Spine

Antibiotics for spondylodiscitis treatment

Antibiotics for spondylodiscitis treatment

Antibiotic therapy is a pillar of treatment for spondylodiscitis and should be a part of the treatment in all cases. Neurologic deficits, sepsis, intraspinal empyema, the failure of conservative treatment, and spinal instability are all indications for surgical treatment 1).

Randomized trials to guide the selection of the appropriate route, duration, or agent for antibiotic therapy are lacking. Practice is based on retrospective case series, expert opinion, and data extrapolated from animal and laboratory data.

Choice

The choice of antibiotics for the treatment of spondylodiscitis depends on several factors, including the suspected or identified causative microorganism, the severity of the infection, and individual patient factors such as allergies and underlying medical conditions. Empirical antibiotic therapy may be initiated before the exact microorganism is identified based on clinical presentation and risk factors. However, once the causative organism is identified through cultures, antibiotic therapy can be adjusted accordingly. Commonly implicated bacteria in pyogenic spondylodiscitis include Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus or MRSA), Streptococcus species, and Escherichia coli.

Here are some antibiotic options commonly used for the treatment of spondylodiscitis:

Empirical Antibiotics: These antibiotics may be started before the specific microorganism is identified. Common choices include:

Intravenous (IV) antibiotics such as ceftriaxone or cefotaxime plus MRSA coverage with vancomycin or daptomycin. Broad-spectrum antibiotics like piperacillin-tazobactam or meropenem in critically ill patients with risk factors for multidrug-resistant organisms. Specific Antibiotics: Once the causative organism is identified, the antibiotics can be tailored to target that particular microorganism. Antibiotics often used for specific bacteria include:

For Staphylococcus aureus, including MRSA: Vancomycin, daptomycin, or linezolid. For Streptococcus species: Penicillin or ceftriaxone. For Escherichia coli and other Gram-negative bacteria: Ceftriaxone, cefotaxime, or fluoroquinolones.

Duration of Treatment

The duration of antibiotic therapy typically ranges from 6 to 12 weeks or longer, depending on the severity of the infection, the response to treatment, and the presence of complications. Prolonged treatment is often necessary to ensure complete eradication of the infection and to prevent relapse.

The appropriate duration of parenteral antibiotic treatment in patients with pyogenic spondylodiscitis after surgical intervention could be guided by the risk factors. The duration of postoperative intravenous antibiotic therapy could be reduced to 3 weeks for patients without positive blood culture or abscess formation 2)

Intravenous to Oral Transition

Intravenous to Oral Transition: In some cases, patients may be transitioned from intravenous to oral antibiotics once they show clinical improvement and are stable. This transition is based on the patient’s clinical response and the recommendations of the healthcare team.

Monitoring

Monitoring: Close monitoring of the patient’s clinical progress, laboratory markers of infection (such as C-reactive protein and erythrocyte sedimentation rate), and imaging studies is essential to assess treatment efficacy and identify any complications.

It’s important for patients to complete the full course of antibiotics as prescribed to prevent relapse and the development of antibiotic resistance.

A nationwide survey of empiric antibiotic treatment for pyogenic spondylodiscitis revealed a large heterogeneity in the standard of care. A combination of a broad-spectrum-β-lactam antibiotic with an additional glycopeptide antibiotic may be justified 3)

Empirical broad-spectrum antibiotic therapy is linked to increased rates of complications such as Clostridium difficile-associated diarrhea and higher healthcare costs 4), and should be reserved for patients presenting with severe sepsis once blood cultures have been taken.

Test

Question 1: Which of the following is NOT an indication for surgical treatment in spondylodiscitis?

A) Neurologic deficits B) Sepsis C) Intraspinal empyema D) Positive blood culture

Question 2: Why might empirical antibiotic therapy be initiated before the exact microorganism is identified in spondylodiscitis?

A) To prevent antibiotic resistance B) To reduce the duration of antibiotic treatment C) To avoid potential side effects of antibiotics D) To provide immediate treatment while awaiting culture results

Question 3: Which of the following is a commonly implicated bacterium in pyogenic spondylodiscitis?

A) Candida albicans B) Escherichia coli C) Mycobacterium tuberculosis D) Streptococcus pneumoniae

Question 4: What is the typical duration of antibiotic therapy for spondylodiscitis?

A) 1-2 weeks B) 2-4 weeks C) 4-6 weeks D) 6-12 weeks or longer

Question 5: Under what circumstances can intravenous antibiotic therapy be reduced to 3 weeks after surgical intervention in spondylodiscitis?

A) Positive blood culture B) Abscess formation C) Clinical improvement D) All of the above

Question 6: When might a patient with spondylodiscitis be transitioned from intravenous to oral antibiotics?

A) Immediately upon diagnosis B) After surgical intervention C) Once blood cultures are taken D) When they show clinical improvement and are stable

Question 7: Why is close monitoring of patients with spondylodiscitis essential during treatment?

A) To assess treatment efficacy B) To prevent antibiotic resistance C) To reduce healthcare costs D) To guide surgical interventions

Question 8: What should patients do to prevent relapse and the development of antibiotic resistance during spondylodiscitis treatment?

A) Start antibiotic treatment as soon as possible B) Take antibiotics until they feel better C) Complete the full course of antibiotics as prescribed D) Reduce the antibiotic dose gradually

Question 9: In what situation might a combination of a broad-spectrum-β-lactam antibiotic with an additional glycopeptide antibiotic be justified in spondylodiscitis treatment?

A) In all cases B) When blood cultures are negative C) In patients with severe sepsis once blood cultures have been taken D) In patients with mild infection

Question 10: What is the potential drawback of starting empirical broad-spectrum antibiotic therapy in spondylodiscitis?

A) Reduced treatment efficacy B) Increased rates of Clostridium difficile-associated diarrhea C) Lower healthcare costs D) Shorter hospital stays

Answers:

D) Positive blood culture D) To provide immediate treatment while awaiting culture results B) Escherichia coli D) 6-12 weeks or longer D) All of the above D) When they show clinical improvement and are stable A) To assess treatment efficacy C) Complete the full course of antibiotics as prescribed C) In patients with severe sepsis once blood cultures have been taken B) Increased rates of Clostridium difficile-associated diarrhea

1)

Herren C, Jung N, Pishnamaz M, Breuninger M, Siewe J, Sobottke R. Spondylodiscitis: Diagnosis and Treatment Options. Dtsch Arztebl Int. 2017 Dec 25;114(51-52):875-882. doi: 10.3238/arztebl.2017.0875. PMID: 29321098; PMCID: PMC5769318.
2)

Li YD, Wong CB, Tsai TT, Lai PL, Niu CC, Chen LH, Fu TS. Appropriate duration of post-surgical intravenous antibiotic therapy for pyogenic spondylodiscitis. BMC Infect Dis. 2018 Sep 17;18(1):468. doi: 10.1186/s12879-018-3377-1. PMID: 30223785; PMCID: PMC6142394.
3)

Lang S, Walter N, Neumann C, Bärtl S, Simon M, Ehrenschwender M, Hitzenbichler F, Alt V, Rupp M. Aktuelle Praxis der empirischen Antibiotikatherapie bei Spondylodiszitis [Current practice of empiric antibiotic treatment for spondylodiscitis]. Orthopadie (Heidelb). 2022 Jul;51(7):540-546. German. doi: 10.1007/s00132-022-04240-x. Epub 2022 Apr 7. PMID: 35391543; PMCID: PMC9249703.
4)

Lillie P, Thaker H, Moss P, et al. Healthcare-associated discitis in the era of antimicrobial resistance. J Clin Rheumatol 2008;14:234-7.

Test your knowledge about Foramen magnum stenosis in Achondroplasia

What is the significance of foramen magnum stenosis in achondroplasia?

a) It is a cosmetic issue with no medical consequences.

b) It can lead to compression of the brainstem and spinal cord, resulting in severe health problems.

c) It only affects adults with achondroplasia.

d) It is completely unrelated to achondroplasia.

What contributes to the narrowing of the foramen magnum in infants with achondroplasia?

a) Growth spurt during adolescence

b) Restricted growth in the first 2 years of life and premature closure of skull plate synchondroses

c) Diet and nutrition

d) Lack of physical activity

How can foramen magnum stenosis be diagnosed?

a) By physical examination alone

b) Through a blood test

c) By acquiring effective neuroimaging

d) By measuring head circumference

Why is standardized imaging protocol essential for children with achondroplasia?

a) It helps in diagnosing achondroplasia itself.

b) It ensures that clinically useful neuroimaging is performed and reduces unnecessary radiation exposure.

c) It is required for insurance purposes.

d) It helps in determining the child's future height.

How did the European Achondroplasia Forum (EAF) contribute to the management of foramen magnum stenosis?

a) By recommending surgery for all cases

b) By providing guidelines for the detection and management of foramen magnum stenosis

c) By developing a new drug

d) By organizing awareness campaigns

What is the Achondroplasia Foramen Magnum Score (AFMS) used for?

a) To assess the severity of sleep apnea in achondroplasia patients

b) To diagnose achondroplasia in infants

c) To evaluate the severity of foramen magnum stenosis in infants with achondroplasia

d) To measure head circumference

What does a high Total Apnea and Hypopnea Index (TAHI) indicate in relation to foramen magnum stenosis?

a) It suggests that the patient has no stenosis.

b) It indicates severe foramen magnum stenosis.

c) It has no correlation with foramen magnum stenosis.

d) It indicates a need for dietary changes.

What is the sensitivity of clinical examination and CRS (cardiorespiratory sleep studies) for predicting the effects of foramen magnum stenosis on the spinal cord?

a) High sensitivity

b) Low sensitivity

c) No sensitivity

d) Moderate sensitivity

How can routine screening with MRI using AFMS benefit infants with achondroplasia?

a) It helps in cosmetic improvements.

b) It has no benefits.

c) It aids in detecting early spinal cord changes and can reduce infant morbidity and mortality.

d) It is only useful for diagnosing other medical conditions.

What percentage of infants required neurosurgery in the study mentioned in the text?

a) 0%

b) 10%

c) 25%

d) 50%

Answers:

b) It can lead to compression of the brainstem and spinal cord, resulting in severe health problems.
b) Restricted growth in the first 2 years and premature closure of skull plate synchondroses
c) By acquiring effective neuroimaging
b) It ensures that clinically useful neuroimaging is performed and reduces unnecessary radiation exposure.
b) By providing guidelines for the detection and management of foramen magnum stenosis
c) To evaluate the severity of foramen magnum stenosis in infants with achondroplasia
b) It indicates severe foramen magnum stenosis.
b) Low sensitivity
c) It aids in detecting early spinal cord changes and can reduce infant morbidity and mortality.
c) 25%

Adult spinal deformity surgery outcome

Adult spinal deformity surgery outcome

Latest PubMed Adult spinal deformity surgery outcome Articles

see also Adult spinal deformity surgery complications

The outcomes of adult spinal deformity surgery can vary depending on various factors, including the specific condition being treated, the severity of the deformity, the patient’s overall health, and the surgical techniques used. Here are some general aspects to consider regarding the outcomes of adult spinal deformity surgery:

Improvement in Spinal Alignment: The primary goal of surgery is to restore a more balanced and aligned spinal column. This can help alleviate symptoms such as pain, difficulty in maintaining proper posture, and problems with mobility. Surgery can correct the curvature, rotation, and overall alignment of the spine, leading to improved spinal balance.

Pain Reduction: Adult spinal deformities often cause chronic back pain and discomfort. Surgery can help alleviate pain by decompressing compressed nerves, stabilizing the spine, and reducing stress on the surrounding structures. Studies have shown that many patients experience significant pain relief following surgery, leading to an improved quality of life.

