Dear Editor,Post-traumatic stress disorder(PTSD)is a major issue for military personnel,with prevalence rates between 1%and 35%in veterans^([1]),significantly higher than in the general population^([2]).Psychological ...Dear Editor,Post-traumatic stress disorder(PTSD)is a major issue for military personnel,with prevalence rates between 1%and 35%in veterans^([1]),significantly higher than in the general population^([2]).Psychological resources,particularly hope,can protect against PTSD and promote post-traumatic growth^([3]).Hope,conceptualized as both a trait and a state,contributes to well-being and resilience and is negatively associated with PTSD symptoms,representing a psychological factor while mitigating the impact of trauma by fostering resilience and adaptive coping mechanisms.展开更多
Traumatic brain injury(TBI)is the paradigmatic example of acute brain injury,defined as sudden and unexpected structural and/or functional damage to the brain.In western countries,TBI is a main cause of prolonged disa...Traumatic brain injury(TBI)is the paradigmatic example of acute brain injury,defined as sudden and unexpected structural and/or functional damage to the brain.In western countries,TBI is a main cause of prolonged disability,and it is even more impactful because it very often affects young people.Contrary to past belief,the cerebral damage caused by TBI is not limited to the short temporal phase following the mechanical insult.Indeed,moderate/severe TBI can trigger several mechanisms of neuronal damage that operate for months or years after the acute injury,potentially leading to neuronal loss and brain atrophy.展开更多
Motor neuron disease includes a heterogeneous group of relentless progressive neurological disorders defined and characterized by the degeneration of motor neurons.Amyotrophic lateral sclerosis is the most common and ...Motor neuron disease includes a heterogeneous group of relentless progressive neurological disorders defined and characterized by the degeneration of motor neurons.Amyotrophic lateral sclerosis is the most common and aggressive form of motor neuron disease with no effective treatment so far.Unfortunately,diagnostic and prognostic biomarkers are lacking in clinical practice.Neurofilaments are fundamental structural components of the axons and neurofilament light chain and phosphorylated neurofilament heavy chain can be measured in both cerebrospinal fluid and serum.Neurofilament light chain and phosphorylated neurofilament heavy chain levels are elevated in amyotrophic lateral sclerosis,reflecting the extensive damage of motor neurons and axons.Hence,neurofilaments are now increasingly recognized as the most promising candidate biomarker in amyotrophic lateral sclerosis.The potential usefulness of neurofilaments regards various aspects,including diagnosis,prognosis,patient stratification in clinical trials and evaluation of treatment response.In this review paper,we review the body of literature about neurofilaments measurement in amyotrophic lateral sclerosis.We also discuss the open issues concerning the use of neurofilaments clinical practice,as no overall guideline exists to date;finally,we address the most recent evidence and future perspectives.展开更多
Multiple system atrophy is a sporadic,progressive,adult-onset,neurodegenerative disorder characte rized by autonomic dysfunction symptoms,parkinsonian features,and cerebellar signs in va rious combinations.An early di...Multiple system atrophy is a sporadic,progressive,adult-onset,neurodegenerative disorder characte rized by autonomic dysfunction symptoms,parkinsonian features,and cerebellar signs in va rious combinations.An early diagnosis of multiple system atrophy is of utmost impo rtance for the proper prevention and management of its potentially fatal complications leading to the poor prognosis of these patients.The current diagnostic criteria incorporate several clinical red flags and magnetic resonance imaging marke rs supporting diagnosis of multiple system atrophy.Nonetheless,especially in the early disease stage,it can be challenging to differentiate multiple system atrophy from mimic disorders,in particular Parkinson’s disease.Electromyography of the external anal sphincter represents a useful neurophysiological tool for diffe rential diagnosis since it can provide indirect evidence of Onuf’s nucleus degeneration,which is a pathological hallmark of multiple system atrophy.However,the diagnostic value of external anal sphincter electromyography has been a matter of debate for three decades due to controve rsial reports in the literature.In this review,after a brief ove rview of the electrophysiological methodology,we first aimed to critically analyze the available knowledge on the diagnostic role of external anal sphincter electromyography.We discussed the conflicting evidence on the clinical correlations of neurogenic abnormalities found at external anal sphincter electro myography.Finally,we repo rted recent prognostic findings of a novel classification of electromyography patterns of the external anal sphincter that could pave the way toward the implementation of this neurophysiological technique for survival prediction in patients with multiple system atrophy.展开更多
