Background: Acquired critical illness weakness (AWCIP) is the most frequent neuromuscular disease in intensive care medicine departments. Its importance is given by the prolongation of hospital stay and the delayed recovery it causes to patients after hospitalization. The main objective of this study was to investigate the association between neuromuscular blocking agents and the development of acquired weakness in critically ill patients. Material and methods: We conducted a prospective study of 103 critically ill patients who were periodically monitored with electromyography. Results: The development of AWCIP was observed in 63 patients. The group of patients who developed AWCIP had a significantly higher utilization of neuromuscular blocking agents than the group who did not develop AWCIP [79.4% vs 50%, OR:3.85 (1.63-9.39), p < 0.02]; likewise, this group of patients had a longer ICU stay [32 days vs 14 days, OR: 1.11 (1.06-1.17), p < 0. 001] and a longer mechanical ventilation time [24 days vs 9 days, OR:1.2 (1.11-1.32), p < 0.001]. Conclusion: Neuromuscular blocking agents are a factor associated with the occurrence of AWCIP. (c) 2024 Elsevier Espana, S.L.U. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Antecedentes La debilidad adquirida del enfermo crítico (DAEC) es la enfermedad neuromuscular más frecuente en los servicios de medicina intensiva. Su importancia está dada por la prolongación de la estancia hospitalaria y la tardía recuperación que presentan los pacientes después del alta hospitalaria. El objetivo principal de este estudio fue abordar la asociación entre bloqueantes neuromusculares y el desarrollo de debilidad adquirida del enfermo crítico. Material y métodos Realizamos un estudio prospectivo de 103 pacientes críticamente enfermos que fueron monitorizados periódicamente con electromiografía. Resultados La aparición de DAEC se objetivó en 63 pacientes. El grupo que desarrolló DAEC tuvo una utilización de bloqueantes neuromusculares significativamente mayor que el grupo que no desarrolló DAEC (79,4% vs. 50%, OR: 3,85 [1,63-9,39], p<0,02); así mismo, este grupo de pacientes tuvo una estancia en la unidad de cuidados intensivos más prolongada (32 días vs. 14 días, OR: 1,11 [1,06-1,17], p<0,001) y un mayor tiempo de ventilación mecánica (24 días vs. 9 días, OR: 1,2 [1,11-1,32], p<0,001). Conclusión Los bloqueantes neuromusculares son un factor asociado a la aparición de DAEC.

Introduction N20 somatosensory evoked potential (SEP) response shows high predictive accuracy of functional recovery in patients with Acute Ischemic Stroke (AIS) undergoing endovascular thrombectomy (https://www.clinicaltrials.gov/ct2/show/NCT04099615; SVIN Journal, in press). This capacity is independent and even higher than clinical and advanced imaging variables. This study aims to validate BraiN20®, a portable, non‐invasive, AI‐based device to monitor in real‐time the presence and characteristics of N20 in AIS. Methods 65 patients with AIS and anterior Large Vessel Occlusion (LVO) undergoing EVT within 24 hours from onset are included in three comprehensive stroke centers of Catalonia, Spain. Eligibility criteria are no significant pre‐stroke functional dependence, baseline NIHSS score equal or higher than 6 points, occlusion (mTICI 0‐1) of the intracranial ICA, MCA‐M1 or M2 suitable for EVT per local protocols, without infarct volume restrictions measured by ASPECT score or by CTP/DWI‐MRI prior to EVT . The primary objective is to confirm an optimal/good reliability of N20 registration before EVT higher than 75% by two blind expert neurophysiologists, assuming a true proportion equal to 87.5%. Secondary endpoints are the predictive accuracy of N20 response recorded by BraiN20® before and after EVT on functional outcome evaluated by the mRS at 7 and 90 days and analyzed by using Receiving Operating Characteristic curves. A futility interim analysis is planned after the inclusion of 25% of the sample. Results The trial is sponsored by Time is Brain S.L. and will start early September 2023. Primary endpoint results are expected by the end of this year. Conclusion BraiN20® could be a useful medical device to predict salvageable brain and functional recovery of patients along the stroke chain.

