Severe Autonomic Dysfunction Research Articles

Study on Paeoniflorin Promoting the Recovery of Motor Function of Rat Spinal Cord Injury by Mediating MAPK/ERK and Akt/mTOR Signal Pathway

Spinal cord injury (SCI) is a devastating disease that can cause severe motor, sensory, and autonomic dysfunction. There is currently no effective treatment. Paeonia lactiflora is a traditional Chinese herbal medicine, which has antispasmodic, analgesic, and blood circulation effects. Paeoniflorin (PEF) is a medicinal plant isolated from Paeoniae Radio, and it is widely used in East Asia. A large number of studies have shown that PEF has a powerful neuroprotective effect. However, the potential mechanism of PEF on SCI needs further study. This project uses Basso Beattie Bresnahan (BBB) motor function score and open field test to evaluate neurological function, and uses immunofluorescence method to detect brain-derived neurotrophic factor (BNDF) and neurotrophin-3 (NT). -3) Protein expression, Western blot is used to detect protein expression level, and RT-PCR is used to detect mRNA expression level. Thus, a rat spinal cord injury model was established to observe the effects of AT/mTOR and MAPK/ERK signal pathways activated by PEF on nerve regeneration and functional recovery in rats with spinal cord injury.

Surveillance for Transthyretin Amyloidosis Progression after Heart Transplantation in the Era of Novel Disease Modifying Therapies

<h3>Purpose</h3> Transthyretin amyloidosis (ATTR) predominantly involves the heart (ATTR-cardiac amyloidosis [CA]) and nerves, and may involve other organs or tissues. Disease modifying therapies improve outcomes in those with ATTR-CA or with neurologic involvement, however their utility post heart transplant (HT) or combined heart/liver transplant is uncertain. We evaluated patients who underwent HT for ATTR-CA to determine the incidence of de novo development or progression of neurologic, GI and soft tissue manifestations of ATTR deposition. <h3>Methods</h3> We performed a review of all patients who underwent HT for ATTR-CA at our center. Baseline demographics and post HT manifestations of TTR deposition were collected. All patients completed the Composite Autonomic Symptom Score (COMPASS-31) and Polyneuropathy Disability Score (PDS). The COMPASS-31 is a questionnaire of autonomic symptoms, with a higher score (0 - 100) indicating more severe autonomic dysfunction. The PDS ranges from 0 (asymptomatic) to 4 (confined to wheelchair/bed). <h3>Results</h3> Twelve patients were included. Mean age at HT was 67 ± 5 yrs, 83.3% male, and 50% Black. Five patients had wild-type and 7 had variant ATTR-CA (6 V122I, 1 T60A). At a mean of 5.2 ± 3.9 yrs post-transplant, 8 patients had symptoms of progressive or de novo ATTR deposition with 4 having involvement in ≥ 2 systems (Figure 1). None had cardiac involvement on PYP imaging (n=5) or serial endomyocardial biopsy. The mean COMPASS-31 was 19.5 (range 0.9 - 45.8) at a median time from HT of 3.9 ± 3.5 years. Three subjects had a PDS of 1 and 1 each scored 2, 3b, and 4, the latter patient was homozygous for the V122I variant. <h3>Conclusion</h3> In our single-center study, > 50% of patients had evidence of progressive or de novo TTR deposition post HT. This adds significant morbidity despite a functioning cardiac allograft. These observations underscore an unmet need for TTR modifying therapies that could slow TTR deposition and significantly improve quality of life post HT for ATTR-CA.

Regional Gray Matter Volume Changes in Parkinson's Disease with Orthostatic Hypotension.

