Department of Radiodiagnosis, Aster MIMS, Kozhikode, Kerala, India

Praveen Mathew

KG Ramakrishnan

Glioma, ITSS, rCBV, Perfusion MRI, Susceptibility

: Perfusion MRI is considered one of the best available methods in grading of gliomas and studies have shown it to be superior to conventional MRI sequences in this regard. Due to its high sensitivity to tumor microvasculature and hemorrhagic products, susceptibility-weighted imaging (SWI) is a promising imaging tool for evaluating angiogenesis, which in turn can help differentiate low grade from high grade gliomas. 
AIMS: This study aims to compare the accuracy of SWI with Perfusion MRI in the grading of gliomas.


BACKGROUND

This study aims to compare the accuracy of SWI with Perfusion MRI in the grading of gliomas.

AIMS

In this prospective study on 40 patients with gliomas of different grades diagnosed based conventional MRI sequences (confirmed later on biopsy), SWI and perfusion MRI images were acquired by a 1.5 T MRI machine. rCBV (Relative cerebral blood volume) values were obtained by Perfusion MRI and ITSS (Intratumoral susceptibility signal) magnitude denoting the number of linear or dot like hypointensities within the tumor, was assessed from SWI images. Receiver operating characteristic (ROC) curve analysis was used to determine the individual diagnostic performances of rCBV and ITSS in grading of the gliomas. Reliability of both diagnostic tests was assessed by kappa statistic along with its 95% CI (confidence interval) and p Value.

METHODS

High ITSS magnitude on SWI (5 and above) had sensitivity of 100% and specificity of 91.7% in predicting High grade gliomas. Positive and negative predictive values were 96.6% and 100% respectively. The overall diagnostic accuracy was 97.5% and the Kappa statistic was 0.94. Similarly a high rCBV value (Above 1.75) on perfusion MRI had sensitivity of 85.7% and specificity of 91.7% in predicting High grade gliomas. Positive and negative predictive values were 96% and 73.3% respectively. The overall diagnostic accuracy was 87.5% and the Kappa statistic was 0.72. p values for all the above results were <0.05. 

RESULTS

The findings in our study show that non-invasive grading of gliomas based on their ITSS magnitude on SWI has a diagnostic accuracy comparable to rCBV values obtained by Perfusion MRI. These findings imply that visual assessment of the degree of intratumoral susceptibility signals in a glioma can predict its grade similar to Perfusion MRI, which has generally been considered the gold standard noninvasive method of grading gliomas.

CONCLUSIONS

Magnetic resonance imaging (MRI) is the gold standard in non-invasive diagnosis and grading of gliomas. Conventional MRI techniques may provide less than optimal information by assessing only the anatomic characteristics of the tumor. New complementary MRI techniques have been developed that provide quantitative parameters which provide functional or physiologic data, thereby improving their accuracy in grading these tumors

INTRODUCTION

Perfusion MRI is one such technique that has become a powerful tool by giving insight into angiogenesis, a critical component of gliomas of higher grade, thereby potentially helping to differentiate low grade from high grade gliomas. Studies have shown that it improves the accuracy in grading of gliomas and is generally considered superior to conventional MRI in this regard

Due to its high sensitivity to tumor microvasculature and hemorrhagic products, susceptibility-weighted imaging (SWI) has recently been included as a potential imaging tool for evaluating angiogenesis and thereby help in grading gliomas. SWI has potential advantages in that it is a non-contrast technique and does not have some of the technical limitations and pitfalls in diagnostic interpretation present in perfusion MRI[5]. This study aims to compare the accuracy of SWI compared to perfusion MRI in grading gliomas.

A total of 40 patients with subsequently histopathologically proven gliomas of different grades were analysed from June 2017 to May 2018 by MRI. Perfusion MRI and SWI images were used to obtain rCBV and ITSS values respectively from each of the gliomas.

Data collection

All patients with suspected gliomas based on conventional MR imaging features were graded based on Perfusion MRI as low grade or high grade ( using an rCBV value of 1.75 as the cut off for differentiation, based on previous valid studies)[2,4] . The rCBV value was calculated from the site of maximal blood volume in the lesion, compared with a contralateral area of normal white matter. Quantitative assessment of intratumoral susceptibility signals (ITSS) was performed in the selected imaging slice that visually showed the highest frequency of ITSS within the tumor. This did not include hypointense lines and dots seen on the other conventional sequences, but only those hypointense foci seen only on the SWI sequence. Results were then be compared with the histopathological grade of the tumor obtained by surgery or stereotactic biopsy.

Imaging analysis

Data was analyzed using SPSS 22.0. Comparison of continuous variables was assessed using independent sample t test. Susceptibility weighted imaging using an ITSS value and Perfusion MRI imaging using an rCBV value were compared with histopathology in distinguishing low grade (grade I and II) and high grade (Grade III and IV) gliomas . ROC curve analysis was used to define the cut off value for ITSS. The pre-fixed cut off value for rCBV based on previous studies as mentioned in the review of literature was 1.75[9]. Sensitivity, Specificity, Positive and Negative predictive values were used to interpret the accuracy of SWI and Perfusion MRI with respect to Histopathology. Reliability of both diagnostic tests was assessed by kappa statistic along with its 95% CI (confidence interval) and p Value. For all tests a p value of < 0.05 was considered as statistically significant.

Statistical analysis

In the study of 40 patients, majority of the gliomas (57.5 %) were grade IV on histopathology (23 patients). Grade I gliomas accounted for 10% of the patients. Grade II and Grade III gliomas accounted for 20% and 12.5% of patients respectively. Grade I and II gliomas are classified as low grade gliomas and grade III and IV are classified as high grade gliomas by convention. By this classification, 70 % (28 cases) of the gliomas in this study were high grade and 30% (12 cases) were low grade.

