Clinical Signi ﬁ cance of Terminal Syringomyelia and Accompanying Congenital Anomalies of Neurosurgical Interest in Adult and Pediatric Patients with Tethered Cord Syndrome

Magnetic resonance imaging (MRI) can be used to examine tethered cord syndrome (TCS) and terminal syringomyelia (TS). Additionally, there is increasing evidence of an association between congenital anomalies and TCS. We aimed to identify the clinical and radiological characteristics of syringomyelia and other anomalies in pediatric and adult patients with TCS. This study included 54 TCS patients (mean age, 17.37 (cid:3) 15.83 years; 31 females) admitted to our department between 2010 and 2019. The patients were divided into two age groups: pediatric ( < 18 years; 63%) and adult ( > 18 years). Clinical ﬁ ndings, direct vertebrae radiographs, lower extremity radiographs, and spinal/cranial MRI ﬁ ndings were used to evaluate all patients. Computed tomography (CT) was performed to reveal the structure of the septum in patients with Diastematomyelia. Cranial ultrasonography or CT was performed if the fontanel was open or closed, respectively, in pediatric hydrocephalus cases. Pelvic ultrasonography and urodynamic tests were performed to evaluate other comorbid anomalies and urinary system pathologies. A thick ﬁ lum terminale (73.3%) and diastematomyelia (44.4%) were found to cause spinal tension. The most common accompanying pathology was syringomyelia (78%). The common symptoms were urinary incontinence and bowel problems (71%), scoliosis (68%), and progressive lower extremity weakness (64.4%). It is dif ﬁ cult to distinguish the exact cause of symptoms in patients with TCS and TS. Due to the greater occurrence of other congenital spinal anomalies accompanying TCS, both preoperative symptoms and clinical ﬁ ndings are more severe in the pediatric group than in the adult group, and postoperative results may be more negative.

the spinal cord, and usually, this is accompanied by a lowplaced conus medullaris. 1,2 Tethered cord is associated with congenital malformations of the spine which are common in children. Congenital TCS occurs during embryonic development. In patients with TCS, tissue from the spinal cord to the sacrum-also known as the filum terminale-causes tension in the spinal cord.
In infants with this syndrome, the symptoms include skin discoloration, bristles, and dimple-shaped pits in the waist area. When diagnosed in childhood, TCS should be controlled before urological, orthopaedic, and neurological problems develop. If treatment is delayed, permanent problems (such as renal failure), uncontrollable bowel and urinary problems (such as urinary and fecal incontinence), scoliosis, and foot deformities are more likely to occur in the future. This may be secondary to other disorders, including meningomyelocele, spinal lipomas, lipomatous filum, and split cord malformations. In adults, TCS occurs mostly due to adhesion that develops following trauma or spinal surgery. 3 The prevalence of syringomyelia is 8.4/per 100,000 persons. 4 Syringomyelia is an abnormal cystic dilatation of the central canal of the spinal cord and occurs due to the accumulation of excessive cerebrospinal fluid (CSF). The CSF fuses to the ependymal layer adjacent to the central canal, causing payment. 5,6 Patients may develop various neurological deficiencies secondary to untreated syringomyelia, some of which may persist despite surgical intervention. Early detection, frequent monitoring, and rapid treatment of the underlying etiology are crucial for minimizing potentially irreversible neurological defects.
Although many theories have been proposed regarding the formation and progression of syringomyelia, the underlying pathogenesis remains unknown. 5,7 Syringomyelia can occur posttrauma and may be associated with Chiari's malformations, intramedullary tumors, meningomyelocele, meningocele, or TCS. It typically occurs in the cervical and/or thoracic segments. 8 Terminal syringomyelia (TS) refers to segmental cystic dilatation of one-third of the caudal part of the spinal cord. With the increasing use of magnetic resonance imaging (MRI) and other advanced technologies, TS has become a remarkable finding in TCS. This study aimed to identify the clinical and radiological characteristics of syringomyelia and other anomalies in pediatric and adult patients with TCS. Also, the other goal we aimed for was to answer the following question: is the tethered cord the main cause of clinical worsening in patients with TCS? Or is the clinical worsening due to congenital anomalies that accompany them?

