Impairment Of Peripheral Nervous System Research Articles

Infrequent patterns in cerebrospinal fluid isofocusing test: Clinical significance and contribution of IgG index and Reiber diagram to their interpretation

Cerebrospinal fluid (CSF) isoelectrofocusing (IEF) is considered as the gold standard for detecting an intrathecal synthesis of IgG, which is a hallmark of multiple sclerosis (MS). This corresponds to the presence of CSF-restricted IgG oligoclonal bands (OCB) (typically type 2 pattern). Moreover, this technique can also detect a systemic immune reaction with passive transfer of IgG (type 3 and 4 patterns) for which the clinical relevance is less understood. The aim of our study was to determine the frequency and disease associations of IEF type 3 and 4 patterns and to investigate the potential usefulness of including quantitative data (IgG index and Reiber Diagram) in interpreting such IEF profiles.Among 544 patients who underwent CSF IEF (Hydragel CSF isofocusing kit, Sebia®, France) in our Laboratory during a six-year-period, those who presented type 3 or 4 patterns were selected. Clinical data and results of other immunological tests were analyzed for 27 patients followed in the Neurological Department.Frequencies of type 3 and type 4 patterns were relatively low (2.3 % and 3.4 % respectively). Among patients with type 3 pattern included in our study (n = 10), 5 were diagnosed with MS. For the 5 other patients, the diagnosis was a clinically isolated syndrome (CIS) (2 cases), a probable auto-immune encephalitis (2 cases) and a possible genetic neurodegenerative disease (1 case). MS patients had an IgG index >0.7 and fell into area 4 of Reiber diagram while non-MS patients had an IgG index <0.7 and fell into area 1, except the last case. Regarding type 4 pattern (n = 17), the diagnoses were as follows: MS (3), CIS (4), Neuromyelitis optica spectrum disorders with positive anti-AQP4 antibodies (3) and anti-NMDAR autoimmune encephalitis (1). The remaining cases had central nervous system impairment related to vascular, metabolic or tumoral etiologies (3) or peripheral nervous system impairment (3). In this group (type 4 pattern), IgG index was <0.7 in 15/17 cases. Interpretation using Reiber diagram showed an abnormal blood-brain barrier for 8/17 patients.Type 3 and 4 IEF patterns are infrequently observed in routine neurology practice. It is important for the diagnostic laboratory professional as well as for the neurologist to understand their clinical relevance. Our findings highlight the contribution of quantitative evaluation of CSF (IgG index, Reiber diagram) for the interpretation of such situations. Despite the small size of our study population, our results emphasize the importance of reporting the exact type of IEF pattern and not only the positivity or not of OCB.

Cardiac remodeling, amyloidosis, neurotrophic signaling and innervation impairment in the Tg2576 model of Alzheimer’s disease

AbstractBackgroundIn Alzheimer’s disease (AD), the characteristic cerebral amyloid β (Aβ) accumulation and tau pathology, are accompanied by a gradual loss of the two main neuromodulators, NGF and BDNF. This AD‐mediated derangement of the brain’s neuro‐signaling pathways may extend to the periphery and, along with potential peripheral amyloid deposition, induce peripheral nervous system impairment, thus affecting other organs, including the heart. However, whether and how AD pathology affects cardiac physiology, neurotrophins, innervation, and heart amyloidosis is still undefined.MethodHere, we describe for the first‐time that cardiac remodeling and neuro‐signaling dysregulation are present in the hearts of Tg2576 mice, a widely used model of AD and cerebral amyloidosis.ResultsEchocardiographic analysis showed significant deterioration of left ventricle function, as demonstrated by a decline of both ejection fraction and fraction shortening in 12‐month‐old Tg2576 mice compared to age‐matched WT littermates. The transgenic mice hearts presented an increase in interstitial fibrosis, with an accumulation of amyloid aggregates, including Aβ, associated with severe cardiac nervous system dysfunction. Tg2576 mice exhibited a depletion in cardiac nerve fiber density, both adrenergic (stained with tyrosine hydroxylase‐ TH) and regenerating nerve terminals (labeled with GAP‐43) compared to the WT mice. This myocardial denervation was accompanied by a decline in NGF and BDNF protein expression as well as GAP‐43 expression in both the brain and heart of Tg2576 mice. Likewise, both human neuroblastoma cells (SH‐SY5Y) and human cardiomyocytes (AC16) challenged with human Aβ‐40 or Aβ‐42 oligomers showed significant downregulation of both BDNF and GAP‐43 activity.ConclusionOverall, this study highlights the deleterious impact of cerebral amyloidosis on the cardiac nervous system and heart physiology, providing potential therapeutic targets, such as neurotrophic factors, to prevent or limit the AD‐mediated degenerative mechanisms on the cardiovascular system.