Background Somatosensory evoked potentials may add substantial prognostic value in patients with acute ischemic stroke and contribute to the selection of patients who may benefit from revascularization therapies beyond the accepted therapeutic time windows. We aimed to study the prognostic accuracy of the N20 somatosensory evoked potential component of the ischemic hemisphere in patients with anterior large‐vessel occlusion undergoing endovascular thrombectomy (EVT). Methods Presence and amplitude of the N20 response were recorded before and after EVT. Its adjusted predictive value for functional independence (modified Rankin scale score, ≤2) at day 7 was analyzed by binary logistic regression adjusting by age, mean arterial blood pressure, National Institute of Health Stroke Scale, Alberta Stroke Program Early CT Score, and serum glucose. N20 predictive power was compared with that of clinical and imaging models by using receiver operating characteristics curve analysis. Results A total of 223 consecutive patients were studied (mean age, 70 years; median National Institute of Health Stroke Scale score, 18). Somatosensory evoked potential recordings identified the presence of N20 in 110 (49.3%), absence in 58 (26%), and not assessable in 55 patients due to radiofrequency interferences in the angiography room. Before EVT, N20 predicted functional independence with a sensitivity of 93% (95% CI, 78%–98%) and negative predictive value of 93% (95% CI, 80%–98%). The adjusted odds ratio for functional independence was 9.9 (95% CI, 3.1–44.6). In receiver operating characteristics curve analysis, N20 amplitude showed a higher area under the curve than prehospital or in‐hospital variables, including advanced imaging. Sensitivity increased to 100% (95% CI, 0.85–1) when N20 was present after EVT. Conclusion Somatosensory evoked potential monitoring is a noninvasive and bedside technique that could help eligibility of patients with acute ischemic stroke for EVT and predict functional recovery.

INTRODUCTION:The phrenic nerve could be easily injured during cardiothoracic surgeries because of its anatomical relationships. The aim of this study is to describe a new, feasible, and reproducible methodology to achieve a continuous intraoperative neuromonitoring of the phrenic nerve.METHODS:Consecutive patients who underwent open-chest surgery were included. The recording active electrode was placed 5 cm superior to the tip of the xiphoid process, and a hook wire inserted at the motor point of the ipsilateral hemidiaphragm was used as the reference electrode.RESULTS:We studied 45 patients (92% men, mean age 67 years). Mean height and weight were 167 ± 6.9 cm and 75.6 ± 12.3 kg, respectively. A reproducible compound motor action potential was recorded in 38 (85%) subjects. The mean latency and amplitude values were 9.68 ± 2.40 ms and 1.36 ± 3.83 mV, respectively. No intraoperative events were recorded.CONCLUSIONS:We reported a new methodology which allows the assessment of phrenic nerve functional integrity during surgical procedures.

Myotonic Dystrophy type 1 (DM1) is a muscular dystrophy with a multi-systemic nature. It was one of the first diseases in which repeat associated non-ATG (RAN) translation was described in 2011, but has not been further explored since. In order to enhance our knowledge of RAN translation in DM1, we decided to study the presence of DM1 antisense (DM1-AS) transcripts (the origin of the polyglutamine (polyGln) RAN protein) using RT-PCR and FISH, and that of RAN translation via immunoblotting and immunofluorescence in distinct DM1 primary cell cultures, e.g., myoblasts, skin fibroblasts and lymphoblastoids, from ten patients. DM1-AS transcripts were found in all DM1 cells, with a lower expression in patients compared to controls. Antisense RNA foci were found in the nuclei and cytoplasm of a subset of DM1 cells. The polyGln RAN protein was undetectable in all three cell types with both approaches. Immunoblots revealed a 42 kD polyGln containing protein, which was most likely the TATA-box-binding protein. Immunofluorescence revealed a cytoplasmic aggregate, which co-localized with the Golgi apparatus. Taken together, DM1-AS transcript levels were lower in patients compared to controls and a small portion of the transcripts included the expanded repeat. However, RAN translation was not present in patient-derived DM1 cells, or was in undetectable quantities for the available methods.

OBJECTIVE:We aimed to determine whether 3D imaging reconstruction allows identifying molecular:clinical associations in myotonic dystrophy type 1 (DM1).METHODS:We obtained myoblasts from 6 patients with DM1 and 6 controls. We measured cytosine-thymine-guanine (CTG) expansion and detected RNA foci and muscleblind like 1 (MBNL1) through 3D reconstruction. We studied dystrophia myotonica protein kinase (DMPK) expression and splicing alterations of MBNL1, insulin receptor, and sarcoplasmic reticulum Ca(2+)-ATPase 1.RESULTS:Three-dimensional analysis showed that RNA foci (nuclear and/or cytoplasmic) were present in 45%-100% of DM1-derived myoblasts we studied (range: 0-6 foci per cell). RNA foci represented <0.6% of the total myoblast nuclear volume. CTG expansion size was associated with the number of RNA foci per myoblast (r = 0.876 [95% confidence interval 0.222-0.986]) as well as with the number of cytoplasmic RNA foci (r = 0.943 [0.559-0.994]). Although MBNL1 colocalized with RNA foci in all DM1 myoblast cell lines, colocalization only accounted for 1% of total MBNL1 expression, with the absence of DM1 alternative splicing patterns. The number of RNA foci was associated with DMPK expression (r = 0.967 [0.079-0.999]). On the other hand, the number of cytoplasmic RNA foci was correlated with the age at disease onset (r = -0.818 [-0.979 to 0.019]).CONCLUSIONS:CTG expansion size modulates RNA foci number in myoblasts derived from patients with DM1. MBNL1 sequestration plays only a minor role in the pathobiology of the disease in these cells. Higher number of cytoplasmic RNA foci is related to an early onset of the disease, a finding that should be corroborated in future studies.