Functional Improvement: Surgery can enhance the patient’s ability to perform daily activities and improve their functional capacity. By correcting spinal alignment, individuals may experience improved mobility, better balance, and an increased ability to participate in physical activities.

Neurological Improvement: In cases where spinal deformity is causing nerve compression or spinal cord compression, surgery can help relieve the pressure on neural structures. This can lead to improvements in neurological function, such as reduced numbness, weakness, or other symptoms associated with nerve compression.

Psychological Well-being: Adult spinal deformities can have a significant impact on a person’s self-image, body image, and overall psychological well-being. Corrective surgery can improve body image, enhance self-esteem, and reduce psychological distress associated with the deformity.

Potential Risks and Complications: Like any surgical procedure, adult spinal deformity surgery carries some risks and potential complications. These may include infection, bleeding, blood clots, implant-related problems, nerve damage, and the potential need for revision surgery. The overall success of the surgery and the extent of the outcomes will depend on various individual factors.

A prospective multicenter analysis demonstrated that operative ASD treatment provided significant improvement in health-related quality of life at a minimum 3-year follow-up (mean 4.1 years), suggesting that the benefits of surgery for ASD remain durable at longer follow-up. These findings should prove useful for counseling, cost-effectiveness assessments, and efforts to improve the safety of care 1)

The Scoli-RISK-1 study enrolled 272 ASD patients undergoing surgery from 15 centers. Inclusion criteria was Cobb angle of >80°, corrective osteotomy for congenital or revision deformity, and/or 3-column osteotomy. The following PROs were measured prospectively at intervals up to 5-years postoperative: ODI, SF36-PCS/MCS, SRS-22, NRS back/leg. Among patients with 5-year follow-up, comparisons were made from both baseline and 2-years postoperative to 5-years postoperative. PROs were analyzed using mixed models for repeated measures.

Results: Seventy-seven patients (28.3%) had 5-year follow-up data. Comparing baseline to 5-year data among these 77 patients, significant improvement was seen in all PROs: ODI (45.2 vs. 29.3, P < 0.001), SF36-PCS (31.5 vs. 38.8, P < 0.001), SF36-MCS (44.9 vs. 49.1, P = 0.009), SRS-22-total (2.78 vs. 3.61, P < 0.001), NRS-back pain (5.70 vs. 2.95, P < 0.001) and NRS leg pain (3.64 vs. 2.62, P = 0.017). In the 2 to 5-year follow-up period, no significant changes were seen in any PROs. The percentage of patients achieving MCID from baseline to 5-years were: ODI (62.0%) and the SRS-22r domains of function (70.4%), pain (63.0%), mental health (37.5%), self-image (60.3%), and total (60.3%). Surprisingly, mean values (P > 0.05) and proportion achieving MCID did not differ significantly in patients with major surgery-related complications compared to those without.

Conclusions: After complex ASD surgery, significant improvement in PROs were seen at 5-years postoperative in ODI, SF36-PCS/MCS, SRS-22r, and NRS-back/leg pain. No significant changes in PROs occurred during the 2 to 5-year postoperative period. Those with major surgery-related complications had similar PROs and proportion of patients achieving MCID as those without these complications 2).

Coronal balance is a major factor impacting the outcomes in adult spinal deformity surgery (ASD). The Obeid-coronal malalignment classification (O-CM) has been proposed to improve the coronal alignment in adult spinal deformity surgery. The aim of the study of Baroncini et al. was to investigate whether a postoperative coronal malalignment (CM) < 20 mm and adherence to the O-CM classification could improve surgical outcomes and decrease the rate of mechanical failure in a cohort of ASD patients.

In this multicenter retrospective analysis of prospectively collected data on all ASD patients who underwent surgical management and had a preoperative CM > 20 mm and a 2-year follow-up. Patients were divided into two groups according to whether or not surgery had been performed in adherence to the guidelines of the O-CM classification and according to whether or not the residual CM was < 20 mm. The outcomes of interest were radiographic data, rate of mechanical complications, and Patient-Reported Outcome Measures.

At 2 years, adherence to the O-CM classification led to a lower rate of mechanical complications (40 vs. 60%). A coronal correction of the CM < 20 mm allowed for a significant improvement in SRS-22 and SF-36 scores and was associated with 3.5 times greater odds of achieving the minimal clinically important difference for the SRS-22.

Adherence to the O-CM classification could reduce the risk of mechanical complications 2 years after ASD surgery. Patients with a residual CM < 20 mm showed better functional outcomes and 3.5 times greater odds of achieving the MCID for the SRS-22 score 3).

Elderly patient outcomes were inconsistent in the published studies. Overall, most elderly patients obtained favorable outcomes with low operative mortality following surgery for adult spinal deformity 4)

1)

Elias E, Bess S, Line B, Lafage V, Lafage R, Klineberg E, Kim HJ, Passias PG, Nasser Z, Gum JL, Kebaish K, Eastlack R, Daniels AH, Mundis G, Hostin R, Protopsaltis TS, Soroceanu A, Hamilton DK, Kelly MP, Gupta M, Hart R, Schwab FJ, Burton D, Ames CP, Shaffrey CI, Smith JS; International Spine Study Group. Outcomes of operative treatment for adult spinal deformity: a prospective multicenter assessment with mean 4-year follow-up. J Neurosurg Spine. 2022 Apr 29:1-10. doi: 10.3171/2022.3.SPINE2295. Epub ahead of print. PMID: 35535835.
2)

Zuckerman SL, Cerpa M, Lenke LG, Shaffrey CI, Carreon LY, Cheung KMC, Kelly MP, Fehlings MG, Ames CP, Boachie-Adjei O, Dekutoski MB, Kabeaish KM, Lewis SJ, Matsuyama Y, Pellisé F, Qiu Y, Schwab FJ, Smith JS; AO Spine Knowledge Forum Deformity and SRS Scoli-RISK-1 Study Group. Patient-Reported Outcomes After Complex Adult Spinal Deformity Surgery: 5-Year Results of the Scoli-Risk-1 Study. Global Spine J. 2022 Oct;12(8):1736-1744. doi: 10.1177/2192568220988276. Epub 2021 Feb 9. PMID: 33557622; PMCID: PMC9609523.
3)

Baroncini A, Frechon P, Bourghli A, Smith JS, Larrieu D, Pellisé F, Pizones J, Kleinstueck F, Alanay A, Kieser D, Cawley DT, Boissiere L, Obeid I; European Spine Study Group (ESSG). Adherence to the Obeid coronal malalignment classification and a residual malalignment below 20 mm can improve surgical outcomes in adult spine deformity surgery. Eur Spine J. 2023 Jul 2. doi: 10.1007/s00586-023-07831-0. Epub ahead of print. PMID: 37393421.
4)

Drazin D, Shirzadi A, Rosner J, Eboli P, Safee M, Baron EM, Liu JC, Acosta FL Jr. Complications and outcomes after spinal deformity surgery in the elderly: review of the existing literature and future directions. Neurosurg Focus. 2011 Oct;31(4):E3. doi: 10.3171/2011.7.FOCUS11145. PMID: 21961866.

Split cord malformation

Split cord malformation

General information

There is no uniformly accepted nomenclature for malformations characterized by duplicate or split spinal cords.

The term split cord malformation (SCM) was first introduced in 1992 by Pang et al., in an attempt to resolve the confusion existing in the pathological definition and the clinical significance of previously existing terminologies in the literature, diastematomyelia and diplomyelia, and the inconsistent usage of these two terms.

Pang et al have proposed the following. The term split cord malformation (SCM) should be used for all double spinal cords, all of which appear to have a common embryologic etiology 1).

The term split cord malformation (SCM) should be used for all double spinal cords, all of which appear to have a common embryologic etiology.

Split cord malformation (SCM) has a rich history and has intrigued physicians for over 200 years. Many well-known figures from the past such as Hans Chiari and Friedrich Daniel von Recklinghausen, both pathologists, made early postmortem descriptions of SCM. With the advent of MRI, these pathological embryological derailments can now often be detected and appreciated early and during life. Our understanding and ability to treat these congenital malformations as well as the terminology used to describe them have changed over the last several decades 2).

Classification

Split cord malformations (SCMs) are among the rare congenital spinal anomalies. In 1992, Pang et al, proposed the “Unified theory of embryogenesis” and explained the formation of SCM type 1 and 2. This theory has been widely accepted in the neurosurgical literature, backed by several studies. However, there have been reports in the literature that defy both, the classification as well as formation of SCMs, based on the unified theory of embryogenesis.

Pang et al. classified spinal cord duplication anomalies into types I and II. The first is characterized by two hemicords, each contained within its own dural sac, and separated by an osteocartillaginous septum. Type II is defined by two hemicords in the same dural sac, separated by a fibrous septum 3) 4).

Type I split cord malformation

Type 1.5 split cord malformation ? 5).

Type 2 split cord malformation.

Much confusion still exists concerning the pathological definitions and clinical significance of double spinal cord malformations. Traditional terms used to describe the two main forms of these rare malformations, diastematomyelia, and diplomyelia, add to the confusion by their inconsistent usage, ambiguities, and implications of their dissimilar embryogenesis. Based on the detailed radiographic and surgical findings of 39 cases of double cord malformations and the autopsy data on two other cases, this study endorses a new classification for double cord malformations and proposes a unified theory of embryogenesis for all their variant forms and features. The new classification recommends the term split cord malformation (SCM) for all double spinal cords. A Type I SCM consists of two hemicords, each contained within its own dural tube and separated by a dura-sheathed rigid osseocartilaginous median septum. A Type II SCM consists of two hemicords housed in a single dural tube separated by a nonrigid, fibrous median septum. These two essential features necessary for typing, the state of the dural tube and the nature of the median septum, do not ever overlap between the two main forms and can always be demonstrated by imaging studies so that accurate preoperative typing is always possible. All other associated structures in SCM such as paramedian nerve roots, myelomeningoceles manqué, and centromedian vascular structures frequently do overlap between types and are not reliable typing criteria. The unified theory of embryogenesis proposes that all variant types of SCMs have a common embryogenetic mechanism. Basic to this mechanism is the formation of adhesions between ecto- and endoderm, leading to an accessory neurenteric canal around which condenses an endomesenchymal tract that bisects the developing notochord and causes formation of two hemineural plates. The altered state of the emerging split neural tube and the subsequent ontogenetic fates of the constituent components of the endomesenchymal tract ultimately determine the configuration and orientation of the hemicords, the nature of the median septum, the coexistence of various vascular, lipomatous, neural, and fibrous oddities within the median cleft, the high association with open myelodysplastic and cutaneous lesions, and the seemingly unlikely relationship with fore and midgut anomalies. The multiple facets of this theory are presented in increasing complexity against the background of known embryological facts and theories; the validity of each facet is tested by comparing structures and phenomena predicted by the facet with actual radiographic, surgical, and histopathological findings of these 41 cases of SCM 6).

A new classification system proposed by Mahapatra and Gupta further divides type I SCM into four categories: Ia, bony spur in the center with equally duplicated cord above and below the spur; type Ib, bony spur at the superior pole with no space above and a large duplicated cord below; Ic, bony spur at the lower pole with a large duplicated cord above; and Id, bony spur straddling the bifurcation with no space above or below the spur 7).

Treatment

The risk of neurological deficits developing increases with age; hence, all patients with SCM should be surgically treated prophylactically even if they are asymptomatic 8).

see Type I Split Cord Malformation treatment.

Outcome

SCMs can lead to progressively worsening scoliosis and gait difficulties if left untreated.

Case series

From 1990 to 2014, 37 patients were operated. Five situations lead to the diagnosis (orthopedic disorders (n = 8), orthopedic and neurological disorders (n = 16), pure neurological disorders (n = 5), no symptoms except cutaneous signs (n = 7), antenatal diagnosis (n = 1)). Scoliosis was the most common associated condition. The level of the spur was always under T7 except in one case. There were more type I (n = 22) than type II (n = 15) SCM.

