Treatment of Syringomyelia Characterized by Focal Dilatation of the Central Canal Using Mesenchymal Stem Cells and Neural Stem Cells.

BACKGROUND: Syringomyelia is a progressive chronic disease that leads to nerve pain, sensory dissociation, and dyskinesia. Symptoms often do not improve after surgery. Stem cells have been widely explored for the treatment of nervous system diseases due to their immunoregulatory and neural replacement abilities. METHODS: In this study, we used a rat model of syringomyelia characterized by focal dilatation of the central canal to explore an effective transplantation scheme and evaluate the effect of mesenchymal stem cells and induced neural stem cells for the treatment of syringomyelia. RESULTS: The results showed that cell transplantation could not only promote syrinx shrinkage but also stimulate the proliferation of ependymal cells, and the effect of this result was related to the transplantation location. These reactions appeared only when the cells were transplanted into the cavity. Additionally, we discovered that cell transplantation transformed activated microglia into the M2 phenotype. IGF1-expressing M2 microglia may play a significant role in the repair of nerve pain. CONCLUSION: Cell transplantation can promote cavity shrinkage and regulate the local inflammatory environment. Moreover, the proliferation of ependymal cells may indicate the activation of endogenous stem cells, which is important for the regeneration and repair of spinal cord injury.

Neck pain and Headache Complicated by Persistent Syringomyelia After Foramen Magnum Decompression for Chiari I Malformation: Improvement with Multimodal Chiropractic Therapies.

BACKGROUND Patients with Arnold-Chiari Malformation I (CM-I) treated with foramen magnum decompression (FMD) can have ongoing neck pain, headaches, and other symptoms complicated by persistent syringomyelia, yet there is little research regarding treatment of these symptoms. CASE REPORT A 62-year-old woman with a history of residual syringomyelia following FMD and ventriculoperitoneal shunt for CM-I presented to a chiropractor with progressively worsening neck pain, occipital headache, upper extremity numbness and weakness, and gait abnormality, with a World Health Organization Quality of Life score (WHO-QOL) of 52%. Symptoms were improved by FMD 16 years prior, then progressively worsened, and had resisted other forms of treatment, including exercises, acupuncture, and medications. Examination by the chiropractor revealed upper extremity neurologic deficits, including grip strength. The chiropractor ordered whole spine magnetic resonance imaging, which demonstrated a persistent cervico-thoracic syrinx and findings of cervical spondylosis, and treated the patient using a multimodal approach, with gentle cervical spine mobilization, soft tissue manipulation, and core and finger muscle rehabilitative exercises. The patient responded positively, and at the 6-month follow-up her WHO-QOL score was 80%, her grip strength and forward head position had improved, and she was now able to eat using chopsticks. CONCLUSIONS This case highlights a patient with neck pain, headaches, and persistent syringomyelia after FMD for CM-I who improved following multimodal chiropractic and rehabilitative therapies. Given the limited, low-level evidence for these interventions in patients with persistent symptoms and syringomyelia after FMD, these therapies cannot be broadly recommended, yet could be considered on a case-by-case basis.

Siringomielia: revisión a propósito de un caso / Syringomyelia: review, case and report

La siringomielia supone un desafío diagnóstico, ya que es una entidad poco reconocida si no se tiene conciencia de su existencia. Al ser un cuadro progresivo, cuya clínica puede presentarse de forma larvada y ser coincidente con otras patologías neurológicas tales como la esclerosis múltiple, su detección suele realizarse en etapas tardías sobre todo en población adulta y más aún cuando se presenta de forma adquirida. Por lo que el estudio imagenológico con Resonancia Magnética adquiere especial relevancia, permitiendo identificar y clasificar la enfermedad, lo que brindará la base para decidir terapía.

Syringomyelia is a diagnostic challenge, since it is a poorly recognized disease, especially if its existence remains unknown. Being a progressive disease, whose clinic can present in a latent way and be coincident with other neurological pathologies such as multiple sclerosis, its detection is usually conducted in late stages, especially in the adult population and even more when it presents in an acquired way. Therefore, the imaging study with Magnetic Resonance acquires special relevance, allowing to be identified and classified, which will provide the basis for deciding on therapy

Active Conservative Management of Primary Spinal Syringomyelia: A Scoping Review and Perspectives for an Activity-based Clinical Approach.