Ischemic lumbosacral plexopathy secondary to an acute aortic dissection is a rare condition that is usually unilateral and frequently accompanied by a simultaneous spinal cord infarction. The functional prognosis relies on the severity of the nervous system involvement being usually worse when the spinal cord is involved. We present a case of a 46-year-old man who suffered an acute type B aortic dissection presenting as acute paraplegia due to bilateral ischemic lumbosacral plexopathy treated with thoracic endovascular aortic repair. An up-to-date review of the literature on ischemic lumbosacral plexus injury is provided.

Introduction: Critical illness myopathy (CIM) and polyneuropathy (CIP) are the most common cause of acquired weakness in intensive care units (ICU).However, its exact pathogenesis remains unclear.Abnormal excitability of muscle due to a sodium channelopathy is one of the mechanisms proposed.The aim of this study is to test for the presence of anti-ganglioside antibodies in serum from patients with CIM or both combined CIM/CIP, since there is evidence that they can cause reversible dysfunction of voltage-gated sodium channels.Methods: In a prospective way, we studied 35 patients admitted in ICU by weekly EMG.When positive spontaneous activity (PSA) was detected, a muscle biopsy was performed.Twenty patients met criteria of CIM; five of them also developed overlapping CIP.We did not detect any kind of abnormality in 10 patients during the follow up period.Sera were analyzed for the presence of antiganglioside antibodies (Ganglioside-profile 2 Euroline, Euroimmun).Results: Overall, positive reactivity against anti-GT1b was found in one patient with CIM, representing 2.8% (1/35) of the total sample.Conclusion: Reduced percentage of patients affected of CIM or CIM/CIP exhibits positive reactive against anti-ganglioside antibodies.Thus, it could be suggested they do not play a primary role in their pathogenesis.

The number of cytosine-thymine-guanine (CTG) repeats (‘CTG expansion size’) in the 3′untranslated region (UTR) region of the dystrophia myotonica-protein kinase (DMPK) gene is a hallmark of myotonic dystrophy type 1 (DM1), which has been related to age of disease onset and clinical severity. However, accurate determination of CTG expansion size is challenging due to its characteristic instability. We compared five different approaches (heat pulse extension polymerase chain reaction [PCR], long PCR-Southern blot [with three different primers sets—1, 2 and 3] and small pool [SP]-PCR) to estimate CTG expansion size in the progenitor allele as well as the most abundant CTG expansion size, in 15 patients with DM1. Our results indicated variability between the methods (although we found no overall differences between long PCR 1 and 2 and SP-PCR, respectively). While keeping in mind the limited sample size of our patient cohort, SP-PCR appeared as the most suitable technique, with an inverse significant correlation found between CTG expansion size of the progenitor allele, as determined by this method, and age of disease onset (r = −0.734, p = 0.016). Yet, in light of the variability of the results obtained with the different methods, we propose that an international agreement is needed to determine which is the most suitable method for assessing CTG expansion size in DM1.

Myotonic Dystrophy type 1 (DM1) is characterized by a high genetic and clinical variability. Determination of the genetic variability in DM1 might help to determine whether there is an association between CTG (Cytosine-Thymine-Guanine) expansion and the clinical manifestations of this condition. We studied the variability of the CTG expansion (progenitor, mode, and longest allele, respectively, and genetic instability) in three tissues (blood, muscle, and tissue) from eight patients with DM1. We also studied the association of genetic data with the patients’ clinical characteristics. Although genetic instability was confirmed in all the tissues that we studied, our results suggest that CTG expansion is larger in muscle and skin cells compared with peripheral blood leukocytes. While keeping in mind that more research is needed in larger cohorts, we have provided preliminary evidence suggesting that the estimated progenitor CTG size in muscle could be potentially used as an indicator of age of disease onset and muscle function impairment.

