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Background: In multiple sclerosis (MS), imaging biomarkers play a crucial role in characterizing the disease at the time of diagnosis. MRI and optical coherence tomography (OCT) provide readily available biomarkers that may help to define the patient's clinical profile. However, the evaluation of cortical and paramagnetic rim lesions (CL, PRL), as well as retinal atrophy, is not routinely performed in clinic., Objective: To identify the most significant MRI and OCT biomarkers associated with early clinical disability in MS., Methods: Brain, spinal cord (SC) MRI, and OCT scans were acquired from 45 patients at MS diagnosis to obtain: brain PRL and non-PRL, CL, SC lesion volumes and counts, brain volumetric metrics, SC C2-C3 cross-sectional area, and retinal layer thickness. Regression models assessed relationships with physical disability (Expanded Disability Status Scale [EDSS]) and cognitive performance (Brief International Cognitive Assessment for Multiple Sclerosis [BICAMS])., Results: In a stepwise regression (R 2  = 0.526), PRL (β = 0.001, p = 0.023) and SC lesion volumes (β = 0.001, p = 0.017) were the most significant predictors of EDSS, while CL volume and age were strongly associated with BICAMS scores. Moreover, in a model where PRL and non-PRL were pooled, only the contribution of SC lesion volume was retained in EDSS prediction. OCT measures did not show associations with disability at the onset., Conclusion: At MS onset, PRL and SC lesions exhibit the strongest association with physical disability, while CL strongly contribute to cognitive performance. Incorporating the evaluation of PRL and CL into the initial MS patient assessment could help define their clinical profile, thus supporting the treatment choice., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cerebrospinal fluid (CSF) and spinal MRIs are often obtained in children with the radiologically isolated syndrome (RIS) for diagnosis and prognosis. Factors affecting the frequency and timing of these tests are unknown., Objective: To determine whether age or sex were associated with (1) having CSF or spinal MRI obtained or (2) the timing of these tests., Methods: We analyzed children (≤ 18 y) with RIS enrolled in an international longitudinal study. Index scans met 2010/2017 multiple sclerosis (MS) MRI criteria for dissemination in space (DIS). We used Fisher's exact test and multivariable logistic regression (covariates = age, sex, MRI date, MRI indication, 2005 MRI DIS criteria met, and race)., Results: We included 103 children with RIS (67% girls, median age = 14.9 y). Children ≥ 12 y were more likely than children < 12 y to have CSF obtained (58% vs. 21%, adjusted odds ratio [AOR] = 4.9, p = 0.03). Pre-2017, girls were more likely than boys to have CSF obtained (n = 70, 79% vs. 52%, AOR = 4.6, p = 0.01), but not more recently (n = 30, 75% vs. 80%, AOR = 0.2, p = 0.1; p = 0.004 for interaction). Spinal MRIs were obtained sooner in children ≥ 12 y (median 11d vs. 159d, p = 0.03)., Conclusions: Younger children with RIS may be at continued risk for misdiagnosis and misclassification of MS risk. Consensus guidelines are needed., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Spinal cord and brain atrophy are common in neuromyelitis optica spectrum disorder (NMOSD) and relapsing-remitting multiple sclerosis (RRMS) but harbor distinct patterns accounting for disability and cognitive impairment., Methods: This study included 209 NMOSD and 304 RRMS patients and 436 healthy controls. Non-negative matrix factorization was used to parse differences in spinal cord and brain atrophy at subject level into distinct patterns based on structural MRI. The weights of patterns were obtained using a linear regression model and associated with Expanded Disability Status Scale (EDSS) and cognitive scores. Additionally, patients were divided into cognitive impairment (CI) and cognitive preservation (CP) groups., Results: Three patterns were observed in NMOSD: (1) Spinal Cord-Deep Grey Matter (SC-DGM) pattern was associated with high EDSS scores and decline of visuospatial memory function; (2) Frontal-Temporal pattern was associated with decline of language learning function; and (3) Cerebellum-Brainstem pattern had no observed association. Patients with CI had higher weights of SC-DGM pattern than CP group. Three patterns were observed in RRMS: (1) DGM pattern was associated with high EDSS scores, decreased information processing speed, and decreased language learning and visuospatial memory functions; (2) Frontal-Temporal pattern was associated with overall cognitive decline; and (3) Occipital pattern had no observed association. Patients with CI trended to have higher weights of DGM and Frontal-Temporal patterns than CP group., Conclusion: This study estimated the heterogeneity of spinal cord and brain atrophy patterns in NMOSD and RRMS patients at individual level, and evaluated the clinical relevance of these patterns, which may contribute to stratifying participants for targeted therapy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose: Degenerative cervical myelopathy (DCM) is a common cause of spinal cord dysfunction. In this study, we explored the potential of magnetization transfer ratio (MTR) for evaluating the structural integrity of spinal cord tracts in patients with clinically significant DCM., Methods: Fifty-three patients with DCM and 41 patients with cervical radiculopathy were evaluated using high-resolution cervical spinal cord magnetic resonance imaging (MRI), which included the magnetization transfer technique. MRI data were analyzed with the Spinal Cord Toolbox (v5.5); MTR values in each spinal tract were calculated and compared between groups after correction for patient age and sex. Correlations between MTR values and patients' clinical disability rate were also evaluated., Results: A statistically significant reduction in the average MTR of the spinal cord white matter, as well as the MTR of the ventral columns and lateral funiculi, was revealed in the DCM group (adjusted p < 0.01 for all comparisons). Furthermore, reductions in MTR values in the fasciculus cuneatus, spinocerebellar, rubrospinal, and reticulospinal tracts were found in patients with DCM (adjusted p < 0.01 for all comparisons). Positive correlations between the JOA score and the MTR within the ventral columns of the spinal cord (R = 0.38, adjusted p < 0.05) and the ventral spinocerebellar tract (R = 0.41, adjusted p < 0.05) were revealed., Conclusion: The findings of our study indicate that demyelination in patients with DCM primarily affects the spinal tracts of the extrapyramidal system, and the extent of these changes is related to the severity of the condition., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This research was to unravel the impact of the lncRNA differentiation antagonizing non-protein coding RNA (DANCR)/microRNA (miR)-146a-5p/mitogen-activated protein kinase 6 (MAPK6) axis on spinal cord injury (SCI)., Methods: SCI mouse models were established and injected with si-DANCR or miR-146a-5p agomir. The recovery of motor function was assessed by Basso Mouse Scale. SCI was pathologically evaluated, and serum inflammatory factors were measured in SCI mice. Mouse spinal cord neurons were injured by H 2 O 2 and transfected, followed by assessment of proliferation and apoptosis. DANCR, miR-146a-5p, and MAPK6 in tissues and cells were detected, as well as their relationship., Results: DANCR increased and miR-146a-5p decreased in SCI. Silencing DANCR or enhancing miR-146a-5p stimulated the proliferation of mouse spinal cord neurons and reduced apoptosis. DANCR was bound to miR-146a-5p to target MAPK6. DANCR affected the proliferation and apoptosis of spinal cord neurons by mediating the miR-146a-5p/MAPK6 axis. Downregulating DANCR or upregulating miR-146a-5p improved inflammation, the destruction of spinal cord tissue structure, and apoptosis in SCI mice., Conclusion: DANCR affects spinal cord neuron apoptosis and inflammation of SCI by mediating the miR-146a-5p/MAPK6 axis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Diabetic neuropathy (DN) is a common neurological complication caused by diabetes mellitus (DM). Axonal degeneration is generally accepted to be the major pathological change in peripheral DN. Taurine has been evidenced to be neuroprotective in various aspects, but its effect on spinal cord axon injury (SCAI) in DN remains barely reported. This study showed that taurine significantly ameliorated axonal damage of spinal cord (SC), based on morphological and functional analyses, in a rat model of DN induced by streptozotocin (STZ). Taurine was also found to induce neurite outgrowth in cultured cerebral cortex neurons with high glucose exposure. Moreover, taurine up-regulated the expression of nerve growth factor (NGF) and neurite outgrowth relative protein GAP-43 in rat DN model and cultured cortical neurons/VSC4.1 cells. Besides, taurine increased the activating phosphorylation signals of TrkA, Akt, and mTOR. Mechanistically, the neuroprotection by taurine was related to the NGF-pAKT-mTOR axis, because either NGF-neutralizing antibody or Akt or mTOR inhibitors was found to attenuate its beneficial effects. Together, our results demonstrated that taurine promotes spinal cord axon repair in a model of SCAI in STZ-induced diabetic rats, mechanistically associating with the NGF-dependent activation of Akt/mTOR pathway., (© 2024. The Author(s).)