Patients with preoperative neurological symptoms (n = 21) were improved in 71.4%. Five out of nine patients that had preoperative bladder dysfunction were improved. Eleven patients needed surgical correction of the scoliosis.

For us, the surgical procedure is mandatory even in case of asymptomatic discovery in order to avoid late clinical deterioration. In any case, the filum terminale need to be cut in order to untether completely the spinal cord. In case a surgical correction of a spinal deformity is needed, we recommend a two-stage surgery, for both SCM type. The SCM surgery can stop the evolution of scoliosis and it may just need an orthopedic treatment with a brace 9).

Over a 16-year period, Mahapatra encountered 300 cases of SCM at AIIMS. Over the same period, more than 1500 cases of NTD were managed. SCM was noticed in 20% of cases with NTD. Skin stigmata were noted in two-third of the cases, and scoliosis and foot deformity were observed in 50% and 48% cases, respectively. Motor and sensory deficits were observed in 80% and 70% cases, respectively. Commonest site affected was lumbar or dorsolumbar (55% and 23%, respectively). In 3% cases, it was cervical in location. Magnetic resonance imaging (MRI) scan revealed a large number of anomalies like lipoma, neuroenteric cyst, thick filum and dermoid or epidermoid cysts. All the patients were surgically treated. In type I, bony spurs were excised, and in type II, bands tethering the cord were released. Associated anomalies were managed in the same sitting. Patients were followed up from 3 months to 3 years.

Overall improvement was noticed in 50% and stabilization in 44% cases and deterioration of neurological status was recorded in 6% cases. However, 50% of those who deteriorated improved to preop status prior to discharge, 7-10 days following surgery.

SCM is rare and not many large series are available. They operated 300 cases and noticed a large number of associated anomalies and also multilevel and multisite splits. Improvement or stabilization was noted in 94% and deterioration in 6% cases. They recommended prophylactic surgery for our asymptomatic patients 10).

Mahapatra et al. in 2005 reported the first 254 cases of SCM treated surgically during a period of 16 years.

Patients’ demographic profiles, imaging studies, operative details, complications, and surgical outcomes were evaluated retrospectively. A new classification based on intraoperative findings is proposed. The mean age of the patients was 7.3 years (female/male 1.5:1). Type I SCM was seen in 156 patients (61.4%) and 98 patients (38.6%) had Type II SCM. Skin stigmata were present in 153 cases (60%); hypertrichosis, being the most common, was seen in 82 cases (32.3%). Asymmetrical lower-limb weakness and sphincter disturbances were present in 173 (68.1%) and 73 (33%) cases, respectively. Of the symptomatic cases, 39% (68 of 173) showed improvement in motor power, 57.9% (33 of 57) experienced sensory improvement, and 27.3% (20 of 73) regained continence. None of the 38 patients in the asymptomatic group had postoperative neurological deterioration. The neurological status was unchanged in 63% of the cases. A new subclassification of Type I SCM is proposed, based on the intraoperative location of a bone spur causing the split, which may have a bearing on surgical dissection and outcome. Based on the authors’ experience with 25 cases of Type I SCM, they have classified the disorder into four subtypes: Type Ia, bone spur located in the center with duplicated cord above and below the spur (12 cases); Type Ib, bone spur at the superior pole with no space above it (four cases); Type Ic, bone spur at the lower pole with large duplicated cord above (three cases); and Type Id, bone spur straddling the bifurcation with no space above or below the spur (six cases). The risk of injury to the hemicords is highest in the Id subtype (four of six patients in this group deteriorated neurologically in the present series, whereas none with subtypes Ia-c worsened).

This is the largest series on SCMs so far reported in the world literature The risk of neurological deficits developing increases with age; hence, all patients with SCM should be surgically treated prophylactically even if they are asymptomatic. This new classification is easy to use and remember and takes into account the use of intraoperative findings that may have a bearing on surgical outcome 11).

Retrospective analysis of 19 cases of SCM, thirteen were grouped under (Pang) type I and 6 in type II. Their ages ranged from 1 month to 9 years (mean 3.5 years). 14 of these were male children. The NOS without neurological signs was detected in 6 cases whereas pure neurological signs without NOS were seen in 8 patients. However, the rest 5 had a mixed picture of NOS and neurological dysfunction. Nine of 19 cases presented with cutaneous stigmata, mainly in the form of a hairy patch. 18 cases had other associated craniospinal anomalies i.e. hydrocephalus, meningomyelocele, syrinx, dermoid, teratoma, etc. Detethering of the cord was done in all cases by the removal of fibrous/bony septum. Associated anomalies were also treated accordingly. Follow up of these cases ranged from 6 months to 6 years. Six cases of NOS group neither showed deterioration nor improvement, and remained static on follow up. However, four of 8 children with neurological signs showed improvement in their motor weakness, and 1 in saddle hypoaesthesia as well as bladder/bowel function. In 5 cases of a mixed group, two had improvement in their weakness and one in hypoaesthesia, but no change was noticed in NOS of this group as well. Hence surgery seemed to be effective, particularly in patients with neurological dysfunction 12).

Proctor and Scott reviewed the results obtained in 16 patients in whom the senior author performed surgery over a 13-year period (average length of follow up almost 8 years).

Presentation, surgical approach, and the outcome are evaluated, and the long-term outcome of neurological status, pain, bowel/bladder disturbance, and spinal deformities are emphasized.

The primary conclusion is that patients with SCM generally tolerate surgery well and experience few complications. Neurological deterioration is rare except in cases in which retethering occurs, (two patients in this series). Although impaired bowel and bladder function was stabilized or improved and pain was reliably relieved postoperatively, preexisting vertebral column deformities usually progressed after surgery and, in most cases, required spinal fusion 13).

In 2000 Forty-eight patients of split cord malformation operated during a six years period were studied clinically and radiologically.

The mean age of symptomatic patients was more than that of asymptomatic ones (6.85 years vs 2.03 years). The dorsolumbar and lumbar regions were most frequently involved and in three cases the cervical spine was affected. Weakness of lower limbs (n=37), muscle atrophy (n=23) and gait disturbance were the most common indicators of motor system involvement. The sensory complaints were mainly hypoesthesia (n=16), trophic ulcer (n=4) and autoamputation (n=3). Hypertrichiosis was the most common cutaneous marker present alone or in combination with other markers in 21 cases. MRI, done in all cases, correctly established the diagnosis. Additional lesions causing tethering were seen in 50% cases and were simultaneously treated. Associated Chiari malformation was seen in 12%. Of the 42 symptomatic patients, 21 improved, in 17 (40%) the neurological deficits stabilized and 4 showed deterioration. Cerebrospinal fluid fistula occurred in 4 patients and 3 had wound infections. Among the asymptomatic patients none had neurological deterioration postoperatively.

Split cord malformations are rare spinal cord disorders. Complete neural axis should be scanned at the first instance to determine associated lesions. Good results can be expected in about 90% patients with minimal complications 14).

Thirty-nine patients with split cord malformations (SCM) were studied in detail with respect to their clinical, radiographic, and surgical findings as well as their outcome data. Eight patients were adults and 31 patients were children. According to the classification endorsed by Part I of the SCM study, 19 patients had Type I SCM (6 adults and 13 children), 18 patients had Type II SCM (2 adults and 16 children), and 2 patients had composite SCM with both lesion types situated in tandem. Six SCMs were cervical, 2 were thoracic, and 31 were in the lumbar region. All 8 adults had pain and progressive sensorimotor deficits at diagnosis. Only 16 of the 31 children had symptoms, and among these, 14 had progressive sensorimotor deficits, but only 6 had pain. The difference in the clinical picture between adults and children is similar to that described in the tethered cord syndrome, except for left-right functional discrepancy, which was prominent in 8 children with SCM but rarely seen in tethered cord syndrome due to other causes. Cutaneous manifestations of either occult or open dysraphic states were present in all but 3 patients; hypertrichosis was by far the best predictor of an underlying SCM, being found in 56% in the series. Neurological deterioration in SCM was independent of the lesion type: the Type I:Type II ratio for symptomatic progression was 13:11. It was also independent of the location of the lesion: 67% of patients with cervical SCMs had symptomatic progression versus 64% of patients with thoracolumbar lesions. High-resolution, thin cut, axial computed tomographic myelography using bone algorithms was more sensitive than magnetic resonance imaging in defining the anatomical details of the SCM. Radiographic classifications of the SCM, using the nature of the median septum and the number of dural tubes as criteria, was always possible without ambiguity. However, whereas every Type I bone septum was identified preoperatively, only 5 Type II fibrous septa were revealed by preoperative imaging, even though a fibrous septum and/or other fibroneurovascular bands were found tethering the hemicords in every Type II case at surgery. Complete imaging studies also showed that all lumbar SCMs had low-lying coni and at least one additional tethering lesion besides the split cords, whereas only 1 of 7 cervical and high thoracic SCMs had a low conus and a second tethering lesion. The surgical goal for SCM was release of the tethered hemicords by eliminating the bone spurs, dural sleeves, fibrous septa, or any fibroneurovascular bands (myelomeningoceles manqué) that might be transfixing the split cord. Type I cases were technically more difficult and had a slightly higher surgical morbidity than Type II cases, especially if an oblique bone septum had asymmetrically divided the cord into one larger hemicord and one smaller, hence, very delicate, hemicord 15).

Case reports

Nazarali et al. reported on two patients who atypically presented with SCM in adulthood and reviewed previous reports 16).

A rare case of a child with a complex spina bifida with two different levels of split cord malformation (SCM) type 1 and single-level type 2, a nonterminal myelocystocele, coccygeal dermal sinus, bifid fatty filum and hydrocephalus, which substantiates the neurenteric canal theory and have further tried to highlight the importance of complete Magnetic resonance imaging (MRI) screening of the whole spine and brain with SCM to rule out other associated conditions. The patient was admitted with a leaking myelocystocele with bilateral lower limb weakness. MRI of the whole spine with a screening of brain was done. Patient underwent 5 operations in the same sitting- (According to classification given by Mahapatra et al.) removal of SCM type 1a at D7-8; removal of SCM type1c at L2-3; removal of SCM type 2 at D10; repair of nonterminal myelocystocele at D6-D10; low-pressure ventriculoperitoneal shunt on right side with excision of dermal coccygeal sinus; and, excision of bifid fatty filum. The clinic radiological findings in our patient further substantiate the multiple accessory neuroenteric canal theory in the development of a composite type of SCM. The physical and neurological signs of SCM and nonterminal myelocystocele should prompt the neurosurgeon to consider performing the screening MRI of the whole spine with the brain to rule out other composite types of SCM and hydrocephalus 17).

A 78-year-old woman presented for evaluation of back pain, urinary dysfunction, leg weakness and progressive equinovarus foot deformity. She reported that shortly after her birth in 1924, she underwent resection of a subcutaneous ‘cyst’ in the lower lumbar area. Seven years prior to evaluation at our institution, she had undergone bilateral total knee arthroplasty for osteoarthritis. After the procedure, she began to experience severe low back pain that radiated into her legs. Weakness of the foot inverters, urinary dysfunction and worsening bilateral equinovarus foot deformity developed in the years following the surgery. MRI revealed a split cord malformation with a tethered spinal cord. Because of the patient’s age and poor medical condition, her symptoms were managed conservatively. This case demonstrates symptomatic deterioration in an elderly patient with a tethered spinal cord after many years of clinical stability 18).

A 32-year-old man with the adult-onset of impairment of sacral functions with lumbar fibrous diastematomyelia is reported. Surgical release of the spinal cord was followed by improvement of the patient’s function 19).