The mean rCBV value (on perfusion MRI) of high grade gliomas was 3.61 ± 3.02 and low grade gliomas was 0.99 ± 0.78, and the mean difference (2.62) between the two groups was statistically significant (P value 0.006).

The rCBV value of the tumor had a good predictive validity in predicting histopathological high grade gliomas, as indicated by area under the curve of 0.921 (95% CI 0.812 to 1.00; p value <0.001).

Out of the histopathologically proved high grade gliomas, 85.7% were shown to be high grade on Perfusion MRI as well, using an rCBV cut off value of 1.75, giving it a sensitivity of 85.7%. Out of the histopathologically proved low grade gliomas, 91.7% of the lesions were low grade on Perfusion MRI as well, giving it a specificity of 91.7%. Positive predictive value was 96.0% and negative predictive
value was 73.3%; the overall diagnostic accuracy was 87.5%. The kappa statistic was 0.72 with a 95% CI of 0.5 to 0.95.


The mean ITSS magnitude on SWI of histopathological high grade gliomas was 16.25 ± 6.54 and low grade gliomas was 2.67 ± 2.84, and the mean difference (13.58) between the two groups was statistically significant (P value<0.001).

Based on the ROC curve analysis, an ITSS value of 5 was chosen as the cut off between high grade and low grade gliomas, as it was the point of maximum sensitivity and specificity.

In our study population, SWI showed better validity parameters than Perfusion MRI in predicting glioma grade, with the greatest difference being in the sensitivity and negative predictive value, in which SWI had values of 100% .The difference was however statistically insignificant with a p value of 0.1 and overlap in the 95 % confidence intervals of all the validity parameters between the two tests.

The present study was conducted with the objective of comparing the accuracy of Susceptibility-weighted Imaging (SWI) with Perfusion MRI in non-invasive grading of gliomas, using an optimal Intratumoral Susceptibility Signal (ITSS) cut-off value derived from the study.

The prospective study included 40 patients with histopathologically proved gliomas, of which 70% (28 in number) belonged to the high grade group and 30% (12 in number) belonged to the low grade group. 

The accuracy of Perfusion MRI in predicting high grade gliomas was determined based on an rCBV threshold value of 1.75 (from previous studies); the accuracy of SWI was determined using an ITSS threshold value of 5, derived from the ROC curve analysis in this study.

The findings in our study show that grading of gliomas based on their ITSS magnitude on SWI has a diagnostic accuracy (sensitivity of 100 % and specificity of 91.7 %) comparable to that of Perfusion MRI based on their relative cerebral blood volume (rCBV) measurements (Sensitivity of 85.7% and specificity of 91.7%). Perfusion MRI has generally been considered the gold standard non-invasive method of grading gliomas and this study shows  SWI to be an equally accurate alternative, the advantage being it does not require contrast administration and is free from software related technical pitfalls often present in perfusion MRI. 

In our study, there was a statistically significant difference between the mean ITSS magnitude of high grade and low grade gliomas, with a mean value of 16.25 ± 6.54 for high grade gliomas and 2.67± 2.84 for low grade gliomas. This result is similar to previous studies by Park et al5], Zhang et al[6]contrast enhanced T1WI (CE-T1WI, Li et al[7]9 of which were grades I-II, and 13 were grades III-IV. All examinations were performed on Signa DEx 3.0 T MRI scanner. Conventional imaging techniques (T1WI, T2WI, T2FLAIR, CE-T1WI and Wang et al8]and there was also a significant correlation between rCBV and tumor grade (r= 0.77; P < 0.001. For example, the study by Li et al7]9 of which were grades I-II, and 13 were grades III-IV. All examinations were performed on Signa DEx 3.0 T MRI scanner. Conventional imaging techniques (T1WI, T2WI, T2FLAIR, CE-T1WI in 22 gliomas showed an ITSS magnitude of 17.7 ± 12.71 in high grade gliomas and   7.9 ± 7.62 in low grade gliomas with a statistically significant difference. 

In our study, using an ITSS magnitude of 5 as the optimal threshold value based on the ROC curve analysis, the sensitivity and specificity in predicting high grade gliomas was found to be 100% and 91.7% respectively. Positive and negative predictive values were 96.6% and 100% respectively. These results are similar to those of the previous study by Park et al[5], who also used the value 5 as their ITSS threshold  in a study population of 41 gliomas (29 high grade and 12 low grade) and obtained a sensitivity of 85.2%, specificity of 92.9%, and positive and negative predictive values of 95.8% and 76.5% respectively.

Similar to perfusion MRI, the role of SWI in grading gliomas is also based on evaluating the process of neoangiogenesis that occurs more in high grade gliomas.  However, unlike perfusion MRI, HR-SWI evaluates the anatomical aspect of the vascularity by assessing the number of tiny new vessels within the tumor, with their accompanying microhaemorrhages because of the leakiness associated with these immature new vessels. These are significantly higher in high grade gliomas than those of low grade.

ITSS quantification on the SWI sequence has a diagnostic performance comparable to Perfusion MRI in the grading of gliomas and is easier to perform and interpret with fewer technical limitations and pitfalls compared to Perfusion MRI, with an added advantage being non-requirement of contrast administration.

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Floriano VH, Torres US, Spotti AR, Ferraz-Filho JRL, Tognola WA. The Role of Dynamic Susceptibility Contrast-Enhanced Perfusion MR Imaging in Differentiating between Infectious and Neoplastic Focal Brain Lesions: Results from a Cohort of 100 Consecutive Patients. PLoS ONE [Internet] 2013 [cited 2018 Jun 20];8(12). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855761/

Law M, Yang S, Wang H, Babb JS, Johnson G, Cha S, et al. Glioma Grading: Sensitivity, Specificity, and Predictive Values of Perfusion MR Imaging and Proton MR Spectroscopic Imaging Compared with Conventional MR Imaging. Am J Neuroradiol 2003;24(10):1989–98. 

