Type I interferon signaling, cognition and neurodegeneration following COVID-19: update on a mechanistic pathogenetic model with implications for Alzheimer's disease.

COVID-19's effects on the human brain reveal a multifactorial impact on cognition and the potential to inflict lasting neuronal damage. Type I interferon signaling, a pathway that represents our defense against pathogens, is primarily affected by COVID-19. Type I interferon signaling, however, is known to mediate cognitive dysfunction upon its dysregulation following synaptopathy, microgliosis and neuronal damage. In previous studies, we proposed a model of outside-in dysregulation of tonic IFN-I signaling in the brain following a COVID-19. This disruption would be mediated by the crosstalk between central and peripheral immunity, and could potentially establish feed-forward IFN-I dysregulation leading to neuroinflammation and potentially, neurodegeneration. We proposed that for the CNS, the second-order mediators would be intrinsic disease-associated molecular patterns (DAMPs) such as proteopathic seeds, without the requirement of neuroinvasion to sustain inflammation. Selective vulnerability of neurogenesis sites to IFN-I dysregulation would then lead to clinical manifestations such as anosmia and cognitive impairment. Since the inception of our model at the beginning of the pandemic, a growing body of studies has provided further evidence for the effects of SARS-CoV-2 infection on the human CNS and cognition. Several preclinical and clinical studies have displayed IFN-I dysregulation and tauopathy in gene expression and neuropathological data in new cases, correspondingly. Furthermore, neurodegeneration identified with a predilection for the extended olfactory network furthermore supports the neuroanatomical concept of our model, and its independence from fulminant neuroinvasion and encephalitis as a cause of CNS damage. In this perspective, we summarize the data on IFN-I as a plausible mechanism of cognitive impairment in this setting, and its potential contribution to Alzheimer's disease and its interplay with COVID-19.

Two case reports of a novel missense mutation in the PNPLA6 gene in two siblings with chorioretinal dystrophy, hypogonadotropic hypogonadism, and cerebellar ataxia.

BACKGROUND: Boucher Neuhäuser Syndrome (BNS) is a rare disease with autosomal recessive inheritance defined by the classical triad; early-onset ataxia, hypogonadism and chorioretinal dystrophy. CASE PRESENTATION: We present two siblings diagnosed with BNS at midlife, identified with homozygous state of a novel PNPLA6 missense mutation. One healthy sibling and the mother were heterozygous carriers of the mutation. The proband presented with the classical triad and the other sibling presented with visual problems at first. The proband was referred to our department by a private Neurologist, in early adulthood, because of hypogonadism, cerebellar ataxia, axonal neuropathy, and chorioretinal dystrophy for further evaluation. The sibling was referred to our department for evaluation, at childhood, due to visual problems. Later, the patient displayed the triad of ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy. The unusual medical history of the two siblings led to further examinations and eventually the diagnosis of the first BNS cases in Cyprus. WES-based ataxia in silico gene panel analysis revealed 15 genetic variants and further filtering analysis revealed the PNPLA6 c.3323G > A variant. Segregation analysis in the family with Sanger sequencing confirmed the PNPLA6 homozygous variant c.3323G > A, p.Arg1108Gln in exon 29. CONCLUSIONS: This highlights the importance of considering rare inherited causes of visual loss, spinocerebellar ataxia, or/and HH in a neurology clinic and the significant role of genetic sequencing in the diagnostic process.

Adult Neoneurogenesis and Oligodendrogenesis in Multiple Sclerosis: A Systematic Review of Human and Animal Studies.

Introduction: The subventricular zone promotes remyelination through activation differentiation of oligodendroglial precursor cells (OPCs) and neural stem cells (NSCs) into mature oligodendrocytes and thus in the adult brain. In multiple sclerosis (MS) this regenerative capability is halted resulting in neurodegeneration. We aimed to systematically search and synthesize evidence on mechanisms and phenomena associated with subventricular zone (SVZ) dysfunction in MS. Materials and Methods: Our systematic review was reported according to the PRISMA-ScR statement. MEDLINE, SCOPUS, ProQuest, and Google Scholar were searched using the terms "subventricular zone" and "multiple sclerosis," including English-written in vivo and postmortem studies. Results: Twenty studies were included. Thirteen studies on models of experimental autoimmune encephalomyelitis (EAE) reported among others strong stathmin immunoreactivity in the SVZ of EAE models, the role of MOG immunization in neurogenesis impairment, the effect of parenchymal OPCs and NSCs in myelin repair, and the importance of ependymal cells (E1/E2) and ciliated B1 cells in SVZ stem cell signaling. CXCR4 signaling and transcriptional profiles of SVZ microglia, Gli1 pathway, and galactin-3 were also explored. Studies in humans demonstrated microstructural SVZ damage in progressive MS and the persistence of black holes near the SVZ, whereas postmortem confirmed the generation of polysialic acid-neural cell adhesion molecule and NG2-positive progenitors through SVZ activation, SVZ stathmin immunoreactivity, Shh pathway, and Gal-3 upregulation. Discussion: Oligodendrogenesis defects translate to reduced remyelination, a hallmark of MS that determines its end-phenotype and disease course. Conclusion: The role of inflammation and subsequent SVZ microenvironment disruption is evident in MS pathology.

