•
Radiographic and Pathologic Features of Spinal Involvement in Diffuse Idiopathic Skeletal Hyperostosis (DISH)
Diagnostic Radiology
Donald Resnick, M.D., and Gen Niwayama, M.D. The vertebral involvement of DISH is described from an evaluation of 215 cadaveric spines and 100 patients with the disease. Radiographic features include linear new bone formation along the anterolateral aspect of the thoracic spine, a bumpy contour, subjacent radiolucency, and irregular and pointed bony excrescences at the superior and inferior vertebral margins in the cervical and lumbar regions. Pathologic features include focal and diffuse calcification and ossification in the anterior longitudinal ligament, paraspinal connective tissue, and annulus fibrosis, degeneration in the peripheral annulus fibrosis fibers, L-, T-, and V-shaped anterolateral extensions of fibrous tissue, hypervascularity, chronic inflammatory cellularinfiltration, and periosteal new bone formation on the anterior surface of the vertebral bodies. INDEX TERMS:
• HE
EXTRASPINAL
Bones, dysostoses. Spine, diseases
Radiology 119:559-568, June 1976
manifestations
of
Forestier's
Tdisease were discussed in a previous article, and diffuse idiopathic skeletal hyperostosis (DISH)was introduced as a more appropriate description of this ossifying diathesis (16). This report describes the radiographic and pathologic features of spinal involvement in this disorder, and details the pathogenetic mechanisms and differential dagnostic considerations of bony outgrowths of the vertebral column.
histologic processing included fixing slabs 1-3 cm thick in neutral buffered formalin for one week, decalcifying in 10% formic acid, and dehydrating in ethanol. Specimens were then double-embedded with 4 % Celloidin in methyl benzoate and paraffin. Eight to 15 micron sections were cut on a type-1400 base sledge microtome and stained with haematoxylin and eosin. In addition, various stages of tissue maceration of the whole and sectioned specimens were prepared using commercial "Clorox" solution.
MATERIAL AND METHODS ANATOMY
One-hundred patients with spinal manifestations of DISH were evaluated with complete radiographic surveys of the cervical, thoracic and lumbar spine. As definite criteria had not previously been established for diagnosing this disorder, we chose certain strict radiographic features of the spine as a pre-requisite in the patients to be included in this series. These criteria were based upon our earlier investigation of the spinal pathology in certain advanced cases of DISH, and included: (a) The presence of "flowing" calcification and ossification along the anterolateral aspects of at least 4 contiguous vertebral bodies with or without associated localized pointed excrescences at the intervening vertebral body-disc junctions. (b) A relative preservation of disc height in the involved areas and the absence of extensive radiographic changes of "degenerative" disc disease, including vacuum phenomena and vertebral body marginal sclerosis. (c) Absence of apophyseal joint bony ankylosis and sacro-iliac joint erosion, sclerosis or bony fusion. The entire anterior vertebral column (first thoracic through fifth lumbar segment) was removed intact from 215 cadavers chosen at random during postmortem examinations at the VA Hospital. Coronal, transverse, and sagittal sections of the specimens were obtained on a band saw, radiographed, and photographed. In selected cases, the
The annulus fibrosis is a concentric series of fibrous lamellae that encloses the nucleus pulposus and strongly unites the vertebral bodies. (Fig. 1). While the essential function of the nucleus is to resist and redistribute compressive forces, a major function of the annulus is to withstand tension which may result from a compressed nucleus or a separation of vertebral bodies. Each vertebral body has on its superior and inferior surfaces a concave central depression and an elevated ring of compact bone representing a traction apophysis for attachment of the annulus and associated longitudinal ligaments (2). The stoutest external fibers, Sharpey's fibers, penetrate the outer bony ring. These fibers also extend beyond the confines of the disc and blend with the vertebral periosteum and anterior longitudinal ligament (ALL). The ALL extends along the ventral surface of the spine from skull to sacrum. It is narrow in the upper cervical region but expands in width as it descends and in the thoracic area covers most of the anterolateral surface of the vertebral bodies. It narrows in the lumbar region and blends into the presacral fibers (11). Its deepest fibers span only one intervertebral articulation, intermediate fibers unite 2 or 3 vertebrae, and a superficial stratum may connect 4 or 5 articular units. Where the ligament is adherent to the an-
1 From the Departments of Radiology (D.R.) and Pathology (G.N.), Veterans Administration Hospital, San Diego, and University Hospital, University of California at San Diego. Accepted for publication in February, 1976. Supported' by VAH Grant #7406. ss
559
560
DONALD RESNICK AND GEN NIWAYAMA
June 1976
CERVICAL
THOHACiC
Fig. 2. Segmental distribution of spinal abnormalities in 63 patients with radiographic evaluation of the entire spine. Figures appearing in areas of overlappingcircle indicate the number of patients with abnormalities in more than one segment of the spine.
Fig. 1. Sagittal sectional anatomy of the vertebral body-intervertebral disc junction. The annulus fibrosis (AF)of the disc surrounds the nucleus pulposus (NP). The superior and inferior surfaces of the vertebral body contain a cartilage-covered central depression (1) and elevated ring of compact bone. The latter is penetrated by peripheral fibers [Sharpey's fibers (2)] of the AF. The anterior longitudinal ligament (ALL) extends over the ventral surface of the spine. It is loosely attached to the disc and adherent to the anterior surface of the vertebral body.
terior surface of the vertebra it also forms its periosteum, but it is most firmly attached to the articular lip at the end of each body. The ALL is loosely attached to the connective tissue band that encircles the annular portion of each disc (8, 17). RESULTS
Radiographic Study-
The 100 patients ranged in age from 49 to 88 years, with an average age of 68 years (TABLE I, Figs. 2 and 3). There were 96 men and 4 women. Although we suspect a male prevalence in DISH, the large number of men in this series reflected the patient population at the VA Hospital. Thoracic Spine (Fig. 4): Radiographs of the thoracic spine, available in all 100 patients, were abnormal in 97 (97 %); it was the pattern and extent of this abnormality which established the diagnosis of DISH in these individuals. Alterations in the thoracic spine were mild to moderate in 41 patients and moderate to severe in 56. In 3 patients, the thoracic spine was normal, but isolated abnormalities in the cervical spine fulfilled the necessary criteria for diagnosis. Thoracic abnormalities were most frequent in the 9th (96 cases), 8th (94 cases), 10th (93 cases) and 7th (91 cases) vertebral bodies (Fig 3). The
lower incidence of abnormalities in the upper thoracic level is noteworthy, although we recognize the difficulty of adequately visualizing this area. Abnormal vertebral bodies were generally continuous in the thoracic spine, although in 5 patients two levels of thoracic spine involvement were separated by an area of normality. Involvement of the entire thoracic spine from the first or second vertebral body through the 12th was noted in 32 patients. The pattern of abnormality in the thoracic spine was remarkably constant. Laminated calcification and ossification appeared along the anterolateral aspects of the vertebral bodies and continued across the disc spaces. The deposited bone varied in thickness from 1 to 20 mm; when broad, it gave the appearance of a radiodense shield in front of the vertebral column. Posterior deposition of bone in the thoracic region was noted in only 6 cases. The contour of the involved spine was usually bumpy, particularly in front of the intervertebral disc. This appearance was produced by two processes: increased deposition of bone at the disc space, frequently merging with bony excrescences on the superior and inferior margins of the vertebra, and a more anterior position of the deposited bone at the level of the intervertebral disc space. Extension of disc material was suggested by radiolucencies within the ossified mass, and took the form of an L-, T-, or Yshaped defect. A smooth contour in the thoracic spine was noted in 15 out of 97 patients. In this group (pseudo-
100 60
68 PATIENTS EXAItlINEO
100 PATIENTS EXAItlINEO
90
90 80
94 PATIENTS EXAItlINEO
80 (f)(f)
~w
50
"10 70
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~~a::
"-0
oz 1Il
5-
30
z~
20
20
10
10
10
Table I: Segment Cervical Thoracic Lumbar
Distribution of Radiographic Abnormalities Number Examined
Number Abnormal
Percent Abnormal
68
53
78% 97% 93%
100
94
97 87
I 2 3 4 5 6 7 CERVICAL
2 3 4 5 6 7 8 9 10 II 12 THORACIC
I 2 3 4 5
51
LUMBOSACRAL
VERTEBRAL BODY
Fig. 3. Distribution of spinal abnormalities according to individual vertebral body level.
