Spinal Cord In Patients Research Articles

Long-term functional outcome after untethering surgery for a tethered spinal cord in patients with anorectal malformations

Anorectal malformation (ARM) is associated with a tethered spinal cord (TSC). Long-term functional outcome of untethering surgery for TSC in patients with ARM has not been well evaluated. Patients aged 7years and older who underwent repair of ARM and spinal magnetic resonance imaging from January 1995 to December 2008 were reviewed retrospectively. Untethering surgery was performed in all patients who were diagnosed with TSC, regardless of the presence or of neurological symptoms. Clinical symptoms reflecting anorectal, urinary, and lower limb function were compared between patients complicated with TSC (TSC group, n=17) and those without TSC (non-TSC group, n=14). The median age at functional evaluation was 11.7 and 12.9years in the TSC and non-TSC groups, respectively (p=0.52). Untethering surgery for TSC was performed at a median age of 1.3years. Preoperative urinary and lower limb dysfunction, except for vesicoureteral reflux in the TSC group in one patient, was improved after surgical detethering. Current anorectal function was comparable between the groups. Long-term functional outcome in patients with ARM and TSC undergoing untethering surgery is equivalent to that in those without TSC. Prophylactic surgical detethering for patients with ARM and TSC can be a treatment of choice to maximize neurological functional outcome.

Neurological status and imaging spinal cord in patients with infectious spondylitis: is it possible to comparisons with spondylogenic myelopathy?

Spend a literary analysis of the role of radiation diagnosis in the first place - magnetic resonance imaging to visualize changes in the spinal cord in infectious spondylitis. Neurological disorders, manifested by radicular symptoms and signs of spinal cord irritation to deep paresis and plegia in violation of the pelvic organs, are observed in the majority of patients with spondylitis and may be due to the spinal cord and its roots and / or a breach of its microcirculation on the background of the pathological process in the vertebrae. Dynamic (pre- and postoperative) imaging of the spinal canal and its contents in tuberculous and nonspecific spondylitis is important for a more complete assessment of the disease, and for the prediction of the dynamics of neurological disorders. (For citation: Makogonova ME, Mushkin AYu, Gavrilov PV. Neurological status and imaging spinal cord in patients with infectious spondylitis: is it possible to comparisons with spondylogenic myelopathy?. Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(2):64-72. doi: 10.17816/RCF15264-72).

Myelopathy secondary to a spinal cord compression induced by C2 nerve tumors during head rotation

IntroductionIt is well known that nerve root tumors developing in the spinal canal can be responsible for spinal cord compression leading to myelopathy and neurological deficits. We report the case of a patient with bilateral C2 neurofibromas presenting with a myelopathy of the upper cervical spine with no spinal cord compression on standard magnetic resonance imaging. The spinal cord compression occurred between the cervical neurofibromas only during head rotation. Case reportA patient with bilateral neurofibromas of the C2 nerve roots showed a progressive neurological deterioration with an intramedullary MRI hypersignal without visible compression. Only an additional MRI carried-out with the head in rotation demonstrated the tumoral dynamic compression. A review of the literature showed that only two similar cases had previously been reported. The largest C2 tumor was completely removed uneventfully. ConclusionDynamic compression of the spinal cord in patients with bilateral C2 nerve root tumors must be routinely investigated even if the standard MRI shows no compression.

Application value of diffusional kurtosis imaging (DKI) in evaluating microstructural changes in the spinal cord of patients with early cervical spondylotic myelopathy

ObjectiveTo investigate the application value of diffusional kurtosis imaging (DKI) in evaluating microstructural changes in the spinal cord of patients with early cervical spondylotic myelopathy (CSM). Patients and methodsTwenty-five patients with early clinical stage CSM and twenty-five healthy controls underwent 3.0T MR scans with conventional MRI sequences and DKI with echo-planar imaging (EPI) sequence. DKI metrics such as fractional anisotropy (FA), mean diffusivity (MD), and mean diffusional kurtosis (MK) values were calculated separately for white matter (WM) and gray matter (GM). ResultsMK of the WM and GM were significantly higher in patients with early CSM than in healthy controls (P<0.005). ConclusionsMK can reflect microstructural changes of white matter and gray matter of spinal cord in patients with early CSM and has the potential to provide new information prior to conventional diffusion metrics such as MD and FA.

