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CLINICAL CASES

Received: March 23^rd 2015

Accepted: October 10^th 2015

Morgagni-Stewart-Morel syndrome. Case report and review of the literature

Abraham Edgar Gracia-Ramos^a

^aDepartamento de Medicina Interna, Subdirección de Servicios Clínicos, Hospital General “General José María Morelos y Pavón”, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Zumpango de Ocampo, Estado de México, México

Communication with: Abraham Edgar Gracia-Ramos

Telephone: (591) 917 7190, extensión 98201

Email: aegr_1982@outlook.com

Background: Hyperostosis frontalis interna (HFI) is a bone overgrowth on the inside of the frontal bone. This alteration can occur in isolation or together with neuropsychiatric symptoms, metabolic and endocrine manifestations which together form the Morgagni-Stewart-Morel syndrome. In this regard, the case of a patient who meets criteria for this syndrome is presented and a review of the literature is performed with focus on its pathophysiology.

Clinical case: A 74 years old female with a history of exposure to wood smoke, vitiligo, type 2 diabetes mellitus, hypertension and cognitive impairment who enters the hospital by malaise, dizziness, anxiety, confusion, disorientation and difficulty walking. In she were performed imaging of the skull where was observed the presence of extensive hyperostosis frontalis interna, cortical atrophy and a left thalamic lacunar infarction. During this hospital stay the presence of grade I obesity, hyperglycemia, hypertriglyceridemia and hyperuricemia was documented.

Conclusions: The patient met the criteria of Morgagni-Stewart-Morel syndrome to manifest the presence of hyperostosis frontalis interna with metabolic, endocrine and neuropsychiatric manifestations. The pathophysiological origin of the syndrome is unknown, although it has been postulated that an endocrine imbalance motivated by genetic and environmental factors may be the cause.

Keywords: Hyperostosis frontalis interna; Frontal bone; Obesity; Diabetes mellitus

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Hyperostosis of the skull refers to a group of pathological intracranial findings, each of them with an independent etiology, with different histological characteristics and locations.¹ In 1964, Perou defined hyperostosis frontalis interna (HFI) as a bilateral dysplastic slow-growing bone proliferation, usually self-limiting and benign, but sometimes progressive and aggressive, which primarily involves the inner table of the skull, with or without participation of the diploë, and with a predilection for the frontal bone,² but which can occasionally spread to the temporal and parietal bones, and the occipital.³ The midline of the skull is respected in most cases.¹ Histologically, it presents normal bone components, including haversian systems, and the lamellar bone shows no evidence of neoplastic cells.³ The differential diagnosis of this entity should be done with the osteophytes in pregnancy, osteoid osteoma, Paget's disease, acromegaly, senile hyperostosis, and other tumorous conditions. However, HFI is easily distinguished by its unique appearance and distribution.^4,5 The prevalence and severity of this disease have increased over time: it is rarely described in historical populations but is common in modern populations.⁵ Moreover, it most often affects women, and the severity of the phenomenon increases with age.^2,6

HFI may appear alone; it is usually found incidentally in X-rays of cranial computed tomography or magnetic resonance imaging,⁷ but may also be accompanied by various metabolic, endocrine, neuropsychiatric, and vascular manifestations, forming different syndromes such as Morgagni syndrome (HFI, obesity, sex gland disorders), Stewart-Morel syndrome (HFI, obesity, mental disorders), Troell-Junet syndrome (HFI, acromegaly, gout, diabetes mellitus), Frölich syndrome (HFI, obesity, stunted growth, pituitary disorder) and Klippel-Trenaunay-Weber syndrome (hypertrophy of soft tissue and bone including HFI, varicose veins, and hemangioma).^1,8,9 Currently, several of these manifestations are grouped into Morgagni-Stewart-Morel syndrome (or Morgagni-Stewart-Morel-Moore syndrome), which is defined by the presence of HFI associated with various metabolic, endocrine, and neuropsychiatric disorders.¹⁰ In this regard, the case of a patient meeting the criteria for such a syndrome is reported here, which, although it is little described, is relevant because the main components are common and, as reported in the literature, show a pathophysiological link.