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DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS
spondylitic pattern of disease), linear ossification along the anterior aspect of the spine was frequently only 1-3 mm thick, and disc extensions and pointed excrescences were not readily apparent. A characteristic radiographic feature of thoracic spine involvement is the presence of a radiolucency (on lateral radiographs) between the newly deposited bone and the underlying vertebral body. Although not usually apparent at each thoracic vertebra, this radiolucency was noted at some thoracic level in 84 of 97 patients, and it frequently ended abruptly at the superior and inferior margins of the vertebral body, where horizontal struts of bone had been deposited. In some patients, an exaggerated concavity along the anterior aspect of the vertebral body produced semicircular rather than linear radiolucencies. Five of the 13 patients without this radiolucency had the pseudospondylitic pattern of disease. Thoracic disc space narrowing was apparent in 32/97 patients. It was generally mild to moderate (30/32) and within the area of hyperostosis (27/32). Bone formation was generally greatest at levels with intact disc spaces. Cervical Spine (Fig. 5): The cervical spine was examined radiographically in 68 patients, and was abnormal in 53 (78 %). Abnormalities were mild to moderate in 29 patients and moderate to severe in 24. The largest bony
Fig. 4. Thoracic spine abnormalities (2 patients). A. Anterior ossification in this spine is very irregular (arrowhead) and pointed excrescences (e) have developed. A radiolucency (Iu) beneath the deposited bone is noted, and horizontal struts of bone (s) are present at the margins of the vertebral body. Radiolucent disc extensions (d) are apparent. B. Despite anterior ossification (arrowheads), the contour of the spine is relatively smooth (pseudo-spondylitic pattern of disease). The radiolucency (Iu) beneath the deposited bone is again evident and posterior bone formation (p) can be noted. The intervertebral discs are narrowed.
561
Diagnostic Had:cJogy
excrescences measured 11-12 mm thick. Abnormalities were most common on the 6th (52 patients) and 5th (51 patients) vertebral bodies; involvement of the tst and 2nd cervical vertebrae was relatively infrequent (Fig. 3). Hyperostosis of the cortex along the anterior surface of the vertebral body occurred initially. Graduallyelongated bony excrescenses appeared at the anterior margin of the vertebra and grew across the disc space. These were most frequent at the inferior lip of the vertebral body, and extended downward. With progression of the disease the bony mass appeared either smooth and armor-like or: bumpy and irregular; this pattern was frequently associated with radiolucent disc extensions, which occasionally isolated a small triangular ossicle in front of the disc space. Radiolucency in the cervical region between the anterior new bone and vertebral body was less frequent than in the thoracic spine, although small circular radiolucencies were
Fig. 5. Cervical spine abnormalities. The anterior bony mass (large arrowhead) contains radiolucent disc extensions (d) which have isolated ossicles (0) in front of the intervertebral disc spaces. A posterior excrescence (small arrowhead) can be seen.
562
DONALD RESNICK AND GEN NIWAYAMA
occasionally seen. Mild to moderate (29 patients) or moderate to severe (6 patients) cervical disc space narrowing was also noted, as were apophyseal joint narrowing and sclerosis (20 patients) and ligamentum nuchae ossification (21 patients). Lumbar Spine (Fig. 6): Radiographs of the lumbar spine, available in 94 patients, were abnormal in 87 (93 % ). In no individual did isolated lumbar spine abnormalities meet the necessary criteria for establishing the diagnosis of DISH. Alterations were mild to moderate in 45 patients and moderate to severe in 42. The largest outgrowths were 19-20 mm. The third lumbar vertebral body (76 patients) was the most common site of abnormality (Fig. 3). As in the cervical spine hyperostosis, the anterior aspect of the vertebral body was the initial manifestation in the lumbar region. With progression, cloud-like increased density and pointed bony excrescences developed, particularly at the anterosuperior aspect of the vertebra, and extended across the disc space. Anterior disc extension
Table II:
June 1976
Length of Radiographic Bony Ankylosis
Number of Fused Vertebral Bodies
Frequency
15 12 14 10 6 8 3 7 4 14
2
3 4 5 6 7 8 9 10 >10
was again seen; occasionally a radiolucency beneath the new bone was identifiable. Smaller posterior outgrowths also were occasionally noted. Disc space narrowing in the affected lumbar regions was mild to moderate in 21 patients and moderate to severe in 9. Apophyseal joint narrowing and sclerosis, identifiable in 43 patients, was most frequent in the 4th lumbar through the 1st sacral segments. Apposition of the spinous processes associated with sclerosis was apparent in 21 patients. Miscellaneous Spinal Features: (a) Lateral asymmetry: although both sides of the vertebral column were frequently involved, a definite predilection for right-sided abnormality in the lower thoracic and upper lumbar region was demonstrable. (b) Osteoporosis: mild osteoporosis of the axial skeleton was evident in many of the patients but its degree was not incompatible with the patients' age. (c) Bony ankylosis: Bony excrescences on the vertebral column resulted in apparent "ankylosis" of adjacent vertebral bodies in 73/100 patients (histologic evidence of such ankylosis was not obtained in these patients, and the incidence of true osseous fusion is probably much lower than this figure would indicates). Segmental ankylosis was most frequent in the thoracic region (69/73 patients) and less common in the cervical (12/73) and lumbar (19/73) spine. Multiple areas of ankylosis were noted in 14 patients, and bony fusion of the lower thoracic and upper lumbar vertebrae in 14. The number of vertebral bodies incorporated into the areas of apparent ankylosis is indicated in TABLE II. (cf) Degenerative disc disease: Disc space narrowing was not infrequent within areas of hyperostosis; it was generally mild and localized and only occasionally associated with marginal sclerosis of the vertebral body, vacuum phenomena, or disc calcification. Pathologic Study
Fig. 6. Lumbar spine abnormalities. Note the anterior hyperostosis (h) of the vertebral bodies, the pointed excrescences (e) and the subjacent radiolucencies (Iu). The height of the intervertebral disc spaces is relatively maintained.
Spines in all 215 cadavers were thoroughly examined. Appropriate cases were chosen which illustrated diseases which might be confused with DISH. Twenty-five (12 %.) of the 215 cadaveric spines fulfilled our criteria for DISH; in 3, severe abnormalities of the entire thoracic and upper lumbar segments were noted. These 25 cadavers were all male, and 24 were Caucasian. The average age at death was 75 years (age range: 46-94 years), agreeing closely with the average age at death of the entire group of cadavers. Common causes of death in the 25 cadavers included pulmonary infection (8), cardiovascular disease (5)
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DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS
and neoplasm (4). Four had been diabetic. We obtained pathologic and radiographic examination of the spine in all 25 cadavers, and histologic evaluation in 17. Abnormalities in individual specimens varied in severity; when severe alterations were present in the central portion of the involved segment, mild changes were frequently noted at its periphery. A sequence and pattern of abnormality thus became apparent. Thoracic spine (Figs. 7 and 8): Shaggy ribbon-like calcification was initially noted adjacent to the anterior aspect of the vertebral body, particularly at its midportion. The calcified collections progressively thickened and extended across the disc space, and visible bony trabeculae appeared. A radiolucency was generally recognizable between the calcified and ossified "deposits and underlying vertebral body, although eventual focal bony fusion partially obliterated this lucency. Pathologically, focal calcification and ossification were noted within the ALL. Occasional islands of metaplastic cartilage within the ligament contributed to bone formation via endochondral ossification. At this early stage, the adjacent intervertebral discs appeared normal. Progressive ossification produces the appearance of a flowing, bumpy contour on sectional radiographs. Anterior extensions at the level of the intervertebral disc create radiolucent defects within the ossification. Irregular hyperostosis on the anterior surface of the vertebral body eventually merges with the overlying ossified ligament. In addition, extensive sclerosis of a large portion of the vertebral body develops coincident with the appearance of pointed excrescences at its superior and inferior margins. Pathologically, degeneration in the outer fibers of the annulus fibrosis was associated with antero-
563
Diagnostic Radiology
=
Fig. 7. Thoracic spine abnormalities. Alterations in the ALL (A anterior). A. and B. A radiograph and photograph of a sagittal section of a thoracic spine reveal ribbon-like calcification adjacent to the anterior aspect of the vertebral body within the ALL (arrowheads). C. More extensive ossification of the ALL (arrowheads) is noted on a radiograph of a sagittal section of the spine. Additional findings include apparent concavity (c) on the anterior surface of the vertebral body, T-shaped disc extensions (d), and horizontal struts of new bone (s). Note the integrity of the intervertebral disc spaces.
lateral extension of the fibrous tissue. These disc extensions create an "umbrella" effect as they grow in and around the fibers of the ALL, which appeared stretched
Fig. 8. Thoracic spine abnormalities. Hyperostosis of the anterior surface of the vertebral bodies (A = anterior). A. and B. On a radiograph and photograph of a sagittal section of a spine, cortical hyperostosis (h), underlying bony sclerosis (sci), and pointed excrescences (e) have developed. C, and D. A radiograph and photograph of a sagittal section of a spine with advanced hyperostosis reveal sclerosis (scI) of a large portion of the vertebral body resulting from periosteal new bone formation, and anterior disc extensions (d). Portions of the ALL are ossified, and degeneration of the peripheral fibers of the annulus fibrosis can be noted.
