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Ophthalmoplegia considered to be Tolosa-Hunt syndrome: A case report
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
Contents lists available at ScienceDirect
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology journal homepage: www.elsevier.com/locate/jomsmp
Ophthalmoplegia considered to be Tolosa-Hunt syndrome: A case report ⁎
Kazuto Okabea,b, , Ryuji Kanekob, Takamasa Kawaib, Daisuke Mochizukib, Shuhei Tsuchiyaa, Hideharu HIbia a b
Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, showa-ku, Nagoya-shi, Aichi, 466-8550, Japan Department of Oral and Maxillofacial Surgery, Toyota Kosei Hospital, 500-1 Josui-cho Ibobara, Toyota-shi, Aichi, 470-0396, Japan
A R T I C LE I N FO
A B S T R A C T
Keywords: Tolosa-Hunt syndrome Painful ophthalmoplegia Dental implant placement
Tolosa-Hunt syndrome (THS) is a type of painful ophthalmoplegia characterized by unilateral orbital pain and oculomotor paresis. This report describes a case of painful ophthalmoplegia considered to be THS. The patient was a 72-year-old woman. After dental implant placement in the left maxillary first molar site, she was referred to our hospital for persistent left periorbital and facial pain, diplopia, and taste disorder. With an initial diagnosis of trigeminal neuralgia, diplopia, and taste disorder, we began administration of carbamazepine and polaprezinc, and asked the department of ophthalmology in our hospital to examine her diplopia. With the increase in serum zinc levels, the taste disorder resolved, but her periorbital pain and diplopia were aggravated, and she had to be hospitalized. As a result of extensive examinations, we suspected her painful ophthalmoplegia was due to cavernous sinus abnormalities; finally, THS was diagnosed. There was significant improvement in the periorbital pain within 48 h after the start of corticosteroid therapy. Since then, she has never suffered from painful ophthalmoplegia. This case indicates that careful evaluation and accurate diagnosis are critical in cases of painful ophthalmoplegia, and the possibility of THS should always be kept in mind.
1. Introduction Painful ophthalmoplegia is a rare pathologic condition characterized by different combinations of ocular conditions, including unilateral periorbital or hemicranial pain, ipsilateral oculomotor paralysis, and oculosympathetic dysfunction. Notably, it can result from various etiologies, such as neoplasms, vascular abnormalities, inflammatory disorders, or infections, as well as other miscellaneous conditions [1]. Tolosa-Hunt syndrome (THS) is a painful ophthalmoplegia disorder, described in the 2013 International Classification of Headache Disorders (Third Edition, ICHD-3 beta) as unilateral orbital pain in association with paralysis of one or more of the third, fourth, and/or sixth cranial nerves [2]. The ocular symptoms are caused by extrinsic compression and secondary dysfunction of neurovascular structures within the cavernous sinus by a nonspecific inflammatory granuloma. Infrequently, when the inflammation extends into the orbital apex and/ or superior orbital fissure, dysfunction of the optic, trigeminal, and facial nerves and sympathetic innervation of the pupil can ensue [3,4]. Oral surgeons frequently encounter neurological diseases, such as trigeminal neuralgia, in their day-to-day clinical practice, but they rarely encounter painful ophthalmoplegia. Notably, the clinical presentation of painful ophthalmoplegia has a wide differential diagnosis,
which can greatly assist oral surgeons in its early accurate diagnosis and management. This report describes the onset, diagnosis, and treatment in a case of painful ophthalmoplegia considered to be THS that developed after dental implant placement. 2. Case report A 72-year-old woman had undergone dental implant placement in the left maxillary first molar region in June 2011 (Fig. 1). She experienced spontaneous pain in the left cheek immediately after surgery. The next day, she developed severe left periorbital pain and visited her dentist. He prescribed loxoprofen sodium 180 mg/day for postoperative pain associated with surgical invasion, which did not provide any pain relief within the next 1 week. At 3 weeks after surgery, she developed diplopia and taste disorder. After consultation with her physician, periorbital pain with diplopia and taste disorder, attributed to the dental implant placement, was diagnosed, and she was referred to our hospital in August 2011. Her medical history was unremarkable and did not include any head trauma or infection. She complained of constant, spontaneous periorbital pain with an intensity of 7/10 on the Numerical Rating Scale (NRS). There was no swelling on her face (Fig. 2A), and hypoesthesia
⁎ Corresponding author at: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, showa-ku, Nagoya-shi, Aichi, 466-8550, Japan. E-mail address: [email protected] (K. Okabe).
https://doi.org/10.1016/j.ajoms.2018.04.001 Received 23 December 2017; Received in revised form 1 March 2018; Accepted 12 April 2018 2212-5558/ © 2018 Asian Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd All rights reserved.