OBJECTIVE: This scoping review aimed to identify and synthesize existing research on active conservative management of primary spinal syringomyelia and associated symptoms and to discuss perspectives for clinical application using an activity-based approach. METHODS: PubMed, Embase, Scopus, and Web of Science were systematically searched for empirical studies of conservative management or therapies of adults with primary spinal syringomyelia from inception to April 2021. In addition, abstracts from relevant conferences were searched. Study characteristics and key findings were extracted, and findings descriptively synthesized. RESULTS: Of 1,186 studies screened, 7 studies met the eligibility criteria (4 single case studies and 3 cohort studies, a total of 90 individuals). The interventions were primarily physiotherapeutic, mostly by posture correction and exercises, and effects were alleviation of pain, improved physical function, improved activities of daily living and quality of life. Analysis of factors triggering symptoms and rationale for choice of intervention based upon these was limited. CONCLUSION: Evidence of active conservative management of primary spinal syringomyelia and associated symptoms is limited. Many variations and limitations in the existing research limit the conclusions. High-quality research is needed to enable healthcare professionals to apply evidencebased active conservative interventions.

Refractory Morvan syndrome responsive to rituximab: a case report and review of the literature.

Morvan Syndrome (MoS) is an autoimmune disorder characterized by peripheral nerve hyperexcitability, autonomic dysfunction, and encephalopathy. We describe the case of a man with a history of thymoma diagnosed with a paraneoplastic MoS with a severe painful neuropathy refractory to immunoglobulins and steroids who had a dramatic and lasting response following treatment with rituximab. We also reviewed the clinical features, comorbidities, laboratory findings, treatment responses, relapses, and long-term outcomes of all published cases of MoS treated with rituximab. This drug appears promising for the treatment of patients with MoS who failed first line therapy with immunoglobulins and steroids.

Multiple therapeutic effects of human neural stem cells derived from induced pluripotent stem cells in a rat model of post-traumatic syringomyelia.

BACKGROUND: Post-traumatic syringomyelia (PTS) affects patients with chronic spinal cord injury (SCI) and is characterized by progressive deterioration of neurological symptoms. To improve surgical treatment, we studied the therapeutic effects of neuroepithelial-like stem cells (NESCs) derived from induced pluripotent stem cells (iPSCs) in a rat model of PTS. To facilitate clinical translation, we studied NESCs derived from Good Manufacturing Practice (GMP)-compliant iPSCs. METHODS: Human GMP-compliant iPSCs were used to derive NESCs. Cryo-preserved NESCs were used off-the-shelf for intraspinal implantation to PTS rats 1 or 10 weeks post-injury, and rats were sacrificed 10 weeks later. In vivo cyst volumes were measured with micro-MRI. Phenotypes of differentiated NESCs and host responses were analyzed by immunohistochemistry. FINDINGS: Off-the-shelf NESCs transplanted to PTS rats 10 weeks post-injury reduced cyst volume. The grafted NESCs differentiated mainly into glial cells. Importantly, NESCs also stimulated tissue repair. They reduced the density of glial scars and neurite-inhibiting chondroitin sulfate proteoglycan 4 (CSPG4), stimulated host oligodendrocyte precursor cells to migrate and proliferate, reduced active microglia/macrophages, and promoted axonal regrowth after subacute as well as chronic transplantation. INTERPRETATION: Significant neural repair promoted by NESCs demonstrated that human NESCs could be used as a complement to standard surgery in PTS. We envisage that future PTS patients transplanted with NESCs will benefit both from eliminating the symptoms of PTS, as well as a long-term improvement of the neurological symptoms of SCI. FUNDING: This work was supported by Vinnova (2016-04134), Karolinska Institutet StratRegen, and the Chinese Scholarship Council.

Effect of mesenchymal stem cells therapy in experimental kaolin induced syringomyelia model.

