INTRODUCTION
Gout is a metabolic disease characterised by recurrent episodes of arthritis associated with the presence of monosodium urate crystals in the tissue or synovial fluid during the attack. Tophi are soft tissue masses made up of urate deposits in and around joints and represent the chronic phase of the disease process. Tophi may cause osseous erosion and are usually associated with hyperuricaemia. The disease may affect any joint and is a common differential diagnosis of acute arthropathy.
Pseudogout, also known as calcium pyrophosphate dihydrate (CPPD) disease, is defined as the deposition of CPPD crystals in the articular or periarticular structures leading to acute, subacute or chronic inflammation of the joints. Chondrocalcinosis is the deposition of the crystals in the hyaline cartilage or fibrocartilage, which can be identified on radiographs. These are known as pseudogout because of their clinical similarity to gouty arthritis.
These forms of crystal-induced arthritis usually affect peripheral joints, including knee, ankle, wrist, and metacarpophalangeal and metatarsophalangeal joints. When the joint fluid is aspirated and examined under the microscope, gouty arthritis is characterised by needle- or rod-shaped and negatively birefringent crystals under polarised light, whereas pseudogout shows positively birefringent crystals. Both may be associated with other inflammatory or endocrine diseases.1
Although gout and pseudogout are common diseases causing inflammatory arthropathy in peripheral joints, involvement of the spine is uncommon. When patients with a history of gout or pseudogout affecting the other joints present with symptoms of sciatica or cauda equine syndrome, spinal crystal arthropathy is usually not considered in the differential diagnosis.
Crystal arthropathy may affect all areas of the spine. Presentations vary and include cervical myelopathy, radiculopathy, spinal stenosis to cauda equina syndrome.
Between 2001 and 2005, 4 cases of crystal arthropathy of the lumbar spine were treated in our hospital. Two had acute cauda equine syndrome and another 2 had spinal stenosis. We reviewed the literature on crystal deposition diseases affecting the spine and highlighted the features of the disease and the differential diagnoses that should be considered when treating patients with a history of gout or pseudogout who present with spinal problems.
CASE REPORTS
Case 1
In June 2002, a 65-year-old man presented with sudden onset of retention of urine and numbness over the scrotal area. He had a 4-day history of right leg numbness and pain without any back pain. He had a history of peripheral gouty arthritis and had tophi deposits over his elbows, wrists, and hands. He was treated with allopurinol while living overseas but discontinued the medication after moving back to Hong Kong. He also had hypertension, renal impairment, and impaired glucose tolerance.
On physical examination he was found to have a non-tender lumbar spine, normal strength in his lower limbs but reduced sensation over the saddle region (S2, S3 dermatome). His abdomen was distended and his bladder full. A per-rectal examination showed lax anal tone with gripping and bulbocavernous reflex absent. A hard nodule was felt in the right lobe of the prostate.
Plain radiographs of the lumbar spine showed diffuse sclerotic changes in the L3 vertebral body (sacralised L5), suggestive of metastatic infiltration. Computed tomographic (CT) myelography revealed extra-dural blockade at the L3/4 disc level (Fig. 1).
His prostatic specific antigen was found to be elevated to 309 ug/l and his urate level increased to 0.60 mmol/l. Other significant blood parameters included an erythrocyte sedimentation rate of 30 mm/hr, a white cell count of 10 x109/l, and alkaline phosphatase level of 84 IU/l. A clinical diagnosis of acute cauda equina syndrome with bony metastases, possibly from a prostate tumour, was made.
An urgent L3 and L4 laminectomy was performed. During the operation, whitish chalky material was found to be discharging from both the L3/4 facet joints into the spinal canal, causing compression of the dural sac. No tumour tissue was found inside the spinal canal. Histological section of the chalky material showed numerous tophaceous deposits with an associated granulomatous response. A transpedicle core biopsy of the L3 vertebral body was also taken and this confirmed the clinical diagnosis of metastastic adenocarcinoma, likely to be of prostatic origin.