Please cite this article as: Okabe, K., Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology (2018), https://doi.org/10.1016/j.ajoms.2018.04.001
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
K. Okabe et al.
Fig. 1. Panoramic radiograph immediately after dental implant placement in the left maxillary first molar region.
consulted the department of neurosurgery and neurology in our hospital to identify the cause of painful ophthalmoplegia. Magnetic resonance angiography (MRA) and magnetic resonance imaging (MRI) revealed only mild, residual cerebral infarction, but no tumors or vascular disorders that could have caused the painful ophthalmoplegia (Fig. 3B). Gadolinium-enhanced MRI identified an abnormal lesion in the left cavernous sinus (Fig. 3C, D). Hematological examinations also did not reveal any abnormal findings. These included complete blood count; glucose, electrolyte, hemoglobin A1c, anti-nuclear antibody, angiotensin-converting enzyme, C-reactive protein, and cytoplasmic anti-neutrophil cytoplasmic antibody levels; liver and renal function; serum protein electrophoresis results; and erythrocyte sedimentation rate. Lumbar puncture was performed, and the cerebrospinal fluid was acicular with normal protein and glucose levels; negative bacterial, fungal, and mycobacterial cultures; and negative cytology results (Table 1). Although the clinical course did not fulfill the criteria indicated by ICHD-3 beta (Table 2), the radiological and hematological findings suggested THS. Systemic symptoms associated with THS, such as back pain, chronic fatigue, arthralgia, and gut problems [5], had not occurred. Two days after admission to our department, the severity of periorbital pain had increased (10/10 on the NRS). After consultations with the departments of neurology, neurosurgery, and ophthalmology, corticosteroid therapy was started: 1000 mg/day pulse intravenous methylprednisolone for 3 days, followed by 60 mg/day oral methylprednisolone. There was significant improvement in the periorbital pain within 48 h (NRS 3/10) after initiation of corticosteroid therapy. Periorbital pain resolved (NRS 0/10) in 7 days, ptosis in 26 days, and diplopia in 40 days. Corticosteroid therapy was tapered gradually and stopped at the end of 5 months. A follow-up MRI performed at 6 months after initiation of corticosteroid therapy was normal (Fig. 4A, B). There was no recurrence of painful ophthalmoplegia for the next 5 years.
was not observed in the Semmes-Weinstein sensory test. An intraoral examination did not reveal any local inflammation such as abscess at the site of the dental implant (Fig. 2B). She underwent a thorough radiographic examination, including computed tomography (CT) and technetium 99 m-methyl diphosphonate (99 mTc-MDP) bone scintigraphy. These examinations did not reveal any relevant abnormalities (Fig. 2C, D). Her body temperature was 36.5 °C, and a blood examination revealed little inflammatory reaction. The peripheral white blood cell count was 5900/μL and C-reactive protein level was 1.2 mg/ dL. A taste examination using the filter paper disc method was performed to examine the taste recognition threshold, because the serum zinc level was low (50 μg/dL). In brief, recognition thresholds for four basic tastes (sweet, salty, sour, and bitter) were evaluated using the same chemical solutions (sucrose, NaCl, tartaric acid, and quinine, respectively). The solutions were sequentially diluted with distilled water into five grades. Concentration number 1 is the lowest and 5 is the highest (0.3, 2.5, 10, 20, and 80% for sucrose; 0.3, 1.25, 5, 10, and 20% for NaCl; 0.02, 0.2, 2, 4, and 8%, for tartaric acid; 0.001, 0.02, 0.1, 0.5, and 4% for quinine). The threshold level of sweet in the left chorda tympani nerve field was higher compared with that on the right side. As other neurological symptoms, facial palsy, tinnitus, vertigo and nystagmus were not observed. Because of the presence of pain focused in the left trigeminal region, absence of any radiographic or hematological abnormalities, and the failure of the nonsteroidal anti-inflammatory drugs prescribed after dental implant placement, we suspected trigeminal neuralgia and prescribed carbamazepine 200 mg/day. In addition, we prescribed polaprezinc 150 mg/day to treat the taste disorder by increasing serum zinc levels. Furthermore, we consulted the department of ophthalmology in our hospital regarding her diplopia, but no organic or neurological abnormalities other than bilateral esotropia were observed in ophthalmic examinations. The taste disorder resolved as the zinc levels increased. In spite of the increased dosage of carbamazepine, her periorbital pain became more severe (NRS 9/10), and was accompanied by an increase in diplopia. In addition, nausea caused by the periorbital pain led to an eating disorder, and she was admitted to our hospital in September 2011. Because of the exacerbation of the periorbital pain and diplopia, we consulted the department of ophthalmology in our hospital again. It was discovered that the diplopia was due to impairment of ocular excursion (Fig. 3A) and ptosis, suggesting a diagnosis of painful ophthalmoplegia due to cranial nerve abnormality. We subsequently
3. Discussion The differential diagnosis of painful ophthalmoplegia is extensive and includes numerous serious etiologies, such as neoplasms (primary intracranial tumors, and local or distant metastasis), vascular abnormalities (aneurysm, carotid dissection, and carotid-cavernous fistula), inflammatory disorders (orbital pseudotumor, giant cell arteritis, sarcoidosis, and THS), infections (fungal and mycobacterial), as well as other miscellaneous conditions (ocular migraine and microvascular 2
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Fig. 2. Photograph and radiograph obtained at first examination: (A) Photograph of facial configuration and (B) intraoral photograph showing no local inflammation. (C) 99 mTc-MDP bone scintigraphy showed no abnormal accumulation in the left maxillary first molar region. (D) Computed tomography showed no inflammatory lesion around the dental implant or in the maxillary sinus.