Selenium, Stroke, and Infection: A Threefold Relationship; Where Do We Stand and Where Do We Go?

Stroke is currently the second most common cause of death worldwide and a major cause of serious long-term morbidity. Selenium is a trace element with pleotropic effects on human health. Selenium deficiency has been associated with a prothrombotic state and poor immune response, particularly during infection. Our aim was to synthesize current evidence on the tripartite interrelationship between selenium levels, stroke, and infection. Although evidence is contradictory, most studies support the association between lower serum selenium levels and stroke risk and outcomes. Conversely, limited evidence on the role of selenium supplementation in stroke indicates a potentially beneficial effect of selenium. Notably, the relationship between stroke risk and selenium levels is bimodal rather than linear, with higher levels of serum selenium linked to disturbances of glucose metabolism and high blood pressure, morbidities which are, in turn, substrates for stroke. Another such substrate is an infection, albeit forming a bidirectional relationship with both stroke and the consequences of impaired selenium metabolism. Perturbed selenium homeostasis leads to impaired immune fitness and antioxidant capacity, which both favor infection and inflammation; specific pathogens may also contend with the host for transcriptional control of the selenoproteome, adding a feed-forward loop to this described process. Broader consequences of infection such as endothelial dysfunction, hypercoagulation, and emergent cardiac dysfunction both provide stroke substrates and further feed-forward feedback to the consequences of deficient selenium metabolism. In this review, we provide a synthesis and interpretation of these outlined complex interrelationships that link selenium, stroke, and infection and attempt to decipher their potential impact on human health and disease. Selenium and the unique properties of its proteome could provide both biomarkers and treatment options in patients with stroke, infection, or both.

Primary Sjögren syndrome-related peripheral neuropathy: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Primary Sjögren syndrome (pSS) is a chronic, systemic, autoimmune disorder characterized by lymphocytic infiltrates of the exocrine organs, leading to sicca symptoms and parotid enlargement. pSS has been linked to various neurological manifestations, including peripheral neuropathy (PN). We aimed to provide a comprehensive analysis of the currently available evidence regarding pSS-related PN. METHODS: A literature search in the PubMed database was performed, and 49 papers were eligible to be included in this systematic review and meta-analysis. RESULTS: The pooled prevalence of PN in pSS is estimated to be 15.0% (95% confidence interval = 10.7%-20.7%). The mean age of pSS patients at PN diagnosis is 59 years. Among the patients with pSS and PN, 83% are females. Neuropathic symptoms usually precede or lead to the pSS diagnosis at a 2:1 ratio in patients with pSS-related PN. The commonest type of pSS-related PN is distal axonal polyneuropathy (80% of patients with pSS-related PN), followed by sensory ganglionopathy. Peripheral and cranial mononeuropathies-particularly trigeminal-are also frequent. Risk factors for developing PN include increasing age and presence of vasculitis. Immune-mediated pathogenetic mechanisms are discussed. Glucocorticoids are the most commonly used treatment option for managing pSS-related PN, when associated with vasculitis, followed by the use of intravenous immunoglobulin. CONCLUSIONS: PN is very common in pSS patients. Evidence on long-term prognosis of PN in pSS is limited, and further research is needed. Research into the use of immunosuppressive medication in nonvasculitic neuropathies in the context of pSS merits further consideration.

Immunoglobulin Use for the Management of Painful Peripheral Neuropathy: A Systematic Review and Meta-Analysis.