Neurodegenerative change in the central nervous system has been suggested as one of the pathophysiological mechanisms of autonomic nervous system dysfunction in Parkinson’s disease (PD). We analyzed gray matter (GM) volume changes and clinical parameters in patients with PD to investigate any involvement in the brain structures responsible for autonomic control in patients with PD having orthostatic hypotension (OH). Voxel-based morphometry was applied to compare regional GM volumes between PD patients with and without OH. Multivariate logistic regression analysis using a hierarchical model was carried out to identify clinical factors independently contributing to the regional GM volume changes in PD patients with OH. The Sobel test was used to analyze mediation effects between the independent contributing factors to the GM volume changes. PD patients with OH had more severe autonomic dysfunction and reduction in volume in the right inferior temporal cortex than those without OH. The right inferior temporal volume was positively correlated with the Qualitative Scoring MMSE Pentagon Test (QSPT) score, reflecting visuospatial/visuoperceptual function, and negatively correlated with the Composite Autonomic Severity Score (CASS). The CASS and QSPT scores were found to be factors independently contributing to regional volume changes in the right inferior temporal cortex. The QSPT score was identified as a mediator in which regional GM volume predicts the CASS. Our findings suggest that a decrease in the visuospatial/visuoperceptual process may be involved in the presentation of autonomic nervous system dysfunction in PD patients.

Association of autonomic symptoms with cerebrospinal fluid biomarkers in Parkinson disease and scans without evidence of dopaminergic deficit.

Dysautonomia is common in patients with Parkinson disease (PD) since disease early phase. Scales for Outcomes in Parkinson's disease – Autonomic (SCOPA-AUT) is a well-designed scale assessing the autonomic dysfunctions of PD patients. Our objectives were to examine the autonomic dysfunction in PD and scan without evidence of dopaminergic deficit (SWEDD) patients and to assess the correlation of autonomic dysfunctions with cerebrospinal fluid (CSF) biomarkers.An analysis of the Parkinson's Progression Markers Initiative (PPMI) data including 414 PD patients, 60 SWEDD patients, and 170 healthy controls (HCs) with baseline CSF biomarker measurements and SCOPA-AUT assessments was presented. Autonomic symptoms including gastrointestinal, urinary, cardiovascular, pupillomotor, thermoregulatory and sexual dysfunctions were assessed by SCOPA-AUT scales. Spearman correlation test was used to examine the correlations between CSF measurements and each section of SCOPA-AUT scales in HCs and subjects with PD or SWEDD.More severe autonomic dysfunctions were observed in patients with SWEDD than those with PD (P < .001). Specifically, patients with PD have lower scores on the urinary scale [4 (0–17) vs 5 (1–18)], pupillomotor scale [0 (0–3) vs 0 (0–3)], thermoregulatory scale [0 (0–4) vs 1.5 (0–10)] and sexual scale [1 (0–6) vs 2 (0–6)] compared with SWEDD patients. Thermoregulatory dysfunction scores were found correlated with CSF α-syn levels in SWEDD group, and gastrointestinal dysfunction scores were correlated with CSF Abeta1–42 in PD group. Additionally, urinary dysfunction scores were correlated with CSF total tau and tau phosphorylated at threonine 181(p-tau181) levels in both HCs and PD patients.

Neuromuscular amyloidosis: Unmasking the master of disguise.

Amyloidosis refers to an etiologically heterogeneous group of protein misfolding diseases, pathologically characterized by extracellular amyloid fibrils producing congophillic amorphous deposits in organs and tissues, which may lead to severe organ dysfunction and mortality. Clinical presentations vary and are often nonspecific, depending on what organs or tissues are affected. In systemic amyloidosis, the peripheral nervous system is commonly affected, whereas the skeletal muscles are only rarely involved. Immunoglobulin light chain (AL) amyloidosis and hereditary transthyretin (ATTRv) amyloidosis are the most frequent types of systemic amyloidosis involving the neuromuscular system. Localized amyloidosis can occur in skeletal muscle, so-called isolated amyloid myopathy. Amyloid neuropathy typically involves small myelinated and unmyelinated sensory and autonomic nerve fibers early in the course of the disease, followed by large myelinated fiber sensory and motor deficits. The relentlessly progressive nature with motor, painful sensory and severe autonomic dysfunction, profound weight loss, and systemic features are distinct characteristics of amyloid neuropathy. Amyloid myopathy presentation differs between systemic amyloidosis and isolated amyloid myopathy. Long-standing symptoms, distal predominant myopathy, markedly elevated creatine kinase level, and lack of peripheral neuropathy or systemic features are highly suggestive of isolated amyloid myopathy. In ATTR and AL amyloidosis, early treatment correlates with favorable outcomes. Therefore, awareness of these disorders and active screening for amyloidosis in patients with neuropathy or myopathy are crucial in detecting these patients in the everyday practice of neuromuscular medicine. Herein, we review the clinical manifestations of neuromuscular amyloidosis and provide a diagnostic approach to this disorder.