References

1) , 6)

Pang D, Dias MS, Ahab-Barmada M. Split cord malformation: Part I: A unified theory of embryogenesis for double spinal cord malformations. Neurosurgery. 1992 Sep;31(3):451-80. Review. PubMed PMID: 1407428.
2)

Saker E, Loukas M, Fisahn C, Oskouian RJ, Tubbs RS. Historical Perspective of Split Cord Malformations: A Tale of Two Cords. Pediatr Neurosurg. 2017;52(1):1-5. PubMed PMID: 27806370.
3)

Pang D, Dias MS, Ahab-Barmada M. Split cord malformation: Part I. A unified theory of embryogenesis for double spinal cord malformations. Neurosurgery 1992;31:451-480.
4)

Pang D, Dias MS, Ahab-Barmada M. Split cord malformation. Part II: Clinical syndrome. Neurosurgery 1992;31:481-500.
5)

Sun M, Tao B, Luo T, Gao G, Shang A. We Are Cautious to Use the Term, ‘Split Cord Malformation Type 1.5’. J Korean Neurosurg Soc. 2022 Aug 22. doi: 10.3340/jkns.2022.0058. Epub ahead of print. PMID: 35989187.
7) , 8) , 11)

Mahapatra AK, Gupta DK. Split cord malformations: a clinical study of 254 patients and a proposal for a new clinical-imaging classification. J Neurosurg. 2005 Dec;103(6 Suppl):531-6. PubMed PMID: 16383252.
9)

Beuriat PA, Di Rocco F, Szathmari A, Mottolese C. Management of split cord malformation in children: the Lyon experience. Childs Nerv Syst. 2018 May;34(5):883-891. doi: 10.1007/s00381-018-3772-3. Epub 2018 Mar 26. Erratum in: Childs Nerv Syst. 2018 May 17;:. Pierre-Aurelien, Beuriat [corrected to Beuriat, Pierre-Aurélien]; Federico, Di Rocco [corrected to Di Rocco, Federico]; Alexandru, Szathmari [corrected to Szathmari, Alexandru]; Carmine, Mottolese [corrected to Mottolese, Carmine]. PubMed PMID: 29582170.
10)

Mahapatra AK. Split cord malformation – A study of 300 cases at AIIMS 1990-2006. J Pediatr Neurosci. 2011 Oct;6(Suppl 1):S41-5. doi: 10.4103/1817-1745.85708. PubMed PMID: 22069430; PubMed Central PMCID: PMC3208912.
12)

Kumar R, Bansal KK, Chhabra DK. Split cord malformation (scm) in paediatric patients: outcome of 19 cases. Neurol India. 2001 Jun;49(2):128-33. PubMed PMID: 11447430.
13)

Proctor MR, Scott RM. Long-term outcome for patients with split cord malformation. Neurosurg Focus. 2001 Jan 15;10(1):e5. PubMed PMID: 16749757.
14)

Jindal A, Mahapatra AK. Split cord malformations–a clinical study of 48 cases. Indian Pediatr. 2000 Jun;37(6):603-7. PubMed PMID: 10869139.
15)

Pang D. Split cord malformation: Part II: Clinical syndrome. Neurosurgery. 1992 Sep;31(3):481-500. Review. PubMed PMID: 1407429.
16)

Nazarali R, Lyon K, Cleveland J, Garrett D Jr. Split cord malformation associated with scoliosis in adults. Proc (Bayl Univ Med Cent). 2019 Mar 27;32(2):274-276. doi: 10.1080/08998280.2019.1573624. eCollection 2019 Apr. Review. PubMed PMID: 31191152; PubMed Central PMCID: PMC6541173.
17)

Khandelwal A, Tandon V, Mahapatra AK. An unusual case of 4 level spinal dysraphism: Multiple composite type 1 and type 2 split cord malformation, dorsal myelocystocele and hydrocephalous. J Pediatr Neurosci. 2011 Jan;6(1):58-61. doi: 10.4103/1817-1745.84411. PubMed PMID: 21977092; PubMed Central PMCID: PMC3173919.
18)

Pallatroni HF, Ball PA, Duhaime AC. Split cord malformation as a cause of tethered cord syndrome in a 78-Year-old female. Pediatr Neurosurg. 2004 Mar-Apr;40(2):80-3. PubMed PMID: 15292638.
19)

Chehrazi B, Haldeman S. Adult onset of tethered spinal cord syndrome due to fibrous diastematomyelia: case report. Neurosurgery. 1985 May;16(5):681-5. PubMed PMID: 3889701.

AO Spine Upper Cervical Injury Classification System

AO Spine Upper Cervical Injury Classification System

Latest AO Spine Upper Cervical Injury Classification System PubMed related Articles

see AO Spine Upper Cervical Injury Classification System

In the pediatric population. While moderate to substantial agreement was found, limitations to applying the Upper Cervical Injury Classification System to the pediatric population exist, and thus the UCCS can be considered a starting point for developing a pediatric classification 1)

Accuracy

Early phase validation demonstrated classification of upper cervical spine injuries using the AO Spine Upper Cervical Injury Classification System to be accurate, reliable, and reproducible. Greater than 80% accuracy was detected for injury classification. The intraobserver reproducibility was excellent, while the interobserver reliability was substantial 2)

The AO Spine Upper Cervical Injury Classification System can be applied with high accuracy, interobserver reliability, and intraobserver reproducibility. However, lower classification accuracy and reliability were found in regions of Africa and Central/South America, especially for severe atlas injuries (IIB and IIC) and atypical hangman’s type fractures (IIIB injuries) 3).

A study reported an acceptable reproducibility of the new AO UCCS and safety in recommending the treatment. Further clinical studies with a larger patient sample, multicenter and international, are necessary to sustain the universal and homogeneity quality of the new AO UCCS 4)

Type A

AO Spine Upper Cervical Injury Classification System Type A

I. Occipital Condyle and Craniocervical junction. Isolated bony injury (condyle) Isolated bony injury (condyle)

II. C1 Ring and C1-2 Joint. Isolated bony only (arch)

III. C2 and C2-3 Joint. Bony injury only without ligamentous, tension band, discal injury

Type B

Type B injuries are the most difficult injury type to correctly classify. They are classified with greater reliability and classification accuracy when evaluated by academic surgeons, hospital-employed surgeons, and surgeons associated with higher-level trauma centers (I or II/III) 5)

Atlas fracture

see also Atlas fracture classification

Axis fracture

see also Axis fracture classification,

AOSpine subaxial cervical spine injury classification system

AOSpine subaxial cervical spine injury classification system.

The AO classification according to Magerl et al. is used for the subaxial spine, whereas the upper cervical spine should be classified separately because the anatomy is different at each level 6)

1)

O’Neill NP, Mo AZ, Miller PE, Glotzbecker MP, Li Y, Fletcher ND, Upasani VV, Riccio AI, Spence D, Garg S, Krengel W, Birch C, Hedequist DJ. The Reliability of the AO Spine Upper Cervical Classification System in Children: Results of a Multi-Center Study. J Pediatr Orthop. 2023 Apr 1;43(4):273-277. doi: 10.1097/BPO.0000000000002363. Epub 2023 Jan 30. PMID: 36706430.
2)

Vaccaro AR, Lambrechts MJ, Karamian BA, Canseco JA, Oner C, Vialle E, Rajasekaran S, Dvorak MR, Benneker LM, Kandziora F, El-Sharkawi M, Tee JW, Bransford R, Joaquim AF, Muijs SPJ, Holas M, Takahata M, Hamouda WO, Kanna RM, Schnake K, Kepler CK, Schroeder GD. AO Spine upper cervical injury classification system: a description and reliability study. Spine J. 2022 Dec;22(12):2042-2049. doi: 10.1016/j.spinee.2022.08.005. Epub 2022 Aug 12. PMID: 35964830.
3)

Lambrechts MJ, Schroeder GD, Karamian BA, Canseco JA, Bransford R, Oner C, Benneker LM, Kandziora F, Shanmuganathan R, Kanna R, Joaquim AF, Chapman JR, Vialle E, El-Sharkawi M, Dvorak M, Schnake K, Kepler CK, Vaccaro AR; AO Spine Upper Cervical Injury Classification International Members. Global Validation of the AO Spine Upper Cervical Injury Classification: Geographic Region Affects Reliability and Reproducibility. Global Spine J. 2022 Aug 29:21925682221124100. doi: 10.1177/21925682221124100. Epub ahead of print. PMID: 36036763.
4)

Maeda FL, Formentin C, de Andrade EJ, Rodrigues PAS, Goyal DKC, Shroeder GD, Patel AA, Vaccaro AR, Joaquim AF. Reliability of the New AOSpine Classification System for Upper Cervical Traumatic Injuries. Neurosurgery. 2020 Mar 1;86(3):E263-E270. doi: 10.1093/neuros/nyz464. PMID: 31642504.
5)

Lambrechts MJ, Schroeder GD, Karamian BA, Canseco JA, Bransford R, Oner C, Benneker LM, Kandziora F, Shanmuganathan R, Kanna R, Joaquim AF, Chapman JR, Vialle E, El-Sharkawi M, Dvorak M, Schnake K, Kepler CK, Vaccaro AR. The AO spine upper cervical injury classification system: Do work setting or trauma center affiliation affect classification accuracy or reliability? Injury. 2022 Oct;53(10):3248-3254. doi: 10.1016/j.injury.2022.08.030. Epub 2022 Aug 15. PMID: 36038389.
6)

Rieger M, Mallouhi A, El-Attal R, Kathrein A, Knop C, Blauth M, Jaschke W. Akutdiagnostik des Wirbelsäulentraumas [Acute diagnosis of spinal trauma]. Radiologe. 2006 Jun;46(6):527-41; quiz 542-3. German. doi: 10.1007/s00117-006-1355-x. PMID: 16607557.

Norwegian Registry for Spine Surgery (NORspine)

Norwegian Registry for Spine Surgery (NORspine)

https://helsedata.no/en/forvaltere/university-hospital-of-north-norway/norwegian-registry-for-spine-surgery/

Latest Pubmed Related Articles

Loss to follow-up may bias outcome assessments in medical registries. A cohort study aimed to analyze and compare patients who failed to respond with those that responded to the Norwegian Registry for Spine Surgery (NORspine).

They analyzed a cohort of 474 consecutive patients operated for lumbar spinal stenosis at four public hospitals in Norway during a two-year period. These patients reported sociodemographic data, preoperative symptoms, and Oswestry Disability Index (ODI), numerical rating scales (NRS) for back and leg pain to NORspine at baseline and 12 months postoperatively. They contacted all patients who did not respond to NORspine after 12 months. Those who responded were termed responsive non-respondents and compared to 12 months respondents.

One hundred forty (30%) did not respond to NORspine 12 months after surgery and 123 were available for additional follow-up. Sixty-four of the 123 non-respondents (52%) responded to a cross-sectional survey done at a median of 50 (36-64) months after surgery. At baseline, non-respondents were younger 63 (SD 11.7) vs. 68 (SD 9.9) years (mean difference (95% CI) 4.7 years (2.6 to 6.7); p = < 0.001) and more frequently smokers 41 (30%) vs. 70 (21%) RR (95%CI) = 1.40 (1.01 to 1.95); p = 0.044. There were no other relevant differences in other sociodemographic variables or preoperative symptoms. We found no differences in the effect of surgery on non-respondents vs. respondents (ODI (SD) = 28.2 (19.9) vs. 25.2 (18.9), MD (95%CI) = 3.0 ( -2.1 to 8.1); p = 0.250).