AIM： To evaluate the myoelectric manifestations of peripheral fatigability in patients with primary biliary cirrhosis in comparison to healthy subjects. METHODS： Sixteen women with primary biliary cirrhosis without ...AIM： To evaluate the myoelectric manifestations of peripheral fatigability in patients with primary biliary cirrhosis in comparison to healthy subjects. METHODS： Sixteen women with primary biliary cirrhosis without comorbidity and 13 healthy women matched for age and body mass index （BMI） completed the selfreported questionnaire fatigue impact scale. All subjects underwent surface electromyography assessment of peripheral fatigability. Anterior tibial muscle isometric voluntary contraction was executed for 20 s at 80% of maximal voluntary isometric contraction. During the exercise electromyographic signal series were recorded and root mean square （expression of central drive） as well as mean and median of electromyographic signal frequency spectrum （estimates of muscle fatigability） were com- puted. Each subject executed the trial two times. EMG parameters were normalized, then linear regression was applied and slopes were calculated. RESULTS： Seven patients were fatigued （median fatigue impact scale score： 38, range： 26-66） and 9 were not fatigued （median fatigue impact scale score： 7, range： 0-17）. The maximal voluntary isometric contraction was similar in patients （82, 54-115 N） and controls （87, 74-101 N）, and in patients with high （81, 54-115 N） and low fatigue impact scale scores （86, 65-106 N）. Root mean square as well as mean and median of frequency spectrum slopes were compared with the Mann-Whitney U test, and no significant difference was found between fatigued and non-fatigued patients and controls. CONCLUSION： No instrumental evidence of peripheral fatigability can be found in women with primary biliary cirrhosis but no comorbidity, suggesting that fatigue in such patients may be of central origin.展开更多
We have read with interest the Letter to the Editor by Drs.Zhuang and Zhong,who presented the clinical data of 68 patients with Wilson’s disease(WD)who were admitted to the hospital before and during the coronavirus ...We have read with interest the Letter to the Editor by Drs.Zhuang and Zhong,who presented the clinical data of 68 patients with Wilson’s disease(WD)who were admitted to the hospital before and during the coronavirus disease 2019(COVID-19)pandemic,and appreciated their findings on hepatic and some extrahepatic manifestations.Nevertheless,given the strong impact of the pandemic on patients with neurological and psychiatric disorders,we would have expected a worsening of the psychiatric and/or neurological impairments in these patients.In contrast,according to the authors,these manifestations remained,somewhat unexpectedly,unchanged.This finding is in contrast with most of the current literature that highlights not only an increased incidence of mental health disorders in the general population but also an exacerbation of neurological and psychiatric symptoms in patients with chronic diseases,especially in those with pre-existing neuropsychiatric disorders,such as WD.Although the study was mainly focused on the hepatic features of WD patients taking anti-copper treatment,a generic and cumulative definition of neurological and psychiatric manifestations,as in this study,does not allow for further considerations.Future studies during and after the pandemic are necessary to clarify the real impact,either direct or indirect,of the COVID-19 pandemic on the neurological and psychiatric symptoms of WD patients.展开更多
We have read with interest the publication that describes the available data related to the use of neuromodulation strategies for the treatment of posttraumatic stress disorder(PTSD).Despite treatment advances,however...We have read with interest the publication that describes the available data related to the use of neuromodulation strategies for the treatment of posttraumatic stress disorder(PTSD).Despite treatment advances,however,a substantial proportion of PTSD patients receiving psychological and/or pharmacological treatment do not reach an adequate clinical response.In their paper,the authors draw attention to the current understanding of the use of repetitive transcranial magnetic stimulation(rTMS)as a potential treatment for PTSD.Most of the previous studies indeed applied both inhibitory(1 Hz)and excitatory(>1 Hz,up to 20 Hz)rTMS to the right and/or left dorsolateral prefrontal cortex.Despite larger therapeutic effects observed when high-frequency stimulation was applied,the question of which side and frequency of stimulation is the most successful is still debated.The authors also reported on the after-effect of rTMS related to neuroplasticity and identified the intermittent theta burst stimulation as a technique of particular interest because of it showed the most effective improvement on PTSD symptoms.However,although numerous studies have highlighted the possible beneficial use of rTMS protocols for PTSD,the exact mechanism of action remains unclear.In their conclusions,the authors stated that rTMS has been demonstrated to be effective for the treatment of PTSD symptoms.Nevertheless,we believe that further research with homogeneous samples,standardized protocols,and objective outcome measures is needed to identify specific therapeutic targets and to better define significant changes when active and sham stimulation procedures are compared.展开更多
