Nicotinic signaling is required for motor learning but not rehabilitation after spinal cord injury

Currently, therapeutic intervention for spinal cord injury is limited. Many approaches rely on strengthening the remaining substrate and driving recovery through rehabilitative training. As compared to learning novel compensatory strategies, rehabilitation focuses on restoring movements lost to injury. Whether rehabilitation of previously learned movements after spinal cord injury requires the molecular mechanisms of motor learning, or if it engages previously trained motor circuits without requiring novel learning. Our findings implicate the latter mechanism, as we demonstrate that nicotinic acetylcholine signaling is required for motor learning but is dispensable for the recovery of previously trained motor behavior after cervical spinal cord injury.

First Manifestation of AQP4-IgG-Positive Neuromyelitis Optica Spectrum Disorder Associated with the COVID-19 mRNA Vaccine BNT162b2

BNT162b2 is one of the effective COVID-19 vaccines. However, some researchers have also reported that the vaccines caused some neurological complications. Here, we present a case of a 52-year-old female who developed aquaporin (AQP) 4-IgG-positive neuromyelitis optica spectrum disorder (NMOSD) fourteen days after the first dose of BNT162b2. She experienced pain of the neck, weakness of the left arm and leg, numbness of the left hand, and impaired temperature sensation of the right leg. MRI showed T2WI hyperintense lesions in the area postrema and cervical spinal cord ranging from C1 to C6 level, and Gd-enhanced lesions from C3 to C5 level; especially left lateral column was predominantly enhanced. Cell-based assays showed anti-AQP4 antibody (AQP4Ab) was positive. We diagnosed AQP4-IgG-positive NMOSD. After high-dose glucocorticoid therapy, she is showing improved symptoms. The present case was characterized by the findings that a Gd-enhanced lesion in the cervical cord localized dominantly at the left lateral column, consistent with the side of the shoulder where the vaccine was injected. Many studies suggested that AQP4-IgG-positive NMOSD development has multistep mechanisms following the blood-brain barrier (BBB) breakdown. We suspected that BNT162b2-associated immune responses lead to BBB disruptions. Through the limitedly damaged BBB, the plasma cells producing AQP4Abs might be recruited to CNS, and AQP4Abs might bind to the cervical cord and the area postrema. A large population-based study revealed that BNT162b2-associated complications were less likely to be observed than COVID-19 infectious symptoms. However, considering the present case, neurologists need to observe the conditions following vaccination.

Scoping review of existing funding sources for DCM research: opportunities and challenges for targeting the AO Spine RECODE-DCM research priorities (Preprint)

BACKGROUND Degenerative Cervical Myelopathy (DCM) is a common, disabling condition of symptomatic cervical spinal cord compression that requires significant research advances to improve patient outcomes. AO Spine RECODE-DCM recently identified the top research priorities for DCM. To effectively address these priorities, appropriate funding of DCM research is essential. OBJECTIVE This review characterises current funding in DCM research to consider its significance and highlight future opportunities. METHODS A systematic review of Web of Science for “cervical” AND “myelopathy” was conducted. Papers exclusively studying DCM, with declared funding, and published between January 1, 1995 and March 21, 2020 were considered eligible. Funding sources were classified by country of origin and organisation type. A grant search was also conducted using Dimensions.ai (Digital Science Ltd, London, United Kingdom). RESULTS A total of 621 papers were included, with 300 unique funding bodies. The top funders were AO Spine (n=87), National Institutes of Health, USA (n=63) and National Natural Science Foundation, China (n=63). The USA (n=242) funded the most DCM research, followed by China (n=209) and Japan (n=116). Funding in the USA was primarily provided by corporate or non-profit organisations (60.3%); in China, by institutions (99.5%). Dimensions.ai data showed 180 DCM research grants explicitly awarded, with a total value of US$45.6 million since 1996. CONCLUSIONS DCM funding appears to be predominantly from USA, China and Japan, aligning with areas of high DCM research activity and underpinning the importance of funding to increasing research capacity. The existing funding sources differ from medical research in general, representing opportunities for future investment in DCM.

