Compressive cervical myelopathy due to calcium pyrophosphate dihydrate deposition in ligamentum flavum: A case report and review of literature

Abstract

Introduction

Symptomatic calcification of ligamentum flavum (CLF) is a rare condition of the cervical spine compared to other degenerative diseases. CLF manifests as myelopathic symptoms due to the compression of the spinal cord. Calcium pyrophosphate dihydrate (CPPD) deposition disease is the most prevalent cause of CLF. This is the first reported case of CLF caused by CPPD in the Middle East.

Presentation of case

A 75-year-old female patient presented with gait disturbance for two years. The imaging studies demonstrated two symmetric bulging masses with a density similar to bone between the inferior border of the C5 laminae and the superior border of the C6 laminae. Histologic evaluation of the resected tissue confirmed the CLF and CPPD disease pathology. The patient underwent a C5-C6 laminectomy. The symptoms resolved, and in a six-month follow-up period, the walking improved.

Discussion

The diagnosis of CLF due to CPPD is based on the interpretation of the symptoms concurrent with MRI, CT scan, and histopathological examination. Due to the high reoccurrence rates of the condition following the pharmacological treatment and sub-optimal response in those with negative inflammatory markers, open decompression with either cervical laminectomy or laminoplasty is considered the gold-standard therapeutic option in CFL due to CPPD deposition disease.

Conclusion

CLF is a rare cervical spine disorder that compresses the spinal cord and manifests as myelopathic symptoms. Early surgical intervention, preferably in the first five months of the disease initiation, is associated with favorable outcomes.

Highlights

• •Calcification of ligamentum flavum is a rare cervical disorder that manifests as myelopathic symptoms.
• •Calcium pyrophosphate dihydrate (CPPD) deposition disease is the most prevalent cause of CLF.
• •Early surgery, preferably within five months of disease onset, improves outcomes.

1. Introduction

Symptomatic calcification of ligamentum flavum (CLF) in the cervical spine is a rare condition compared to other degenerative diseases [1,2]. CLF mainly happens due to crystal deposition in the central part of the ligamentum flavum and the majority of studies have identified calcium pyrophosphate dihydrate (CPPD) deposition as the main driver of this condition [1,3]. Posterior compression of the spinal cord that develops as a consequence of cervical CLF leads to myelopathy and following neurological deficits [2,4]. The initial symptoms are loss of vibration, proprioception, and functional gait worsened by motor weakness and paresthesia [2].

In order to distinguish cervical CLF from other causes of dorsal spinal cord compression syndromes radiological imaging, analysis of cerebrospinal fluid, and histopathological examination are required [4]. Diagnosis of cervical CLF can be challenging as it could mimic other lesions like tumors if the depositions accumulate significantly at a single point [5]. Also, in some cases, it is shown that factors like trauma could initiate the symptoms of cervical CLF and lead to its diagnosis [6]. The gold-standard therapeutic option for myelopathy due to cervical CLF is laminectomy and decompressive surgery [2]. Long-term follow-up of patients undergoing decompressive surgery for cervical CLF showed to have promising relief of symptoms with no major post-operative complications [[7], [8], [9]].

In this study, we report a 75-year-old female patient presented with symptoms of cervical myelopathy subsequent to cervical CLF due to CPPD disease. The study originated from the Middle East which has not been reported any previous case from this region. Also, the manuscript is enriched with a review of similar literature and reported cases from different populations. The findings of this study may contribute to the management of CLF due to CPPD disease in patients with different ethnicities and living in developing parts of the world, as only the timely diagnosis and appropriate management of the condition could relieve the symptoms and prevent more severe and adverse complications of the condition. This case report has been reported in line with the SCARE 2020 Criteria [10].

2. Case presentation

2.1. History and physical examination

A 75-year-old female patient was admitted to our hospital with inability to walk in the past two years which was progressive, and she could not walk anymore at the time of referral. The patient had a history of coronary artery bypass graft surgery six years ago. Her past medical history was positive for hypertension and type II diabetes mellitus, and she was receiving antihypertension and anti-hyperglycemia medications. On physical examination, the patient was able to walk only with assistance indicative of Nurick disability score of four. She had Hyperreflexia in the upper and lower limbs. Babinski's reflexes and Hoffman's signs were positive.

2.2. Radiologic findings

Lateral plain radiographic X-ray showed an unusual posterior mass at the C5-C6 junction. Computed tomography (CT) scan showed two symmetric bulging masses with a density similar to bone between the inferior border of the C5 laminae and the superior border of the C6 laminae (Fig. 1). Cervical magnetic resonance imaging (MRI) showed cord compression at the same level as the signal change of the spinal cord (Fig. 2). Brain and thoracic spinal cord MRIs were unremarkable. Lumbar spinal MRI showed multi-level stenosis.

Fig. 1.

Axial (a) and sagittal (b) cervical CT scans. The red arrows indicate calcification of the ligamentum flavum located between the laminae of the fifth and sixth vertebrae, attributed to calcium pyrophosphate deposition.