Objective: To investigate the source of an unusual and previously unreported v olume conducted potential on motor nerve conduction studies. In a case of subacu te ulnar neuropathy at wrist (UNW) selectively involving ...Objective: To investigate the source of an unusual and previously unreported v olume conducted potential on motor nerve conduction studies. In a case of subacu te ulnar neuropathy at wrist (UNW) selectively involving the deep motor branch, we recorded from the hypothenar eminence a large positive wave(2.5 ms-2 mV) pre ceding the negative takeoff of the delayed distal ulnar motor response. Methods: We performed multiple channels motor and sensory ulnar nerve (UN) conduction st udies; these included selective electrical stimulation and anaesthetic block of UN branches and also selective recording of motor responses by single fibre need les; data were confirmedby an intraoperative neurophysiological study and correl ated with MRI and surgical findings. Results: Detailed neurophysiological invest igation demonstrated the generation of this waveform from the palmaris brevis (P B) muscle. MRI and surgical exploration documented a hypertrophy of this muscle. Conclusions: In type II°UNW, depolarization of a spared palmaris brevis muscle may be recorded as a positive wave preceding the delayed abductor digiti minimi motor response.Significance: We underline the peculiar localizing value of this volume conducted ’meaningful artefact’in that particular setting. It actually represented an early neurographic analogue of what is known as the clinical ‘P almaris Brevis Sign’in long standing type II°UNW.展开更多
Among multiple sclerosis(MS)susceptibility genes,the strongest non-human leukocyte antigen(HLA)signal in the Italian population maps to the TNFSF14 gene encoding LIGHT,a glycoprotein involved in dendritic cell(DC)matu...Among multiple sclerosis(MS)susceptibility genes,the strongest non-human leukocyte antigen(HLA)signal in the Italian population maps to the TNFSF14 gene encoding LIGHT,a glycoprotein involved in dendritic cell(DC)maturation.Through fine-mapping in a large Italian dataset(4,198 patients with MS and3,903 controls),we show that the TNFSF14 intronic SNP rs1077667 is the primarily MS-associated variant in the region.Expression quantitative trait locus(e QTL)analysis indicates that the MS risk allele is significantly associated with reduced TNFSF14 messenger RNA levels in blood cells,which is consistent with the allelic imbalance in RNA-Seq reads(P<0.0001).The MS risk allele is associated with reduced levels of TNFSF14 gene expression(P<0.01)in blood cells from 84 Italian patients with MS and 80 healthy controls(HCs).Interestingly,patients with MS are lower expressors of TNFSF14 compared to HC(P<0.007).Individuals homozygous for the MS risk allele display an increased percentage of LIGHT-positive peripheral blood myeloid DCs(CD11 c+,P=0.035)in 37 HCs,as well as in in vitro monocyte-derived DCs from 22 HCs(P=0.04).Our findings suggest that the intronic variant rs1077667 alters the expression of TNFSF14 in immune cells,which may play a role in MS pathogenesis.展开更多
Recently Zhang et al.(2024) published their study entitled “Lentivirus-modified hematopoietic stem cell gene therapy for advanced symptomatic juvenile metachromatic leukodystrophy: A long-term follow-up pilot study....Recently Zhang et al.(2024) published their study entitled “Lentivirus-modified hematopoietic stem cell gene therapy for advanced symptomatic juvenile metachromatic leukodystrophy: A long-term follow-up pilot study.” The authors present three metachromatic leukodystrophy(MLD) patients treated with gene therapy and claim stabilization or even improvement, despite advanced symptomatic disease stage. The metachromatic leukodystrophy initiative(MLDi)(Schoenmakers et al., 2022), an international collaborative network and registry for MLD, urges caution in interpreting these results, as the evidence raises several critical concerns. These claims risk fostering false hope among MLD patients and their families, particularly given the significant gaps in the data provided(Fig. 1).展开更多