Purpose: Cervical Spondylotic Myelopathy (CSM) is a degenerative condition that leads to loss of cervical spinal cord (CSC) integrity. Various spinal cord Magnetic Resonance Imaging (MRI) methods can identify and characterize the extent of this damage. This systematic review aimed to evaluate the diagnostic, biomarker, and predictive utilities of different spinal cord MRI methods in clinical research studies of CSM. The aim was to provide a comprehensive understanding of the progress in this direction for future studies and effective diagnosis and management of CSM., Methods: A comprehensive literature search was conducted on PubMed and EMBASE from 2010 to 2022 according to PRISMA guidelines. Studies with non-human subjects, less than 3T magnetic field strength, non-clinical design, or not quantitatively focusing on the structural integrity of CSC were excluded. The extracted data from each study included demographics, disease severity, MRI machine characteristics, quantitative metrics, and key findings in terms of diagnostic, biomarker, and predictive utilities of each MRI method. The risk of bias was performed using the guide from AHRQ. The quality of evidence was assessed separately for each type of utility for different MRI methods using GRADE., Results: Forty-seven studies met the inclusion criteria, utilizing diffusion-weighted imaging (DTI) (n = 39), magnetization transfer (MT) (n = 6), MR spectroscopy (n = 3), and myelin water imaging (n = 1), as well as a combination of MRI methods (n = 12). The metric fractional anisotropy (FA) showed the highest potential in all facets of utilities, followed by mean diffusivity. Other promising metrics included MT ratio and intracellular volume fraction, especially in multimodal studies. However, the level of evidence for these promising metrics was low due to a small number of studies. Some studies, mainly DTI, also reported the usefulness of spinal cord MRI in mild CSM., Conclusions: Spinal cord MRI methods can potentially facilitate the diagnosis and management of CSM by quantitatively interrogating the structural integrity of CSC. DTI is the most promising MRI method, and other techniques have also shown promise, especially in multimodal configurations. However, this field is in its early stages, and more studies are needed to establish the usefulness of spinal cord MRI in CSM., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Spinal cord MRI is not routinely performed for multiple sclerosis (MS) monitoring. Here, we explored whether spinal cord MRI activity offers any added value over brain MRI activity for clinical outcomes prediction in MS. This is a retrospective, monocentric study including 830 MS patients who underwent longitudinal brain and spinal cord MRI [median follow-up 7 years (range: < 1-26)]. According to the presence (or absence) of MRI activity defined as at least one new T2 lesion and/or gadolinium (Gd) enhancing lesion, each scan was classified as: (i) brain MRI negative/spinal cord MRI negative; (ii) brain MRI positive/spinal cord MRI negative; (iii) brain MRI negative/spinal cord MRI positive; (iv) brain MRI positive/spinal cord MRI positive. The relationship between such patterns and clinical outcomes was explored by multivariable regression models. When compared with the presence of brain MRI activity alone: (i) Gd + lesions in the spine alone and both in the brain and in the spinal cord were associated with an increased risk of concomitant relapses (OR = 4.1, 95% CI 2.4-7.1, p < 0.001 and OR = 4.9, 95% CI 4.6-9.1, p < 0.001, respectively); (ii) new T2 lesions at both locations were associated with an increased risk of disability worsening (HR = 1.4, 95% CI = 1.0-2.1, p = 0.05). Beyond the presence of brain MRI activity, new spinal cord lesions are associated with increased risk of both relapses and disability worsening. In addition, 16.1% of patients presented asymptomatic, isolated spinal cord activity (Gd + lesions). Monitoring MS with spinal cord MRI may allow a more accurate risk stratification and treatment optimization., (© 2023. The Author(s).)

Purpose: The aim of this study is to estimate the prognostic value of some features documented on preoperative MRI study in patients with acute cervical spinal cord injury., Methods: The study was conducted in patients operated for cervical spinal cord injury (cSCI) from April 2014 to October 2020. The quantitative analysis on preoperative MRI scans included: length of the spinal cord intramedullary lesion (IMLL the canal diameter at the level of maximal spinal cord compression (MSCC) and the presence of intramedullary hemorrhage. The canal diameter at the MSCC was measured on the middle sagittal FSE-T2W images at the maximum level of injury. The America Spinal Injury Association (ASIA) motor score was used for neurological assessment at hospital admission. At 12-month follow-up all patients were examined with the SCIM questionnaire., Results: At linear regression analysis, the length of the spinal cord lesion [β coefficient -10.35, 95% confidence interval (CI)-13.71 to-6.99; p < 0.001], the diameter of the canal at the level of the MSCC (β coefficient 6.99, 95% CI 0.65 to 13.33; p = 0.032), and the intramedullary hemorrhage (β coefficient  - 20.76, 95% CI - 38.70 to - 2.82; p = 0.025), were significantly associated with the score at the SCIM questionnaire at one year follow-up: shorter spinal cord lesion, greater diameter of the canal at the level of the MSCC, and absence of intramedullary hemorrhage were predictors of better outcome., Conclusion: According to the findings of our study, the spinal length lesion, canal diameter at the level of spinal cord compression and intramedullary hematoma documented by the preoperative MRI study were associated with the prognosis of patients with cSCI., (© 2023. The Author(s).)

Background: The purpose was to clarify diagnostic clues and pitfalls in cranio-cervical junction arteriovenous fistulas (CCJ AVFs) with congestive myelopathy., Methods: In a multicenter observational study by the Neurospinal Society of Japan, we described the demographics, clinical courses, imaging findings, and outcomes of consecutive patients with CCJ AVFs presenting with congestive myelopathy between 2009 and 2019., Results: Twenty-seven patients were included (mean age, 70 years; male, 96%). Progressive symptoms within one day to one month were more common (63%) than chronic symptoms. Myelopathic symptoms were characterized by ascending paralysis beginning from the legs, involving the trunk and arms, and sometimes ending in the brainstem. Fifteen patients (56%) received a misdiagnosis, including acute transverse myelitis. The most common MRI findings were venous congestive edema of the cervical cord (96%) and the brainstem (63%) and surrounding vascular flow voids (100%). The mean extension of congestive edema was 5.5 ± 2.9 vertebral segments. The most common angiographic findings were a dural AVF (78%) at the C1 level (81%) with descending venous drainage (85%). Seven patients (26%) were administered steroids, which resulted in neurological decline in 3. Neurosurgical obliteration of the AVF led to improvements in MRI findings in 75% and a functional status in 67%; however, 44% remained dependent., Conclusions: The myelopathy of CCJ AVFs was characterized by acute ascending paralysis in elderly men. A misdiagnosis was common because of the acute presentation due to a longitudinally extensive spinal cord lesion. Dilated vessels on MRI were a key finding for the correct diagnosis. What is already known on this topic? Slowly progressive myelopathy is a well-known symptom that results from impaired spinal venous drainage due to thoracolumbar AVFs. Although cranio-cervical junction arteriovenous fistulas (CCJ AVFs) constitute a treatable cause of congestive myelopathy, detailed information is not currently available due to their rarity. What does this study add? CCJ AVFs often presented with acute ascending myelopathy in elderly men due to a longitudinally extending cervical cord lesion with surrounding flow voids. Steroid pulse therapy was not effective or even harmful to congestive myelopathy, while neurosurgical treatment effectively obliterated AVFs. How might this study affect research, practice or policy? The results obtained revealed diagnostic clues and pitfalls from the largest dataset of patients with CCJ AVFs in a multicenter cohort., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose: The ventriculus terminalis (VT), also called the fifth ventricle, is a small cavity containing cerebrospinal fluid (CSF) that is in the conus medullaris in continuity with the central canal of the spinal cord. In adults, persistent VT is a very rare entity, and the diagnosis is incidental in most cases. Rarely, VT may become symptomatic for still-uncertain reasons but most often for its cystic dilatation. The management of these selected cases is still controversial and sometimes associated with unsatisfactory outcomes., Methods: We performed a critical review of the existing literature on the management of symptomatic VT in adults. The etiology, pathophysiology, and treatment of VT are presented and discussed, focusing on the best timing for surgery., Results: Conservative management, marsupialization, or the placement of a T drain have been reported. The existing classifications describe the most correct approach for each clinical presentation, but scarce importance has been given to the delay from symptoms' onset to surgical treatment., Conclusion: Although different cases have been described in the literature, this rare pathology remains unknown to most neurosurgeons., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Spinal cord injury (SCI) is a very serious clinical traumatic illness with a very high disability rate. It not only causes serious functional disorders below the injured segment, but also causes unimaginable economic burden to social development. Exosomes are nano-sized cellular communication carriers that exist stably in almost all organisms and cell types. Because of their capacity to transport proteins, lipids, and nucleic acids, they affect various physiological and pathological functions of recipient cells and parental cells. Autophagy is a process that relies on the lysosomal pathway to degrade cytoplasmic proteins and organelles and involves a variety of pathophysiological processes. Exosomes and autophagy play critical roles in cellular homeostasis following spinal cord injury. Presently, the coordination mechanism of exosomes and autophagy has attracted much attention in the early efficacy of spinal cord injury. In this review, we discussed the interaction of autophagy and exosomes from the perspective of molecular mechanisms, which might provide novel insights for the early therapeutic application of spinal cord injury., (© 2022. The Author(s).)