region [15]. The underlying cause is as yet unclear, though trauma, inflammation, bleeding, and foreign body reactions are considered to play a role. In the present case, painful ophthalmoplegia developed after dental implant placement, so we suspected inflammation due to postoperative infection or surgical invasion to be the underlying cause. Anatomically, inflammation of the maxillary molar region easily spreads to the paranasal sinus. Because of the thin bony septum between the paranasal sinus and orbit, inflammation originating in the maxillary region often spreads via the paranasal sinus directly into the orbit and further into the cavernous sinus [16]. In the case reported here, an inflammatory lesion was observed in the cavernous sinus, but not around the dental implant or in the maxillary sinus. Therefore, the relation between the dental implant placement and THS could not be clarified. Interestingly, however, THS triggered by a dental procedure, which closely resembled this case, has been reported in the past. Shimizu et al. reported a case of carotid cavernous sinus fistula (CCF) caused by dental implant placement that had been suspected progressing to THS [17]. It was believed that infection due to implant placement spread via the blood stream to the maxillary and sphenoid sinuses, and subsequently to the cavernous sinus, resulting in the formation of
infarcts secondary to diabetes) [1]. A systematic approach to the evaluation of painful ophthalmoplegia can lead to rapid and timely identification of serious disorders that can be associated with significant morbidity or mortality if left untreated. Although some diseases can be diagnosed by radiographic and hematological examinations, neoplasms, such as malignant lymphoma, chordoma, giant cell leukemia, and epidermoid tumor, may be difficult to distinguish from THS, since they exhibit similar early clinical symptoms [6–9]. In fact, they show similar image findings and temporarily respond to corticosteroids, in a manner similar to THS [6–10]. Therefore, many experts believe that one should not hesitate to perform invasive procedures such as openhead biopsy in cases for a definite diagnosis [8,9]. Bacterial [11,12] and fungal [13,14] infections spreading to the cavernous sinus also exhibit symptoms closely resembling those of THS. If bacteria or fungi are not detected in the cerebrospinal fluid test, biopsy of the cavernous sinus is the only way to arrive at a diagnosis. Since corticosteroids exacerbate infections, it is critical to arrive at a conclusive diagnosis before starting treatment. Nonspecific inflammatory granuloma causing THS, confirmed in various organs, often occurs around the orbit in the head and neck 3
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Fig. 3. Clinical examinations at admission: (A) Hess screen test showed impairment of left ocular excursion. (B) Magnetic resonance angiography image of the internal carotid artery showed no tumors or vascular disorders. (C) T1-weighted and (D) T2-weighted gadolinium-enhanced magnetic resonance image showed an abnormal lesion (arrows) in the left cavernous sinus. Table 1 Results of blood and cerebrospinal fluid examinations at admission. (Blood examinations) WBC RBC Hemoglobin Platelet Total protein AST ALT ALP γ-GTP BUN UA Sodium Potassium Chloride Glucose HbA1c C-reactive protein Iron Zinc Coppper TSH FT4 FT3 ACE
6.7 × 103 /μL 4.89 × 106 /μL 14.7 g/dL 174 × 103 /μL 6.8 g/dL 17 IU/L 13 IU/L 228 IU/L 20 IU/L 0.7 mg/dL 19.6 mg/dL 138 mEq/L 4.8 mEq/L 105 mEq/L 108 mg/dL 5.7 % 1.2 mg/dL ↑ 91 μg/dL 61 μg/dL ↓ 104 μg/dL 1.26 μU/mL 1.54 ng/dL 2.82 pg/mL 8.8 IU/L
C3 C4 CH50 IgG IgA IgM ANA Anti-SM Anti-ds-DNA MPO-ANCA PR3-ANCA HZV IgG HZV IgM HSV IgG HSV IgM
105 mg/dL 19 mg/dL 42.9 U/mL 1075 mg/dL 212 mg/dL 42 mg/dL < 1.0 U/mL – < 20 IU/mL < 10 EU < 10 EU 14.6 ↑ 0.3 40.8 0.41
(CSF examinations) Cell count Protein Glucose ADA Color Bacteria Fungus
1 /μL 33.6 mg/dL 100 mg/dL < 1.1 IU/L Clear – –
Table 2 Diagnostic criteria for Tolosa-Hunt syndrome (ICHD-3 beta). A. B.
C.
D.
Unilateral headache fulfilling criterion C Both of the following: 1. granulomatous inflammation of the cavernous sinus, superior orbital fissure or orbit, demonstrated by MRI or biopsy 2. paresis of one or more of the ipsilateral IIIrd, IVth and/or VIth cranial nerves Evidence of causation demonstrated by both of the following: 1. headache has preceded paresis of the IIIrd, IVth and/or VIth nerves by 2 weeks, or developed with it 2. headache is localized around the ipsilateral brow and eye Not better accounted for by another ICHD-3 diagnosis.
ICHD3: International Classification of Headache Disorders (Third Edition).
