- Email: [email protected]
Two patients with primary sellar leiomyomas, a rare entity
Case Reports / Journal of Clinical Neuroscience 20 (2013) 897–901
In 2005 he underwent extensive neurological and neuropsychological evaluation, which comprised: Rey 15-Word List, Rey Complex Figure, Trail Making Test, Stroop Color-Word test, Colored Progressive Matrices, Frontal Assessment Battery, the ‘‘FAS’’ and Animal Naming test, Mini Mental State Examination (MMSE), and Neuropsychiatric Inventory (NPI). The patient obtained a baseline MMSE score of 25/30 and subsequent neuropsychological assessments highlighted the gradual deterioration of his cognitive status (for example, the MMSE at 3 years’ follow-up: 23/30). His behavioral disturbances worsened: depression and marked loss of interest (NPI subscale for depression = 4, for apathy = 8) in addition to his increasing anxiety and irritability. Therapy with sertraline (maximum dose reached 100 mg/day) was then established: significant improvement in mood (NPI = 2) and apathy (NPI = 2) was achieved and cognitive performance was ameliorated (MMSE = 28). These benefits were confirmed in the following 2 years of follow-up. 3. Discussion We described the onset of cognitive deterioration and behavioral impairment in a patient affected by BD. The most significant aspect of our report is the extensive retrospective as well as follow-up examinations and neuropsychological assessments performed (20 years). The patient’s disease history could be divided in two parts: (i) symptoms and signs characteristic of BD; and (ii) subsequent neurological manifestations and cognitive impairments of NBS. Oktem-Tanor et al.10 stated that the stage and the nature of cognitive impairment do not appear to be correlated with the burden and location of parenchymal lesions; nevertheless, reports of apathetic patients have described ponto-mesencephalic lesions as occurred in by our patient, which suggest, in our opinion, a hypothetical correlation.
897
The use of the selective serotonin reuptake inhibitor (SSRI), sertraline, resulted in a significant improvement in both behavioral disturbances (apathy, depression and irritability) and cognitive performance (MMSE gain of 5 points). These results can probably be attributed to the pharmacological profile of sertraline, a potent SSRI, as well as its ability to inhibit dopamine uptake.12 The latter could explain the remarkable improvement in apathetic behavior. References 1. International Study Group for Behçet’s Disease. Criteria for diagnosis of Behçet’s disease. Lancet 1990;335:1078–80. 2. Akman-Demir G, Serdarog˘lu P, Tasçi B. Clinical patterns of neurological involvement in Behçet’s desease: evaluation of 200 patients. The NeuroBehcet Study Group. Brain 1999;122:2171–81. 3. Serdarog˘lu P. Behçet’s disease and the nervous system. J Neurol 1998;245:197–205. 4. Siva A, Kantarci OH, Saip S, et al. Behçet’s disease: diagnostic and prognostic aspects of neurological involvement. J Neurol 2001;248:95–103. 5. Kidd D. The prevalence of headache in Behçet’s syndrome. Adv Exp Med Biol 2003;528:377–9. 6. Siva A, Yazici H. Behçet’s disease. In: Levine S, Doruk E, editors. Handbook of systemic autoimmune diseases, neurology volume – the neurologic involvement in systemic autoimmune disorders. Elsevier Science; 2004. 7. Kidd D, Steuer A, Denman AM, et al. Neurological complications in Behçet’s syndrome. Brain 1999;122:2183–94. 8. Aykutlu E, Baykan B, Serdaroglu P, et al. Epileptic seizures in Behçet’s disease. Epilepsia 2002;43:832–5. 9. Namer IJ, Karabudak R, Zileli T, et al. Peripheral nervous system involvement in Behçet’s disease. Eur Neurol 1987;26:235–40. 10. Oktem-Tanor O, Baykan-Kurt B, Gurvit IH, et al. Neuropsychological follow-up of 12 patients with Neuro-Behçet disease. J Neurol 1999;246:113–9. 11. Monastero R, Camarda C, Pipia C, et al. Cognitive impairment in Behçet’s disease patients without overt neurological involvement. J Neurol Sci 2004;220:99–104. 12. Kitaichi Y, Nakagawa T, Boku S, et al. Sertraline increases extracellular levels not only of serotonin, but also of dopamine in the nucleus accumbens and striatum of rats. Eur J Pharmacol 2010;647:90–6.
doi:http://dx.doi.org/10.1016/j.jocn.2012.03.048
Two patients with primary sellar leiomyomas, a rare entity Andrew Ko a, David K. Su a, Donald Born b, Anthony DeSantis c, R. Alan Failor c, Manuel Ferreira Jr. a,⇑ a b c
Department of Neurosurgery, University of Washington School of Medicine, 1959 NE Pacific Way, Seattle, WA 98195, USA Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA Department of Endocrinology, University of Washington School of Medicine, Seattle, WA, USA
a r t i c l e
i n f o
Article history: Received 24 June 2012 Accepted 4 July 2012
Keywords: Natural history Pituitary Prolactinemia Sellar leiomyoma Tumor
a b s t r a c t Leiomyomas are benign smooth muscle tumors commonly found in the genitourinary or gastrointestinal tracts. Rarely, they present as primary intracranial extra-axial brain tumors. Most of these lesions have been described in immunocompromised patients, but have been found very rarely in the immunocompetent patient. We present two patients with sporadic sellar leiomyomas. The first patient is a 25-year-old woman who presented with a 2-year history of amenorrhea and a heterogeneous lesion. The second is a 53-year-old man who presented with headaches and progressive panhypopituitarism, and a large cystic lesion expanding the sella. In both patients, transnasal transphenoidal surgery was performed for resection of the tumor. We review the intraoperative findings, neuropathology and immunohistochemistry and the clinical follow-up. A literature search, which revealed only two prior reported cases of sporadic sellar leiomyomas, and subsequent review led us to conclude that the natural history of sellar leiomyomas relates to the immune status of the patient and that these tumors may cause pituitary dysfunction through infiltration of the gland, mass effect and compression, or even potentially as a byproduct of prolactin secretion intrinsic to the tumor itself. Complete surgical resection of these infiltrating tumors may not be advisable when pituitary function is intact. Long-term endocrine follow-up in these patients is advised. Ó 2012 Published by Elsevier Ltd.
⇑ Corresponding author. Tel.: +1 206 543 357; fax: +1 206 543 8315. E-mail address: [email protected] (M. Ferreira Jr.).