Purpose: This study investigates the feasibility of ultrafast fluid sensitive techniques for evaluation of pediatric spinal cord syrinx. Rapid imaging could obviate the need for sedation, which is often required for children undergoing lengthier standard spine imaging., Methods: Children undergoing standard spine imaging for Chiari malformation, suspected Chiari malformation, or syrinx were included. Patients who provided informed consent were imaged with rapid acquisition sagittal and axial T2 HASTE spine sequences in addition to standard spine imaging. Standard and rapid spine imaging were then reviewed separately by a pediatric neuroradiologist. The presence or absence of syrinx, syrinx diameter, and length were assessed. The degree of cerebellar tonsillar ectopia, conus position, and evaluation of the filum were also recorded., Results: Seventy-six patients aged 1 month to 18 years (mean 7 years) met the inclusion criteria. The sensitivity and specificity of rapid spine imaging for syrinx was 87.8% and 94.7% respectively. All syrinxes > 2.3 mm in diameter were identified with the rapid spine sequences. There was no statistically significant difference between rapid and standard spine imaging in assessment of syrinx diameter or length. Compared with standard spine imaging, rapid spine sequences demonstrated a 100% sensitivity for low-lying conus and a 98.2% sensitivity for cerebellar tonsillar ectopia. The filum was identified on only 31.6% of the rapid spine studies., Conclusion: Rapid T2 imaging demonstrated a high sensitivity for the presence and extent of spinal cord syrinx and may provide an alternative to traditional, lengthier standard spine imaging in selected patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The aim of the study was to assess the prevalence and characteristics of spinal cord cavernous malformations (SCCM) and intraosseous spinal vascular malformations (ISVM) in a pediatric familial cerebral cavernous malformation (FCCM) cohort and evaluate clinico-radiological differences between children with (SCCM +) and without (SCCM-) SCCM., Methods: All patients with a pediatric diagnosis of FCCM evaluated at three tertiary pediatric hospitals between January 2010 and August 2021 with [Formula: see text] 1 whole spine MR available were included. Brain and spine MR studies were retrospectively evaluated, and clinical and genetic data collected. Comparisons between SCCM + and SCCM- groups were performed using student-t/Mann-Whitney or Fisher exact tests, as appropriate., Results: Thirty-one children (55% boys) were included. Baseline spine MR was performed (mean age = 9.7 years) following clinical manifestations in one subject (3%) and as a screening strategy in the remainder. Six SCCM were detected in five patients (16%), in the cervico-medullary junction (n = 1), cervical (n = 3), and high thoracic (n = 2) regions, with one appearing during follow-up. A tendency towards an older age at first spine MR (P = 0.14) and [Formula: see text] 1 posterior fossa lesion (P = 0.13) was observed in SCCM + patients, lacking statistical significance. No subject demonstrated ISVM., Conclusion: Although rarely symptomatic, SCCM can be detected in up to 16% of pediatric FCCM patients using diverse spine MR protocols and may appear de novo. ISVM were instead absent in our cohort. Given the relative commonality of asymptomatic SCCM, serial screening spine MR should be considered in FCCM starting in childhood., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Levels of neuro-filament light chain (NFL) correlate with clinical and radiological activity in multiple sclerosis (MS) and have been used as a surrogate biomarker of axonal destruction related to inflammatory activity. The main objective of this work is to explore the specific contribution of acute inflammation within the spinal cord to the elevation of NFL levels., Patients and Methods: MS patients with a baseline study of NFL at diagnosis of the disease and a brain and spinal cord MRI scan were selected. Patients were classified according to the presence, number and location of gadolinium enhancing lesion (GEL) and the relationship between NFL levels and both brain and spinal cord GEL were explored., Results: Seventy-seven patients were selected. NFL levels were significantly higher in patients with only one GEL restricted to the brain than those without GEL (1702 pg/ml vs 722.7 pg/mL, p = 0.03) and correlated with number. However, no differences were seen among patients with GEL limited to the spinal cord and those without GEL (735.2 pg/ml vs 722.7 pg/mL)., Conclusion: Our study reaffirms the value of NFL levels in monitoring asymptomatic inflammatory activity in the brain measured by GEL. However, NFL concentration is not as useful when only inflammatory activity occurs in the spinal cord., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose: The application of conventional magnetic resonance imaging (MRI) in combination with diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) to diagnose acute traumatic cervical SCI has not been studied. This study explores the role of MRI with DTI-DTT in the diagnosis of acute traumatic cervical spinal cord injury (SCI)., Methods: Thirty patients with acute traumatic cervical SCI underwent conventional MRI and DTI-DTT. Conventional MRI was used to detect the intramedullary lesion length (IMLL) and intramedullary hemorrhage length (IMHL). DTI was used to detect the spinal cord's fractional anisotropy (FA) and apparent diffusion coefficient value, and DTT detected the imaginary white matter fiber volume and the connection rates of fiber tractography (CRFT). Patients' neurological outcome was determined using the American Spinal Injury Association (ASIA) Impairment Scale (AIS) grades., Results: Patients were divided into group A (without AIS grade conversion) and group B (with AIS grade conversion). The IMLL and IMHL of group A were significantly higher than those of group B. The FA and CRFT of group A were significantly lower than those of group B. The final AIS grade was negatively correlated with the IMLL and IMHL, and positively correlated with the FA and CRFT. According to imaging features based on conventional MRI and DTI-DTT, we propose a novel classification and diagnostic procedure., Conclusions: The combination of conventional MRI with DTI-DTT is a valid diagnostic approach for SCI. Lower IMLL and IMHL, and higher FA value and CRFT are linked to better neurological outcomes., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Measures to define treatment response, such as no evidence of disease activity (NEDA), are routinely used in multiple sclerosis (MS) clinical practice. Although spinal cord involvement is a frequent feature of MS, its magnetic resonance imaging (MRI) monitoring is not routinely performed., Objective: To assess the impact of spinal cord MRI in the definition of NEDA in a cohort of people with MS (pwMS) with available spinal cord imaging performed as for routine monitoring., Methods: We included 115 pwMS undergoing treatment with first-line disease-modifying therapies (DMTs) and retrospectively analyzed the presence of NEDA in the whole cohort, either considering or not spinal cord imaging., Results: When considering only clinical and brain MRI measures, 97 out of 115 pwMS (84.3%) satisfied the criteria for NEDA. In the same cohort, the number of pwMS with NEDA significantly decreased to 88 (76.5%) (p < 0.01) when considering also spinal cord imaging., Conclusion: These findings suggest that, in routine clinical practice, spinal cord MRI monitoring in pwMS under first-line DMTs leads to a slight but significant change in the proportion of subjects classified as clinically and radiologically stable according to the NEDA definition., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Introduction: Isolated spinal cord angiitis (ISCA) is very rare disease. But, it is frequently encountered in the differential diagnosis of atypical spinal cord syndromes., Case Presentation and Review of the Literature: We present a 31-year-old male who presented with progressive paraparesis, and diagnosed with pathologically confirmed ISCA. Longitudinal cystic transverse myelitis was documented in spinal MRI. He responded well to cyclophosphamide and steroid combination, and no relapse was noted during the 4-year follow-up. A standard systematic analysis of the germane literature disclosed 15 more ISCA cases. In total 16 cases (mean age: 46.5, 10 males), ISCA was diagnosed with pathological evaluation in all (Biopsy in 11, Autopsy in 5). MRI lesion is characterized by usually multisegmental longitudinal and sometimes cystic expansile lesions. In seven cases, it was described as "(pseudo)tumoral" by the authors. Albeit absence of elevation of CSF protein/WBC or "compatible" spinal MRI lesion may aid to exclude ISCA to some extent, pathological confirmation is currently necessary for the diagnosis. In 11 cases, ISCA was treated similar to primary supratentorial vasculitis. Mortality rate is 31%., Discussion: ISCA diagnosis, a typical example of which we have presented here, can only be established by tissue examination. However, noninvasive diagnostic criteria are critically needed. Our data suggest that this can only be possible with multinational multicenter prospective registry., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Severe spinal cord injury causes permanent loss of function and sensation throughout the body. The trauma causes a multifaceted torrent of pathophysiological processes which ultimately act to form a complex structure, permanently remodeling the cellular architecture and extracellular matrix. This structure is traditionally termed the glial/fibrotic scar. Similar cellular formations occur following stroke, infection, and neurodegenerative diseases of the central nervous system (CNS) signifying their fundamental importance to preservation of function. It is increasingly recognized that the scar performs multiple roles affecting recovery following traumatic injury. Innovative research into the properties of this structure is imperative to the development of treatment strategies to recover motor function and sensation following CNS trauma. In this review, we summarize how the regeneration potential of the CNS alters across phyla and age through formation of scar-like structures. We describe how new insights from next-generation sequencing technologies have yielded a more complex portrait of the molecular mechanisms governing the astrocyte, microglial, and neuronal responses to injury and development, especially of the glial component of the scar. Finally, we discuss possible combinatorial therapeutic approaches centering on scar modulation to restore function after severe CNS injury., (© 2021. The Author(s).)