The Association Between REM Sleep Behavior Disorder and Autonomic Dysfunction in Parkinson's Disease.

REM behavior disorder (RBD) can occur in the context of neurodegenerative alpha-synucleinopathies, such as Parkinson's disease (PD). PD patients with RBD (PD-pRBD) represent more severe symptoms and signs compared with those without RBD (PD-nRBD). On another note, autonomic dysfunction in PD patients is categorized as one of the most prominent non-motor symptoms and has been lately the field of interest in research. In the current study, we longitudinally studied autonomic dysfunction in PD-pRBD and PD-nRBD groups. This study was conducted on 420 drug-naïve PD patients selected from the Parkinson's Progression Markers Initiative database. The RBD Screening Questionnaire was used to define the presence of probable RBD. SCOPA-AUT was used to assess autonomic dysfunction. Additionally, dopamine transporter deficits on [123I] FP-CIT SPECT imaging was performed for all of the patients. Out of 420 PD patients, 158 individuals (37.6%) were considered to have probable RBD (PD-pRBD) and others without RBD (PD-nRBD). Except for pupillomotor function, all the autonomic symptoms were significantly more severe in PD-pRBD group. In PD-nRBD group, caudate striatal binding ratio was negatively correlated with SCOPA-AUT scores, while no significant correlation was observed in PD-pRBD group. Finally, there was a significant difference considering the longitudinal changes of SCOPA-AUT total between PD-pRBD and PD-nRBD groups, suggesting a more severe autonomic decline in PD-pRBD patients. Our results indicate that PD-pRBD patients have more severe autonomic dysfunction. These results support the theory that PD patients can be categorized based on the clinical presentation, possibly representing differences in the disease pathophysiology.

Anti-NMDAR Encephalitis Presenting as Stroke-like Episodes in Children: A Case Series from a Tertiary Care Referral Centre from Southern India.

ABSTRACTBackground:Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is one of the common causes of treatable encephalitis in children characterized by severe memory deficit, speech disturbances, seizures, autonomic dysfunction, and movement disorders. Hemiparesis/stroke-like episode is not a usual presenting complaint of NMDAR encephalitis. The objective of this study was to report confirmed cases of seropositive anti-NMDAR encephalitis in children who presented with hemiparesis/stroke-like episodes.Materials and Methods:Retrospective review of charts of patients with a diagnosis of NMDAR encephalitis was performed at the pediatric neurology department attached to a tertiary care hospital for 6 years from March 2014 to February 2020. Only those case records with NMDAR seropositivity in the cerebrospinal fluid were collected and those who presented with stroke-like episode/hemiparesis were retrieved separately and the data were extracted in a predesigned proforma and analyzed.Results:Six children of 24 seropositive anti-NMDAR encephalitis presented with hemiparesis/stroke-like episode. All the six patients presented with hemiparesis, behavioral changes, and regression of speech. Three children had seizures and one child had Epilepsia partialis continua. Two children had dystonia and choreoathetosis. Methylprednisolone followed by oral steroids were administered in all patients. Cases 1, 2, and 4 made a full recovery within 7 days, but cases 3, 5, and 6 showed improvement after 20 days following additional IVIG. Four children have cognitive decline and behavioral problems. Case 6 had relapse and recovered with rituximab.Conclusion:Anti-NMDA receptor encephalitis which is a potentially treatable disease should be considered in the differential diagnosis when a child presents with hemiparesis/stroke-like episode.

