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Gone in the blink of an eye – A Tolosa-Hunt syndrome variant
Journal of Clinical Neuroscience xxx (xxxx) xxx
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Case report
Gone in the blink of an eye – A Tolosa-Hunt syndrome variant Farzan Dholoo a, Amanda Shabana b, Myrella Paschali c, Amit K.J. Mandal a, Constantinos G Missouris a,d,⇑ a
Wexham Park Hospital, Frimley Health NHS Foundation Trust, Internal Medicine, Berkshire, UK Frimley Park Hospital, Frimley Health NHS Foundation Trust, Internal Medicine, Berkshire, UK c Brigham and Women’s Hospital, Harvard Medical School, Anesthesiology, Perioperative & Pain Medicine, Boston, MA 02467, USA d University of Cyprus Medical School, Cardiology, Nicosia, Cyprus b
a r t i c l e
i n f o
Article history: Received 5 September 2019 Accepted 16 December 2019 Available online xxxx Keywords: Tolosa–Hunt syndrome Tolosa–Hunt variant Ophthalmoplegia Oculomotor nerve
a b s t r a c t Tolosa-Hunt syndrome is a rare disorder characterized by severe peri-orbital headache and ophthalmoplegia resulting from pseudotumour in the cavernous sinus compressing structures within it, namely cranial nerves III, IV, and VI and the superior divisions of cranial nerve V. We report the case of a 47 year old female who presented with painless left unilateral ptosis and complete external ophthalmoplegia. Magnetic Resonance Imaging (MRI) identified an enhancing heterogeneous mass filling the left cavernous sinus, following the course of the oculomotor nerve. After 2 weeks symptoms and signs resolved and there was a parallel resolution of the MRI findings, without the administration of corticosteroids. As far as we are aware this is one of the first reports of Tolosa-Hunt syndrome variant, with painless neurological involvement confined solely to the oculomotor nerve, and with complete resolution without pharmacological intervention. Ó 2019 Elsevier Ltd. All rights reserved.
1. Case A 47-year-old female presented with a 10 day history of painless monocular diplopia in the left eye and drooping of the left upper eyelid. The patient denied head trauma. Past medical history was unremarkable, and she was not taking any medications. There was complete ptosis of the left eye, which was positioned downward and outward and unable to adduct, infraduct or supraduct. There was anisocoria (pupillary diameter greater in the left eye) with a sluggish light reflex in the left eye. These features were consistent with a complete oculomotor (III) nerve palsy. Computed tomography (CT) cerebral angiography and venography did not demonstrate aneurysms or vascular malformation. Magnetic Resonance Imaging (MRI) with gadolinium identified a heterogeneous mass filling the left cavernous sinus with a contiguous tail of enhancement following the course of the oculomotor nerve (Fig. 1). Laboratory investigations including angiotensin converting enzyme, lactate dehydrogenase, antinuclear antibody, anti-double stranded deoxyribonucleic acid antibody, anti-smooth muscle antibody, anti-neutrophil cytoplasmic antibody, serum protein
⇑ Corresponding author at: Departments of Cardiology and Internal Medicine, Frimley Health NHS Foundation Trust, Wexham Street, Slough, UK. E-mail addresses: [email protected] (F. Dholoo), [email protected] (A. Shabana), [email protected] (M. Paschali), [email protected] (A.K.J. Mandal), [email protected] (C.G Missouris).
electrophoresis (notably immunoglobulin IgG4) and glycosylated haemoglobin were normal. Fluorescent treponemal antibody tests and Lyme serologies were unyielding. Cerebrospinal fluid studies were normal (cytology, serology for Lyme disease and syphilis, angiotensin converting enzyme and cultures for bacteria, fungi, and mycobacteria). Mantoux test was negative. Positive emission tomography showed avid lymph nodes in the left infra-clavicular fossa and axilla. Biopsy of a left level IV neck node revealed benign reactive lymphoid tissue. The main differentials of tuberculosis, sarcoidosis, lymphoma, carcinomatosis, autoimmune disease and IgG4 related disease were felt to be less likely and a diagnosis of non-specific inflammatory process in the cavernous sinus, anatomically related to the oculomotor nerve, possibly an isolated oculomotor schwannoma, was therefore made. In the absence of pain, it was decided to withhold corticosteroids and watch and wait. The ptosis and eye movements improved within 1 week, and there was complete resolution of the third nerve palsy after 2 weeks, without pharmacological intervention. This coincided with disappearance of the mass within the cavernous sinus (Figure), allowing a refined diagnosis of TolosaHunt syndrome, with painless neurological involvement confined to the oculomotor nerve. 2. Discussion First described in 1954 by Tolosa and further elucidated by Hunt in 1961, the Tolosa-Hunt syndrome (THS) has a reported inci-
https://doi.org/10.1016/j.jocn.2019.12.037 0967-5868/Ó 2019 Elsevier Ltd. All rights reserved.