CCF with THS. Simsek et al. reported a case of painful ophthalmoplegia considered to be THS occurring shortly after extraction of a maxillary first molar, and wondered whether it may have resulted from the effect of the intraoral local anesthetic injection [18]. The estimated incidence of ophthalmic complications after induction of local anesthesia is 1/ 1000 [19]. It has been hypothesized that intravenous injection of the local anesthetic fluid may be responsible for these complications. Improper size and placement of the needle can cause damage to the venous pterygoid plexus, and the anesthetic solution may flow via small emissary veins through the foramen ovale and into the cavernous sinus. In rare cases, symptoms appeared hours or days after the injection and lasted for weeks, sometimes persisting permanently [20–22]. Corticosteroids are the treatment of choice for THS because the pain is highly responsive to steroids [23]. The optimal dose or duration of treatment has not been determined yet. A reasonable approach is to administer high-dose steroids (1 mg/kg) tapered slowly over 3–4
ACE: Angiotensin-converting enzyme; ANA: Anti-nuclear antibody; Anti-SM: Anti-smith antibody; Anti-ds-DNA: Anti-double stranded DNA IgG antibody; MPO-ANCA: Myeloperoxidase-anti-neutrophil cytoplasmic antibody; PR3ANCA: Proteinase 3-anti-neutrophil cytoplasmic antibody; ADA: Adenosine deaminase.
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Fig. 4. Imaging findings 6 months after corticosteroid therapy: (A) T1-weighted and (B) T2-weighted magnetic resonance image of the cavernous sinus showed no recurrence.
months or longer. Furthermore, steroid pulse therapy may prevent recurrence. In a previous study, recurrence occurred in 44.2% of patients with THS who received regular steroid treatment and in only 9.1% of those who were treated with steroid pulse therapy [24]. In cases with recurrent attacks or steroid-induced complications, focal radiotherapy has been efficacious [25]. After corticosteroid therapy, follow-up MRI examinations typically show much improvement, or even complete resolution of the initial lesion. Importantly, follow-up MRI must be performed 6–12 months after corticosteroid therapy so as to document persistent lesion resolution and ensure that the diagnosis was accurate [1]. Some of the neurological disorders encountered by oral surgeons exhibit few pathological changes. Therefore, frequently because of inadequate examination, pathological changes in THS may remain undetected, and the disease may be misdiagnosed as a psychosomatic disorder [26]. THS essentially remains a diagnosis of exclusion [1]; thus, the differential diagnosis is very important. For patients with painful ophthalmoplegia, careful and extensive diagnostic evaluations should be performed in coordination with the related department, and the possibility of THS should be kept in mind.
carotid infraclinoid aneurysm. J Neurol Neurosurg Psychiatry 1954;17:300–2. [4] Hunt WE, Meagher JN, Lefever HE, Zeman W. Painful ophthalmoplegia: its relation to indolent inflammation of the carvernous sinus. Neurology 1961;11:56–62. [5] Hannerz J. Recurrent Tolosa-Hunt syndrome: a report of ten new cases. Cephalalgia 1999(Suppl. 25):33–5. [6] Flowler TJ, Earl CJ, McAllister VL, McDonald WI. Tolosa-Hunt syndrome. The dangers of an eponym. Br J Ophthalmol 1975;59:149–54. [7] Julien J, Ferrer X, Drouillard J, Philippe JC, Desbordes P. Cavernous sinus syndrome due to lymphoma. J Neurol Neurosurg Psychiatry 1984;47:558–60. [8] Roman-Goldstein SM, Jones A, Delashaw JB, McMenomey S, Neuwelt EA. Atypical central nervous system lymphoma at the cranial base: report of four cases. Neurosurgery 1998;43:613–5. [9] Slamovits TL, Cahill KV, Sibony PA, Dekker A, Johnson BL. Orbital fine-needle aspiration biopsy in patients with cavernous sinus syndrome. J Neurosurg 1983;59:1037–42. [10] Kline LB. The Tolosa-Hunt syndrome. Surv Ophthalmol 1982;27:79–95. [11] Ohta S, Nishizawa S, Namba H, Sugimura H. Bilateral cavernous sinus actinomycosis resulting in painful ophthalmoplegia. Case Rep J Neurosurg 2002;96:600–2. [12] Tobias S, Lee JH, Tomford JW. Rare actinobacillus infection of the cavernous sinus causing painful ophthalmoplegia: case report. Neurosurgery 2002;51:807–9. [13] Endo H, Beppu T, Arai H, Ogasawara K, Suzuki T, Suzuki M, et al. A case report of aspergillus granuloma in the cavernous sinus. No Shinkei Geka 2001;29:325–9. [14] Hase T, Kurita H, Matsumoto E, Kuroda H, Hashimoto M, Shinoda S. A case of cavernous sinus aspergillosis. No