564
June 1976
DONALD RESNICK AND GEN NIWAYAMA
over the protruding fibrous tissue. Ossification develops within the blended fibers of the annulus and the ALL. We also noted hypervascularity and an occasional mild chronic inflammatory cellular infiltrate surrounding the ALL adjacent to the degenerating annulus. Periosteal new bone formation on the anterior aspect of the vertebral body was continuous with irregular osteophyte formation near the attachment of the ALL to the vertebral body. Eventually, regional ossification involved the ALL, paravertebral connective tissue, and annulus fibrosis. Lumbar Spine: The earliest abnormalities in the lumbar region consisted of hyperostosis and sclerosis of the anterior aspect of the vertebral body. Small pointed bony excrescences developed at the superior and inferior margins of the vertebra and grew across the intervertebral disc space. The changes on pathologic examination were similar to those in the thoracic spine, with degeneration in the peripheral portion of the annulus, fibrous expansions, and periosteal sclerosis and osteophyte formation, although ALL calcification and ossification were absent or mild. Late Changes (Fig. 9): With severe involvement, a bizarre appearance of the entire spine became evident. Flange-shaped and armor-like deposits covered the right anterolateral surface of the spine in the thoracic region and
Late changes in the thoracic and lumbar spine (A On a radiograph and photograph of a transverse section of a thoracic spine with advanced hyperostosis, the basis of the characteristic radiolucency (Iu) beneath the deposited bone (arrowhead) becomes apparent. A space exists between the ossified ligament (curved arrow) and subjacent vertebral body (open arrow) which is obliterated on the right side of the specimen by focal bony ankylosis (straight arrow).
the lateral and anterior surfaces in the lumbar region. The left lateral edge of the deposited bone was frequently sharply demarcated. Bony ankylosis was noted in the thoracic spine, although close external inspection revealed that the outgrowths commonly interdigitated, and their undulating and irregular surfaces were separated by thin fibrous extensions from the annulus fibrosis. This was confirmed on sagittal sections by alternate layers of bone and ligamentous and fibrous tissue. True bony ankylosis was infrequent in the lumbar spine. DISCUSSION
DISH has been previously noted in the literature under a variety of names. Spondylitis ossificans ligamentosa was described by Oppenheimer (12) in a study of 282 persons with calcification or ossification of vertebral ligaments. Of this group, ligamentous changes in the absence of lesions of the vertebral bodies, intervertebral discs and apophyseal joints developed in 18 patients. Patients in this subgroup were generally over the age of 55 years and asymptomatic; involvement was most frequent in the thoracic spine. The ALL appeared attached to the vertebral bodies and its length appeared to be increased. Oppenheimer indicated that ligament ossification required two pre-existing components: disuse related to vertebral immobility, and rarefaction of the adjacent bone. His observations and those of Leriche and Policard (10) suggested that immobilization increased the chance of transformation of dedifferentiated connective tissue into bone, and that the lime salts de-
Fig. 9.
= anterior, R = right). A. and B.
=
Fig. 10. Ankylosing spondylitis (A anterior). A. and B. A radiograph and photograph of a sagittal section of a macerated thoracic spine from a cadaver with ankylosing spondylitis reveal thin vertical syndesmophytes (arrowheads) extending between adjacent vertebral bodies. The bone is osteoporotic and the intervertebral discs, biconvex.
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DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS
posited in the new bone originated from the adjacent rarefied vertebral body. Ligamentous ossification was therefore not the cause but the effect of decreased mobility. Ott (15) introduced the term spondylosis hyperostotica in a clinical and radiographic evaluation of 11 men and 4 women with ligamentous ossification, and stressed the mild evolution of the disease. He regarded the changes as severe spondylosis deformans. Smith et al. (19) described physiologic vertebralligamentous calcification in 53 patients, 32 of whom had pain and stiffness of the spine. The patients were generally over the age of 60 years, and abnormalities were most frequent in the thoracic region. Osteoporosis was almost uniformly absent, and mild degenerative changes of the sacroiliac joints were occasionally visible on the radiographs. The ossified ALL ranged from 5 to 10 mm in thickness and appeared "flabby," particularly at the level of the intervertebral disc (as if it were too long for the underlying spine). Coexisting osteophytes were noted. These investigators stated that trauma was not an important etiologic agent, and that an initial decrease in spinal mobility in older patients lessened the degree of mechanical stress on the ligaments, resulting in their degeneration, calcification, and ossification. The clinical and radiographic findings of this disorder were further elucidated by .Sutro et al. (21), who utilized the descriptive title generalized juxta-articular ossification of ligaments of the vertebral column. Their patients were usually asymptomatic and without restricted motion. No specific etiology was recognized. Forestier et al. (7) described senile ankylosing hyperostosis of the spine. The first adjective was eventually omitted as younger patients were discovered to have the same disorder. In an evaluation of 245 patients, 65 % of whom were men, Forestier and Lagier (6) commented upon the characteristic involvement of the anterior and right lateral aspect of the thoracolumbar region of the spine. They found that the radiographic features in this segment included undulating laminated ossification. In the cervical and lumbar regions, cortical hyperostosis of the anterior surface of the vertebral body, a cloud-like shadow in front of the disc, and irregular and thick spur formation were sequential radiographic observations. Utilizing pathologic specimens, these investigators outlined ossification which encompassed the ALL, paravertebral connective tissue, and peripheral portion of the disc. An association between hyperostosis of the spine and similar outgrowths in extraspinal locations was noted, a relationship which has been further delineated in more recent publications (9, 16, 21). Vernon-Roberts et al. (22) investigated the pathologic changes in the vertebral column in this syndrome based upon an autopsy study of 500 cadavers. They reported an incidence of ankylosing hyperostosis in 6 % , and described the thoracic spinal manifestations in 20 specimens. Their findings included syndesmophytosis of varying severity (100 %), lateral extensions of fibrous tissue arising from
565
Diagnostic Radiology
the annulus fibrosis (100 %), bony accretion on the surfaces of the vertebral body (100%), bony ankylosis (40 % ), ossification in the ALL (15 %), and marked narrowing of the intervertebral disc spaces (10%). In addition, a high incidence of osteoporosis (100%) and Schmorl's nodes (85 %) was noted. They conjectured that the initial alteration in the disorder was a predominantly right-sided anterolateral extension of fibrous tissue from the intervertebral disc which evoked periosteal new bone formation. Our radiographic and pathologic investigation of cadaveric spines agrees in part with these previous reports. In the thoracic spine, ALL calcification and ossification were early abnormalities associated with chondroid metaplasia and endochondral ossification. In addition, peripheral tears of the annulus fibrosis, anterolateral extensions of fibrous tissue arising from the intervertebral disc, hypervascularity, and chronic inflammatory cells were apparent. Periosteal bony accretion was a conspicuous manifestation associated with irregular bony excrescences on the margins of the vertebral body. In comparison with a previous study (22), our cadavers did not demonstrate striking osteoporosis or Schmorl's nodes. In the lumbar spine ligament, calcification and ossification were much less frequent, although other abnormalities were similar to those in the thoracic region. The evolving radiographic picture of DISH, particularly in the thoracic spine, included several distinctive findings: (a) A flowing pattern of new bone along the anterolateral aspect of the spine associated with a bumpy contour, particularly at the level of the intervertebral disc; (b) A linear or semicircular radiolucency between the vertebral body and overlying laminated bone; (c) L-, T-, or Y-shaped radiolucent defects within the ossified mass at the level of the disc space.