BACKGROUND: Immunoglobulins (IG) are widely used for the treatment of a variety of immune-mediated diseases. The exact mechanism of action remains unknown, but IG modulate the expression and function of Fc receptors, interfere with complement activation and production of cytokines, neutralize pathogenic autoantibodies, and affect the activation and effector functions of B and T lymphocytes. Immunoglobulins are usually delivered intravenously, and are effective in ameliorating motor symptoms, and/or preventing disease progression in immune-mediated neuropathies, including Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. OBJECTIVE: The aim of this systematic review and meta-analysis was to study the potential of IG for the treatment of painful peripheral neuropathy (PPN). The outcome of interest was the percentage of patients with PPN who achieved pain relief following IG administration. METHODS: We performed a systematic literature search on March 17, 2022, in the PubMed database without any publication date restrictions. We also looked for unpublished or ongoing trials in clinicaltrials.org. Pain reduction following IG treatment had to be within the aims (primary or secondary). RESULTS: The aforementioned literature search strategy revealed five studies (two open-label, three randomized placebo-controlled) eligible to be included. The pooled estimate of the percentage of patients with PPN who received immunoglobulins and reported pain relief was found to be 65% (95% CI 58-71%). The likelihood of achieving pain relief with immunoglobulin treatment was 2.9 times higher (95% CI 1.6-5.2) compared to placebo (p = 0.0003). CONCLUSION: The use of IG for the treatment of pain due to peripheral neuropathy has a potential therapeutic benefit. Further studies across patients with different types of painful peripheral neuropathy are needed to better characterize this effect. Registration number on PROSPERO: CRD42022319614.

EEG Recordings as Biomarkers of Pain Perception: Where Do We Stand and Where to Go?

INTRODUCTION: The universality and complexity of pain, which is highly prevalent, yield its significance to both patients and researchers. Developing a non-invasive tool that can objectively measure pain is of the utmost importance for clinical and research purposes. Traditionally electroencephalography (EEG) has been mostly used in epilepsy; however, over the recent years EEG has become an important non-invasive clinical tool that has helped increase our understanding of brain network complexities and for the identification of areas of dysfunction. This review aimed to investigate the role of EEG recordings as potential biomarkers of pain perception. METHODS: A systematic search of the PubMed database led to the identification of 938 papers, of which 919 were excluded as a result of not meeting the eligibility criteria, and one article was identified through screening of the reference lists of the 19 eligible studies. Ultimately, 20 papers were included in this systematic review. RESULTS: Changes of the cortical activation have potential, though the described changes are not always consistent. The most consistent finding is the increase in the delta and gamma power activity. Only a limited number of studies have looked into brain networks encoding pain perception. CONCLUSION: Although no robust EEG biomarkers of pain perception have been identified yet, EEG has potential and future research should be attempted. Designing strong research protocols, controlling for potential risk of biases, as well as investigating brain networks rather than isolated cortical changes will be crucial in this attempt.

Management of MDA-5 antibody positive clinically amyopathic dermatomyositis associated interstitial lung disease: A systematic review.

INTRODUCTION: Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive clinically amyopathic dermatomyositis (CADM) is frequently associated with rapidly progressive interstitial lung disease (RP-ILD) and high mortality rates. There is a lack of data on management of this often fatal condition. The aim of this systematic review was to evaluate current evidence that assesses the available management options and discuss the associated management challenges. MATERIAL AND METHODS: This systematic review was conducted according to PRISMA guidelines.  Online databases were searched from inception to April of 2021 using the search terms: "dermatomyositis" OR "amyopathic dermatomyositis" OR "clinically amyopathic dermatomyositis" AND "MDA-5″ OR "melanoma differentiation-associated gene-5″ OR "CADM-140″ AND "management" OR "treatment" OR "therapy" OR "therapeutics". Articles assessing the use of pharmacologic agents on 10 or more patients with MDA5-antibody positive CADM associated with ILD were included. Narrative or systematic reviews and meta-analyses were not eligible for inclusion. RESULTS: A total of 15 eligible studies and 399 unique patients were selected. We identified only one open-label randomized controlled trial (RCT) that examined the management of anti-MDA5 antibody CADM/DM-ILD. Further, 3 cohort studies with prospective arms matched against historical controls, 10 retrospective cohort studies, and 1 retrospective case series were included. A combined therapeutic regimen of high-dose systemic glucocorticoids and other immunosuppressive agents such as calcineurin inhibitors and/or cyclophosphamide, administered early, appears to give the highest rates of survival in those with RP-ILD, while additional therapies such as plasma exchange can be added for refractory disease. Further, tofacitinib and rituximab might have a place in the therapeutic armamentarium of this challenging to treat condition.   Early detection and treatment are of extreme importance, given the risk for rapid decline and high mortality in this subset of patients. CONCLUSION: There are limited RCTs evaluating the treatment of ILD associated with MDA5-antibody positive CADM. Initiating a combined immunosuppressive therapeutic regimen early in the disease course improves overall morbidity and mortality. RCTs and larger prospective studies are needed to provide high-quality evidence to inform future treatment guidelines.