Shinkei Geka 2013;41:901–6. [15] Kovach SJ, Fischer AC, Katzman PJ, Salloum RM, Ettinghausen SE, Madeb R, et al. Inflammatory myofibroblastic tumors. J Surg Oncol 2006;94:385–91. [16] Colbert S, Cameron M, Williams J. Septic thrombosis of the cavernous sinus and dental infection. Br J Oral Maxillofac Surg 2011;49:e25–6. [17] Shimizu Y, Tsutsumi, Yasumoto Y, Ito M. Carotid cavernous sinus fistula caused by dental implant-associated infection. Am J Otolaryngol 2012;33:352–5. [18] Simsek IB, Kiziloglu OY, Ziylan S. Painful ophthalmoplegia following dental procedure. Neuro-Ophthalmol 2013;37:165–8. [19] Steenen SA, Dubois L, Saeed P, de Lange J. Ophthalmologic complications after intraoral local anesthesia: case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;113:e1–5. [20] Magliocca KR, Kessel NC, Cortrightet GW. Transient diplopia following maxillary local anesthetic injection. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:730–3. [21] Marinho RO. Abducent nerve palsy following dental local analgesia. Br Dent J 1995;179:69–70. [22] Goldenberg AS. Transient diploma from a posterior alveolar injection. J Endod 1990;16:550–1. [23] Eshbaugh CG, Siatkowski RM, Smith JL, Kline LB. Simultaneous, multiple cranial neuropathies in diabetes mellitus. J Neuroophthalmol 1995;15:219–24. [24] Colnaghi S, Versino M, Marchioni E, Pichiecchio A, Bastianello S, Cosi V, et al. ICHD-Ⅱ diagnostic criteria for Tolosa-Hunt syndrome in idiopathic inflammatory syndromes of the orbit and/or the cavernous sinus. Cephalalgia 2008;28:577–84. [25] Mormont E, Laloux P, Vauthier J, Osseman M. Radiotherapy in a case of TolosaHunt syndrome. Cephalalgia 2000;20:931–3. [26] Watabe Y, Imataka G, Saito S, Iwanami H, Suzuki S, Kanaya H, et al. Tolosa-Hunt syndrome tentatively diagnosed as psychosomatic disease in a 15-year-old: a case report. Dokkyo J Med Sci 2014;41:177–81.
Funding The authors did not receive any support in the form of grants. Ethical approval Informed consent for publication of this case was obtained from the patient’s guardian prior to submission of this paper. Conflict of interest The authors declare no conflicts of interest related to this paper. References [1] Gladstone JP. An approach to the patient with painful ophthalmoplegia, with a focus on Tolosa-Hunt syndrome. Curr Pain Headache Rep 2007;11:317–25. [2] Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders 3rd edition (beta version). [3] Tolosa E. Periarteritic lesions of the carotid siphon with the clinical features of a
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Contents lists available at ScienceDirect
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology journal homepage: www.elsevier.com/locate/jomsmp
Ophthalmoplegia considered to be Tolosa-Hunt syndrome: A case report ⁎
Kazuto Okabea,b, , Ryuji Kanekob, Takamasa Kawaib, Daisuke Mochizukib, Shuhei Tsuchiyaa, Hideharu HIbia a b
Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, showa-ku, Nagoya-shi, Aichi, 466-8550, Japan Department of Oral and Maxillofacial Surgery, Toyota Kosei Hospital, 500-1 Josui-cho Ibobara, Toyota-shi, Aichi, 470-0396, Japan
A R T I C LE I N FO
A B S T R A C T
Keywords: Tolosa-Hunt syndrome Painful ophthalmoplegia Dental implant placement
Tolosa-Hunt syndrome (THS) is a type of painful ophthalmoplegia characterized by unilateral orbital pain and oculomotor paresis. This report describes a case of painful ophthalmoplegia considered to be THS. The patient was a 72-year-old woman. After dental implant placement in the left maxillary first molar site, she was referred to our hospital for persistent left periorbital and facial pain, diplopia, and taste disorder. With an initial diagnosis of trigeminal neuralgia, diplopia, and taste disorder, we began administration of carbamazepine and polaprezinc, and asked the department of ophthalmology in our hospital to examine her diplopia. With the increase in serum zinc levels, the taste disorder resolved, but her periorbital pain and diplopia were aggravated, and she had to be hospitalized. As a result of extensive examinations, we suspected her painful ophthalmoplegia was due to cavernous sinus abnormalities; finally, THS was diagnosed. There was significant improvement in the periorbital pain within 48 h after the start of corticosteroid therapy. Since then, she has never suffered from painful ophthalmoplegia. This case indicates that careful evaluation and accurate diagnosis are critical in cases of painful ophthalmoplegia, and the possibility of THS should always be kept in mind.