Direksunthorn T, Chawalparit O, Sangruchi T, Witthiwej T, Tritrakarn S-O, Piyapittayanan S, et al. Diagnostic performance of perfusion MRI in differentiating low-grade and high-grade gliomas: advanced MRI in glioma, A Siriraj project. J Med Assoc ThailChotmaihetThangphaet 2013;96(9):1183–90. 

Al-Okaili RN, Krejza J, Wang S, Woo JH, Melhem ER. Advanced MR Imaging Techniques in the Diagnosis of Intraaxial Brain Tumors in Adults. RadioGraphics 2006;26(suppl_1):S173–89. 

Park MJ, Kim HS, Jahng G-H, Ryu C-W, Park SM, Kim SY. Semiquantitative Assessment of Intratumoral Susceptibility Signals Using Non-Contrast-Enhanced High-Field High-Resolution Susceptibility-Weighted Imaging in Patients with Gliomas: Comparison with MR Perfusion Imaging. Am J Neuroradiol 2009;30(7):1402–8. 

Zhang H, Tan Y, Wang X-C, Qing J-B, Wang L, Wu X-F, et al. Susceptibility-weighted imaging: the value in cerebral astrocytomas grading. Neurol India 2013;61(4):389–95. 

Li C, Ai B, Li Y, Qi H, Wu L. Susceptibility-weighted imaging in grading brain astrocytomas. Eur J Radiol 2010;75(1):e81-85. 

Wang X, Zhang H, Tan Y, Qin J, Wu X, Wang L, et al. Combined value of susceptibility-weighted and perfusion-weighted imaging in assessing who grade for brain astrocytomas. J MagnReson Imaging JMRI 2014;39(6):1569–74. 

Role of Susceptibility-weightedImaging in Grading of Gliomas Compared to Perfusion MRI, with Histopathology as the Gold Standard

#111827

Department of Orthopaedics, Aster MIMS Hospital, Kottakkal Malappuram District,  Kerala, India. 

Dr Faizal M Ikbal MS1

Department of Neurosurgery, Aster MIMS Hospital, Kottakkal Malappuram District,  Kerala, India. 

Dr Hassan Muhammad MS,  PhD

Dr Kadavil R Shaji MD2

Low backache, keyhole-surgery, daycare-surgery, Discectomy, Endoscopic Indication, Inter-laminar, Transforaminal.

Perfusion MRI is considered one of the best available methods in grading of gliomas and studies have shown it to be superior to conventional MRI sequences in this regard. Due to its high sensitivity to tumor microvasculature and hemorrhagic products, susceptibility-weighted imaging (SWI) is a promising imaging tool for evaluating angiogenesis, which in turn can help differentiate low grade from high grade gliomas. 
AIMS: This study aims to compare the accuracy of SWI with Perfusion MRI in the grading of gliomas.


: In this prospective study on 40 patients with gliomas of different grades diagnosed based conventional MRI sequences (confirmed later on biopsy), SWI and perfusion MRI images were acquired by a 1.5 T MRI machine. rCBV (Relative cerebral blood volume) values were obtained by Perfusion MRI and ITSS (Intratumoral susceptibility signal) magnitude denoting the number of linear or dot like hypointensities within the tumor, was assessed from SWI images. Receiver operating characteristic (ROC) curve analysis was used to determine the individual diagnostic performances of rCBV and ITSS in grading of the gliomas. Reliability of both diagnostic tests was assessed by kappa statistic along with its 95% CI (confidence interval) and p Value.

Similar to perfusion MRI, the role of SWI in grading gliomas is also based on evaluating the process of neoangiogenesis that occurs more in high grade gliomas.  However, unlike perfusion MRI, HR-SWI evaluates the anatomical aspect of the vascularity by assessing the number of tiny new vessels within the tumor, with their accompanying microhaemorrhages because of the leakiness associated with these immature new vessels. These are significantly higher in high grade gliomas than those of low grade.



Direksunthorn T, Chawalparit O, Sangruchi T, Witthiwej T, Tritrakarn S-O, Piyapittayanan S, et al. Diagnostic performance of perfusion MRI in differentiating low-grade and high-grade gliomas: advanced MRI in glioma, A Siriraj project. J Med Assoc ThailChotmaihetThangphaet 2013;96(9):1183–90.

	Park MJ, Kim HS, Jahng G-H, Ryu C-W, Park SM, Kim SY. Semiquantitative Assessment of Intratumoral Susceptibility Signals Using Non-Contrast-Enhanced High-Field High-Resolution Susceptibility-Weighted Imaging in Patients with Gliomas: Comparison with MR Perfusion Imaging. Am J Neuroradiol 2009;30(7):1402–8. 

Low back pain is a major clinical problem that results in an important socioeconomic burden. The percutaneous endoscopic lumbar discectomy technique developed by Yeung, also known as PELD, is currently the flagship of minimally invasive transforaminal decompression. Kambin and Gellman first introduced PELD in 1983. PELD has been further developed with the Yeung endoscopic spine system and transforaminal endoscopic spine system.

PELD surgery- short term results and follow-up of 230 patients, reporting patient satisfaction, in terms of duration of surgery and early recovery.

Objective

A prospective study was performed on all 230 patients who had undergone PELD between September 2018 and July 2019 at Aster Mims Kottakkal. This included patients who presented with intervertebral disc prolapse, both central and paracentral disc herniation, or radiculopathy. A narrative review was conducted to outline the basic principles, surgical techniques, and clinical outcomes of lumbar and cervical disc herniation. 