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Case Reports / Journal of Clinical Neuroscience 20 (2013) 897–901
2.1. Patient 1
elevated at 32 ng/mL. The remainder of her endocrinological evaluation was unremarkable. Her neurological examination on presentation was normal and she had no visual symptoms or findings. A MRI of the brain revealed a 7 mm 10 mm 17 mm mixed cystic and solid mass in the posterior sella, eccentric to the right side. The mass demonstrated heterogeneous hypoenhancement relative to normal pituitary tissue. The lesion was slightly hypointense on T2-weighted MRI, a finding consistent with previous reports of intracranial leiomyomas5 (Fig. 1a). The decision was made to proceed with a microscopic transnasal, transphenoidal procedure to obtain a diagnosis and, if possible, resect the lesion. At surgery, the lesion was quite firm and attached to the pituitary stalk. Multiple biopsies were taken. Frozen section examination of the tissue identified nodules of fibrous tissue not consistent with adenoma or craniopharyngioma. Given the uncertain diagnosis and the intimate attachment of the tumor to the pituitary stalk, a subtotal resection (STR) was performed. Postoperatively, the patient recovered without event. Due to a persistently elevated prolactin level of 27 ng/mL, continued amennorhea, and her desire to become pregnant, the patient was started on cabergoline at 0.25 mg twice per week. At her latest follow up, the patient had normalisation of prolactin, with a level of 6 ng/mL. She remained hypogonadal. The remainder of her pituitary function remained normal. Postoperative MRI showed that about 50% of the tumor had been resected (Fig. 1c).
A 24-year-old woman presented with recent onset headache and a 4-year history of amenorrhea and infertility. She denied a history of galactorrhea during that time. Her prolactin was mildly
2.1.1. Histopathology Multiple samples were sent for histopathological assessment, including portions of normal-appearing pituitary gland as well as
1. Introduction Leiomyomas are benign tumors originating from smooth muscle cells. They are relatively common in the genitourinary and gastrointestinal tracts. They present uncommonly as primary intracranial skull-base lesions, with 21 cases reported in the literature to date.1–17 Even more rarely, they present as primary intrasellar masses, with only two prior cases having been reported.8,9 Diagnosis relies on histopathology, as the radiographic appearance and clinical presentation of these lesions is variable.5 A subset of these tumors, appearing in those in immunocompromised states, seems to be associated with the Epstein-Barr virus.2,3,8,11,14,17,18 In general, little is known about the natural history of intracranial leiomyomas as they are rare. Here we present two primary sellar leiomyomas in patients without known immunocompromise. Both presented with endocrine abnormalities. The first was treated surgically at initial presentation, while the other was treated conservatively for 10 years before undergoing surgery. Examination of these two cases may elucidate several aspects of the natural history of these rare tumors.
2. Case reports
Fig. 1. Sellar leiomyomas. (a) Pre-operative coronal MRI in Patient 1 (left, T1-weighted with contrast enhancement; right, T2-weighted) demonstrating a heterogeneous appearing solid lesion, eccentric to the right and abutting the pituitary gland and stalk. (b) Pre-operative sagittal MRI in Patient 2 (left, T1-weighted with contrast enhancement; right, T2-weighted) demonstrating a large cystic, non-enhancing lesion with nodule. The image on the left was obtained 7 years prior to the image on the right, demonstrating no significant change over that time. Eight-month post-operative T1-weighted with contrast enhancement MRI: (c) coronal in Patient 1 showing partial resection; and (d) sagittal in Patient 2 showing resection of the nodular lesion.
Case Reports / Journal of Clinical Neuroscience 20 (2013) 897–901
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Fig. 2. Histopathology and immunohistochemistry in Patient 1: showing (a) nests of glandular cells with infiltrating fibrous, spindle cell lesion (hematoxylin and eosin, 10); (b) prolactin staining of glandular nests consistent with pituitary gland ( 10); (c) infiltrating tumor into the adjacent region (negative CD34 stain ( 10); and (d) infiltrating smooth muscle cells positive for actin1A4 stain ( 10).
the tough, fibrous lesion. Hematoxylin and eosin (H&E) staining of the lesion revealed spindle cells arranged in fascicles, impinging upon areas of normal appearing pituitary gland. There were no mitotic figures, no signs of nuclear atypia and no necrosis. Immunohistochemistry showed uniformly positive staining for actin 1A4 (smooth muscle actin, SMA), desmin and actin. Nests of glandular cells were positive for synaptophysin, and these stained variably and appropriately for adenohypophyseal markers (Fig. 2). 2.2. Patient 2 A 50-year-old man with a 10-year history of chronic headache and panhypopituitarism was referred to our center for treatment of a complex, cystic sellar lesion that was increasing in size. At our initial evaluation, the patient reported only an increase in severity of his headaches. The patient was neurologically intact with no sign of visual deficit at a recent ophthalmologic examination. The patient was initially diagnosed with a sellar lesion incidentally via an MRI of the brain obtained during an evaluation for low back pain and headache 10 years prior. Interestingly, the patient’s prolactin level was elevated at 22.9 ng/mL, while the remainder of his endocrine laboratory tests reflected his longstanding panhypopituitarism. MRI revealed a fluid-filled sellar lesion measuring 30 mm 25 mm 25 mm with an anteriorly-based, enhancing nodule. This nodule was hypointense on T2-weighted MRI, a finding consistent with imaging characteristics reported for other intracranial leiomyomas5 (Fig. 1b). The lesion was accessed via an endoscopic, transnasal, transphenoidal approach. A thick, fibrous lesion was encountered once the dura was opened. Multiple specimens were sent for pathology, and frozen section revealed a spindle cell neoplasm. The lesion was extremely adherent to adjacent structures but was resected in its entirety. A small hole in the diaphragma sellae resulted in a cerebrospinal fluid (CSF) leak, which was repaired with a fat graft and septal mucosal flap. The repair was protected with lumbar drainage for 5 days. Nonetheless, the patient returned 2 weeks la-
ter with a delayed CSF leak. This was treated successfully with repeat lumbar drainage. At the most-recent follow-up, MRI revealed persistence of the cyst but no residual enhancing cyst wall or lesion. There was no evidence of a persistent CSF leak. He continued to have panhypopituitarism. 2.2.1. Histopathology Multiple samples were sent for histopathologic evaluation. H&E staining showed spindle cells arranged in fascicles amidst fibrous connective tissue and glandular nests of cells consistent with adenohypophysis (Fig. 3a). There were no mitotic figures and no necrosis. Immunohistochemistry showed uniform positivity for actin 1A4 (SMA), desmin and myosin staining. The glandular nests of cells were positive for synaptophysin and pancytokeratin (Fig. 3). 3. Discussion The first primary intracranial leiomyoma was reported in 1968.9 Since then, 21 cases of intracranial, benign smooth-muscle tumors have been reported. Only one patient with metastatic intracranial leiomyoma has been reported,19 and 12 patients with metastatic intracranial leiomyosarcomas, with four involving the skull base,20 making metastatic tumors even rarer. The incidence of these benign primary tumors may be increasing, as 16 cases have been reported since 1998. Of these, three-quarters (12/16) have been reported in patients in an immunocompromised state, either from immunosuppressive therapy for organ transplant or from infection with the human immunodeficiency virus. In these cases, the tumor appears to be associated with the Epstein-Barr virus.2,3,8,11,14,17,18 The immune status of the patient seems to be an important determinant of the natural history of intracranial leiomyomas. Extrauterine smooth muscle tumors in immunocompromised patients are more likely to be classified as leiomyosarcoma based on the presence and number of mitotic figures (>4 per high power
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Case Reports / Journal of Clinical Neuroscience 20 (2013) 897–901
Fig. 3. Histopathology and immunohistochemistry in Patient 2: showing (a) fibrous, spindle cell lesion infiltrating glandular nests of pituitary gland (hematoxylin and eosin, 10); (b) synaptophysin staining confirming the presence of pituitary gland amongst the spindle-cell lesion ( 10); (c) smooth muscle actin (actin 1A4) stain of fascicles interspersed with the glandular nests demonstrated in (b), again demonstrating the infiltrative nature of this neoplasm ( 10).