Materials and Methods
This study was approved by the ethics committee of our university.

Patient Population
We retrospectively examined the medical records of 54 patients with TCS who were surgically treated at the neurosurgery clinic of Afyonkarahisar Health Sciences University between January 2010 and December 2019. The patients were divided into two age groups: group 1 (pediatric patients, aged <18 years) and group 2 (adults, aged !18 years).

Inclusion Criteria
Inclusion criteria of this study are as follows: • Patients diagnosed with TCS and treated surgically.
• Patients with newly developed or worsening neurological defects. • Patients with poor quality of life (back pain, leg pain, cranky legs, etc.).

Exclusion Criteria
Exclusion criteria of this study are as follows: • TCS patients without active complaints and not treated surgically. • Chiari's malformation with symptoms and requiring an operation. • Adult patients who were fully quadriplegic or paraplegic.

Radiological Evaluations
Spinal and cranial MRI was performed on patients with TCS as part of our standard protocol. The imaging was conducted using a 1.5 Tesla General Electric Signa MRI scanner (General Electric Healthcare, Milwaukee, Wisconsin, United States). The vertebra and lower extremities were evaluated using radiography in all cases. Computed tomography (CT) (Toshiba Medical Systems Corporation, Japan) was performed to reveal the structure of the septum dividing the cord in patients with diastematomyelia. Cranial ultrasonography or CT was performed if the fontanel was open or closed, respectively, in pediatric patients with hydrocephalus. Pelvic ultrasonography and urodynamic tests were performed to evaluate other comorbid anomalies and urinary system pathologies.

Surgical Treatment and Follow-up
All patients were treated following standard surgical principles. Surgical treatment was aimed at primary spinal malformation, and surgery was performed upward from the most caudal area of the cord. This rule did not apply to diastematomyelia. The standard postoperative follow-up periods for our surgical patients are 1 week, 1 month, 3 months, 6 months, and 1 year. However, the patients included in this study were followed-up for at least 2 years (average, 3.5 years).

Surgical Procedure
Under general anesthesia and intraoperative neurophysiological monitoring (IONM), patients were positioned prone. Midline intrusion was performed at the S1 to S2 level. After the paraspinal muscles were sequenced, a laminectomy was performed using a high-speed drill or Kerrison's rongeur. The ligamentum flavum and adipose tissue were then removed. The microscope was placed in the operation area. The dura mater was opened from the midline and fixed to the paravertebral muscles with sutures. After exposing all the nerve roots, filum terminale, and arachnoid bands, the filum terminale was selected using IONM.
The filum terminale contains large vessels, is whitish, and looks lighter than roots. 9,10 The IONM probe was used to determine whether the tissue was neural, as this helped avoid cutting one of the roots instead of the tense filum terminale. The roots were pulled back sideways, and the filum terminale was cut. All connective tissues and the conus medullaris connected to the caudal part of the spinal cord were released. After hemostasis was achieved watertight, duraplasty was performed using 5.0 sutures. Using fibrin adhesive products, anatomical layers are tightly closed. If accompanied by diastematomyelia, the bone septum or fibrous band were resected before the untethering procedure.

Statistical Analysis
Statistical analyses were performed using IBM SPSS Statistics for Windows, version 25 (IBM Corp., Armonk, New York, United States) and Microsoft Excel. Standard descriptive statistics (mean AE standard deviation) was calculated, and Wilcoxon's signed ranks test was used to compare groups. Statistical significance was set at p < 0.05.
The most common clinical findings in groups 1 and 2 were bladder/bowel dysfunction (64.5 and 30%, respectively) and weakness in the lower extremity (58.8 and 30%, respectively).