Fully Characterized Mature Human iPS- and NMP-Derived Motor Neurons Thrive Without Neuroprotection in the Spinal Contusion Cavity

Neural cell interventions in spinal cord injury (SCI) have focused predominantly on transplanted multipotent neural stem/progenitor cells (NSPCs) for animal research and clinical use due to limited information on survival of spinal neurons. However, transplanted NSPC fate is unpredictable and largely governed by injury-derived matrix and cytokine factors that are often gliogenic and inflammatory. Here, using a rat cervical hemicontusion model, we evaluate the survival and integration of hiPSC-derived spinal motor neurons (SMNs) and oligodendrocyte progenitor cells (OPCs). SMNs and OPCs were differentiated in vitro through a neuromesodermal progenitor stage to mimic the natural origin of the spinal cord. We demonstrate robust survival and engraftment without additional injury site modifiers or neuroprotective biomaterials. Ex vivo differentiated neurons achieve cervical spinal cord matched transcriptomic and proteomic profiles, meeting functional electrophysiology parameters prior to transplantation. These data establish an approach for ex vivo developmentally accurate neuronal fate specification and subsequent transplantation for a more streamlined and predictable outcome in neural cell-based therapies of SCI.

Feasibility of Diffusion Kurtosis Imaging in Evaluating Cervical Spinal Cord Injury in Multiple Sclerosis

Background：Quantitative evaluation of cervical spinal cord (CSC) injury in multiple sclerosis has always been a difficulty. The present study aimed to evaluate the lesion, normal-appearing gray matter (GM) and white matter (WM) damage, and therapeutic effect using diffusion kurtosis imaging (DKI) on CSC of patients with multiple sclerosis.Methods: A total of 48 patients with MS and 30 healthy adults, underwent routine MR scan and DKI of CSC. DKI-metrics were measured in the lesions and in the normal-appearing gray and white matter. MS patients were divided into those with and without T2-hyperintense lesions. Disability was assessed by the expanded disability status scale before and after therapy.Results：1) Significant differences were detected in MK, MD, and FA values between patients and healthy subjects (P < 0.05) and between patients with CSC T2-hyperintense and patients without T2-hyperintense (P < 0.05); 2) Compared to healthy, GM-MK and WM-FA were statistically reduced in patients without T2-hyperintense (P < 0.05). 3) Significant differences were observed in MK, MD, and FA between patients with T2-hyperintense after therapy (P < 0.05), as well as GM-MK and WM-FA in patients without T2-hyperintense (P < 0.05); 4) EDSS was correlated with MK values, as well as EDSS scores and MK values after therapy.Conclusions：1) DKI-metrics can detect and quantitatively evaluate the changes in cervical spinal cord micropathological structure; 2) MK values are sensitive metrics to detect the damage of gray matter; 3) MK values quantitatively evaluate the clinical disability progression and the therapeutic effect in MS patients.

Cervical Spinal Cord Atrophy can be Accurately Quantified Using Head Images

Background Spinal cord atrophy provides a clinically relevant metric for monitoring MS. However, the spinal cord is imaged far less frequently than brain due to artefacts and acquisition time, whereas MRI of the brain is routinely performed. Objective To validate spinal cord cross-sectional area measurements from routine 3DT1 whole-brain MRI versus those from dedicated cord MRI in healthy controls and people with MS. Methods We calculated cross-sectional area at C1 and C2/3 using T2*-weighted spinal cord images and 3DT1 brain images, for 28 healthy controls and 73 people with MS. Correlations for both groups were assessed between: (1) C1 and C2/3 using cord images; (2) C1 from brain and C1 from cord; and (3) C1 from brain and C2/3 from cord. Results and Conclusion C1 and C2/3 from cord were strongly correlated in controls ( r = 0.94, p<0.0001) and MS ( r = 0.85, p<0.0001). There was strong agreement between C1 from brain and C2/3 from cord in controls ( r = 0.84, p<0.0001) and MS ( r = 0.81, p<0.0001). This supports the use of C1 cross-sectional area calculated from brain imaging as a surrogate for the traditional C2/3 cross-sectional area measure for spinal cord atrophy.