Early cortico-muscular coherence and cortical network changes in Parkinson's patients treated with MRgFUS.

Introduction: To investigate cortical network changes using Magnetoencephalography (MEG) signals in Parkinson's disease (PD) patients undergoing Magnetic Resonance-guided Focused Ultrasound (MRgFUS) thalamotomy. Methods: We evaluated the MEG signals in 16 PD patients with drug-refractory tremor before and after 12-month from MRgFUS unilateral lesion of the ventralis intermediate nucleus (Vim) of the thalamus contralateral to the most affected body side. We recorded patients 24 h before (T0) and 24 h after MRgFUS (T1). We analyzed signal epochs recorded at rest and during the isometric extension of the hand contralateral to thalamotomy. We evaluated cortico-muscular coherence (CMC), the out-strength index from non-primary motor areas to the pre-central area and connectivity indexes, using generalized partial directed coherence. Statistical analysis was performed using RMANOVA and post hoct-tests. Results: Most changes found at T1 compared to T0 occurred in the beta band and included: (1) a re-adjustment of CMC distribution; (2) a reduced out-strength from non-primary motor areas toward the precentral area; (3) strongly reduced clustering coefficient values. These differences mainly occurred during motor activation and with few statistically significant changes at rest. Correlation analysis showed significant relationships between changes of out-strength and clustering coefficient in non-primary motor areas and the changes in clinical scores. Discussion: One day after MRgFUS thalamotomy, PD patients showed a topographically reordered CMC and decreased cortico-cortical flow, together with a reduced local connection between different nodes. These findings suggest that the reordered cortico-muscular and cortical-networks in the beta band may represent an early physiological readjustment related to MRgFUS Vim lesion.

Early Onset Inherited Peripheral Neuropathies: The Experience of a Specialized Referral Center for Genetic Diagnosis Achievement.

BACKGROUND: Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of inherited peripheral neuropathies. Although the typical disease onset is reported in the second decade, earlier onsets are not uncommon. To date, few studies on pediatric populations have been conducted and the achievement of molecular diagnosis remains challenging. METHODS: During the last 24 years we recruited 223 patients with early-onset hereditary peripheral neuropathies (EOHPN), negative for PMP22 duplication, 72 of them referred by a specialized pediatric hospital. Genetic testing for CMT-associated genes has been carried out with a range of different techniques. RESULTS: Of the 223 EOHPN cases, 43% were classified as CMT1 (demyelinating), 49% as CMT2 (axonal), and 8% as CMTi (intermediate). Genetic diagnosis was reached in 51% of patients, but the diagnostic yield increased to 67% when focusing only on cases from the specialized pediatric neuromuscular centers. Excluding PMP22 rearrangements, no significant difference in diagnostic rate between demyelinating and axonal forms was identified. De novo mutations account for 38% of cases. CONCLUSIONS: This study describes an exhaustive picture of EOHPN in an Italian referral genetic center and analyzes the molecular diagnostic rate of a heterogeneous cohort compared with one referred by a specialized pediatric center. Our data identify MPZ, MFN2, GDAP1, and SH3TC2 genes as the most frequent players in EOHPN. Our study underlines the relevance of a specific neurological pediatric expertise to address the genetic testing and highlights its importance to clarify possible unexpected results when neuropathy is only a secondary clinical sign of a more complex phenotype.

What have we learned in fluorescein-guided resection of brain metastases? An update after 79 consecutive cases.