Antibody Deficiency in Patients with Biallelic KARS1 Mutations.

Biallelic KARS1 mutations cause KARS-related diseases, a rare syndromic condition encompassing central and peripheral nervous system impairment, heart and liver disease, and deafness. KARS1 encodes the t-RNA synthase of lysine, an aminoacyl-tRNA synthetase, involved in different physiological mechanisms (such as angiogenesis, post-translational modifications, translation initiation, autophagy and mitochondrial function). Although patients with immune-hematological abnormalities have been individually described, results have not been collectively discussed and functional studies investigating how KARS1 mutations affect B cells have not been performed.Here, we describe one patient with severe developmental delay, sensoneurinal deafness, acute disseminated encephalomyelitis, hypogammaglobulinemia and recurrent infections. Pathogenic biallelic KARS1 variants (Phe291Val/ Pro499Leu) were associated with impaired B cell metabolism (decreased mitochondrial numbers and activity). All published cases of KARS-related diseases were identified. The corresponding authors and researchers involved in the diagnosis of inborn errors of immunity or genetic syndromes were contacted to obtain up-to-date clinical and immunological information. Seventeen patients with KARS-related diseases were identified. Recurrent/severe infections (9/17) and B cell abnormalities (either B cell lymphopenia [3/9], hypogammaglobulinemia [either IgG, IgA or IgM; 6/15] or impaired vaccine responses [4/7]) were frequently reported. Immunoglobulin replacement therapy was given in five patients. Full immunological assessment is warranted in these patients, who may require detailed investigation and specific supportive treatment.

Abstract P2013: Cardiac Remodeling, Amyloidosis, Neurotrophic Signaling, And Innervation Impairment In The Tg2576 Model Of Alzheimer's Disease

Background: In Alzheimer's disease (AD), the characteristic cerebral amyloid β (Aβ) deposition and tau pathology are accompanied by a progressive loss of the two main neuromodulators, NGF and BDNF. This AD-mediated derangement of the brain's neuro-signaling pathway may extend to the periphery and, along with potential peripheral amyloid deposition, induce peripheral nervous system impairment, thus affecting other organs, including the heart. However, whether and how AD pathology affects cardiac physiology, neurotrophins, innervation, and heart amyloidosis is still unclear. Method: Here, we describe for the first time that cardiac remodeling and neuro-signaling dysregulation are present in the hearts of Tg2576 mice, a widely used model of AD and cerebral amyloidosis. Results: Echocardiographic analysis showed significant deterioration of left ventricle function, as demonstrated by a decline of both ejection fraction and fraction shortening in 12-month-old Tg2576 mice compared to age-matched WT littermates. The transgenic mice hearts displayed an increase in interstitial fibrosis, with an accumulation of amyloid aggregates, including Aβ, associated with severe cardiac nervous system dysfunction. Tg2576 mice exhibited a depletion in cardiac nerve fiber density, both adrenergic (stained with tyrosine hydroxylase- TH) and regenerating nerve terminals (labeled with GAP-43), compared to the WT mice. This myocardial denervation was accompanied by a decline in NGF and BDNF protein expression as well as GAP-43 expression in both the brain and heart of Tg2576 mice. Likewise, human neuroblastoma cells (SH-SY5Y) and human cardiomyocytes (AC16) challenged with human Aβ-40 or, Aβ-42 oligomers showed significant downregulation of both BDNF and GAP-43 activity. Conclusion: Overall, this study highlights the harmful impact of cerebral amyloidosis on the cardiac nervous system and heart physiology, providing potential therapeutic targets, such as neurotrophic factors, to prevent or limit AD-mediated degenerative mechanisms in the cardiovascular system.