BACKGROUND: Syringomyelia is a pathological cavitation of the spinal cord. In this study, we examined whether a syrinx cavity would limit itself with axonal regeneration and stem cell activity in the cavity, and we evaluated subjects on a functional basis. METHODS: Groups were designated as kaolin, trauma, kaolin-trauma, and saline groups. Also divided out of the syringomyelia treated groups were those given human mesenchymal stem cells (hMSCs). All groups were evaluated with immunohistochemistry, electron microscopy, confocal microscopy and functionally. RESULTS: The kaolin-trauma group had a significant correction of BBB score with hMSCs therapy. The syrinx cavity measurements showed significant improvement in groups treated with hMSCs. The tissue surrounding the syrinx cavity, however, appeared to be better organized in groups treated with hMSCs. The process of repair and regeneration of damaged axons in the lesion were more improved in groups treated with hMSCs. Using confocal microscopy, fluorescence of hMSCs was observed in the central canal, in the ependymal tissue, and around the lesion. CONCLUSIONS: It was concluded that axonal repair accelerated in groups receiving stem cells, and thus, stem cells may be effective in recovery of neural tissue and myelin damage in syringomyelia.

The management of Chiari malformation type 1 and syringomyelia in children: a review of the literature.

In anticipation of the "Chiari and Syringomyelia Consensus Conference" held in Milan in 2019, we performed a systematic literature review on the management of Chiari malformation type 1 (CM1) and syringomyelia (Syr) in children.We aimed to summarize the available evidence and identify areas where consensus has not been reached and further research is needed.In accordance with PRISMA guidelines, we formulated seven questions in Patients-Interventions-Comparators-Outcomes (PICO) format. Six PICOs concerned CM1 children with/without additional structural anomalies (Syr, craniosynostosis, hydrocephalus, tethered cord, and cranio-vertebral junction anomalies), and one PICO Syr without CM1. We searched Medline, Embase, Cochrane, and NICE databases from January 1, 1999, to May 29, 2019. Cohort studies, controlled and randomized clinical trials (CCTs, RCTs), and systematic reviews were included, all pertinent only to patients ≤ 18 years of age.For CM1, 3787 records were found, 460 full texts were assessed and 49 studies (46 cohort studies, one RCT, and two systematic reviews) were finally included. For Syr, 376 records were found, 59 full texts were assessed, and five studies (one RCT and four cohort studies) were included. Data on each PICO were synthetized narratively due to heterogeneity in the inclusion criteria, outcome measures, and length of follow-up of the included studies.Despite decades of experience on CM1 and Syr management in children, the available evidence remains limited. Specifically, there is an urgent need for collaborative initiatives focusing on the adoption of shared inclusion criteria and outcome measures, as well as rigorous prospective designs, particularly RCTs.

Syringomyelia: diagnosis and management.

In the pre-MR era syringomyelia often presented late, as a crippling neurological disorder. Today, most cases are diagnosed earlier, with less pronounced deficits. We are therefore presented with new challenges, including understanding the significance of various presenting symptoms, knowing when surgery might help and being aware of other treatments that could benefit someone living with the effects of syringomyelia, or its underlying cause.

Transplantation of Human Neural Precursor Cells Reverses Syrinx Growth in a Rat Model of Post-Traumatic Syringomyelia.

