The Maxillofacial Center for Diagnostics & Research

This Page: Text and Commentary on Abstracts of Maxillofacial Osteonecrosis (NICO)      

Abstracts, Etc. Pertaining to Maxillofacial Osteonecrosis/NICO

The histopathology of Neuralgia-Inducing Cavitational Osteonecrosis (NICO). Bouquot JE, Roberts AM, Person P, Christian J. West Virginia University, Morgantown, WV; New York University, New York, NY

Presented to the International Association for Dental Research in Dublin, Ireland, June, 1989.
Reference: J Dent Res 1989; 68:952.

Recent research has indicated that trigeminal neuralgia (TN) may be related to lesions external to the CNS. This concept is corroborated by the successful treatment of more than 1,800 TN patients via curettage of unusual cavitating osteomyelitis lesions of the jaws. The present investigation is the first to microscopically evaluate and characterize a large number of such lesions. Tissue samples were collected from 126 NICO lesions in the jaws of medically diagnosed TN or atypical facial neuralgia patients, processed routinely, stained with H&E, and reviewed by a pathologist. All lesions demonstrated unusual microscopic features: a densely fibrotic and avascular central core within a highly vascularized connective tissue capsule; numerous angular fragments of necrotic cancellous bone with no evidence of resorption, involucrum or neutrophils (no suppuration); a complete lack of osteoclastic activity with minimal bony remodeling; occasional (n = 3) traumatic neuromas. Various non-specific anaerobic m/o were cultured. Conclusions: NICO cavities are not typical osteomyelitis lesions - actually, salient features of acute or chronic osteomyelitis are seldom seen in NICO tissues. The generalized avascular fibrosis of NICO lesions is most likely the result of abnormal healing or repair of an initiating intraosseous inflammation (periapical pathoses, periodontitis, trauma?), possibly aggravated by an intrinsic bone factor, focal hypoxia, focal immune suppression, or abnormal macrophage function.

Osteomyelitis in 100% of 190 jawbone samples from patients with trigeminal neuralgia and atypical facial neuralgia. Bouquot J, Roberts R, Person P, Christian J. West Virginia University, Morgantown, WV; New York University, New York, NY

Presented to the American Academy of Oral Pathology, San Diego, CA, April, 1990.
Reference: Proceedings of Annual Meeting, American Academy of Oral Pathology, 1990.

Trigeminal neuralgia (TN) now appears to usually result from injury or lesions external to the CNS, most frequently adjacent to the gasserian ganglion.  A recent theory has postulated more distant peripheral nerve injuries within the maxilla and mandible for at least some TN cases, and numerous TN patients have been successfully treated via curettage of unusual, cavitating areas of chronic, nonsuppurative osteomyelitis.  the present investigation is the first to microscopically evaluate and characterize a large number of such jaw lesions.  Tissue samples were collected from 190 mandibular and maxillary lesions in medically diagnosed TN or atypical facial neuralgia patients, processed and stained routinely (H&E), and reviewed by a single pathologist with special training in bone pathology.  All samples demonstrated an avascular and unusually dense fibrosis of marrow spaces.  Also noted: angular fragments of necrotic bone with minimal attempt at resorption; a sprinkling of mature lymphocytes; a lack of histiocytes and neurtrophils; a lack of osteoblastic and osteoclastic activity; a lack of involucrum formation; a lack of normal bone marrow.  This fibrotic osteomyelitis produced irregular and occasionally hollow cavities within the bone, appears to cause degeneration (demyelination?) of adjacent peripheral nerves, is seldom tender but frequently is found in a trigger-point area, frequently yields varied and nonspecific anaerobes on culture, and is thought to be slowly progressive.  We suggest the diagnostic term Neuralgia-Inducing Cavitational Osteonecrosis (NICO) for this entity.

Jaw NICO (Neuralgia-Inducing Cavitational Osteonecrosis) in facial neuralgias. Bouquot J, Roberts A, Person P, Christian J. West Virginia University, Morgantown, WV; New York University, New York, NY

Presented to the 5th Biennial Congress of the International Association of Oral Pathologists, in
Tokyo, Japan, July, 1990.