Fig. 2.

Cervical myelopathy induced by pressure from ligamentum flavum calcification due to calcium pyrophosphate deposition disease, as evidenced in MRI.

2.3. Laboratory tests

An assessment was conducted to determine the presence of an underlying metabolic disorder, such as hemochromatosis, hyperparathyroidism, or hypothyroidism. However, the results of the calcium profile, iron profile, and thyroid-stimulating hormone (TSH) tests all fell within the normal range.

2.4. Surgical procedure

The patient underwent surgery with a diagnosis of myelopathy as a result of spinal cord compression due to CLF. Under general anesthesia, patient was carefully put into a prone position with a Philadelphia collar around the neck, and a posterior approach was used to access the cervical spine. A posterior midline incision was made. After opening the skin, muscles were elevated subperiosteally, and the C5 and C6 lamina were confirmed by C-Arm intraoperatively. The lateral borders of laminae of C5 and C6 vertebrae were carefully delineated by a small bur, and then laminectomy was completed by Kerrison rongeur. After laminectomy, the posterior mass attached to the laminae was completely removed. No instrumentation was inserted, and no fusion was done. The incision was closed over the drain in multiple layers. Histologic evaluation of the resected tissue confirmed the CLF and CPPD disease pathology (Fig. 3, Fig. 4).

Fig. 3.

Histologic examination of the resected tissue during the laminectomy.

Fig. 4.

The presence of calcium pyrophosphate dehydrate (CCPD) deposits was observed through the use of polarized light microscopy.

2.5. Patient follow-up

Patient was followed up for six months. She started to walk with walker on her own at the end of the follow-up period and experienced an uneventful period after surgery. In the 6-month follow-up period, no reoccurrence of the disease was detected.

3. Discussion

Ligamentum flavum is an anatomical structure that connects the lamina of two adjacent vertebrae [1]. Degenerative alteration of the ligamentum flavum is a frequent finding associated with the intervertebral aging process [1]. The primary pathological alteration that occurs in the setting of ligamentum flavum degeneration is hypertrophy, ossification, and calcification [1]. The exact prevalence of CLF is unclear; however, a large-scale study demonstrated the prevalence rate of about 1 % for cervical CLF in patients with neck problems [11]. Cervical CLF may present with various symptoms including neck, myelopathic symptoms such as sensory numbness, pain, gait disturbance, bladder dysfunction, and abnormal deep tendon reflexes [2].

The accurate pathophysiology of CLF development is unknown; however, several studies suggested CPPD could play an important role in CLF [8]. CPPD disease which is also known as pseudogout can affect joints and cause synovitis in extremities [12]. In the vertebral column, CPPD crystals can accumulate in the disc, apophyseal joints, interspinous ligament, supraspinous ligament, ligamentum flavum, and transverse ligament of the atlas [1]. It is suggested there is a strong association between symptomatic CPPD deposit disease and aging as one study from the United Kingdom reported the overall prevalence of this condition increasing from 3.7 % in the 55–59 years age group to 17.5 % in the 80–84 years age [13]. Aging, sex, metabolic diseases, mechanical stress, and endocrine imbalance are factors that possess an important role in the development of CPPD deposit in the CLF, and among the mentioned favors, aging has the most effect [2].

Our findings in the reported case in this study are comparable with previously published literature. There are a wide range of similar conditions including cervical myelopathy due to CLF caused by CPPD deposit [[2], [3], [4],8,14], or CLF cases with other crystals without any evidence of CPPD deposit [15]. The details of similar cases with cervical myelopathy due to CLF caused by CPPD deposition are summarized in (Table 1). As evident from literature, most of these cases were elder female patients experiencing symptoms of cervical myelopathy and neck pain with majority of them having the CLF involvement in mid and lower levels of the cervical spine, who needed surgical intervention including laminectomy or laminoplasty with or without fusion or use of instrument to relieve the symptoms. Most of the similar cases have uneventful periods after surgery and their myelopathic symptoms alleviated significantly. Also, sampling the findings of similar cases shows most of the affected patients with CFL due to CPPD deposition have comorbidities including diabetes mellitus and hypertension [2,4], alike to our presented case.

Table 1.

Characteristics of previous case reports of myelopathy due to cervical calcification of ligamentum flavum diagnosed with calcium pyrophosphate dihydrate deposition disease.