Kaur et al. found that 30% of patients did not respond to NORspine at 12 months after spine surgery. Non-respondents were somewhat younger and smoked more frequently than respondents; however, there were no differences in patient-reported outcome measures. The findings suggest that attrition bias in NORspine was random and due to non-modifiable factors. 1).

Data were obtained from the Norwegian Registry for Spine Surgery. The primary outcome was change in the neck disability index (NDI) 1 yr after surgery. Secondary endpoints were the European myelopathy score (EMS), quality of life (EuroQoL 5D [EQ-5D]), numeric rating scales (NRS) for headache, neck pain, and arm pain, complications, and perceived benefit of surgery assessed by the Global Perceived Effect (GPE) scale.

They included 905 patients operated between January 2012 and June 2018. There were significant improvements in all patient-reported outcome measures (PROMs) including NDI (mean -10.0, 95% CI -11.5 to -8.4, P < .001), EMS (mean 1.0, 95% CI 0.8-1.1, P < .001), EQ-5D index score (mean 0.16, 95% CI 0.13-0.19, P < .001), EQ-5D visual analogue scale (mean 13.8, 95% CI 11.7-15.9, P < .001), headache NRS (mean -1.1, 95% CI -1.4 to -0.8, P < .001), neck pain NRS (mean -1.8, 95% CI -2.0 to -1.5, P < .001), and arm pain NRS (mean -1.7, 95% CI -1.9 to -1.4, P < .001). According to GPE scale assessments, 229/513 patients (44.6%) experienced “complete recovery” or felt “much better” at 1 yr. There were significant improvements in all PROMs for both mild and moderate-to-severe DCM. A total of 251 patients (27.7%) experienced adverse effects within 3 mo.

Surgery for DCM is associated with significant and clinically meaningful improvement across a wide range of PROMs 2).

multicenter cohort study included 11,081 patients operated with lumbar microdiscectomy, registered at the Norwegian Registry for Spine Surgery. Follow-up was 1 year. Uni- and multivariate logistic regression analyses were used to assess potential prognostic factors for previously defined cut-offs for failure and worsening on the Oswestry Disability Index scores 12 months after surgery. Since the cut-offs for failure and worsening are different for patients with low, moderate, and high baseline ODI scores, the multivariate analyses were run separately for these subgroups. Data were split into a training (70%) and a validation set (30%). The model was developed in the training set and tested in the validation set. A prediction (%) of an outcome was calculated for each patient in a risk matrix.

Results: The prognostic model produced six risk matrices based on three baseline ODI ranges (low, medium, and high) and two outcomes (failure and worsening), each containing 7 to 11 prognostic factors. Model discrimination and calibration were acceptable. The estimated preoperative probabilities ranged from 3 to 94% for failure and from 1 to 72% for worsening in our validation cohort.

Conclusion: We developed a prognostic model for failure and worsening 12 months after surgery for lumbar disc herniation. The model showed acceptable calibration and discrimination, and could be useful in assisting physicians and patients in clinical decision-making process prior to surgery 3).

A study is based on data from the Norwegian Registry for Spine Surgery (NORspine). Patients who had decompressive surgery in the period from 7/1-2007 to 11/3-2013 at 31 hospitals were included. The patients was divided into four groups based on preoperative Numeric Rating Scale (NRS)-score for lower extremity pain. Patients in group 1 had insignificant pain, group 2 had mild or moderate pain, group 3 severe pain and group 4 extremely severe pain. The primary outcome was change in the Oswestry Disability Index (ODI). Successfully treated patients were defined as patients reporting at least 30% reduction of baseline ODI, and the number of successfully treated patients in each group were recorded.

Results: In total, 3181 patients were eligible; 154 patients in group 1; 753 in group 2; 1766 in group 3; and 528 in group 4. Group 1 had significantly less improvement from baseline in all the clinical scores 12 months after surgery compared to the other groups. However, with a mean reduction of 8 ODI points and 56% of patients showing a reduction of at least 30% in their ODI score, the proportion of patients defined as successfully treated in group 1, was not significantly different from that of other groups.

Conclusion: This national register study shows that patients with insignificant lower extremity pain had less improvement in primary and secondary outcome parameters from baseline to follow-up compared to patients with more severe lower extremity pain 4).

A total of 6840 patients with lumbar disc herniation were operated and followed for 12 months, according to the standard protocol of the Norwegian Registry for Spine Surgery (NORspine). Patients reporting to be unchanged or worse on the Global Perceived Effectiveness (GPE) scale at 12-month follow-up were classified as “failure”, and those considering themselves “worse” or “worse than ever” after surgery were classified as “worsening”. These two dichotomous outcomes were used as anchors in analyses of receiver operating characteristics (ROC) to define cutoffs for failure and worsening on commonly used PROMs, namely, the Oswestry Disability Index (ODI), the EuroQuol 5D (EQ-5D), and Numerical Rating Scales (NRS) for back pain and leg pain.

Results: “Failure” after 12 months for each PROM, as an insufficient improvement from baseline, was (sensitivity and specificity): ODI change <13 (0.82, 0.82), ODI% change <33% (0.86, 0.86), ODI final raw score >25 (0.89, 0.81), NRS back-pain change <1.5 (0.74, 0.86), NRS back-pain % change <24 (0.85, 0.81), NRS back-pain final raw score >5.5 (0.81, 0.87), NRS leg-pain change <1.5 (0.81, 0.76), NRS leg-pain % change <39 (0.86, 0.81), NRS leg-pain final raw score >4.5 (0.91, 0.85), EQ-5D change <0.10 (0.76, 0.83), and EQ-5D final raw score >0.63 (0.81, 0.85). Both a final raw score >48 for the ODI and an NRS >7.5 were indicators for “worsening” after 12 months, with acceptable accuracy.

Conclusion: The criteria with the highest accuracy for defining failure and worsening after surgery for lumbar disc herniation were an ODI percentage change score <33% for failure and a 12-month ODI raw score >48. These cutoffs can facilitate shared decision-making among doctors and patients, and improve quality assessment and comparison of clinical outcomes across surgical units. In addition to clinically relevant improvements, we propose that rates of failure and worsening should be included in reporting from clinical trials 5).

1)

Kaur S, Alhaug OK, Dolatowski FC, Solberg TK, Lønne G. Characteristics and outcomes of patients who did not respond to a national spine surgery registry. BMC Musculoskelet Disord. 2023 Mar 4;24(1):164. doi: 10.1186/s12891-023-06267-3. PMID: 36871007.
2)

Gulati S, Vangen-Lønne V, Nygaard ØP, Gulati AM, Hammer TA, Johansen TO, Peul WC, Salvesen ØO, Solberg TK. Surgery for Degenerative Cervical Myelopathy: A Nationwide Registry-Based Observational Study With Patient-Reported Outcomes. Neurosurgery. 2021 Jul 29:nyab259. doi: 10.1093/neuros/nyab259. Epub ahead of print. PMID: 34325471.
3)

Werner DAT, Grotle M, Småstuen MC, Gulati S, Nygaard ØP, Salvesen Ø, Ingebrigtsen T, Solberg TK. A prognostic model for failure and worsening after lumbar microdiscectomy: a multicenter study from the Norwegian Registry for Spine Surgery. Acta Neurochir (Wien). 2021 Jul 10. doi: 10.1007/s00701-021-04859-3. Epub ahead of print. PMID: 34245366.
4)

Hermansen E, Myklebust TÅ, Austevoll IM, Rekeland F, Solberg T, Storheim K, Grundnes O, Aaen J, Brox JI, Hellum C, Indrekvam K. Clinical outcome after surgery for lumbar spinal stenosis in patients with insignificant lower extremity pain. A prospective cohort study from the Norwegian registry for spine surgery. BMC Musculoskelet Disord. 2019 Jan 22;20(1):36. doi: 10.1186/s12891-019-2407-5. PMID: 30669998; PMCID: PMC6343340.
5)

Werner DAT, Grotle M, Gulati S, Austevoll IM, Lønne G, Nygaard ØP, Solberg TK. Criteria for failure and worsening after surgery for lumbar disc herniation: a multicenter observational study based on data from the Norwegian Registry for Spine Surgery. Eur Spine J. 2017 Oct;26(10):2650-2659. doi: 10.1007/s00586-017-5185-5. Epub 2017 Jun 14. PMID: 28616747.

Condoliase for lumbar disc herniation

Condoliase for lumbar disc herniation

Latest Pubmed Related Articles

Percutaneous chemonucleolysis with condoliase has been available for painful lumbar disc herniation since 2018 in Japan.

In the 1980s, chemonucleolysis with chymopapain, a protease, was widely used as the intermediate treatment between conservative therapy and surgical therapy in Western countries. However, since chymopapain was withdrawn from the market in 2002 for non-scientific commercial reasons, chemonucleolysis has not been a therapeutic option for LDH. Condoliase (chondroitin sulfate ABC endolyase), a glycosaminoglycan-degrading enzyme, was approved by the drug regulatory authority in Japan as a newer intradiscal therapy for LDH after clinical studies conducted in Japan demonstrated efficacy and safety for patients with LDH 1)

Condoliase as a first-line treatment option ahead of surgical treatment for LDH is superior, from a cost perspective to surgical treatment from the beginning. Condoliase is also a cost-effective alternative to non-surgery conservative treatment 2).

Multicenter, randomized, double-blind, dose-finding studies

Patients between 20 and 70 years of age with unilateral leg pain, positive findings on the straight leg raise test, and LDH were recruited. All eligible patients were randomly assigned to receive condoliase (1.25, 2.5, or 5 U) or placebo. The primary end point was a change in the worst leg pain from preadministration (baseline) to week 13. The secondary end points were changes from baseline in the following items: worst back pain, Oswestry Disability Index (ODI), SF-36, and neurological examination. For pharmacokinetic and pharmacodynamic analyses, plasma condoliase concentrations and serum keratan sulfate concentrations were measured. The safety end points were adverse events (AEs) and radiographic and MRI parameters. Data on leg pain, back pain, abnormal neurological findings, and imaging parameters were collected until week 52. RESULTS A total of 194 patients received an injection of condoliase or placebo. The mean change in worst leg pain from baseline to week 13 was -31.7 mm (placebo), -46.7 mm (1.25 U), -41.1 mm (2.5 U), and -47.6 mm (5 U). The differences were significant at week 13 in the 1.25-U group (-14.9 mm; 95% CI -28.4 to -1.4 mm; p = 0.03) and 5-U group (-15.9 mm; 95% CI -29.0 to -2.7 mm; p = 0.01) compared with the placebo group. The dose-response improvement in the worst leg pain at week 13 was not significant (p = 0.14). The decrease in the worst leg pain in all 3 condoliase groups was observed from week 1 through week 52. Regarding the other end points, the worst back pain and results of the straight leg raise test, ODI, and SF-36 showed a tendency for sustained improvement in each of the condoliase groups until week 52. In all patients at all time points, plasma condoliase concentrations were below the detectable limit (< 100 μU/ml). Serum keratan sulfate concentrations significantly increased from baseline to 6 hours and 6 weeks after administration in all 3 condoliase groups. No patient died or developed anaphylaxis or neurological sequelae. Five serious AEs occurred in 5 patients (3 patients in the condoliase groups and 2 patients in the placebo group), resolved, and were considered unrelated to the investigational drug. Severe AEs occurred in 10 patients in the condoliase groups and resolved or improved. In the condoliase groups, back pain was the most frequent AE. Modic type 1 change and decrease in disc height were frequent imaging findings. Dose-response relationships were observed for the incidence of adverse drug reactions and decrease in disc height. CONCLUSIONS Condoliase significantly improved clinical symptoms in patients with LDH and was well tolerated. While all 3 doses had similar efficacy, the incidence of adverse drug reactions and decrease in disc height were dose dependent, thereby suggesting that 1.25 U would be the recommended clinical dose of condoliase. Clinical trial registration no.: NCT00634946 (clinicaltrials.gov) 3).

