Calcium pyrophosphate dihydrate of the ligamentum flavum in the cervical spine – A review of the literature
- Department of Orthopaedics, University of Rochester, Rochester, New York, United States.
Addisu Mesfin, Department of Orthopaedics, University of Rochester, Rochester, New York, United States.
DOI:10.25259/SNI_684_2022Copyright: © 2022 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Mark Ehioghae, Mark C. Lawlor, Addisu Mesfin. Calcium pyrophosphate dihydrate of the ligamentum flavum in the cervical spine – A review of the literature. 14-Oct-2022;13:470
How to cite this URL: Mark Ehioghae, Mark C. Lawlor, Addisu Mesfin. Calcium pyrophosphate dihydrate of the ligamentum flavum in the cervical spine – A review of the literature. 14-Oct-2022;13:470. Available from: https://surgicalneurologyint.com/surgicalint-articles/calcium-pyrophosphate-dihydrate-of-the-ligamentum-flavum-in-the-cervical-spine-a-review-of-the-literature/
Background: Calcium pyrophosphate dihydrate (CPPD) deposition, also known as pseudogout, in the cervical ligamentum flavum (CLF), is a rare disease which can cause spinal cord signaling changes leading to rapid deterioration in function. The natural history of cervical myelopathy as a result of CPPD deposition within the CLF is not well understood. Our objective is to describe the presentation, imaging findings, and treatment options of CPPD deposition or pseudogout of the cervical spine.
Methods: Using PubMed, we analyzed studies published from 1978 to 2022. Key words used were “pseudogout,” “CPPD deposit disease,” “cervical yellow ligament,” “CLF,” and “cervical spine.” We excluded “crowned dense syndrome” and “ossification of ligament flavum.” Using a department database, we queried for patients treated for CPPD of the cervical spine.
Results: Twenty clinical studies on CPPD of the cervical spine with 69 patients aged between 15 and 92 years (mean = 72) were identified. Neck pain and numbness of the hands were the most common symptoms. Diabetes mellitus and hypertension were the most common comorbidities. Males and females were affected at equal rates. C4-C5 and C5-C6 were the most affected segments. Earlier surgical treatment produced better outcomes. A laminectomy and fusion or laminoplasty were the most common procedures performed with most patients experiencing some return of neurologic function.
Conclusion: Although rare, CPPD deposit disease in the CLF should be readily considered as a differential diagnosis due to the continuously aging population. CPPD’s progressively worsening nature makes an early diagnosis and treatment important in improving the patient’s overall quality of life.
Keywords: Calcium pyrophosphate dihydrate, Cervical fusion, Cervical laminectomy, Cervical spine, Cervical stenosis, Laminoplasty, Ligamentum flavum, Myelopathy
Calcium pyrophosphate dihydrate (CPPD) deposit disease, also known as pseudogout and formerly known as articular chondrocalcinosis, was first defined by Zitnan and Sit’aj in 1958.[
The natural history of cervical myelopathy as a result of CPPD deposition within the CLF is not well understood.[
A total of 20 clinical studies on CPPD deposit disease in the CLF were identified with 69 patients included for analysis. We analyzed all clinical studies published before 2022. The first report was in 1978 and the most recent in 2021. We identified articles using PubMed with references listed as peer-reviewed publications. Key words used included “pseudogout, “CPPD deposit disease,” “cervical yellow ligament,” “CLF,” and “cervical spine.” We excluded “crowned dense syndrome” and “ossification of ligament flavum.”
Using the department’s database, two cases of CPPD deposit disease in the CLF were identified. The clinical and histological evidence is discussed.
A 60-year-old woman, with cervical myelopathy, presenting with balance and gait abnormalities. Magnetic resonance imaging (MRI) and computed tomography (CT) identified a dorsal lesion compressing the spinal cord emanating from the ligamentum flavum at the C4-C5, C5-C6, and C6-C7 levels [
Sagittal Computed tomography (a), T2-weighted Magnetic resonance imaging (b), and (c,d,e) Axial T2-weighted images of calcium pyrophosphate dehydrate (CPPD) deposit disease in the cervical ligamentum flavum (CLF) of a 60-year-old female with cervical myelopathy presenting with balance and gait abnormalities. Sagittal yellow images circle (a,b) denotes a CPPD compression lesion in C4-C5, C5-C6, and C6-C7 CLF lamina. Axial images present spinal canal stenosis.