Clinical Significance of Incidental Focal 18F-FDG Uptake in the Spinal Cord of Patients with Cancer

We investigated the incidence, location, and clinical significance of focal 18F-FDG uptake of the spinal cord in patients with cancer. We reviewed the medical records of 22,937 consecutive adult patients with known or suspicious malignancy who underwent 18F-FDG PET/CT. PET/CT scans with incidental focal spinal cord uptake were selected and retrospectively reviewed to determine the presence, location, number, and maximum standardized uptake value (SUVmax) of any focal hypermetabolic lesions of the spinal cord. In subjects with focal spinal uptake, clinical characteristics and clinical follow-up results, including follow-up PET/CT, were reviewed. Incidental focal spinal cord uptake was observed in 69 of 22,937 adult patients (incidence = 0.3%; M:F = 31:38; age, 55.8 ± 14.7years). Seventy-eight focal hypermetabolic lesions on spinal cord in the PET/CT scans of the 69 study subjects were analyzed. The most common sites of focal spinal cord uptake were the T12 vertebra (47/78; 60.3%) and L1 vertebra (20/78; 25.6%). Multifocal cord uptake was found in 8 of 69 patients (11.6%). The average SUVmax for cord uptake was 2.5 ± 0.5 (range, 1.4∼3.9). There was no clinical or imaging evidence of abnormalities in the spinal cord, both at the time of PET/CT and during clinical follow-up. Although incidental focal 18F-FDG uptake of the spinal cord is rare in patients with cancer, it may be physiological or benign, but it should not be considered as malignant involvement. Common sites for the uptake were in the T12 and L1 spine levels.

MRI Signal Intensity Classification in Cervical Ossification of the Posterior Longitudinal Ligament: Predictor of Surgical Outcomes.

Prospective cohort study. To investigate whether classification of increased signal intensity (ISI) on magnetic resonance imaging (MRI) of spinal cord in patients with cervical ossification of the posterior longitudinal ligament (C-OPLL) reflects severity of myelopathy and surgical outcome. The relationship between classification of ISI on C-OPLL and severity is unknown. The 119 consecutive patients (91 men, 28 women) with C-OPLL who underwent surgery were enrolled. T2-weighted MRI was performed before surgery and ISI was classified into three groups as follows, Grade 0, none; Grade 1, light (obscure); and Grade 2, intense (bright). The severity of myelopathy and surgical outcome were evaluated by the Japanese Orthopedic Association score. To determine factors that influence ISI, the change of the spinal cord cross-sectional area (SCA) during flexion and extension was calculated by computed tomography after myelography. The preoperative MRI showed 55 patients in Grade 0, 46 patients in Grade 1, and 18 patients in Grade 2. The preoperative Japanese Orthopedic Association score (Grade 0, 11.2; Grade 1, 10.3; Grade 2, 9.6 points) and surgical outcome got worsened with increasing ISI grade. The patients in Grade 2 had a longer duration of disease, while those in Grade 1 and Grade 2 had a larger change of SCA during flexion and extension (Grade 0, 4.8 mm; Grade 1, 7.3 mm; Grade 2, 7.8 mm). However age, alignment of the cervical spine, range of motion, and occupying ratio of the ossification were not different in the three grades. Grade of ISI correlated with preoperative severity of myelopathy and surgical outcome in patients with C-OPLL. Increased signal intensity of the spinal cord on MRI was associated with a larger change in SCA and longer duration of disease. 3.

The first successful report of the in vitro life cycle of Chinese Leishmania: the in vitro conversion of Leishmania amastigotes has been raised to 94% by testing 216 culture medium compound.