Peripheral nerve injuries are a heterogeneous group of lesions that may occurs secondary to various causes.Several different classifications have been used to describe the pathophysiological mechanisms leading to the ...Peripheral nerve injuries are a heterogeneous group of lesions that may occurs secondary to various causes.Several different classifications have been used to describe the pathophysiological mechanisms leading to the clinical deficit,from simple and reversible compression-induced demyelination,to complete transection of nerve axons.Neurophysiological data localize,quantify,and qualify(demyelination vs.axonal loss)the clinical and subclinical deficits.High-resolution ultrasound can demonstrate the morphological extent of nerve damage,fascicular echotexture(epineurium vs.perineurium,focal alteration of the cross-section of the nerve,any neuromas,etc.),and the surrounding tissues.High field magnetic resonance imaging provides high contrast neurography by fat suppression sequences and shows structural connectivity through the use of diffusion-weighted sequences.The aim of this review is to provide clinical guidelines for the diagnosis of nerve injuries,and the rationale for instrumental evaluation in the preoperative and postoperative periods.While history and clinical approach guide neurophysiological examination,nerve conduction and electromyography studies provide functional information on conduction slowing and denervation to assist in monitoring the onset of re-innervation.High-resolution nerve imaging complements neurophysiological data and allows direct visualization of the nerve injury while providing insight into its cause and facilitating surgical treatment planning.Indications and limits of each instrumental examination are discussed.展开更多
Severe Acute Respiratory Syndrome Coronavirus(SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components.Dendritic cells(DCs)play a key role in the defense against viral infections,...Severe Acute Respiratory Syndrome Coronavirus(SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components.Dendritic cells(DCs)play a key role in the defense against viral infections,for instance plasmacytoid DCs(pDCs),have the capacity to produce vast amounts of interferon-alpha(IFN-α).In COVID-19 there is a deficit in DC numbers and IFN-αproduction,which has been associated with disease severity.In this work,we described that in addition to the DC deficiency,several DC activation and homing markers were altered in acute COVID-19 patients,which were associated with multiple inflammatory markers.Remarkably,previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+myeloid DCs and pDCs seven months after SARS-CoV-2 infection.Moreover,the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients,while no restoration of integrinβ7 and indoleamine 2,3-dyoxigenase(IDO)levels were observed.These findings contribute to a better understanding of the immunological sequelae of COVID-19.展开更多
基金supported by the Institut de Recherche Biomédicale des Armées(Brétigny-sur-Orge,France).
文摘Dear Editor,Post-traumatic stress disorder(PTSD)is a major issue for military personnel,with prevalence rates between 1%and 35%in veterans^([1]),significantly higher than in the general population^([2]).Psychological resources,particularly hope,can protect against PTSD and promote post-traumatic growth^([3]).Hope,conceptualized as both a trait and a state,contributes to well-being and resilience and is negatively associated with PTSD symptoms,representing a psychological factor while mitigating the impact of trauma by fostering resilience and adaptive coping mechanisms.
文摘Traumatic brain injury(TBI)is the paradigmatic example of acute brain injury,defined as sudden and unexpected structural and/or functional damage to the brain.In western countries,TBI is a main cause of prolonged disability,and it is even more impactful because it very often affects young people.Contrary to past belief,the cerebral damage caused by TBI is not limited to the short temporal phase following the mechanical insult.Indeed,moderate/severe TBI can trigger several mechanisms of neuronal damage that operate for months or years after the acute injury,potentially leading to neuronal loss and brain atrophy.
文摘Motor neuron disease includes a heterogeneous group of relentless progressive neurological disorders defined and characterized by the degeneration of motor neurons.Amyotrophic lateral sclerosis is the most common and aggressive form of motor neuron disease with no effective treatment so far.Unfortunately,diagnostic and prognostic biomarkers are lacking in clinical practice.Neurofilaments are fundamental structural components of the axons and neurofilament light chain and phosphorylated neurofilament heavy chain can be measured in both cerebrospinal fluid and serum.Neurofilament light chain and phosphorylated neurofilament heavy chain levels are elevated in amyotrophic lateral sclerosis,reflecting the extensive damage of motor neurons and axons.Hence,neurofilaments are now increasingly recognized as the most promising candidate biomarker in amyotrophic lateral sclerosis.The potential usefulness of neurofilaments regards various aspects,including diagnosis,prognosis,patient stratification in clinical trials and evaluation of treatment response.In this review paper,we review the body of literature about neurofilaments measurement in amyotrophic lateral sclerosis.We also discuss the open issues concerning the use of neurofilaments clinical practice,as no overall guideline exists to date;finally,we address the most recent evidence and future perspectives.