PELD allows intra-operative protection of the nerve roots, and communication with the patient under local anaesthesia. However, the learning curve for PELD is steeper than that of conventional microsurgery, and proper surgical indications and a good working channel position are important. PELD approaches should be tailored to remove disc fragments specific to various types of HD.
We observed 184 successful cases (80%) and 3 infected patients (1.3%) with discitis, one of which relapsed, the other two being converted to open surgery. We observed 2 cases of impending cauda equina syndrome and 10 cases of degenerative lumbar canal stenosis. Radiculitis patients (n=7, 3%), were effectively treated with oral steroids. The complication rate was <5%, similar to that of conventional open techniques.


PELD may be an ideal surgical technique for LDH. Preliminary results demonstrate a high efficacy rate, with few surgical complications. Given recent technical advancements, surgical indications for endoscopic spine surgery are still expanding and the clinical results have become more practical and reliable.

Low back pain is a major clinical problem, that results in an significant socioeconomic burden.1 Its incidence appears to be increasing, despite technical and therapeutic advances in diagnosis and treatment. Surgery is advantageous over conservative treatment in most cases of back pain caused by lumbar spinal stenosis.2 Over recent years, various percutaneous, minimally invasive intradiscal techniques have been developed, directed at the mechanical process of discus herniation, with the underlying aim of capitalizing on the advantages of operative therapy, with as few of the disadvantages as possible. 

Posterolateral Selective Endoscopic Discectomy (SED) and radiofrequency (RF) thermal annuloplasty, a percutaneous endoscopic technique developed by Yeung,3,4 also known as PELD, is currently the flagship of minimally invasive transforaminal decompression. Kambin and Gellman first introduced PELD in 1983 to remove affected disc material under local anaesthesia, for direct neural decompression.5 PELD was further developed with the Yeung endoscopic spine system (YESS) and  transforaminal endoscopic spine system (TESSYS) techniques, and thereby became a feasible alternative for lumbar disc herniation (LDH) treatment. 

In contrast to traditional open surgical techniques, PELD involves a lateral rather than midline approach, introducing an endoscope to the disc space through the foramin, thus avoiding damage to the vital lumbar structures. The annulus is cut and prolapsed disc material retrieved through the annular tear, keeping the dural tube free from compression, and therefore providing immediate relief to the patient.

Patient apprehension towards open surgery, and the complications of anaesthesia associated with patients with multiple comorbidities (including CAD, CKD, diabetes and reliance on antiplatelets), for whom open surgery and regional and general anaesthesia pose a risk, yet we can easily perform endoscopic surgery under local anaesthesia, have led us to conduct a review on how the endoscopic technique differs from conventional open lumbar discectomy. 

Here, we analyse the short term results of percutaneous endoscopic  transforaminal lumbar discectomy in terms of patient satisfaction, based on a cohort of 230 patients treated at Aster Mims Kottakkal during the period of September 2018 to July 2019.

To review the results from short term follow-up of 230 patients receiving PELD surgery, reporting patient satisfaction in terms of duration of surgery and likelihood of early recovery. 

A prospective study review was performed on all 230 patients who underwent PELD between September 2018 and July 2019, performed by a team of 5 doctors. This included patients who presented with intervertebral disc prolapse, or both central and paracentral disc herniation. All patients had radiculopathy, which was resistant to medical treatment. The height and width of the foramen, LDH type, and positional relationship between LDH and the foramen were radiologically evaluated prior to surgery.

All cases underwent PELD on a single vertebral level, based on standard indications, with patients in the prone position. Chart review was carried out, and preoperative, intraoperative, and postoperative radiographic reviews were performed. Patient satisfaction was defined as a maintained reduction in pain and absence of recurrence within a 24 month period, with no further surgery being necessary.

A literature search of the transforaminal approach to LDH was carried out, with a focus on surgical indications for percutaneous endoscopic discectomy and corresponding clinical outcomes in the lumbar region and spine, in cases involving percutaneous or full endoscopic discectomy, carried out with a working channel endoscope.

Statistical comparisons of proportions were performed using Fisher’s exact test. P values less than 0.05 were considered statistically significant. 

There are a range of studies available which indirectly or directly compare open surgical patient outcomes to PELD and other endoscopic outcomes. Five such studies were systematically reviewed in 2016 by Peng et al.,9 which report similar clinical outcomes across a range of different measures, yet greater patient satisfaction with PELD, with 91% of patients being satisfied with their surgeries.

Among more recent studies, a single centre study of 10,228 patients by Choi et al. over a 12 year period showed a successful post-operative outcome rate of 95.7%.10 Positive outcomes were judged by indications for reoperation within 6 weeks. The most common cause of failure was incomplete removal of the herniated disc, with a third of these cases the result of incorrect positioning of the working channel, highlighting the importance of tailoring the PELD approach in each case based on pre-operative indications.

A study by Choi et al,11 comparing satisfaction in 23 patients with large LDH (>50% of spinal canal occupied) undergoing open lumbar microdiscectomy (OLD), and 20 receiving PELD, measured significantly higher patient satisfaction in the PELD group, as reported using a pain and movement questionnaire. Additionally, a loss of disc height in the OLD group was avoided with PELD. The frequency of recurrence or reoperation within 24 months was 10%. However, a longitudinal study made in Korea showed no difference in the reoperation rates observed with OLD and PELD between 1973 and 2018.

Song et al. compared PELD outcomes of 30 patients to those of 30 patients receiving microendoscopic discectomy (MED), which also uses an endoscope, but does not integrate radiofrequency technology.13 Clinical markers of operative success were similar across both groups, with the PELD group having a faster post-operative recovery.

Indications for PELD were as follows- Song et al. included patients with MRI and MR imaging indications, differential pain in the waist and lower limb(s) in conjunction with positive results for either the femoral or sciatic nerve stretch tests,13. Choi et al. also included patients with MRI imaging indications,10,11 and used imaging results used to infer the optimal approach. Wildermuth et al. demonstrate similar accuracy with MRI imaging and functional myelography in identifying measurements of the lumbar dural sac.