Guillain–Barré syndrome as a parainfectious manifestation of SARS-CoV-2 infection: A case series

The global SARS-CoV-2 pandemic posed an unprecedented challenge to almost all fields of medicine and Neurology is not an exception. Collecting information about its complications and related conditions will help clinicians to become more confident in managing this disease. Guillain-Barre Syndrome (GBS) is mostly described as a post-infectious phenomenon and its occurrence during acute phase of illness is of interest. GBS has recently been reported during the active phase of COVID-19 for the first time. Severity and fast progression of GBS associated with COVID-19 have also been shown in recent studies. Here we report three cases of GBS during the active phase of COVID-19 with severe symptoms and fast progression to quadriplegia and facial diplegia over 2 days, which led to death in one case due to severe autonomic dysfunction. We suggest SARS-CoV-2 might be associated with rather a severe, rapidly progressive and life-threatening phenotype of GBS.

End Stage Clinical Features and Cause of Death of Behavioral Variant Frontotemporal Dementia and Young-Onset Alzheimer's Disease.

Background:Limited literature exists regarding the clinical features of end stage behavioral variant frontotemporal dementia (bvFTD). This data is indispensable to inform and prepare family members as well as professional caregivers for the expected disease course and to anticipate with drug-based and non-pharmacological treatment strategies.Objective:The aim of the present study was to describe end stage bvFTD in a broad explorative manner and to subsequently evaluate similarities and dissimilarities with the end stage of the most prevalent form of young-onset dementia, Alzheimer’s disease (yoAD).Methods:We analyzed medical files on patients, using a mixed model of qualitative and quantitative approaches. Included were previously deceased patients with probable bvFTD and probable yoAD. End stage was defined as the last 6 months prior to death. Primary outcome measures comprised somatic, neurological, and psychiatric symptoms and the secondary outcome measure was cause of death.Results:Out of 89 patients, a total of 30 patients were included (bvFTD; n = 12, yoAD; n = 18). Overall, the end stages of bvFTD and yoAD were characterized by a broad spectrum of clinical symptoms including severe autonomic dysfunction and an increased muscle tone. Patients with bvFTD displayed more mutism compared with yoAD while compulsiveness was only present in bvFTD.Conclusion:Our study describes the full clinical spectrum of end stage bvFTD and yoAD. In this study, symptoms extend far beyond the initial behavioral and cognitive features. By taking both somatic, psychiatric, and neurological features into account, family members and professional caregivers may anticipate (non) pharmacological treatment.

Progress in clinical trials of cell transplantation for the treatment of spinal cord injury: how many questions remain unanswered?

Spinal cord injury can lead to severe motor, sensory and autonomic nervous dysfunctions. However, there is currently no effective treatment for spinal cord injury. Neural stem cells and progenitor cells, bone marrow mesenchymal stem cells, olfactory ensheathing cells, umbilical cord blood stem cells, adipose stem cells, hematopoietic stem cells, oligodendrocyte precursor cells, macrophages and Schwann cells have been studied as potential treatments for spinal cord injury. These treatments were mainly performed in animals. However, subtle changes in sensory function, nerve root movement and pain cannot be fully investigated with animal studies. Although these cell types have shown excellent safety and effectiveness in various animal models, sufficient evidence of efficacy for clinical translation is still lacking. Cell transplantation should be combined with tissue engineering scaffolds, local drug delivery systems, postoperative adjuvant therapy and physical rehabilitation training as part of a comprehensive treatment plan to provide the possibility for patients with SCI to return to normal life. This review summarizes and analyzes the clinical trials of cell transplantation therapy in spinal cord injury, with the aim of providing a rational foundation for the development of clinical treatments for spinal cord injury.

Sporadic Cerebellar Ataxia: Multiple System Atrophy and Mono System Atrophy

Cerebellar ataxia-predominant multiple system atrophy (MSA-C) and cortical cerebellar atrophy are representative diseases of adult-onset sporadic degenerative ataxia. Both diseases are distinctly different because of α-synuclein pathology. However, it takes approximately 2 years for cerebellar ataxia to progress to concomitant severe autonomic dysfunction in patients with MSA-C. The period of only cerebellar ataxia (mono system atrophy) may extend to more than 10 years. Understanding mono system atrophy is vital for the early diagnosis and drug development for MSA. In this review, we discuss mono system atrophy focusing on the concept and natural history and the possibility of the of early diagnosis and disease-modifying therapy for MSA.

