Spine

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/

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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

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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.

Spinal cord injury epidemiology

Spinal cord injury epidemiology

Latest

see also Cervical spine fracture epidemiology.

Thoracolumbar spine fracture epidemiology

Pediatric cervical spine injury epidemiology.

Spinal cord injury epidemiology is changing as preventative interventions reduce injuries in younger individuals, and there is an increased incidence of incomplete injuries in aging populations. With decompressive surgery and proactive interventions to improve spinal cord perfusion, early treatment has become more intensive. Accurate data, including specialized outcome measures, are crucial to understanding the impact of epidemiological and treatment trends. Dedicated SCI clinical research and data networks and registries have been established in the United States, Canada, Europe, and several other countries.

Traumatic spinal cord injuries (TSCIs) affect up to 500,000 people worldwide each year, and their high morbidity is associated with substantial individual and societal burden and socioeconomic impact 1) 2).

TSCIs most commonly affect young males and result from road traffic accidents, but recent reports also highlight their increasing incidence in older adults as a result of low-energy falls 3) 4) 5).

Kelly-Hedrick et al. reviewed four registry networks, The NACTN Spinal Cord Injury Registry, The Spinal Cord Injury Model Systems (SCIMS) Database, The Rick Hansen Spinal Cord Injury Registry (RHSCIR), and the European Multi-Center Study about Spinal Cord Injury Study (EMSCI). They compared the registries’ focuses, data platforms, advanced analytics use, and impacts. They also describe how registries’ data can be combined with EHR or shared using federated analysis to protect registrants’ identities. These registries have identified changes in epidemiology, recovery patterns, complication incidence, and the impact of practice changes like early decompression. They’ve also revealed latent disease-modifying factors, helped develop clinical trial stratification models and served as matched control groups in clinical trials. Advancing SCI clinical science for personalized medicine requires advanced analytical techniques, including machine learning, counterfactual analysis, and the creation of digital twins. Registries and other data sources help drive innovation in SCI clinical science 6).

1)

WHO. Spinal Cord Injury, Fact Sheet. Available at 2013 http://www.who.int/mediacentre/factsheets/fs384/en/
2)

Singh A., Tetreault L., Kalsi-Ryan S., Nouri A., Fehlings M.G. (2014). Global prevalence and incidence of traumatic spinal cord injury. Clin. Epidemiol. 6, 309–331
3)

Noonan V.K., Fingas M., Farry A., Baxter D., Singh A., Fehlings M.G., Dvorak M.F. (2012). Incidence and prevalence of spinal cord injury in Canada: a national perspective. Neuroepidemiology 38, 219–226
4)

Selvarajah S., Hammond E.R., Haider A.H., Abularrage C.J., Becker D., Dhiman N., Hyder O., Gupta D., Black J.H., 3rd, Schneider E.B. (2014). The burden of acute traumatic spinal cord injury among adults in the United States: an update. J. Neurotrauma 31, 228–238
5)

Wyndaele M., Wyndaele J.J. (2006). Incidence, prevalence and epidemiology of spinal cord injury: what learns a worldwide literature survey? Spinal Cord 44, 523–529
6)

Kelly-Hedrick M, Abd-El-Barr M, Aarabi B, Curt A, Howley SP, Harrop JS, Kirshblum S, Neal CJ, Noonan VK, Park C, Ugiliweneza B, Tator C, Toups EG, Fehlings MG, Williamson T, Guest J. The Importance of Prospective Registries and Clinical Research Networks in the Evolution of Spinal Cord Injury Care. J Neurotrauma. 2022 Dec 28. doi: 10.1089/neu.2022.0450. Epub ahead of print. PMID: 36576020.

Charlson comorbidity index (CCI)

Charlson comorbidity index (CCI)

http://touchcalc.com/calculators/cci_js

https://www.mdcalc.com/charlson-comorbidity-index-cci

The purpose of the study was to assess whether the Charlson Comorbidity Index (CCI) was associated with in-hospital death and short-term functional outcome in elderly patients (age ≥ 70) with intracerebral hemorrhage (ICH).