Chinese Leishmania isolate MHOM/CN/90/SC10H2 (L. H2), which was obtained from the spinal cords of patients from the Sichuan province of China, is an uncharacterized, pathogenic species closely related to Leishmania tarentolae. The in vitro transformation rate of L. H2 promastigotes into amastigotes has not been studied. This study is the first to successfully define the in vitro life cycle of L. H2 by investigating the percent conversion of L.H2 promastigotes to amastigotes in vitro under 216 different culture conditions. The highest proportion of L. H2 amastigotes observed (94%) was significantly higher than that previously reported. After conversion, the axenic amastigotes remained viable as verified by the levels of stage-specific genes (Gp46, A2 and β-tubulin) detected by RT-PCR. Meanwhile, morphological and protein characterizations of these axenic amastigotes were carried out in order to confirm the successful conversion. Specific antibodies were only able to detect 46 kDa, 52 kDa and 75 kDa proteins in samples isolated from axenic amastigotes. Afterward, these converted axenic amastigotes were transformed into the promastigote form by altering the culture condition. These converted axenic promastigotes still have the ability to infect macrophages, and their morphology changed back to the amastigote form following infection. These findings will assist further investigations into the biological characteristics of the host-parasite relationship and the process of pathogenesis.

Prevalence of brain and spinal cord inclusions, including dipeptide repeat proteins, in patients with the C9ORF72 hexanucleotide repeat expansion: a systematic neuropathological review.

The current literature shows no consensus on the localization and number of characteristic neuronal inclusions [p62 and dipeptide repeat proteins (DRPs) positive, TDP-43-negative and TDP-43 positive] in the brain and spinal cord of patients with the hexanucleotide repeat expansion on chromosome 9 (C9ORF72-positive patients). This may be due to small sample sizes. A valid brain map of the inclusions in C9ORF72-positive patients may improve clinicopathological correlations and may serve as a reference for neuropathologists. We performed a systematic review on 42 pathological studies to assess the pooled prevalence rates and density (a measure of the number of inclusions per brain region) of (phosphorylated)-TDP-43, p62 and DRP neuronal inclusions in seven brain regions and the spinal cord of 261 C9ORF72-positive patients with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and ALS-FTD. In the cerebellum and hippocampus, the pooled prevalence rates of TDP-43 neuronal cytoplasmic inclusions (NCIs; cerebellum: 3.9%; hippocampus: 68.3%) were lower than those of DRP (cerebellum: 97.2%; hippocampus 97.1%). Moreover, TDP-43 inclusion density was lower compared with p62 inclusion density in these regions. The pooled prevalence rate of TDP-43 NCI in the substantia nigra was high (94.4%). The findings of this systematic review largely confirm findings of previous smaller studies on the localization and prevalence of inclusions in the central nervous system of C9ORF72-positive patients. The high prevalence of TDP-43 inclusions in the substantia nigra is a relatively new finding and is probably related to the relatively high prevalence of parkinsonism in C9ORF72-positive patients.

The Influence of Diabetes on Surgical Outcomes in Cervical Myelopathy.

A retrospective cohort. The objective of the study was to determine what effect, if any, diabetes has on surgical outcomes in patients with cervical spondylotic myelopathy (CSM). Diabetes is known to impair healing and has been shown to affect outcomes in lumbar surgery, but few studies have assessed outcomes in cervical surgery, and cervical myelopathy in particular. The records of 113 patients operated on by one surgeon were reviewed. Inclusion criteria were a diagnosis of CSM with a Nurick score, surgical interventions, and minimum 2 years follow-up. Patients were divided into two groups according to diabetes status (33 diabetic patients vs. 80 controls) and diabetic patients were further categorized by degree of perioperative glucose control. Simple and multiple regression analyses were done to compare outcomes as recorded by the Nurick score, controlling for age, gender, duration of symptoms, alcohol use, cocaine use, surgical approach, prior surgery, and signal change on preoperative magnetic resonance imaging. There was no relationship between diabetes status and preoperative Nurick score. However, diabetes status was associated with impaired improvement in Nurick score. Average perioperative glucose in diabetic individuals was linearly associated with impaired improvement in Nurick score. We conclude that hyperglycemia may impair postoperative healing of the spinal cord in patients with CSM. 3.

Distinct T cell signatures define subsets of patients with multiple sclerosis.