The challenges of COVID-19 for people with dementia with Lewy bodies and family caregivers.

The challenges of COVID-19 for people with dementia with Lewy bodies and family caregivers.

Association of specific biotypes in patients with Parkinson disease and disease progression.

ObjectiveTo identify biotypes in patients with newly diagnosed Parkinson disease (PD) and to test whether these biotypes could explain interindividual differences in longitudinal progression.MethodsIn this longitudinal analysis, we use a data-driven approach clustering PD patients from the Parkinson's Progression Markers Initiative (n = 314, age 61.0 ± 9.5, years 34.1% female, 5 years of follow-up). Voxel-level neuroanatomic features were estimated with deformation-based morphometry (DBM) of T1-weighted MRI. Voxels with deformation values that were significantly correlated (p < 0.01) with clinical scores (Movement Disorder Society–sponsored revision of the Unified Parkinson’s Disease Rating Scale Parts I–III and total score, tremor score, and postural instability and gait difficulty score) at baseline were selected. Then, these neuroanatomic features were subjected to hierarchical cluster analysis. Changes in the longitudinal progression and neuroanatomic pattern were compared between different biotypes.ResultsTwo neuroanatomic biotypes were identified: biotype 1 (n = 114) with subcortical brain volumes smaller than heathy controls and biotype 2 (n = 200) with subcortical brain volumes larger than heathy controls. Biotype 1 had more severe motor impairment, autonomic dysfunction, and much worse REM sleep behavior disorder than biotype 2 at baseline. Although disease durations at the initial visit and follow-up were similar between biotypes, patients with PD with smaller subcortical brain volume had poorer prognosis, with more rapid decline in several clinical domains and in dopamine functional neuroimaging over an average of 5 years.ConclusionRobust neuroanatomic biotypes exist in PD with distinct clinical and neuroanatomic patterns. These biotypes can be detected at diagnosis and predict the course of longitudinal progression, which should benefit trial design and evaluation.

Alterations in the fecal microbiota of patients with spinal cord injury.

ObjectivesSpinal cord injury (SCI) is associated with severe autonomic dysfunction. Patients with SCI often suffer from a lack of central nervous system control over the gastrointestinal system. Therefore, we hypothesized that patients with SCI would cause intestinal flora imbalance. We investigated alterations in the fecal microbiome in a group of patients with SCI.MethodsMicrobial communities in the feces of 23 patients and 23 healthy controls were investigated using high-throughput Illumina Miseq sequencing targeting the V3-V4 region of the 16S ribosomal RNA (rRNA) gene. The relative abundances between the fecal microbiota at the genus level in patients with SCI and healthy individuals were determined using cluster analysis.ResultsThe structure and quantity of fecal microbiota differed significantly between patients with SCI and healthy controls, but the richness and diversity were not significantly different. A two-dimensional heatmap showed that the relative abundances of forty-five operational taxonomic units (OTUs) were significantly enriched either in SCI or healthy samples. Among these, 18 OTUs were more abundant in healthy controls than in patients with SCI, and 27 OTUs were more abundant in the SCI group than in healthy controls.ConclusionOur study showed that patients with SCI exhibited microbiome dysbiosis.

White Matter Hyperintensities Mediate Impact of Dysautonomia on Cognition in Parkinson's Disease.