Posttraumatic syringomyelia (PTS) is a serious condition of progressive expansion of spinal cord cysts, affecting patients with spinal cord injury years after injury. To evaluate neural cell therapy to prevent cyst expansion and potentially replace lost neurons, we developed a rat model of PTS. We combined contusive trauma with subarachnoid injections of blood, causing tethering of the spinal cord to the surrounding vertebrae, resulting in chronically expanding cysts. The cysts were usually located rostral to the injury, extracanalicular, lined by astrocytes. T2*-weighted magnetic resonance imaging (MRI) showed hyperintense fluid-filled cysts but also hypointense signals from debris and iron-laden macrophages/microglia. Two types of human neural stem/progenitor cells-fetal neural precursor cells (hNPCs) and neuroepithelial-like stem cells (hNESCs) derived from induced pluripotent stem cells-were transplanted to PTS cysts. Cells transplanted into cysts 10 weeks after injury survived at least 10 weeks, migrated into the surrounding parenchyma, but did not differentiate during this period. The cysts were partially obliterated by the cells, and cyst walls often merged with thin layers of cells in between. Cyst volume measurements with MRI showed that the volumes continued to expand in sham-transplanted rats by 102%, while the cyst expansion was effectively prevented by hNPCs and hNESCs transplantation, reducing the cyst volumes by 18.8% and 46.8%, respectively. The volume reductions far exceeded the volume of the added human cells. Thus, in an animal model closely mimicking the clinical situation, we provide proof-of-principle that transplantation of human neural stem/progenitor cells can be used as treatment for PTS.

Management of Chiari malformation type I and syringomyelia during pregnancy and delivery.

OBJECTIVE: Although a recurrent question in clinical practice, the management of Chiari malformation type I (CMI) and/or syringomyelia during pregnancy and delivery is still debated. The aim of this study was to investigate the modalities of delivery and anesthesia in women presenting with CMI and/or syringomyelia at a national reference center, and to question their potential role in the natural history of these conditions. STUDY DESIGN: We conducted a retrospective cohort study using a standardized questionnaire, a customized clinical severity score and data from medical records. RESULTS: 83 patients were included in the final analysis: 32 had CMI without syringomyelia, 27 had CMI with syringomyelia and 24 had non-foraminal syringomyelia. Most patients (55/83) were not diagnosed at the time of their pregnancy, 12 had surgery before being pregnant and 16 were diagnosed but not operated. Most women underwent vaginal delivery (62 %) and neuraxial (i.e. epidural or spinal) anesthesia (69 %). However, the proportion of cesarean procedures increased to 53.6 % and even 83.3 % when considering only patients already diagnosed or operated on, respectively. Nonetheless, neither vaginal compared to cesarean delivery (change in clinically severity score: -1.5 ± 0.4 versus -0.9 ± 0.4, p = 0.4) nor neuraxial compared to general anesthesia (-1.2 ± 0.3 versus -1.5 ± 0.6, p = 0.7) were associated with increased clinical deterioration. CONCLUSION: Although individual evaluation is mandatory, this study supports that neither delivery nor anesthesia modalities affect the natural history for the vast majority of patients with CMI and/or syringomyelia.

Syrinx Secondary to Chiari-like Tonsillar Herniation in Spontaneous Intracranial Hypotension.

OBJECTIVE: Syrinx development in patients with spontaneous intracranial hypotension (SIH) has rarely been described. To better understand this entity, we compared the clinical and radiographic findings in a series of patients with SIH and acquired Chiari-like tonsillar herniation with and without syrinx formation. METHODS: Six patients with syrinx in the setting of SIH and Chiari-like tonsillar herniation were retrospectively identified. The clinical and radiographic findings and outcomes were compared with those from a control group of patients with SIH and Chiari-like tonsillar herniation without syrinx. RESULTS: The patients with SIH and syrinx had had a higher opening pressure than had the control group (mean, 14.0 cm H2O vs. 7.4 cm H2O; P = 0.02) and a higher body mass index (mean, 33 kg/m2 vs. 26 kg/m2; P = 0.01). The patients with syrinx had had an average obex displacement of 3.7 ± 2.2 mm below the plane of the foramen magnum compared with a position of 1.9 ± 3.1 mm above the plane of the foramen magnum in the control group (P = 0.004). The mean tonsillar descent was 12.7 ± 4.7 mm below the foramen magnum in those with syrinx compared with 5.9 ± 2.5 in the control group (P = 0.009). The clinical symptoms had improved in 83.3% of the patients with syrinx and 75% of the control patients after spinal cerebrospinal fluid leak closure. Three patients (50%) also had radiographic syrinx reduction. CONCLUSION: Our results have shown that SIH can be an underrecognized cause of syrinx with key differences in body habitus and obex displacement compared with SIH without syrinx. In patients with tonsillar herniation into the foramen magnum associated with syrinx, the presence of SIH should be considered to avoid unnecessary foramen magnum decompression, even in those with a normal opening pressure.