BACKGROUND: Cerebral metastasis (CM) is the most common malignancy affecting the brain. Individualized treatment of CM still represents a challenge for neuro-oncological teams: in patient eligible for surgery, complete tumor removal is the most relevant predictor of overall survival (OS) and neurological outcome. The development of surgical microscopes harboring specific filter able to elicit the fluorescent response from sodium fluorescein (SF) has facilitated fluorescein-guided microsurgery and the identification of pathological tumor tissue, especially at the tumor margins. In this study, we analyzed the effect of SF on the visualization and resection of a large monoinstitutional cohort of CM. METHODS: Surgical database of FLUOCERTUM study (Besta Institute, Milan, Italy) was retrospectively reviewed to find CM surgically removed with a fluorescein-guided technique from March 2016 to December 2022. SF was intravenously injected (5 mg/kg) immediately after induction of general anesthesia. Tumors were removed using a microsurgical technique with the YELLOW560 filter (Carl Zeiss Meditec, Oberkochen, Germany). In the most recent cases, biopsies at the tumor margins were performed to evaluate the ability of fluorescein to discriminate between fluorescent and nonfluorescent tissue at the lesion borders. RESULTS: Seventy-nine patients were included; most of them showed a bright, diffuse fluorescent staining that markedly enhanced tumor visibility; 11 melanomas presented a specific faint enhancement of the black pigmented central nodule with high fluorescence at tumor boundaries. Only in a minimal percentage of cases (N.=4-5.1%), fluorescein enhancement was tenuous, thus not providing a significant help during tumor resection. Altogether, in more than 90% of cases, SF was considered useful in the identification of tumoral tissue and in achieving a high rate of CM resection; thus, gross total resection was achieved in 96.2% (N.=76) of patients and in no case the detection of tumor remnants was an unexpected event. The resulted sensitivity and specificity of fluorescein in identifying tumor tissue at the tumor margin was 88.9% with a predictive positive value of 88.9%. No adverse event was registered during the postoperative course. CONCLUSIONS: The use of SF is a valuable method for safe fluorescence-guided tumor resection. Our data showed a positive effect of fluorescein-guided surgery on intraoperative visualization during resection of CM, suggesting a role in improving the extent of resection of these lesions.

Scoping Review on the Diagnosis, Prognosis, and Treatment of Pediatric Disorders of Consciousness.

BACKGROUND AND OBJECTIVES: Comprehensive guidelines for the diagnosis, prognosis, and treatment of disorders of consciousness (DoC) in pediatric patients have not yet been released. We aimed to summarize available evidence for DoC with >14 days duration to support the future development of guidelines for children, adolescents and young adults aged 6 months-18 years. METHODS: This scoping review was reported based on Preferred Reporting Items for Systematic reviews and Meta-Analyses-extension for Scoping Reviews guidelines. A systematic search identified records from 4 databases: PubMed, Embase, Cochrane Library, and Web of Science. Abstracts received 3 blind reviews. Corresponding full-text articles rated as "in-scope" and reporting data not published in any other retained article (i.e., no double reporting) were identified and assigned to 5 thematic evaluating teams. Full-text articles were reviewed using a double-blind standardized form. Level of evidence was graded, and summative statements were generated. RESULTS: On November 9, 2022, 2,167 documents had been identified; 132 articles were retained, of which 33 (25%) were published over the past 5 years. Overall, 2,161 individuals met the inclusion criteria; female patients were 527 of 1,554 (33.9%) cases included, whose sex was identifiable. Of 132 articles, 57 (43.2%) were single case reports and only 5 (3.8%) clinical trials; the level of evidence was prevalently low (80/132; 60.6%). Most studies included neurobehavioral measures (84/127; 66.1%) and neuroimaging (81/127; 63.8%); 59 (46.5%) were mainly related to diagnosis, 56 (44.1%) to prognosis, and 44 (34.6%) to treatment. Most frequently used neurobehavioral tools included the Coma Recovery Scale-Revised, Coma/Near-Coma Scale, Level of Cognitive Functioning Assessment Scale, and Post-Acute Level of Consciousness scale. EEG, event-related potentials, structural CT, and MRI were the most frequently used instrumental techniques. In 29/53 (54.7%) cases, DoC improvement was observed, which was associated with treatment with amantadine. DISCUSSION: The literature on pediatric DoCs is mainly observational, and clinical details are either inconsistently presented or absent. Conclusions drawn from many studies convey insubstantial evidence and have limited validity and low potential for translation in clinical practice. Despite these limitations, our work summarizes the extant literature and constitutes a base for future guidelines related to the diagnosis, prognosis, and treatment of pediatric DoC.

Neurophysiology-Guided Laser Interstitial Thermal Therapy: A Synergistic Approach For Motor Function Preservation. Technical Note.

