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Background and Objectives: There is growing evidence of the contribution of neuroinflammation, and in particular microglia, in the pathogenesis of amyotrophic lateral sclerosis (ALS). TREM2 gene plays a crucial role in shaping microglia in neurodegenerative conditions. To deepen the understanding of TREM2 in ALS and investigate the performance of TREM2 as a biomarker, we profiled TREM2 expression levels in spinal cord, cerebrospinal fluid and blood of patients with sporadic ALS. We also wanted to investigate whether the combined measurement of sTREM2 in fluids could improve the diagnostic yield of total and phosphorylated TDP-43 levels., Methods: We performed a case-control study to profile overall and transcript-specific TREM2 mRNA levels by RT-qPCR and protein expression levels by Western-blot in postmortem specimens of spinal cord from ALS patients and controls. In parallel, we measured soluble TREM2 (sTREM2) protein levels and full length and phosphorylated TDP-43 (tTDP-43 and pTDP-43) by ELISA in CSF and serum from ALS patients vs healthy controls. Patients were prospectively recruited from an ALS unit of a tertiary hospital and fulfilled El Escorial revised criteria. After bivariate analysis, a logistic regression model was developed to identify adjusted estimates of the association of sTREM2 levels in CSF and serum with ALS status., Results: Overall and transcript-specific TREM2 mRNA were upregulated in the spinal cord of ALS patients (n = 21) compared to controls (n = 19). Similar changes were observed in TREM2 protein levels (p < 0.01) in spinal cord of ALS patients vs healthy controls. We also detected significantly higher sTREM2 levels in CSF (p-value < 0.01) of ALS patients (n = 46) vs controls (n = 46) and serum (p-value < 0.001) of ALS patients (n = 100) vs controls (n = 100). In a logistic regression model, both CSF and serum sTREM2 remained independently associated with ALS status with OR = 3.41 (CI 95 %=1.34-8.66) (p-value < 0.05) and OR = 3.38 (CI 95 %: 1.86-6.16) (p-value < 0.001), respectively. We also observed that pTDP-43 levels in CSF is an independent predictor of ALS (p-value < 0.05)., Conclusions: Our results support the role of TREM2 in ALS pathophysiology and demonstrates that the three TREM2 transcripts are deregulated in ALS in postmortem human specimens of spinal cord. We hypothesise about the possible influence of systemic-peripheral inflammation in the disease. Finally, we conclude that pTDP-43 levels in CSF could be a biomarker of ALS, and sTREM2 measurement in CSF and blood emerge as potential non-invasive biomarker in ALS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Median nerve somatosensory evoked potentials (SEPs) may present changes during cavernous malformation (CM) resection unrelated to new post-operative sensory deficits. We performed intraoperative neurophysiological monitoring of median SEPs (m-SEPs) in three patients who underwent CM resection (surgery) near the sensory-motor cortex. The only preoperative clinical manifestations in all patients were seizures. All patients presented m-SEPs alterations on the side of the lesion during the procedure. Two patients presented permanent changes in the cortical potentials. In the third patient, the cortical and subcortical components suffered temporal fluctuations to return to baselines at the end of the surgery. None of these patients developed new post-operative clinical deficits. During brain cavernous malformation resection, significant fluctuations in the amplitude of different components of m-SEPs may occur. These changes may be due to excitability variations on m-SEP generators and do not translate into new post-operative neurological deficits., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: To correlate intraoperative changes of the laryngeal adductor reflex (LAR), alone or in combination with corticobulbar motor evoked potential of vocal muscles (vocal-CoMEPs), with postoperative laryngeal function after posterior fossa and brainstem surgery., Methods: We monitored 53 patients during cerebellar-pontine angle and brainstem surgeries. Vocal-CoMEPs and LAR were recorded from an endotracheal tube with imbedded electrodes or hook-wires electrodes. A LAR significant change (LAR-SC) defined as ≥ 50% amplitude decrement or loss, was classified as either transient or permanent injury to the vagus or medullary pathways by the end of the surgery., Results: All patients with permanent LAR loss (n = 5) or LAR-SC (n = 3), developed postoperative laryngeal dysfunction such as aspiration/pneumonia and permanent swallowing deficits (5.6%). Vocal-CoMEP findings refined postoperative vocal motor dysfunction. All seven patients with transient LAR-SC or loss, reverted by changing the surgical approach, did not present permanent deficits., Conclusions: Permanent LAR-SCs or loss correlated with postoperative laryngeal dysfunction and predicted motor and sensory dysfunction of the vagus nerve and reflexive medullary pathways. In contrast, a LAR-SC or loss, averted by a timely surgical adjustment, prevented irreversible damage., Significance: Monitoring of the LAR, with vocal-CoMEPs, may enhance safety to resect complex posterior fossa and brainstem lesions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The discovery of new biomarkers would be very valuable to improve the detection of early Alzheimer's disease (AD). DNA methylation marks may serve as epigenetic biomarkers of early AD. Here we identified epigenetic marks that are present in the human hippocampus from the earliest stages of AD. A previous methylome dataset of the human AD hippocampus was used to select a set of eight differentially methylated positions (DMPs) since early AD stages. Next, bisulphite pyrosequencing was performed in an expanded homogeneous cohort of 18 pure controls and 35 hippocampal samples with neuropathological changes of pure AD. Correlation between DNA methylation levels in DMPs and phospho-tau protein burden assessed by immunohistochemistry in the hippocampus was also determined. We found four DMPs showing higher levels of DNA methylation at early AD stages compared to controls, involving ELOVL2, GIT1/TP53I13 and the histone gene locus at chromosome 6. DNA methylation levels assessed by bisulphite pyrosequencing correlated with phospho-tau protein burden for ELOVL2 and HIST1H3E/HIST1H3 F genes. In this discovery study, a set of four epigenetic marks of early AD stages have been identified in the human hippocampus. It would be worth studying in-depth the specific pathways related to these epigenetic marks. These early alterations in DNA methylation in the AD hippocampus could be regarded as candidate biomarkers to be explored in future translational studies., Abbreviations: AD: Alzheimer's disease; DMPs: Differentially methylated positions; CSF: Cerebrospinal fluid; βA42: β-amyloid 42; PET: positron emission tomography; 5mC: 5-methyl cytosine; CpG: cytosine-guanine dinucleotides; ANK1 : ankyrin-1; BIN1 : amphiphysin II; p-tau: hyperphosphorylated tau; CERAD: Consortium to Establish A Registry for Alzheimer's Disease; SD: standard deviation; ANOVA: one-way analysis of variance; VLCFAs: very long-chain fatty acids; DHA: docosahexaenoic acid; mTOR: mechanistic target of rapamycin.