Objective:We investigated T cell responses to myelin proteins in the blood of healthy controls and 2 groups of patients with relapsing-remitting multiple sclerosis (RRMS) who exhibited lesions either predominantly in the brain or predominantly in the spinal cord in order to assess whether distinct neuroinflammatory patterns were associated with different myelin protein–specific T cell effector function profiles and whether these profiles differed from healthy controls.Methods:Peripheral blood mononuclear cells were obtained from patients with brain-predominant RRMS, patients with spinal cord–predominant RRMS, and age-matched healthy controls and analyzed by enzyme-linked immunosorbent spot assays to quantify interferon gamma–secreting (Th1) and interleukin 17–secreting (Th17) cells responding directly ex vivo to myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG).Results:Although MBP and MOG elicited different responses, patients with multiple sclerosis (MS) who had spinal cord–predominant lesions exhibited significantly higher Th17:Th1 ratios in response to both MBP and MOG compared to patients with brain-predominant MS. Incorporating the cytokine responses to both antigens into logistic regression models showed that these cytokine responses were able to provide good discrimination between patients with distinct neuroinflammatory patterns.Conclusions:Our findings suggest that the localization of lesions within the brain vs the spinal cord in patients with MS is associated with different effector T cell responses to myelin proteins. Further investigation of the relationship between T cell effector function, antigen specificities, and lesion sites may reveal features of pathogenic pathways that are distinct to patients with different neuroinflammatory patterns.

Early indicators of relapses vs pseudorelapses in neuromyelitis optica spectrum disorder.

Objective:The purpose of this study was to review cases of neuromyelitis optica spectrum disorder (NMOSD) relapses and pseudorelapses to identify early features that differentiate between them at onset of symptoms.Methods:This was a retrospective analysis of 74 hospitalizations of patients with NMOSD who were admitted to the Johns Hopkins Hospital for workup and treatment of a presumed relapse. Standard workup included MRI and blood and urine testing for metabolic and infectious etiologies. The gold standard for a relapse was defined as new or worsening symptoms and a change in neurologic examination correlating with a new or enhancing MRI lesion. A pseudorelapse was a clinical exacerbation with similar symptoms and signs but the MRI was negative, and workup identified an alternative cause for the symptoms that, when treated, resulted in the improvement of neurologic symptoms. Factors considered to be early predictors of relapses vs pseudorelapses were analyzed using the Fisher test.Results:Among 74 NMOSD hospitalizations for presumed relapse, 57 were confirmed relapses while 17 had a negative MRI and an identifiable cause of pseudorelapse. The most common causes of pseudorelapse were infection, pain, and dysautonomia. The only early predictor that reliably differentiated relapse from pseudorelapse among this NMOSD patient population was vision loss (p = 0.039). Race, sex, presentations of weakness, numbness, and bowel/bladder dysfunction, white blood cell count, and urinary tract infection were not different among patients with relapses vs pseudorelapses.Conclusions:Vision loss in NMOSD is strongly suggestive of a true relapse vs a pseudorelapse. Pseudorelapses localized to the spinal cord in patients with previous myelitis presented similarly to true relapses and could only be ruled out by a negative MRI.

Reduction of cytosolic phospholipase A2α upregulation delays the onset of symptoms in SOD1G93A mouse model of amyotrophic lateral sclerosis.

BackgroundAmyotrophic lateral sclerosis (ALS) is a fatal multifactorial neurodegenerative disease characterized by selective death of motor neurons in the cortex, brainstem, and spinal cord. Cytosolic phospholipase A2 alpha (cPLA2α) upregulation and activation in the spinal cord of patients with sporadic ALS and in the spinal cord of human mutant SOD1G93A (hmSOD1) transgenic mice were recently reported.MethodscPLA2α upregulation in the brainstem and spinal cord was reduced by brain infusion of a specific antisense oligonucleotide against cPLA2α (AS), and the effect was evaluated on disease progression and brain cell activation.ResultsWe found that the elevation of cPLA2α protein expression in the spinal cord was first detected at 6-week-old hmSOD1 mice and remained elevated during their whole life span. Reduction of the elevated expression of cPLA2α in the spinal cord of hmSOD1 mice by brain infusion of an AS at week 15 (shortly before the appearance of the disease symptoms), for a duration of 6 weeks, delayed the loss of motor neuron function in comparison with hmSOD1 mice and with sense brain-infused hmSOD1 mice. To characterize the effect of cPLA2α upregulation on different processes taking place at the appearance of the disease symptoms, mice were brain infused with AS or with sense at week 15 for 3–4 weeks. The AS treatment that reduced cPLA2α upregulation in the spinal cord of AS-treated hmSOD1 mice (as analyzed at week 18–19) prevented the reduction in the number of the neurons (detected by NeuN) and inhibited astrocyte activation (detected by GFAP) and microglia activation (detected by Iba-1 and by CD40). In addition, AS treatment blunted the upregulation of the proinflammatory enzyme-inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) detected in hmSOD1 mice.ConclusionsSince specific reduction of cPLA2α in the brainstem and spinal cord significantly attenuated the development of the disease, cPLA2α may offer an efficient target for treatment of ALS.