Differential Diagnosis Ankylosing Spondylitis (Fig. 10): The clinical, radiographic and pathologic features of ankylosing spondylitis (AS) differ from those of DISH. AS predominantly affects young adults and causes considerable signs and symptoms; DISH affects middle-aged and elderly patients and may be asymptomatic or associated with mild to moderate restriction of motion. The syndesmophytes which characterize AS are slender, vertically oriented bony bridges which connect adjacent vertebral bodies, and represent ossification within the peripheral portion of the annulus fibrosis (4, 5). Chondroid metaplasia and ossification may eventually involve large portions of the annulusand nucleus pulposus, but ossification of the ALL and the adjacent connective tissue, (noted in DISH) is not apparent. The exuberant flowing excrescences and vertebral body hyperostosis of DISH are easily distinguished from the syndesmophytosis and vertebral body osteitis of AS. In addition, bony ankylosis of the apophyseal and sacroiliac joints, characteristic of AS, is not seen in DISH. "Degenerative" Disc Disease (Fig. 11): Degenerative disc disease, osteoarthrosis of the anterior synarthroses of the spine (20), and intervertebral chondrosis (18) are
566
DONALD RESNICK AND GEN NIWAYAMA
June 1976
=
Fig. 11. Intervertebral chondrosis and osteochondrosis (R = right, L left). A. and B. Advanced intervertebral (osteo-) chondrosis. Note, on this radiograph and photograph of a coronal section from a cadaveric spine, the presence of vacuum phenomena (v), intervertebral disc space narrowing (n), vertebral body sclerosis (sci), and osteophyte formation (arrowheads). Extensive degeneration of the nucleus pulposus and annulus fibrosis has occurred.
terms applied to alterations of the intervertebral discs related to the physiologic and pathologic dehydration which occurs with advancing age. Histologically, these changes affect predominantly the nucleus pulposus, resulting in a desiccated and friable surface which may become discolored. Cleft formation may extend into the annulus fibrosis. Radiographically, one notes vacuum phenomena within the disc and disc space narrowing. Abnormalities in the adjacent vertebral body [intervertebral osteochondrosis (18)] represent a more severe stage of the disease, and consist of sclerosis beneath the cartilage end-plates, intravertebral body protrusion of disc material (Schmorl's nodes), and small osteophytes at the bone margins. These changes differ considerably from the ligament ossification, extensive bony excrescences, and relatively intact disc spaces characteristic of DISH.
Spondylosis Deformans (Fig. 12): This common disorder results in spinal osteophytosis (3). Although opinions on the pathogenesis of these outgrowths vary, most investigators implicate increased mobility of the adjacent segment of the spine, resulting in stress on the fibers which attach the ALL to the vertebral body (1, 13, 14). The new bone may extend into the triangular space devoid of ligaments which exists between the vertebral edge and the site of attachment of the ALL (4, 12), or invade any of the overlying soft tissues (11). Schmorl (18) demonstrated tears in the peripheral portion (Sharpey's fibers) of the annulus fibrosus which he felt were an initial manifestation of spondylosis deformans. With further separation in these fibers, the disc was no longer anchored to the vertebral body and, particularly in the presence of a nucleus pulposus without degeneration
Fig. 12. Spondylosis deformans (A = anterior). A.-C. Sagittal sections of the spine illustrating sequential abnormalities of spondylosls deformans. Initially, degeneration of the peripheral portion of the annulus fibrosis (straight arrows) and prolapse of fibrous tissue (curved arrows) occur. The ALL is stretched over the protruding intervertebral disc (open arrow). Osteophyte formation occurs at its anterior attachment to the vertebral body (arrowheads), which may eventually produce vertebral body ankylosis.
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DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS
Vol. 119
Table III:
Diagnostic Radiology
Differential Diagnosis of Radiographic Findings Disease
Site Vertebral bodies
Intervertebral discs
Apophyseal joints Sacroiliac joints Peripheral skeleton
Dish
Ankylosing Spondylitis
"Flowing" ossification and hyperostosis; large osteophytes; bony ankylosis frequent radiographically, less frequent pathologically Normal or mild decrease in height
Thin syndesmophytes; osteitis with "squaring"; extensive bony ankylosis radiographically and pathologically Normal or convex in shape
Normal or mild sclerosis; occasional osteophytes Para-articu lar osteophytes
Erosions, sclerosis and bony ankylosis Erosions, sclerosis and bony ankylosis "whiskerin g", arthritis
"whiskering", para-articular osteophytes; ligament calcification and ossification, hyperotosis
and with all its turgor, prolapse of a portion of the annulus occurred. With further protrusion, the ALL was stretched, and osteophytes developed at its attachment to the anterior surface of the vertebral body. Our observations of pathologic alterations in DISH include findings consistent with spondylosis deformans. Cleft like defects in the annulus fibrosus, prolapse of disc material, and pointed bony excrescences at the vertebral attachment of the ALL were apparent. In the lumbar spine, the resulting outgrowths were larger and more irregular than those usually noted in spondylosis deformans; in the thoracic spine, ligamentous ossification was a significant feature. Apparently DISH differs quantitatively and qualitatively from typical spondylosis, and represents regional ossification encompassing ligaments, paraspinal connective tissue and annulus fibrosus, and periosteal new bone formation on the anterior surface of the vertebra.
DISH-A Disease Entity? The radiographic and pathologic features of DISH differ considerably from those of AS and intervertebral osteochondrosis (TABLE III), most resembling severe spondylosis deformans, but demonstrating radiographic and pathologic differences. In a patient with extensive spinal manifestations the radiographic findings are distinctive, but when only minor or localized alterations are apparent it is difficult to separate cases of DISH from those of spondylosis deformans. Utilizing diagnostic criteria selected to exclude most cases of typical spondylosis, we found spinal manifestations of DISH in 12 % of our routine autopsies. DISH may not represent a disease per se but rather a vulnerable state in which extensive ossification results from an exaggerated response of the body in some patients to stimuli which produce only modest new bone formation in others. As such, it is a common ossifying diathesis in middle-aged and elderly patients. Evidence that these patients are "bone formers" includes their high incidence of associated extraspinal hyperostoses at the sites of ligament and tendon attachment. In addition, we have recently noted extensive local heterotopic ossification in the
Intervertebral Osteochondrosis Sclerosis of superior and inferior surfaces
Moderate to serve decrease in height "vacuum" phenomena Normal Normal Normal
early postoperative period following total hip arthroplasty in 2 of our patients. Hypotheses suggesting that DISH may be related to other diseases including acromegaly, hypoparathyroidism, hypervitaminosis A, and fluorosis have not been substantiated; it therefore remains a condition of unknown etiology at present. ACKNOWLEDGMENTS: The authors gratefully acknowledge the assistance of Clark Neal and Bonnie Walker in procuring the specimens; Peggy Mackey and Mary Gonsalves for preparing the histologic sections; Carol Barrier, RT, for technical aid; Sue Brown, Janet Julien and Paula Nicholas for the drawings and photography; and Janet Zatlokowicz for secretartal help.
REFERENCES 1. Beadle OA: The intervertebral discs. Medical Research Council Special Report Series No 161, London, 1931 2. Bick EM: The osteohistology of the normal human vertebra; its relation to scoliosis and certain lesions incident to growth and senescence. J Mt Sinai Hosp 19:490-527, Sep-Oct 1952 3. Bick EM: Vertebral osteophytosis. Pathologic basis of its roentgenology. Am J Roentgenol 73:979-983, Jun 1955 4. Collins DH: The Pathology of Articular and Spinal Diseases. Baltimore, Williams and Wilkins, 1950, pp 305-313 5. Cruickshank B: Pathology of ankylosinq spondylitis. Bull Rheum Dis 10:211-215, 1960 6. Forestier J, Lagier R: Ankylosing hyperostosis of the spine. Clin Orthop 74:65-83, Jan 1971 7. Forestier J, Rotes Querol J: Senile ankylosing hyperostosis of the spine. Ann Rheum Dis 9:321-330, Dec 1950 8. Francois RJ, Dhem A: Microradiographic study of the normal human vertebral body. Acta Anat 89:251-265, 1974 9. Harris J, Carter AR, Glick EN, et al: Ankylosing hyperostosis. I. Clinical and radiological features. Ann Rheum Dis 33:210-215, May
1974 10.
Leriche R, Policard A: Les problemas de la physiologie normale et pathologique de I'os. Paris, Masson & Cie, 1926 11. Nathan H: Osteophytes of the vertebral column. An anatomical study of their development according to age, race, and sex with considerations as to their etiology and significance. J Bone Joint Surg 44A:243-268, Mar 1962 12. Oppenheimer A: Calcification and ossification of vertebral ligaments (spondylitis ossificans ligamentosa): roentgen study of pathogenesis and clinical significance. Radiology 38: 160-173, Feb
1942 13.