Primary Sjögren's syndrome (pSS)-related cerebellar ataxia: a systematic review and meta-analysis.

BACKGROUND: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder characterized by lymphocytic infiltrates of the exocrine glands, particularly the salivary and lacrimal glands, resulting in oral and ocular dryness. pSS has been linked to various neurological manifestations, including cerebellar dysfunction. We aimed to provide a comprehensive analysis of the currently available evidence regarding pSS-related cerebellar ataxia. METHODS: A systematic literature search in the PubMed database was performed and 19 papers were eligible to be included in this paper. RESULTS: The pooled prevalence of cerebellar ataxia in pSS is estimated to be 1.5% (95% CI 0.3-6.8%). pSS patients with cerebellar involvement have a female-to-male ratio of 6:1. Although most of the patients are adults in their fifth decade of life when diagnosed, cases of children with pSS and cerebellar involvement have been reported. Typical cerebellar ataxia related to pSS manifests with vermian dysfunction, namely gait ataxia and/or cerebellar speech. Cerebellar ataxia due to pSS may also mimic degenerative cerebellar ataxia, especially when the onset is progressive. CONCLUSIONS: The diagnostic approach to a patient with cerebellar ataxia of unknown etiology should include evaluation for an underlying pSS. A thorough history and clinical examination, antibody testing, brain MRI imaging and/or MRS of the cerebellum will assist in establishing the diagnosis. Setting up a joint neuro-rheumatology clinic can be valuable given that rheumatic and neurological diseases share comorbidities.

Adjuvant physical exercise for the management of painful polyneuropathy.

INTRODUCTION: Physical exercise appeared to be effective, when implemented as an adjuvant to the pharmacotherapy option, in a variety of painful conditions. Peripheral neuropathic pain (PNP) is very prevalent and affects up to two-thirds of individuals with polyneuropathy (PN), regardless of etiology. The aim of this systematic review was to evaluate the currently available studies that assess adjuvant physical exercise for the management of PNP. METHODS: A systematic literature search was conducted in the PubMed international database. For the systematic search, three medical subject headings (MeSH) were used. Term A was 'physical exercise' OR 'exercise' OR 'activity' OR 'workout' OR 'training'; term B was 'pain' OR 'painful'; term C was 'neuropathy' OR 'polyneuropathy.' Additionally, three filters were used: human subjects, English language, and full text. The reference lists of eligible papers and relevant reviews were also meticulously searched in order to include further relevant studies. Six papers eligible to be included were identified. RESULTS: Physical exercise in various forms can be of benefit in the management of PNP when used as an adjuvant to the standard care. Overall, using the American Society of Interventional Pain Physicians (ASIPP) criteria, the current best available evidence exists for both aerobic and muscle strengthening exercise programs (level II evidence). The intensity of the exercise seems to play a significant role, with higher intensity interval training programs being more promising, though this remains to be confirmed in future studies. CONCLUSIONS: Physical exercise is a promising non-pharmacological intervention for the management of PNP. Future RCTs should be conducted to make a face-to-face comparison of the available exercise treatments with the aim to design specific exercise programs for patients with PNP.

Machine Learning in Pain Medicine: An Up-To-Date Systematic Review.

INTRODUCTION: Pain is the unpleasant sensation and emotional experience that leads to poor quality of life for millions of people worldwide. Considering the complexity in understanding the principles of pain and its significant impact on individuals and society, research focuses to deliver innovative pain relief methods and techniques. This review explores the clinical uses of machine learning (ML) for the diagnosis, classification, and management of pain. METHODS: A systematic review of the current literature was conducted using the PubMed database library. RESULTS: Twenty-six papers related to pain and ML research were included. Most of the studies used ML for effectively classifying the patients' level of pain, followed by use of ML for the prediction of manifestation of pain and for pain management. A less common reason for performing ML analysis was for the diagnosis of pain. The different approaches are thoroughly discussed. CONCLUSION: ML is increasingly used in pain medicine and appears to be more effective compared to traditional statistical approaches in the diagnosis, classification, and management of pain.