Methylmercury (MeHg) is known to cause serious neurological deficits in humans. In this study, we investigated the occurrence of MeHg-mediated neuropathic pain and identified the underlying pathophysiological mechanism in a rat model of MeHg exposure. Rats were exposed to MeHg (20 ppm in drinking water) for 3 weeks. Neurological damage was observed in the primary afferent neuronal system, including the dorsal root nerve and the dorsal column of the spinal cord. The MeHg-exposed rats showed hyperalgesia/allodynia, compared to controls, as evidenced by a significant decrease in the threshold of mechanical pain evaluated using an algometer with calibrated forceps. Immunohistochemistry revealed the accumulation of activated microglia in the dorsal root nerve, dorsal column, and dorsal horn of the spinal cord. Western blot analyses of the dorsal part of the spinal cord demonstrated an increase in inflammotoxic and inflammatory cytokines and a neuronal activation related protein, phospho-CRE bunding protein (CREB). The results suggest that dorsal horn neuronal activation was mediated by inflammatory factors excreted by accumulated microglia. Furthermore, analyses of the cerebral cortex demonstrated increased expression of phospho-CREB and thrombospondin-1, which is known to be an important factor for excitatory synapse formation, specifically in the somatosensory cortical area. In addition, the expression of pre- and post-synaptic markers was increased in this cortex area. These results suggested that the new cortical circuit was wired specifically in the somatosensory cortex. In conclusion, MeHg-mediated dorsal horn neuronal activation with inflammatory microglia might induce somatosensory cortical rewiring, leading to hyperalgesia/allodynia.

Peripheral nerve injury is associated with spinal microgliosis which plays a pivotal role in the development of neuropathic pain behavior. Several agents of primary afferent origin causing the microglial reaction have been identified, but the type(s) of primary afferents that release these mediators are still unclear. In this study, specific labeling of C-fiber spinal afferents by lectin histochemistry and selective chemodenervation by capsaicin were applied to identify the type(s) of primary afferents involved in the microglial response. Comparative quantitative morphometric evaluation of the microglial reaction in central projection territories of intact and injured peripheral nerves in the superficial (laminae I and II) and deep (laminae III and IV) spinal dorsal horn revealed a significant, about three-fold increase in microglial density after transection of the sciatic or the saphenous nerve. Prior perineural treatment of these nerves with capsaicin, resulting in a selective defunctionalization of C-fiber afferent fibers failed to affect spinal microgliosis. Similarly, peripheral nerve injury-induced increase in microglial density was unaffected in rats treated neonatally with capsaicin known to result in a near-total loss of C-fiber dorsal root fibers. Perineural treatment with capsaicin per se did not evoke a significant increase in microglial density. These observations indicate that injury-induced spinal microgliosis may be attributed to phenotypic changes in injured myelinated primary afferent neurons, whereas the contribution of C-fiber primary sensory neurons to this neuroimmune response is negligible. Spinal myelinated primary afferents may play a hitherto unrecognized role in regulation of neuroimmune and perisynaptic microenvironments of the spinal dorsal horn.

A striking and debilitating property of the nervous system is that damage to this tissue can cause chronic intractable pain, which persists long after resolution of the initial insult. This neuropathic form of pain can arise from trauma to peripheral nerves, the spinal cord, or brain. It can also result from neuropathies associated with disease states such as diabetes, human immunodeficiency virus/AIDS, herpes, multiple sclerosis, cancer, and chemotherapy. Regardless of the origin, treatments for neuropathic pain remain inadequate. This continues to drive research into the underlying mechanisms. While the literature shows that dysfunction in numerous loci throughout the CNS can contribute to chronic pain, the spinal cord and in particular inhibitory signalling in this region have remained major research areas. This review focuses on local spinal inhibition provided by dorsal horn interneurons, and how such inhibition is disrupted during the development and maintenance of neuropathic pain.

Lower urinary tract (LUT) dysfunction presents early in multiple system atrophy (MSA), usually initially as urinary urgency, frequency and incontinence, and voiding difficulties/urinary retention becomes apparent over time. We have observed a subset of patients who instead presented initially with urinary retention requiring catheterisation. At presentation, these patients had only subtle neurological signs that would not fulfil the diagnostic criteria of MSA; however, the anal sphincter electromyography (EMG) was abnormal and they reported bowel and sexual dysfunction, suggesting localisation at the level of the sacral spinal cord. They subsequently developed classical neurological signs, meeting the diagnostic criteria for probable MSA. One patient was confirmed to have MSA at autopsy. We postulate that in a subset of patients with MSA, the disease begins in the sacral spinal cord and then spreads to other regions resulting in the classical signs of MSA. The transmissibility of alpha-synuclein has been demonstrated in animal models and the spread of pathology from sacral cord to other regions of the central nervous system is therefore plausible. Patients presenting with urinary retention and mild neurological features would be an ideal group for experimental trials evaluating neuroprotection in MSA.