基金supported by the Italian Ministry of Health (’Ricerca Corrente’2020-2021)(to MT)。
文摘Multiple system atrophy is a sporadic,progressive,adult-onset,neurodegenerative disorder characte rized by autonomic dysfunction symptoms,parkinsonian features,and cerebellar signs in va rious combinations.An early diagnosis of multiple system atrophy is of utmost impo rtance for the proper prevention and management of its potentially fatal complications leading to the poor prognosis of these patients.The current diagnostic criteria incorporate several clinical red flags and magnetic resonance imaging marke rs supporting diagnosis of multiple system atrophy.Nonetheless,especially in the early disease stage,it can be challenging to differentiate multiple system atrophy from mimic disorders,in particular Parkinson’s disease.Electromyography of the external anal sphincter represents a useful neurophysiological tool for diffe rential diagnosis since it can provide indirect evidence of Onuf’s nucleus degeneration,which is a pathological hallmark of multiple system atrophy.However,the diagnostic value of external anal sphincter electromyography has been a matter of debate for three decades due to controve rsial reports in the literature.In this review,after a brief ove rview of the electrophysiological methodology,we first aimed to critically analyze the available knowledge on the diagnostic role of external anal sphincter electromyography.We discussed the conflicting evidence on the clinical correlations of neurogenic abnormalities found at external anal sphincter electro myography.Finally,we repo rted recent prognostic findings of a novel classification of electromyography patterns of the external anal sphincter that could pave the way toward the implementation of this neurophysiological technique for survival prediction in patients with multiple system atrophy.
文摘AIM： To evaluate the myoelectric manifestations of peripheral fatigability in patients with primary biliary cirrhosis in comparison to healthy subjects. METHODS： Sixteen women with primary biliary cirrhosis without comorbidity and 13 healthy women matched for age and body mass index （BMI） completed the selfreported questionnaire fatigue impact scale. All subjects underwent surface electromyography assessment of peripheral fatigability. Anterior tibial muscle isometric voluntary contraction was executed for 20 s at 80% of maximal voluntary isometric contraction. During the exercise electromyographic signal series were recorded and root mean square （expression of central drive） as well as mean and median of electromyographic signal frequency spectrum （estimates of muscle fatigability） were com- puted. Each subject executed the trial two times. EMG parameters were normalized, then linear regression was applied and slopes were calculated. RESULTS： Seven patients were fatigued （median fatigue impact scale score： 38, range： 26-66） and 9 were not fatigued （median fatigue impact scale score： 7, range： 0-17）. The maximal voluntary isometric contraction was similar in patients （82, 54-115 N） and controls （87, 74-101 N）, and in patients with high （81, 54-115 N） and low fatigue impact scale scores （86, 65-106 N）. Root mean square as well as mean and median of frequency spectrum slopes were compared with the Mann-Whitney U test, and no significant difference was found between fatigued and non-fatigued patients and controls. CONCLUSION： No instrumental evidence of peripheral fatigability can be found in women with primary biliary cirrhosis but no comorbidity, suggesting that fatigue in such patients may be of central origin.
文摘We have read with interest the Letter to the Editor by Drs.Zhuang and Zhong,who presented the clinical data of 68 patients with Wilson’s disease(WD)who were admitted to the hospital before and during the coronavirus disease 2019(COVID-19)pandemic,and appreciated their findings on hepatic and some extrahepatic manifestations.Nevertheless,given the strong impact of the pandemic on patients with neurological and psychiatric disorders,we would have expected a worsening of the psychiatric and/or neurological impairments in these patients.In contrast,according to the authors,these manifestations remained,somewhat unexpectedly,unchanged.This finding is in contrast with most of the current literature that highlights not only an increased incidence of mental health disorders in the general population but also an exacerbation of neurological and psychiatric symptoms in patients with chronic diseases,especially in those with pre-existing neuropsychiatric disorders,such as WD.Although the study was mainly focused on the hepatic features of WD patients taking anti-copper treatment,a generic and cumulative definition of neurological and psychiatric manifestations,as in this study,does not allow for further considerations.Future studies during and after the pandemic are necessary to clarify the real impact,either direct or indirect,of the COVID-19 pandemic on the neurological and psychiatric symptoms of WD patients.