field); furthermore, their clinical behavior may be better correlated to immune status than to histopathological features.14 Multifocal presentation of leiomyomas has been reported in the immunocompromised patient,3,14,18 but not in other patients. It may be useful, then, to consider these lesions as two distinct groups: sporadic and those associated with the immunocompromised state. Including this report, most (6/10) sporadic intracranial leiomyomas have arisen in sellar (2/10) or para-sellar (4/10) locations.1,9,10,15 These lesions are thought to arise from smooth muscle present in the rich vasculature supplying this region of the skull base.14 Endocrine dysfunction may be the initial presentation of these tumors. A sporadic sellar leiomyoma has been associated with secondary hypothyroidism.8 Patient 2 in the present report presented with panhypopituitarism. Both patients presented with mildly elevated serum prolactin levels, presumably as a result of pituitary stalk compression and therefore decreased dopamine egress to the lactotrophe cells. However, it is also biologically plausible that the hyperprolactinemia is a result of direct tumor secretion of prolactin. In vitro studies of leiomyoma cells in culture have shown the ability to produce and secrete prolactin, and in vivo levels of serum prolactin have been correlated with the presence of proliferating smooth muscle cells of fibroid tumors.21–24 Serum prolactin levels have been proposed as a diagnostic marker for uterine leiomyomas.25 Altered pituitary function has been described in patients with leiomyoma, specifically, a diminished follicle-stimulating hormone response to gonadotropin
releasing hormone and increased serum prolactin levels in response to thyrotropin releasing hormone.24 There has been a case report of hyperprolactinemia initially attributed to dysfunction of the pituitary axis resolving after hysterectomy for uterine leiomyomas.26 Cabergoline, a dopamine receptor agonist, has been used effectively to treat uterine leiomyomas, resulting in decrease in the size of these tumors.27,28 In the two patients in the present report, the tumor was intimately associated with the pituitary gland, with fascicles of tumor cells interspersed within glandular tissue (Figs. 2 and 3), thus increasing risk to the gland itself during surgical resection. In patients with intact pituitary function, where a frozen section shows a spindle cell neoplasm infiltrating glandular tissue, the consideration for a conservative approach to prevent panhypopituitarism may be warranted. Whether the use of a medical treatment option (for example, dopamine agonist therapy) could reverse hormonal abnormalities, reduce tumor size, and allow the surgeon to avoid attempting a total resection that would place the patient at risk for panhypopituitarism, is unknown. Finally, both patients reported here presented with longstanding symptoms. In Patient 1 there was a several-year history of amenorrhea and hypogonadism before diagnosis. The hypogonadism persisted despite normalization of her prolactin. Patient 2 was followed for 10 years with panhypopituitarism without a definitive diagnosis. This indolent course suggests that these tumors, at least in sporadic occurrences, are slow-growing. Progression of the residual tumor, after STR, occurs rarely.10 As Patient 2 demonstrates, the infiltrating nature of these lesions may eventually cause panhypopituitarism, and long-term endocrine follow-up of these patients is advisable. Despite the small sample size and the rarity of these lesions, we have made several conclusions: the presentation and natural history of sellar leiomyomas is related to the immune status of the patient, and as mentioned in previous studies, it is important to add leiomyoma to the differential diagnosis in immunocompromised patients with dural-based intracranial lesions. In sporadic cases, they appear to be slow-growing lesions, where up to 10 years of conservative treatment may result in little change in tumor size. The sellar location of these tumors may cause endocrine abnormalities by several mechanisms including: compression of the normal pituitary gland or stalk, intrinsic secretion of prolactin by the tumor itself, or infiltration of the gland by smooth muscle. Finally, the infiltrating nature of these tumors, and their slow growth, supports a conservative approach to surgical resection when pituitary function is intact, with confirmation of diagnosis and decompression of adjacent structures being the goals of surgery rather than complete resection. There remains a possibility that tumor growth may be controllable through the use of dopaminergic agents. Longterm endocrinological follow-up is recommended for these patients.
References 1. Ali AE, Fazl M, Bilbao JM. Primary intracranial leiomyoma: a case report and literature review. Virchows Arch 2006;449:382–4. 2. Bargiela A, Rey JL, Diaz JL, et al. Meningeal leiomyoma in an adult with AIDS: CT and MRI with pathological correlation. Neuroradiology 1999;41:696–8. 3. Citow JS, Kranzler L. Multicentric intracranial smooth-muscle tumor in a woman with human immunodeficiency virus. Case report. J Neurosurg 2000;93:701–3. 4. Dorwal P, Kaul S, Arora D, et al. Intracranial leiomyoma in a male patient. Indian J Pathol Microbiol 2010;53:837–9. 5. Hua W, Xu F, Mao Y, et al. Primary intracranial leiomyomas: report of two cases and review of the literature. Clin Neurol Neurosurg 2009;111:907–12. 6. Karpinski NC, Yaghmai R, Barba D, et al. Case of the month: March 1999–A 26 year old HIV positive male with dura based masses. Brain Pathol 1999;9:609–10. 7. Kim SH, Youm JY, Song SH, et al. Primary intracranial leiomyoma. Case illustration. J Neurosurg 1999;90:171.