Potential mechanism of SARS-CoV-2-associated central and peripheral nervous system impairment.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is more than merely a respiratory disease, as it also presents with various neurological symptoms. SARS‐CoV‐2 may infect the central nervous system (CNS) and thus is neurotropic. However, the pathophysiological mechanism of coronavirus disease 2019 (COVID‐19)‐associated neuropathy remains unclear. Many studies have reported that SARS‐CoV‐2 enters the CNS through the hematogenous and neuronal routes, as well as through the main host neurological immune responses and cells involved in these responses. The neurological immune responses to COVID‐19 and potential mechanisms of the extensive neuroinflammation induced by SARS‐CoV‐2 have been investigated. Although CNS infection with SARS‐CoV‐2 was shown to lead to neuronal impairment, certain aspects of this mechanism remain controversial and require further analysis. In this review, we discussed the pathway and mechanisms of SARS‐CoV‐2 invasion in the CNS, and associated clinical manifestations, such as anosmia, headache, and hyposmia. Moreover, the mechanism of neurological damage caused by SARS‐CoV‐2 may provide potential treatment methods for patients presenting with SARS‐CoV‐2‐associated neuropathy.

Neurofilament light chain as adisease severity biomarker in ATTRv: data from a single-centre experience.

Hereditary transthyretin amyloidosis (ATTRv) is a treatable multisystem disorder with prevalent peripheral nervous system impairment. Besides neurophysiological measures, there are few markers to monitor disease progression. Neurofilament light chain (NfL) has recently been considered a sensitive biomarker for neuroaxonal damage in this setting. To evaluate NfL levels in a cohort of ATTRv patients and pre-symptomatic carriers and correlate the serum concentrations with other markers of disease severity. We analysed NfL serum from 17 ATTRv patients or carriers and 26 controls. An exhaustive clinical and instrumental evaluation was performed in all patients. NfL levels were significantly higher in ATTRv cases when compared with controls. A significant correlation was found between NfL values and NIS scale, Sudoscan values from feet, interventricular septum thickness, and Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) questionnaire. We confirm that NfL is a reliable and promising biomarker to evaluate the ATTRv severity and monitor its progression.

Muscle MRI as a Useful Biomarker in Hereditary Transthyretin Amyloidosis: A Pilot Study

Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a severe and heterogeneous multisystem condition with a prevalent peripheral nervous system impairment, due to mutations in the transthyretin gene. Considering the introduction of different disease-modifying therapies in the last few years, a need of reliable biomarkers is emerging. In this study, we evaluated muscle MRI in a cohort of ATTRv patients in order to establish if the severity of muscle involvement correlated with disease severity. Linear regression analysis showed a significant positive correlation between the total fatty infiltration score and NIS, NIS-LL, and Norfolk, and an inverse correlation with Sudoscan registered from feet. In conclusion, we demonstrated the role of muscle MRI in ATTRv as possible disease biomarker, both for diagnostic purposes and for assessing the severity of the disease.

A Phase II Study of the Efficacy and Tolerance of Azacytidine (AZA) in Steroid Dependent/Refractory Systemic Autoimmune and Inflammatory Disorders (SAID) Associated with MDS or CMML (GFM- AZA-SAID -trial)