Hirano et al. suggest inclusion of patients with recurrent disc herniation after microdiscectomy, who are high risk for general anaesthesia, have LDH at L3-4 or above, or are emergency cases.15 They do not recommend PELD with limited accessibility to the disc space, bony canal stenosis, large and hard herniated nucleus pulposus (HNP), or HNP with a vertical migration of more than 10 mm.

A steep learning curve is described for PELD, as explored by Lee et al;16 Hirano et al also describe lessons learned from early procedures, in which 16% of patients experienced unfavourable outcomes,6,15 yet these became rare events with increasing surgical experience. Specifically, Hirano et al. describe the following difficulties regarding PELD training6: (1) Posterior procedures have been performed for decades by spine surgeons, so they are familiar with posterior anatomy. However, PELD is a posterolateral approach, and the intervertebral foramen anatomical structure is relatively new to surgeons; (2) Anatomical landmarks are absent, and (3) tissue differences between the annulus fibrosus and posterior longitudinal ligament (PLL), or the PLL and dura matter, are vague. 

The demographics and surgical approaches of case patients are shown in Table 1. Two patients presented with impending cauda equina syndrome and 10 with degenerative lumbar canal stenosis. 

80% of patients who returned for one and two-year follow-ups reported successful outcomes requiring no further treatment, with an average 90% reduction in reported pain, and early ambulation. Three patients had an infection (discitis), of which one had a relapse. The other two cases were converted to open surgery.  Sterilization methods were revised, and all instruments autoclaved. These patients were managed post-operatively with IV antibiotics for 24 hours, followed by oral antibiotics for 1 week. On the initial post-operative follow up, we recorded no permanent complications. 

The overall complication rate was <5%, including transient dysesthesia, the most common postoperative complaint, which occurred in approximately 5%-15% of cases. Dysesthesia is almost always transient. Three patients had post-surgical radiculitis, which was effectively treated with oral steroids. With these exceptions, all patients were satisfied with their results, received relief of pre op pain and experienced early recovery. Our rates of reoperation, and combined reoperation and recurrence, are similar to those of other studies reporting results from earlier years of PELD implementation (P>0.05, Figure 1), and are congruent with the 95.7% of 10,228 patients considered to have had successful outcomes by Choi et al. at 6 weeks post-surgery (P>0.05), although this study includes all negative outcomes reported within 24 months.

Based on the observations of this study and the literature, we propose the following inclusion and exclusion indications for PELD surgery:


level disc prolapse, ideally with unilateral radiculopathy.

Revision cases- in this study, patients seeking consultation following a transient successful or partially successful or unsuccessful translaminar discectemy were offered endoscopic discectomy.

Multilevel bilateral foraminal stenosis- for such cases, the procedure must be staged, with an inter-surgery interval varying from 3 weeks to 3 months. 

Patients with psychomotor symptoms (even if they are indicated to be under adequate cover of antidepressants and are receiving suitable counselling).

Central bony-canal stenosis is an absolute contraindication to the procedure.

Preliminary results with PELD surgery demonstrate a high efficacy rate, with few surgical complications.6,9,10,11,13 The indications for operative discectomy are larger discus protrusions, and extrusions that show signs of nerve root compression on MRI. Smaller, focal protrusions, without nerve root compression, appear to be less apt to spontaneously resorb, and have a less favorable natural resolution. In comparison with open surgery, minimally invasive spinal surgery has repeatedly shown short-term benefits, including shorter operation and lower complication rates.9-11 By preserving paraspinal muscle, and avoiding iatrogenic facet injury, PELD gives superior patient outcomes in comparison with conventional OLD, in terms of a shorter hospital stay,9,10 often with same-day discharge, less postoperative pain,10 and reduced intraoperative blood loss.

Proper surgical indications and a good working channel position are important for successful PELD.6,8,15,16 The “surgeon factor” is critical, as each endoscopic surgeon needs to possess a wide range of surgical experience and skills to determine the procedures and techniques that work best, limited only by their own surgical experience and ability. The learning curve of PELD is perceived to be longer and steeper than that of conventional microsurgery,6,15,16 due to the unfamiliarity of most surgeons with the anatomy of the intervertebral foramen. Despite these complications, some studies report an acceptable PELD learning curve with sufficient preparation and pre-operative training, such as attending seminars, hands-on training, or learning at advanced surgical centres.

PELD has a number of advantages over OLD. Firstly, that it can be performed under local anaesthesia, which supports communication between patients and surgeons during the operation and is beneficial to intraoperative protection of the nerve root and rapid mobilization postoperatively. Secondly, approach-related complications, such as dural tear and cerebrospinal fluid fistulas,7 are minimised in patients receiving PELD. Finally, PELD retains the motor segment, and thus decreases the incidence of fusion diseases such as adjacent segment disease. 

Some patients are particularly suited to PELD. PELD is the simplest way to remove foraminal stenosis when encountered, removing the need for fusion. In this study, foraminal stenosis was present in 4.3% of patients, and the benefits of PELD are likely to be greater in this subgroup. Most patients suffering from LDH are elderly, with various medical comorbidities. A shorter operative time and reduced blood loss have been demonstrated to help in reducing potential complications in such cohorts.6 PELD has also shown promise for treating serial multilevel LDH.

Theoretically, PELD is assumed to be superior in terms of postoperative low back pain, because normal paraspinal structures are more likely to be preserved.18 However, PELD also poses several challenges, such as higher incidences of postoperative chronic low back pain and recurrence. Within a 12 month follow-up period, two patients underwent reoperation at the operated level or another lumbar level after PELD. No further reoperation was required within 24 months, suggesting the follow-up period was sufficient to capture most complications. The rate of reoperation was similar to that seen with conventional procedures, and to that reported across similar single and multi centre studies.  We therefore consider that PELD for recurrent disc herniation yielded favorable outcomes within our centre. 