Case Reports / Journal of Clinical Neuroscience 20 (2013) 901–903 8. Kleinschmidt-DeMasters BK, Mierau GW, Sze CI, et al. Unusual dural and skullbased mesenchymal neoplasms: a report of four cases. Hum Pathol 1998;29:240–5. 9. Kroe DJ, Hudgins WR, Simmons JC, et al. Primary intrasellar leiomyoma. Case report. J Neurosurg 1968;29:189–91. 10. Kulkarni V, Rajshekhar V, Chandi SM. Orbital apex leiomyoma with intracranial extension. Surg Neurol 2000;54:327–30. 11. Kumar S, Santi M, Vezina G, et al. Epstein-Barr virus-associated smooth muscle tumor of the basal ganglia in an HIV+ child: case report and review of the literature. Pediatr Dev Pathol 2004;7:198–203. 12. Lai PH, Yang CF, Huang CH, et al. Primary intracranial leiomyoma: case report. Neuroradiology 1998;40:238–41. 13. Lin SL, Wang JS, Huang CS, et al. Primary intracerebral leiomyoma: a case with eosinophilic inclusions of actin filaments. Histopathology 1996;28:365–9. 14. Suankratay C, Shuangshoti S, Mutirangura A, et al. Epstein-Barr virus infectionassociated smooth-muscle tumors in patients with AIDS. Clin Infect Dis 2005;40:1521–8. 15. Thierauf P, Weiland H. Intracranial leiomyoma. Med Welt 1978;29:1280–2. 16. Wang KC, Kim CJ, Cho BK, et al. Cerebral leiomyoma in a child. J Korean Med Sci 1997;12:378–82. 17. Zevgaridis D, Tsonidis C, Kapranos N, et al. Epstein-Barr virus associated primary intracranial leiomyoma in organ transplant recipient: case report and review of the literature. Acta Neurochir (Wien) 2009;151:1705–9. 18. Gallien S, Zuber B, Polivka M, et al. Multifocal Epstein-Barr virus-associated smooth muscle tumor in adults with AIDS: case report and review of the literature. Oncology 2008;74:167–76. 19. Alessi G, Lemmerling M, Vereecken L, et al. Benign metastasizing leiomyoma to skull base and spine: a report of two cases. Clin Neurol Neurosurg 2003;105:170–4.
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20. Sandruck J, Escobar P, Lurain J, et al. Uterine leiomyosarcoma metastatic to the sphenoid sinus: a case report and review of the literature. Gynecol Oncol 2004;92:701–4. 21. Daly DC, Walters CA, Prior JC, et al. Prolactin production from proliferative phase leiomyoma. Am J Obstet Gynecol 1984;148:1059–63. 22. Nowak RA, Rein MS, Heffner LJ, et al. Production of prolactin by smooth muscle cells cultured from human uterine fibroid tumors. J Clin Endocrinol Metab 1993;76:1308–13. 23. Chapitis J, Riddick DH, Betz LM, et al. Physicochemical characterization and functional activity of fibroid prolactin produced in cell culture. Am J Obstet Gynecol 1988;158:846–53. 24. Ylikorkala O, Kauppila A, Rajala T. Pituitary gonadotrophins and prolactin in patients with endometrial cancer, fibroids or ovarian tumours. Br J Obstet Gynaecol 1979;86:901–4. 25. Baban RS. Serum protein and prolactin as diagnostic markers. Saudi Med J 2009;30:1411–5. 26. Cordiano V. Complete remission of hyperprolactinemia and erythrocytosis after hysterectomy for a uterine fibroid in a woman with a previous diagnosis of prolactin-secreting pituitary microadenoma. Ann Hematol 2005;84:200–2. 27. Melli MS, Farzadi L, Madarek EO. Comparison of the effect of gonadotropinreleasing hormone analog (diphereline) and cabergoline (dostinex) treatment on uterine myoma regression. Saudi Med J 2007;28:445–50. 28. Sayyah-Melli M, Tehrani-Gadim S, Dastranj-Tabrizi A, et al. Comparison of the effect of gonadotropin-releasing hormone agonist and dopamine receptor agonist on uterine myoma growth. Histologic, sonographic, and intra-operative changes. Saudi Med J 2009;30:1024–33.
doi:http://dx.doi.org/10.1016/j.jocn.2012.07.001
Image-guided transoral biopsy in a boy with Grisel’s syndrome Francesco Di Cola a,⇑, Tommaso Cutilli b, Danilo De Paulis c, Renato J. Galzio a,c a b c
Neurosurgery, Department of Health Sciences, University of L’Aquila, Piazza Salvatore Tommasi, Coppito, 67100 L’Aquila, Italy Maxillofacial Surgery, Department of Health Sciences, University of L’Aquila, L’Aquila, Italy Department of Neurosurgery, ‘‘San Salvatore’’ City Hospital, L’Aquila, Italy
a r t i c l e
i n f o
Article history: Received 18 October 2011 Accepted 14 March 2012
Keywords: Grisel’s syndrome Transoral biopsy Neuronavigation
a b s t r a c t Grisel’s syndrome is a disease characterized by an atlanto–axial rotatory subluxation following acute inflammation of the upper respiratory tract. The syndrome has a good prognosis as it usually heals with antibiotics, despite the delayed serious complications that have been reported. When neuroradiological investigation does not allow an accurate differential diagnosis between a tumor and osteomyelitis, an image-guided transoral biopsy is a safe, fast, minimally invasive, as well as effective, procedure. Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction Grisel’s syndrome1 is a relatively common disease that usually occurs in children. It is characterized by an atlanto–axial rotatory subluxation following an acute inflammation of the upper respiratory tract or, rarely, otorhinolaryngological surgery. The most frequent symptoms of this condition are neck pain and a stiff neck, with the head fixed in the ‘‘cock robin’’ position. Usually, contrast-enhanced MRI of the cervical spine is the gold standard for diagnosis, showing inflammation of both the dens and periodontoid tissue. The syndrome has a good prognosis as it usually heals with antibiotics, despite the reported possibilities of delayed serious complications. We report a very young boy with suspected Grisel’s syndrome, whose MRI scan showed an altered and not clearly defined signal in the dens. We decided to perform a neuronavigation-assisted, ⇑ Corresponding author. Tel./fax: +39 0862 368233. E-mail address: [email protected] (F. Di Cola).