Background: Systemic autoimmune and inflammatory diseases (SAIDs) occur in 10-15% of MDS or CMML patients. They are often severe, difficult to treat and steroid resistant/dependent disorders. In a retrospective report of 22 patients with steroid-dependent MDS/CMML associated SAID, we observed promising results with azacytidine (AZA) on the SAID component (Fraison et al, Leuk Res, 2016). In this prospective French nationwide trial, we aimed at confirming this effect prospectively.Patients and Methods: This open-label, single-arm multicenter, phase II study included MDS/CMML patients with IPSS/CPSS int 2 or high, or lower IPSS/CPSS but with significant cytopenias, especially ESA resistant anemia (or, for CMML, proliferative features) and SAID with steroid dependence and/or resistance. The primary endpoint was response rate (RR, including CR and PR) of SAID after 6 cycles of AZA. Secondary endpoints included RRof SAID after 3 cycles of AZA, response of MDS, time to MDS progression (including to AML), overall survival (OS) and safety. AZA was used at 75 mg/m²/d x 7 days, every 4 weeks for a minimum of 6 cycles (unless overt disease progression occurred before). At the onset of AZA, prednisone (PRED) was administered at 1 mg/kg during 1 month and then decreased progressively over 6 months.Results: 30 patients were included between July 2017 and June 2020, 29 of whom received AZA and were considered evaluable: median age 72 [range 68-78], 69% males; WHO: MDS ML (n=11; 41%), CMML (n=11, 41%), MDS-RS (n=2, 7%), EB-1 (n=1) and EB-2 (n=1), unclassified (n=3); IPSS-R : good (n=15, 54%), very good (n=3; 11%, each), intermediate (n=7; 25%) and very poor profile (n=3; 11%) (all CMML had WBC <13G/l and could be classified by IPSS-R). SAIDs features included non-infectious fever (n=5; 17%), skin lesions (n=14; 48%), joint involvement (n=18; 68%), chondritis (n=6; 21%) and peripheral nervous system impairment (n=3; 10%). 11 (38%) /28 tested patients had UBA1 mutation (VEXAS syndrome), while inin the remaining cases SAID was vasculitis (n=5), rheumatic disease (n=6), neutrophilic dermatosis (n=2) and others (n=5).19 patients (65.5%, IC95% [45.7.82.1]) obtained a SAID response after 6 cycles (including 8 CR and 11 PR), while 17 (58.6% (IC95% [38.9; 76.5]) patients achieved an IWG 2006 hematological response (7 CR, 9 SD with HI and 1 marrow CR). All the 13 patients who received 12 cycles of AZA achieved SAID CR or PR at 12 months, and 10 of them had a hematological response (6 CR, 1PR, 2 HI, 1 marrow CR). The SAID response rate at 12 month was at 72.4% (IC95% : [51.3;85.6]). SAIDs complete/partial response occurred in 3/9 (33%) UBAI-positive versus 8/19 (42%) non-mutated cases. No significant prognostic factor of SAID response after 6 cycles, including sex, age, WHO classification, IPSS-R, UBA1 and TET-2 mutation status was found. With a median follow-up of 18.5 months [11.8; 24.3], 9 (31%) patients had died, with a 1-year OS of 82.3% (IC95% [69.4; 97.7]. At least one SAE occurred in 23 patients, with a median of 2 events/patient [1.5; 5.5]. Death was due to infection (n=5, two of them in patients with good IPSS-R, but severe steroid dependent SAID), MDS progression (n=2), or unrelated causes (n=2).Conclusion We confirmed prospectively an effect of AZA on the autoimmune/inflammatory component in two thirds of MDS/CMML patients with steroid dependent / refractory concomitant systemic autoimmune/inflammatory disease. No significant difference in AZA response was noted between UBA1 mutated and unmutated MDS patients. The adverse events and mortality rates, often from infectious origin, appear to be those expected in such an MDS population, potentially worsened by the associated SAID and background of immunosuppressive treatment (especially steroids) DisclosuresTerriou: Alexion, AstraZeneca Rare Disease: Consultancy, Membership on an entity's Board of Directors or advisory committees. Vey: Amgen: Honoraria; BMS: Honoraria; BIOKINESIS: Consultancy, Research Funding; NOVARTIS: Consultancy, Honoraria, Research Funding; SERVIER: Consultancy; JAZZ PHARMACEUTICALS: Honoraria; JANSSEN: Consultancy. Ades: ABBVIE: Honoraria; TAKEDA: Honoraria; CELGENE/BMS: Honoraria; NOVARTIS: Honoraria; JAZZ: Honoraria, Research Funding; CELGENE: Research Funding. Fenaux: Abbvie: Honoraria, Research Funding; JAZZ: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Celgene/BMS: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Syros Pharmaceuticals: Honoraria.