BACKGROUND: Laser interstitial thermal therapy (LITT) is a minimally invasive ablative technique with specific indications for neuro-oncology, especially in the case of lesions in eloquent areas. Even being performed through a small catheter under stereotactic conditions, the risk of damaging vital structures such as white matter tracts or cortical eloquent areas is not negligible. The mechanism of damage can be related to catheter insertion or to excessive laser ablation. An accurate preoperative workup, aimed at locating the eloquent structures, can be combined with a real-time intraoperative neurophysiologic monitoring to reduce surgical morbidity while maximizing the efficacy of LITT. METHODS: We developed a synergistic approach for neurophysiology-guided LITT based on state-of-the-art technologies, namely, magnetoencephalography, diffusion tensor imaging, and intraoperative neurophysiologic monitoring. RESULTS: As a result, we improved the planning phase thanks to a more precise representation of functional structures that allows the simulation of different trajectories and the identification of the most suitable trajectory to treat the lesion while respecting the functional boundaries. Catheter insertion is conducted under continuous neurophysiologic feedback and the ablation phase is modeled on the functional boundaries identified by stimulation, allowing it to be extremely accurate. CONCLUSIONS: An integrated approached guided by neurophysiology is able to reduce the surgical morbidity even in a relatively accurate technique such as LITT. To the best of our knowledge, this represents the first report on this synergistic approach which could really impact the treatment of tumors in eloquent areas. Future studies are needed in the effort to implement this approach in functional or epilepsy neurosurgery as well.

MRI-guided focused-ultrasound thalamotomy in essential tremor: Immediate and delayed changes in cortico-muscular coherence and cortico-cortical out-strength.

OBJECTIVE: Drug-resistant essential tremor (ET) can be treated by Magnetic-Resonance-guided Focused-Ultrasound (MRgFUS) targeted to thalamic ventralis-intermediate nucleus (ViM). We are presenting the results obtained in ET patients by evaluating the cortico-muscular coherence (CMC) and the out-strength among cortical areas. METHODS: We recorded MEG-EMG signals in 16 patients with predominant tremor on the right upper limb. The examination was performed the day before MRgFUS (T0) treatment, 24 hours (T1), and 3-months (T2) after lesioning the left ViM. Normalized CMC (nCMC) and cortico-cortical out-strength among cortical areas were assessed during isometric extension of the right hand. RESULTS: According to the Essential Tremor Rating Assessment Scale, 13 of 16 patients were considered responders. At T1, in the beta-band, nCMC increased in the left hemisphere, namely in the areas directly involved in motor functions. At T2, the nCMC in non-motor areas decreased and the out-strength from other examined cortical areas toward the left motor-area decreased. CONCLUSIONS: In patients positively responding to MRgFUS, the CMC increased in the motor-area of the treated hemisphere immediately after the treatment, while the reorganization of CMC and cortico-cortical out-strength toward the cortical motor area occurred with a delay. SIGNIFICANCE: The effective treatment with MRgFUS corresponds with a readjustment of the CMC and of the communication between cortical areas.

Cyrcadian Rhythm, Mood, and Temporal Patterns of Eating Chocolate: A Scoping Review of Physiology, Findings, and Future Directions.

This paper discusses the effect of chrononutrition on the regulation of circadian rhythms; in particular, that of chocolate on the resynchronization of the human internal biological central and peripheral clocks with the main external synchronizers, light-dark cycle and nutrition-fasting cycle. The desynchronization of internal clocks with external synchronizers, which is so frequent in our modern society due to the tight rhythms imposed by work, social life, and technology, has a negative impact on our psycho-physical performance, well-being, and health. Taking small amounts of chocolate, in the morning at breakfast at the onset of the active phase, helps speed up resynchronization time. The high flavonoid contents in chocolate promote cardioprotection, metabolic regulation, neuroprotection, and neuromodulation with direct actions on brain function, neurogenesis, angiogenesis, and mood. Although the mechanisms of action of chocolate compounds on brain function and mood as well as on the regulation of circadian rhythms have yet to be fully understood, data from the literature currently available seem to agree in suggesting that chocolate intake, in compliance with chrononutrition, could be a strategy to reduce the negative effects of desynchronization. This strategy appears to be easily implemented in different age groups to improve work ability and daily life.

Significance and clinical suggestions for the somatosensory evoked potentials increased in amplitude revealed by a large sample of neurological patients.