This was a retrospective cohort of aged ICH patients (≥70 years old) admitted within 24 hours of ICH onset. The CCI was derived using hospital discharge ICD-9 CM codes and patient history obtained from standardized case report forms. Multivariable logistic regression was used to determine the independent effect of the CCI score on clinical outcomes.

In this cohort of 248 aged ICH patients, comorbid conditions were common, with CCI scores ranging from 2 to 12. Logistic regression showed that the CCI score was independently predictive of 1-month functional outcome (OR = 1.642, P < 0.001) and in-hospital death (OR = 1.480, P = 0.003). Neither ICH volume nor the presence of IVH was an independent predictive factor for the 1-month functional outcome or in-hospital mortality (P < 0.05).

Comorbid medical conditions as assessed by the CCI independently influence short-term outcomes in aged ICH patients. The characteristics of the hematoma itself, such as intracerebral hemorrhage volume and the presence of IVH, seem to have a reduced effect on it 1).

Complications in spine trauma patients with Ankylosing spinal disorders may be driven by comorbidity burden rather than operative or injury-related factors. The Charlson Comorbidity Index (CCI) may be a valuable tool for the evaluation of this unique population 2)

Charlson Comorbidity Index (CCI) provides a simple way of predicting recurrence in patients with chronic subdural hematoma and should be incorporated into decision-making processes, when counseling patients 3).

Data show that elderly with a good performance status and few co-morbidity may be treated as younger patients; moreover, age confirms a negative impact on survival while (CCI) ≤ 2 did not correlate with overall survival (OS) 4).

Charlson comorbidity index (CCI), functional status computed by the Karnofsky performance scale (KPS)), tumor characteristics (size, location, isocitrate dehydrogenase mutation, and O-6-methylguanine-DNA methyltransferase promoter methylation status), and treatment parameters (volumetrically quantified extent of resection and adjuvant therapy), evidence that aside established prognostic parameters (age and KPS) for glioblastoma patient outcome, the CCI additionally significantly impacts outcome and may be employed for preoperative patient stratification 5).

Maximal resection and radiochemotherapy treatment completion are associated with longer OS, and age alone should not preclude elderly patients from receiving surgery and adjuvant treatment. However, only a few patients were able to finish the proposed treatments. Poor performance and high comorbidity index status might compromise the benefit of treatment aggressiveness and must be considered in therapeutic decision 6).

Latest articles

References

1)

Zhang T, Chen R, Wen D, Wang X, Ma L. The prognostic value of the Charlson comorbidity index in aged patients with intracerebral hemorrhage. BMC Neurol. 2022 Nov 28;22(1):443. doi: 10.1186/s12883-022-02980-z. PMID: 36443745.
2)

Lakomkin N, Mikula AL, Pinter ZW, Wellings E, Alvi MA, Scheitler KM, Pennington Z, Lee NJ, Freedman BA, Sebastian AS, Fogelson JL, Bydon M, Clarke MJ, Elder BD. Perioperative risk stratification of spine trauma patients with ankylosing spinal disorders: a comparison of 3 quantitative indices. J Neurosurg Spine. 2022 May 27:1-7. doi: 10.3171/2022.4.SPINE211449. Epub ahead of print. PMID: 35623371.
3)

Martinez-Perez R, Tsimpas A, Rayo N, Cepeda S, Lagares A. Role of the patient comorbidity in the recurrence of chronic subdural hematomas. Neurosurg Rev. 2020 Mar 7. doi: 10.1007/s10143-020-01274-7. [Epub ahead of print] PubMed PMID: 32146611.
4)

Balducci M, Fiorentino A, De Bonis P, Chiesa S, Manfrida S, D’Agostino GR, Mantini G, Frascino V, Mattiucci GC, De Bari B, Mangiola A, Miccichè F, Gambacorta MA, Colicchio G, Morganti AG, Anile C, Valentini V. Impact of age and co-morbidities in patients with newly diagnosed glioblastoma: a pooled data analysis of three prospective mono-institutional phase II studies. Med Oncol. 2012 Dec;29(5):3478-83. doi: 10.1007/s12032-012-0263-3. Epub 2012 Jun 7. PubMed PMID: 22674154.
5)

Ening G, Osterheld F, Capper D, Schmieder K, Brenke C. Charlson comorbidity index: an additional prognostic parameter for preoperative glioblastoma patient stratification. J Cancer Res Clin Oncol. 2015 Jan 11. [Epub ahead of print] PubMed PMID: 25577223.
6)

Pereira AF, Carvalho BF, Vaz RM, Linhares PJ. Glioblastoma in the elderly: Therapeutic dilemmas. Surg Neurol Int. 2015 Nov 16;6(Suppl 23):S573-S582. eCollection 2015. PubMed PMID: 26664927.