Our results suggest that PELD that avoids the occurrence of iatrogenic normal-tissue injury may be an ideal surgical technique for addressing LDH. The procedure is effective for preservation of the facet joint. Based on the preservation of normal anatomic structure, its usefulness could be maximized in patients with serial multilevel LDHs. Given recent technical advancements, the number of surgical indications for endoscopic spine surgery are increasing, and clinical results have become more practical and reliable. PELD techniques should be tailored to remove disc fragments in various forms of HD. 

PELD allows a short hospital stay, which reduces total costs and results in a direct economic advantage. As most patients suffering from LDH are elderly, with various medical comorbidities, a shorter operative time and reduced blood loss are clear advantages.

Duthey B. Update on 2004 Background Paper, BP 6.24 Low back pain. World Health Organization; 2013

Amundsen T, Weber H, Nordal HJ, Magnaes B, Abdelnoor M, Lilleas F. Lumbar spinal stenosis: conservative or surgical management?: A prospective 10-year study. Spine. 2000;25:1424-35. 

Yeung AT, Gore S. In-vivo Endoscopic Visualization of Patho-anatomy in Symptomatic Degenerative Conditions of the Lumbar Spine II: Intradiscal, Foraminal, and Central Canal Decompression. Surg Technol Int. 2011;Dec 1;XXI:299-319.

Yeung, AT. Endoscopic medial branch and dorsal ramusrhizotomy for chronic Axial back pain: a Pilot Study. Lecture presented at: International 25th Jubilee Course on Percutaneus Endoscopic Spine surgery and Complementary Techniques; 2007 Jan 24-25; Zurich, Switzerland. 

Kambin, P, Gellman H. Percutaneous Lateral Discectomy of the Spine: A Preliminary Report. Clin Orthop. 1983;174:127-32.

Hirano Y, Pawar S, Bansil R, Watanabe K. Advantages of Endoscope-Assisted Disc-FX in Surgical Management of Lumbar Disc Herniation: A Report of 10 Cases. J Spine. 2018;7:15.

Cornefjord M, Olmarker K, Rydevik B, Nordborg C. Mechanical and biochemical injury of spinal nerve roots: a morphological and neurophysiological study. Eur Spine J. 1996;5(3):187-192.

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PELD (Percutaneous Endoscopic Lumbar Discectomy): Prospective Study of 230 Cases, Indications, Patient Satisfaction and Recovery

Consultant Pediatric Neurologist, Medcare Women and Children Hospital, Dubai and Aster Hospital, Al Qusais, Dubai, UAE

Dr Vivek Mundada,MBBS, DCH, MRCPCH, FRCPCH, CCT

There are many ‘non-epileptic’ episodes which can mimic an epileptic seizure and are not uncommon in children including neonates. Most of these conditions have favorable prognosis. Hence, clinicians should be aware of such differential diagnosis, as incorrect diagnosis of epilepsy has huge ramification on the child as well as their families. 

Diagnosis of epilepsy is like a jigsaw puzzle and can often take time if important pieces of the information are missing. The first step in the multiaxial classification of epilepsy is to make sure that the paroxysmal episode which a child had was epileptic or non-epileptic. This step is almost always clinical and relies on the history-taking skill of the clinician. Videos of such episodes are extremely helpful and occasionally investigations can help. However, there is no investigation to ‘rule out’ or to ‘confirm’ epilepsy as many times; an EEG can be ordered after a single suspected seizure episode. 

There are many ‘non-epileptic’ episodes which can mimic an epileptic seizure and are not uncommon in children including neonates. Most of these conditions have favorable prognosis. Hence, clinicians should be aware of such differential diagnosis, as incorrect diagnosis of epilepsy has huge ramification on the child as well as their families. In uncertain situations, such children should be referred to a child neurologist

A 6-month-old, ex-preterm male infant was referred to the author by a pediatrician with history of suspected epileptic spasms. He was already started on an antileptic medication by the same pediatrician. On the very next day, the infant was seen. Fortunately, the parents also had videos of the episodes, which these days all epileptologists find quite useful. In the first instance, the author was not convinced that those paroxysmal episodes were epileptic spasms. Moreover, going through the detailed history, it was thought that those episodes were ‘non-epileptic’.

On examination, the infant had generalized dystonia as well as spasticity. His weight was under 0.4th centile for age and sex. The episodes were more in numbers after the feeds and after witnessing them in the ward, it was confirmed that they were in fact due to severe gastro-esophageal reflux disease. Eventually, the episodes plummeted in severity and frequency once the anti-reflux medications were started. The antiepileptic medication was stopped as it was not needed. Clearly, no EEG was needed here as it would have been misleading or not helpful in “ruling out” epilepsy as the diagnosis.

This is not an unusual story for many of the pediatric neurologists. Just like a surgeon should know when ‘not to operate’, a neurologist should also know when a seizure is not an epileptic one. This is because, the rate of misdiagnosis is very high especially in the pediatric population. Almost one in three children are misdiagnosed with epilepsy and the consequences are not just on these children but are also on their families (1). The rate of misdiagnosis is even higher in children with severe intellectual impairment (2) 

Confident diagnosis of non-epileptic seizures in children is often more challenging than making a positive diagnosis of epilepsy. However, this challenge must be overcome to avoid parental anxiety, unwarranted investigations and potentially harmful and unnecessary treatments. In addition to this, there is a risk of missing another serious diagnosis such as Long QT syndrome that can be life threatening because of the risk of ventricular tachyarrhythmias (Torsades de pointes) (3) The diagnosis of epilepsy is mainly a clinical one. Hence it depends on the good history taking skill. 

What is an epileptic seizure and epilepsy?

An epileptic seizure by definition is a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain (4) whereas, epilepsy is called when 

At least two unprovoked (or reflex) seizures occur greater than 24 hours apart.