OBJECTIVES: To investigate the relationship between N20-P25 peak-to-peak amplitude (N20p-P25p) of somatosensory evoked potentials (SEPs) and the occurrence of abnormalities of the peripheral and/or central sensory pathways and of myoclonus/epilepsy, in 308 patients with increased SEPs amplitude from upper limb stimulation. METHODS: We compared cortical response (N20p-P25p) in different groups of patients identified by demographic, clinical, and neurophysiological factors and performed a cluster analysis for classifying the natural occurrence of subgroups of patients. RESULTS: No significant differences of N20p-P25p were found among different age-dependent groups, and in patients with or without PNS/CNS abnormalities of sensory pathways, while myoclonic/epileptic patients showed higher N20p-P25p than other groups. Cluster analysis identified four clusters of patients including myoclonus/epilepsy, central sensory abnormalities, peripheral sensory abnormalities, and absence of myoclonus and sensory abnormalities. CONCLUSIONS: Increased N20p-P25p prompts different possible pathophysiological substrates: larger N20p-P25p in patients with cortical myoclonus and/or epilepsy is likely sustained by strong cortical hyperexcitability, while milder increase of N20p-P25p could be underpinned by plastic cortical changes following abnormalities of sensory pathways, or degenerative process involving the cortex. SEPs increased in amplitude cannot be considered an exclusive hallmark of myoclonus/epilepsy. Indeed, in several neurological disorders, it may represent a sign of adaptive, plastic, and/or degenerative cortical changes.

Does observance of Ramadan affect sleep in athletes and physically active individuals? A systematic review and meta-analysis.

The purpose of this systematic review and meta-analysis is to provide an accurate description of the effect of Ramadan observance on sleep duration, sleep quality, daily nap duration, and daytime sleepiness in athletes and physically active individuals. Five electronic databases (PubMed, Web of Science, Scopus, Wiley, and Taylor and Francis) were used to search for relevant studies conducted with athletes or physically active individuals during Ramadan, published in any language, and available before May 23, 2021. Studies that included assessments of sleep quantity and/or quality, and/or daytime sleepiness, and/or daily naps in athletes and physically active individuals were included. The methodological quality of the studies was assessed using "QualSyst". Of the 18 papers included in this study (298 participants in total), 14 were of strong quality, two were moderate, and the remaining two were rated as weak. Individuals who continued to train during Ramadan experienced a decrease in sleep duration (number of studies, K = 17, number of participants, N = 289, g = -0.766, 95% confidence interval [CI] -1.199 to -0.333, p = 0.001). Additionally, the global score of the Pittsburgh Sleep Quality Index increased from 4.053 (K = 5, N = 65, 95% CI 3.071-5.034) pre-Ramadan, to 5.346 (95% CI 4.362-6.333) during Ramadan, indicating a decrease in sleep quality. The duration of daytime naps increased during compared to pre-Ramadan (K = 2, N = 31, g = 1.020, 95% CI 0.595-1.445, p = 0.000), whereas Epworth Sleepiness Scale scores remained unchanged during versus pre-Ramadan (K = 3, N = 31, g = 0.190, 95% CI -0.139-0.519, p = 0.257). In conclusion, individuals who continued to train during Ramadan experienced a decrease in sleep duration, impairment of sleep quality, and increase in daytime nap duration, with no change in daytime sleepiness levels.

Diagnosis and treatment of Chiari malformation type 1 in children: the International Consensus Document.

BACKGROUND: Chiari malformation type 1 (CM1) is a rare condition where agreed classification and treatment are still missing. The goal of this study is to achieve a consensus on the diagnosis and treatment of CM1 in children. METHODS: A multidisciplinary panel formulated 57 provisional statements based on a review of the literature. Thirty-four international experts (IE) participated in a Delphi study by independently rating each statement on a 4-point Likert scale ("strongly disagree," "disagree," "agree," "strongly agree"). Statements that were endorsed ("agree" or "strongly agree") by < 75% of raters were re-formulated, or new statements were added, and another Delphi round followed (up to a maximum of three). RESULTS: Thirty-five IE were contacted and 34 agreed to participate. A consensus was reached on 30/57 statements (52.6%) after round 1. Three statements were added, and one removed. After round 2, agreement was reached on 56/59 statements (94.9%). Finally, after round 3, which took place during the 2019 Chiari Consensus Conference (Milan, Italy), agreement was reached on 58/59 statements (98.3%) about four main sections (Definition and Classification, Planning, Surgery, Isolated Syringomyelia). Only one statement did not gain a consensus, which is the "definition of radiological failure 24 month post-surgery." CONCLUSIONS: The consensus document consists of 58 statements (24 on diagnosis, 34 on treatment), serving clinicians and researchers following children with CM1. There is a clear need for establishing an international network and registry and to promote collaborative studies to increase the evidence base and optimize the long-term care of this patient population.

Role of sleep deprivation in immune-related disease risk and outcomes.