Vancomycin

Vancomycin

Vancomycin is a glycopeptide antibiotic medication.

Blood levels may be measured to determine the correct dose.

When taken by mouth it is poorly absorbed.

Vancomycin Cerebrospinal Fluid Pharmacokinetics

A study described the cerebrospinal fluid (CSF) exposure of vancomycin in 8 children prescribed intravenous vancomycin therapy for cerebral ventricular shunt infection. Vancomycin CSF concentrations ranged from 0.06 to 9.13 mg/L and the CSF: plasma ratio ranged from 0 to 0.66. Two of 3 children with a staphylococcal CSF infection had CSF concentrations greater than the minimal inhibitory concentration at the end of the dosing interval 1).

Cerebrospinal fluid (CSF) penetration and the pharmacokinetics of vancomycin were studied after continuous infusion (50 to 60 mg/kg of body weight/day after a loading dose of 15 mg/kg) in 13 mechanically ventilated patients hospitalized in an intensive care unit. Seven patients were treated for sensitive bacterial meningitis and the other six patients, who had a severe concomitant neurologic disease with intracranial hypertension, were treated for various infections. Vancomycin CSF penetration was significantly higher (P < 0.05) in the meningitis group (serum/CSF ratio, 48%) than in the other group (serum/CSF ratio, 18%). Vancomycin pharmacokinetic parameters did not differ from those obtained with conventional dosing. No adverse effect was observed, in particular with regard to renal function 2).

Ichinose et al. evaluated the concentration of Vancomycin in the plasma and CSF of postoperative neurosurgical patients with bacterial meningitis and evaluated the factors that affect the transferability of VCM to CSF. The concentrations of VCM in plasma (trough) and CSF were determined in eight patients (four males and four females) with bacterial meningitis who were treated with VCM using High-performance liquid chromatography. The ratio of the VCM concentrations in CSF/plasma was also calculated by estimating the blood VCM concentration at the same time as the VCM concentration in CSF was measured. The results showed that the VCM concentration in CSF was 0.9-12.7 µg/mL and the CSF/plasma VCM concentration ratio was 0.02-0.62. They examined the effect of drainage on the transferability of VCM to CSF, which showed that the VCM concentration in CSF and the CSF/plasma VCM concentration ratio were significantly higher in patients not undergoing drainage than in patients who were undergoing drainage. The CSF protein and glucose concentrations, which are diagnostic indicators of meningitis, were positively correlated with the VCM concentration in CSF and the CSF/plasma VCM concentration ratio. Thus, VCM transferability to CSF may be affected by changes in the status of the blood-brain barrier and blood-cerebrospinal fluid barrier due to drainage or meningitis 3).

Indications

Vancomycin Indications.

Vancomycin powder

see Vancomycin powder.

Intraventricular Vancomycin

Intraventricular Vancomycin

1)

Autmizguine J, Moran C, Gonzalez D, Capparelli EV, Smith PB, Grant GA, Benjamin DK Jr, Cohen-Wolkowiez M, Watt KM. Vancomycin cerebrospinal fluid pharmacokinetics in children with cerebral ventricular shunt infections. Pediatr Infect Dis J. 2014 Oct;33(10):e270-2. doi: 10.1097/INF.0000000000000385. PMID: 24776517; PMCID: PMC4209191.
2)

Albanèse J, Léone M, Bruguerolle B, Ayem ML, Lacarelle B, Martin C. Cerebrospinal fluid penetration and pharmacokinetics of vancomycin administered by continuous infusion to mechanically ventilated patients in an intensive care unit. Antimicrob Agents Chemother. 2000 May;44(5):1356-8. doi: 10.1128/AAC.44.5.1356-1358.2000. PMID: 10770777; PMCID: PMC89870.
3)

Ichinose N, Shinoda K, Yoshikawa G, Fukao E, Enoki Y, Taguchi K, Oda T, Tsutsumi K, Matsumoto K. Exploring the Factors Affecting the Transferability of Vancomycin to Cerebrospinal Fluid in Postoperative Neurosurgical Patients with Bacterial Meningitis. Biol Pharm Bull. 2022;45(9):1398-1402. doi: 10.1248/bpb.b22-00361. PMID: 36047211.