A recent etiologic theory for trigeminal and atypical facial neuralgia (N & AFN) presumes neural damage some distance from the brain stem, i.e. low-grade chronic osteomyelitis around peripheral nerves in the jaws. The present study analyses clinical, radiographic and histologic features of 619 jawbone samples in 224 TN and AFN patients from 3 WV hospitals. All patients were examined surgically and all had NICO jaw lesions, characterized by nonresorbing fragments of necrotic bone, lymphocytes, few PMNs, very few histiocytes, and frequent cavity formation. A nonspecific mix of anaerobic bacteria were cultured. Cavities were usually located in the molar and bicuspid areas of the mandible or the molar and cuspid areas of the maxilla, and usually coincided with trigger points. Average patient age at NICO diagnosis was 49 years, but young adults were also affected. The majority of cases were in females. Duration of TN or AFN prior to NICO diagnosis ranged from several months to decades. Radiographic evidence of NICO lesions, noted in a majority of cases, included: generalized loss of trabeculae ("anemia bone") in a nonexpansile area of mild to moderate tenderness, complete radiolucency with "moth-eaten" borders, retention of lamina dura after tooth extraction, or thickened trabeculae in a radiolucent background. Many NICO cavities demonstrated little or no radiographic change.

Ischemic osteonecrosis of the jaws in 2,023 patients with facial pain. J. Bouquot, R. McMahon. The Maxillofacial Center, Morgantown West Virginia; Indiana University School of Dentistry, Indianapolis, Indiana

Presented to the American Academy of Orofacial Pain, San Diego, California; February, 1997.
Reference: J Orofacial Pain 1997; 11:180.

The paper summarizes the clinicopathologic features of 2,023 patients with chronic, "idiopathic" facial pain in whom ischemic osteonecrosis was found on biopsy of alveolar bone. This form of osteonecrosis, also called NICO (neuralgia-inducing cavitational osteonecrosis), demonstrated a 1:3 male:female ratio, a 40-60 year typical patient age, a predilection for third molar sites, and a tendency for multiple site involvement (40%). Two-thirds of patients had been diagnosed with atypical facial neuralgia, 24% with nonspecific pain, and 10% with trigeminal neuralgia. Microscopically, NICO demonstrated ischemic features such as reticular fatty degeneration, venous dilatation, multifocal loss of osteocytes, and minimal remodelling activity. Features of infarction included fat necrosis with 'oil cyst' formation, extravasation and necrosis of erythrocytes, microcracking and delamination of bone, proteinaceous and calcific marrow detritus (including NICO globules), and a minimal inflammatory cell response. Nerves in affected areas often demonstrated degenerative changes. This disease should be included in the differential diagnosis of idiopathic facial pain, especially since surgical debridement reduces or eliminates the pain in a large proportion of affected patients.

Subpontic osteonecrosis: imaging and microscopic features in 38 patients with "idiopathic" chronic pain. J. Bouquot, M. LaMarche. The Maxillofacial Center, Morgantown, WV and Lake Stevens, Washington.

Presented to the American Academy of Oral & Maxillofacial Pathology; Dallas, Texas; May, 1998.
Reference: Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998; 86:209-210.