Musculoskeletal Pain Due to Wheelchair Use: A Systematic Review and Meta-Analysis.

INTRODUCTION: Wheelchair users are at a high risk of experiencing non-neuropathic pain of musculoskeletal origin as a result of being wheelchair-bound. The aim of this systematic review was to establish the prevalence of musculoskeletal pain in wheelchair users that is attributable to wheelchair use, and to describe the different pain syndromes and discuss risk factors and management options. METHODS: After a systematic MEDLINE search, we identified 40 papers eligible for inclusion. RESULTS: The pooled prevalence of musculoskeletal pain at any location was 50% (95% CI 33-67%). The most common pain syndrome was shoulder pain (pooled prevalence 44%, 95% CI 36-52%). Wheelchair users were 5.8 times as likely to suffer from shoulder pain as controls (95% CI 2.7-12.2, p < 0.0001). Other pain syndromes included neck, elbow, wrist, hand and low back pain. Older age and increased duration of wheelchair use were the most significant determinants of pain in wheelchair users. CONCLUSIONS: Musculoskeletal pain as a result of wheelchair use is very common amongst wheelchair users. Management of pain should follow national and international guidelines. Optimal adjustment of seating position may prevent pain, and is important to be taken into consideration.

Myelopathy associated with SARS-COV-2 infection. A systematic review.

Background׃COVID-19 (CoranaVirus disease 2019) is an ongoing infectious disease caused by the RNA SARS-CoV-2 virus (Severe Acute Respiratory Syndrome CoronaVirus-2). More than one-third of COVID-19 patients report neurological symptoms and cases of neurological diseases are increasingly accumulating. The aim of this systematic review was to characterize all - to date - reported cases with COVID-19 related myelopathy. Methods׃Eighteen papers were included in this review. Patients of all ages could be affected, although there is a predilection for middle-aged people. Results׃There were no significant co-morbidities or immunodeficiencies in the affected patients. COVID-19 related myelopathy started roughly within the first month after COVID-19 onset, either concomitantly with COVID-19 symptoms or within 10 days after their remission. The vast majority of cases fulfilled our criteria for postinfectious transverse myelitis. However, some cases were considered to have had parainfectious or infectious myelitis or, in one case, vascular myelopathy. Motor, sensory and bowel and/or bladder symptoms predominated the clinical presentation of myelopathies, explained mainly by centrally localized and longitudinally extensive lesions within the cervical and/or thoracic segments of the spinal cord. Occasionally lesions were complicated by necrosis and hemorrhages. Treatment with corticosteroids, intravenous immunoglobulin or plasma exchange was offered mostly a mild to marked improvement within a period of some weeks. Conclusions׃ Considering the imminent arrival of new vaccines against COVID-19 pandemic, and their potential risk for postvaccination transverse myelitis, this characterization of COVID-19 related myelopathy is of utmost importance.

Pharmacological Management of Painful Peripheral Neuropathies: A Systematic Review.

INTRODUCTION: Peripheral neuropathic pain (PNP) arises either acutely or in the chronic phase of a lesion or disease of the peripheral nervous system and is associated with a notable disease burden. The management of PNP is often challenging. The aim of this systematic review was to evaluate current evidence, derived from randomized controlled trials (RCTs) that have assessed pharmacological interventions for the treatment of PNP due to polyneuropathy (PN). METHODS: A systematic search of the PubMed database led to the identification of 538 papers, of which 457 were excluded due to not meeting the eligibility criteria, and two articles were identified through screening of the reference lists of the 81 eligible studies. Ultimately, 83 papers were included in this systematic review. RESULTS: The best available evidence for the management of painful diabetic polyneuropathy (DPN) is for amitriptyline, duloxetine, gabapentin, pregabalin and venlafaxine as monotherapies and oxycodone as add-on therapy (level II of evidence). Tramadol appears to be effective when used as a monotherapy and add-on therapy in patients with PN of various etiologies (level II of evidence). Weaker evidence (level III) is available on the effectiveness of several other agents discussed in this review for the management of PNP due to PN. DISCUSSION: Response to treatment may be affected by the underlying pathophysiological mechanisms that are involved in the pathogenesis of the PN and, therefore, it is very important to thoroughly investigate patients presenting with PNP to determine the causes of this neuropathy. Future RCTs should be conducted to shed more light on the use of pharmacological approaches in patients with other forms of PNP and to design specific treatment algorithms.

Vegetarian Diets and Eating Disorders in Adolescents and Young Adults: A Systematic Review.