Oppenheimer A: Diseases of the apophyseal (intervertebral) articulations. J Bone Joint Surg 20:285-313, Apr 1938 14. Oppenheimer A: The apophyseal intervertebral articulations, roentgenologically considered. Radiology 30:724-740, Jun 1938
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15. Ott VR: Uber die Spondylosis hyperostotica. Schweiz Med Wochenschr 83:790-799,22 Aug 1953 16. Resnick D, Shaul SR, Robins JM: Diffuse idiopathic skeletal hyperostosis(DISH): Forestier's diseasewith extraspinalmanifestations. Radiology 115:513-524, Jun 1975 17. RothmanRH,Simeone FA: The Spine. Philadelphia, Saunders, 1975 18. Schmorl G, Junghanns H: The Human Spine in Health and Disease, ed by EF Besemann. New York and London, Grune & Stratton, 2d ed, 1971, pp 141-151,186-198,354-357 19. Smith CF, Pugh DG, Polley HF: Physiologic vertebral ligamentous calcification: An aging process. Am J Roentgenol 74: 1049-1058, Dec 1955 20. Sokoloff L: Pathology and pathogenesis of osteoarthritis. Degenerative disease of the spinal column. [In] Hollander JL, ed: Ar-
June 1976
thritis and Allied Conditions. Philadelphia, Lea & Febiger, 1966, pp 855-857 21. Sutro CJ, Ehrlich DE, Witten M: Generalized juxta-articular ossification of ligamentsof the vertebral column and of the ligamentous and tendinous tissues of the extremities (also known as Bechterew's disease, osteophytosis and spondylosis deformans). Bul! Hosp Joint Dis 17:343-357, Oct 1956 22. Vernon-Roberts B, Pirie CJ, Trenwith V: Pathology of the dorsal spine in ankylosing hyperostosis. Ann Rheum Dis 33:281-288, 1974 Department of Radiology Veterans Administration Hospital 3350 La Jolla Village Drive San Diego, Calif. 92161
Radiographic and Pathologic Features of Spinal Involvement in Diffuse Idiopathic Skeletal Hyperostosis (DISH)
Diagnostic Radiology
Donald Resnick, M.D., and Gen Niwayama, M.D. The vertebral involvement of DISH is described from an evaluation of 215 cadaveric spines and 100 patients with the disease. Radiographic features include linear new bone formation along the anterolateral aspect of the thoracic spine, a bumpy contour, subjacent radiolucency, and irregular and pointed bony excrescences at the superior and inferior vertebral margins in the cervical and lumbar regions. Pathologic features include focal and diffuse calcification and ossification in the anterior longitudinal ligament, paraspinal connective tissue, and annulus fibrosis, degeneration in the peripheral annulus fibrosis fibers, L-, T-, and V-shaped anterolateral extensions of fibrous tissue, hypervascularity, chronic inflammatory cellularinfiltration, and periosteal new bone formation on the anterior surface of the vertebral bodies. INDEX TERMS:
• HE
EXTRASPINAL
Bones, dysostoses. Spine, diseases
Radiology 119:559-568, June 1976
manifestations
of
Forestier's
Tdisease were discussed in a previous article, and diffuse idiopathic skeletal hyperostosis (DISH)was introduced as a more appropriate description of this ossifying diathesis (16). This report describes the radiographic and pathologic features of spinal involvement in this disorder, and details the pathogenetic mechanisms and differential dagnostic considerations of bony outgrowths of the vertebral column.
histologic processing included fixing slabs 1-3 cm thick in neutral buffered formalin for one week, decalcifying in 10% formic acid, and dehydrating in ethanol. Specimens were then double-embedded with 4 % Celloidin in methyl benzoate and paraffin. Eight to 15 micron sections were cut on a type-1400 base sledge microtome and stained with haematoxylin and eosin. In addition, various stages of tissue maceration of the whole and sectioned specimens were prepared using commercial "Clorox" solution.
MATERIAL AND METHODS ANATOMY
One-hundred patients with spinal manifestations of DISH were evaluated with complete radiographic surveys of the cervical, thoracic and lumbar spine. As definite criteria had not previously been established for diagnosing this disorder, we chose certain strict radiographic features of the spine as a pre-requisite in the patients to be included in this series. These criteria were based upon our earlier investigation of the spinal pathology in certain advanced cases of DISH, and included: (a) The presence of "flowing" calcification and ossification along the anterolateral aspects of at least 4 contiguous vertebral bodies with or without associated localized pointed excrescences at the intervening vertebral body-disc junctions. (b) A relative preservation of disc height in the involved areas and the absence of extensive radiographic changes of "degenerative" disc disease, including vacuum phenomena and vertebral body marginal sclerosis. (c) Absence of apophyseal joint bony ankylosis and sacro-iliac joint erosion, sclerosis or bony fusion. The entire anterior vertebral column (first thoracic through fifth lumbar segment) was removed intact from 215 cadavers chosen at random during postmortem examinations at the VA Hospital. Coronal, transverse, and sagittal sections of the specimens were obtained on a band saw, radiographed, and photographed. In selected cases, the
The annulus fibrosis is a concentric series of fibrous lamellae that encloses the nucleus pulposus and strongly unites the vertebral bodies. (Fig. 1). While the essential function of the nucleus is to resist and redistribute compressive forces, a major function of the annulus is to withstand tension which may result from a compressed nucleus or a separation of vertebral bodies. Each vertebral body has on its superior and inferior surfaces a concave central depression and an elevated ring of compact bone representing a traction apophysis for attachment of the annulus and associated longitudinal ligaments (2). The stoutest external fibers, Sharpey's fibers, penetrate the outer bony ring. These fibers also extend beyond the confines of the disc and blend with the vertebral periosteum and anterior longitudinal ligament (ALL). The ALL extends along the ventral surface of the spine from skull to sacrum. It is narrow in the upper cervical region but expands in width as it descends and in the thoracic area covers most of the anterolateral surface of the vertebral bodies. It narrows in the lumbar region and blends into the presacral fibers (11). Its deepest fibers span only one intervertebral articulation, intermediate fibers unite 2 or 3 vertebrae, and a superficial stratum may connect 4 or 5 articular units. Where the ligament is adherent to the an-
1 From the Departments of Radiology (D.R.) and Pathology (G.N.), Veterans Administration Hospital, San Diego, and University Hospital, University of California at San Diego. Accepted for publication in February, 1976. Supported' by VAH Grant #7406. ss
559
560
DONALD RESNICK AND GEN NIWAYAMA
June 1976
CERVICAL
THOHACiC
Fig. 2. Segmental distribution of spinal abnormalities in 63 patients with radiographic evaluation of the entire spine. Figures appearing in areas of overlappingcircle indicate the number of patients with abnormalities in more than one segment of the spine.
Fig. 1. Sagittal sectional anatomy of the vertebral body-intervertebral disc junction. The annulus fibrosis (AF)of the disc surrounds the nucleus pulposus (NP). The superior and inferior surfaces of the vertebral body contain a cartilage-covered central depression (1) and elevated ring of compact bone. The latter is penetrated by peripheral fibers [Sharpey's fibers (2)] of the AF. The anterior longitudinal ligament (ALL) extends over the ventral surface of the spine. It is loosely attached to the disc and adherent to the anterior surface of the vertebral body.