Background: Spinal cord (SC) involvement correlates with poor prognosis in patients with multiple sclerosis (MS). Nevertheless, there is no consensus on the use of SC-MRI at follow-up, mainly because of the belief that SC lesions are nearly always symptomatic., Objectives: The aim of the present study was to investigate the frequency of asymptomatic SC combined unique activity (CUA, new/enlarging T2 or gadolinium-positive [Gd+] lesions) on MRI in a cohort of patients diagnosed with clinically isolated syndrome (CIS) or relapsing-remitting MS (RRMS)., Methods: We retrospectively investigated all scans showing SC-CUA in patients with CIS or RRMS referred to a single Italian MS centre. We determined whether they were symptomatic and whether they had associated brain radiological activity., Results: In 340 SC-MRI scans with SC-CUA (230 patients), SC-CUA was asymptomatic in 31.2%; 12.1% of SC-CUA had neither clinical activity nor brain radiological activity (44.5% and 25.4%, respectively, considering only follow-up SC-CUA). At multivariate analysis asymptomatic SC-CUAs were associated with older age at onset (34.0 ± 10.37 vs 31.0 ± 9.99 years, p = 0.006), non-spinal onset (76.4 vs 47.4%, p < 0.001), lower EDSS score at MRI (1.8 ± 0.93 vs 2.4 ± 1.28, p = 0.001) and lower number of Gd+ SC lesions (0.1 ± 0.33 vs 0.3 ± 0.54, p = 0.04), compared to symptomatic SC-CUAs., Conclusions: A substantial proportion of our patients had SC-CUA without clinical symptoms and/or without concomitant brain MRI activity. In these patients, SC-CUA was the only sign of disease activity, suggesting that regular SC-MRI follow-up is required for reliable assessment of radiological activity and may improve the management of patients with MS.

Introduction: We present a patient with idiopathic spinal cord herniation (ISCH) whose dura mater was histopathologically examined to elucidate its pathogenesis., Case Report: A 33-year-old previously healthy man presented with progressive walking difficulty, spasticity of the right lower leg, and hyperesthesia below the right chest. Neuroimaging revealed right ventral displacement of the spinal cord at T5-6. The diagnosis was ISCH and he underwent release of the herniation from the ventral dural opening. Dural biopsy at the edge of the ventral opening and in the dorsal durotomy was performed. Postoperatively, his gait was improved. Histopathological examination of the ventral dural specimen showed non-specific degeneration, i.e., loose arrangements of collagen fibers, edematous changes, minor inflammatory cell infiltration, and angiogenesis. The specimen from the dorsal durotomy was normal., Conclusion: It is unclear whether the observed degeneration besides the ventral opening was the primary cause of ISCH or reflected secondary changes resulting from cumulative damage due to pulsation of the herniated spinal cord. However, the degeneration limited to the ventral opening suggests that ISCH was a local event in an individual with a normal dural theca.

This study examined the relation between lumbar spinal motor neuron (SMN) indices and motor function proximate to death in community-dwelling older adults. Older adults (N = 145) participating in the Rush Memory and Aging Project underwent structured clinical testing proximate to death and brain and spinal cord autopsy at time of death. Ten motor performances were summarized by a composite global motor score. Choline acetyltransferase immunostaining was used to identify spinal motor neurons of the L4/5 segment. SMN counts and area and ventral horn area were collected. Linear regression modeling showed that the association of SMN counts and density with global motor scores proximate to death varied with sex. Separate models in men and women showed that this significant interaction was due to the association of higher SMN counts and density with higher global motor scores proximate to death in men but not women. These associations were unchanged when we controlled for indices of brain pathologies or chronic health conditions. In 38 cases with counts of activated microglia available, higher counts of activated microglia were associated with lower SMN counts. Activated spinal microglia and loss of spinal motor neurons may contribute to motor impairments in older men.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that leads to the eventual death of motor neurons. Described cases of familial ALS have emphasized the significance of protein misfolding and aggregation of two functionally related proteins, FUS (fused in sarcoma) and TDP-43, implicated in RNA metabolism. Herein, we performed a comprehensive analysis of the in vivo model of FUS-mediated proteinopathy (ΔFUS(1-359) mice). First, we used the Noldus CatWalk system and confocal microscopy to determine the time of onset of the first clinical symptoms and the appearance of FUS-positive inclusions in the cytoplasm of neuronal cells. Second, we applied RNA-seq to evaluate changes in the gene expression profile encompassing the pre-symptomatic and the symptomatic stages of disease progression in motor neurons and the surrounding microglia of the spinal cord. The resulting data show that FUS-mediated proteinopathy is virtually asymptomatic in terms of both the clinical symptoms and the molecular aspects of neurodegeneration until it reaches the terminal stage of disease progression (120 days from birth). After this time, the pathological process develops very rapidly, resulting in the formation of massive FUS-positive inclusions accompanied by a transcriptional "burst" in the spinal cord cells. Specifically, it manifests in activation of a pro-inflammatory phenotype of microglial cells and malfunction of acetylcholine synapse transmission in motor neurons. Overall, we assume that the highly reproducible course of the pathological process, as well as the described accompanying features, makes ΔFUS(1-359) mice a convenient model for testing potential therapeutics against proteinopathy-induced decay of motor neurons.

Purpose: Melanotic schwannoma (MS) is rare, accounting for less than 1% of primary peripheral nerve sheath tumors, and most often occurs in the paraspinal nerve roots. Intramedullary MS is exceedingly rare, and to the best of our knowledge, only nine cases have been reported in literature., Methods and Results: We present a 47-year-old male, who underwent excision of thoracic intraspinal space-occupying lesion 6 years ago, as the 10th known case to date of intradural intramedullary MS that had a more invasive growth pattern than those reported before, and we review the diagnosis, clinicopathologic features, treatment and prognosis of intramedullary MS., Conclusions: Intramedullary MS' behavior is unpredictable and can have an aggressive clinical course such as recurrence and metastasis.

Background: Standard fluoroscopic guidance (C-arm fluoroscopy) has been routinely used for intraoperative localization of spinal level for surgical removal of intraspinal tumour, while it is not suitable for selected patients, e.g. pregnant women, who need to avoid radiation exposure. Fusion imaging of real-time ultrasound (US) and magnetic resonance imaging (MRI) is a radiation-free technique which has been reported to have good localization accuracy in managing several conditions., Clinical Presentation: A 37-year-old pregnant patient, presented with a progressively aggravating lower back pain for 20 days and was incapable of lying supine with lower extremities swelling for 1 week, was referred to our hospital in her 18th week of gestation. Lumbar MRI identified an L1 level intraspinal lesion, and surgery was planned. To avoid the ionizing radiation generated by fluoroscopy, volume navigation technique (VNT) based fusion imaging of US and MRI was used to localize the intraspinal lesion, which was removed entirely via minimally invasive interlaminar approach. Pathological examination confirmed the diagnosis of ependymoma of the conus medullaris. Her symptoms were largely relieved after the operation, and a healthy baby was delivered at the 40th week of pregnancy., Conclusion: We presented the first case of using VNT based fusion imaging of real-time US/MRI to guide the surgical resection of an intraspinal tumour. Future study with larger patient number is needed to validate this technique as an alternative to fluoroscopy in patients who need to avoid radiation exposure.

Purpose: To report the case of a pediatric patient with intramedullary spinal aneurysm., Methods: A 9-year-old boy presented with low back pain and subsequent gait disturbance. He had no history of trauma. After admission, MRI revealed an intramedullary spinal cord mass lesion surrounded by hemorrhage at the cervical-thoracic junction. Initial treatment was started with intravenous methylprednisolone and bed rest. Neurological deficit disappeared under careful observation for a few months. Surgical intervention was applied for diagnosis and resection of the mass lesion to prevent recurrent hemorrhage., Results: Intraoperative ultrasound sonography helped to diagnose the lesion as a spinal cord aneurysm, prior to midline myelotomy. Monitoring of transcranial muscle evoked potentials helped to avoid spinal cord damage during surgery. There has been no evidence of spinal aneurysm on MRI for 3 years after surgery and no neurological deterioration., Conclusion: To our knowledge, this is a first report of an intramedullary spinal cord aneurysm at the cervical-thoracic junction in a pediatric patient. Careful observation after initial symptoms followed by surgical intervention was favorable in this case.