1. Introduction Painful ophthalmoplegia is a rare pathologic condition characterized by different combinations of ocular conditions, including unilateral periorbital or hemicranial pain, ipsilateral oculomotor paralysis, and oculosympathetic dysfunction. Notably, it can result from various etiologies, such as neoplasms, vascular abnormalities, inflammatory disorders, or infections, as well as other miscellaneous conditions [1]. Tolosa-Hunt syndrome (THS) is a painful ophthalmoplegia disorder, described in the 2013 International Classification of Headache Disorders (Third Edition, ICHD-3 beta) as unilateral orbital pain in association with paralysis of one or more of the third, fourth, and/or sixth cranial nerves [2]. The ocular symptoms are caused by extrinsic compression and secondary dysfunction of neurovascular structures within the cavernous sinus by a nonspecific inflammatory granuloma. Infrequently, when the inflammation extends into the orbital apex and/ or superior orbital fissure, dysfunction of the optic, trigeminal, and facial nerves and sympathetic innervation of the pupil can ensue [3,4]. Oral surgeons frequently encounter neurological diseases, such as trigeminal neuralgia, in their day-to-day clinical practice, but they rarely encounter painful ophthalmoplegia. Notably, the clinical presentation of painful ophthalmoplegia has a wide differential diagnosis,
which can greatly assist oral surgeons in its early accurate diagnosis and management. This report describes the onset, diagnosis, and treatment in a case of painful ophthalmoplegia considered to be THS that developed after dental implant placement. 2. Case report A 72-year-old woman had undergone dental implant placement in the left maxillary first molar region in June 2011 (Fig. 1). She experienced spontaneous pain in the left cheek immediately after surgery. The next day, she developed severe left periorbital pain and visited her dentist. He prescribed loxoprofen sodium 180 mg/day for postoperative pain associated with surgical invasion, which did not provide any pain relief within the next 1 week. At 3 weeks after surgery, she developed diplopia and taste disorder. After consultation with her physician, periorbital pain with diplopia and taste disorder, attributed to the dental implant placement, was diagnosed, and she was referred to our hospital in August 2011. Her medical history was unremarkable and did not include any head trauma or infection. She complained of constant, spontaneous periorbital pain with an intensity of 7/10 on the Numerical Rating Scale (NRS). There was no swelling on her face (Fig. 2A), and hypoesthesia
⁎ Corresponding author at: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, showa-ku, Nagoya-shi, Aichi, 466-8550, Japan. E-mail address: [email protected] (K. Okabe).
https://doi.org/10.1016/j.ajoms.2018.04.001 Received 23 December 2017; Received in revised form 1 March 2018; Accepted 12 April 2018 2212-5558/ © 2018 Asian Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd All rights reserved.
Please cite this article as: Okabe, K., Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology (2018), https://doi.org/10.1016/j.ajoms.2018.04.001
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
K. Okabe et al.
Fig. 1. Panoramic radiograph immediately after dental implant placement in the left maxillary first molar region.
consulted the department of neurosurgery and neurology in our hospital to identify the cause of painful ophthalmoplegia. Magnetic resonance angiography (MRA) and magnetic resonance imaging (MRI) revealed only mild, residual cerebral infarction, but no tumors or vascular disorders that could have caused the painful ophthalmoplegia (Fig. 3B). Gadolinium-enhanced MRI identified an abnormal lesion in the left cavernous sinus (Fig. 3C, D). Hematological examinations also did not reveal any abnormal findings. These included complete blood count; glucose, electrolyte, hemoglobin A1c, anti-nuclear antibody, angiotensin-converting enzyme, C-reactive protein, and cytoplasmic anti-neutrophil cytoplasmic antibody levels; liver and renal function; serum protein electrophoresis results; and erythrocyte sedimentation rate. Lumbar puncture was performed, and the cerebrospinal fluid was acicular with normal protein and glucose levels; negative bacterial, fungal, and mycobacterial cultures; and negative cytology results (Table 1). Although the clinical course did not fulfill the criteria indicated by ICHD-3 beta (Table 2), the radiological and hematological findings suggested THS. Systemic symptoms associated with THS, such as back pain, chronic fatigue, arthralgia, and gut problems [5], had not occurred. Two days after admission to our department, the severity of periorbital pain had increased (10/10 on the NRS). After consultations with the departments of neurology, neurosurgery, and ophthalmology, corticosteroid therapy was started: 1000 mg/day pulse intravenous methylprednisolone for 3 days, followed by 60 mg/day oral methylprednisolone. There was significant improvement in the periorbital pain within 48 h (NRS 3/10) after initiation of corticosteroid therapy. Periorbital pain resolved (NRS 0/10) in 7 days, ptosis in 26 days, and diplopia in 40 days. Corticosteroid therapy was tapered gradually and stopped at the end of 5 months. A follow-up MRI performed at 6 months after initiation of corticosteroid therapy was normal (Fig. 4A, B). There was no recurrence of painful ophthalmoplegia for the next 5 years.