Background: The role of the microglia-related gene triggering receptor expressed in myeloid cells 2 (TREM2) in primary tauopathies, such as progressive supranuclear palsy (PSP), still remains unclear., Objectives: The objective of this study was to profile overall and transcript-specific TREM2 expression levels in the substantia nigra (SN) of PSP patients and controls., Methods: SN samples from neuropathologically confirmed PSP cases (n = 24) and controls (n = 14) were used to measure TREM2 and TREM2-modulating gene Membrane-spanning 4-domains subfamily A member 4A (MS4A4A) mRNA levels by real-time quantitative polymerase chain reaction. Correlation with hyperphosphorylated tau protein burden was assessed., Results: Overall TREM2 and each of the 3 TREM2 transcripts mRNA levels were significantly increased in the SN of PSP cases versus controls. TREM2 mRNA levels positively correlated with hyperphosphorylated tau burden in SN, specifically in neurons. The MS4A4A gene was also upregulated in PSP patients versus controls., Conclusions: These results add evidence to the involvement of microglia in the disease process of PSP. These findings support the idea that different tauopathies may share common patterns of deregulation in innate immune molecular pathways. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)

The article Is the new ASNM intraoperative neuromonitoring supervision "guideline" a trustworthy guideline? A commentary, written by Stanley A. Skinner, Elif Ilgaz Aydinlar, Lawrence F. Borges, Bob S. Carter, Bradford L. Currier, Vedran Deletis, Charles Dong, John Paul Dormans, Gea Drost, Isabel Fernandez‑Conejero, E. Matthew Hoffman, Robert N. Holdefer, Paulo Andre Teixeira Kimaid, Antoun Koht, Karl F. Kothbauer, David B. MacDonald, John J. McAuliffe III, David E. Morledge, Susan H. Morris, Jonathan Norton, Klaus Novak, Kyung Seok Park, Joseph H. Perra, Julian Prell, David M. Rippe, Francesco Sala, Daniel M. Schwartz, Martín J. Segura, Kathleen Seidel, Christoph Seubert, Mirela V. Simon, Francisco Soto, Jeffrey A. Strommen, Andrea Szelenyi, Armando Tello, Sedat Ulkatan, Javier Urriza and Marshall Wilkinson, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 05 January 2019 without open access. With the author(s)' decision to opt for Open Choice the copyright of the article changed on 30 January 2019 to © The Author(s) 2019 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made. The original article has been corrected.