Modern societies are experiencing an increasing trend of reduced sleep duration, with nocturnal sleeping time below the recommended ranges for health. Epidemiological and laboratory studies have demonstrated detrimental effects of sleep deprivation on health. Sleep exerts an immune-supportive function, promoting host defense against infection and inflammatory insults. Sleep deprivation has been associated with alterations of innate and adaptive immune parameters, leading to a chronic inflammatory state and an increased risk for infectious/inflammatory pathologies, including cardiometabolic, neoplastic, autoimmune and neurodegenerative diseases. Here, we review recent advancements on the immune responses to sleep deprivation as evidenced by experimental and epidemiological studies, the pathophysiology, and the role for the sleep deprivation-induced immune changes in increasing the risk for chronic diseases. Gaps in knowledge and methodological pitfalls still remain. Further understanding of the causal relationship between sleep deprivation and immune deregulation would help to identify individuals at risk for disease and to prevent adverse health outcomes.

Global, regional, and national burden of Guillain-Barré syndrome and its underlying causes from 1990 to 2019.

BACKGROUND: This article presents the first detailed analysis of the prevalence and disability burden of Guillain-Barré syndrome (GBS) from 1990 to 2019 by cause, age, sex, and Socio-demographic Index (SDI) in 204 countries and territories. METHODS: Data from the Global Burden of Diseases Study (GBD) 2019 were used. GBD 2019 modelled the prevalence of GBS using hospital and claims data. Years lived with disability (YLDs) were estimated as the product of the GBS prevalence and the disability weight. This article also reported proportions in the age-standardised prevalence rate that were due to six underlying causes of GBS. RESULTS: In 2019, there were 150,095 [95% uncertainty intervals (UI) 119,924 to 188,309] total cases of GBS worldwide, which resulted in 44,407 (95% UI 28,016 to 64,777) YLDs. Globally, there was a 6.4% (95% UI 3.6 to 9.5) increase in the age-standardised prevalence of GBS per 100,000 population between 1990 and 2019. High-income Asia Pacific [1.9 (95% UI: 1.5 to 2.4)] and East Asia [0.8 (95% UI: 0.6 to 1.0)] had the highest and lowest age-standardised prevalence rates (per 100,000), respectively, in 2019. Nationally, Japan [6.4 (95% UI: 5.3 to 7.7)] and China [0.8 (95% UI: 0.6 to 1.0)] had the highest and lowest age-standardised prevalence rates (per 100,000). The age-standardised burden of GBS increased with increasing age and was higher in males in all age groups. Furthermore, the age-standardised prevalence of GBS (per 100,000) had a positive association with the level of development, as measured by SDI, although this association was not strong. Upper respiratory infections and unknown causes accounted for the highest proportions of underlying causes. CONCLUSIONS: Globally, the prevalence of GBS continues to increase. Geographical differences and strategies aimed at preventing infectious diseases should be considered in future health policy planning and decision-making processes. This study had several limitations, such as using the same disability weight for all causes and a reliance on hospital- and self-reported data, which should be addressed in future research.

Recurrence, Reactivation, or Inflammatory Rebound of SARS-CoV-2 Infection With Acute Vestibular Symptoms: A Case Report and Revision of Literature.

A case of recurrent coronavirus disease 2019 (COVID-19) with neurovestibular symptoms was reported. In March 2020, a physician working in an Italian pediatric hospital had flu-like symptoms with anosmia and dysgeusia, and following a reverse transcription PCR (RT/PCR) test with a nasopharyngeal swab tested positive for SARS-CoV-2. After home quarantine, 21 days from the beginning of the symptoms, the patient tested negative in two subsequent swabs and was declared healed and readmitted to work. Serological testing showed a low level of immunoglobulin G (IgG) antibody title and absence of immunoglobulin M (IgM). However, 2 weeks later, before resuming work, the patient complained of acute vestibular syndrome, and the RT/PCR test with mucosal swab turned positive. On the basis of the literature examined and reviewed for recurrence cases and vestibular symptoms during COVID-19, to our knowledge this case is the first case of recurrence with vestibular impairment as a neurological symptom, and we defined it as probably a viral reactivation. The PCR retest positivity cannot differentiate re-infectivity, relapse, and dead-viral RNA detection. Serological antibody testing and viral genome sequencing could be always performed in recurrence cases.

Occupational Injuries and Use of Benzodiazepines: A Systematic Review and Metanalysis.

