Protective Mechanism of Stem Cells from Human Exfoliated Deciduous Teeth in Treating Spinal Cord Injury.

Spinal cord injury (SCI) induces devastating permanent deficits. Recently, cell transplantation therapy has become a notable treatment for SCI. Although stem cells from human exfoliated deciduous teeth (SHED) are an attractive therapy, their precise mechanism of action remains to be elucidated. In this study, we explored one of the neuroprotective mechanisms of SHED treatment at the subacute stage after SCI. We used a rat clip compression SCI model. The animals were randomly divided into three groups: SCI, SCI + phosphate-buffered saline (PBS), and SCI + SHED. The SHED or PBS intramedullary injection was administered immediately after SCI. After SCI, we explored the effects of SHED on motor function, as assessed by the Basso-Beattie-Bresnahan score and the inclined plane method, the signal transduction pathway, especially the Janus kinase (JAK) and the signal transducer and activator of transcription 3 (STAT3) pathway, the apoptotic pathway, and the expression of neurocan, one of the chondroitin sulfate proteoglycans. SHED treatment significantly improved functional recovery from Day 14 relative to the controls. Western blot analysis showed that SHED significantly reduced the expression of glial fibrillary acidic protein (GFAP) and phosphorylated STAT3 (p-STAT3) at Tyr705 on Day 10 but not on Day 5. However, SHED had no effect on the expression levels of Iba-1 on Days 5 or 10. Immunohistochemistry revealed that p-STAT3 at Tyr705 was mainly expressed in GFAP-positive astrocytes on Day 10 after SCI, and its expression was reduced by administration of SHED. Moreover, SHED treatment significantly induced expression of cleaved caspase 3 in GFAP-positive astrocytes only in the epicenter lesions on Day 10 after SCI but not on Day 5. The expression of neurocan was also significantly reduced by SHED injection on Day 10 after SCI. Our results show that SHED plays an important role in reducing astrogliosis and glial scar formation between Days 5 and 10 after SCI, possibly via apoptosis of astrocytes, ultimately resulting in improvement in neurological functions thereafter. Our data revealed one of the neuroprotective mechanisms of SHED at the subacute stage after SCI, which improved functional recovery after SCI, a serious condition.

Efficacy of Spinal Cord Stimulation Using Differential Target Multiplexed Stimulation for Intractable Pain of Hereditary Neuropathy with Liability to Pressure Palsies: A Case Report.

Hereditary neuropathy with liability to pressure palsies is an extremely rare genetic disorder; it is an autosomal dominant disorder with a high incidence of neuropathic and/or musculoskeletal pain. A case of achieving pain relief by spinal cord stimulation using differential target multiplexed stimulation for a 44-year-old female patient with hereditary neuropathy with liability to pressure palsies who was experiencing severe pain in her back, face, and all four limbs is presented. In her early teens, the initial symptoms were numbness and weakness of a limb after movement, which improved spontaneously. Transient pain in her back followed by systemic and persistent muscle weakness and pain developed. Deletion of the gene for peripheral myelin protein 22 was detected by peripheral nerve biopsy. The diagnosis of hereditary neuropathy with liability to pressure palsies was made in her early thirties. A spinal cord stimulation trial was performed because her severe pain continued despite administering many medications. Therefore, two spinal cord stimulation systems were implanted at the C3-5 and Th8-9 levels by two procedures. Pain in her back, arms, and legs decreased from 8 to 1, 5 to 1, and 6 to 2 on the numerical rating scale, respectively. Furthermore, opioid usage was tapered. The pain of hereditary neuropathy with liability to pressure palsies has a complicated pathogenesis and is resistant to pharmacological treatment. Spinal cord stimulation using differential target multiplexed stimulation may be a viable treatment option.

Comparative Study of Surgical Outcomes of Occipitocervical and Atlantoaxial Fusion for Retro-Odontoid Pseudotumor.