Magnetic resonance imaging assessment of degenerative cervical myelopathy: a review of structural changes and measurement techniques.

Degenerative cervical myelopathy encompasses a spectrum of age-related structural changes of the cervical spine that result in static and dynamic injury to the spinal cord and collectively represent the most common cause of myelopathy in adults. Although cervical myelopathy is determined clinically, the diagnosis requires confirmation via imaging, and MRI is the preferred modality. Because of the heterogeneity of the condition and evolution of MRI technology, multiple techniques have been developed over the years in an attempt to quantify the degree of baseline severity and potential for neurological recovery. In this review, these techniques are categorized anatomically into those that focus on bone, ligaments, discs, and the spinal cord. In addition, measurements for the cervical spine canal size and sagittal alignment are also described briefly. These tools have resulted collectively in the identification of numerous useful parameters. However, the development of multiple techniques for assessing the same feature, such as cord compression, has also resulted in a number of challenges, including introducing ambiguity in terms of which methods to use and hindering effective comparisons of analysis in the literature. In addition, newer techniques that use advanced MRI are emerging and providing exciting new tools for assessing the spinal cord in patients with degenerative cervical myelopathy.

Evaluation of NADPH oxidases as drug targets in a mouse model of familial amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by progressive loss of motor neurons, gliosis, neuroinflammation and oxidative stress. The aim of this study was to evaluate the involvement of NADPH oxidases (NOX) in the oxidative damage and progression of ALS neuropathology. We examined the pattern of NOX expression in spinal cords of patients and mouse models of ALS and analyzed the impact of genetic deletion of the NOX1 and 2 isoforms as well as pharmacological NOX inhibition in the SOD1G93A ALS mouse model.A substantial (10–60 times) increase of NOX2 expression was detected in three etiologically different ALS mouse models while up-regulation of some other NOX isoforms was model-specific. In human spinal cord samples, high NOX2 expression was detected in microglia. In contrast to previous publications, survival of SOD1G93A mice was not modified upon breeding with constitutive NOX1 and NOX2 deficient mice. As genetic deficiency of a single NOX isoform is not necessarily predictive of a pharmacological intervention, we treated SOD1G93A mice with broad-spectrum NOX inhibitors perphenazine and thioridazine. Both compounds reached in vivo CNS concentrations compatible with NOX inhibition and thioridazine significantly decreased superoxide levels in the spinal cord of SOD1G93A mice in vivo. Yet, neither perphenazine nor thioridazine prolonged survival. Thioridazine, but not perphenazine, dampened the increase of microglia markers in SOD1G93A mice. Thioridazine induced an immediate and temporary enhancement of motor performance (rotarod) but its precise mode of action needs further investigation. Additional studies using specific NOX inhibitors will provide further evidence on the relevance of NOX as drug targets for ALS and other neurodegenerative disorders.

Is Preoperative Duration of Symptoms a Significant Predictor of Functional Status and Quality of Life Outcomes in Patients Undergoing Surgery for the Treatment of Degenerative Cervical Myelopathy?