Clinical case

74-year-old woman with a history of chronic exposure to wood smoke, Vitiligo of 20 years of evolution without treatment, hypertension identified 15 years ago and under control with enalapril, diabetes mellitus type 2 of 8 years of diagnosis treated with glyburide and metformin, and a history of anterograde amnesia reported by relatives of 6 months evolution. Her current condition began 24 hours before her hospital admission with the presence of malaise, dizziness, anxiety, confusion, disorientation, and difficulty walking.

Upon entering the Continuous Admission Area, a blood pressure figure of 190/100 mm Hg was documented. Physical examination found impaired higher mental functions and right hemiparesis. A simple cranial computed tomography reported uniform and normal brain parenchyma, cortical atrophy, and compensatory ventriculomegaly but with multiple nodules on the inner surface of the frontal bone and both parietal lobes (Figure 1). Skull MRI documented a recent left thalamic lacunar infarct and confirmed the presence of cranial enostosis (Figure 2). The electroencephalogram was normal for the patient’s age, without epileptiform activity or data consistent with encephalopathy.

The patient was hospitalized in the Internal Medicine Department, where she received treatment for cerebrovascular disease with atorvastatin and aspirin from the neurology department. Also, she initially received antihypertensive treatment based on prazosin and subsequently amlodipine. However, her endocrine and metabolic state received further study through her history and findings from imaging studies. Her weight was 68 kg and height 1.48 m, with a body mass index of 31.04 kg/m² body surface. Her laboratory tests reported: glucose 115 mg/dL (normal 70-100); glycated hemoglobin 7.6% (normal 4.0-6.0); uric acid 6.48 mg/dL (normal 2.0-6.0), and triglycerides 272 mg/dL (normal 50-150). Blood count and nitrogen and total cholesterol determination, together with their subunits, were all normal. In the hormonal profile, the determination of 1,24 dihydroxycholecalciferol, parathyroid hormone, growth hormone, luteinizing hormone, follicle stimulating hormone, estradiol, prolactin, thyroid stimulating hormone, thyroxine, free thyroxine, triiodothyronine, adrenocorticotropic hormone, and morning cortisol were normal. Only total testosterone was reported at 0.03 ng/dL (normal 1.42-9.23).

After 6 days of hospitalization, the patient recovered from the acute state of confusion, but with persistence of right hemiparesis as a sequela of cerebral vascular disease. She was discharged and is still followed by the Neurology department of our unit.

Discussion

This case is a woman in the eighth decade of life with a history of exposure to wood smoke, vitiligo, hypertension, diabetes mellitus, and cognitive impairment, in whom the presence of HFI is documented, also associated with obesity, hypertriglyceridemia, and hyperuricemia, thereby integrating the diagnosis of Morgagni-Stewart-Morel syndrome. HFI is characterized by the presence of one or, more frequently, multiple nodules located bilaterally in the inner table of the frontal bone, although it can spread to the temporal and parietal bones and the occipital, and respect the midline.^1,3 This entity is found in isolation in archaeological studies of skeletons prior to the 18^th century,^11,12 except for some studies in isolated historic towns such as in the ancient city of Qatna, Syria, and Pueblo Bonito, New Mexico, where a high prevalence is reported.^13,14 Currently, the prevalence ranges from 0.8 to 12.8%.^12,15

It is believed that the period of the industrial revolution was the turning point in the prevalence of HFI, where economic conditions, availability of food, and caloric intake improved dramatically in a large proportion of the population, leading to an increase in life expectancy, but also with an increased incidence of metabolic and endocrine disorders, which may have a role in the development of HFI.¹⁵ It is 4 to 5 times more common in women, with the highest prevalence in the postmenopause phase (40-60%),¹⁵ and its presence in men has been associated with gonadal disorders, where a positive relationship between HFI and androgen suppression has been documented,¹⁶ suggesting the hypothesis that prolonged estrogen stimulation during the reproductive period could explain its prevalence in females.^1,2