Serum ANCA as Disease Biomarkers: Clinical Implications Beyond Vasculitis.

Usually associated with autoimmune diseases, anti-neutrophil cytoplasmic antibodies are also detected in other conditions, such as infections, malignancies, and after intake of certain drugs. Even if the mechanisms of production and their pathogenic role have not been fully elucidated yet, ANCA are widely recognized as a clinically alarming finding due to their association with various disorders. While ANCA target several autoantigens, proteinase-3, and myeloperoxidase are the ones proved to be most frequently related to chronic inflammation and tissue damage in murine models. Albeit these autoantibodies could be present as an isolated observation without any implications, ANCA are frequently used in clinical practice to guide the diagnosis in a suspect of small vessel vasculitis. Conditions that should prompt the clinician to test ANCA status range from various forms of lung disease to renal or peripheral nervous system impairment. ANCA positivity in the presence of an autoimmune disease, especially rheumatoid arthritis, or connective tissue diseases, is frequently correlated with more clinical complications and treatment inefficacy, even in the absence of signs of vasculitis. For this reason, it has been postulated that ANCA could represent the final expression of an immune dysregulation rather than a pathogenic event responsible for organs damage. Recently, it has also been proposed that ANCA specificity (PR3 or MPO) could possibly define ANCA-associated vasculitides better than clinical phenotype. This review aims at summarizing the latest advancements in the field of ANCA study and clinical interpretation.

COVID - 19 - a New Challenging Disease for Intensivists and Cardiologists. From Basic Science to the Clinical Setting

A novel coronavirus causing Acute Respiratory Distress Syndrome (SARS-CoV-2) has been considered the cause of a large number of lower respiratory tract infections leading to severe respiratory failure in many cases. However, the evidence-based hospital reports show that the COVID -19 infestation may range from an asymptomatic or minimally symptomatic course with an almost bizarre deterioration of life parameters (“silent hypoxia”) through to critically ill patients with multiple organ failure including that of the lungs, kidneys, nervous system and other organs. Moreover, this coronavirus disease may cause significant lung damage in asymptomatic COVID-19 positive patients who recover at home.The virus enters through the angiotensin-converting enzyme 2 receptor (ACE2) widely expressed in the cardiovascular system and other organs and tissues, which can result in myocardial injury, myocarditis, acute myocardial infarction, heart failure, arrhythmias, brain stroke, acute pleuritis, pneumonia and venous thromboembolic events. COVID -19 - induced failure of some central mechanisms controlling breathing and the circulation may explain the mismatch between the clinical symptoms and the objective physiologic life parameters in many patients treated by intensivists or cardiologists. The severity of coronavirus disease is dependent on numerous factors including the magnitude of the host immune response, the impairment of central and peripheral nervous system, age, co-morbidities (e.g. diabetes, arterial hypertension, obesity, chronic heart failure) and presumably genetic proclivity. A brand-new treatment approach with use of alternative or experimental therapies such us Extracorporeal Membrane Oxygenation (ECMO), plasmapheresis, proinflammatory interleukins - targeted drugs, covalescent plasma transfusion, virus replication inhibitors is obviously needed in some COVID-19 patients.

Neurological Nuance: Sporadic Burkitt's Lymphoma Presenting with Guillain–Barre Syndrome

AbstractBurkitt's lymphoma (BL) is a high-grade mature B cell neoplasm. Primary lymphoma of the central nervous system (CNS) is very rare. In contrast, BL can be localized in any part of the body and may spread to the CNS. Peripheral nervous system impairment caused by BL has been thoroughly described. However, Guillain–Barre syndrome (GBS) does not commonly appear as an initial manifestation of BL. We presented the case of a young child with sporadic BL with neuromeningeal involvement and spinal cord compression whose first clinical manifestation was the appearance of GBS. Lymphoma should be taken into account, especially in children presenting with the clinical features of acute polyradiculoneuropathy.