OBJECTIVE: To compare the surgical and radiographic outcomes of occipitocervical fusion (OCF) with those of atlantoaxial fusion (AAF) in patients with cervical myelopathy caused by retroodontoid pseudotumors (ROPs). METHODS: This retrospective, comparative study included 26 patients; 12 underwent occipitocervical fusion (OCF) (group O) and 14 retroodontoid pseudotumor (AAF) (group A) with a minimum 2-year follow-up. Neurologic outcomes were evaluated using the Japanese Orthopedic Association (JOA) score. Radiologic assessment included the maximum anteroposterior (AP) diameter of the anteroposterior-retroodontoid pseudotumor (AP-ROP), C2-7 angle, O-C2 angle, C1-2 angle, atlantodental interval (ADI), range of motion (ROM) of the ADI, C2-C7 sagittal vertical axis (C2-7 SVA), and T1 slope. Global spinal alignments (pelvic incidence [PI] minus lumbar lordosis [LL] [PI-LL], pelvic tilt, sacral slope, and C7 sagittal vertical axis) were also compared between the groups. RESULTS: Both groups had equally good clinical outcomes with equal complication rates. Three patients had a three-level fusion, 5 cases had a four-level fusion, and 4 cases had more than five-level fusion in group O. All cases had a single-level fusion in group A. Surgical time was significantly shorter in group A. AP-ROP was significantly downsized postoperatively in both groups and was more prominent in group O. C2-7 SVA was significantly increased and C2-7A ROM was significantly reduced in group O at the final follow-up. The PI-LL showed a significant increase in group O at the final follow-up. CONCLUSIONS: Although OCF and AAF were similarly effective for cervical myelopathy with ROP, AAF was less invasive, and spinal alignment was better maintained postoperatively in AAF than OCF.

Radiographic Prediction of the Occipito-C2 Angle Variation with Changes in Distance between the Mandible and Cervical Vertebrae: A Preliminary Study.

The Occipito (O) -C2 angle reflects the correct craniocervical spine alignment; however, the poor image quality of standard intraoperative fluoroscopy at times lead to inaccurate measurements. Herein, we preliminarily investigated the relationship between the O-C2 angle and the Gonion-C2 distance, which is based on the positioning of the mandible and the cervical spine. We enrolled patients who underwent cervical spine radiography in neutral, flexion, and extension positions from January 2020 to October 2020. The difference by posture changes for each parameter was defined as the Δ value, and the Spearman's rank correlation coefficient was determined. Furthermore, we determined the cutoff value of the ΔGonion-C2 distance to predict a decrease of > 10° in the ΔO-C2 angle, which is reported to be related to dysphagia and dyspnea. Seventy-four patients were included. Spearman's rank correlations for the neutral, flexion, and extension positions were 0.630 (P < 0.001), 0.471 (P < 0.001), and 0.625 (P < 0.001), respectively, while the cutoff values of the ΔGonion-C2 distance for predicting > 10° in the ΔO-C2 angle were 9.3 mm for the neutral flexion change (sensitivity: 0.435, specificity: 0.882) and 8.3 mm for the extension-neutral change (sensitivity: 0.712, specificity: 0.909). The O-C2 angle and Gonion-C2 distances correlated; however, this correlation was weaker in the flexed position. Nevertheless, the ΔGonion-C2 distance can be used as a warning sign for postoperative complications after posterior occipital bone fusion surgery, because a decrease of > 10° in the ΔO-C2 angle can be predicted with high specificity.

Pineal parenchymal tumor of intermediate differentiation with late spinal dissemination 13 years after initial surgery: illustrative case.

BACKGROUND: Pineal parenchymal tumors of intermediate differentiation (PPTIDs) are rare in the pineal gland. A case of PPTID that disseminated to the lumbosacral spine 13 years after the total resection of a primary intracranial tumor has been reported. OBSERVATIONS: A 14-year-old female presented with headache and diplopia. Magnetic resonance imaging revealed a pineal tumor that induced obstructive hydrocephalus. A biopsy and endoscopic third ventriculostomy were performed. Histological diagnosis revealed a grade II PPTID. Two months later, the tumor was removed via craniotomy because the postoperative Gamma Knife surgery was ineffective. Histological diagnosis confirmed PPTID, although the grade was revised from II to III. Postoperative adjuvant therapy was not performed, because the lesion had been irradiated and gross total tumor removal was achieved. She has had no recurrence in 13 years. However, pain around the anus newly appeared. Magnetic resonance imaging of the spine revealed a solid lesion in the lumbosacral spine. The lesion was subtotally resected, and histological diagnosis revealed grade III PPTID. Postoperative radiotherapy was performed, and she had no recurrence 1 year after radiotherapy. LESSONS: Remote dissemination of PPTID can occur several years after the initial resection. Regular follow-up imaging, including the spinal region, should be encouraged.