Please cite this article as: F. Dholoo, A. Shabana, M. Paschali et al., Gone in the blink of an eye – A Tolosa-Hunt syndrome variant, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.12.037
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Case report/Journal of Clinical Neuroscience xxx (xxxx) xxx
Fig. 1. MRI brain demonstrating a heterogeneous mass filling the left cavernous sinus (A and B) with a contiguous tail of enhancement extending posteriorly following the course of the oculomotor nerve (C) and complete resolution of the mass within the cavernous sinus after 2 weeks without pharmacological intervention (D versus E and F versus G).
dence of less than one in a million individuals per year [1]. It is characterised by idiopathic granulomatous inflammation of the cavernous sinus and/or superior orbital fissure leading to secondary dysfunction of the structures within, namely cranial nerves III, IV, VI, and the superior divisions of cranial nerve V. The majority of patients present with severe unilateral orbital pain and paralysis of one or more associated cranial nerves.
Typical MRI findings are engorgement of the cavernous sinus with abnormal tissue that strongly enhances with gadolinium, abnormal convexity of the wall and focal narrowing of the intracavernous internal carotid artery [2]. These findings are not unique to THS and may also be found in other diseases, such as lymphoma, meningioma and granulomatous disease. Biopsy of the lesion is the definitive diagnostic test, but this is seldom necessary unless there
Please cite this article as: F. Dholoo, A. Shabana, M. Paschali et al., Gone in the blink of an eye – A Tolosa-Hunt syndrome variant, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.12.037
Case report/Journal of Clinical Neuroscience xxx (xxxx) xxx
is failure of response to corticosteroid treatment. Resolution of orbital pain within 1–3 days of treatment, also serves as diagnostic affirmation [3]. THS frequently masquerades as other conditions and there are no unifying or pathognomonic characteristics. Furthermore, it is suspected that the spectrum of clinical presentations of the syndrome might be wider than was previously recognized [4]. Emphasis is laid upon this being a diagnosis of exclusion which can only be made once the life-threatening processes within the differential diagnosis have been adequately excluded. Acquired painless third nerve ophthalmoplegia is a rare clinical presentation. Indeed, our patient did not meet the diagnostic criteria for THS. We postulate therefore, that the process was limited to the course of the oculomotor nerve with little or no mass effect within the cavernous sinus, resulting in isolated, self-limiting, painless paresis of the third nerve. For want of a diagnosis, we are assuming a THS variant. Contributors FD conceived the study and collected data and had a major role in writing the manuscript. AS performed the literature search and had also a major role in writing the manuscript. MP interpreted the data and revised the manuscript for intellectual content. AKJM was involved in the care of the patient as an attending physician, interpreted the data and revised the manuscript for intellectual content. CGM was involved in the care of the patient as an attending physician, oversaw the project and edited the manuscript up to submission.
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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgements We thank Dr. Matthew Bull and Dr. Elena Boyd for their ongoing help with the analysis and interpretation of images used in this article. Funding No funding was sourced for the project. Patient consent for publication Verbal and written consent was obtained from the patient. References [1] Iaconetta G, Stella L, Esposito M, et al. Tolosa-Hunt syndrome extending in the cerebello-pontine angle. Cephalalgia 2005;25:746–50. [2] Razek AA, Castillo M. Imaging lesions of the cavernous sinus. AJNR Am J Neuroradiol 2009;30:444–52. [3] Zhang X, Zhang W, Liu R, et al. Factors that influence Tolosa-Hunt syndrome and the short-term response to steroid pulse treatment. J Neurol Sci 2014;341:13–6. [4] Hung C, Chang K, Chen Y, et al. Clinical and radiological findings suggesting disorders other than Tolosa-Hunt syndrome among ophthalmoplegic patients: a retrospective analysis. Headache: J Head Face Pain 2015;55:252–64.