Background: Epilepsy, ataxia, sensorineural deafness, and tubulopathy (EAST syndrome) is a rare channelopathy due to KCNJ10 mutations. So far, only mild cerebellar hypoplasia and/or dentate nuclei abnormalities have been reported as major neuroimaging findings in these patients., Methods: We analyzed the clinical and brain MRI features of two unrelated patients (aged 27 and 23 years) with EAST syndrome carrying novel homozygous frameshift mutations (p.Asn232Glnfs*14and p.Gly275Valfs*7) in KCNJ10, detected by whole exome sequencing., Results: Brain MRI examinations at 8 years in Patient 1 and at 13 years in Patient 2 revealed a peculiar brain and spinal cord involvement characterized by restricted diffusion of globi pallidi, thalami, brainstem, dentate nuclei, and cervical spinal cord in keeping with intramyelinic edema. The follow-up studies, performed, respectively, after 19 and 10 years, showed mild cerebellar atrophy and slight progression of the brain and spinal cord T2 signal abnormalities with increase of the restricted diffusion in the affected regions., Conclusion: The present cases harboring novel homozygous frameshift mutations in KCNJ10 expand the spectrum of brain abnormalities in EAST syndrome, including mild cerebellar atrophy and intramyelinic edema, resulting from abnormal function of the Kir4.1 inwardly rectifying potassium channel at the astrocyte endfeet, with disruption of water-ion homeostasis.

The acute phase of spinal cord injury is characterized by excitotoxic and inflammatory events that mediate extensive neuronal loss in the gray matter. Neural crest stem cells (NCSCs) can exert neuroprotective and anti-inflammatory effects that may be mediated by soluble factors. We therefore hypothesize that transplantation of NCSCs to acutely injured spinal cord slice cultures (SCSCs) can prevent neuronal loss after excitotoxic injury. NCSCs were applied onto SCSCs previously subjected to N-methyl-D-aspartate (NMDA)-induced injury. Immunohistochemistry and TUNEL staining were used to quantitatively study cell populations and apoptosis. Concentrations of neurotrophic factors were measured by ELISA. Migration and differentiation properties of NCSCs on SCSCs, laminin, or hyaluronic acid hydrogel were separately studied. NCSCs counteracted the loss of NeuN-positive neurons that was otherwise observed after NMDA-induced excitotoxicity, partly by inhibiting neuronal apoptosis. They also reduced activation of both microglial cells and astrocytes. The concentration of brain-derived neurotrophic factor (BDNF) was increased in supernatants from SCSCs cultured with NCSCs compared to SCSCs alone and BDNF alone mimicked the effects of NCSC application on SCSCs. NCSCs migrated superficially across the surface of SCSCs and showed no signs of neuronal or glial differentiation but preserved their expression of SOX2 and Krox20. In conclusion, NCSCs exert neuroprotective, anti-apoptotic and glia-inhibitory effects on excitotoxically injured spinal cord tissue, some of these effects mediated by secretion of BDNF. However, the investigated NCSCs seem not to undergo neuronal or glial differentiation in the short term since markers indicative of an undifferentiated state were expressed during the entire observation period.

Introduction: Spinal cord infarction followed by minor trauma in pediatric patients is rare and causes serious paralysis. Fibrocartilaginous embolism (FCE) is a possible diagnosis and there have been no consecutive magnetic resonance imaging (MRI) reports. Here, we report a case of an acute complete paraplegia with spinal cord infarction and longitudinal spinal cord signal change following minor trauma in an 8-year-old girl., Case Description: An 8-year-old girl presented to our hospital emergency services with total paraplegia 2 h after she hit her back and neck after doing a handstand and falling down. She completely lost pain, temperature sensation, and a sense of vibration below her bilateral anterior thighs. Four hours later on MRI, the T2-weighted sequence showed no spinal cord compression or signal change in vertebral bodies. The patient was treated with rehabilitation after complete bed rest. A week after the trauma, the T2-weighted sequence indicated longitudinal extension of the lesion between T11 and C6 vertebral level with ring-shaped signal change. In addition, the diffusion-weighted MRI showed increased signal below C6 vertebral level. Two weeks after the trauma, we performed the T2 star sequence images, which showed minor bleeding at T11 vertebral area and spinal cord edema below C6. Four weeks after the trauma, MRI showed minor lesion at C6 vertebral level, but spinal cord atrophy was observed at T11 vertebral level without disc signal change. Thirteen weeks after the trauma, her cervical spinal cord became almost intact and severe atrophy of the spinal cord at T11 vertebral level. At 1 year following her injury, complete paraplegia remained with sensory loss below T11 level., Conclusion: Her clinical presentation, lack of evidence for other plausible diagnosis, and consecutive MRI findings made FCE at T11 vertebral level with pencil-shaped softening the most likely diagnosis. In addition, consecutive cervical MRI indicated minor cervical spinal cord injury. This Grand Round case highlights the consecutive MRI in a case with double spinal cord lesion with longitudinal spinal cord signal change.

Leukocyte infiltration into the central nervous system (CNS) is a key pathological feature in multiple sclerosis (MS) and the MS animal model experimental autoimmune encephalomyelitis (EAE). Recently, preventing leukocyte influx into the CNS of MS patients is the main target of MS therapies and insight into cell behaviour in the circulation is needed for further elucidation of such therapies. In this study, we aimed at in vivo visualization of monocytes in a time-dependent manner during EAE. Using intravital two-photon microscopy (IVM), we imaged CX3CR1 gfp/gfp mice during EAE, visualizing CX3CR1-GFP + monocytes and their dynamics in the spinal cord vasculature. Our observations showed that intraluminal crawling of CX3CR1-GFP + monocytes increased even before the clinical onset of EAE due to immunization of the animals. Furthermore, intraluminal crawling remained elevated during ongoing clinical disease. Besides, the displacement of these cells was larger during the peak of EAE compared to the control animals. In addition, we showed that the enzyme tissue transglutaminase (TG2), which is present in CNS-infiltrated cells in MS patients, is likewise found in CX3CR1-GFP + monocytes in the spinal cord lesions and at the luminal side of the vasculature during EAE. It might thereby contribute to adhesion and crawling of monocytes, facilitating extravasation into the CNS. Thus, we put forward that interference with monocyte adhesion, by e.g. inhibition of TG2, should be applied at a very early stage of EAE and possibly MS, to effectively combat subsequent pathology.

Introduction: We investigated whether MR diffusion tensor imaging (DTI) analysis of the cervical spinal cord could aid the (differential) diagnosis of sensory neuronopathies, an underdiagnosed group of diseases of the peripheral nervous system., Methods: We obtained spinal cord DTI and T2WI at 3 T from 28 patients, 14 diabetic subjects with sensory-motor distal polyneuropathy, and 20 healthy controls. We quantified DTI-based parameters and looked at the hyperintense T2W signal at the spinal cord posterior columns. Fractional anisotropy and mean diffusivity values at C2-C3 and C3-C4 levels were compared between groups. We also compared average fractional anisotropy (mean of values at C2-C3 and C3-C4 levels). A receiver operating characteristic (ROC) curve was used to determine diagnostic accuracy of average fractional anisotropy, and we compared its sensitivity against the hyperintense signal in segregating patients from the other subjects., Results: Mean age and disease duration were 52 ± 10 and 11.4 ± 9.3 years in the patient group. Eighteen subjects had idiopathic disease and 6 dysimmune etiology. Fractional anisotropy at C3-C4 level and average fractional anisotropy were significantly different between patients and healthy controls (p < 0.001 and <0.001) and between patients and diabetic subjects (p = 0.019 and 0.027). Average fractional anisotropy presented an area under the curve of 0.838. Moreover, it had higher sensitivity than visual detection of the hyperintense signal (0.86 vs. 0.54), particularly for patients with short disease duration., Conclusion: DTI-based analysis enables in vivo detection of posterior column damage in sensory neuronopathy patients and is a useful diagnostic test for this condition. It also helps the differential diagnosis between sensory neuronopathy and distal polyneuropathies.