Previous investigators have identified focal areas of alveolar tenderness, elevated mucosal temperature, radiographic abnormality, and increased radioisotope uptake ("hot spots") within the quadrant of pain in patients with chronic, idiopathic facial pain (phantom pain, atypical facial neuralgia, atypical facial pain, etc.). Local anesthesia tests have been developed to further aid in the isolation of alveolar bone involved with local inflammatory or ischemic changes in patients with idiopathic facial pain. The present retrospective investigation attempts to microscopically evaluate intramedullary bone in a certain subset of such patients, namely those with histories of endodontics, extraction and bridge placement in an area of "idiopathic" pain. Cases from 12 states were identified through tissue samples, histories and radiographs submitted to a national biopsy service. Of the 38 consecutive idiopathic facial pain patients thus identified, 32 were female. Approximately 90% of subpontic bone demonstrated either ischemic osteonecrosis (68%), chronic osteomyelitis (21%) or a combination of the two diseases (11%). More than 84% of cases had abnormal radiographic changes in subpontic bone, and 5 of 9 (56%) patients who underwent radioisotope bone scan showed hot spots in the region. Of the 14 patients who had laboratory testing for coagulation disorders, 71% were positive for thrombophilia, hypofibrinolysis, or both (normal: 4-7%). Ten pain-free patients with abnormal subpontic bone on radiographs are also discussed. The authors suggest intraosseous ischemia and low-grade inflammation as a significant explanatory mechanism for at least some cases of atypical facial pain, and also offer it as an explanation for poor healing of extraction sockets and positive radioisotope scans.

Elevated anti-myelin antibodies in patients with maxillofacial osteonecrosis (NICO). R. McMahon, J. Bouquot, P. Mahan, M. Saxen. Indiana University; Maxillofacial Center, Morgantown, West Virginia; and University of Florida.

Presented to the International Association of Oral Pathologists, Capetown, South Africa; September, 1998. Reference: J Oral Pathol Med 1998; 27:345-346.

Maxillofacial osteonecrosis (NICO), with multifocal ischemia and infarction of marrow, is associated with "idiopathic" facial pain. Trigeminal nerves are entrapped within the diseased marrow and we hypothesize that chronic exposure to damaged nerves are a source of abnormal stimulation of lymphocytic production of anti-peripheral nerve myelin (anti-PNM) antibodies, which in turn can damage additional myelin.
Objective: Our purpose was to compare levels of anti-PNM antibodies in maxillofacial osteonecrosis patients with normal controls and with patients having demyelinating diseases.
Methods & Materials: Frozen sera from 9 osteonecrosis patients with "atypical" facial pain was submitted to the Myelin Research Laboratory (University of Maryland) for component-1-fixation and transfer assay determination of levels of anti-PNM antibodies. Determinations were also performed for 22 normal controls and 96 neurology patients.
Results: 8 of the 9 osteonecrosis patients demonstrated anti-PNM antibody levels above normal; 5 were considerably above normal (>20 units/ml; normal = <0.7 units/ml). The proportion of osteonecrosis patients with elevated anti-PNM antibody levels was greater than that found in systemic demyelinating disorders.
Conclusion: Damaged nerves in osteonecrosis can be a source of stimulation of potentially damaging autoantibodies against peripheral nerve myelin. These may play a role in continued pain or the development of demyelinating diseases.

Bone marrow edema syndrome, new disease or early presentation of ischemic osteonecrosis? J. Bouquot, R. McMahon. The Maxillofacial Center for Diagnostics & Research, Morgantown, West Virginia; and the RIIB (Residual Infection In Bone) Project, Indiana University.

Presented to the International Association of Oral Pathologists, Capetown, South Africa; September, 1998.
Reference: J Oral Pathol Med 1998; 27:345-346.

A new pathologic entity, bone marrow edema syndrome (BMES), has been described in long bones. It is associated with deep bone pain, false negative radiographs, intramedullary hypertension, ischemia, infarction, and coagulopathies. The histopathology has been described as a wispy, loose fibrosis between adipocytes (reticular fatty degeneration), focal marrow hemorrhage (microinfarction), serous ooze (plasmostasis), focal fat necrosis, and dilated sinusoids. Bone remains predominantly viable.
Objective: To compare the histopathology of BMES with that of ischemic osteonecrosis of maxillofacial bones, often referred to as NICO (neuralgia-inducing cavitational osteonecrosis).
Methods & Materials: 1,000 intramedullary tissue samples from patients with facial pain, and with a diagnosis of ischemic osteonecrosis (NICO), were retrieved from the Latvala Inflammatory Bone Tissue Registry of The Maxillofacial Center. These were reviewed for established microscopic features of BMES. Bone pathology experts in the field were consulted.
Results: 75.7% of marrow samples demonstrated most of the criteria for BMES; 48.7% of those showed focal fat necrosis; 30.7% showed partially nonviable bone. The most consistent features were sinusoidal dilation and reticular fatty degeneration.
Conclusion: BMES is histopathologically identical to early or mild forms of ischemic osteonecrosis. It may not be a separate disease entity. Conversely, many osteonecrosis cases may be misdiagnosed.