terior surface of the vertebra it also forms its periosteum, but it is most firmly attached to the articular lip at the end of each body. The ALL is loosely attached to the connective tissue band that encircles the annular portion of each disc (8, 17). RESULTS
Radiographic Study-
The 100 patients ranged in age from 49 to 88 years, with an average age of 68 years (TABLE I, Figs. 2 and 3). There were 96 men and 4 women. Although we suspect a male prevalence in DISH, the large number of men in this series reflected the patient population at the VA Hospital. Thoracic Spine (Fig. 4): Radiographs of the thoracic spine, available in all 100 patients, were abnormal in 97 (97 %); it was the pattern and extent of this abnormality which established the diagnosis of DISH in these individuals. Alterations in the thoracic spine were mild to moderate in 41 patients and moderate to severe in 56. In 3 patients, the thoracic spine was normal, but isolated abnormalities in the cervical spine fulfilled the necessary criteria for diagnosis. Thoracic abnormalities were most frequent in the 9th (96 cases), 8th (94 cases), 10th (93 cases) and 7th (91 cases) vertebral bodies (Fig 3). The
lower incidence of abnormalities in the upper thoracic level is noteworthy, although we recognize the difficulty of adequately visualizing this area. Abnormal vertebral bodies were generally continuous in the thoracic spine, although in 5 patients two levels of thoracic spine involvement were separated by an area of normality. Involvement of the entire thoracic spine from the first or second vertebral body through the 12th was noted in 32 patients. The pattern of abnormality in the thoracic spine was remarkably constant. Laminated calcification and ossification appeared along the anterolateral aspects of the vertebral bodies and continued across the disc spaces. The deposited bone varied in thickness from 1 to 20 mm; when broad, it gave the appearance of a radiodense shield in front of the vertebral column. Posterior deposition of bone in the thoracic region was noted in only 6 cases. The contour of the involved spine was usually bumpy, particularly in front of the intervertebral disc. This appearance was produced by two processes: increased deposition of bone at the disc space, frequently merging with bony excrescences on the superior and inferior margins of the vertebra, and a more anterior position of the deposited bone at the level of the intervertebral disc space. Extension of disc material was suggested by radiolucencies within the ossified mass, and took the form of an L-, T-, or Yshaped defect. A smooth contour in the thoracic spine was noted in 15 out of 97 patients. In this group (pseudo-
100 60
68 PATIENTS EXAItlINEO
100 PATIENTS EXAItlINEO
90
90 80
94 PATIENTS EXAItlINEO
80 (f)(f)
~w
50
"10 70
~E: -....J
~~a::
"-0
oz 1Il
5-
30
z~
20
20
10
10
10
Table I: Segment Cervical Thoracic Lumbar
Distribution of Radiographic Abnormalities Number Examined
Number Abnormal
Percent Abnormal
68
53
78% 97% 93%
100
94
97 87
I 2 3 4 5 6 7 CERVICAL
2 3 4 5 6 7 8 9 10 II 12 THORACIC
I 2 3 4 5
51
LUMBOSACRAL
VERTEBRAL BODY
Fig. 3. Distribution of spinal abnormalities according to individual vertebral body level.
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DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS
spondylitic pattern of disease), linear ossification along the anterior aspect of the spine was frequently only 1-3 mm thick, and disc extensions and pointed excrescences were not readily apparent. A characteristic radiographic feature of thoracic spine involvement is the presence of a radiolucency (on lateral radiographs) between the newly deposited bone and the underlying vertebral body. Although not usually apparent at each thoracic vertebra, this radiolucency was noted at some thoracic level in 84 of 97 patients, and it frequently ended abruptly at the superior and inferior margins of the vertebral body, where horizontal struts of bone had been deposited. In some patients, an exaggerated concavity along the anterior aspect of the vertebral body produced semicircular rather than linear radiolucencies. Five of the 13 patients without this radiolucency had the pseudospondylitic pattern of disease. Thoracic disc space narrowing was apparent in 32/97 patients. It was generally mild to moderate (30/32) and within the area of hyperostosis (27/32). Bone formation was generally greatest at levels with intact disc spaces. Cervical Spine (Fig. 5): The cervical spine was examined radiographically in 68 patients, and was abnormal in 53 (78 %). Abnormalities were mild to moderate in 29 patients and moderate to severe in 24. The largest bony
Fig. 4. Thoracic spine abnormalities (2 patients). A. Anterior ossification in this spine is very irregular (arrowhead) and pointed excrescences (e) have developed. A radiolucency (Iu) beneath the deposited bone is noted, and horizontal struts of bone (s) are present at the margins of the vertebral body. Radiolucent disc extensions (d) are apparent. B. Despite anterior ossification (arrowheads), the contour of the spine is relatively smooth (pseudo-spondylitic pattern of disease). The radiolucency (Iu) beneath the deposited bone is again evident and posterior bone formation (p) can be noted. The intervertebral discs are narrowed.
561
Diagnostic Had:cJogy
excrescences measured 11-12 mm thick. Abnormalities were most common on the 6th (52 patients) and 5th (51 patients) vertebral bodies; involvement of the tst and 2nd cervical vertebrae was relatively infrequent (Fig. 3). Hyperostosis of the cortex along the anterior surface of the vertebral body occurred initially. Graduallyelongated bony excrescenses appeared at the anterior margin of the vertebra and grew across the disc space. These were most frequent at the inferior lip of the vertebral body, and extended downward. With progression of the disease the bony mass appeared either smooth and armor-like or: bumpy and irregular; this pattern was frequently associated with radiolucent disc extensions, which occasionally isolated a small triangular ossicle in front of the disc space. Radiolucency in the cervical region between the anterior new bone and vertebral body was less frequent than in the thoracic spine, although small circular radiolucencies were
Fig. 5. Cervical spine abnormalities. The anterior bony mass (large arrowhead) contains radiolucent disc extensions (d) which have isolated ossicles (0) in front of the intervertebral disc spaces. A posterior excrescence (small arrowhead) can be seen.
562
DONALD RESNICK AND GEN NIWAYAMA
occasionally seen. Mild to moderate (29 patients) or moderate to severe (6 patients) cervical disc space narrowing was also noted, as were apophyseal joint narrowing and sclerosis (20 patients) and ligamentum nuchae ossification (21 patients). Lumbar Spine (Fig. 6): Radiographs of the lumbar spine, available in 94 patients, were abnormal in 87 (93 % ). In no individual did isolated lumbar spine abnormalities meet the necessary criteria for establishing the diagnosis of DISH. Alterations were mild to moderate in 45 patients and moderate to severe in 42. The largest outgrowths were 19-20 mm. The third lumbar vertebral body (76 patients) was the most common site of abnormality (Fig. 3). As in the cervical spine hyperostosis, the anterior aspect of the vertebral body was the initial manifestation in the lumbar region. With progression, cloud-like increased density and pointed bony excrescences developed, particularly at the anterosuperior aspect of the vertebra, and extended across the disc space. Anterior disc extension
Table II:
June 1976
Length of Radiographic Bony Ankylosis
Number of Fused Vertebral Bodies
Frequency
15 12 14 10 6 8 3 7 4 14
2
3 4 5 6 7 8 9 10 >10
was again seen; occasionally a radiolucency beneath the new bone was identifiable. Smaller posterior outgrowths also were occasionally noted. Disc space narrowing in the affected lumbar regions was mild to moderate in 21 patients and moderate to severe in 9. Apophyseal joint narrowing and sclerosis, identifiable in 43 patients, was most frequent in the 4th lumbar through the 1st sacral segments. Apposition of the spinous processes associated with sclerosis was apparent in 21 patients. Miscellaneous Spinal Features: (a) Lateral asymmetry: although both sides of the vertebral column were frequently involved, a definite predilection for right-sided abnormality in the lower thoracic and upper lumbar region was demonstrable. (b) Osteoporosis: mild osteoporosis of the axial skeleton was evident in many of the patients but its degree was not incompatible with the patients' age. (c) Bony ankylosis: Bony excrescences on the vertebral column resulted in apparent "ankylosis" of adjacent vertebral bodies in 73/100 patients (histologic evidence of such ankylosis was not obtained in these patients, and the incidence of true osseous fusion is probably much lower than this figure would indicates). Segmental ankylosis was most frequent in the thoracic region (69/73 patients) and less common in the cervical (12/73) and lumbar (19/73) spine. Multiple areas of ankylosis were noted in 14 patients, and bony fusion of the lower thoracic and upper lumbar vertebrae in 14. The number of vertebral bodies incorporated into the areas of apparent ankylosis is indicated in TABLE II. (cf) Degenerative disc disease: Disc space narrowing was not infrequent within areas of hyperostosis; it was generally mild and localized and only occasionally associated with marginal sclerosis of the vertebral body, vacuum phenomena, or disc calcification. Pathologic Study
Fig. 6. Lumbar spine abnormalities. Note the anterior hyperostosis (h) of the vertebral bodies, the pointed excrescences (e) and the subjacent radiolucencies (Iu). The height of the intervertebral disc spaces is relatively maintained.