Management of Chiari I Deformity in Children and Adolescents: A Report from the Consensus Taskforce of the Brazilian Society of Pediatric Neurosurgery

Much controversy remains on the current management of Chiari I deformity (CID) in children, with many clinical, surgical and ethic-legal implications. The Brazilian Society of Pediatric Neurosurgery (SBNPed, in the Portuguese acronym) has put together a panel of experts to analyze updated published data on the medical literature about this matter and come up with several recommendations for pediatric neurosurgeons and allied health professionals when dealing with CID. Their conclusions are reported herein, along with the respective scientific background.

CASPR2 autoimmunity in children expanding to mild encephalopathy with hypertension.

OBJECTIVE: To delineate autoimmune disease in association with contactin-associated protein 2 (CASPR2) antibodies in childhood, we reviewed the clinical phenotype of children with CASPR2 antibodies. METHODS: Retrospective assessment of patients recruited through laboratories specialized in autoimmune CNS disease. RESULTS: Ten children with serum CASPR2 antibodies were identified (age at manifestation 18 months to 17 years). Eight children with CASPR2 antibody titers from ≥1:160 to 1:5,120 had complex autoimmune diseases with an age-dependent clinical phenotype. Two children with structural epilepsy due to CNS malformations harbored nonspecific low-titer CASPR2 antibodies (serum titers 1:80). The clinical symptoms of the 8 children with high-titer CASPR2 antibodies were general weakness (8/8), sleep dysregulation (8/8), dysautonomia (8/8) encephalopathy (7/8), neuropathic pain (7/8), neuromyotonia (3/8), and flaccid paresis (3/8). Adolescents (3/8) showed pain, neuromyotonia, and encephalopathy, whereas younger children (5/8) displayed severe hypertension, encephalopathy, and hormonal dysfunction mimicking a systemic disease. No tumors were identified. Motor symptoms remitted with immunotherapy. Mild behavioral changes persisted in 1 child, and autism spectrum disorder was diagnosed during follow-up in a young boy. CONCLUSION: High-titer CASPR2 antibodies are associated with Morvan syndrome in children as young as 2 years. However, CASPR2 autoimmunity mimics systemic disease and hypertensive encephalopathy in children younger than 7 years. The outcome following immunotherapy was mostly favorable; long-term behavioral impairment may occur in younger children.

Persistent Syringomyelia After Posterior Fossa Decompression for Chiari Malformation.

BACKGROUND: Chiari malformation (CM) is often comorbid with syringomyelia. The treatment of CM via posterior fossa decompression (PFD) may not improve syringomyelia in up to 40% of patients, based on historical cohorts. Management of these patients is problematic, as both reoperation and syrinx shunting have high failure rates in the long term. METHODS: We retrospectively reviewed our cases in which patients with CM type 1 or 1.5 and syringomyelia underwent PFD without postoperative improvement in syringomyelia. Symptomatology and radiographic measurements were collected at presentation and on the first and latest available postoperative scans and analyzed. We present 2 cases to illustrate the challenges in the management of these patients. RESULTS: Our cohort consisted of 48 consecutive patients with CM and syringomyelia who underwent PFD. Of these, 41 patients had postoperative improvement in or resolution of syringomyelia. We subsequently studied the cohort of 7 patients who underwent PFD with (n = 5) or without (n = 2) durotomy and demonstrated worsening of syringomyelia following surgery. This cohort had mean (±SEM) preoperative syrinx area of 23.9 ± 10.0 mm2. Postoperatively, the mean syrinx area increased to 40.5 ± 9.6 mm2 and 57.3 ± 12.5 mm2 on the first and latest postoperative scans available (P = 0.02), for an increase of 106.9% ± 94.4% and 186.0% ± 107.4% (P = 0.04). Presenting symptoms included occipital headache, paresthesias, visual deterioration, and paraspinal pain. On last follow-up (mean 13.9 ± 4.9 months), the majority of symptoms were resolved in this cohort, despite persistence of syringomyelia. CONCLUSIONS: In this small cohort of unique patients, syrinx resolution was not achieved via decompression surgery. Despite "radiographic failure," good symptom control was achieved, with most patients remaining or becoming asymptomatic postoperatively, thus supporting our rationale for what has largely been a conservative approach in this population.