transoral biopsy of the dens to clearly define the lesion and to provide adequate treatment. 2. Case report A 6-year-old boy was admitted to the San Salvatore City Hospital after 2 days of neck pain and a ‘‘cock robin’’ head position, with the head rotated to the right; the medical history revealed a recent pharyngitis (about 10 days before admission) that was resolved with broad-spectrum antibiotics, while the examination was otherwise negative. MRI of the cervical spine, before and after the addition of gadolinium contrast (Fig. 1), showed an altered, and not clearly defined, signal in the apex of the dens. The dens apex, as well as the surrounding soft tissue, seemed to have an irregular morphology: this area of altered signal, together with the adjacent dura mater, showed intense contrast enhancement. The transverse ligament was not affected. In addition, both brain and dorsolumbar contrast-enhanced MRI were performed, with no evidence of further lesions. Plain radiographs of the cervical spine and a thin-
In 2005 he underwent extensive neurological and neuropsychological evaluation, which comprised: Rey 15-Word List, Rey Complex Figure, Trail Making Test, Stroop Color-Word test, Colored Progressive Matrices, Frontal Assessment Battery, the ‘‘FAS’’ and Animal Naming test, Mini Mental State Examination (MMSE), and Neuropsychiatric Inventory (NPI). The patient obtained a baseline MMSE score of 25/30 and subsequent neuropsychological assessments highlighted the gradual deterioration of his cognitive status (for example, the MMSE at 3 years’ follow-up: 23/30). His behavioral disturbances worsened: depression and marked loss of interest (NPI subscale for depression = 4, for apathy = 8) in addition to his increasing anxiety and irritability. Therapy with sertraline (maximum dose reached 100 mg/day) was then established: significant improvement in mood (NPI = 2) and apathy (NPI = 2) was achieved and cognitive performance was ameliorated (MMSE = 28). These benefits were confirmed in the following 2 years of follow-up. 3. Discussion We described the onset of cognitive deterioration and behavioral impairment in a patient affected by BD. The most significant aspect of our report is the extensive retrospective as well as follow-up examinations and neuropsychological assessments performed (20 years). The patient’s disease history could be divided in two parts: (i) symptoms and signs characteristic of BD; and (ii) subsequent neurological manifestations and cognitive impairments of NBS. Oktem-Tanor et al.10 stated that the stage and the nature of cognitive impairment do not appear to be correlated with the burden and location of parenchymal lesions; nevertheless, reports of apathetic patients have described ponto-mesencephalic lesions as occurred in by our patient, which suggest, in our opinion, a hypothetical correlation.
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The use of the selective serotonin reuptake inhibitor (SSRI), sertraline, resulted in a significant improvement in both behavioral disturbances (apathy, depression and irritability) and cognitive performance (MMSE gain of 5 points). These results can probably be attributed to the pharmacological profile of sertraline, a potent SSRI, as well as its ability to inhibit dopamine uptake.12 The latter could explain the remarkable improvement in apathetic behavior. References 1. International Study Group for Behçet’s Disease. Criteria for diagnosis of Behçet’s disease. Lancet 1990;335:1078–80. 2. Akman-Demir G, Serdarog˘lu P, Tasçi B. Clinical patterns of neurological involvement in Behçet’s desease: evaluation of 200 patients. The NeuroBehcet Study Group. Brain 1999;122:2171–81. 3. Serdarog˘lu P. Behçet’s disease and the nervous system. J Neurol 1998;245:197–205. 4. Siva A, Kantarci OH, Saip S, et al. Behçet’s disease: diagnostic and prognostic aspects of neurological involvement. J Neurol 2001;248:95–103. 5. Kidd D. The prevalence of headache in Behçet’s syndrome. Adv Exp Med Biol 2003;528:377–9. 6. Siva A, Yazici H. Behçet’s disease. In: Levine S, Doruk E, editors. Handbook of systemic autoimmune diseases, neurology volume – the neurologic involvement in systemic autoimmune disorders. Elsevier Science; 2004. 7. Kidd D, Steuer A, Denman AM, et al. Neurological complications in Behçet’s syndrome. Brain 1999;122:2183–94. 8. Aykutlu E, Baykan B, Serdaroglu P, et al. Epileptic seizures in Behçet’s disease. Epilepsia 2002;43:832–5. 9. Namer IJ, Karabudak R, Zileli T, et al. Peripheral nervous system involvement in Behçet’s disease. Eur Neurol 1987;26:235–40. 10. Oktem-Tanor O, Baykan-Kurt B, Gurvit IH, et al. Neuropsychological follow-up of 12 patients with Neuro-Behçet disease. J Neurol 1999;246:113–9. 11. Monastero R, Camarda C, Pipia C, et al. Cognitive impairment in Behçet’s disease patients without overt neurological involvement. J Neurol Sci 2004;220:99–104. 12. Kitaichi Y, Nakagawa T, Boku S, et al. Sertraline increases extracellular levels not only of serotonin, but also of dopamine in the nucleus accumbens and striatum of rats. Eur J Pharmacol 2010;647:90–6.
doi:http://dx.doi.org/10.1016/j.jocn.2012.03.048
Two patients with primary sellar leiomyomas, a rare entity Andrew Ko a, David K. Su a, Donald Born b, Anthony DeSantis c, R. Alan Failor c, Manuel Ferreira Jr. a,⇑ a b c
Department of Neurosurgery, University of Washington School of Medicine, 1959 NE Pacific Way, Seattle, WA 98195, USA Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA Department of Endocrinology, University of Washington School of Medicine, Seattle, WA, USA
a r t i c l e
i n f o
Article history: Received 24 June 2012 Accepted 4 July 2012
Keywords: Natural history Pituitary Prolactinemia Sellar leiomyoma Tumor
a b s t r a c t Leiomyomas are benign smooth muscle tumors commonly found in the genitourinary or gastrointestinal tracts. Rarely, they present as primary intracranial extra-axial brain tumors. Most of these lesions have been described in immunocompromised patients, but have been found very rarely in the immunocompetent patient. We present two patients with sporadic sellar leiomyomas. The first patient is a 25-year-old woman who presented with a 2-year history of amenorrhea and a heterogeneous lesion. The second is a 53-year-old man who presented with headaches and progressive panhypopituitarism, and a large cystic lesion expanding the sella. In both patients, transnasal transphenoidal surgery was performed for resection of the tumor. We review the intraoperative findings, neuropathology and immunohistochemistry and the clinical follow-up. A literature search, which revealed only two prior reported cases of sporadic sellar leiomyomas, and subsequent review led us to conclude that the natural history of sellar leiomyomas relates to the immune status of the patient and that these tumors may cause pituitary dysfunction through infiltration of the gland, mass effect and compression, or even potentially as a byproduct of prolactin secretion intrinsic to the tumor itself. Complete surgical resection of these infiltrating tumors may not be advisable when pituitary function is intact. Long-term endocrine follow-up in these patients is advised. Ó 2012 Published by Elsevier Ltd.
