal carotid occlusion is related to collateral arteries. J Neurol Neurosurg Psychiatry 2006;77:729-733. 2. Persoon S, Klijn C, Algra A, et al. Bilateral carotid artery occlusion with transient or moderately disabling ischaemic stroke: Clinical features and long-term outcome. J Neurol 2009;256:1728-1735.
918.e11
3. Melgar MA, Mariwalla N, Gloss DS, et al. Recurrent lymphocytic hypophysitis and bilateral intracavernous carotid artery occlusion. An observation and review of the literature. Neurol Res 2006;28:177-183. 4. Caturegli P, Newschaffer C, Olivi A, et al. Autoimmune hypophysitis. Endocr Rev 2005;26:599-614. 5. Rumana M, Kirmani A, Khursheed A, et al. Lymphocytic hypophysitis with normal pituitary function mimicking a pituitary adenoma: A case report and review of literature. Clin Neuropathol 2010;29:26-31. 6. De Bellis A, Bizzarro A, Bellastella A. Pituitary antibodies and lymphocytic hypophysitis. Best Pract Res Clin Endocrinol Metab 2005;19:67-84.