BACKGROUND: Eating disorders are more common among adolescents and young adults. An increase in the rates of these disorders has been reported during the last years. Meanwhile, vegetarianism is becoming more popular in these age groups. The purpose of the present paper is to evaluate the association between eating disorders and vegetarian diets in adolescents and young adults. METHODS: Systematic review of related articles published in PubMed, PsycInfo and Google Scholar up to 30 May 2019. RESULTS: A total of 20 studies (14,391 subjects) were deemed eligible for this systematic review. The majority of the studies reported significant correlations between vegetarianism and eating disorders. However, due to the cross-sectional design, a causal link between eating disorders and vegetarian status cannot be established. CONCLUSIONS: Vegetarianism seems to be associated with eating disorders. Longitudinal studies are needed to establish temporal patterns between vegetarianism and the emergence of disordered eating.

A European questionnaire survey on epilepsy monitoring units' current practice for postoperative psychogenic nonepileptic seizures' detection.

BACKGROUND: In cases undergoing epilepsy surgery, postoperative psychogenic nonepileptic seizures (PNES) may be underdiagnosed complicating the assessment of postsurgical seizures' outcome and the clinical management. We conducted a survey to investigate the current practices in the European epilepsy monitoring units (EMUs) and the data that EMUs could provide to retrospectively detect cases with postoperative PNES and to assess the feasibility of a subsequent postoperative PNES research project for cases with postoperative PNES. METHODS: We developed and distributed a questionnaire survey to 57 EMUs. Questions addressed the number of patients undergoing epilepsy surgery, the performance of systematic preoperative and postoperative psychiatric evaluation, the recording of sexual or other abuse, the follow-up period of patients undergoing epilepsy surgery, the performance of video-electroencephalogram (EEG) and postoperative psychiatric assessment in suspected postoperative cases with PNES, the existence of electronic databases to allow extraction of cases with postoperative PNES, the data that these bases could provide, and EMUs' interest to participate in a retrospective postoperative PNES project. RESULTS: Twenty EMUs completed the questionnaire sheet. The number of patients operated every year/per center is 26.7 ( ±â€¯19.1), and systematic preoperative and postoperative psychiatric evaluation is performed in 75% and 50% of the EMUs accordingly. Sexual or other abuse is systematically recorded in one-third of the centers, and the mean follow-up period after epilepsy surgery is 10.5 ±â€¯7.5 years. In suspected postoperative PNES, video-EEG is performed in 85% and psychiatric assessment in 95% of the centers. An electronic database to allow extraction of patients with PNES after epilepsy surgery is used in 75% of the EMUs, and all EMUs that sent the sheet completed expressed their interest to participate in a retrospective postoperative PNES project. CONCLUSION: Postoperative PNES is an underestimated and not well-studied entity. This is a European survey to assess the type of data that the EMUs surgical cohorts could provide to retrospectively detect postoperative PNES. In cases with suspected PNES, most EMUs perform video-EEG and psychiatric assessment, and most EMUs use an electronic database to allow extraction of patients developing PNES.

Non-Pharmacological Management of Painful Peripheral Neuropathies: A Systematic Review.

INTRODUCTION: Peripheral neuropathic pain (PNP) is defined as the neuropathic pain that arises either acutely or in the chronic phase of a lesion or disease affecting the peripheral nervous system. PNP is associated with a remarkable disease burden, and there is an increasing demand for new therapies to be used in isolation or combination with currently available treatments. The aim of this systematic review was to evaluate the current evidence, derived from randomized controlled trials (RCTs) that assess non-pharmacological interventions for the treatment of PNP. METHODS: After a systematic Medline search, we identified 18 papers eligible to be included. RESULTS: The currently best available evidence (level II of evidence) exist for painful diabetic peripheral neuropathy. In particular, spinal cord stimulation as adjuvant to conventional medical treatment can be effectively used for the management of patients with refractory pain. Similarly, adjuvant repetitive transcranial magnetic stimulation of the motor cortex is effective in reducing the overall pain intensity, whereas adjuvant static magnetic field therapy can lead to a significant decrease in exercise-induced pain. Weaker evidence (level III of evidence) exists for the use of acupuncture as a monotherapy and neurofeedback, either as an add-on or a monotherapy approach, for treatment of painful chemotherapy-induced peripheral neuropathy CONCLUSIONS: Future RCTs should be conducted to shed more light in the use of non-pharmacological approaches in patients with PNP.