⇑ Corresponding author. Tel.: +1 206 543 357; fax: +1 206 543 8315. E-mail address: [email protected] (M. Ferreira Jr.).
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2.1. Patient 1
elevated at 32 ng/mL. The remainder of her endocrinological evaluation was unremarkable. Her neurological examination on presentation was normal and she had no visual symptoms or findings. A MRI of the brain revealed a 7 mm 10 mm 17 mm mixed cystic and solid mass in the posterior sella, eccentric to the right side. The mass demonstrated heterogeneous hypoenhancement relative to normal pituitary tissue. The lesion was slightly hypointense on T2-weighted MRI, a finding consistent with previous reports of intracranial leiomyomas5 (Fig. 1a). The decision was made to proceed with a microscopic transnasal, transphenoidal procedure to obtain a diagnosis and, if possible, resect the lesion. At surgery, the lesion was quite firm and attached to the pituitary stalk. Multiple biopsies were taken. Frozen section examination of the tissue identified nodules of fibrous tissue not consistent with adenoma or craniopharyngioma. Given the uncertain diagnosis and the intimate attachment of the tumor to the pituitary stalk, a subtotal resection (STR) was performed. Postoperatively, the patient recovered without event. Due to a persistently elevated prolactin level of 27 ng/mL, continued amennorhea, and her desire to become pregnant, the patient was started on cabergoline at 0.25 mg twice per week. At her latest follow up, the patient had normalisation of prolactin, with a level of 6 ng/mL. She remained hypogonadal. The remainder of her pituitary function remained normal. Postoperative MRI showed that about 50% of the tumor had been resected (Fig. 1c).
A 24-year-old woman presented with recent onset headache and a 4-year history of amenorrhea and infertility. She denied a history of galactorrhea during that time. Her prolactin was mildly
2.1.1. Histopathology Multiple samples were sent for histopathological assessment, including portions of normal-appearing pituitary gland as well as
1. Introduction Leiomyomas are benign tumors originating from smooth muscle cells. They are relatively common in the genitourinary and gastrointestinal tracts. They present uncommonly as primary intracranial skull-base lesions, with 21 cases reported in the literature to date.1–17 Even more rarely, they present as primary intrasellar masses, with only two prior cases having been reported.8,9 Diagnosis relies on histopathology, as the radiographic appearance and clinical presentation of these lesions is variable.5 A subset of these tumors, appearing in those in immunocompromised states, seems to be associated with the Epstein-Barr virus.2,3,8,11,14,17,18 In general, little is known about the natural history of intracranial leiomyomas as they are rare. Here we present two primary sellar leiomyomas in patients without known immunocompromise. Both presented with endocrine abnormalities. The first was treated surgically at initial presentation, while the other was treated conservatively for 10 years before undergoing surgery. Examination of these two cases may elucidate several aspects of the natural history of these rare tumors.
2. Case reports
Fig. 1. Sellar leiomyomas. (a) Pre-operative coronal MRI in Patient 1 (left, T1-weighted with contrast enhancement; right, T2-weighted) demonstrating a heterogeneous appearing solid lesion, eccentric to the right and abutting the pituitary gland and stalk. (b) Pre-operative sagittal MRI in Patient 2 (left, T1-weighted with contrast enhancement; right, T2-weighted) demonstrating a large cystic, non-enhancing lesion with nodule. The image on the left was obtained 7 years prior to the image on the right, demonstrating no significant change over that time. Eight-month post-operative T1-weighted with contrast enhancement MRI: (c) coronal in Patient 1 showing partial resection; and (d) sagittal in Patient 2 showing resection of the nodular lesion.
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Fig. 2. Histopathology and immunohistochemistry in Patient 1: showing (a) nests of glandular cells with infiltrating fibrous, spindle cell lesion (hematoxylin and eosin, 10); (b) prolactin staining of glandular nests consistent with pituitary gland ( 10); (c) infiltrating tumor into the adjacent region (negative CD34 stain ( 10); and (d) infiltrating smooth muscle cells positive for actin1A4 stain ( 10).