Social aspects of occupational diseases in clothing industry in Bulgaria

Abstract Background The clothing industry is traditionally well developed branch of industry in Bulgaria Harmful factors of manufacture are forced posture, monotonous work, noise, vibration, poisons etc. At the beginning of 2016, the persons directly employed in the sector add up to 92 000, representing 6% of the employees in Bulgaria. An impairment of musculoskeletal and peripheral nervous system is frequent among these people in relation with the exposure of their professional experience. The aim of the study is to observe the influence of occupational diseases in clothing industry on social and emotional wellbeing of the employees. Methods For the purposes of the study, 103 persons employed in clothing industry, with impairments of the musculoskeletal system and the peripheral nervous system, were investigated. They were admitted to the Department of Occupational Diseases, of the University Hospital in Pleven during the period 2014-2017. Data were collected by interview, documents review and clinical examination. Results Analysis of the results revealed a statistically significant inverse association between performance of daily life activities and length of exposure of patients (p &amp;lt; 0.05). This means that increasing length of exposure restrict the abilities of the investigated persons to perform daily life activities. About 62% of the respondents are often and long standing patients, with more than 4 cases of hospitalization and over 30 days of disability per year. In 68% of the subjects the average duration of one illness exceeds 10 days. Long period of disability affect their income, working position and family relationships. More than a half of people surveyed (56%) cannot afford the recommended rehabilitation which retards the process of recovering. All these facts affect their mood and health self-esteem. Concussion Occupational diseases in clothing industry affect quality of life, social and professional performance of the employees. Key messages In clothing industry many risk factors affect workers’ health. There is a significant association between length of occupational experience in this branch and social aspects of occupational diseases. Occupational diseases in clothing industry affect capability of work and daily routines of employees. They have been associated with long and expensive period treatment and rehabilitation.

Arsenic exposure with reference to neurological impairment: an overview.

Arsenic (As) toxicity has become a public health and environmental problem, which is a serious issue in certain parts of the world. Many people are exposed to As through contaminated drinking water, food and soil, through occupation, etc. Chronic As exposure is linked to various hostile health effects including skin problems, cancer, diabetes, cardiovascular disease, reproductive and developmental and neurological problems in exposed subjects. Experimental existing data indicate that chronic As exposure affects the nervous system by impairing the nerve and brain tissues of the exposed animals, and clinical studies indicate that As exposure leads to both central nervous system and peripheral nervous system impairments and also causes depression, memory impairment and difficulty in problem solving, affects body coordination, etc. Various prenatal and postnatal studies with respect to As exposure also suggest that developing offspring and young children are susceptible to As exposure. The only solution to this serious health problem is to stop occupational As exposure and provide As free drinking water to the affected population.

Hexane exposure and persistent peripheral neuropathy in automotive technicians

Automotive technicians are commonly exposed to organic and chlorinated solvents, particularly through use of cleaning products. Mainly during the period 1989–2002, n-hexane was a component of some of these products. In other occupational contexts, n-hexane has been shown to be a cause of peripheral neuropathy. The purpose of the present study was to investigate whether previous exposures to low concentrations of n-hexane were a cause of persistent peripheral neuropathy in automotive technicians.Enrolled in the study were 830 San Francisco Bay Area automotive technicians. Each participant underwent a battery of tests to investigate peripheral nervous system impairment. Test results regressed against estimated hexane and total solvent exposures showed only limited evidence of association with solvent exposures. Exposures to both hexane and general solvents were well below their occupational exposure limits.Generally, our results provide reassurance about persistent peripheral neuropathic effects in automotive technicians who previously used hexane-containing automotive cleaning products. This may reflect repair processes, since the exposures occurred some years previous to the study. However, we cannot exclude the possibility that the absence of observed effect in this study may be attributable to low exposures, exposure misclassification and/or the healthy worker survivor effect.