Objective: To improve the recognition and possibly prevent confounding peripheral activation of the facial nerve caused by leaking transcranial electrical stimulation (TES) current during corticobulbar tract monitoring., Methods: We applied a single stimulus and a short train of electrical stimuli directly to the extracranial portion of the facial nerve. We compared the peripherally elicited compound muscle action potential (CMAP) of the facial nerve with the responses elicited by TES during intraoperative monitoring of the corticobulbar tract., Results: A single stimulus applied directly to the facial nerve at subthreshold intensities did not evoke a CMAP, whereas short trains of subthreshold stimuli repeatedly evoked CMAPs. This is due to the phenomenon of sub- or near-threshold super excitability of the cranial nerve. Therefore, the facial responses evoked by short trains TES, when the leaked current reaches the facial nerve at sub- or near-threshold intensity, could lead to false interpretation., Conclusions: Our results revealed a potential pitfall in the current methodology for facial corticobulbar tract monitoring that is due to the activation of the facial nerve by subthreshold trains of stimuli. This study proposes a new criterion to exclude peripheral activation during corticobulbar tract monitoring., Significance: The failure to recognize and avoid facial nerve activation due to leaking current in the peripheral portion of the facial nerve during TES decreases the reliability of corticobulbar tract monitoring by increasing the possibility of false interpretation., (Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Narcolepsy is a disease that involves an alteration in the generation and organisation of sleep. The main symptoms are excessive daytime sleepiness and cataplexy, followed by hypnagogic hallucinations, sleep paralysis and disrupted nocturnal sleep. The prevalence of typical narcolepsy oscillates between 25-50: 100.000 in general. Recently there has been a peak incidence in patients born in the month of March. According to the new classification, the Multiple Sleep Latency Test (MSLT) is mandatory for diagnosing narcolepsy without cataplexy, and advisable for diagnosing narcolepsy with cataplexy. Until now, the attempt has been made to control each symptom by its own specific treatment. At present, new American and European treatment guidelines propose new drugs that act on all the symptoms. The application of new criteria of diagnosis and treatment has improved the diagnosis, giving better options of treatment.

Until now, there have been no reports on eliciting the blink reflex (BR) during anesthesia at a depth compatible with surgery. We introduce a novel method for eliciting the R1 component of the BR under inhalation or total intravenous anesthesia by using a short train of four to seven stimuli applied over the supraorbital nerve. Recording is done from the ipsilateral orbicularis oculi muscle. We set out to record the BR in 27 patients (age 1-78 years) without involvement of the facial nerve, trigeminal nerve, or brainstem. The BR could not be recorded in only 4 patients (recordability: 86.2%). All patients received at least one bolus of propofol while in surgery. Using this method, the BR was recorded on 4 awake healthy subjects. Boluses of propofol and muscle relaxants should be avoided in order to successfully record the responses. BR recording is feasible in patients under general anesthesia by using this novel technique. Muscle Nerve 39: 642-646, 2009.

Summary: Introduction. Nonsystemic vasculitic neuropathy (NSVN) is an inflammatory disorder of the vasa nervorum which usually is expressed as a mononeuritis multiplex. We present a patient with NSVN with histological confirmination focused on the neurophysiological findings at the early stages., Case Report: A 36 years-old woman presented with paresthesia and weakness in her right hand followed by left footdrop. The first neurophysiologic examination showed low amplitude of the right median nerve (RMN) CMAP with proximal stimulation. A second examination showed signs of axonal damage in several nerves, including the RMN., Conclusions: The acute ischemic damage of a nerve can give a pattern of conduction block in the electroneurographic study as in the RMN of the presented case. This phenomenon is referred as "pseudo-conduction block", since it is transient and evolves towards a definite pattern of axonal neuropathy. When a vasculitic neuropathy is suspected, repeated neurophysiologic studies are necessary in order to ensure a proper (appropriate) characterization of the lesional patterns.