A 70-year-old woman, with cervical myelopathy, presenting with balance and gait abnormalities resulting in falls. MRI and CT demonstrated a dorsal based compression of the spinal cord emanating from the ligamentum flavum at the C4-C5 [
Sagittal computed tomography (CT) (a), T2-weighted magnetic resonance imaging (b), axial CT (c), and T2-weighted (d) images of calcium pyrophosphate dehydrate (CPPD) deposit disease in the cervical ligamentum flavum (CLF) of a 70-year-old female with cervical myelopathy presenting with balance and gait abnormalities experienced falls. The yellow circles (a,b,c,d) denotes a CPPD compression lesion in C4-C5 CLF lamina.
Various factors play a role in the development of CPPD in the CLF such as aging, metabolic diseases, mechanical stress, and endocrine imbalance.[
Overall, aging is a major risk factor for CPPD deposit disease in the CLF. The prevalence of CPPD deposit disease increases from 3.7% to 17.5% as age groups increase from 55–59 to 80–84, respectively.[
While CPPD in the CLF has a mean onset age of 72–73 years, on rare occasions, it can be observed in the pediatric population. Morino et al. 2016[
Although the direct cause of pseudogout is still unclear, some reported that metabolic risk factors for CPPD deposit disease in the CLF are hyperthyroidism, hypothyroidism, hyperparathyroidism, osteoarthritis, diabetes mellitus, arthrosclerosis, hypertension and hemochromatosis, Wilson’s disease, hypophosphatasia, hypomagnesemia, and loop diuretics use.[
The cervical spine is an area of high mobility. As such, the ligamentum flavum is highly elastic in this section of the spine leaving it susceptible to microscopic tears.[
The origin of CPPD deposit disease in the CLF is unknown but three factors may influence its deposition: (i) metabolic disorders; (ii) sporadic inheritance; and (iii) familial inheritance.[
Morphologically, the central region of the CLF is the primary area affected as it becomes surrounded by denigrative fibers due to CPPD deposition.[
CPPD is frequently associated with generalized collagen degeneration.[
The primary methods of diagnosis of CPPD in the CLF are through a combination of symptomatology, MRI, CT, and histopathology.
The symptoms of CPPD deposit disorder are progressive in nature with global worsening and loss of function with time.[
CPPD deposition disease in the CLF is commonly mistaken for ossification of ligamentum flavum (OLF) which is more often centrally identified in the lower thoracic spine and generally localized to a single level.[
CPPD deposition does not extend to the posterior facet joints while OLF always extends to the posterior facet joint. CPPD deposition is not continuous with the lamina and OLF shows continuity with the lamina.[
Although gout and CPPD deposit disease present similarly in their ability to deposit crystals into joints, cartilage, and ligaments causing an inflammatory response,[
Sagittal CT [
Sagittal and axial MRI with T1- and T2-weighted imaging [
CPPD nodules show low signal intensity in T1- and T2-weighted image surrounded by areas of high and medium signal intensity considered an appearance of edematous change. Lu et al. 2021[
As discussed, prognostic factors of CPPD deposition disease in the CLF include age, comorbidities, rate of deterioration, severity and duration of symptoms, and spinal cord signal changes.
Management of CPPD deposition disease in the CLF is dependent on the course of the disease. Although CPPD crystals can cause inflammation, many patients do not present with abnormally high inflammatory markers.[
A laminectomy is a highly effective method of relieving cervical myelopathy caused by CPPD lesion as the symptomatic lesions are typically confined to specific spinal segments.[
Early surgical treatment produces better long-term outcome and return of neurological function.[
Although a rare condition, the prevalence of CPPD in the CLF indicates that it should be considered as a differential diagnosis particularly as the age of the population increases. CPPD’s progressively worsening nature makes an early diagnosis and treatment important in improving the patient’s overall quality of life and functional outcome.
Patients’ consent not required as patients’ identities were not disclosed or compromised.
There are no conflicts of interest.
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