One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years.

Diagnosis of an epilepsy syndrome can be made even after the first seizure

So, any seizure which is not due to the abnormal electric activity in the brain is “non-epileptic”. Such episodes are often stereotyped and most of them tend to occur within the same context or environment. 

Some of the common non-epileptic episodes seen in children are discussed below.

These can be either blue (prolonged expiratory apnea) or pallid breath-holding spells. Typically, these are triggered by an initial emotional or physical provocation which then leads to crying and then followed by a silent pause. This results in either a blue or pale color change. The attacks typically terminate with a sudden gasp and rapid return of consciousness. Prolonged and severe episodes can lead to loss of consciousness with increased tone in the limbs.

They are more common in children between 6 and 12 months of age. Typically, an increase in their frequency is seen by the age of 2 years. Nearly half of children grow out of these by 4 years of age (5)

Parental education and reassurance are needed in such cases. Also, treatment with iron for any iron deficiency is recommended (6). EEG is not required but a standard 12-lead ECG and a referral to pediatric cardiology should be considered. In pallid breath holding spell with bradycardia, a pacemaker implant may be considered in some cases. (7)

This is an episode which is triggered by a painful stimulus. Such stimulus, by vagal stimulation causes pronounced bradycardia or even cardiac arrest and relative cerebral ischemia leading to an ‘anoxic seizure’. A careful history will always identify the triggers in such episodes, as these are almost always the provoked episodes. The most common trigger is pain or fright such is venipuncture, trapping fingers in a door or minor head injury etc.

During an episode, children can become stiff and can have cyanosis along with few brief myoclonic or clonic movements affecting some or all the four limbs. The eyes can be deviated upwards. Urinary incontinence can occur as well. This particular phase can be misinterpreted as an epileptic seizure

Reflex anoxic seizures (RAS) are common in children between 6 months to 2 years of age; although it can happen in adolescents and even in adults. They are more common in girls than boys. 

The successful management involve correct diagnosis of RAS and making sure that there is no underlying cardiac arrhythmia; reassurance of the parents and the avoidance of any unnecessary investigation like EEG. Cardiac pacing may be considered in frequent and severe RAS which affects the child and the family's quality of life 

An useful website for the parents is the Syncope Trust and Reflex Anoxic Seizures website (‘STARS’; http://www.stars.org.uk)

Such episodes are commonly mistaken as ‘absence seizures’. Daydreaming episodes are commoner in children with learning difficulties. They are more commonly seen in the primary school age children. Children during such episodes can be interrupted by a stimuli like touch or tickle. They do not manifest during any interesting activities and are very situational. Unlike typical absence seizures, they are not frequent in numbers and cannot be induced by hyperventilation 

These episodes involve clusters of myoclonic movements involving various body parts like head, trunk, neck, limbs, eyes and head nodding episodes. They typically have onset between 3 to 9 months and tend to disappear by 3 years of age. Several episodes can occur during a single day.

These infants are neurodevelopmentally normal and the EEG is also normal. An EEG may be considered, especially to rule out myoclonic epilepsy of infancy or epileptic spasms when there is such suspicion 

5. Infantile gratification disorder and shuddering

This is often under-recognized or under-diagnosed in children. These episodes are self-stimulating behavior and hence were called has infantile masturbation. These are self-limiting and tend to disappear by 2 years of age

Such episodes can easily be misdiagnosed as epileptic seizures. Usually, a child is sitting in a high chair or a car seat with a strap between the legs. The episode happens when the child is bored. The child can stare into space rocking back and forth with the legs crossed and making grunting noises. Such episode can stop with distraction, although the child can be annoyed with such distraction. Videos of such episodes can often facilitate the diagnosis

Shuddering episodes are characterized by tremors of the head, arms and shoulders as if the infant is shivering. An episode can last for few seconds and can come in clusters. Spontaneous resolution is the norm.

Tics are sudden, rapid, recurrent, non-rhythmic motor movements or vocalizations usually appearing in bouts while waxing and waning in frequency and intensity. Tics occur predominantly in children and mean age of onset is around 5 years. These can be either motor or vocal. Motor tics are common in face, neck or shoulder group of muscles. Some of the common motor tics are eye blinking, nose, mouth twitching and shoulder jerks; whereas common vocal tics are throat clearing, grunting and sniffing like sounds. Coprolalia (uttering socially inappropriate words) can occur in up to 20% of individuals. Motor tics usually start in the face and tend to extend caudally and are more common than the vocal tics. They typically can disappear during sleep 

The severity of the tics is dependent on factors such as anxiety and stress. They can even be more evident during relaxation like while watching television. 

More than two third of the cases can have associated comorbidity. Attention deficit hyperactivity is the most common association followed by obsessive compulsive disorder. Other comorbidities include sleep impairment, learning difficulties, anxiety disorders, conduct disorders etc. 

Night terror can occur in up to 1-6% of children. They are more common in children between 3 and 12 years of age, with a peak between 5 and 7 years of age. During a typical episode, a sudden arousal from non-dreaming sleep occurs, usually about one and half hours or so after falling asleep. The child wakes up suddenly from sleep, sits or even jumps out of the bed and usually screams with fear. The child appears frightened and confused. There episodes can be associated with tachycardia, tachypnoea, flushed face, bed wetting or dilated pupils (15). Such episodes can be easily be mistaken for nocturnal frontal lobe epilepsy. In case of dilemma, a sleep study or video- EEG telemetry like investigations can be useful.

Syncope is a transient loss of consciousness resulting from an insufficient supply of oxygen to the brain (16). There is usually a sudden decrease in cerebral perfusion as the result of reduction in cerebral blood flow. 