Introduction Longstanding compression of the spinal cord in patients with degenerative cervical myelopathy (DCM) may result in irreversible neural tissue damage. This study aims to analyze whether a longer duration of symptoms is associated with poor surgical outcomes and to determine the optimal timing for decompressive surgery. Material and Methods Three hundred and fifty patients with symptomatic DCM were prospectively enrolled in either the CSM-North America or International study at 12 sites in North America. For each patient, extensive demographic information was collected, including age, co-morbidities, and a self-reported estimate of preoperative duration of symptoms. Postoperative functional status and quality of life were evaluated at 6-, 12- and 24-months using the modified Japanese Orthopaedic Association (mJOA), Nurick grade, Neck Disability Index (NDI) and Short-Form-36 (SF-36) Physical (PCS) and Mental (MCS) Component Scores. Change scores between baseline and 12-month follow-up were computed for each outcome measure. Duration of symptoms was dichotomized into a “short” and “long” group at several cut-offs. An iterative mixed model analytic approach procedure was used to evaluate differences in change scores on the mJOA, Nurick, SF-36 MCS and PCS and NDI between duration groups in 1-month increments. Two models were constructed: 1) an unadjusted model between duration of symptoms and surgical outcome and 2) a model adjusting for significant independent covariates identified through stepwise regression analysis. Results Our cohort consisted of 201 (57.43%) men and 149 (42.57%) women, with a mean age of 57.49 ± 11.77 years (range: 29–87 years). The mean duration of symptoms was 25.71 ± 36.68 months (range: 1–240 months). In unadjusted analysis, patients with a duration of symptoms shorter than 4 months had significantly better functional outcomes based on the mJOA ( p = 0.04) than patients with a longer duration of symptoms (&gt;4 months). On average, patients with a shorter duration of symptom improved by 3.71 on the mJOA, whereas those with a duration 4 months or longer only exhibited a 2.96 mean gain. Twelve months was identified as the next important cut-off beyond which patients had a significantly worse outcomes on the mJOA; however, this difference was smaller. Following adjusted analysis, cut-offs of 4 and 12 months remained significant. Duration of symptoms was not associated with Nurick or SF-36 PCS or MCS in either the unadjusted or adjusted models. Conclusion Patients who are operated on within 4 months of symptom presentation have better mJOA outcomes. It is recommended that patients with DCM are diagnosed in a timely fashion and referred early for surgical consultation. Our study does not support the traditional conservative “watchful waiting” approach to symptomatic patients with DCM.

Dynamic properties of SOD1 mutants can predict survival time of patients carrying familial amyotrophic lateral sclerosis

One of the reasons for the death of motor neurons of the brain and spinal cord in patients with amyotrophic lateral sclerosis is known to be formation of subcellular protein aggregates that are caused by mutations in the SOD1 gene. Patient survival time was earlier shown to have limiting correlation with thermostability change of SOD1 mutant forms of patients’ carriers. We hypothesized that aggregation of mutant SOD1 may occur not only due to the protein destabilization, but through formation of novel interatomic bonds which stabilize “pathogenic” conformations of the mutant as well. To estimate these effects in the present paper, we performed statistical analysis of occupancy of intramolecular hydrogen bonds, hydrogen bonds between the protein and water molecules, and water bridges with use of molecular dynamics simulation for 38 mutant SOD1 forms. Multiple regression model based on these kinds of bonds demonstrated correlation with patient survival time significantly better (R = .9, p-value < 10−11) than the thermostability of SOD1 mutants only. It was shown that the occupancy of intramolecular hydrogen bonds between amino acid residues is a key determinant (R = .89, p-value < 10−10) in predicting patients’ survival time.

Detection of hyperphosphorylated tau protein and α-synuclein in spinal cord of patients with Alzheimer's disease.

The aim of this study was to investigate the neuropathological features of the spinal cord in patients suffering with Alzheimer’s disease (AD). Spinal cord tissue collected from three AD patients and eight controls was selected for the study. Data were collected at T2, T8, T10, L4, and S2 spinal levels. The sections were subjected to hematoxylin and eosin and Gallyas–Braak staining methods and then were immunostained with antibodies such as phosphorylated tau protein (AT8), α-synuclein, Aβ, amyloid precursor protein, ubiquitin, and TDP-43. Pathological changes exhibited by the biomarkers were detected by microscopy. Neurofibrillary tangles (NFTs) were detectable in spinal anterior horn motor neurons in two of the three AD patients. AT8-positive axons or axon-like structures and AT8 expression in glial cells were detected in all three AD cases. Hyperphosphorylation of tau protein was detected in spinal anterior horn cells, glial cells, and axons, and its severity was associated with NFTs in the brain tissue. α-Synuclein-positive Lewy bodies and scattered Lewy-like neuritis were detected in the medial horn of the thoracic spinal cord and ventral sacral gray matter, respectively, in one patient who had AD with Lewy bodies. Neither amyloid deposition nor amyloid precursor protein and TDP-43 expression was detected in the spinal cord of AD patients. Spinal cord of AD patients was observed to contain phosphorylated tau protein and α-synuclein immunoreactive structures, which may play a role in dyskinesia and autonomic dysfunction in advanced AD.