Postoperatively, while his bladder function improved, the patient still had numbness and decreased sensation over the saddle area. He could walk unaided. Later, he underwent bilateral orchidectomy and had a course of palliative radiotherapy to the lumbar spine. He was put on long-term allopurinol for the gout.
Case 2
In December 2005, a 63-year-old man presented with a one-year history of bilateral lower limb pain with numbness. He had a history of gout and hypertension and allopurinol was being used to control the gout. His claudication time was 10 minutes. Sphincter function was normal. There was no history of trauma and he did not complain of low back pain. Physical examination showed no peripheral gouty tophus. The lumbosacral spine was non-tender and the straight leg raise angle was 70
Radiography of his lumbosacral spine showed degenerative changes and a grade I spondylolisthesis at L4/5, with instability. Magnetic resonance imaging (MRI) of the lumbosacral spine demonstrated severe spinal canal stenosis at L4/5 with a prolapsed intervertebral disc at L4/5, hypertrophy of the ligamentum flavum and facet joints. His blood analysis showed a urate level of 0.22 mmol/l; his erythrocyte sedimentation rate and alkaline phosphatase level were normal.
He was treated with physiotherapy for the spinal stenosis but the symptoms persisted. A posterior decompression with an L4 and L5 laminectomy and transforaminal lumbar interbody fusion and L4 and L5 pedicle screw fixation was then performed. Intraoperatively, we noticed an L4/5 spinal stenosis with ligamentum flavum and facet joint hypertrophy and a broad-based prolapsed intervertebral disc. We also found chalky material deposited over the juxtaarticular tissue and ligamentum flavum, causing inflammatory changes in the epidural space.
Histological examination of the juxta-articular tissue and ligamentum flavum showed scattered aggregates of acellular amorphous basophilic material in fibrous tissue. When the soft tissue was examined under polarised light, it demonstrated abundant negatively birefringent needle-shaped crystals compatible with the diagnosis of spinal gout.
The patient's symptoms improved after surgery and he could tolerate walking unaided for more than one hour.
Case 3
In September 2004, a 79-year-old woman presented with a 2-week history of increasing numbness in both her lower limbs. She had a history of on-andoff back pain, aggravated by walking, for years. She complained of a sense of incomplete bladder emptying. Her ability to walk was impaired and she had recurrent falls one week before admission.
A physical examination revealed local tenderness over the lower lumbar spine. The motor power was normal in both lower limbs, as was sensation. Both knee and ankle reflexes were absent. The anal tone was normal, and residual urine, checked by bladder scan, was at a normal level, on admission. Plain radiographs of the lumbar spine showed degenerative changes with a collapsed L4 (Fig. 2).
She was treated with physiotherapy for spinal stenosis but there was no improvement and she developed urinary retention one week later. The power in both lower limbs also deteriorated to grade 4/5 and sensation diminished from L3 downwards. The anal tone became lax but peri-anal sensation was preserved.
MRI scans of the lumbar spine revealed a marked stenosis at the L3/4 level with a hypertrophic ligamentum flavum (Fig 3). A diagnosis of spinal stenosis with cauda equina syndrome was made.
During an emergency L3 laminectomy, deposits of whitish chalky material were found in the ligamentum flavum, which was swollen and inflamed, causing severe thecal sac and nerve root compression. Histological examination of the ligamentum flavum showed fibrous tissue mingled with multiple aggregates of rhomboid crystals. The crystals showed positive birefringence, suggestive of calcium pyrophosphate.
Postoperatively, the numbness over both lower limbs improved. There was some return of the anal tone, but the patient still needed intermittent urinary catheterisation. Her lower limb strength also improved and she could walk independently on discharge.