Up to 15% of children can experience such episode before they turn 18. Such episodes are more common in females in their adolescence.
Syncope can be sudden or gradual in onset and can be associated with various different motor phenomenon like hypotonia, extensor spasm like movement of the upper limbs or hyermotor movements like jerking of the limbs. Urinary incontinence can be associated in syncope and hence is not a pathognomonic sign of epileptic seizure. The key to diagnosis is the history immediately preceding the attack and the occurrence of pallor during the attack.


There are various different types of syncope. A reflex syncope is triggered by some stimulus, like pain or shock; orthostatic syncope happens on standing up quickly from sitting or lying position; convulsive syncope is when there is associated abnormal postures or a convulsion; sudden syncope is when there is no warning sign (and hence carries a risk of injury) whereas gradual onset syncope has some pre-syncopal symptoms such as dizziness, nausea, feeling cold or sweaty etc. 

9. Psychogenic Non-Epileptic Seizures (PNES)

These episodes mimic epileptic seizures and hence it is important to correctly diagnose such episodes so that the correct management can be provided to the affected individuals. People with PNES usually present to the same clinicians who deal with individuals with epilepsy.   Nearly one in ten children with suspected epilepsy referred to a secondary care clinic actually has PNES

The estimated prevalence of such seizures is around 50 per 100,000. There is however no best terminology available to describe such episodes and these are called by various different names like pseudo seizures, psychogenic seizures, functional/hysterical, dissociative or conversion seizures. Most of these terms are often confusing. 

Children can have both- epileptic as well as PNES coexisting together which can make the diagnosis a challenge. In such cases, the outcome usually is less favorable. In adults, there is often a history of physical or sexual abuse or associated mental health issues like complex personality disorders, anxiety or depression. Moreover, the quality of life can be equally affected like in the patients with epilepsy 

The treatment should always be focused on psychological rather than medical issues for better outcome.

Some of the features which can differentiate a PNES from an epileptic seizure are- 

Tremors and shaking of limbs rather than actual tonic and clonic jerks 

Variability in motor symptoms such as jerking or shaking

Side-to-side head movements or thrashing movements

Self-protective mechanisms to avoid injuries

Prolonged periods of lying without actual loss of consciousness or awareness

Preserved corneal reflex during the episode along with responsive pupils

10.  Motor stereotypies and other movement disorders

Motor stereotypies are common, repetitive, rhythmic movements with typical onset in early childhood. They are most often described in children with autism spectrum disorder (ASD) and intellectual disability (ID). Such movements are usually bilateral with a fixed pattern. Common motor stereotypies are hand flapping, waving, or rotating. They can usually be stopped by distraction such as by calling one's name.

They are classified as primary (physiological and common examples are pencil tapping, hair twisting, nail biting) and secondary (pathological and depending upon the presence of additional signs or symptoms). Nearly half of the children with ASD can have secondary motor stereotypies.

The biggest differential features from motor tics is the absence of premonitory urges prior to the motor stereotypies. Also unlike tics, stereotypies can have onset before the age of 3 years. ADHD, ASD and OCD are the commonest comorbidities found with complex motor stereotypies 

Children with dyskinetic cerebral palsy can have various dyskinesias which often can mimic epileptic seizures. For example, repetitive twisting movements of dystonia, status dystonicus or choreoathetoid movements can be mistaken as an epileptic seizure. 

Never forget the basics- history, history and history!

Accurate diagnosis sometimes cannot be possible in the first consultation itself and often more information- such as good description or video of the episodes are needed. Sometimes, the clinician can imitate the episode in the clinic to get the clear picture of them. Even after these, investigations like video-EEG telemetry might be needed. It is hence necessary not to order unnecessary investigations or start any treatment like anti-epileptic medications before confirmation of the diagnosis. 

The health professional should be prepared to say ‘I do not know’ in situations where insufficient evidence is present and more information is needed to come to the conclusion. Also, avoiding terms like ‘seizures’ or ‘convulsions’ can be helpful as their usage can project a biased opinion. Instead, they can be referred as ‘events’ or ‘episodes’. Often, a detailed history itself can solve the mystery in nearly half of the patients (19). Often such children are ‘labelled’ with epilepsy and are started on anti-epileptic medication even before referring to a pediatric neurologist. So, in a tertiary hospital clinic, the pediatric neurologist can face challenges in expunging the given label of ‘epilepsy’. 

Investigations are to support the clinical diagnosis of epilepsy and not to rule out epilepsy! A video of the episode can be the first sought investigation. Such video can be also shared with another health professional with the parent’s consent where another opinion is needed. 

The diagnosis of an epileptic seizure is mostly clinical one and there is no single best diagnostic test for it. Interictal EEG lacks both specificity and specificity. Patients with epilepsies can have normal EEGs and patients without epilepsy may show electroencephalographic abnormalities (22). Video-EEG telemetry can be a useful investigation in certain cases if such facility is available in the hospital. Alternatively, ambulatory EEG can be considered. 

ECG should be obtained in all ‘convulsive’ seizures and in cases where cardiac cause is suspected. These children should be referred to a pediatric cardiologist so that appropriate cardiovascular investigations can be arranged.

Neuroimaging has limited role and brain MRI can be considered only in cases like benign paroxysmal torticollis of infancy, paroxysmal tonic upgaze of infancy and spasmus nutans. 

Other investigations like impedance study (e.g. in Sandifer syndrome), genetic investigations (e.g. in paroxysmal dyskinesias, hemiplegic migraine and hyperekplexia), electrolytes (e.g. in jitteriness), sleep study and polysomnography (e.g. in narcolepsy and cataplexy) should be considered and used judiciously depending on the clinical suspicion 

Paroxysmal non-epileptic seizures can be result of number of neurological, cardiac, psychogenic and other miscellaneous conditions. As they can mimic epileptic seizures, misdiagnosis is common in such patients. Clinicians, hence should be aware of such differential diagnoses to avoid psychological, physiological and socio-economic consequences to the children and their parents.

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february-2020

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