Radiological Outcomes
The terminal end of the conus medullaris was located at the L2-5 and L5-S2 levels in 74 (n ¼ 40) and 15% (n ¼ 8), respectively, of the 54 patients. Six (11%) of the patients were anatomically normal (T12-L2). However, when evaluated from a single-level point of view, the tethered cord was most commonly detected at the L5 level.
Accompanying pathologies were detected in 82.4% of the patients in group 1; however, no congenital anomaly or pathology was detected in 50% of the patients in group 2. ►Table 2 details the accompanying pathologies in the adult and pediatric groups.
There was a significant difference in the incidence of syringomyelia between groups 1 and 2 (p < 0.05). Syringomyelia levels, the widest dimensions, and syrinx indexes were measured in patients with syringomyelia. A statistically significant difference was found between the preoperative and postoperative measurements (p < 0.05). Detailed data for all groups are provided in ►Tables 3 and 4. Accompanying nonneurosurgical pathologies included club feet (18.5%), congenital hip dislocation (9.2%), and kidney anomalies (7.4%). This ranking was not different between the groups (►Table 2).

Treatment and Follow-up
Untethered surgery was performed on all patients, and only one patient underwent both untethered surgery and syrinx drainage.
Of the 34 patients included in group 1, the motor, sensory, and urinary functions were intact in 41, 41, and 35% of patients, respectively, during the preoperative period. The remaining patients had functional disorders to varying degrees. Compared with the preoperative period, 70, 70, and 54.5% of the patients with the aforementioned disorders showed functional improvement in motor, sensory, and urinary functions, respectively. Of the 20 patients included in group 2, the motor, sensory, and urinary functions were intact in 65, 70, and 65% of patients, respectively. Following surgery, 85.7, 83.3, and 50% of patients in group 2 experienced functional improvements in motor, sensory, and urinal functions, respectively. The clinical findings did not
Sadrameli et al 11 found that urinary incontinence or retention, followed by lower back/leg pain and lower extremity weakness, was the most frequent symptom in the pediatric population. In the pediatric group in our study, the most frequent clinical symptoms were urinary and/or stool incontinence, gait disturbance, and lower back/leg pain.
Erkan et al 12 reported that 62.5, 37.5, 68.8, 12.5, 43.8, 21.9, and 46.9% of pediatric patients presented with lower extremity muscular weakness, bilateral long-tract signs, sensory deficits, lower back pain, urinary incontinence, fecal incontinence, and progressive scoliosis, respectively. Several studies have also found similar results for presenting symptoms. In our study, we found urinary and/or fecal incontinence; lower extremity weakness; sensory deficits; gait impairment; pain in the back, waist, and legs; skin lesions and increased hair growth; restless leg; and leg atrophy and foot asymmetry in 71, 64.4, 60, 55.5, 37.7, 64.4, 31, and 17.7%, respectively, of the pediatric population.
To date, the largest study on the association of spinal anatomical disorders with TCS and TS has been conducted by Erkan et al. 14 This study reported progressive kyphoscoliosis, hemivertebrae, block vertebrae, and an unsegmented bar in 50, 67, 13, and 20% of patients, respectively. In our study, we detected kyphoscoliosis in 64.8% of patients, and hemivertebrae, butterfly vertebrae, block vertebrae, and other fusion defects in 42.5% of patients.

Syringomyelia
Several authors have linked the pathogenesis of syringomyelia with fluid accumulation and changes in local spinal blood flow and oxidative metabolism. 1,6 Syringomyelia that occurs in the distal third of the spinal cord is called TS, and several studies have linked TS to tethered cord. 1,6,15,16 In a study 17 involving 90 patients with occult spinal dysraphism, TS was detected by MRI in 27% of the cases. In this study, TS often appeared in the tense filum terminale and was accompanied by anorectal anomalies (67%), meningocele manqué (54%), and diastematomyelia (38%). Syringomyelia was found to be below the T6 level in all patients, except in one patient who had holocord syringomyelia. In a similar study, Erkan et al 14 found that of 132 patients with tethered cords, 32 (24%) had TS. According to Iskandar et al, 17 38, 34, and 28 of syrinxes were below the T8 level and covered the lower thoracic (T8-T12), lumbar (L1-S1), and thoracolumbar (T8-L4) regions, respectively.