the tough, fibrous lesion. Hematoxylin and eosin (H&E) staining of the lesion revealed spindle cells arranged in fascicles, impinging upon areas of normal appearing pituitary gland. There were no mitotic figures, no signs of nuclear atypia and no necrosis. Immunohistochemistry showed uniformly positive staining for actin 1A4 (smooth muscle actin, SMA), desmin and actin. Nests of glandular cells were positive for synaptophysin, and these stained variably and appropriately for adenohypophyseal markers (Fig. 2). 2.2. Patient 2 A 50-year-old man with a 10-year history of chronic headache and panhypopituitarism was referred to our center for treatment of a complex, cystic sellar lesion that was increasing in size. At our initial evaluation, the patient reported only an increase in severity of his headaches. The patient was neurologically intact with no sign of visual deficit at a recent ophthalmologic examination. The patient was initially diagnosed with a sellar lesion incidentally via an MRI of the brain obtained during an evaluation for low back pain and headache 10 years prior. Interestingly, the patient’s prolactin level was elevated at 22.9 ng/mL, while the remainder of his endocrine laboratory tests reflected his longstanding panhypopituitarism. MRI revealed a fluid-filled sellar lesion measuring 30 mm 25 mm 25 mm with an anteriorly-based, enhancing nodule. This nodule was hypointense on T2-weighted MRI, a finding consistent with imaging characteristics reported for other intracranial leiomyomas5 (Fig. 1b). The lesion was accessed via an endoscopic, transnasal, transphenoidal approach. A thick, fibrous lesion was encountered once the dura was opened. Multiple specimens were sent for pathology, and frozen section revealed a spindle cell neoplasm. The lesion was extremely adherent to adjacent structures but was resected in its entirety. A small hole in the diaphragma sellae resulted in a cerebrospinal fluid (CSF) leak, which was repaired with a fat graft and septal mucosal flap. The repair was protected with lumbar drainage for 5 days. Nonetheless, the patient returned 2 weeks la-
ter with a delayed CSF leak. This was treated successfully with repeat lumbar drainage. At the most-recent follow-up, MRI revealed persistence of the cyst but no residual enhancing cyst wall or lesion. There was no evidence of a persistent CSF leak. He continued to have panhypopituitarism. 2.2.1. Histopathology Multiple samples were sent for histopathologic evaluation. H&E staining showed spindle cells arranged in fascicles amidst fibrous connective tissue and glandular nests of cells consistent with adenohypophysis (Fig. 3a). There were no mitotic figures and no necrosis. Immunohistochemistry showed uniform positivity for actin 1A4 (SMA), desmin and myosin staining. The glandular nests of cells were positive for synaptophysin and pancytokeratin (Fig. 3). 3. Discussion The first primary intracranial leiomyoma was reported in 1968.9 Since then, 21 cases of intracranial, benign smooth-muscle tumors have been reported. Only one patient with metastatic intracranial leiomyoma has been reported,19 and 12 patients with metastatic intracranial leiomyosarcomas, with four involving the skull base,20 making metastatic tumors even rarer. The incidence of these benign primary tumors may be increasing, as 16 cases have been reported since 1998. Of these, three-quarters (12/16) have been reported in patients in an immunocompromised state, either from immunosuppressive therapy for organ transplant or from infection with the human immunodeficiency virus. In these cases, the tumor appears to be associated with the Epstein-Barr virus.2,3,8,11,14,17,18 The immune status of the patient seems to be an important determinant of the natural history of intracranial leiomyomas. Extrauterine smooth muscle tumors in immunocompromised patients are more likely to be classified as leiomyosarcoma based on the presence and number of mitotic figures (>4 per high power
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Fig. 3. Histopathology and immunohistochemistry in Patient 2: showing (a) fibrous, spindle cell lesion infiltrating glandular nests of pituitary gland (hematoxylin and eosin, 10); (b) synaptophysin staining confirming the presence of pituitary gland amongst the spindle-cell lesion ( 10); (c) smooth muscle actin (actin 1A4) stain of fascicles interspersed with the glandular nests demonstrated in (b), again demonstrating the infiltrative nature of this neoplasm ( 10).
field); furthermore, their clinical behavior may be better correlated to immune status than to histopathological features.14 Multifocal presentation of leiomyomas has been reported in the immunocompromised patient,3,14,18 but not in other patients. It may be useful, then, to consider these lesions as two distinct groups: sporadic and those associated with the immunocompromised state. Including this report, most (6/10) sporadic intracranial leiomyomas have arisen in sellar (2/10) or para-sellar (4/10) locations.1,9,10,15 These lesions are thought to arise from smooth muscle present in the rich vasculature supplying this region of the skull base.14 Endocrine dysfunction may be the initial presentation of these tumors. A sporadic sellar leiomyoma has been associated with secondary hypothyroidism.8 Patient 2 in the present report presented with panhypopituitarism. Both patients presented with mildly elevated serum prolactin levels, presumably as a result of pituitary stalk compression and therefore decreased dopamine egress to the lactotrophe cells. However, it is also biologically plausible that the hyperprolactinemia is a result of direct tumor secretion of prolactin. In vitro studies of leiomyoma cells in culture have shown the ability to produce and secrete prolactin, and in vivo levels of serum prolactin have been correlated with the presence of proliferating smooth muscle cells of fibroid tumors.21–24 Serum prolactin levels have been proposed as a diagnostic marker for uterine leiomyomas.25 Altered pituitary function has been described in patients with leiomyoma, specifically, a diminished follicle-stimulating hormone response to gonadotropin
releasing hormone and increased serum prolactin levels in response to thyrotropin releasing hormone.24 There has been a case report of hyperprolactinemia initially attributed to dysfunction of the pituitary axis resolving after hysterectomy for uterine leiomyomas.26 Cabergoline, a dopamine receptor agonist, has been used effectively to treat uterine leiomyomas, resulting in decrease in the size of these tumors.27,28 In the two patients in the present report, the tumor was intimately associated with the pituitary gland, with fascicles of tumor cells interspersed within glandular tissue (Figs. 2 and 3), thus increasing risk to the gland itself during surgical resection. In patients with intact pituitary function, where a frozen section shows a spindle cell neoplasm infiltrating glandular tissue, the consideration for a conservative approach to prevent panhypopituitarism may be warranted. Whether the use of a medical treatment option (for example, dopamine agonist therapy) could reverse hormonal abnormalities, reduce tumor size, and allow the surgeon to avoid attempting a total resection that would place the patient at risk for panhypopituitarism, is unknown. Finally, both patients reported here presented with longstanding symptoms. In Patient 1 there was a several-year history of amenorrhea and hypogonadism before diagnosis. The hypogonadism persisted despite normalization of her prolactin. Patient 2 was followed for 10 years with panhypopituitarism without a definitive diagnosis. This indolent course suggests that these tumors, at least in sporadic occurrences, are slow-growing. Progression of the residual tumor, after STR, occurs rarely.10 As Patient 2 demonstrates, the infiltrating nature of these lesions may eventually cause panhypopituitarism, and long-term endocrine follow-up of these patients is advisable. Despite the small sample size and the rarity of these lesions, we have made several conclusions: the presentation and natural history of sellar leiomyomas is related to the immune status of the patient, and as mentioned in previous studies, it is important to add leiomyoma to the differential diagnosis in immunocompromised patients with dural-based intracranial lesions. In sporadic cases, they appear to be slow-growing lesions, where up to 10 years of conservative treatment may result in little change in tumor size. The sellar location of these tumors may cause endocrine abnormalities by several mechanisms including: compression of the normal pituitary gland or stalk, intrinsic secretion of prolactin by the tumor itself, or infiltration of the gland by smooth muscle. Finally, the infiltrating nature of these tumors, and their slow growth, supports a conservative approach to surgical resection when pituitary function is intact, with confirmation of diagnosis and decompression of adjacent structures being the goals of surgery rather than complete resection. There remains a possibility that tumor growth may be controllable through the use of dopaminergic agents. Longterm endocrinological follow-up is recommended for these patients.