The severity of HFI varies widely in shape and size, and can be classified using radiological (indirect) or morphological (direct) methods.¹ Based on radiological observations, HFI can be classified into 3 categories: positive, negative, and inconclusive. In positive cases, HFI is seen in skull x-rays and is characterized by a large irregularity of the endocraneal surface of the frontal bone with variably increased density; in cases classified as negative, there are no identifiable abnormalities in x-rays; in the inconclusive cases, there are minimal identifiable positive changes.³ The radiological criteria for assessing HFI are: Grade 0, no bone formation; Grade I, initial bone formation in the endocranium; Grade II, prominent and rounded bone thickening in the internal table; Grade III, extensive skull thickening with irregular nodules.¹⁷ The morphological and histopathological classification of the disease divides it into 4 levels of severity: Type A, one or multiple isolated bone elevations less than 10 mm in diameter located on the intracranial surface of the frontal bone; Type B, nodular bone formation that occupies less than 25% of the frontal bone; Type C, nodular bone formation affecting less than 50% of the frontal; Type D, continuous nodular bony overgrowth involving more than 50% of the frontal.¹⁵ This classification has been modified adding Type E, which is designated as HFI with severe expansion into soft tissue.¹ The morphological classification has been adapted for use in computed tomography images of the skull with a sensitivity of 84%, a specificity of 90.5%, and a positive predictive value of 91%.^3,5 According to the morphological features found in the digital reconstruction images of the skull tomography and magnetic resonance imaging, our patient was classed into Type D.   

HFI usually produces no symptoms, but if the bone nodules protrude extensively (bullet-like), or if they are too large, the underlying soft tissue such as the dura or brain can be compressed or affected.^1,9,10,18 Some studies have indicated brain atrophy in connection with HFI,^18,19 although it is unclear whether HFI causes brain atrophy through chronic cerebral compression, or whether nodular growth occupies the space created by brain degeneration.¹² The neurological manifestations that have been linked to brain compression in patients affected by HFI include cognitive impairment,^19,20 headache,²¹ transcortical motor aphasia, Parkinson’s,²² dementia, epilepsy,^23,24 and intracranial hypertension.²⁵ Psychiatric manifestations such as behavioral disturbances and depression have also been associated.^10,12 Regarding this, it is believed that the cognitive impairment of 6 months evolution mentioned in the patient, manifested by anterograde amnesia, may be due to encephalic compression caused by HFI and, by that token, the acute neurological deficits that brought about medical care can be explained by uncontrolled hypertension and the ischemic lesion in the left thalamus identified in the magnetic resonance imaging of the brain. 

On the other hand, the presence of HFI together with neuropsychiatric, metabolic, and endocrine abnormalities define Morgagni-Stewart-Morel syndrome (or Morgagni-Stewart-Morel-Moore syndrome).^10,16 This condition was first described in 1719 by Giovanni Battista Morgagni, who noted an association between HFI, obesity, and hirsutism (Morgagni syndrome).^1,8-10 In 1928 Stewart and in 1929 Morel documented its relationship with psychiatric symptoms and persistent headache (Stewart-Morel syndrome).^1,3,10 In 1955, noting the association between HFI, obesity, and diabetes mellitus, Moore called this condition metabolic craniopathy.¹³ Currently Morgagni-Stewart-Morel syndrome has been associated with various metabolic and hormonal disorders such as obesity, diabetes mellitus, hirsutism, hypercholesterolemia, hyperuricemia,¹⁰ acromegaly,⁹ hyperprolactinemia,²⁶ menstrual disorders,²⁷ and thyroid disorders;^9,10 as well as neuropsychiatric disorders such as depression,¹⁰ headache, cognitive impairment, behavioral disorders,^12,20,28 vestibular disorders,²⁷ schizophrenia,²⁸ and seizures.²⁹ In this regard, the patient met the necessary criteria to be considered a carrier of this syndrome, manifesting HFI with obesity, diabetes mellitus, hyperuricemia, hypertriglyceridemia, and cognitive impairment, all components reported in the literature defining it.    