Background: Benzodiazepines have been widely used in clinical practice for over four decades and continue to be one of the most consumed and highly prescribed class of drugs available in the treatment of anxiety, depression, and insomnia. The literature indicates that Benzodiazepine users at a significantly increased risk of Motor Vehicle accidents compared to non-users but the impact on injuries at workplace is not well-defined. We aimed to investigate whether use of benzodiazepine is associated with increased risk of occupational injuries (OI). Methods: PubMed, Embase, and Scopus databases were searched. A meta-analysis was performed to calculate odds ratio (OR) and 95% confidence interval (CI) among case controls, cross-sectional studies, either questionnaire or laboratory exams based. Results: A total of 13 studies met inclusion criteria, involving 324,168 OI from seven different countries, with an estimated occurrence of benzodiazepine positivity of 2.71% (95% CI 1.45-4.98). A total of 14 estimates were retrieved. Of them, 10 were based on laboratory analyses, three on institutional databases, while one study was based on questionnaires. Regarding the occupational groups, three estimates focused on commercial drivers (0.73%, 95% CI 0.12-4.30), that exhibited a reduced risk ratio for benzodiazepine positivity compared to other occupational groups (RR 0.109, 95% CI 0.063-0.187). Eventually, no increased risk for benzodiazepine positivity was identified, either from case control studies (OR 1.520, 95% CI 0.801-2.885, I 2 76%), or cross sectional studies, when only laboratory based estimates were taken in account (OR 0.590, 95% CI 0.253-1.377, I 2 63%). Conclusions: Even though benzodiazepines have the potential to increase injury rates among casual and chronic users, available evidence are insufficient to sustain this hypothesis, particularly when focusing on laboratory-based studies (i.e., studies the characterized the benzodiazepine immediately before the event).

The heterozygous deletion c.1509_1510delAG in exon 14 of FUS causes an aggressive childhood-onset ALS with cognitive impairment.

We report a case of childhood-onset ALS with a FUS gene mutation presenting cognitive impairment and a rapid clinical progression. The patient, an 11-year-old girl, presented with right distal upper limb weakness and mild intellectual disability at the Griffith Mental Development Scales. The disease rapidly worsened and the patient became tetraplegic and bed-ridden 2 years after symptom onset. A c.1509_1510delAG mutation in exon 14 of the FUS gene was detected, resulting in a predicted truncated protein, p.G504Wfs*12, lacking the nuclear localization signal. The levels of FUS mRNA in the proband were not significantly different compared to controls. Western immunoblot analysis showed that one antibody (500-526) detected in the proband ~50% of the amount of FUS protein compared to controls, while 3 other antibodies (2-27, 400-450 and FUS C-terminal), which recognize both wild type and the mutated FUS, detected 60% to 75% of the amount of the protein. These findings indicate that p.G504Wfs*12 FUS is more prone to undergo post-translational modification respect to wild type FUS.

CSF sphingomyelin: a new biomarker of demyelination in the diagnosis and management of CIDP and GBS.

OBJECTIVE: To validate sphingomyelin (SM) dosage in the cerebrospinal fluid (CSF) of patients affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain-Barré syndrome (GBS) as a reliably assessable biomarker. METHODS: We prospectively enrolled 184 patients from six Italian referral centres, in whom CSF SM levels were quantified by a fluorescence-based assay optimised and patented in our laboratory. RESULTS: We confirmed increased levels of SM in the CSF of patients affected by typical CIDP (n=35), atypical CIDP (n=18) and acute inflammatory demyelinating polyradiculoneuropathy, AIDP (n=12) compared with patients affected by non-demyelinating neurological diseases, used as controls (n=85) (p<0.0001, p=0.0065 and p<0.0001, respectively). In patients with CIDP classified for disease stage, SM was higher in active CIDP compared with both controls and stable CIDP (p<0.0001), applying for a selective tool to treatment tailoring or withdrawal. SM was also increased in AIDP compared with axonal GBS, discerning the demyelinating from axonal variant of the disease. SM did not correlate with CSF protein levels, stratifying patients independently from commonly used CSF indexes, and displaying high specificity to avoid potential misdiagnosis. Finally, SM correlated with the main clinical scores and some neurophysiological parameters in patients with CIDP and AIDP. CONCLUSIONS: CSF SM is a diagnostic and staging wet biomarker for acquired demyelinating neuropathies and may effectively improve the management of patients affected by GBS and CIDP.