Effects of Medications and Subthalamic Nucleus-Deep Brain Stimulation on the Cutaneous Silent Period in Patients With Parkinson's Disease

ObjectivesWe sought to evaluate whether the cutaneous silent period (CSP) could be an electrophysiological indicator reflective of the effects of therapy for Parkinson's disease (PD), including anti-PD medications or deep brain stimulation (DBS).Material and MethodsWe recorded the CSP in 43 patients with PD prior to and following the administration of medication during a pre-DBS evaluation (30 cases) and the “on” and “off” states of subthalamic nucleus DBS (13 cases). The CSP was elicited from the abductor pollicis brevis muscle by an electrical stimulation of the index finger that was 2, 4, and 15 times stronger than the sensory threshold (ST). We measured changes in latencies, including the onset, duration, and end of CSP, and waveform scores from 0 to 3. The correlation between the CSP score and unified PD rating score part III (UPDRS-III) also was assessed.ResultsThe onset latency and duration of CSP were significantly different between high- (15ST) and low-strength stimulations (2ST and 4ST). However, there were no significant latency changes (onset, duration, end of CSP) before and after receiving medication, or during the on and off state of the DBS. Anti-PD medications substantially increased the CSP waveform score only in the 4ST state. However, the waveform score significantly increased in all stimuli states during the DBS-on state. Both medication and the DBS-on state decreased the UPDRS-III. Nevertheless, there was no statistically significant correlation between the UPDRS-III and CSP waveform scores.ConclusionDifferent onset latencies and the duration of CSP between low- and high-strength stimuli support the hypotheses proposing two different reflex pathways. Despite being independent from the UPDRS-III, the CSP may be an electrophysiological indicator reflective of the changes in inhibitory activity to the spinal α-motoneuron in response to anti-PD medications and DBS.     

Metabolic and Nutritional Issues Associated with Spinal Muscular Atrophy

Spinal muscular atrophy (SMA), the main genetic cause of infant death, is a neurodegenerative disease characterized by the selective loss of motor neurons in the anterior horn of the spinal cord, accompanied by muscle wasting. Pathomechanically, SMA is caused by low levels of the survival motor neuron protein (SMN) resulting from the loss of the SMN1 gene. However, emerging research extends the pathogenic effect of SMN deficiency beyond motor neurons. A variety of metabolic abnormalities, especially altered fatty acid metabolism and impaired glucose tolerance, has been described in isolated cases of SMA; therefore, the impact of SMN deficiency in metabolic abnormalities has been speculated. Although the life expectancy of these patients has increased due to novel disease-modifying therapies and standardization of care, understanding of the involvement of metabolism and nutrition in SMA is still limited. Optimal nutrition support and metabolic monitoring are essential for patients with SMA, and a comprehensive nutritional assessment can guide personalized nutritional therapy for this vulnerable population. It has recently been suggested that metabolomics studies before and after the onset of SMA in patients can provide valuable information about the direct or indirect effects of SMN deficiency on metabolic abnormalities. Furthermore, identifying and quantifying the specific metabolites in SMA patients may serve as an authentic biomarker or therapeutic target for SMA. Here, we review the main epidemiological and mechanistic findings that link metabolic changes to SMA and further discuss the principles of metabolomics as a novel approach to seek biomarkers and therapeutic insights in SMA.     

The fate and function of oligodendrocyte progenitor cells after traumatic spinal cord injury

Oligodendrocyte progenitor cells (OPCs) are the most proliferative and dispersed population of progenitor cells in the adult central nervous system, which allows these cells to rapidly respond to damage. Oligodendrocytes and myelin are lost after traumatic spinal cord injury (SCI), compromising efficient conduction and, potentially, the long-term health of axons. In response, OPCs proliferate and then differentiate into new oligodendrocytes and Schwann cells to remyelinate axons. This culminates in highly efficient remyelination following experimental SCI in which nearly all intact demyelinated axons are remyelinated in rodent models. However, myelin regeneration comprises only one role of OPCs following SCI. OPCs contribute to scar formation after SCI and restrict the regeneration of injured axons. Moreover, OPCs alter their gene expression following demyelination, express cytokines and perpetuate the immune response. Here, we review the functional contribution of myelin regeneration and other recently uncovered roles of OPCs and their progeny to repair following SCI.     

Stage-specific regulation of oligodendrocyte development by Hedgehog signaling in the spinal cord

Elucidation of signaling pathways that control oligodendrocyte (OL) development is a prerequisite for developing novel strategies for myelin repair in neurological diseases. Despite the extensive work outlining the importance of Hedgehog (Hh) signaling in the commitment and generation of OL progenitor cells (OPCs), there are conflicting reports on the role of Hh signaling in regulating OL differentiation and maturation. In the present study, we systematically investigated OPC specification and differentiation in genetically modified mouse models of Smoothened (Smo), an essential component of the Hh signaling pathway in vertebrates. Through conditional gain-of-function strategy, we demonstrated that hyperactivation of Smo in neural progenitors induced transient ectopic OPC generation and precocious OL differentiation accompanied by the co-induction of Olig2 and Nkx2.2. After the commitment of OL lineage, Smo activity is not required for OL differentiation, and sustained expression of Smo in OPCs stimulated cell proliferation but inhibited terminal differentiation. These findings have uncovered the stage-specific regulation of OL development by Smo-mediated Hh signaling, providing novel insights into the molecular regulation of OL differentiation and myelin repair.     