Treatment and Follow-up
When not accompanied by TS and other anomalies, TCS is typically treated by surgically cutting the tense filum terminale and liberating the cord. Congenital neurosurgical lesions (including meningocele, diastematomyelia, and intradural lipoma) are primarily removed surgically. However, researchers differ on treatment strategies for TS. In the past, syringomyelia was treated with chemotherapy and radiotherapy. 18 The natural evolution of the tethered cord and coexisting syringomyelia are often interrelated, as the proper treatment of the tethered cord reduces the syringomyelic cavity. 19,20 Syrinx drainage in TS is also controversial. Erkan et al 14 divided patients into two groups according to the surgical protocol as follows: (1) those who underwent the procedure to release the tethered cord (group I, n ¼ 16), and (2) those in whom this procedure was combined with additional syrinx drainage (group II, n ¼ 14) . After a year of follow-up, patients in group II showed better clinical outcomes than those in group I (78 vs. 45%, respectively). Additionally, improvements in motor, sensory, and urinary deficits were observed in 50, 50, and 30% of patients in group I and in 78, 92, and 70% of patients in group II, respectively. In a study linking the tense cord syndrome to aortic coarctation, Hsu et al 6 found that the syrinx decreased after the liberalization of the tethered cord. Ng and Seow 20 reported that in a patient whose tethered cord preceded lumbar syrinx formation-as demonstrated by serial radiographic imaging-the syrinx resolved after surgical untethering. In a 3.5-year follow-up study of 34 patients, Beaumont et al 13 examined patients in the following two groups: (1) the TCS group (TCS, n ¼ 24) and (2) the TCS group with TS (TCS þ TS, n ¼ 10). The incidence of TS was 29%; only one patient underwent surgical drainage of the syrinx, and all the other patients underwent only tethered cord release. All patients who were asymptomatic preoperatively remained asymptomatic postoperatively. In the TCS þ TS group, all patients either improved clinically after tethered cord release or improved and became asymptomatic. In the TCS group without TS, most patients improved or became asymptomatic. However, a very small number of these patients experienced no change or a worsening of symptoms. Patients who did not have a preoperative syrinx did not develop a syrinx postoperatively. In a limited number of patients, postoperative MRI demonstrated either no change or a reduction in the size of the syrinx.
Of the 42 patients with TCS included in our study, the tethered cord was released and the syrinx was drained in only one patient. In the postoperative follow-up, 37% of the 27 patients with syringomyelia in group 1 exhibited no changes in the size of the syringomyelia. The size of the syringomyelia decreased significantly and the syrinx was completely lost in 44.4 and 18.6% of the patients, respective-ly. Postoperative follow-up of syringomyelia patients in group 2 showed no changes in the size of the syringomyelia in eight patients and a significant decrease in size in 50% of the patients. The syrinx was completely lost in 37.5% of the patients (►Tables 3 and 5).
Several researchers have focused on the relationship between TCS and TS. This study attached importance to the clinical symptoms of patients with TCS and evaluated the relationship between TCS and TS. However, our clinical findings suggest that compared with TS, accompanying congenital neurosurgical anomalies may be more important in TCS and aggravate the associated symptoms to a greater degree.
To prove this, we compared criteria such as symptoms, accompanying pathologies, and benefit from surgery in pediatric and adult patients (►Table 7). Syrinx and congenital anomalies occurred at a lower rate in adult patients than in pediatric patients. Moreover, the clinical findings and symptoms were milder and more tolerable in adult patients than in pediatric patients. Adult patients also achieved more favorable postoperative outcomes than pediatric patients.

Limitations
This study has a few limitations. Though we included all documented TCS cases in our hospital over a 10-year period, the sample size was relatively small (n ¼ 54). Moreover, the sample did not represent a wide geographical area, as all the patients were from Afyonkarahisar and surrounding locations.
This was a single-center study, and other institutes may follow different approaches. Moreover, the study was retrospective. Further prospective randomized studies with larger sample sizes and longer follow-ups are required to improve the generalizability of our results.

Conclusion
When TCS is accompanied by TS and/or other congenital anomalies, the patient's symptoms and clinical findings are more severe. Additionally, the possibility of postoperative recovery after surgery decreases. However, TCS alone is not accompanied by as many dramatic findings as previously thought. Although an important syndrome, TCS is a tolerable and highly curable syndrome. A multidisciplinary team consisting of a neurosurgeon, orthopaedist, urologist, radiologist, and physiotherapist should follow TCS patients closely to detect early clinical or radiological findings.