Spines in all 215 cadavers were thoroughly examined. Appropriate cases were chosen which illustrated diseases which might be confused with DISH. Twenty-five (12 %.) of the 215 cadaveric spines fulfilled our criteria for DISH; in 3, severe abnormalities of the entire thoracic and upper lumbar segments were noted. These 25 cadavers were all male, and 24 were Caucasian. The average age at death was 75 years (age range: 46-94 years), agreeing closely with the average age at death of the entire group of cadavers. Common causes of death in the 25 cadavers included pulmonary infection (8), cardiovascular disease (5)
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DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS
and neoplasm (4). Four had been diabetic. We obtained pathologic and radiographic examination of the spine in all 25 cadavers, and histologic evaluation in 17. Abnormalities in individual specimens varied in severity; when severe alterations were present in the central portion of the involved segment, mild changes were frequently noted at its periphery. A sequence and pattern of abnormality thus became apparent. Thoracic spine (Figs. 7 and 8): Shaggy ribbon-like calcification was initially noted adjacent to the anterior aspect of the vertebral body, particularly at its midportion. The calcified collections progressively thickened and extended across the disc space, and visible bony trabeculae appeared. A radiolucency was generally recognizable between the calcified and ossified "deposits and underlying vertebral body, although eventual focal bony fusion partially obliterated this lucency. Pathologically, focal calcification and ossification were noted within the ALL. Occasional islands of metaplastic cartilage within the ligament contributed to bone formation via endochondral ossification. At this early stage, the adjacent intervertebral discs appeared normal. Progressive ossification produces the appearance of a flowing, bumpy contour on sectional radiographs. Anterior extensions at the level of the intervertebral disc create radiolucent defects within the ossification. Irregular hyperostosis on the anterior surface of the vertebral body eventually merges with the overlying ossified ligament. In addition, extensive sclerosis of a large portion of the vertebral body develops coincident with the appearance of pointed excrescences at its superior and inferior margins. Pathologically, degeneration in the outer fibers of the annulus fibrosis was associated with antero-
563
Diagnostic Radiology
=
Fig. 7. Thoracic spine abnormalities. Alterations in the ALL (A anterior). A. and B. A radiograph and photograph of a sagittal section of a thoracic spine reveal ribbon-like calcification adjacent to the anterior aspect of the vertebral body within the ALL (arrowheads). C. More extensive ossification of the ALL (arrowheads) is noted on a radiograph of a sagittal section of the spine. Additional findings include apparent concavity (c) on the anterior surface of the vertebral body, T-shaped disc extensions (d), and horizontal struts of new bone (s). Note the integrity of the intervertebral disc spaces.
lateral extension of the fibrous tissue. These disc extensions create an "umbrella" effect as they grow in and around the fibers of the ALL, which appeared stretched
Fig. 8. Thoracic spine abnormalities. Hyperostosis of the anterior surface of the vertebral bodies (A = anterior). A. and B. On a radiograph and photograph of a sagittal section of a spine, cortical hyperostosis (h), underlying bony sclerosis (sci), and pointed excrescences (e) have developed. C, and D. A radiograph and photograph of a sagittal section of a spine with advanced hyperostosis reveal sclerosis (scI) of a large portion of the vertebral body resulting from periosteal new bone formation, and anterior disc extensions (d). Portions of the ALL are ossified, and degeneration of the peripheral fibers of the annulus fibrosis can be noted.
564
June 1976
DONALD RESNICK AND GEN NIWAYAMA
over the protruding fibrous tissue. Ossification develops within the blended fibers of the annulus and the ALL. We also noted hypervascularity and an occasional mild chronic inflammatory cellular infiltrate surrounding the ALL adjacent to the degenerating annulus. Periosteal new bone formation on the anterior aspect of the vertebral body was continuous with irregular osteophyte formation near the attachment of the ALL to the vertebral body. Eventually, regional ossification involved the ALL, paravertebral connective tissue, and annulus fibrosis. Lumbar Spine: The earliest abnormalities in the lumbar region consisted of hyperostosis and sclerosis of the anterior aspect of the vertebral body. Small pointed bony excrescences developed at the superior and inferior margins of the vertebra and grew across the intervertebral disc space. The changes on pathologic examination were similar to those in the thoracic spine, with degeneration in the peripheral portion of the annulus, fibrous expansions, and periosteal sclerosis and osteophyte formation, although ALL calcification and ossification were absent or mild. Late Changes (Fig. 9): With severe involvement, a bizarre appearance of the entire spine became evident. Flange-shaped and armor-like deposits covered the right anterolateral surface of the spine in the thoracic region and
Late changes in the thoracic and lumbar spine (A On a radiograph and photograph of a transverse section of a thoracic spine with advanced hyperostosis, the basis of the characteristic radiolucency (Iu) beneath the deposited bone (arrowhead) becomes apparent. A space exists between the ossified ligament (curved arrow) and subjacent vertebral body (open arrow) which is obliterated on the right side of the specimen by focal bony ankylosis (straight arrow).
the lateral and anterior surfaces in the lumbar region. The left lateral edge of the deposited bone was frequently sharply demarcated. Bony ankylosis was noted in the thoracic spine, although close external inspection revealed that the outgrowths commonly interdigitated, and their undulating and irregular surfaces were separated by thin fibrous extensions from the annulus fibrosis. This was confirmed on sagittal sections by alternate layers of bone and ligamentous and fibrous tissue. True bony ankylosis was infrequent in the lumbar spine. DISCUSSION
DISH has been previously noted in the literature under a variety of names. Spondylitis ossificans ligamentosa was described by Oppenheimer (12) in a study of 282 persons with calcification or ossification of vertebral ligaments. Of this group, ligamentous changes in the absence of lesions of the vertebral bodies, intervertebral discs and apophyseal joints developed in 18 patients. Patients in this subgroup were generally over the age of 55 years and asymptomatic; involvement was most frequent in the thoracic spine. The ALL appeared attached to the vertebral bodies and its length appeared to be increased. Oppenheimer indicated that ligament ossification required two pre-existing components: disuse related to vertebral immobility, and rarefaction of the adjacent bone. His observations and those of Leriche and Policard (10) suggested that immobilization increased the chance of transformation of dedifferentiated connective tissue into bone, and that the lime salts de-
Fig. 9.
= anterior, R = right). A. and B.
=
Fig. 10. Ankylosing spondylitis (A anterior). A. and B. A radiograph and photograph of a sagittal section of a macerated thoracic spine from a cadaver with ankylosing spondylitis reveal thin vertical syndesmophytes (arrowheads) extending between adjacent vertebral bodies. The bone is osteoporotic and the intervertebral discs, biconvex.
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DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS
posited in the new bone originated from the adjacent rarefied vertebral body. Ligamentous ossification was therefore not the cause but the effect of decreased mobility. Ott (15) introduced the term spondylosis hyperostotica in a clinical and radiographic evaluation of 11 men and 4 women with ligamentous ossification, and stressed the mild evolution of the disease. He regarded the changes as severe spondylosis deformans. Smith et al. (19) described physiologic vertebralligamentous calcification in 53 patients, 32 of whom had pain and stiffness of the spine. The patients were generally over the age of 60 years, and abnormalities were most frequent in the thoracic region. Osteoporosis was almost uniformly absent, and mild degenerative changes of the sacroiliac joints were occasionally visible on the radiographs. The ossified ALL ranged from 5 to 10 mm in thickness and appeared "flabby," particularly at the level of the intervertebral disc (as if it were too long for the underlying spine). Coexisting osteophytes were noted. These investigators stated that trauma was not an important etiologic agent, and that an initial decrease in spinal mobility in older patients lessened the degree of mechanical stress on the ligaments, resulting in their degeneration, calcification, and ossification. The clinical and radiographic findings of this disorder were further elucidated by .Sutro et al. (21), who utilized the descriptive title generalized juxta-articular ossification of ligaments of the vertebral column. Their patients were usually asymptomatic and without restricted motion. No specific etiology was recognized. Forestier et al. (7) described senile ankylosing hyperostosis of the spine. The first adjective was eventually omitted as younger patients were discovered to have the same disorder. In an evaluation of 245 patients, 65 % of whom were men, Forestier and Lagier (6) commented upon the characteristic involvement of the anterior and right lateral aspect of the thoracolumbar region of the spine. They found that the radiographic features in this segment included undulating laminated ossification. In the cervical and lumbar regions, cortical hyperostosis of the anterior surface of the vertebral body, a cloud-like shadow in front of the disc, and irregular and thick spur formation were sequential radiographic observations. Utilizing pathologic specimens, these investigators outlined ossification which encompassed the ALL, paravertebral connective tissue, and peripheral portion of the disc. An association between hyperostosis of the spine and similar outgrowths in extraspinal locations was noted, a relationship which has been further delineated in more recent publications (9, 16, 21). Vernon-Roberts et al. (22) investigated the pathologic changes in the vertebral column in this syndrome based upon an autopsy study of 500 cadavers. They reported an incidence of ankylosing hyperostosis in 6 % , and described the thoracic spinal manifestations in 20 specimens. Their findings included syndesmophytosis of varying severity (100 %), lateral extensions of fibrous tissue arising from
565
Diagnostic Radiology
the annulus fibrosis (100 %), bony accretion on the surfaces of the vertebral body (100%), bony ankylosis (40 % ), ossification in the ALL (15 %), and marked narrowing of the intervertebral disc spaces (10%). In addition, a high incidence of osteoporosis (100%) and Schmorl's nodes (85 %) was noted. They conjectured that the initial alteration in the disorder was a predominantly right-sided anterolateral extension of fibrous tissue from the intervertebral disc which evoked periosteal new bone formation. Our radiographic and pathologic investigation of cadaveric spines agrees in part with these previous reports. In the thoracic spine, ALL calcification and ossification were early abnormalities associated with chondroid metaplasia and endochondral ossification. In addition, peripheral tears of the annulus fibrosis, anterolateral extensions of fibrous tissue arising from the intervertebral disc, hypervascularity, and chronic inflammatory cells were apparent. Periosteal bony accretion was a conspicuous manifestation associated with irregular bony excrescences on the margins of the vertebral body. In comparison with a previous study (22), our cadavers did not demonstrate striking osteoporosis or Schmorl's nodes. In the lumbar spine ligament, calcification and ossification were much less frequent, although other abnormalities were similar to those in the thoracic region. The evolving radiographic picture of DISH, particularly in the thoracic spine, included several distinctive findings: (a) A flowing pattern of new bone along the anterolateral aspect of the spine associated with a bumpy contour, particularly at the level of the intervertebral disc; (b) A linear or semicircular radiolucency between the vertebral body and overlying laminated bone; (c) L-, T-, or Y-shaped radiolucent defects within the ossified mass at the level of the disc space.