Risk factors in "idiopathic" osteonecrosis of the jaws: seven of ten NICO patients have hereditary clotting disorders. McMahon R, Glueck C, Bouquot J. The Maxillofacial Center, Morgantown, West Virginia and Jewish Hospital of Cincinnati, Cincinnati, Ohio.

Presented to

NICO (neuralgia-inducing cavitational osteonecrosis) is the alveolar bone counterpart to ischemic osteonecrosis. In the hip, 73% of osteonecrosis cases have thrombophilia or hypofibrinolysis. The purpose of the present study was to determine whether or not these risk factors were also associated with NICO. Measures of fibrinolytic activity were obtained in 49 patients (42 females) with atypical facial neuralgia/pain, biopsy-proven osteonecrosis of the jaws and recurrence after NICO surgery. Results: 72% of patients had thrombophilia or hypofibrinolysis: 18 had primary thrombophilia (6=low protein C; 12=resistance to activated protein C); 8 had hypofibrinolysis (all with low levels of stimulated tissue plasminogen activator, TPA-Fx, the major stimulator of fibrinolysis; 3 also with concurrent high plasminogen activator inhibitor, PAI-Fx, the major inhibitor of fibrinolysis); 10 had high Lp(a), a major atherogenic hypofibrinolytic lipoprotein. Of the 12 patients with resistance to activated protein C, 7 had this trait alone. All tissue samples demonstrated reticular fatty degeneration (marrow fibrosis), marrow infarctions, fibrin plugs and sludging, and/or dilated marrow sinusoids, all signs of impaired marrow microcirculation. Conclusions: As with osteonecrosis of other bones, primary thrombophilia and hypofibrinolysis are common, inheritable, risk factors for "idiopathic" osteonecrosis of the jaws (NICO) and may contribute to the pain of atypical facial neuralgia as well to treatment failures in NICO surgery.

Ischemic osteonecrosis of the jaws in 2,023 patients with facial pain. J. Bouquot, R. McMahon. The Maxillofacial Center, Morgantown, West Virginia; Indiana University School of Dentistry, Indianapolis, Indiana.

Presented to the Biennial Congress of the International Association of Oral Pathology in York, England, 1996.
Reference: J Oral Pathol Med 1996; 25:271.

This paper summarizes the clinicopathologic features of 2,023 patients with chronic, "idiopathic" facial pain in whom ischemic osteonecrosis was found on biopsy of alveolar bone. This disease, also called NICO (neuralgia-inducing cavitational osteonecrosis), demonstrated a 1:3 male:female ratio, a 40-60 year typical patient age, a predilection for third molar sites, and a tendency toward multiple-site involvement (40%). Two-thirds of patients had been diagnosed with atypical facial neuralgia, 24% with nonspecific pain, and 10% with trigeminal neuralgia prior to biopsy. Microscopically, NICO demonstrated ischemic features such as reticular fatty degeneration, venous dilatation, multifocal loss of osteocytes, and minimal remodelling. Features of infarction included fat necrosis with 'oil cyst' formation, extravasation of degenerated erythrocytes, microcracking and delamination of bone, proteinaceous and calcific marrow detritus (including NICO globules), and a minimal inflammatory cell response. Nerves in affected areas sometimes demonstrated degenerative changes. This disease should be included in the differential diagnosis of idiopathic facial pain, especially since surgical debridement reduces or eliminates the pain in a large proportion of affected patients.