was not observed in the Semmes-Weinstein sensory test. An intraoral examination did not reveal any local inflammation such as abscess at the site of the dental implant (Fig. 2B). She underwent a thorough radiographic examination, including computed tomography (CT) and technetium 99 m-methyl diphosphonate (99 mTc-MDP) bone scintigraphy. These examinations did not reveal any relevant abnormalities (Fig. 2C, D). Her body temperature was 36.5 °C, and a blood examination revealed little inflammatory reaction. The peripheral white blood cell count was 5900/μL and C-reactive protein level was 1.2 mg/ dL. A taste examination using the filter paper disc method was performed to examine the taste recognition threshold, because the serum zinc level was low (50 μg/dL). In brief, recognition thresholds for four basic tastes (sweet, salty, sour, and bitter) were evaluated using the same chemical solutions (sucrose, NaCl, tartaric acid, and quinine, respectively). The solutions were sequentially diluted with distilled water into five grades. Concentration number 1 is the lowest and 5 is the highest (0.3, 2.5, 10, 20, and 80% for sucrose; 0.3, 1.25, 5, 10, and 20% for NaCl; 0.02, 0.2, 2, 4, and 8%, for tartaric acid; 0.001, 0.02, 0.1, 0.5, and 4% for quinine). The threshold level of sweet in the left chorda tympani nerve field was higher compared with that on the right side. As other neurological symptoms, facial palsy, tinnitus, vertigo and nystagmus were not observed. Because of the presence of pain focused in the left trigeminal region, absence of any radiographic or hematological abnormalities, and the failure of the nonsteroidal anti-inflammatory drugs prescribed after dental implant placement, we suspected trigeminal neuralgia and prescribed carbamazepine 200 mg/day. In addition, we prescribed polaprezinc 150 mg/day to treat the taste disorder by increasing serum zinc levels. Furthermore, we consulted the department of ophthalmology in our hospital regarding her diplopia, but no organic or neurological abnormalities other than bilateral esotropia were observed in ophthalmic examinations. The taste disorder resolved as the zinc levels increased. In spite of the increased dosage of carbamazepine, her periorbital pain became more severe (NRS 9/10), and was accompanied by an increase in diplopia. In addition, nausea caused by the periorbital pain led to an eating disorder, and she was admitted to our hospital in September 2011. Because of the exacerbation of the periorbital pain and diplopia, we consulted the department of ophthalmology in our hospital again. It was discovered that the diplopia was due to impairment of ocular excursion (Fig. 3A) and ptosis, suggesting a diagnosis of painful ophthalmoplegia due to cranial nerve abnormality. We subsequently
3. Discussion The differential diagnosis of painful ophthalmoplegia is extensive and includes numerous serious etiologies, such as neoplasms (primary intracranial tumors, and local or distant metastasis), vascular abnormalities (aneurysm, carotid dissection, and carotid-cavernous fistula), inflammatory disorders (orbital pseudotumor, giant cell arteritis, sarcoidosis, and THS), infections (fungal and mycobacterial), as well as other miscellaneous conditions (ocular migraine and microvascular 2
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Fig. 2. Photograph and radiograph obtained at first examination: (A) Photograph of facial configuration and (B) intraoral photograph showing no local inflammation. (C) 99 mTc-MDP bone scintigraphy showed no abnormal accumulation in the left maxillary first molar region. (D) Computed tomography showed no inflammatory lesion around the dental implant or in the maxillary sinus.
region [15]. The underlying cause is as yet unclear, though trauma, inflammation, bleeding, and foreign body reactions are considered to play a role. In the present case, painful ophthalmoplegia developed after dental implant placement, so we suspected inflammation due to postoperative infection or surgical invasion to be the underlying cause. Anatomically, inflammation of the maxillary molar region easily spreads to the paranasal sinus. Because of the thin bony septum between the paranasal sinus and orbit, inflammation originating in the maxillary region often spreads via the paranasal sinus directly into the orbit and further into the cavernous sinus [16]. In the case reported here, an inflammatory lesion was observed in the cavernous sinus, but not around the dental implant or in the maxillary sinus. Therefore, the relation between the dental implant placement and THS could not be clarified. Interestingly, however, THS triggered by a dental procedure, which closely resembled this case, has been reported in the past. Shimizu et al. reported a case of carotid cavernous sinus fistula (CCF) caused by dental implant placement that had been suspected progressing to THS [17]. It was believed that infection due to implant placement spread via the blood stream to the maxillary and sphenoid sinuses, and subsequently to the cavernous sinus, resulting in the formation of
infarcts secondary to diabetes) [1]. A systematic approach to the evaluation of painful ophthalmoplegia can lead to rapid and timely identification of serious disorders that can be associated with significant morbidity or mortality if left untreated. Although some diseases can be diagnosed by radiographic and hematological examinations, neoplasms, such as malignant lymphoma, chordoma, giant cell leukemia, and epidermoid tumor, may be difficult to distinguish from THS, since they exhibit similar early clinical symptoms [6–9]. In fact, they show similar image findings and temporarily respond to corticosteroids, in a manner similar to THS [6–10]. Therefore, many experts believe that one should not hesitate to perform invasive procedures such as openhead biopsy in cases for a definite diagnosis [8,9]. Bacterial [11,12] and fungal [13,14] infections spreading to the cavernous sinus also exhibit symptoms closely resembling those of THS. If bacteria or fungi are not detected in the cerebrospinal fluid test, biopsy of the cavernous sinus is the only way to arrive at a diagnosis. Since corticosteroids exacerbate infections, it is critical to arrive at a conclusive diagnosis before starting treatment. Nonspecific inflammatory granuloma causing THS, confirmed in various organs, often occurs around the orbit in the head and neck 3
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Fig. 3. Clinical examinations at admission: (A) Hess screen test showed impairment of left ocular excursion. (B) Magnetic resonance angiography image of the internal carotid artery showed no tumors or vascular disorders. (C) T1-weighted and (D) T2-weighted gadolinium-enhanced magnetic resonance image showed an abnormal lesion (arrows) in the left cavernous sinus. Table 1 Results of blood and cerebrospinal fluid examinations at admission. (Blood examinations) WBC RBC Hemoglobin Platelet Total protein AST ALT ALP γ-GTP BUN UA Sodium Potassium Chloride Glucose HbA1c C-reactive protein Iron Zinc Coppper TSH FT4 FT3 ACE
6.7 × 103 /μL 4.89 × 106 /μL 14.7 g/dL 174 × 103 /μL 6.8 g/dL 17 IU/L 13 IU/L 228 IU/L 20 IU/L 0.7 mg/dL 19.6 mg/dL 138 mEq/L 4.8 mEq/L 105 mEq/L 108 mg/dL 5.7 % 1.2 mg/dL ↑ 91 μg/dL 61 μg/dL ↓ 104 μg/dL 1.26 μU/mL 1.54 ng/dL 2.82 pg/mL 8.8 IU/L
C3 C4 CH50 IgG IgA IgM ANA Anti-SM Anti-ds-DNA MPO-ANCA PR3-ANCA HZV IgG HZV IgM HSV IgG HSV IgM
105 mg/dL 19 mg/dL 42.9 U/mL 1075 mg/dL 212 mg/dL 42 mg/dL < 1.0 U/mL – < 20 IU/mL < 10 EU < 10 EU 14.6 ↑ 0.3 40.8 0.41
(CSF examinations) Cell count Protein Glucose ADA Color Bacteria Fungus
1 /μL 33.6 mg/dL 100 mg/dL < 1.1 IU/L Clear – –
Table 2 Diagnostic criteria for Tolosa-Hunt syndrome (ICHD-3 beta). A. B.