Intraoperative neurophysiological monitoring (IONM) makes it possible to determine the status of neurological function during surgery. It guides the surgeon and minimises the risk of injury. This paper describes the different techniques available for IONM in spine surgery (somatosensory evoked potentials, motor evoked potentials, neurography, electromyography, reflexes and dermatomic evoked potentials), which neurophysiologists employ depending on the nerve structures at risk. In order for monitoring to be successful, coordination between all members of the surgical team is essential. In the event of IONM registering alterations, the neurophysiologist must first check the integrity of the recording system. The anaesthetist should then assess blood pressure, oxygen levels, ventilation and haematocrit values, and revert recent anaesthetic changes. Finally, the surgeon must stop the procedure and try to determine the cause of the event, and correct it if possible.

IONM uses different neurophysiological techniques during surgery time, thus avoiding possible lesions to the neurological structures, making surgery safer and better. We describe two types of IONM: mapping techniques and monitoring techniques, as well as their advantages, disadvantages and complications. We look into the more useful techniques in this field, as well as providing orientation about its use according to the surgical areas and the neurological structures under risk. In conclusion, we affirm that IONM is one of the most important advances in modern neurosurgery.

Summary: A small series of high-frequency wavelets overlapping the earliest part of the N20 wave (high-frequency oscillations, HFOs) can be observed in the somatosensory evoked potentials (SSEPs) of normal subjects after filtering then with a high-pass filter (>500 Hz). These HFOs have been related to interneuronal activity in the primary somatosensory cortex. In patients with cortical myoclonus there is a sensorimotor cortical hyperexcitability, expressed neurophysiologically as high-amplitude waves in the SSEPs (giant SSEPs). There have been contradicting reports in the literature on the changes in the HFOs in these patients. The authors studied HFOs in a group of 20 patients with cortical myoclonus of different origins and in a control group by means of time-frequency transforms, comparing the results obtained with the amplitude and latency of the classical SSEP waves. All controls had normal HFOs, with two components. Nine patients had no HFOs, nine patients had low-amplitude and/or delayed HFOs, and the remaining two patients, the only without ataxia, had high-amplitude HFOs with a long latency. These results suggest heterogeneity in the pathophysiology of cortical myoclonus, which might be related to the different systems affected.

Neurocysticerosis is an affection of the central nervous system by the larvae of the Taenia solium. Although its diagnosis in our country is exceptional, in recent years a notable increase in the number of cases diagnosed has been observed, due to the phenomenon of immigration from countries where the disease is endemic. The most frequent form of presentation of neurocysticercosis is seizures, followed by headache. To diagnose it we must evaluate the epidemiological data, the clinical record and confirm this through neuroimage and immunological studies. The treatment selected should be pharmacological, principally with albendazole, and surgery reserved for cases where the former fails. Hygienic measures and the treatment of patients with teniasis are of great importance. Neurocysticerosis has ceased to be an exceptional diagnosis and given the foreseeable increase of its incidence in our milieu, health professionals must understand this disease and include it at higher levels of the algorithms of differential diagnosis.

Objective: We review the mechanisms that may involved in the pathophysiology of dystonia., Development: The role of basal ganglia, spinal and brainstem interneurons, and primary motor cortex in dystonia will be discussed. Abnormalities in the discharge pattern of internal pallidum or thalamus, secondary to basal ganglia disorders might be the cause of disbalance between excitatory and inhibitory mechanisms in motor cortex. Other factors such as excessive repetition of a movement or abnormal sensory afferent discharges may be participating in cortical reorganization., Conclusions: Overlapping of the cortical representation of dystonic muscles due to enlargement of cortical maps could explain overflow and co-contraction phenomena. The study of the exact role of these factors in each type of dystonia is a challenge for the future that opens the door for new therapeutic approaches.

Introduction: Digital treatment of electrical signals coming from the central nervous system on stimulation of the optic nerve path offers an objective method for evaluation of visual evoked potentials (VEP) shown graphically on a cerebral map., Objective: To evaluate the topographical distribution of VEP in cases of optic neuropathy adding this parameter to the usual parameters of latency and amplitude., Material and Methods: We studied 35 patients with suspected optic neuropathy and normal findings on basic ophthalmological examination, in whom VEP and VEP mapping (VEPM) was done., Results: In 26% of the cases there was no response for evaluation with the usual VEP recording techniques, whilst in those with VEPM this percentage was reduced to 11.5%. In the other cases there was a potential with characteristic distribution in the occipital areas and a maximally positive dipole posteriorly., Conclusion: VEPM is an objective method for evaluation of the visual pathway offering better discrimination than the usual VEP in more severe cases of neuropathy.