文摘We have read with interest the publication that describes the available data related to the use of neuromodulation strategies for the treatment of posttraumatic stress disorder(PTSD).Despite treatment advances,however,a substantial proportion of PTSD patients receiving psychological and/or pharmacological treatment do not reach an adequate clinical response.In their paper,the authors draw attention to the current understanding of the use of repetitive transcranial magnetic stimulation(rTMS)as a potential treatment for PTSD.Most of the previous studies indeed applied both inhibitory(1 Hz)and excitatory(>1 Hz,up to 20 Hz)rTMS to the right and/or left dorsolateral prefrontal cortex.Despite larger therapeutic effects observed when high-frequency stimulation was applied,the question of which side and frequency of stimulation is the most successful is still debated.The authors also reported on the after-effect of rTMS related to neuroplasticity and identified the intermittent theta burst stimulation as a technique of particular interest because of it showed the most effective improvement on PTSD symptoms.However,although numerous studies have highlighted the possible beneficial use of rTMS protocols for PTSD,the exact mechanism of action remains unclear.In their conclusions,the authors stated that rTMS has been demonstrated to be effective for the treatment of PTSD symptoms.Nevertheless,we believe that further research with homogeneous samples,standardized protocols,and objective outcome measures is needed to identify specific therapeutic targets and to better define significant changes when active and sham stimulation procedures are compared.
文摘Objective: To investigate the source of an unusual and previously unreported v olume conducted potential on motor nerve conduction studies. In a case of subacu te ulnar neuropathy at wrist (UNW) selectively involving the deep motor branch, we recorded from the hypothenar eminence a large positive wave(2.5 ms-2 mV) pre ceding the negative takeoff of the delayed distal ulnar motor response. Methods: We performed multiple channels motor and sensory ulnar nerve (UN) conduction st udies; these included selective electrical stimulation and anaesthetic block of UN branches and also selective recording of motor responses by single fibre need les; data were confirmedby an intraoperative neurophysiological study and correl ated with MRI and surgical findings. Results: Detailed neurophysiological invest igation demonstrated the generation of this waveform from the palmaris brevis (P B) muscle. MRI and surgical exploration documented a hypertrophy of this muscle. Conclusions: In type II°UNW, depolarization of a spared palmaris brevis muscle may be recorded as a positive wave preceding the delayed abductor digiti minimi motor response.Significance: We underline the peculiar localizing value of this volume conducted ’meaningful artefact’in that particular setting. It actually represented an early neurographic analogue of what is known as the clinical ‘P almaris Brevis Sign’in long standing type II°UNW.
基金supported by the Italian Foundation of Multiple Sclerosis(FISM,2011/R/142015/R/10,2019/R-Multi/033)by the Italian Ministry of Health(RF-2016-02361294)the AGING Project for Department of Excellence at the Department of Translational Medicine(DIMET),Universitàdel Piemonte Orientale,Novara,Italy+1 种基金supported by Consorzio Interuniversitario di Biotecnologie(CIB)partially supported by Multiple MS project(Horizon 2020 European Grant 733161),Stockholm。
文摘Among multiple sclerosis(MS)susceptibility genes,the strongest non-human leukocyte antigen(HLA)signal in the Italian population maps to the TNFSF14 gene encoding LIGHT,a glycoprotein involved in dendritic cell(DC)maturation.Through fine-mapping in a large Italian dataset(4,198 patients with MS and3,903 controls),we show that the TNFSF14 intronic SNP rs1077667 is the primarily MS-associated variant in the region.Expression quantitative trait locus(e QTL)analysis indicates that the MS risk allele is significantly associated with reduced TNFSF14 messenger RNA levels in blood cells,which is consistent with the allelic imbalance in RNA-Seq reads(P<0.0001).The MS risk allele is associated with reduced levels of TNFSF14 gene expression(P<0.01)in blood cells from 84 Italian patients with MS and 80 healthy controls(HCs).Interestingly,patients with MS are lower expressors of TNFSF14 compared to HC(P<0.007).Individuals homozygous for the MS risk allele display an increased percentage of LIGHT-positive peripheral blood myeloid DCs(CD11 c+,P=0.035)in 37 HCs,as well as in in vitro monocyte-derived DCs from 22 HCs(P=0.04).Our findings suggest that the intronic variant rs1077667 alters the expression of TNFSF14 in immune cells,which may play a role in MS pathogenesis.