Lumbar decompression surgery for spinal canal stenosis outcome

Lumbar decompression surgery for spinal canal stenosis outcome

Lumbar laminectomy, represents the standard operative treatment for lumbar spinal stenosis, but this procedure is often combined with fusion surgery. It is still discussed whether minimal-invasive decompression procedures are sufficient and if they compromise spinal stability as well.

Decompression of lumbar spinal stenosis without fusion led to a significant and similar reduction of back pain and leg pain in a short-term and a long-term follow-up group. Patients without previous surgery benefited significantly better, whereas patients with previous decompression benefited regarding back pain, especially for long-term follow-up with a clear trend in favor of leg pain 1).

Currently, there is interest in minimally invasive surgery and various technical modifications of decompressive lumbar laminectomy without fusion.

Particularly, depression has been shown to be associated with less improvement following lumbar fusion surgery 2) 3) 4) 5) 6) 7) 8).

Karp et al. 9) reviewed 158 patients who underwent epidural spinal injections for low-back pain with or without radiculopathy. These investigators found that depression and sleep disturbance were prognostic of worse Patient-Reported Outcome Measurement Information System (PROMIS) outcomes following epidural spinal injections.

Hägg et al. 10) performed a randomized controlled trial of 264 patients with severe chronic low-back pain who underwent either surgical or nonsurgical treatment, and assessed the impact of underlying affective disorders. They found that baseline depression correlated with worse outcomes following both operative and nonoperative treatment.

Interestingly, they also observed that depressed patients tended to have better outcomes with nonoperativecare, whereas nondepressed patients tended to have better outcomes with fusion.

In the study of Lubelski et al. 11) found that worsening depression (as measured by the PHQ-9) independently significantly predicted worse EQ-5D index outcomes following conservative treatment for LSS (p = 0.0002). This effect was most evident when comparing patients with severe depression, who improve 0.14 points less than those with no depression. This difference exceeds the MCID and confirms that depression is a poor prognostic factor for QOL improvement following nonoperative treatment for LSS. Further investigation is needed to determine whether treatment of depression prior to conservative or surgical management of LSS will improve posttreatment QOL outcomes. There are several limitations that should be considered when interpreting the results. Multiple treating physicians were included, and factors such as participation in physical therapy, treatment with NSAIDs, opioid medications and other nonsurgical treatments varied by practitioner and patient; this increases the variability, but also improves the generalizability.

They adjusted for the increased variability by using the random effect in the regression models. Many patients were also lost to follow-up at the 4-month evaluation.

The cohorts were similar for most characteristics; however, there were statistically significant, albeit small differences for estimated percent below poverty threshold and median income by zip code. The analysis is only valid for patients who did follow-up assessments at these time points. Additionally, this was a retrospective study with a relatively short follow-up period.

Prospectively designed studies with longer follow-up are needed to further validate the findings. Nonetheless, this is the largest study investigating the correlation between depression and QOL outcomes following conservative management of LSS.

Lubelski et al. have used the validated PHQ-9 measure of depression and have found a statistically and clinically significant impact on EQ-5D index outcomes.

The results of this study suggest that depressed patients with LSS have significantly less improvement following conservative management compared with nondepressed patients. Both physicians and surgeons who treat patients with LSS should consider using validated questionnaires such as the PHQ-9 for pretreatment evaluation of depression, to better assess the likelihood of success following treatment. Further investigation is needed to evaluate the effect of depression treatment prior to management of the spinal disorder. Future prospective studies with longer follow-up intervals may be useful in further evaluating the QOL outcomes in this patient population 12).