Unilateral laminotomy for bilateral decompression and balloon kyphoplasty to decompress lumber canal stenosis aggravated by osteoporotic vertebral compression fractures: A technical note.

Background: The optimal treatment of lumbar canal stenosis (LCS) associated with osteoporotic vertebral fractures (OVFs) remains unclear. Here, we have combined a minimally invasive unilateral laminotomy for bilateral decompression (ULBD) alone with balloon kyphoplasty (BKP) for LCS aggravated by OVF. Methods: ULBD with BKP was performed in three patients who showed LCS associated with OVFs on MR images with progressive lower extremity neurological deficits. Clinical outcomes were assessed using the numerical rating scale (NRS) and the Japanese Orthopaedic Association (JOA) score. Radiological outcomes were evaluated using multiple parameters (i.e., fractured vertebral body height, lumbar lordosis [LL], and focal angle of the fractured vertebral body). Results: Over 6 postoperative months, the NRS and JOA scores were clearly improved while radiological parameters remained maintained (i.e., loss of fractured vertebral body height was only 0.3-1.4 mm in all cases). Two of the three cases showed restoration of LL and focal angle postoperatively. Conclusion: The combination of ULBD with BKP is an effective option for LCS aggravated by OVF.

Diagnosis and Treatment Strategies for Arachnoiditis Ossificans Following Subarachnoid Hemorrhage: A Case Report.

Arachnoiditis ossificans (AO) is a rare disease, wherein ossified lesions in the subarachnoid space obstruct the flow of spinal fluid or compress the spinal cord, thereby causing myelopathy. Here we describe a rare case of AO and discuss the diagnosis and treatment strategies for this disease. A 66-year-old man with a history of subarachnoid hemorrhage presented with gait disturbance and dysuria for 7 months. Spinal magnetic resonance imaging and computed tomography (CT) myelography showed syringomyelia at the T5-T8 level and dorsally tethered spinal cord at the T8-T10 level. Preoperative noncontrast CT was not performed. The patient was diagnosed with adhesive arachnoiditis and underwent arachnoidolysis. However, intraoperative findings showed the presence of ossification lesions on the dorsal surface of the spinal cord, and intraoperative ultrasound (IOU) showed a hyperintense lesion with acoustic shadowing on the dorsal surface of the spinal cord, with limited visibility of the spinal cord. After removal of the lesions, IOU showed untethered and well-decompressed spinal cord and restoration of cerebrospinal fluid pulsation. Based on these findings, the patient was finally diagnosed with AO, which is an extremely rare disease, with an unknown frequency of occurrence. Therefore, all patients with adhesive spinal arachnoiditis require a preoperative noncontrast CT scan to evaluate for ossification lesions. In this case, we were fortunate to be able to treat AO with IOU, which demonstrated specific findings.

Laminectomy triggers symptomatic growth of spinal schwannoma in a patient with schwannomatosis.

Background: Schwannomatosis (SWN) is genetically similar to neurofibromatosis type 2 (NF2) and represents a NF2 gene mutation. Previous studies have shown that these mutations in both neurons and Schwann cells can lead to the development of schwannomas after nerve crush injuries. Here, we reviewed the potential pathoanatomical mechanisms for the development of a trauma-induced spinal schwannomas in a 55-year-old male with SWN. Case Description: A 49-year-old male had originally undergone a L3-L5 lumbar laminectomy for stenosis; the schwannomas seen on the preoperative magnetic resonance imaging (MRI) were not resected. Now at age 55, he newly presented with low back pain and numbness in the left L5 dermatome, and he was diagnosed with an L4 vertebral level cauda equina tumor on MRI. Following gross-total resection, the histopathological assessment revealed a Ki-67 labeling index 5-10% in hotspots (i.e., slightly higher than the normal range of schwannomas) and a 20% mosaic loss of SMARCB1. Based on these criteria, he was diagnosed as having SWN. Conclusion: In this patient with SWN, compression/physical trauma to nerves of the cauda equina during the L3-L5 laminectomy 6 years ago likely caused the progression of schwannoma.

Atypical radiographic case of arachnoid web without scalpel sign.