Occurrence of cerebral small vessel disease at diagnosis of MPO-ANCA-associated vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) often causes peripheral nervous system impairments. However, little is known about subclinical involvements of the central nervous system in AAV. We investigated the frequency and progression of cerebral small vessel disease (SVD) in patients with AAV. This single-center, case-control study comprised 56 patients with myeloperoxidase (MPO)-ANCA-positive AAV. Cerebral SVD presenting periventricular and deep white matter hyperintensities was assessed using brain magnetic resonance imaging (MRI). Seventy-five patients with non-stroke-associated neurological diseases were employed as controls. At clinical diagnosis of MPO-ANCA-positive AAV, the frequency of periventricular hyperintensities in the AAV group was significantly higher than that in the control group (P = 0.014). Shinohara and Fazekas grades of periventricular hyperintensities in the AAV group were significantly higher than those in the control group (P = 0.019 and 0.020, respectively). In the AAV group, atherosclerosis-related factors, such as age and hypertension, were not associated with the Shinohara grades of periventricular hyperintensities, whereas serum CRP levels were significantly associated (odds ratio = 6.000, 95% confidence interval 1.648-21.840, P = 0.004). MRI changes were followed in 23 patients with AAV until 2years after 6months of diagnosis. Six of these patients worsened the grades of periventricular hyperintensities, while two of 27 in the control group worsened the grades (P = 0.013). Inflammatory events are associated with the occurrence of cerebral SVD before clinical diagnosis of MPO-ANCA-positive AAV. The patients may be continuously exposed to the risk of cerebral SVD after immunosuppressive therapy.

Exploring the Roles of Central and Peripheral Nervous System Function in Gait Stability: Preliminary Insights from Cancer Survivors

BackgroundImpairments in central and/or peripheral nervous systems are known to be associated with altered gait; however, the interplay between cognitive function, peripheral sensation, and orbital gait stability remains largely unclear. Elucidating these relationships is expected to provide a clearer understanding of potential fall risk factors across various populations and targets for novel interventions. Many patients diagnosed with cancer are treated with chemotherapy agents known to be neurotoxic to the central and/or peripheral nervous systems that can contribute to movement deficiencies, making this population a novel model to investigate these relationships. Research QuestionThe purpose of this exploratory study was to investigate how central and peripheral nervous system impairments associate with orbital stability during single- and dual-task gait. MethodsTwenty cancer survivors were enrolled and separated into three groups: no prior chemotherapy exposure (CON, n = 6), and prior treatment with chemotherapy and having no/mild chemotherapy-induced peripheral neuropathy (CIPN) symptoms (-CIPN, n = 8) or moderate/severe CIPN symptoms (+CIPN, n = 6). Testing included single- and dual-task (i.e., serial sevens) treadmill walking as well as a computerized test of executive function. Maximum Floquet multipliers were calculated to assess orbital stability during gait. ResultsWorse executive function was associated with decreased orbital stability during the dual-task condition in the +CIPN group (Spearman’s ρ = 0.94, P = 0.017). Additionally, decreased orbital stability during dual-task gait was observed for the -CIPN group compared to the CON group (ES = 1.96, P = 0.019). SignificanceExecutive dysfunction was associated with decreased gait stability during challenging dual-task gait in survivors with sensory symptoms of CIPN. The association between combined central and peripheral nervous system impairments and decreased gait stability in cancer survivors provides a novel demonstration of potential compensatory strategies that accompany deficiencies in these functions. Future work is needed to confirm these relationships and whether they hold in other populations.

Clinical manifestations of nervous system impairments in diabetes mellitus

Diabetes mellitus is one of the frequent diseases. The article describes diabetic neuropathy as the actual problem of modern neurology. It also provides the classification of central and peripheral nervous system impairments in diabetes mellitus and detailed description of such diseases as distal symmetric sensorimotor polyneuropathy, diabetic encephalopathy, acute neuropsychic disorders, cerebrovascular diseases and features of cognitive impairment in diabetes mellitus. Great attention is paid to the tactics of managing patients with above forms. The role of alpha-lipoic acid products in the treatment of diabetic impairments of the nervous system is thoroughly considered.