In cases of lumbar spinal stenosis (LSS) treated with surgical decompression, a postoperative magnetic resonance imaging (MRI) is sometimes required. In the experience of a study, the obtained decompression observed on early postoperative MRI tends to be disappointing compared to the decompression achieved intraoperatively. This raises the question of whether the early postoperative MRI, performed after lumbar decompression, is a fair representation of the ‘real’ decompression. A study investigated the correlation between intraoperative and postoperative measurements of the lumbar spinal canal.

Surgical decompression of the spinal canal effectively decreases the compression of the dural sac. However, early postoperative MRI after lumbar decompression does not adequately represent the decompression achieved intraoperatively 13).

Back pain improvement

Through the 1st postoperative year, patients with lumbar stenosis-without spondylolisthesis, scoliosis, or sagittal malalignment-and clinically significant back pain improved after decompression-only surgery 14).

The most common surgical method currently used is lumbar laminectomy, with complete decompression; this technique has a 5-year follow-up effective rate of 81.6% 15).

Complications

Apart from acute complications such as hematoma and infections, same-level recurrent lumbar stenosis and adjacent-segment disease (ASD) are factors that can occur after index lumbar spine surgery.

While looking for predictors of revision surgery due to re-stenosis, instability or same/adjacent segment disease none of these were found. Within our cohort no significant differences concerning demographic, peri-operative and radiographic data of patients with or without revision wer noted. Patients, who needed revision surgery were older but slightly healthier while more likely to be male and smoking. Surprisingly, significant differences were noted regarding the distribution of intraoperative and early postoperative complications among the 6 main surgeons while these weren’t obious within the intial index group of late revisions 16).

A systematic review was conducted using MEDLINE for literature published through December 2014. The first question focused on the effectiveness of lumbar spine surgery for symptomatic lumbar spinal stenosis in elderly patients. The second question focused on safety of surgical intervention on this elderly population with emphasis on perioperative complication rates.

Review of 11 studies reveals that the majority of elderly patients exhibit significant symptomatic improvement, with overall benefits observed for pain (change visual analog scale4.4 points) and disability (change Oswestry Disability Index 23 points). Review of 11 studies reveals that perioperative complications were infrequent and acceptable with pooled estimates of mortality (0.5%), inadvertent durotomy (5%), and wound infection (2%). Outcomes seem less favorable with greater complication rates among patients with diabetesor obesity.

Based on largely low-quality, retrospective evidence, Shamji et al. recommend that elderly patients should not be excluded from surgical intervention for symptomatic lumbar spinal stenosis 17).

Revision surgery

Fusion Is Not a Safeguard to Prevent Revision Surgery in Lumbar Spinal Stenosis 18).

A cohort study showed no significant association between the type of index operation for Degenerative Lumbar Spinal Stenosis-decompression alone or fusion-and the need for revision surgery or the outcomes of pain, disability, and quality of life among patients after 3 years. Number of revision operations was associated with more pain and worse quality of life 19).

1)

Geiger MF, Bongartz N, Blume C, Clusmann H, Müller CA. Improvement of Back and Leg Pain after Lumbar Spinal Decompression without Fusion. J Neurol Surg A Cent Eur Neurosurg. 2018 Dec 5. doi: 10.1055/s-0038-1669473. [Epub ahead of print] PubMed PMID: 30517963.
2)

Aalto TJ, Malmivaara A, Kovacs F, Herno A, Alen M, Salmi L, et al: Preoperative predictors for postoperative clinical outcome in lumbar spinal stenosis: systematic review. Spine (Phila Pa 1976) 31:E648–E663, 2006
3)

Adogwa O, Parker SL, Shau DN, Mendenhall SK, Aaronson OS, Cheng JS, et al: Preoperative Zung Depression Scale predicts outcome after revision lumbar surgery for adjacent segment disease, recurrent stenosis, and pseudarthrosis. Spine J 12:179–185, 2012
4)

Adogwa O, Parker SL, Shau DN, Mendenhall SK, Bydon A, Cheng JS, et al: Preoperative Zung depression scale predicts patient satisfaction independent of the extent of improvement after revision lumbar surgery. Spine J 13:501–506, 2013
5)

Arpino L, Iavarone A, Parlato C, Moraci A: Prognostic role of depression after lumbar disc surgery. Neurol Sci 25:145– 147, 2004
6)