Introduction: The purpose of this study was to determine the added value of the perimedullary spinal vein enlargement sign on magnetic resonance imaging (MRI) in distinguishing intradural-extramedullary tumors (IDEMTs) from intramedullary spinal tumors (IMTs)., Methods: Two hundred and eight consecutive spinal intradural tumors with histopathologic confirmation (21 IMTs, 187 IDEMTs) were enrolled. Two readers blinded to the final pathological diagnosis and clinical data independently assessed the venous enlargement sign to determine the agreement between them and jointly distinguished IDEMTs from IMTs according to the common MRI findings. Sensitivity, specificity, and accuracy for the diagnosis of IDEMTs were calculated for the common MRI findings, vein enlargement sign, and a combination of both., Results: Intraobserver agreement and interobserver agreement for both readers was excellent. The sensitivity, specificity, and accuracy of common MRI findings for differentiating IDEMTs from IMTs were 83.4, 95.2, and 89.3 %, respectively. Thirty-one IDEMTs were mistakenly diagnosed as IMTs, in which seven were cases with vein enlargement signs. By applying the vein enlargement sign to the common MRI findings, the specificity remained at 95.2 %, while the sensitivity improved to 89.3 % and the accuracy increased to 92.3 %., Conclusion: The spinal perimedullary vein enlargement sign is useful in assessing intradural tumors and to differentiate IDEMTs from IMTs.

Objective: To evaluate clinical and radiological outcomes of growing rod (GR) in the management of Early Onset Scoliosis (EOS) with intraspinal anomalies., Background Data: The effect of repeated distractions following GR, in the presence of intraspinal anomalies has not been studied., Methods: During 2007-2012, 46 patients underwent fusionless surgery. Out of these 46 patients, 13 patients had one or more intraspinal anomalies. 11 patients had undergone prior neurosurgical procedure while 2 (filum terminale lipoma and syringomyelia) did not. A total of 88 procedures were conducted during the treatment period; 13 index surgeries, 74 distractions of GR and 1 unplanned surgery., Results: The age at surgery was 6.8 ± 2.5 years (3.5-12 years). 11 patients had congenital scoliosis and 2 had idiopathic scoliosis. A total of 19 (41.30 %) intraspinal anomalies [Tethered Cord Syndrome (TCS) 08, Split Cord Malformation (SCM) 08, Syringomyelia 01, Meningomyelocele 01, Filum terminale Lipoma 01] were seen. The average lengthening procedures per patient were 5.7 (4-9) with distraction interval of 6.7 (6-7.25) months. Pre-operative Cobb angle was 78.50 ± 18.1 (54-114°) and improved to 53.10 ± 16.70 (36-84°) at final follow-up. A total of 15 complications related to implant (9), wound (2), anesthesia (2) and neurological (2) occurred in 7 patients. Among the two neurological complications, one patient sustained fall in the post-op period and reported to the emergency department with paraplegia and broken proximal screw. While other patient experienced MEP changes during index procedure. None of the patients had any neurological complications during repeated lengthening procedures., Conclusion: The most common cord anomalies associated with EOS in our study are TCS and SCM. Although presence of previous intraspinal anomaly does not seem to increase the incidence of neurological deficit, use of neuromonitoring is advisable for all index procedure and selected distractions., Study Design: Level 4 (case series).

Purpose: Degenerative disc disease (DDD) is a common disabling condition for millions of individuals. Injection of xenogenic juvenile chondrocytes (XJC) into the disc space has been shown to have a therapeutic potential for disc repair. In the current study, XJC were injected extra-discally on neural structures in an in vivo rat hemilaminectomy model to compare the histological and behavioral effects on XJC and fibrin glue carrier., Methods: Twenty-four rats were assigned to four groups: cells plus carrier, carrier alone, sham hemi-laminectomy, and a positive control (nerve root ligation). A right-sided hemilaminectomy was performed and the study material was placed on and around the exposed L4 nerve root and the spinal cord. Pre- and postoperatively mechanical allodynia was tested on the ipsilateral hind paw using the von Frey up-down method. The lumbar spines were harvested after 6 and 12 weeks for nerve histology and TNF-α quantification., Results: After a brief period of hyperalgesia, the von Frey data indicate there are no adverse effects of placing XJC on spinal nerve roots in rats. However ligation of nerve root showed significant allodynia compared to the other groups. These behavioral data were supported by histological analyses., Conclusions: While these results need to be confirmed over a larger period of time, they suggest that XJC transplantation into the disc space shows no adverse effect on nerve tissue.

Chronic post-surgical pain (CPSP) is a normal and significant symptom in clinical surgery, such as breast operation, biliary tract operation, cesarean operation, uterectomy and thoracic operation. Severe chronic post-surgical pain could increase post-surgical complications, including myocardial ischemia, respiratory insufficiency, pneumonia and thromboembolism. However, the underlying mechanism is still unknown. Herein, a rat CPSP model was produced via thoracotomy. After surgery, in an initial study, 5 out of 12 rats after surgery showed a significant decrease in mechanical withdrawal threshold and/or increase in the number of acetone-evoked responses, and therefore classified as the CPSP group. The remaining seven animals were classified as non-CPSP. Subsequently, open-chest operation was performed on another 30 rats and divided into CPSP and non-CPSP groups after 21-day observation. Protein expression levels in the dorsal spinal cord tissue were determined by 12.5 % SDS-PAGE. Finally, differently expressed proteins were identified by LC MS/MS and analyzed by MASCOT software, followed by Gene Ontology cluster analysis using PANTHER software. Compared with the non-CPSP group, 24 proteins were only expressed in the CPSP group and another 23 proteins expressed differentially between CPSP and non-CPSP group. Western blot further confirmed that the expression of glutaminase 1 (GLS1) was significantly higher in the CPSP than in the non-CPSP group. This study provided a new strategy to identify the spinal proteins, which may contribute to the development of chronic pain using differential proteomics, and suggested that GLS1 may serve as a potential biomarker for CPSP.

Typical multiple sclerosis (MS) lesions occur in the brain as well as in the spinal cord. However, two extreme magnetic resonance imaging phenotypes appear occasionally: those with predominantly spinal cord lesions (MS + SL) and those with cerebral lesions and no detectable spinal lesions (MS + CL). We assessed whether morphological differences can be found between these two extreme phenotypes. We examined 19 patients with MS + SL, 18 with MS + CL and 20 controls. All subjects were examined using magnetic resonance imaging, including anatomical and diffusion tensor imaging sequences. Voxel-based morphologic and regions of interest-based analyses and tract-based spatial statistics were performed. Patients also underwent neuropsychological testing. Demographic, clinical and neuropsychological characteristics did not differ between MS + SL and MS + CL patients. Patients with MS + SL showed significantly larger putamen volumes than those with MS + CL which correlated negatively with disability. Compared to controls, only MS + CL revealed clear cortical and deep gray matter atrophy, which correlated with cerebral lesion volume. Additionally, extensive white matter microstructural damage was found only in MS + CL compared to MS + SL and controls in the tract-based spatial statistics. Higher putamen volumes in MS + SL could suggest compensatory mechanisms in this area responsible for motor control. Widely reduced fractional anisotropy values in MS + CL were caused by higher cerebral lesion volume and thus presumably stronger demyelination, which subsequently leads to higher global gray matter atrophy.

Pediatric spine pathology poses a diagnostic challenge for radiologists. Acquired spine pathology often yields nonspecific signs and symptoms in children, especially in the younger age groups, and diagnostic delay can carry significant morbidity. This review is focused on some of the more common diagnostic dilemmas we face when attempting to evaluate and diagnose acquired pediatric spine anomalies in daily practice. An understanding of some of the key differentiating features of these disease processes in conjunction with pertinent history, physical exam, and advanced imaging techniques can indicate the correct diagnosis.