Patients with Parkinson's disease (PD) present with a broad spectrum of nonmotor features including autonomic disorders. More severe autonomic dysfunction in PD is associated with increased cognitive deficits. The presence of cerebral small-vessel disease, measured by T2-weighted magnetic resonance imaging white matter hyperintensity (WMH) burden, is also observed in patients with PD with faster cognitive decline. To investigate whether baseline orthostatic hypotension and autonomic dysfunction in early-stage PD affect later cognitive decline via mediation through cerebral small-vessel disease. De novo PD patients (N = 365) and age-matched controls (N = 174) with baseline T2-weighted/ fluid-attenuated inversion recovery scans were selected from the Parkinson's Progression Markers Initiative. WMHs were automatically segmented. Mediation analysis was used to assess whether WMH load mediates the effect of orthostatic hypotension and autonomic dysfunction (measured by Scales for Outcomes in Parkinson's Disease-Autonomic) on future cognitive decline (measured by Montreal Cognitive Assessment) in an average of 4 years of follow-up. Mediation analysis supported the existence of a full mediation of WMHs on the effect of diastolic orthostatic hypotension in patients with PD and future cognitive decline (average causal mediation effect: ab = -0.032, 95% confidence interval = -0.064 to -0.01, P = 0.01). There was also a partial mediation for overall autonomic dysfunction (ab = -0.027, 95% confidence interval = -0.054 to 0.00, P = 0.02). WMHs fully mediate the effect of diastolic orthostatic hypotension and partially mediate the effect of autonomic dysregulation on future cognitive decline in patients with PD. Our findings support the hypothesis that autonomic dysfunction in early clinical stages predisposes the brain to WMHs through dysregulation of the blood flow in the small vessels. This in turn increases the risk of future cognitive impairment in early PD.

Characteristics of the 24-h ambulatory blood pressure monitoring in patients with Parkinson's disease - the SFC BP multicentre study in China.

Cardiovascular dysautonomia can be present at early, late and even prodromal stages of Parkinson's disease. This study aimed to describe the characteristics of 24-h ambulatory blood pressure (BP) monitoring and investigate the frequency of cardiovascular dysautonomia in Parkinson's disease without an abnormal BP history. Parkinson's disease patients without history of abnormal BP were consecutively enrolled from three Chinese centres, on whom office BP measurement, neurological evaluations and 24-h ambulatory BP monitoring were performed. Totally, 101 Parkinson's disease patients (42.6% women) with an average age of 66.6 ± 8.2 years were included in our cohort, and data analysis revealed that 26 (25.74%) patients suffered from orthostatic hypotension, among whom 18 (69.23%) were symptomatic. Patients with orthostatic hypotension compared with those without had significantly higher nocturnal SBP level, and more severe nonmotor symptoms, autonomic dysfunction and cognitive impairment. Further, 54 out of 101 (53.47%) individuals had a reverse dipping pattern in SBP and/or DBP. Reverse dippers had more cases of orthostatic hypotension (P < 0.001), and more severe nonmotor symptoms. SBP dipping ratio of less than -2.98% generated 76.9% of sensitivity, 69.3% of specificity, 46.5% of positive predictive value (PPV), 89.7% of negative predictive value (NPV) and 77.4% of accuracy, while diastolic dipping ratio of less than -1.80% generated 76.9% of sensitivity, 70.7% specificity, 47.6% of PPV, 89.8% of NPV and 77.8% of accuracy for suspecting orthostatic hypotension. Orthostatic hypotension can occur in one-fourth Parkinson's disease patients without abnormal BP history, and reverse dipping was present in more than half of patients with Parkinson's disease. Reverse dipping pattern was helpful to suspect orthostatic hypotension.

Polyradiculitis in autoimmune encephalitis: a case report and review

BackgroundLimbic encephalitis is a subacute progressive disorder characterized by disturbances in memory and behavior along with seizures. Antibodies against leucine-rich glioma-inactivated 1 (LGI1) are associated with a subtype of encephalitis which along with the abovementioned symptoms is also characterized by severe pain and autonomic dysfunction. The classical radiological presentation of LGI1 encephalitis is that of amygdala and hippocampal enlargement unilaterally or bilaterally with a T2 hyperintensity. Extratemporal involvement is considered a rare feature.Case descriptionWe present the only known case in our knowledge of anti-LGI1 encephalitis in a 47-year-old male presenting as dorsal root ganglia and spinal nerve enhancement on imaging.DiscussionClinicians should be aware of this atypical presentation and consider anti-LGI1 encephalitis as a possible diagnosis when presented with such a neuroradiological feature.