Case series

Ohtonari et al. investigated clinical and radiographic outcomes three months after the administration because secondary surgical removal is most required during this period for insufficient pain relief, and analyzed whether the differences in intradiscal injection areas affected the clinical outcomes. They retrospectively investigated 47 consecutive patients (males, 31; median age, 40 years) three months after the administration. Clinical outcomes were evaluated using the Japanese Orthopaedic Association Back Pain Questionnaire (JOABPEQ), a visual analog scale (VAS) score for low back pain, and VAS scores for pains and numbness in the lower limbs. Radiographic outcomes were analyzed in 41 patients, using parameters such as mid-sagittal disc height and maximal protrusion length of herniation on MRI preoperatively and at the final follow-up. The postoperative median evaluation period was 90 days. The effective rate of low back pain based on the pain-related disorders at baseline and the last follow-up in the JOABPEQ reached 79.5%. The postoperative proportion of VAS scores recovery ≥ 2 points and ≥ 50% for pains in the lower limbs were 80.9% and 66.0%, respectively, revealing satisfactory effectiveness. Preoperative median mid-sagittal disc height significantly reduced from 9.5 to 7.6 mm postoperatively. There were no significant differences in pain relief in the lower limbs by injection areas in the center and the dorsal 1/3rd near the herniation of the nucleus pulposus. Chemonucleolysis with condoliase revealed satisfactory short-term outcomes after the administration regardless of intradiscal injection areas 4).

101 patients who underwent chemonucleolysis with condoliase from January 2019 to December 2021. Patients were divided into good outcome (i.e., favorable outcome) and poor outcome (i.e., requiring additional surgical treatment) groups. Patient demographics and imaging findings were collected. Clinical outcomes were evaluated using the numerical rating scale and Japanese Orthopaedic Association scores at baseline and at 1- and 3-month follow-up. Pretreatment indicators for additional surgery were compared between the 2 groups. Results: There was a significant difference in baseline leg numbness between the good outcome and poor outcome groups (6.27 ± 1.90 vs. 4.42 ± 2.90, respectively; p = 0.033). Of the 101 included patients, 32 received a preoperative computed tomography scan. In those patients, the presence of calcification or ossification in disc hernia occurred more often in the poor outcome group (61.5% vs. 5.3%, respectively; p &lt; 0.001; odds ratio = 22.242; p = 0.014). Receiver-operating characteristics curve analysis for accompanying calcification or ossification showed an area under the curve of 0.858 (95% confidence interval, 0.715-1.000; p = 0.001). Conclusions: Calcified or ossified disc herniation may be useful predictors of unsuccessful treatment in patients with condoliase administration 5).

Sixty-seven patients (44 men, 23 women; mean age, 46.7 ± 18.0 years) were analyzed. Time-course changes in disc height, disc degeneration, and herniation size were assessed. For clinical outcomes assessment, visual analog scale (VAS) scores for leg and back pain and the Oswestry disability index (ODI) were obtained at baseline and the 3-month, 1-year, and 2-year follow-ups. We obtained a questionnaire from these patients at two years to assess satisfaction and recommendation. Condoliase therapy was considered to be effective in patients whose VAS score for leg pain improved by ≥ 50% at 2 years from baseline and who did not require surgery.

Results: Condoliase therapy was effective in 51 patients (76.1%). Eight patients (11.9%) required surgery due to ineffectiveness of the therapy. Condoliase therapy was ineffective in five out of six patients with a history of discectomy. The ODI and VAS scores for leg and back pain significantly improved from three months to two years. Of the patients, 80% satisfied with their outcomes, and 85% recommended this therapy. Progression of disc degeneration was observed in 57.1% of patients at three months; however, 30% recovered to baseline at two years. The mean disc height decreased at three months, but recovered slightly at one year and remained stable until two years. No recurrent disc herniation was observed.

Conclusions: Chemonucleolysis with condoliase was effective in 78% of patients with LDH for 2 years. Chemonucleolysis-induced disc degeneration was slightly recovered and maintained for two years post-injection. This treatment resulted in high patient satisfaction and recommendations 6).

137 LDH patients treated through condoliase at four Japanese institutions and assessed its effectiveness among different age categories on alleviation of visual analog scale (VAS) of leg pain, low back pain and numbness, as well as ODI and JOA scores. Moreover, we divided them into either a “group-A” category if a ≥50% improvement in baseline leg pain VAS was observed or “group-N” if VAS leg pain improved &lt;50%. Next, we assessed the differences in clinical and demographic distribution between group-A and group-N. Results: Fifty-five patients were classified as group-A (77.5%) and 16 patients were allocated to group-N (22.5%). A significant difference in Pfirrmann classification was found between both cohorts, with grade IV suggested to be most receptive. A posterior disc angle &gt; 5° was also found to approach statical significance. In all age groups, average VAS scores showed improvement. However, 75% of adolescent patients showed deterioration in Pfirrmann classification following treatment. Conclusions: Intradiscal condoliase injection is an effective treatment for LDH, even in patients with large vertebral translation and posterior disc angles, regardless of age. However, since condoliase imposes a risk of progressing disc degeneration, its indication for younger patients remains controversial 7).

Medical records and radiographic findings were reviewed retrospectively for 127 patients with LDH (88 male, 39 female, mean age: 46.6 ± 17.1 years, mean follow-up: 9.8 ± 7.8 months) who underwent chemonucleolysis with intradiscal condoliase injection at our center since September 2018. Condoliase (1.25 U/mL; 1 mL volume) was injected toward the middle of the affected intervertebral nucleus pulposus using a 21-gauge disc-puncture needle.

Results: Cases in which the Pfirrmann grade did and did not progress in the 3 months after the injection were included in groups P (progression, n = 49) and NP (non-progression, n = 78), respectively. Logistic regression analysis of progression of Pfirrmann grade post-injection showed significant associations with age <40 years (p = 0.013, odds ratio (OR): 3.69, 95% confidence interval (CI): 1.32-10.31), Pfirrmann Grade II or III at baseline (p = 0.021, OR: 3.51, 95% CI: 1.24-9.64), and a high-intensity MRI signal in the herniation (p = 0.047, OR: 2.97, 95% CI: 1.03-8.87). Patients in group P had significantly higher rates of disc height decrease ≥20%, reduced herniated disc size, and improved VAS for pain, but both groups had significant decreases in pain. No cases had an anaphylactic shock or neurologic sequelae.

Conclusions: These results show the safety and efficacy of chemonucleolysis with condoliase for treatment of painful LDH. Progression of Pfirrmann criteria on MRI at 3 months after injection was significantly associated with an improved clinical outcome 8).

Seventy patients (85.4%) were classified into the effective (E) group and 12 patients (14.6%) into the less-effective (L) group. Surgical treatment was required in four patients. No severe adverse complications were reported; 41.3% of the patients developed disc degeneration of Pfirrmann grade 1 or more at the injected disc level. Univariate analysis revealed that young age (p = 0.036), without history of epidural or nerve root block (p = 0.024), and injection into the central portion of the intervertebral disc (p = 0.014) were significantly associated with clinical effectiveness. A logistic regression analysis revealed that injection into the central portion of the intervertebral disc (p = 0.049; odds ratio, 4.913; 95% confidence interval, 1.006-26.204) was significantly associated with clinical effectiveness.

Conclusions: Chemonucleolysis with condoliase is a safe and effective treatment for painful LDH; 85.4% of the patients showed improvement after the treatment without severe adverse events. To obtain the best outcome, condoliase should be injected into the center of the intervertebral disc 9).

Forty-seven patients (20 women, 27 men; mean age 48 years) were included. The herniation level was L2/3 in one patient, L3/4 in two, L4/5 in 23, and L5/S1 in 21. Median symptom duration was 8 months. The mean VAS and ODI improved significantly from the baseline to 3-month follow-up (p < 0.01). Group E included 33 patients (70.2%) and group I included 14, three of whom had a history of discectomy. The rates of spondylolisthesis and posterior intervertebral angle ≥5° were significantly higher in group I than in group E. However, the rates of trans-ligamentous type and herniation with high signal intensity on T2-weighted images (highT2) were significantly higher in group E. Reduction of disc herniation was more frequently observed in group E.

Conclusions: Condoliase injection resulted in significantly improved symptoms in patients with LDH. Condoliase therapy was less effective for patients with a history of discectomy, spondylolisthesis, or those with a posterior intervertebral angle ≥5°, while trans-ligamentous type and high T2 herniation were associated with increased efficacy 10)

A total of 52 patients (mean age, 45.0 years) were enrolled and classified according to whether the injection was effective (E group, n=40, 76.9%) or less effective (L group, n=9, 17.3%). Three patients (5.8%) underwent herniotomy for residual pain within 6 months of the injection. There were no severe adverse events. Reduction of herniation was seen on MRI more often in the E group than in the L group. The effectiveness in patients with transligamentous LDH was similar to that in patients with subligamentous LDH. High-intensity signal change in the area of LDH on pretreatment T2-weighted MRI was a significant predictor of successful leg pain relief.

Conclusions: An intradiscal condoliase injection was a safe and effective treatment for painful radiculopathy caused by LDH. Leg pain was more likely to improve in patients with high-intensity signal change in the area of LDH before treatment 11).

In total, 84 patients were recruited (52 men, 32 women; mean age, 44.2 ± 17.1 [16-86 years]). The duration of illness was 6.7 ± 6.8 (1.5-30) months. All patient-based outcomes significantly improved at 4 weeks after the administration compared with pretreatment. The intervertebral disc height decreased significantly at four weeks after condoliase administration compared with that before administration. Progression of intervertebral disc degeneration occurred in 50% of the patients. Eleven patients underwent herniotomy due to poor treatment effects. Moreover, treatment in 77.4% of the patients was considered effective. A logistic regression analysis revealed that L5/S1 disk administration (p = 0.029; odds ratio, 5.94; 95% confidence interval, 1.20-29.45) were significantly associated with clinical effectiveness.

Conclusions: Condoliase disk administration improved pain and quality of life over time. Condoliase disk administration was more effective in L5/S1 intervertebral administration 12).

47 patients who received condoliase, 34 were enrolled in this study. The mean age of the patients was 33 years. The average duration since the onset of disease was 8.6 months. We evaluated patients’ low back and leg pain using a numerical rating scale (NRS) score at two time points (before therapy and 3 months after therapy). We divided the patients into two groups (good group (G): NRS score improvement ≥ 50%, poor group (P): NRS score improvement < 50%). The parameters evaluated were age, disease duration, body mass index (BMI), and positive or negative straight leg raising test results. In addition, the loss of disc height and preoperative radiological findings were evaluated. Results: In terms of low back and leg pain, the G group included 9/34 (26.5%) and 21/34 (61.8%) patients, respectively. Patients’ age (low back pain G/P, 21/36.5 years) was significantly lower in the G group for low back pain (p = 0.001). High-intensity change in the protruded nucleus pulposus (NP) and spinal canal occupancy by the NP ≥ 40% were significantly high in those with leg pain in the G groups (14/21, p = 0.04; and 13/21, p = 0.03, respectively). Conclusions: The efficacy of improvement in leg pain was significantly correlated with high-intensity change and size of the protruded NP. Condoliase was not significantly effective for low back pain but could have an effect on younger patients 13).

42 patients with LDH who underwent intradiscal condoliase injection. Patients with and without a ≥50% improvement from baseline of leg pain at 3 months after injection were defined as responders and non-responders, respectively. Clinical features and radiological findings were compared between these groups.