The pathophysiological origin of Morgagni-Stewart-Morel syndrome is unknown, although it has been postulated that the cause may be an endocrine imbalance motivated by genetic and environmental factors.^8,29 It is thought that environmental factors, such as high caloric intake, cause obesity and hyperglycemia. This, in turn, leads to dysfunction in hormone production of adipocytes, causing an increase in leptin, which could stimulate bone overgrowth.^1,4,10 Estrogen is thought to intervene in the formation of HFI by stimulating bone growth in the frontal bone, and this alteration may be encouraged by prolonged estrogen exposure during the reproductive period, as well as consumption of phytoestrogens in the diet.^1,2 In addition, the prevalence of HFI in the frontal bone could be explained by the presence of a separate angiosome composed of numerous dome-like vascular anastomoses.¹ Finally, the presence of HFI, depending on its severity, causes the compression of underlying soft tissue (meninges, brain), causing neuropsychiatric manifestations.^1,9,10,18 With this, we can establish the interrelationship between the clinical manifestations of the patient: metabolic and endocrine disorders (obesity, diabetes mellitus type 2) brought about increased leptin production, which, along with the greater estrogen production characteristic of the female gender, led to the development of HFI, which, by its severity, caused the cognitive impairment that was found. 

Conclusion

This case meets the criteria for the diagnosis of Morgagni-Stewart-Morel syndrome, introducing a number of clinical features documented in the literature that make up the syndrome (HFI, obesity, diabetes mellitus, hyperuricemia, hypertriglyceridemia, and cognitive impairment). This syndrome is one of the least understood and reported, however, the differential diagnosis is important due to the relevance of each of the events that comprise it, because they should not be interpreted in isolation, since, as discussed in the literature so far, they seem to have a pathophysiological relationship.