C.
D.
Unilateral headache fulfilling criterion C Both of the following: 1. granulomatous inflammation of the cavernous sinus, superior orbital fissure or orbit, demonstrated by MRI or biopsy 2. paresis of one or more of the ipsilateral IIIrd, IVth and/or VIth cranial nerves Evidence of causation demonstrated by both of the following: 1. headache has preceded paresis of the IIIrd, IVth and/or VIth nerves by 2 weeks, or developed with it 2. headache is localized around the ipsilateral brow and eye Not better accounted for by another ICHD-3 diagnosis.
ICHD3: International Classification of Headache Disorders (Third Edition).
CCF with THS. Simsek et al. reported a case of painful ophthalmoplegia considered to be THS occurring shortly after extraction of a maxillary first molar, and wondered whether it may have resulted from the effect of the intraoral local anesthetic injection [18]. The estimated incidence of ophthalmic complications after induction of local anesthesia is 1/ 1000 [19]. It has been hypothesized that intravenous injection of the local anesthetic fluid may be responsible for these complications. Improper size and placement of the needle can cause damage to the venous pterygoid plexus, and the anesthetic solution may flow via small emissary veins through the foramen ovale and into the cavernous sinus. In rare cases, symptoms appeared hours or days after the injection and lasted for weeks, sometimes persisting permanently [20–22]. Corticosteroids are the treatment of choice for THS because the pain is highly responsive to steroids [23]. The optimal dose or duration of treatment has not been determined yet. A reasonable approach is to administer high-dose steroids (1 mg/kg) tapered slowly over 3–4
ACE: Angiotensin-converting enzyme; ANA: Anti-nuclear antibody; Anti-SM: Anti-smith antibody; Anti-ds-DNA: Anti-double stranded DNA IgG antibody; MPO-ANCA: Myeloperoxidase-anti-neutrophil cytoplasmic antibody; PR3ANCA: Proteinase 3-anti-neutrophil cytoplasmic antibody; ADA: Adenosine deaminase.
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Fig. 4. Imaging findings 6 months after corticosteroid therapy: (A) T1-weighted and (B) T2-weighted magnetic resonance image of the cavernous sinus showed no recurrence.
months or longer. Furthermore, steroid pulse therapy may prevent recurrence. In a previous study, recurrence occurred in 44.2% of patients with THS who received regular steroid treatment and in only 9.1% of those who were treated with steroid pulse therapy [24]. In cases with recurrent attacks or steroid-induced complications, focal radiotherapy has been efficacious [25]. After corticosteroid therapy, follow-up MRI examinations typically show much improvement, or even complete resolution of the initial lesion. Importantly, follow-up MRI must be performed 6–12 months after corticosteroid therapy so as to document persistent lesion resolution and ensure that the diagnosis was accurate [1]. Some of the neurological disorders encountered by oral surgeons exhibit few pathological changes. Therefore, frequently because of inadequate examination, pathological changes in THS may remain undetected, and the disease may be misdiagnosed as a psychosomatic disorder [26]. THS essentially remains a diagnosis of exclusion [1]; thus, the differential diagnosis is very important. For patients with painful ophthalmoplegia, careful and extensive diagnostic evaluations should be performed in coordination with the related department, and the possibility of THS should be kept in mind.
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Funding The authors did not receive any support in the form of grants. Ethical approval Informed consent for publication of this case was obtained from the patient’s guardian prior to submission of this paper. Conflict of interest The authors declare no conflicts of interest related to this paper. References [1] Gladstone JP. An approach to the patient with painful ophthalmoplegia, with a focus on Tolosa-Hunt syndrome. Curr Pain Headache Rep 2007;11:317–25. [2] Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders 3rd edition (beta version). [3] Tolosa E. Periarteritic lesions of the carotid siphon with the clinical features of a
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