Differential Diagnosis Ankylosing Spondylitis (Fig. 10): The clinical, radiographic and pathologic features of ankylosing spondylitis (AS) differ from those of DISH. AS predominantly affects young adults and causes considerable signs and symptoms; DISH affects middle-aged and elderly patients and may be asymptomatic or associated with mild to moderate restriction of motion. The syndesmophytes which characterize AS are slender, vertically oriented bony bridges which connect adjacent vertebral bodies, and represent ossification within the peripheral portion of the annulus fibrosis (4, 5). Chondroid metaplasia and ossification may eventually involve large portions of the annulusand nucleus pulposus, but ossification of the ALL and the adjacent connective tissue, (noted in DISH) is not apparent. The exuberant flowing excrescences and vertebral body hyperostosis of DISH are easily distinguished from the syndesmophytosis and vertebral body osteitis of AS. In addition, bony ankylosis of the apophyseal and sacroiliac joints, characteristic of AS, is not seen in DISH. "Degenerative" Disc Disease (Fig. 11): Degenerative disc disease, osteoarthrosis of the anterior synarthroses of the spine (20), and intervertebral chondrosis (18) are
566
DONALD RESNICK AND GEN NIWAYAMA
June 1976
=
Fig. 11. Intervertebral chondrosis and osteochondrosis (R = right, L left). A. and B. Advanced intervertebral (osteo-) chondrosis. Note, on this radiograph and photograph of a coronal section from a cadaveric spine, the presence of vacuum phenomena (v), intervertebral disc space narrowing (n), vertebral body sclerosis (sci), and osteophyte formation (arrowheads). Extensive degeneration of the nucleus pulposus and annulus fibrosis has occurred.
terms applied to alterations of the intervertebral discs related to the physiologic and pathologic dehydration which occurs with advancing age. Histologically, these changes affect predominantly the nucleus pulposus, resulting in a desiccated and friable surface which may become discolored. Cleft formation may extend into the annulus fibrosis. Radiographically, one notes vacuum phenomena within the disc and disc space narrowing. Abnormalities in the adjacent vertebral body [intervertebral osteochondrosis (18)] represent a more severe stage of the disease, and consist of sclerosis beneath the cartilage end-plates, intravertebral body protrusion of disc material (Schmorl's nodes), and small osteophytes at the bone margins. These changes differ considerably from the ligament ossification, extensive bony excrescences, and relatively intact disc spaces characteristic of DISH.
Spondylosis Deformans (Fig. 12): This common disorder results in spinal osteophytosis (3). Although opinions on the pathogenesis of these outgrowths vary, most investigators implicate increased mobility of the adjacent segment of the spine, resulting in stress on the fibers which attach the ALL to the vertebral body (1, 13, 14). The new bone may extend into the triangular space devoid of ligaments which exists between the vertebral edge and the site of attachment of the ALL (4, 12), or invade any of the overlying soft tissues (11). Schmorl (18) demonstrated tears in the peripheral portion (Sharpey's fibers) of the annulus fibrosus which he felt were an initial manifestation of spondylosis deformans. With further separation in these fibers, the disc was no longer anchored to the vertebral body and, particularly in the presence of a nucleus pulposus without degeneration
Fig. 12. Spondylosis deformans (A = anterior). A.-C. Sagittal sections of the spine illustrating sequential abnormalities of spondylosls deformans. Initially, degeneration of the peripheral portion of the annulus fibrosis (straight arrows) and prolapse of fibrous tissue (curved arrows) occur. The ALL is stretched over the protruding intervertebral disc (open arrow). Osteophyte formation occurs at its anterior attachment to the vertebral body (arrowheads), which may eventually produce vertebral body ankylosis.
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Vol. 119
Table III:
Diagnostic Radiology
Differential Diagnosis of Radiographic Findings Disease
Site Vertebral bodies
Intervertebral discs
Apophyseal joints Sacroiliac joints Peripheral skeleton
Dish
Ankylosing Spondylitis
"Flowing" ossification and hyperostosis; large osteophytes; bony ankylosis frequent radiographically, less frequent pathologically Normal or mild decrease in height
Thin syndesmophytes; osteitis with "squaring"; extensive bony ankylosis radiographically and pathologically Normal or convex in shape
Normal or mild sclerosis; occasional osteophytes Para-articu lar osteophytes
Erosions, sclerosis and bony ankylosis Erosions, sclerosis and bony ankylosis "whiskerin g", arthritis
"whiskering", para-articular osteophytes; ligament calcification and ossification, hyperotosis
and with all its turgor, prolapse of a portion of the annulus occurred. With further protrusion, the ALL was stretched, and osteophytes developed at its attachment to the anterior surface of the vertebral body. Our observations of pathologic alterations in DISH include findings consistent with spondylosis deformans. Cleft like defects in the annulus fibrosus, prolapse of disc material, and pointed bony excrescences at the vertebral attachment of the ALL were apparent. In the lumbar spine, the resulting outgrowths were larger and more irregular than those usually noted in spondylosis deformans; in the thoracic spine, ligamentous ossification was a significant feature. Apparently DISH differs quantitatively and qualitatively from typical spondylosis, and represents regional ossification encompassing ligaments, paraspinal connective tissue and annulus fibrosus, and periosteal new bone formation on the anterior surface of the vertebra.
DISH-A Disease Entity? The radiographic and pathologic features of DISH differ considerably from those of AS and intervertebral osteochondrosis (TABLE III), most resembling severe spondylosis deformans, but demonstrating radiographic and pathologic differences. In a patient with extensive spinal manifestations the radiographic findings are distinctive, but when only minor or localized alterations are apparent it is difficult to separate cases of DISH from those of spondylosis deformans. Utilizing diagnostic criteria selected to exclude most cases of typical spondylosis, we found spinal manifestations of DISH in 12 % of our routine autopsies. DISH may not represent a disease per se but rather a vulnerable state in which extensive ossification results from an exaggerated response of the body in some patients to stimuli which produce only modest new bone formation in others. As such, it is a common ossifying diathesis in middle-aged and elderly patients. Evidence that these patients are "bone formers" includes their high incidence of associated extraspinal hyperostoses at the sites of ligament and tendon attachment. In addition, we have recently noted extensive local heterotopic ossification in the
Intervertebral Osteochondrosis Sclerosis of superior and inferior surfaces
Moderate to serve decrease in height "vacuum" phenomena Normal Normal Normal
early postoperative period following total hip arthroplasty in 2 of our patients. Hypotheses suggesting that DISH may be related to other diseases including acromegaly, hypoparathyroidism, hypervitaminosis A, and fluorosis have not been substantiated; it therefore remains a condition of unknown etiology at present. ACKNOWLEDGMENTS: The authors gratefully acknowledge the assistance of Clark Neal and Bonnie Walker in procuring the specimens; Peggy Mackey and Mary Gonsalves for preparing the histologic sections; Carol Barrier, RT, for technical aid; Sue Brown, Janet Julien and Paula Nicholas for the drawings and photography; and Janet Zatlokowicz for secretartal help.
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