References 1. Ali AE, Fazl M, Bilbao JM. Primary intracranial leiomyoma: a case report and literature review. Virchows Arch 2006;449:382–4. 2. Bargiela A, Rey JL, Diaz JL, et al. Meningeal leiomyoma in an adult with AIDS: CT and MRI with pathological correlation. Neuroradiology 1999;41:696–8. 3. Citow JS, Kranzler L. Multicentric intracranial smooth-muscle tumor in a woman with human immunodeficiency virus. Case report. J Neurosurg 2000;93:701–3. 4. Dorwal P, Kaul S, Arora D, et al. Intracranial leiomyoma in a male patient. Indian J Pathol Microbiol 2010;53:837–9. 5. Hua W, Xu F, Mao Y, et al. Primary intracranial leiomyomas: report of two cases and review of the literature. Clin Neurol Neurosurg 2009;111:907–12. 6. Karpinski NC, Yaghmai R, Barba D, et al. Case of the month: March 1999–A 26 year old HIV positive male with dura based masses. Brain Pathol 1999;9:609–10. 7. Kim SH, Youm JY, Song SH, et al. Primary intracranial leiomyoma. Case illustration. J Neurosurg 1999;90:171.
Case Reports / Journal of Clinical Neuroscience 20 (2013) 901–903 8. Kleinschmidt-DeMasters BK, Mierau GW, Sze CI, et al. Unusual dural and skullbased mesenchymal neoplasms: a report of four cases. Hum Pathol 1998;29:240–5. 9. Kroe DJ, Hudgins WR, Simmons JC, et al. Primary intrasellar leiomyoma. Case report. J Neurosurg 1968;29:189–91. 10. Kulkarni V, Rajshekhar V, Chandi SM. Orbital apex leiomyoma with intracranial extension. Surg Neurol 2000;54:327–30. 11. Kumar S, Santi M, Vezina G, et al. Epstein-Barr virus-associated smooth muscle tumor of the basal ganglia in an HIV+ child: case report and review of the literature. Pediatr Dev Pathol 2004;7:198–203. 12. Lai PH, Yang CF, Huang CH, et al. Primary intracranial leiomyoma: case report. Neuroradiology 1998;40:238–41. 13. Lin SL, Wang JS, Huang CS, et al. Primary intracerebral leiomyoma: a case with eosinophilic inclusions of actin filaments. Histopathology 1996;28:365–9. 14. Suankratay C, Shuangshoti S, Mutirangura A, et al. Epstein-Barr virus infectionassociated smooth-muscle tumors in patients with AIDS. Clin Infect Dis 2005;40:1521–8. 15. Thierauf P, Weiland H. Intracranial leiomyoma. Med Welt 1978;29:1280–2. 16. Wang KC, Kim CJ, Cho BK, et al. Cerebral leiomyoma in a child. J Korean Med Sci 1997;12:378–82. 17. Zevgaridis D, Tsonidis C, Kapranos N, et al. Epstein-Barr virus associated primary intracranial leiomyoma in organ transplant recipient: case report and review of the literature. Acta Neurochir (Wien) 2009;151:1705–9. 18. Gallien S, Zuber B, Polivka M, et al. Multifocal Epstein-Barr virus-associated smooth muscle tumor in adults with AIDS: case report and review of the literature. Oncology 2008;74:167–76. 19. Alessi G, Lemmerling M, Vereecken L, et al. Benign metastasizing leiomyoma to skull base and spine: a report of two cases. Clin Neurol Neurosurg 2003;105:170–4.
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doi:http://dx.doi.org/10.1016/j.jocn.2012.07.001
Image-guided transoral biopsy in a boy with Grisel’s syndrome Francesco Di Cola a,⇑, Tommaso Cutilli b, Danilo De Paulis c, Renato J. Galzio a,c a b c
Neurosurgery, Department of Health Sciences, University of L’Aquila, Piazza Salvatore Tommasi, Coppito, 67100 L’Aquila, Italy Maxillofacial Surgery, Department of Health Sciences, University of L’Aquila, L’Aquila, Italy Department of Neurosurgery, ‘‘San Salvatore’’ City Hospital, L’Aquila, Italy
a r t i c l e
i n f o
Article history: Received 18 October 2011 Accepted 14 March 2012
Keywords: Grisel’s syndrome Transoral biopsy Neuronavigation
a b s t r a c t Grisel’s syndrome is a disease characterized by an atlanto–axial rotatory subluxation following acute inflammation of the upper respiratory tract. The syndrome has a good prognosis as it usually heals with antibiotics, despite the delayed serious complications that have been reported. When neuroradiological investigation does not allow an accurate differential diagnosis between a tumor and osteomyelitis, an image-guided transoral biopsy is a safe, fast, minimally invasive, as well as effective, procedure. Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction Grisel’s syndrome1 is a relatively common disease that usually occurs in children. It is characterized by an atlanto–axial rotatory subluxation following an acute inflammation of the upper respiratory tract or, rarely, otorhinolaryngological surgery. The most frequent symptoms of this condition are neck pain and a stiff neck, with the head fixed in the ‘‘cock robin’’ position. Usually, contrast-enhanced MRI of the cervical spine is the gold standard for diagnosis, showing inflammation of both the dens and periodontoid tissue. The syndrome has a good prognosis as it usually heals with antibiotics, despite the reported possibilities of delayed serious complications. We report a very young boy with suspected Grisel’s syndrome, whose MRI scan showed an altered and not clearly defined signal in the dens. We decided to perform a neuronavigation-assisted, ⇑ Corresponding author. Tel./fax: +39 0862 368233. E-mail address: [email protected] (F. Di Cola).
transoral biopsy of the dens to clearly define the lesion and to provide adequate treatment. 2. Case report A 6-year-old boy was admitted to the San Salvatore City Hospital after 2 days of neck pain and a ‘‘cock robin’’ head position, with the head rotated to the right; the medical history revealed a recent pharyngitis (about 10 days before admission) that was resolved with broad-spectrum antibiotics, while the examination was otherwise negative. MRI of the cervical spine, before and after the addition of gadolinium contrast (Fig. 1), showed an altered, and not clearly defined, signal in the apex of the dens. The dens apex, as well as the surrounding soft tissue, seemed to have an irregular morphology: this area of altered signal, together with the adjacent dura mater, showed intense contrast enhancement. The transverse ligament was not affected. In addition, both brain and dorsolumbar contrast-enhanced MRI were performed, with no evidence of further lesions. Plain radiographs of the cervical spine and a thin-