Author (year), reference	Number of cases	Sex	Age	Symptoms	Level of involvement	Treatment
Baba et al. (1993), [8]	8	All female	Average: 72 (range: 63–75)	Cervical myeloradiculopathy	Range: C3–4 to C7-T1	En bloc laminectomy (5 cases) and open-door expansive laminoplasty (3 cases)
Shaffrey (1995), [5]	1	Male	43	Upper cervical neck pain	C1–2	En bloc lesion resection with 1 cm muscle around it + laminectomy at C1–3
Pascal-Moussellard (1999), [15]	1	Female	72	Numbness in hands + ataxic gait + lower limb weakness	C4–5	Posterior decompressive C4–5 laminectomy
Yamagami (2000), [18]	1	Male	52	Bilateral numbness of fingers	C5–6	Posterior C4–6 laminectomy
Cabre (2001), [19]	6	5 Females + 1 Male	Average: 73 (range: 64–79)	Subacute myelopathy (5 cases) + asymptomatic (1 case)	Range: C3–4 to C6–7	Decompressive surgery (2 cases)
Muthukumar (2003), [14]	2	Female	70 and 55	Myelopathy	C3–7 and C5–6	Decompressive laminectomy
Lin (2006), [16]	1	Female	74	Progressive weakness in upper extremities	C3–6	C3–6 laminectomy
Yabuki (2008), [9]	3	2 Females + 1 Male	60, 69, 70	Cervical myelopathy	Range: C3–4 to C67	Endoscopic decompression
Mwaka (2009), [3]	26	15 Females + 11 Males	Average: 73.1 (range: 50–86)	Myelopathy (16 cases) + myeloradiculopathy (7 cases) + radiculopathy (3 cases)	Range: C2–3 to C7-T1	En bloc open-door laminoplasty (26 cases) + microscopic laminotomy (3 cases)
Morino (2016), [7]	1	Male	15	Spastic tetraplesia (Coffin–Lowry syndrome) + ataxia	C2–7	C1–7 laminectomy
Chang (2020), [20]	2	1 Female + 1 Male	77 and 68	Cervical myelopathy	C3–4	Decompressive laminectomy
Kimura (2020), [6]	1	Male	78	Mild tetraplegia following falling	C4–5	C3 laminectomy and C4–5 laminoplasty
Lu (2021), [4]	18	4 Females + 14 Males	Average: 75.9 (range: 59–87)	Myelopathy and neck pain (most cases)	Range: C1–2 to C7-T1	Decompression (13 cases) + decompression with fusion (5 cases)
Ehioghae (2022), [2]	2	Female	60 and 70	Cervical myelopathy	C4–7 and C4–5	C4–6 laminoplasty with instrumentation and C3 and C7 partial laminectomies (1 case) + C3–6 laminectomy and instrumented posterior spinal fusion

The diagnosis of CLF due to CPPD is based on the interpretation of the symptoms concurrent with MRI, CT scan, and histopathological examination [2]. Differentiation of CLF due to CPPD and ossification of ligamentum flavum is an important step in the management of the CLF due to CPPD and implementation of proper therapeutic option [2]. CPPD frequently affects multiple levels and often occurs in the cervical spine, while ossification is characterized by a single-level involvement and may occur in any location [1,12,16]. A sagittal CT scan is the best imaging modality for diagnosing CPPD in CLF and demonstrates a high-density mass located in the interlaminar region of the affected section of the ligamentum flavum [2]. MRI is another imaging modality that could be applied in order to diagnose this disorder, and CPPD depositions are characterized by an isointense lesion in the T1-weighted imaging, a mixed density mass in the T2-weighted imaging, and a peripheral enhancement on the post-contrast MRI images [17].

Management of the CLF due to CPPD depends on various factors. In the setting of abnormally high inflammatory factors, patients respond well in one to three weeks of non-surgical treatments such as non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and low-dose colchicine [2]. Due to the high reoccurrence rate of this condition following the pharmacological treatment and sub-optimal response in those with negative inflammatory markers, open decompression with either cervical laminectomy or laminoplasty is considered the gold-standard therapeutic option in CFL due to CPPD deposition disease [2]. Outcomes of surgical intervention are usually favorable, while some symptoms may persist and it depends on various factors including the severity and duration of the lesion [2]. Early decompressive laminectomy is superior to late intervention, and it is showed that laminectomy in the first five months from the onset of the symptoms has the best outcomes and improvement of the neurological function, while surgical intervention after 24 months is associated with the residual parasympathetic dysfunction [2,4]. Decompressive laminectomy may be associated with intraoperative complications such as dural tear due to the adherence of the crystal to the dura matter [6,18].

4. Conclusion

CLF due to CPPD deposition disease is a rare disorder in the cervical spine that causes dorsal spinal cord compression and manifests as myelopathic symptoms. The diagnosis is based on history, physical examination, imaging studies, and histopathological examination. Early surgical intervention, preferably in the first five months of the disease, is associated with favorable outcomes.

Abbreviations

CLF

calcification of ligamentum flavum

CPPD

calcium pyrophosphate dihydrate

CT

computed tomography

MRI

magnetic resonance imaging

TSH

thyroid-stimulating hormone

NSAIDs

non-steroidal anti-inflammatory drugs

CRediT authorship contribution statement

MBA and KK conceptualized the study. SA drafted the initial manuscript. SBF and ES collected the patient's data. HA revised the initial manuscript. All the authors read and approved the final version of manuscript.

Declaration of competing interest

The authors declare that they have no competing interests.

Data availability

The material presented in this study is available from the corresponding author on a reasonable request.