Chaichana KL, Mukherjee D, Adogwa O, Cheng JS, McGirt MJ: Correlation of preoperative depression and somatic perception scales with postoperative disability and quality of life after lumbar discectomy. J Neurosurg Spine 14:261– 267, 2011
7)

Sinikallio S, Aalto T, Airaksinen O, Herno A, Kröger H, Viinamäki H: Depressive burden in the preoperative and early recovery phase predicts poorer surgery outcome among lumbar spinal stenosis patients: a one-year prospective follow-up study. Spine (Phila Pa 1976) 34:2573–2578, 2009
8)

Trief PM, Grant W, Fredrickson B: A prospective study of psychological predictors of lumbar surgery outcome. Spine (Phila Pa 1976) 25:2616–2621, 2000
9)

Karp JF, Yu L, Friedly J, Amtmann D, Pilkonis PA: Negative affect and sleep disturbance may be associated with response to epidural steroid injections for spine-related pain. Arch Phys Med Rehabil 95:309–315, 2014
10)

Hägg O, Fritzell P, Ekselius L, Nordwall A: Predictors of outcome in fusion surgery for chronic low back pain. A report from the Swedish Lumbar Spine Study. Eur Spine J 12:22–33, 2003
11) , 12)

Lubelski D, Thompson NR, Bansal S, Mroz TE, Mazanec DJ, Benzel EC, Khalaf T. Depression as a predictor of worse quality of life outcomes following nonoperative treatment for lumbar stenosis. J Neurosurg Spine. 2015 Mar;22(3):267-72. doi: 10.3171/2014.10.SPINE14220. Epub 2014 Dec 19. PubMed PMID: 25525957.
13)

Schenck C, van Susante J, van Gorp M, Belder R, Vleggeert-Lankamp C. Lumbar spinal canal dimensions measured intraoperatively after decompression are not properly rendered on early postoperative MRI. Acta Neurochir (Wien). 2016 May;158(5):981-8. doi: 10.1007/s00701-016-2777-5. Epub 2016 Mar 23. PubMed PMID: 27005673; PubMed Central PMCID: PMC4826663.
14)

Crawford CH 3rd, Glassman SD, Mummaneni PV, Knightly JJ, Asher AL. Back pain improvement after decompression without fusion or stabilization in patients with lumbar spinal stenosis and clinically significant preoperative back pain. J Neurosurg Spine. 2016 Nov;25(5):596-601. PubMed PMID: 27285666.
15)

Bouras T, Stranjalis G, Loufardaki M, Sourtzis I, Stavrinou LC, Sakas DE. Predictors of long-term outcome in an elderly group after laminectomy for lumbar stenosis. J Neurosurg Spine. 2010;59:329–34.
16)

Melcher C, Paulus AC, Roßbach BP, Gülecyüz MF, Birkenmaier C, Schulze-Pellengahr CV, Teske W, Wegener B. Lumbar spinal stenosis – surgical outcome and the odds of revision-surgery: Is it all due to the surgeon? Technol Health Care. 2022 Jun 10. doi: 10.3233/THC-223389. Epub ahead of print. PMID: 35754243.
17)

Shamji MF, Mroz T, Hsu W, Chutkan N. Management of Degenerative Lumbar Spinal Stenosis in the Elderly. Neurosurgery. 2015 Oct;77 Suppl 4:S68-74. doi: 10.1227/NEU.0000000000000943. PubMed PMID: 26378360.
18)

Austevoll IM, Ebbs E. Fusion Is Not a Safeguard to Prevent Revision Surgery in Lumbar Spinal Stenosis. JAMA Netw Open. 2022 Jul 1;5(7):e2223812. doi: 10.1001/jamanetworkopen.2022.23812. PMID: 35881401.
19)

Ulrich NH, Burgstaller JM, Valeri F, Pichierri G, Betz M, Fekete TF, Wertli MM, Porchet F, Steurer J, Farshad M; Lumbar Stenosis Outcome Study Group. Incidence of Revision Surgery After Decompression With vs Without Fusion Among Patients With Degenerative Lumbar Spinal Stenosis. JAMA Netw Open. 2022 Jul 1;5(7):e2223803. doi: 10.1001/jamanetworkopen.2022.23803. PMID: 35881393.