Silent post-traumatic syringomyelia and syringobulbia.

INTRODUCTION: Post-traumatic syringomyelia is a complication of traumatic spinal cord injury consisting in the development of a cavity within the spinal cord. Once considered an uncommon complication, its diagnosis has increased due to increased attention and advances in medical technology. Common symptoms of the syrinx are a sensory loss of the dissociated type with pain and temperature loss and the preservation of fine touch and vibratory sensation. Eventually, a deterioration of motor function with muscle wasting may occur. CASE PRESENTATION: We present the case of a 36-year-old woman who sustained a sport accident in 1996, resulting in AIS A, T7 paraplegia. She underwent a magnetic resonance imaging (MRI) examination because of neck and left shoulder pain that resolved after a short anti-inflammatory treatment. The MRI showed a large cavity involving the cord beneath T6 and the medulla. Septations were present at both the spinal cord and medulla levels. With regard to vertebral status, the MRI showed the presence of severe kyphosis at the fracture level together with spinal cord compression. The neurological examination was normal except for the pre-existing paraplegia and of a slight heat and pain sensation deficit in the C8 dermatome. DISCUSSION: We discuss the need of regular follow-up examinations as even large syrines with involvement of the brainstem may be asymptomatic. We also discuss the possible pathogenetic factors including the type of treatment of the vertebral lesion.

Klippel-Feil Syndrome With Auxiliary Anterior Cervical Meningomyelocele and Thoracic Syringomyelia: A Case Report.

STUDY DESIGN: Case report. OBJECTIVE: Since this is the first ever case of a male patient with Klippel-Feil syndrome (KFS) with anterior cervical meningomyelocele and syringomyelia. All four previously reported cases were female patients. This makes this case unique. SUMMARY OF BACKGROUND DATA: KFS with auxiliary anterior cervical meningomyelocele is a rare entity. To the best of our knowledge so far only four cases are reported. METHODS: A 22-year-old male patient was presented to neurology outpatient department with 2-year history of left hand paresthesia and progressive weakness. The diagnostic evaluation showed KFS with auxiliary anterior cervical meningomyelocele and thoracic syringomyelia. RESULTS: Patient was sent to neurosurgery department for intervention. After discussing the possible risks and complications of intervention he opted for conservative therapy and declined the surgery. CONCLUSION: The paucity of data is the key reason for any recommended protocol for management of such patients but the available literature recommends neurosurgical intervention in symptomatic patients. LEVEL OF EVIDENCE: 5.

Scoliosis in patients with Chiari malformation type I.

The literature about the association between Chiari malformations (CMs) and scoliosis has been growing over the last three decades; yet, no consensus on the optimal management approach in this patient population has been reached. Spinal anomalies such as isolated syrinxes, isolated CM, and CM with a syrinx are relatively common among patients with presumed idiopathic scoliosis (IS), a rule that also applies to scoliosis among CM patients as well. In CM patients, scoliosis presents with atypical features such as early onset, left apical or kyphotic curvature, and neurological deficits. While spinal X-rays are essential to confirm the diagnosis of scoliosis among CM patients, a magnetic resonance imaging (MRI) is also recommended in IS patients with atypical presentations. Hypotheses attempting to explain the occurrence of scoliosis in CM patients include cerebellar tonsillar compression of the cervicomedullary junction and uneven expansion of a syrinx in the horizontal plane of the spinal cord. Early detection of scoliosis on routine spinal examination and close follow-up on curve stability and progression are essential initial steps in the management of scoliosis, especially in patients with CM, who may require full spine MRI to screen for associated neuro-axial anomalies; bracing and spinal fusion may be subsequently pursued in high-risk patients.