Results: Of the 42 patients, 32 (76.2%) were responders and 10 (23.8%) were non-responders. Of 8 patients with a history of discectomy at the same level as LDH, 6 (75.0%) were responders. Non-responders had a significantly longer time from onset to treatment, smaller herniated volume before treatment, lower percentage reduction of herniated mass, and less intervertebral disc degeneration before treatment. There were no significant differences in LDH types (subligamentous extrusion or transligamentous extrusion types), high-intensity area within the herniation, changes in disc height, and region of condoliase injection between the two groups.

Conclusions: Intradiscal condoliase injection had a good short-term therapeutic effect in patients with LDH, including in transligamentous extrusion-type and revision cases as well as subligamentous extrusion-type cases. Administration of intradiscal condoliase injection may be most effective in patients with a larger herniated mass volume before treatment, and least effective in cases with a longer time and less intervertebral disc degeneration before treatment 14).

A total of 82 and 81 patients received an injection of condoliase and placebo, respectively. The average changes in worst leg pain from baseline to week 13 (primary endpoint) were -49.5 mm in the condoliase group and -34.3 mm in the placebo group, and the difference of -15.2 mm was significant (95% confidence interval, -24.2 to -6.2; P = 0.001). Significant improvements were observed in the condoliase groups, compared with the placebo group, in most secondary endpoints at 1 year after administration. In the condoliase group, back pain, Modic type 1 change, and decrease in disc height were frequently reported, without any clinically relevant consequences.

Conclusion: Condoliase significantly improved symptoms in patients with LDH and was well tolerated. Condoliase is a novel and potent chemonucleolytic drug for the treatment of LDH 15).

Case reports

It has been available for painful lumbar disc herniation since 2018 in Japan.

A 25-year-old man with a history of LDH in L4/5, who underwent transforaminal full endoscopic lumbar discectomy when he was 17 years old, complained of severe pain radiating to his left leg for 1 month. The straight leg-raising test was limited to 25° on the left side. Lumbar T2-weighted magnetic resonance imaging (MRI) showed intracanal, left-sided transligamentous disc herniation at L4/5 with high-signal intensity. Because the conservative treatment with oral analgesics and selective left L5 nerve root block failed, the patient requested intradiscal condoliase injection instead of revision surgery. There were no adverse events reported after the condoliase treatment, and the pain radiating to the left leg improved within 2 weeks. A lumbar MRI performed 2 months after treatment revealed that the disc herniation had significantly decreased in size. The straight leg-raising test examined 3 months after treatment was negative. In this case, the disc herniation was of the transligamentous type and showed a high-signal intensity on T2-weighted MRI which could be suitably treated by condoliase injection therapy. This case report is the first to suggest that intradiscal condoliase injection could be a useful and novel conservative treatment option to treat postoperative rec-LDH 16).

References

1)

Matsuyama Y, Chiba K. Condoliase for treatment of lumbar disc herniation. Drugs Today (Barc). 2019 Jan;55(1):17-23. doi: 10.1358/dot.2019.55.1.2899445. PMID: 30740609.
2)

Takaki S, Miyama H, Iwasaki M. Cost-effectiveness analysis of intradiscal condoliase injection vs. surgical or conservative treatment for lumbar disc herniation. J Med Econ. 2023 Jan-Dec;26(1):233-242. doi: 10.1080/13696998.2023.2173465. PMID: 36794375.
3)

Matsuyama Y, Chiba K, Iwata H, Seo T, Toyama Y. A multicenter, randomized, double-blind, dose-finding study of condoliase in patients with lumbar disc herniation. J Neurosurg Spine. 2018 May;28(5):499-511. doi: 10.3171/2017.7.SPINE161327. Epub 2018 Feb 9. PMID: 29424676.
4)

Ohtonari T, Torii R, Noguchi S, Kitagawa T, Nishihara N. Short-term clinical and radiographic outcomes of chemonucleolysis with condoliase for painful lumbar disc herniation and analysis regarding intradiscal injection area. Neurosurg Rev. 2023 Feb 23;46(1):59. doi: 10.1007/s10143-023-01966-w. PMID: 36813932.
5)

Takeuchi S, Hanakita J, Takahashi T, Inoue T, Minami M, Suda I, Nakamura S, Kanematsu R. Predictive Factors for Poor Outcome following Chemonucleolysis with Condoliase in Lumbar Disc Herniation. Medicina (Kaunas). 2022 Dec 18;58(12):1868. doi: 10.3390/medicina58121868. PMID: 36557070; PMCID: PMC9781337.
6)

Banno T, Hasegawa T, Yamato Y, Yoshida G, Arima H, Oe S, Ide K, Yamada T, Kurosu K, Nakai K, Matsuyama Y. Condoliase therapy for lumbar disc herniation -2 year clinical outcome. J Orthop Sci. 2022 Nov 21:S0949-2658(22)00317-7. doi: 10.1016/j.jos.2022.11.005. Epub ahead of print. PMID: 36424250.
7)

Oshita Y, Matsuyama D, Sakai D, Schol J, Shirasawa E, Emori H, Segami K, Takahashi S, Yagura K, Miyagi M, Saito W, Imura T, Nakazawa T, Inoue G, Hiyama A, Katoh H, Akazawa T, Kanzaki K, Sato M, Takaso M, Watanabe M. Multicenter Retrospective Analysis of Intradiscal Condoliase Injection Therapy for Lumbar Disc Herniation. Medicina (Kaunas). 2022 Sep 15;58(9):1284. doi: 10.3390/medicina58091284. PMID: 36143959; PMCID: PMC9501482.
8)

Kobayashi K, Sato K, Ando T. Factors associated with disc degeneration based on Pfirrmann criteria after condoliase treatment for lumbar disc herniation. J Orthop Sci. 2022 Aug 24:S0949-2658(22)00230-5. doi: 10.1016/j.jos.2022.08.001. Epub ahead of print. PMID: 36030156.
9)

Okada E, Suzuki S, Nori S, Tsuji O, Nagoshi N, Yagi M, Fujita N, Nakamura M, Matsumoto M, Watanabe K. The effectiveness of chemonucleolysis with condoliase for treatment of painful lumbar disc herniation. J Orthop Sci. 2021 Jul;26(4):548-554. doi: 10.1016/j.jos.2020.06.004. Epub 2020 Jul 23. PMID: 32713796.
10)

Banno T, Hasegawa T, Yamato Y, Yoshida G, Yasuda T, Arima H, Oe S, Ushirozako H, Yamada T, Ide K, Watanabe Y, Matsuyama Y. Clinical outcome of condoliase injection treatment for lumbar disc herniation: Indications for condoliase therapy. J Orthop Sci. 2021 Jan;26(1):79-85. doi: 10.1016/j.jos.2020.02.002. Epub 2020 Feb 25. PMID: 32111547.
11)

Hirai T, Takahashi T, Tanaka T, Motoyoshi T, Matsukura Y, Yuasa M, Inose H, Yoshii T, Okawa A. Intradiscal Injection with Condoliase (Chondroitin Sulfate ABC Endolyase) for Painful Radiculopathy Caused by Lumbar Disc Herniation. Spine Surg Relat Res. 2021 Oct 11;6(3):252-260. doi: 10.22603/ssrr.2021-0151. PMID: 35800623; PMCID: PMC9200423.
12)

Inoue M, Sainoh T, Kojima A, Yamagata M, Morinaga T, Mannoji C, Ataka H, Yamashita M, Takahashi H, Saito J, Fujiyoshi T, Ishikawa T, Eguchi Y, Kato K, Orita S, Inage K, Shiga Y, Norimoto M, Umimura T, Shiko Y, Kawasaki Y, Aoki Y, Ohtori S. Efficacy and Safety of Condoliase Disc Administration as a New Treatment for Lumbar Disc Herniation. Spine Surg Relat Res. 2021 Jun 11;6(1):31-37. doi: 10.22603/ssrr.2021-0035. PMID: 35224244; PMCID: PMC8842352.
13)

Ishibashi K, Fujita M, Takano Y, Iwai H, Inanami H, Koga H. Chemonucleolysis with Chondroitin Sulfate ABC Endolyase for Treating Lumbar Disc Herniation: Exploration of Prognostic Factors for Good or Poor Clinical Outcomes. Medicina (Kaunas). 2020 Nov 19;56(11):627. doi: 10.3390/medicina56110627. PMID: 33228119; PMCID: PMC7699387.
14)

Nakajima H, Kubota A, Maezawa Y, Watanabe S, Honjoh K, Ohmori H, Matsumine A. Short-Term Outcome and Predictors of Therapeutic Effects of Intradiscal Condoliase Injection for Patients with Lumbar Disc Herniation. Spine Surg Relat Res. 2020 Nov 20;5(4):264-271. doi: 10.22603/ssrr.2020-0126. PMID: 34435150; PMCID: PMC8356240.
15)

Chiba K, Matsuyama Y, Seo T, Toyama Y. Condoliase for the Treatment of Lumbar Disc Herniation: A Randomized Controlled Trial. Spine (Phila Pa 1976). 2018 Aug 1;43(15):E869-E876. doi: 10.1097/BRS.0000000000002528. PMID: 29257028.
16)

Funayama T, Setojima Y, Shibao Y, Noguchi H, Miura K, Eto F, Sato K, Kono M, Asada T, Takahashi H, Tatsumura M, Koda M, Yamazaki M. A Case of Postoperative Recurrent Lumbar Disc Herniation Conservatively Treated with Novel Intradiscal Condoliase Injection. Case Rep Orthop. 2022 Feb 15;2022:3656753. doi: 10.1155/2022/3656753. PMID: 35211348; PMCID: PMC8863464.

Degenerative cervical myelopathy

Degenerative cervical myelopathy

J.Sales-Llopis

Neurosurgery Service, Alicante University General Hospital, Alicante, Spain.

The assessment, diagnosis, operative and nonoperative management of degenerative cervical myelopathy (DCM) have evolved rapidly over the last 20 years. A clearer understanding of the pathobiology of DCM has led to attempts to develop objective measurements of the severity of myelopathy, including technology such as multiparametric magnetic resonance imaging, biomarkers, and ancillary clinical testing. New pharmacological treatments have the potential to alter the course of surgical outcomes, and greater innovation in surgical techniques have made surgery safer, more effective and less invasive. Future developments for the treatment of DCM will seek to improve the diagnostic accuracy of imaging, improve the objectivity of clinical assessment, and increase the use of surgical techniques to ensure the best outcome is achieved for each individual patient 1).

Goel was troubled by the fact that his several PubMed and MEDLINE indexed articles on the subject published in leading journals dedicated to the study of the spine have not found any place in the huge reference list of 137 articles 2)

Definition

Degenerative cervical myelopathy definition.

Epidemiology

Degenerative cervical myelopathy epidemiology.

Etiology

Degenerative cervical myelopathy etiology.

Pathophysiology

A review of Tetreault et al. summarizes current knowledge of the pathophysiology of DCM and describes the cascade of events that occur after compression of the spinal cord, including ischemia, destruction of the blood-spinal cord barrier, demyelination, and neuronal apoptosis. Important features of the diagnosis of DCM are discussed in detail, and relevant clinical and imaging findings are highlighted. Furthermore, this review outlines valuable assessment tools for evaluating functional status and quality of life in these patients and summarizes the advantages and disadvantages of each. Other topics of this review include epidemiology, the prevalence of degenerative changes in the asymptomatic population, the natural history and rates of progression, risk factors of diagnosis (clinical, imaging and genetic), and management strategies 3).

Histological findings

MEDLINE and Embase were systematically searched (CRD42021281462) for primary research reporting on histological findings of DCM in the human cadaveric spinal cord tissue. Data were extracted using a piloted proforma. The risk of bias was assessed using Joanna Briggs Institute critical appraisal tools. Findings were compared to a systematic review of animal models (Ahkter et al. 2020 Front Neurosci 14).