Case 4
In September 2004, a 72-year-old woman had a leftsided L5 hemi-laminectomy for leg numbness done in another hospital 2 years before admission. She presented with bilateral buttock pain associated with lower limb numbness on walking which developed one year after the spinal operation. She had a history of stomach and cervical tumours surgically removed many years previously. There was no evidence of recurrence.
On admission, she could only tolerate walking for 5 minutes. There was no sphincter disturbance. A physical examination revealed weakness of the left extensor hallucis longus and decreased sensation bilaterally over the L5 dermatome. The ankle reflexes were absent on both sides. Her renal and liver function tests were unremarkable. A radiograph of her lumbar spine showed old collapse fractures of L1 and L5 (Fig. 4a); CT showed old osteoporotic collapse fractures of L1 and L5 (Fig. 4b); MRI showed marked spinal stenosis with compression of the thecal sac at the L4/5 level caused by the combination of posterior bony protrusion from the collapsed L5 vertebral body, L4/5 disc bulging and L4/5 facet joint hypertrophy (Fig. 4c).
On surgical exploration, the ligamentum flavum was found to have been removed on the left side and was swollen and hypertrophied on the right side at the L4/5 level, due to deposition of whitish chalky material. The chalky material was also found in the epidural space, encasing the right L5 nerve root. A histological examination of the ligamentum flavum identified positively birefringent crystals of calcium pyrophosphate. Her claudication improved after the operation.
DISCUSSION
The prevalence of gout ranges from 0.2 to 0.4% in a western population with an annual incidence of 0.01 to 0.015%.2 Gout is commonly found in peripheral joints as sedimentation of monosodium urate crystals because crystal solubility decreases with temperature, leading to tophus formation in avascular tissues (e.g. tendons) and tissues at lower temperatures. Pseudogout usually causes calcification over cartilage such as the meniscus in the knee. The reason why these crystal deposition diseases occasionally involve the spine is unknown. This might be related to local tissue change such as a previous injury, tissue necrosis, or degenerative disease of the spine.3
47 cases of gout and 66 cases of pseudogout involving the spine have been reported in patients aged from 27 to 84 years (Tables 1 and 2). All segments of the spine were affected, although gouty involvement is more common in the lumbar spine, while the cervical spine is more likely to be affected by pseudogout. Of 47 spinal gout cases, 11 were in the cervical spine, 9 in the thoracic spine and 27 in the lumbar spine.2-16 Of 66 spinal pseudogout cases, 40 were in the cervical spine, 6 in the thoracic spine, and 20 in the lumbar spine.1,5,17-24
In the cervical spine the usual presentation is cervical myelopathy, caused by crystal deposition in the ligamentum flavum, resulting in direct cord compression or C1/2 subluxation. In the lumbar spine, gout may involve the epidural space, intradural compartment, ligamentum flavum, discovertebral junction, the pedicles, facet joint capsule and the neural foramen.3 Similarly, pseudogout can also involve the ligamentum flavum, intervertebral disc, facet joint capsule and neural foramen. Of the 27 lumbar gout cases, 14 involved the facet joints while the ligamentum flavum was the second most common site. The situation was similar in the lumbar pseudogout cases with facet joints involved in 5 cases. In our patients, the ligamentum flavum and facet joint capsules were involved and the crystals were discharged into the epidural space, causing thecal sac compression. So, the clinical presentations in both gout and pseudogout of the lumbar spine were similar. Either could present as spinal stenosis, lumbar radiculopathy, spondylolisthesis, or cauda equina syndrome.
Spinal gout more commonly affected males while pseudogout was more common in females. Our 4 patients conformed to this pattern. Of the 27 patients with lumbar spinal gout, 14 had a known history of hyperuricaemia and half of them had peripheral gouty arthropathy. Of the others, 12 had no history of gout. One of our patients with spinal gout had both hyperuricaemia and peripheral gouty arthritis. Such a history should alert the surgeon to the possibility of gouty involvement of the spine.