Please cite this article as: F. Dholoo, A. Shabana, M. Paschali et al., Gone in the blink of an eye – A Tolosa-Hunt syndrome variant, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.12.037
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Case report
Gone in the blink of an eye – A Tolosa-Hunt syndrome variant Farzan Dholoo a, Amanda Shabana b, Myrella Paschali c, Amit K.J. Mandal a, Constantinos G Missouris a,d,⇑ a
Wexham Park Hospital, Frimley Health NHS Foundation Trust, Internal Medicine, Berkshire, UK Frimley Park Hospital, Frimley Health NHS Foundation Trust, Internal Medicine, Berkshire, UK c Brigham and Women’s Hospital, Harvard Medical School, Anesthesiology, Perioperative & Pain Medicine, Boston, MA 02467, USA d University of Cyprus Medical School, Cardiology, Nicosia, Cyprus b
a r t i c l e
i n f o
Article history: Received 5 September 2019 Accepted 16 December 2019 Available online xxxx Keywords: Tolosa–Hunt syndrome Tolosa–Hunt variant Ophthalmoplegia Oculomotor nerve
a b s t r a c t Tolosa-Hunt syndrome is a rare disorder characterized by severe peri-orbital headache and ophthalmoplegia resulting from pseudotumour in the cavernous sinus compressing structures within it, namely cranial nerves III, IV, and VI and the superior divisions of cranial nerve V. We report the case of a 47 year old female who presented with painless left unilateral ptosis and complete external ophthalmoplegia. Magnetic Resonance Imaging (MRI) identified an enhancing heterogeneous mass filling the left cavernous sinus, following the course of the oculomotor nerve. After 2 weeks symptoms and signs resolved and there was a parallel resolution of the MRI findings, without the administration of corticosteroids. As far as we are aware this is one of the first reports of Tolosa-Hunt syndrome variant, with painless neurological involvement confined solely to the oculomotor nerve, and with complete resolution without pharmacological intervention. Ó 2019 Elsevier Ltd. All rights reserved.
1. Case A 47-year-old female presented with a 10 day history of painless monocular diplopia in the left eye and drooping of the left upper eyelid. The patient denied head trauma. Past medical history was unremarkable, and she was not taking any medications. There was complete ptosis of the left eye, which was positioned downward and outward and unable to adduct, infraduct or supraduct. There was anisocoria (pupillary diameter greater in the left eye) with a sluggish light reflex in the left eye. These features were consistent with a complete oculomotor (III) nerve palsy. Computed tomography (CT) cerebral angiography and venography did not demonstrate aneurysms or vascular malformation. Magnetic Resonance Imaging (MRI) with gadolinium identified a heterogeneous mass filling the left cavernous sinus with a contiguous tail of enhancement following the course of the oculomotor nerve (Fig. 1). Laboratory investigations including angiotensin converting enzyme, lactate dehydrogenase, antinuclear antibody, anti-double stranded deoxyribonucleic acid antibody, anti-smooth muscle antibody, anti-neutrophil cytoplasmic antibody, serum protein
⇑ Corresponding author at: Departments of Cardiology and Internal Medicine, Frimley Health NHS Foundation Trust, Wexham Street, Slough, UK. E-mail addresses: [email protected] (F. Dholoo), [email protected] (A. Shabana), [email protected] (M. Paschali), [email protected] (A.K.J. Mandal), [email protected] (C.G Missouris).
electrophoresis (notably immunoglobulin IgG4) and glycosylated haemoglobin were normal. Fluorescent treponemal antibody tests and Lyme serologies were unyielding. Cerebrospinal fluid studies were normal (cytology, serology for Lyme disease and syphilis, angiotensin converting enzyme and cultures for bacteria, fungi, and mycobacteria). Mantoux test was negative. Positive emission tomography showed avid lymph nodes in the left infra-clavicular fossa and axilla. Biopsy of a left level IV neck node revealed benign reactive lymphoid tissue. The main differentials of tuberculosis, sarcoidosis, lymphoma, carcinomatosis, autoimmune disease and IgG4 related disease were felt to be less likely and a diagnosis of non-specific inflammatory process in the cavernous sinus, anatomically related to the oculomotor nerve, possibly an isolated oculomotor schwannoma, was therefore made. In the absence of pain, it was decided to withhold corticosteroids and watch and wait. The ptosis and eye movements improved within 1 week, and there was complete resolution of the third nerve palsy after 2 weeks, without pharmacological intervention. This coincided with disappearance of the mass within the cavernous sinus (Figure), allowing a refined diagnosis of TolosaHunt syndrome, with painless neurological involvement confined to the oculomotor nerve. 2. Discussion First described in 1954 by Tolosa and further elucidated by Hunt in 1961, the Tolosa-Hunt syndrome (THS) has a reported inci-
https://doi.org/10.1016/j.jocn.2019.12.037 0967-5868/Ó 2019 Elsevier Ltd. All rights reserved.