Camptocormia in Parkinson's disease (PD) is an axial postural disorder usually accompanied by histopathological changes in the paravertebral muscles of unknown etiology. The diagnostic potential of magnetic resonance imaging (MRI) of back muscles in camptocormia has not been systematically assessed. Our objective was to characterize pathological muscle changes with MRI and to develop radiological criteria for camptocormia. The criteria edema, swelling and fatty degeneration in 20 idiopathic PD patients with camptocormia were assessed using MRI (T1w and short tau inversion recovery (STIR) sequences) of the lumbar trunk muscles and compared with 20 group-matched PD patients without camptocormia. Edema and fatty degeneration of the paravertebral muscles were significantly more frequent in camptocormia. Edema correlated negatively and fatty degeneration positively with the duration of camptocormia and not PD. Swelling of the paravertebral muscles, edema and swelling of the quadratus lumborum muscle and rare edema of the psoas muscle were only found in camptocormia patients. In this case-control study the defined MRI criteria distinguish the group of PD patients with camptocormia versus those without. Our findings suggest dynamic changes in the MRI signals over time in the paravertebral muscles: edema and swelling are found initially, followed by fatty atrophic degeneration 2-3 years after the beginning of camptocormia. Muscle MRI qualifies as a tool for categorizing phases of camptocormia as acute or chronic, with potential consequences for therapeutic approaches. The involvement of muscles beyond an isolated impairment of the paravertebral muscles implies a more systemic view with a deregulation of lumbar trunk muscles.

Purpose: Hypertrophic craniocervical pachymeningitis (HCP) is a rare disease causing chronic inflammatory hypertrophy of the cranial and spinal dura mater. To increase awareness of this condition, we report the details of a case here., Methods: We reviewed the case of a 78-year-old man presenting with a rare case of HCP and summarized the clinical features, laboratory evaluations and treatment of the case., Results: In this case, the HCP involved the intracranial dura and high cervical regions, manifesting as lower cranial nerve palsies, headache, and neck pain, developing over 7 months. Magnetic resonance imaging revealed thickening of the dura in the craniocervical region with peripheral enhancement. Steroid therapy was commenced and the symptoms improved rapidly., Conclusions: HCP can be diagnosed by MRI and laboratory investigations. In this case corticosteroid treatment was effective, although care must be taken when slowly reducing the dose. This case highlights HCP as a cause of progressive cerebellomedullar and cervical spinal cord symptoms.

Developmental studies of spinal cord injury in which regrowth of axons occurs across the site of transection rarely distinguish between the recovery of motor-controlling pathways and that of ascending axons carrying sensory information. We describe the morphological changes that occur in the dorsal column (DC) of the grey short-tailed opossum, Monodelphis domestica, following spinal cord injury at two early developmental ages. The spinal cords of opossums that had had their mid-thoracic spinal cords completely transected at postnatal day 7 (P7) or P28 were analysed. Profiles of neurofilament immunoreactivity in transected cords showing DC development were differentially affected by the injury compared with the rest of the cord and cytoarchitecture was modified in an age- and site-dependent manner. The ability of DC neurites to grow across the site of transection was confirmed by injection of fluorescent tracer below the injury. P7 transected cords showed labelling in the DC above the site of original transection indicating that neurites of this sensory tract were able to span the injury. No growth of any neuronal processes was seen after P28 transection. Thus, DC is affected by spinal injury in a differential manner depending on the age at which the transection occurs. This age-differential response, together with other facets of remodelling that occur after neonatal spinal injury, might explain the locomotor adaptations and recovery observed in these animals.

Introduction: The purpose of this study was to analyse MR imaging features and lesion patterns as defined by compromised vascular territories, correlating them to different clinical syndromes and aetiological aspects., Methods: In a 19.8-year period, clinical records and magnetic resonance imaging (MRI) features of 55 consecutive patients suffering from spinal cord ischemia were evaluated., Results: Aetiologies of infarcts were arteriosclerosis of the aorta and vertebral arteries (23.6%), aortic surgery or interventional aneurysm repair (11%) and aortic and vertebral artery dissection (11%), and in 23.6%, aetiology remained unclear. Infarcts occurred in 38.2% at the cervical and thoracic level, respectively, and 49% of patients suffered from centromedullar syndrome caused by anterior spinal artery ischemia. MRI disclosed hyperintense pencil-like lesion pattern on T2WI in 98.2%, cord swelling in 40%, enhancement on post-contrast T1WI in 42.9% and always hyperintense signal on diffusion-weighted imaging (DWI) when acquired., Conclusion: The most common clinical feature in spinal cord ischemia is a centromedullar syndrome, and in contrast to anterior spinal artery ischemia, infarcts in the posterior spinal artery territory are rare. The exclusively cervical location of the spinal sulcal artery syndrome seems to be a likely consequence of anterior spinal artery duplication which is observed preferentially here.

Purpose: The aim of this study was to evaluate the usefulness of diffusion tensor imaging (DTI) in the detection of cervical spinal cord integrity alterations in different stages of degenerative spine disease, as well as to compare DTI parameters with selected cervical spinal stenosis measurements., Methods: One hundred and thirty-two symptomatic patients (mean age 53.58 years) with different stages of cervical spondylosis and twenty-five control subjects (mean age 45.78 years) were enrolled in the study. DTI was performed with a 1.5 T MR scanner. Three hundred and forty-nine spine segments from C2/C3 to C5/C6 were evaluated and divided into five groups according to the degree of spinal cord compression. The values of fractional anisotropy (FA) and apparent diffusion coefficient at each level were calculated and their correlations with the degree of stenosis were analyzed., Results: FA values differed significantly (p < 0.0001) at all levels between the control group and patients with cervical degenerative disease, including subjects without spinal cord compression visible on plain MR images. A significant (p < 0.01) positive correlation between the mean FA values and anteroposterior diameter of the spinal canal as well as space available for the spinal cord index was demonstrated at all investigated levels., Conclusion: DTI is capable of revealing impairment of the cervical spinal cord microstructure at the very early stage of degenerative spine disease, even prior to spinal cord compression visible on plain MR. Anteroposterior spinal canal diameter as well as space available for the cord index is well related to spinal cord tissue integrity defined by DTI.

Objective: The goal of this study was to identify anterior spinal artery (ASA) occlusion by CT angiography in cervical spondylotic myelopathy (CSM) and amyotrophy (CSA) with T2-weighted hyperintensity of MR image of documented small intramedullary high signal intensity known as "snake-eye appearance" (SEA)., Method: One hundred and six patients with CSM were admitted to the investigator group between June 2010 and June 2013. Intramedullary high signal intensity was found in 42 cases and was divided into two types, SEA and non-SEA. SEA was observed in 10 patients, including seven CSM patients and three CSA patients. All SEA patients were performed CT angiography of ASA after admission., Results: The ASA was visualized in all 10 patients. ASA incomplete occlusion was found in one CSA patient and one CSM patient. No ASA occlusion was found in other CSA and CSM patients with SEA., Conclusion: ASA occlusion is not commonly seen in CSM and CSA patients with SEA. Pathological changes about SEA in CSM and CSA have no close correlation with ASA occlusion, but may be with anterior radiculomedullary arteries.

Purpose: Dural tear is one of the common complications of spinal surgery leading to cerebrospinal fluid leakage followed by serial secondary symptoms. However, little is known about pathological changes of the spinal cord after dural tear. In the present study, we aimed to study the pathological changes in the spinal cord after dural tear with and without autologous fascia repair., Methods: Sixty Sprague-Dawley rats were used for dural tear and autologous fascia graft repair models. Three days and 1 week after surgery, the pathological changes in the spinal cord were analyzed by immunohistochemistry, Western blot, enzyme-linked immunosorbent assay and spinal somatosensory evoked potentials test., Results: Neuroinflammation was found in the parenchyma of the spinal cord characterized by gliosis, increased expression of inflammatory factors and infiltration of exogenesis immunocells in the rats without repair, which impaired the sensory conduction function of the spinal cord at the early stage of injury. Repairing with autologous fascia could attenuate neuroinflammation and help to maintain normal sensory conduction function of the spinal cord., Conclusion: Dural tear could cause a series of inflammatory reactions in the spinal cord and further impair its sensory conduction function at the early stage of injury. Repairing with autologous fascia was a necessary and effective way to prevent the neuroinflammation and to maintain the normal function of the spinal cord.