Motor and somatosensory evoked potential spinal cord monitoring during intubation and neck extension for thyroidectomy in a Down syndrome boy with atlantoaxial instability

Intubation or neck extension can compress the spinal cord in patients with craniocervical instability. Protective motor evoked potential (MEP) and somatosensory evoked potential (SEP) monitoring of these maneuvers is an obvious consideration when these patients undergo already-monitored spinal surgery, but might be overlooked when they undergo other normally unmonitored procedures. Here we report monitoring intubation and neck extension for the unusual indication of thyroidectomy in a Down syndrome boy with atlantoaxial instability. Transcranial electric stimulation thenar MEPs and optimized median nerve SEPs were acquired about every minute throughout intubation and neck extension under propofol and remifentanil anesthesia without neuromuscular blockade. Potentials were stable and there was no neurologic deficit. This approach could protect craniocervical instability patients against cord compression when they undergo intubation and neck extension for surgical procedures that would not otherwise indicate spinal cord monitoring.

Inositol Hexakisphosphate Kinase 2 Promotes Cell Death in Cells with Cytoplasmic TDP-43 Aggregation.

TAR DNA-binding protein 43 (TDP-43) has been identified as a major component of ubiquitin-positive inclusions in the brains and spinal cords of patients with frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) or amyotrophic lateral sclerosis (ALS). The phosphorylated C-terminal fragment of TDP-43 forms aggregates in the neuronal cytoplasm, possibly resulting in neuronal cell death in patients with FTLD-U or ALS. The inositol pyrophosphate known as diphosphoinositol pentakisphosphate (InsP7) contains highly energetic pyrophosphate bonds. We previously reported that inositol hexakisphosphate kinase type 2 (InsP6K2), which converts inositol hexakisphosphate (InsP6) to InsP7, mediates cell death in mammalian cells. Moreover, InsP6K2 is translocated from the nucleus to the cytosol during apoptosis. In this study, we verified that phosphorylated TDP-43 co-localized and co-bound with InsP6K2 in the cytoplasm of anterior horn cells of the spinal cord. Furthermore, we verified that cell death was augmented in the presence of cytoplasmic TDP-43 aggregations and activated InsP6K2. However, cells with only cytoplasmic TDP-43 aggregation survived because Akt activity increased. In the presence of both TDP-43 aggregation and activated InsP6K2 in the cytoplasm of cells, the expression levels of HSP90 and casein kinase 2 decreased, as the activity of Akt decreased. These conditions may promote cell death. Thus, InsP6K2 could cause neuronal cell death in patients with FTLD-U or ALS. Moreover, InsP6K2 plays an important role in a novel cell death pathway present in FTLD-U and ALS.

Accumulation of phosphorylated α-synuclein in subpial and periventricular astrocytes in multiple system atrophy of long duration.

The histological hallmark of multiple system atrophy (MSA) is accumulation of phosphorylated α-synuclein in oligodendrocytes. However, it is uncertain whether phosphorylated α-synuclein accumulates in astrocytes of MSA patients. We immunohistochemically examined the frontal and temporal lobes, basal ganglia, cerebellum, brainstem and spinal cord of patients with MSA (n = 15) and Lewy body disease (n = 20), and also in control subjects (n = 20). Accumulation of abnormally phosphorylated and aggregated α-synuclein was found in subpial and periventricular astrocytes in six of the 15 patients with MSA (40%). The structures were confined to the subpial surface of the ventro-lateral part of the spinal cord and brainstem, as well as the subependymal region of the lateral ventricles. They were not visualized by Gallyas-Braak staining, and were immunonegative for ubiquitin and p62. Immunoelectron microscopy revealed that the phosphorylated α-synuclein-immunoreactive structures in astrocytes were non-fibrillar and associated with granular and vesicular structures. The extent of phosphorylated α-synuclein-immunoreactive astrocytes was correlated with disease duration. No such structures were found in Lewy body disease or controls. Accumulation of phosphorylated α-synuclein can occur in subpial and periventricular astrocytes in patients with MSA, especially in those with a long disease duration.