Background: Spinal arachnoid webs (SAW) occur when abnormally thickened bands of arachnoid membranes commonly located dorsal to the thoracic spine cause blockage of normal cerebrospinal fluid (CSF) flow, resulting in focal cord compression and myelopathy. The pathognomonic MR finding for SAW is the "positive scalpel sign" comprised of an enlarged dorsal CSF space with a normal ventral subarachnoid space. The main differential diagnostic consideration for SAW is idiopathic spinal cord herniation (ISCH); however, for ISCH, MR studies classically demonstrate ventral displacement of the spinal cord through an anterior dural defect. Here, we describe a 60-year-old female with an atypical SAW at the T3-T4 level (i.e., the preoperative MR failed to demonstrate the "positive scalpel sign"). Nevertheless, at surgery, intraoperative ultrasonography confirmed that SAW was present and was decompressed/marsupialized/removed. Case Description: A 60-year-old female presented with sensory impairment to both lower extremities. The thoracic MR images showed an enlarged dorsal CSF space at the T3-T4 level but without the "scalpel sign" suggesting "interruption" of CSF flow by thickened bands of focal dorsal arachnoidal tissues. Although the initial preoperative diagnosis was ISCH, intraoperative ultrasound (IOUS) confirmed the presence of a thickened arachnoid band, confirming the diagnosis of a SAW that was appropriately decompressed/resected. Conclusion: Correctly, establishing the preoperative diagnosis of a SAW based on MR imaging may sometimes be difficult as the typical "scalpel sign" may not be present in all patients. Notably, in cases like this one, IOUS may critically confirm the diagnosis of SAW thus leading to appropriate SAW decompression/removal.

Driver Genetic Mutations in Spinal Cord Gliomas Direct the Degree of Functional Impairment in Tumor-Associated Spinal Cord Injury.

Genetic analysis in glioma has been developed recently. Spinal cord glioma is less common than intracranial glioma. Thus, the clinical significance of genetic mutations in spinal cord gliomas remains unclear. Furthermore, because the spinal cord is an important communication channel between the brain and the rest of the body, increased attention should be paid to its functional prognosis. In this study, we investigated the functional prognosis and driver genetic mutations in eight patients with spinal cord gliomas (World Health Organization grade I, three cases; grade II, two cases; grade III/IV, three cases). IDH mutations were detected in all grade II cases and H3F3A mutations were detected in all grade III/IV cases. The functional status of grade I and II gliomas remained unchanged or improved 1 year after surgery, whereas grade III/IV gliomas remained unchanged or deteriorated. Spinal glioma progenitor cells with H3F3A mutations were associated with accelerated tumor-associated spinal cord injury, which led to functional impairment. Conversely, the presence of IDH mutations, which are rarely reported in spinal gliomas, indicated a relatively favorable functional prognosis.

Two cases of solitary fibrous tumor/hemangiopericytoma with different clinical features according to the World Health Organization classification: case report and review of the literature.

Solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) have been classified as one entity by the World Health Organization in 2016 due to gene fusion between NAB2 and STAT6. In the Central Nervous System (CNS), a hypocellular, collagenized tumor with a classic SFT phenotype is considered grade I, whereas more densely cellular tumors mostly corresponding to the HPC phenotype are classified as grade II or III (anaplastic) depending in mitotic count (<5 vs. >5 mitoses per 10 high-power fields). Herein, we report two cases of targeted SFT/HPC in which pathological differences and WHO grading affect clinical features. A 75-year-old woman presented with headache and had an intradural extramedullary tumor at the C1 to C2 level. The tumor was well-circumscribed and attached only to the dura mater. It was totally removed and diagnosed SFT/HPC grade I. In contrast, a 68-year-old woman presented with numbness in the right upper limb and had an intradural extramedullary tumor at the medulla to C3 levels The tumor was irregularly marginated and strongly adherent to the spinal cord and involved the vertebral artery. It was sub totally removed and diagnosed SFT/HPC grade II. To the best of our knowledge, there are only 12 cases of SFT/HPC at the craniocervical junction, including the present two cases, of which four that were adherent to the spinal cord or involved the vertebral artery were grade II or III. Although the location of the tumor was almost the same, there were significant differences in the intraoperative findings according to the WHO grading.