Jun, Gal, Cd74, and C1qb as potential indicator for neuropathic pain.

Neuropathic pain is a kind of pain caused by primary or secondary impairment or dysfunction of peripheral or central nervous system. Patients with neuropathic pain were often with poor clinical outcome. We screened the differentially expressed genes between sciatic nerve injury and dorsal root ganglion gene in the sham operation model. Microarray and the spared nerve injury module were used to explore the molecular mechanism of neuropathic pain by injuries and the differentially expressed genes (DEGs) were identified out. Besides, the bioinformatics methods were used to figure out the signaling pathways and expression regulation pattern these DEGs were enriched in, which may provide a basis for the molecular research and medicine target of therapy. Besides, protein-protein interaction network analysis was performed on these selected intersection genes. A total of 40 DEGs were screened out and only pctp gene was down-regulated, the left 39 genes were all up-regulated. Then, GO and KEGG enrichment analysis were performed on these intersection genes by DAVID software. Furthermore, protein-protein interaction network analysis was used to analyze the critical genes of neuropathic pain. Finally, four genes, that is, Jun, Gal, Cd74, and C1qb were identified to have strong interactions with other genes, which may function as the prognostic and predictive genes of neuropathic pain caused by peripheral injuries. Our results suggested that four differentially expressed genes, Jun, Gal, Cd74, and C1qb, had the potential to serve as prognostic or predictive markers for neuropathic pain, suggesting a potential application in the improvement of prognostic tools and treatments.

AAVrh10 Gene Therapy Ameliorates Central and Peripheral Nervous System Disease in Canine Globoid Cell Leukodystrophy (Krabbe Disease).

Globoid cell leukodystrophy (GLD), or Krabbe disease, is an inherited, neurologic disorder that results from deficiency of a lysosomal enzyme, galactosylceramidase. Most commonly, deficits of galactosylceramidase result in widespread central and peripheral nervous system demyelination and death in affected infants typically by 2 years of age. Hematopoietic stem-cell transplantation is the current standard of care in children diagnosed prior to symptom onset. However, disease correction is incomplete. Herein, the first adeno-associated virus (AAV) gene therapy experiments are presented in a naturally occurring canine model of GLD that closely recapitulates the clinical disease progression, neuropathological alterations, and biochemical abnormalities observed in human patients. Adapted from studies in twitcher mice, GLD dogs were treated by combination intravenous and intracerebroventricular injections of AAVrh10 to target both the peripheral and central nervous systems. Combination of intravenous and intracerebroventricular AAV gene therapy had a clear dose response and resulted in delayed onset of clinical signs, extended life-span, correction of biochemical defects, and attenuation of neuropathology. For the first time, therapeutic effect has been established in the canine model of GLD by targeting both peripheral and central nervous system impairments with potential clinical implications for GLD patients.

Central conduction abnormalities in patients receiving levodopa-carbidopa intestinal gel infusion.

In recent years, several studies have reported a relatively high frequency of polyneuropathy in patients with Parkinson's disease (PD), in particular, in patients receiving levodopa-carbidopa intestinal gel (LCIG) infusion. In spite of the several patients investigated with nerve conduction studies, no study has prospectively explored a possible central nervous system involvement of patients receiving LCIG infusion. We prospectively evaluated eight PD patients receiving LCIG infusion, who underwent neurophysiological evaluations with nerve conduction studies, visual, somatosensory and motor evoked potentials before LCIG infusion, and 1 and 6months after. At 6months follow-up, we found significant reduction in sural nerve SNAP amplitude, increase of central sensory conduction time N22-P40, and increases of central motor conduction time recorded from I dorsal interosseous and tibialis anterior. In PD patients with LCIG infusion, we found a subclinical neurophysiological impairment of both peripheral and central nervous system.