Three reported cases of spinal gout had symptoms mimicking spinal infection.4,8,10 They had an acute onset of fever and low back pain with neurological deficits. The epidural deposition of crystals may mimic an epidural abscess.12 The diagnosis can only be confirmed by a histological examination of tissues removed during surgical decompression. There has been one reported case of spinal pseudogout mimicking spinal infection.19 The diagnosis was confirmed by fine needle aspiration and the patient was treated conservatively.
Making a preoperative diagnosis is difficult and in most cases patients were treated with a surgical decompression and a laminectomy. Most diagnoses were made on finding chalky, whitish material during surgery, and confirmed by histological examination. The radiological features of spinal gout are non-specific and include such findings as degenerative spondylosis, discovertebral erosions, bone destruction leading to joint subluxation, spinal deformities, spontaneous fusion and, occasionally, pathological fractures.3 Fenton et al.14 described the 'classic' findings of lobular juxta-articular masses with attenuation densities greater than that of surrounding muscle, well-defined intra-articular and juxta-articular osseous erosions with sclerotic borders as gouty involvement in the lumbar spine on CT. On MRI, tophi have homogenous intermediate to low signal intensities on T1-weighted images. The T2-weighted image varies, ranging from a homogenous high signal intensity to a homogenous low signal intensity. The tophi are enhanced after gadolinium diethylene-triamine-penta-acetic acid administration, varying from homogeneous enhancement to heterogeneous peripheral enhancement.3 This may be helpful for differentiating the fluid phase of synovial cysts or infection from the solid phase of gouty tophi. The above findings may also be found in degenerative, inflammatory, infective or neoplastic processes. In pseudogout, plain radiographs may demonstrate radio-opaque shadows at the posterior margin of the spinal canal. CT scanning may show the lesions as nodular or ovoid calcified lesions continuous with the lamina that may compromise the spinal canal. Similarly, MRI may demonstrate round or oval hypointense masses, just like gouty tophi, in the ligamentum flavum in both T1- and T2-weighted images.25
The diagnosis of crystal deposition disease of the spine can only be confirmed by histology. In gout, the tissues display characteristic granulomatous infiltrates of multinucleated giant cells, histiocytes, fibroblasts and needle-shaped, negatively birefringent crystals under polarised light microscopy.11 The identification of rod- or rectangular-shaped crystals with positively birefringent crystals confirms the diagnosis of pseudogout.25 Where there is no neural compression, a biopsy of the nodules around the ligamentum flavum and the facet joint region may establish the diagnosis. Nonetheless, this is a difficult approach for a needle biopsy and the diagnosis has only been reportedly made this way in only one case of spinal pseudogout19 and 3 cases of spinal gout.7,14,15 All of these four patients were treated conservatively.
A high index of suspicion can help clinicians make the correct diagnosis in patients with the clinical features, particularly hyperuricaemia and peripheral gouty involvement, and the characteristic radiological features. However, surgical decompression may still be required due to the development of neural compression. Although the clinical presentation of spinal pseudogout is similar to that of spinal gout, these patients may not have peripheral arthritis and gout tophi, or any abnormal blood parameters. In such a scenario, it may be difficult to make a correct diagnosis until it is revealed at operation.
Several patients have been treated conservatively with colchicine, non-steroidal anti-inflammatory drugs and even prednisolone to control pain in acute episodes, followed by urate-lowering agents such as allopurinol or probenecid to prevent further relapses.8
CONCLUSION
Crystal deposition disease of the spine is rare. With a high index of suspicion, a diagnosis can be made from the patient's clinical history of gout or pseudogout and the findings of CT or MRI scans. However, many cases can only be confirmed by histological examination of biopsies or surgically resected material, together with polarised light microscopy.
© 2007 Western Pacific Orthopaedic Association Provided by ProQuest LLC. All Rights Reserved.
Source: Journal of Orthopaedic Surgery