References

1. Raikos A, Paraskevas GK, Yusuf F, Kordali P, Meditskou S, Al-Haj A, et al. Etiopathogenesis of hiperostosis frontal interna: A mystery still. Ann Anat. 2011;193(5):453-458.
2. Nikolic S, Djonic D, Zivkovic V, Babic D, Jukovic F, Djuric M. Rate of ocurrente, gross appearance, and age relation of hyperostosis frontalis interna in females. A prospective autopsy study. Am J Forensic Med Pathol. 2010;31(3):205-207.
3. Hajdu T, Fóthi E, Bernert Z, Molnár E, Lovász G, Kovári I, et al. Appearance of hyperostosis frontalis interna in some osteoarcheological series from Hungary. Homo. 2009;60(3):185-205.
4. Rühli FJ, Henneberg M. Are hyperostosis frontalis interna and leptin linked? A hypothetical approach about hormonal influence on human microevolution. Med Hypotheses. 2002;58(5):378-381.
5. May H, Peled N, Dar G, Hay O, Abbas J, Masharawi Y, et al. Identifying and classifying hiperostosis frontalis interna via computerized tomography. Anat Rec. 2010;293(12):2007-2011.
6. May H, Peled N, Dar G, Abbas J, Hershkovitz I. Hyperostosis frontalis interna: whats does it tell us about our health? Am J Hum Biol 2011;23(3):392-397.
7. Waclawik AJ. Hyperostosis frontalis interna. Arch Neurol. 2006;63(2):291.
8. She R, Szakacs J. Hyperostosis frontalis interna: case report and review of literature. Ann Clin Lab Sci. 2004;34(2):206-208.
9. Chaljub G, Johnson RF 3rd, Johnson RF Jr, Sitton CW. Unusual exuberant hyperostosis frontalis interna: MRI. Neuroradiology. 1999;41(1):44-45.
10. Attanasio F, Granziera S, Giantin V, Manzato E. Full penetrance of Morgagni-Stewart-Morel syndrome in a 75-year-old woman: case report and review of the literature. J Clin Endocrinol Metab. 2013;98(2): 453-457.
11. Antón SC. Endocranial hyperostosis in Sangiran 2, Gibraltar 1, and Shanidar 5. Am J Phys Anthropol. 1997;102(1):111-122.
12. Devriendt W, Piercecchi-Marti MD, Adalian P, Sanvoisin A, Dutuor O, Leonetti G. Hyperostosis frontalis interna: forensic issues. J Forensic Sci. 2005;50 (1):143-146.
13. Flohr S, Witzel C. Hyperostosis frontalis interna – A marker of social status? Evidence from the Bronce-Age “high society”of Qatna, Syria. Homo. 2011;62 (1):30-43.
14. Mulhern DM, Wilczak CA, Dudar JC. Brief communication: unusual finding at Pueblo Bonito: multiple cases of hyperostosis frontalis interna. Am J Phys Anthropol. 2006;130(4):480-484.
15. Herskovitz I, Greenwald C, Rothschild BM, Latimer B, Dutour O, Jellema LM, et al. Hyperostosis frontalis interna: an anthropological perspective. Am J Phys Anthropol 1999;103(3):303-325.
16. May H, Peled N, Dar G, Abbas J, Medlej B, Masharawi Y, et al. Hyperostosis frontalis interna and androgen suppression. Anat Rec. 2010;293(8):1333-1336.
17. Barber G, Watt I, Rogers J. A comparison of radiological and palaeopathological diagnostic criteria for hyperostosis frontalis interna. Int J Osteoarchaeol. 1997;7(2):157-164.
18. Talarico EF Jr, Prather AD, Hardt KD. A case of extensive hyperostosis frontalis interna in a 87-years-old female human cadaver. Clin Anat. 2008;21(3): 259-268.
19. De Zubicaray GI, Chalk JB, Rose SE, Semple J, Smith GA. Deficits on self ordered tasks associated with hyperostosis frontalis interna. J Neurol Neurosurg Psychiatry. 1997;63(3):309-314.
20. Paulus KS, Magnano I, Aiello I, Sechi GP, Rosati G, Casu AR, et al. P300 and executive function alterations: possible links in a case of Morgagni-Stewart-Morel syndrome. Neurol Sci. 2002;22(6):459-462.
21. Ramchandren S, Liebeskind DS. Headache in a patient with Klinefelter´s syndrome and hyperostosis frontalis interna. J Headache Pain. 2007;8(6): 342-344.
22. Brodoehl S, Klingner C, Mentzel H, Bar KJ. Transcortical motor aphasia and unilateral parkinsonism in a case of hyperostosis frontalis. Neurology. 2013; 80(16):1536-1537.
23. Kocabas H, Sezer I, Melikoglu MA, Gurbuz U, Illeez O, Ozbudak IH, et al. Hyperostosis frontalis interna in a patient with giant cell arteritis. Mod Rheumatol. 2008;18(2):181-183.
24. Sohmiya M, Tanaka M, Sotomatsu A, Aihara Y, Okamoto K. Three elderly cases of hyperostosis cranii with various clinical symptoms. Nihon Ronen Igakkai Zasshi. 2001;38(2):218-223.
25. Elliott C, Johnson E, Chow M. Hyperostosis frontalis interna requiring craniotomy for intracranial hypertension. Can J Neurol Sci. 2014;41(1):109-111.
26. Pawlikowski M, Komorowski J. Hyperostosis frontalis, galactorrhoea/hyperprolactinaemia, and Morgagni-Stewart-Morel syndrome. Lancet. 1983;1 (8322):474.
27. Nallegowda M, Singh U, Khanna M, Yadav SL, Choudhary AR, Thakar A. Morgagni Stewart Morel syndrome - Additional features. Neurol India. 2005; 53:117-119.
28. Yamakawa K, Mizutani K, Takahashi M, Matsui M, Mezaki T. Hyperostosis frontalis interna associated with hypogonadism in an elderly man. Age Ageing. 2006;35(2):202-203.
29. Koller MF, Papassotiropoulos A, Henke K, Behrends B, Noda S, Kratzer A. Evidence of a genetic basis of Morgagni-Stewart-Morel syndrome. A case report of identical twins. Neurodegener Dis. 2005;2(2)56-60.

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