Therapeutic effect of regulating autophagy in spinal cord injury: a network meta-analysis of direct and indirect comparisons

Objective:An increasing number of studies indicate that autophagy plays an important role in the pathogenesis of spinal cord injury,and that regulating autophagy can enhance recovery from spinal cord injury.However,the effect of regulating autophagy and whether autophagy is detrimental or beneficial after spinal cord injury remain unclear.Therefore,in this study we evaluated the effects of autophagy regulation on spinal cord injury in rats by direct and indirect comparison,in an effort to provide a basis for further research.Data source:Relevant literature published from inception to February 1,2018 were included by searching Wanfang,CNKI,Web of Science,MEDLINE(OvidSP),PubMed and Google Scholar in English and Chinese.The keywords included"autophagy","spinal cord injury",and"rat".Data selection:The literature included in vivo experimental studies on autophagy regulation in the treatment of spinal cord injury(including intervention pre-and post-spinal cord injury).Meta-analyses were conducted at different time points to compare the therapeutic effects of promoting or inhibiting autophagy,and subgroup analyses were also conducted.Outcome measure:Basso,Beattie,and Bresnahan scores.Results:Of the 622 studies,33 studies of median quality were included in the analyses.Basso,Beattie,and Bresnahan scores were higher at 1 day(MD=1.80,95%CI:0.81-2.79,P=0.0004),3 days(MD=0.92,95%CI:0.72-1.13,P<0.00001),1 week(MD=2.39,95%CI:1.85-2.92,P<0.00001),2 weeks(MD=3.26,95%CI:2.40-4.13,P<0.00001),3 weeks(MD=3.13,95%CI:2.51-3.75,P<0.00001)and 4 weeks(MD=3.18,95%CI:2.43-3.92,P<0.00001)after spinal cord injury with upregulation of autophagy compared with the control group(drug solvent control,such as saline group).Basso,Beattie,and Bresnahan scores were higher at 1 day(MD=6.48,95%CI:5.83-7.13,P<0.00001),2 weeks(MD=2.43,95%CI:0.79-4.07,P=0.004),3 weeks(MD=2.96,95%CI:0.09-5.84,P=0.04)and 4 weeks(MD=4.41,95%CI:1.08-7.75,P=0.01)after spinal cord injury with downregulation of autophagy compared with the control group.Indirect comparison of upregulation and downregulation of autophagy showed no differences in Basso,Beattie,and Bresnahan scores at 1 day(MD=-4.68,95%CI:-5.840 to-3.496,P=0.94644),3 days(MD=-0.28,95%CI:-2.231-1.671,P=0.99448),1 week(MD=1.83,95%CI:0.0076-3.584,P=0.94588),2 weeks(MD=0.81,95%CI:-0.850-2.470,P=0.93055),3 weeks(MD=0.17,95%Cl:-2.771-3.111,P=0.99546)or 4 weeks(MD=-1.23,95%Cl:-4.647-2.187,P=0.98264)compared with the control group.Conclusion:Regulation of autophagy improves neurological function,whether it is upregulated or downregulated.There was no difference between upregulation and downregulation of autophagy in the treatment of spinal cord injury.The variability in results among the studies may be associated with differences in research methods,the lack of clearly defined autophagy characteristics after spinal cord injury,and the limited autophagy monitoring techniques.Thus,methods should be standardized,and the dynamic regulation of autophagy should be examined in future studies.     

Evidence-Based Nursing Care for Spinal Nursing Immobilization: A Systematic Review

IntroductionA high degree of suspicion for spinal injury after trauma is commonplace in an emergency department, and spinal immobilization is considered an accepted intervention to prevent the progression of a potential injury. This systematic review was conducted to gain insight into the best research evidence related to nursing interventions for patients with trauma presenting with a suspected spinal injury.MethodsA systematic search of online databases was conducted in April 2019 for relevant research using specific search terms. The studies were selected on the basis of pre-established eligibility criteria, and the quality was appraised using the Critical Appraisal Skills Programme tool.ResultsNineteen included articles were synthesized thematically on the basis of the outcomes from interventions directed at a suspected spinal injury. The main findings were that spinal immobilization may compromise pulmonary function and airway management, cause pain and pressure ulcers, and be inappropriate with penetrating trauma. Furthermore, there was insufficient evidence to support the safety and efficacy of the hard neck collar and long backboard.DiscussionPatients would benefit from a more selective and cautious approach to spinal immobilization. Emergency nurses should use the evidence to facilitate informed decision-making in balancing the benefits of spinal immobilization against harm when considering the needs and values of the patient.