Please cite this article as: F. Dholoo, A. Shabana, M. Paschali et al., Gone in the blink of an eye – A Tolosa-Hunt syndrome variant, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.12.037
2
Case report/Journal of Clinical Neuroscience xxx (xxxx) xxx
Fig. 1. MRI brain demonstrating a heterogeneous mass filling the left cavernous sinus (A and B) with a contiguous tail of enhancement extending posteriorly following the course of the oculomotor nerve (C) and complete resolution of the mass within the cavernous sinus after 2 weeks without pharmacological intervention (D versus E and F versus G).
dence of less than one in a million individuals per year [1]. It is characterised by idiopathic granulomatous inflammation of the cavernous sinus and/or superior orbital fissure leading to secondary dysfunction of the structures within, namely cranial nerves III, IV, VI, and the superior divisions of cranial nerve V. The majority of patients present with severe unilateral orbital pain and paralysis of one or more associated cranial nerves.
Typical MRI findings are engorgement of the cavernous sinus with abnormal tissue that strongly enhances with gadolinium, abnormal convexity of the wall and focal narrowing of the intracavernous internal carotid artery [2]. These findings are not unique to THS and may also be found in other diseases, such as lymphoma, meningioma and granulomatous disease. Biopsy of the lesion is the definitive diagnostic test, but this is seldom necessary unless there
Please cite this article as: F. Dholoo, A. Shabana, M. Paschali et al., Gone in the blink of an eye – A Tolosa-Hunt syndrome variant, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.12.037
Case report/Journal of Clinical Neuroscience xxx (xxxx) xxx
is failure of response to corticosteroid treatment. Resolution of orbital pain within 1–3 days of treatment, also serves as diagnostic affirmation [3]. THS frequently masquerades as other conditions and there are no unifying or pathognomonic characteristics. Furthermore, it is suspected that the spectrum of clinical presentations of the syndrome might be wider than was previously recognized [4]. Emphasis is laid upon this being a diagnosis of exclusion which can only be made once the life-threatening processes within the differential diagnosis have been adequately excluded. Acquired painless third nerve ophthalmoplegia is a rare clinical presentation. Indeed, our patient did not meet the diagnostic criteria for THS. We postulate therefore, that the process was limited to the course of the oculomotor nerve with little or no mass effect within the cavernous sinus, resulting in isolated, self-limiting, painless paresis of the third nerve. For want of a diagnosis, we are assuming a THS variant. Contributors FD conceived the study and collected data and had a major role in writing the manuscript. AS performed the literature search and had also a major role in writing the manuscript. MP interpreted the data and revised the manuscript for intellectual content. AKJM was involved in the care of the patient as an attending physician, interpreted the data and revised the manuscript for intellectual content. CGM was involved in the care of the patient as an attending physician, oversaw the project and edited the manuscript up to submission.
3
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgements We thank Dr. Matthew Bull and Dr. Elena Boyd for their ongoing help with the analysis and interpretation of images used in this article. Funding No funding was sourced for the project. Patient consent for publication Verbal and written consent was obtained from the patient. References [1] Iaconetta G, Stella L, Esposito M, et al. Tolosa-Hunt syndrome extending in the cerebello-pontine angle. Cephalalgia 2005;25:746–50. [2] Razek AA, Castillo M. Imaging lesions of the cavernous sinus. AJNR Am J Neuroradiol 2009;30:444–52. [3] Zhang X, Zhang W, Liu R, et al. Factors that influence Tolosa-Hunt syndrome and the short-term response to steroid pulse treatment. J Neurol Sci 2014;341:13–6. [4] Hung C, Chang K, Chen Y, et al. Clinical and radiological findings suggesting disorders other than Tolosa-Hunt syndrome among ophthalmoplegic patients: a retrospective analysis. Headache: J Head Face Pain 2015;55:252–64.
Please cite this article as: F. Dholoo, A. Shabana, M. Paschali et al., Gone in the blink of an eye – A Tolosa-Hunt syndrome variant, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.12.037