文摘Recently Zhang et al.(2024) published their study entitled “Lentivirus-modified hematopoietic stem cell gene therapy for advanced symptomatic juvenile metachromatic leukodystrophy: A long-term follow-up pilot study.” The authors present three metachromatic leukodystrophy(MLD) patients treated with gene therapy and claim stabilization or even improvement, despite advanced symptomatic disease stage. The metachromatic leukodystrophy initiative(MLDi)(Schoenmakers et al., 2022), an international collaborative network and registry for MLD, urges caution in interpreting these results, as the evidence raises several critical concerns. These claims risk fostering false hope among MLD patients and their families, particularly given the significant gaps in the data provided(Fig. 1).
文摘Peripheral nerve injuries are a heterogeneous group of lesions that may occurs secondary to various causes.Several different classifications have been used to describe the pathophysiological mechanisms leading to the clinical deficit,from simple and reversible compression-induced demyelination,to complete transection of nerve axons.Neurophysiological data localize,quantify,and qualify(demyelination vs.axonal loss)the clinical and subclinical deficits.High-resolution ultrasound can demonstrate the morphological extent of nerve damage,fascicular echotexture(epineurium vs.perineurium,focal alteration of the cross-section of the nerve,any neuromas,etc.),and the surrounding tissues.High field magnetic resonance imaging provides high contrast neurography by fat suppression sequences and shows structural connectivity through the use of diffusion-weighted sequences.The aim of this review is to provide clinical guidelines for the diagnosis of nerve injuries,and the rationale for instrumental evaluation in the preoperative and postoperative periods.While history and clinical approach guide neurophysiological examination,nerve conduction and electromyography studies provide functional information on conduction slowing and denervation to assist in monitoring the onset of re-innervation.High-resolution nerve imaging complements neurophysiological data and allows direct visualization of the nerve injury while providing insight into its cause and facilitating surgical treatment planning.Indications and limits of each instrumental examination are discussed.
基金This work was supported by Consejeria de Transformacion Economica,Industria,Conocimiento y Universidades Junta de Andalucia(research Project CV20-85418)Consejeria de salud Junta de Andalucia(Research Contract RH-0037-2020 to JV)the Instituto de Salud Carlos III(CP19/00159 to AGV,FI17/00186 to MRJL,FI19/00083 to MCGC,CM20/00243 to APG,and COV20/00698 to support COHVID-GS)+2 种基金the Red Temática de Investigación Cooperativa en SIDA(RD16/0025/0020 and RD16/0025/0026)which is included in the Acción Estratégica en Salud,Plan Nacional de Investigación Científica,Desarrollo e Innovación Tecnológica,2008 to 2011 and 2013 to 2016,Instituto de Salud Carlos III,Fondos FEDERERM was supported by the Spanish Research Council(CSIC).
文摘Severe Acute Respiratory Syndrome Coronavirus(SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components.Dendritic cells(DCs)play a key role in the defense against viral infections,for instance plasmacytoid DCs(pDCs),have the capacity to produce vast amounts of interferon-alpha(IFN-α).In COVID-19 there is a deficit in DC numbers and IFN-αproduction,which has been associated with disease severity.In this work,we described that in addition to the DC deficiency,several DC activation and homing markers were altered in acute COVID-19 patients,which were associated with multiple inflammatory markers.Remarkably,previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+myeloid DCs and pDCs seven months after SARS-CoV-2 infection.Moreover,the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients,while no restoration of integrinβ7 and indoleamine 2,3-dyoxigenase(IDO)levels were observed.These findings contribute to a better understanding of the immunological sequelae of COVID-19.