The search yielded 4127 unique records. After the abstract and full-text screening, 19 were included in the final analysis, reporting on 150 autopsies (71% male) with an average age at death of 67.3 years. All findings were based on hematoxylin and eosin (H&E) staining. The most commonly reported grey matter findings included neuronal loss and cavity formation. The most commonly reported white matter finding was demyelination. Axon loss, gliosis, necrosis, and Schwann cell proliferation were also reported. Findings were consistent amongst cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament. Cavitation was notably more prevalent in human autopsies compared to animal models.

Few human spinal cord tissue studies have been performed. Neuronal loss, demyelination and cavitation were common findings. Investigating the biological basis of DCM is a critical research priority. Human spinal cord specimen may be an underutilized but complementary approach 4).

Clinical features

Degenerative cervical myelopathy clinical features

Scales

European myelopathy score.

As a widespread used scale, the Modified Japanese Orthopaedic Association scale (mJOA) should be translated and culturally adapted 5).

see Cervical spine stenosis scales

Diagnosis

Degenerative cervical myelopathy diagnosis.

Differential diagnosis

Degenerative Cervical Myelopathy Differential Diagnosis.

Treatment

Degenerative cervical myelopathy treatment

Outcome

see Degenerative cervical myelopathy outcome.

Research

Degenerative cervical myelopathy research.

Randomized, controlled trials

A National Institutes of Health-funded (1R13AR065834-01) investigator meeting was held before the initiation of the trial to bring multiple stakeholders together to finalize the study protocol. Study investigators, coordinators, and major stakeholders were able to attend and discuss strengths of, limitations of, and concerns about the study. The final protocol was approved for funding by the Patient-Centered Outcomes Research Institute (CE-1304-6173). The trial began enrollment on April 1, 2014 6).

Case series

see Degenerative cervical myelopathy case series.

Case reports

Degenerative cervical myelopathy case reports

References

1)

Wilson JRF, Badhiwala JH, Moghaddamjou A, Martin AR, Fehlings MG. Degenerative Cervical Myelopathy; A Review of the Latest Advances and Future Directions in Management. Neurospine. 2019 Sep;16(3):494-505. doi: 10.14245/ns.1938314.157. Epub 2019 Aug 26. PubMed PMID: 31476852; PubMed Central PMCID: PMC6790745.
2)

Goel A. Degenerative Cervical Myelopathy. Neurospine. 2019 Dec;16(4):793-795. doi: 10.14245/ns.1938384.192. Epub 2019 Dec 31. PubMed PMID: 31905465.
3)

Tetreault L, Goldstein CL, Arnold P, Harrop J, Hilibrand A, Nouri A, Fehlings MG. Degenerative Cervical Myelopathy: A Spectrum of Related Disorders Affecting the Aging Spine. Neurosurgery. 2015 Oct;77 Suppl 4:S51-67. doi: 10.1227/NEU.0000000000000951. PubMed PMID: 26378358.
4)

Dohle E, Beardall S, Chang A, Mena KPC, Jovanović L, Nath U, Lee KS, Smith AH, Thirunavukarasu AJ, Touzet AY, Norton EJ, Mowforth OD, Kotter MRN, Davies BM. Human spinal cord tissue is an underutilised resource in degenerative cervical myelopathy: findings from a systematic review of human autopsies. Acta Neurochir (Wien). 2023 Feb 23. doi: 10.1007/s00701-023-05526-5. Epub ahead of print. PMID: 36820887.
5)

Augusto MT, Diniz JM, Rolemberg Dantas FL, Fernandes de Oliveira M, Rotta JM, Botelho RV. Development of the Portuguese version of the modified Japanese Orthopaedic Association Score: cross-cultural adaptation, reliability, validity and responsiveness. World Neurosurg. 2018 Jun 1. pii: S1878-8750(18)31127-6. doi: 10.1016/j.wneu.2018.05.173. [Epub ahead of print] PubMed PMID: 29864576.
6)

Ghogawala Z, Benzel EC, Heary RF, Riew KD, Albert TJ, Butler WE, Barker FG 2nd, Heller JG, McCormick PC, Whitmore RG, Freund KM, Schwartz JS. Cervical Spondylotic Myelopathy Surgical Trial: Randomized, Controlled Trial Design and Rationale. Neurosurgery. 2014 Oct;75(4):334-346. PubMed PMID: 24991714.

NFTI-QOL

NFTI-QOL

The NFTI-QOL is a robustly constructed disease-specific QOL questionnaire for neurofibromatosis type 2. It correlates strongly and significantly with EuroQOL and all SF-36 domains (p < 0.01). It is straightforward and quick (≤3 minutes) for patients to complete and easy to score. It is suitable as a quantitative method of assessing QOL in NF2 both in a clinical setting and as an outcome measure for treatment. The NFTI-QOL has been validated for adults (>16 years) in the United Kingdom, and could be adapted for use in other countries 1).

The aim of the study of Lawson McLean et al was to produce and validate a German version of the NFTI-QOL (NFTI-QOL-D) and to correlate QOL scores with a depression score (PHQ-9) and clinical disease severity.

The original English-language NFTI-QOL was translated into German and then back-translated in order to preserve the questionnaire’s original concepts and intentions. A link to an online survey encompassing the NFTI-QOL-D and the PHQ-9 depression questionnaire was then sent to 97 patients with NF2 by email. The respondents’ scores were compared to clinician-reported disease severity scores.

77 patients completed the online survey in full. Internal consistency among NFTI-QOL-D responses was strong (Cronbach’s alpha: 0.74). Both PHQ-9 and clinician disease severity scores correlated with NFTI-QOL-D scores (Pearson correlation coefficient rho 0.63 and 0.62, respectively).

The NFTI-QOL-D is a reliable and useful tool to assess patient-reported QOL in German-speaking patients with neurofibromatosis type 2. The correlation of QOL with both psychological and physical disease parameters underlines the importance of individualized interdisciplinary patient care for NF2 patients, with attention paid to mental well-being as well as to somatic disease manifestations 2).

Case series

Data were evaluated for 288 NF2 patients (n = 464 visits) attending the English national NF2 clinics from 2010 to 2012. The male-to-female ratio was equal and the mean age was 42.2 (SD 17.8) years. The analysis included NFTI-QOL eight-item score, ClinSev graded as mild, moderate, or severe, and GenSev as a rank order of the number of NF2 mutations (graded as mild, moderate, severe). The mean (SD) 8.7 (5.4) score for NFTI-QOL for either a first visit or all visits 9.2 (5.4) was similar to the published norm of 9.4 (5.5), with no significant relationships with age or gender. NFTI-QOL internal reliability was good, with a Cronbach’s alpha score of 0.85 and test re-test reliability r = 0.84. NFTI related to ClinSev (r = 0.41, p < 0.001; r = 0.46 for all visits), but weakly to GenSev (r = 0.16, p < 0.05; r = 0.15 for all visits). ClinSev related to GenSev (r = 0.41, p < 0.001; r = 0.42 for all visits). NFTI-QOL showed good reliability and ability to detect significant longitudinal changes in the QOL of individuals. The moderate relationships of NFTI-QOL with a clinician- and genetic-rated severity suggest that NFTI-QOL taps into NF2 patient experiences that are not encompassed by ClinSev rating or genotype 3)

1)

Hornigold, R. E., Golding, J. F., Leschziner, G., Obholzer, R., Gleeson, M. J., Thomas, N., Walsh, D., Saeed, S., & Ferner, R. E. (2012). The NFTI-QOL: A Disease-Specific Quality of Life Questionnaire for Neurofibromatosis 2. Journal of Neurological Surgery. Part B, Skull Base, 73(2), 104-111. https://doi.org/10.1055/s-0032-1301396
2)

Lawson McLean AC, Freier A, Lawson McLean A, Kruse J, Rosahl S. The German version of the neurofibromatosis 2 impacts on quality of life questionnaire correlates with severity of depression and physician-reported disease severity. Orphanet J Rare Dis. 2023 Jan 6;18(1):3. doi: 10.1186/s13023-022-02607-z. PMID: 36604703.
3)

Ferner RE, Shaw A, Evans DG, McAleer D, Halliday D, Parry A, Raymond FL, Durie-Gair J, Hanemann CO, Hornigold R, Axon P, Golding JF. Longitudinal evaluation of quality of life in 288 patients with neurofibromatosis 2. J Neurol. 2014 May;261(5):963-9. doi: 10.1007/s00415-014-7303-1. Epub 2014 Mar 12. PMID: 24619350; PMCID: PMC4008785.

Anterior sacral meningocele

Anterior sacral meningocele

Anterior sacral meningoceles are congenital lesions that consist of a spinal fluid-filled sac in the pelvis communicating by a small neck with the spinal subarachnoid space through a defect in the sacrum. They protrude into retroperitoneal and presacral space. 1) 2).

The wall of the sac consists of two layers, an inner arachnoid membrane and outer dura mater, which extends into the retroperitoneal presacral space from the sacral spinal canal 3).

Anterior sacral meningocele was first described in 1837 as a part of neural tube defect (NTD) spectrum.

It may be associated with a syndrome like Currarino syndrome 4) which includes anorectal malformations, sacral bony defect and presacral mass; and Marfan syndrome wherein the etiology may be disorder of collagen biosynthesis and structure at the dural level 5).

Epidemiology

Anterior sacral meningocele epidemiology

Anterior sacral meningocele in Marfan syndrome

Anterior sacral meningocele in Marfan syndrome

Classification

Anterior sacral meningocele classification.

Etiology

Anterior sacral meningocele etiology.

Pathology

Associated malformations are found:

spina bifida

spinal dysraphism

bicornuate uterus

imperforate anus 6).

Clinical features

Anterior sacral meningocele clinical features.

Diagnosis

Anterior sacral meningocele diagnosis.

Differential diagnosis

Anterior sacral meningocele differential diagnosis.

Complications

Anterior sacral meningocele complications.

Treatment

Anterior Sacral Meningocele Treatment.

Case reports

Anterior sacral meningocele case reports.

1)

Villarejo F, Scavone C, Blazquez MG, Pascual-Castroviejo I, Perez-Higueras A, Fernandez-Sanchez A, Garcia Bertrand C. Anterior sacral meningocele: review of the literature. Surg Neurol. 1983 Jan;19(1):57-71. doi: 10.1016/0090-3019(83)90212-4. PMID: 6828997.
2)

Sharma V, Mohanty S, Singh DR. Uncommon craniospinal dysraphism. Ann Acad Med Singap. 1996 Jul;25(4):602-8. PMID: 8893940.
3)

Somuncu S, Aritürk E, Iyigün O, Bernay F, Rizalar R, Günaydin M, Gürses N. A case of anterior sacral meningocele totally excised using the posterior sagittal approach. J Pediatr Surg. 1997 May;32(5):730-2. doi: 10.1016/s0022-3468(97)90018-x. PMID: 9165463.
4)

CALIHAN RJ. Anterior sacral meningocele. Radiology. 1952 Jan;58(1):104-8. doi: 10.1148/58.1.104. PMID: 14883380.
5)

North RB, Kidd DH, Wang H. Occult, bilateral anterior sacral and intrasacral meningeal and perineurial cysts: case report and review of the literature. Neurosurgery. 1990 Dec;27(6):981-6. doi: 10.1097/00006123-199012000-00020. PMID: 2274142.
6)

Dahan H, Arrivé L, Wendum D, Docou le Pointe H, Djouhri H, Tubiana JM. Retrorectal developmental cysts in adults: clinical and radiologic-histopathologic review, differential diagnosis, and treatment. Radiographics. 2001 May-Jun;21(3):575-84. doi: 10.1148/radiographics.21.3.g01ma13575. PMID: 11353107.