Tachycardia control in septic shock with esmolol and ivabradine: a comparison on heart function.

Persisting tachycardia is often observed in resuscitated septic shock patients, and it is an independent risk factor for increased mortality. Recently, several drugs, such as esmolol and ivabradine, have been proved to be beneficial in HR control, but their overall impact on cardiac functions needs further investigation. The aim of this study is to study the effects of the two drugs on heart function in a protocol of polymicrobial septic shock and resuscitation. Twelve pigs were divided into three experimental groups: the esmolol-treated group (n=4), the ivabradine-treated group (n=5) and the control group (n=3). Cardiac autonomic activity was estimated by heart rate variability (HRV) indices and baroreflex sensitivity (BRS). The Buckberg index was adopted to evaluate myocardial oxygenation efficiency. Septic shock induced a severe autonomic dysfunction and a lower cardiac efficiency, not resolved by fluids resuscitation. The administration of the drugs improved both the HRV and the BRS, but this favourable condition was preserved after noradrenaline administration only in the esmolol group. The interaction of esmolol with the autonomic system is beneficial in septic shock to restore an improved condition of HRV and control, while ivabradine is not as effective when administered in adjunction to noradrenaline.

0787 Autonomic Dysfunction and Phenoconversion in Idiopathic/Isolated REM Sleep Behavior Disorder

Abstract Introduction REM-sleep behavior disorder (RBD) is a common finding among patients with synucleinopathies. We aimed to determine the degree of autonomic dysfunction in patients presenting with idiopathic RBD (iRBD), and the predictive value of autonomic dysfunction for phenoconversion to a defined neurodegenerative disease. Methods We searched our electronic medical record for patients diagnosed with iRBD who also underwent standardized autonomic function testing within 6 months of iRBD diagnosis, and who had clinical follow-up of at least 3 years following iRBD diagnosis. Patients who received a diagnosis of phenoconversion within 3 months of autonomic testing were excluded. The composite autonomic severity score (CASS) was derived and compared between phenoconverters and non-converters using chi-square and Wilcoxon rank-sum tests. Results We identified 18 patients who fulfilled in- and exclusion criteria. Average age at autonomic testing was 67 ± 6.6 years. Twelve (67%) patients phenoconverted during the follow-up period; 6 developed PD, the other 6 DLB. Fifteen (83%) patients had at least mild autonomic dysfunction. There were no significant differences between overall converters and non-converters in total CASS or CASS subscores. However, iRBD patients who developed DLB had significantly higher total and cardiovagal CASS scores compared with those who developed PD (p &amp;lt;0.05), and a trend for higher adrenergic CASS scores compared to those who developed PD and those who did not phenoconvert (p=0.08 for each). Conclusion Autonomic dysfunction was seen in 83% of iRBD patients, and more severe baseline cardiovagal and adrenergic autonomic dysfunction in iRBD was associated with phenoconversion to DLB but not PD. Prospective studies are needed to confirm the value of autonomic testing for predicting phenoconversion and disease phenotype in iRBD. Support

Transplantation Strategies for Spinal Cord Injury Based on Microenvironment Modulation.

Spinal cord injury (SCI) is different from peripheral nerve injury; it results in devastating and permanent damage to the spine, leading to severe motor, sensory and autonomic dysfunction. SCI produces a complex microenvironment that can result in hemorrhage, inflammation and scar formation. Not only does it significantly limit regeneration, but it also challenges a multitude of transplantation strategies. In order to promote regeneration, researchers have recently begun to focus their attention on strategies that manipulate the complicated microenvironment produced by SCI. And some have achieved great therapeutic effects. Hence, reconstructing an appropriate microenvironment after transplantation could be a potential therapeutic solution for SCI. In this review, first, we aim to summarize the influential compositions of the microenvironment and their different effects on regeneration. Second, we highlight recent research that used various transplantation strategies to modulate different microenvironments produced by SCI in order to improve regeneration. Finally, we discuss future transplantation strategies regarding SCI.