We aimed to determine whether 3D imaging reconstruction allows identifying molecular:clinical associations in myotonic dystrophy type 1 (DM1).We obtained myoblasts from 6 patients with DM1 and 6 controls. We measured cytosine-thymine-guanine (CTG) expansion and detected RNA foci and muscleblind like 1 (MBNL1) through 3D reconstruction. We studied dystrophia myotonica protein kinase (DMPK) expression and splicing alterations of MBNL1, insulin receptor, and sarcoplasmic reticulum Ca(2+)-ATPase 1.Three-dimensional analysis showed that RNA foci (nuclear and/or cytoplasmic) were present in 45%-100% of DM1-derived myoblasts we studied (range: 0-6 foci per cell). RNA foci represented <0.6% of the total myoblast nuclear volume. CTG expansion size was associated with the number of RNA foci per myoblast (r = 0.876 [95% confidence interval 0.222-0.986]) as well as with the number of cytoplasmic RNA foci (r = 0.943 [0.559-0.994]). Although MBNL1 colocalized with RNA foci in all DM1 myoblast cell lines, colocalization only accounted for 1% of total MBNL1 expression, with the absence of DM1 alternative splicing patterns. The number of RNA foci was associated with DMPK expression (r = 0.967 [0.079-0.999]). On the other hand, the number of cytoplasmic RNA foci was correlated with the age at disease onset (r = -0.818 [-0.979 to 0.019]).CTG expansion size modulates RNA foci number in myoblasts derived from patients with DM1. MBNL1 sequestration plays only a minor role in the pathobiology of the disease in these cells. Higher number of cytoplasmic RNA foci is related to an early onset of the disease, a finding that should be corroborated in future studies.

Late onset Pompe disease (LOPD) is a genetic disorder characterized by slowly progressive skeletal and respiratory muscle weakness. Symptomatic patients are treated with enzyme replacement therapy (ERT) with alglucosidase alpha (rhGAA). Although most of ERT treated patients develop antibodies against rhGAA, their influence on clinical progression is not completely known. We studied the impact of anti-rhGAA antibodies on clinical progression of 25 ERT treated patients. We evaluated patients at visit 0 and, after 1 year, at visit 1. We performed several muscle function tests, conventional spirometry and quantitative muscle MRI (qMRI) using 3-point Dixon analysis of thigh muscles at both visits. We also obtained serum samples at both visits and anti-rhGAA antibodies were quantified using ELISA. Antibody titers higher than 1:200 were identified in 18 patients (72%) of our cohort. Seven patients (28%) did not develop antibodies (0 to < 1:200), 17 patients (68%) developed low to intermediate titers (1:200 to < 1:31,200) and 1 patient (4%) developed high titers ( > 1:31,200). We analyzed the effect of low and intermediate antibody titers in clinical and radiological progression. There were no differences between the results of muscle function tests, spirometry or fat fraction analyzed using qMRI between patients with and without antibodies groups at baseline. Moreover, antibody titers did not influence muscle function test, spirometry results or qMRI results at year 1 visit. Most of the LOPD patients developed antibodies against ERT that persisted over time at low or intermediate levels. However, antibodies at these low and intermediate titers might not influence clinical response to the drug.

Carriage of interruptions in CTG repeats of the myotonic dystrophy protein kinase gene has been associated with a broad spectrum of myotonic dystrophy type 1 (DM1) phenotypes, mostly mild. However, the data available on interrupted DM1 patients and their phenotype are scarce. We studied 49 Spanish DM1 patients, whose clinical phenotype was evaluated in depth. Blood DNA was obtained and analyzed through triplet-primed polymerase chain reaction (PCR), long PCR-Southern blot, small pool PCR, AciI digestion, and sequencing. Five patients of our registry (10%), belonging to the same family, carried CCG interruptions at the 3'-end of the CTG expansion. Some of them presented atypical traits such as very late onset of symptoms ( > 50 years) and a severe axial and proximal weakness requiring walking assistance. They also showed classic DM1 symptoms including cardiac and respiratory dysfunction, which were severe in some of them. Sizes and interrupted allele patterns were determined, and we found a contraction and an expansion in two intergenerational transmissions. Our study contributes to the observation that DM1 patients carrying interruptions present with atypical clinical features that can make DM1 diagnosis difficult, with a later than expected age of onset and a previously unreported aging-related severe disease manifestation.

OBJECTIVE:Hemispatial neglect is a frequent condition usually following nondominant hemispheric brain injury. It strongly affects rehabilitation strategies and everyday life activities. It is associated with behavioral and cognitive disability with a strong impact on patient's life.METHODS:We reviewed the published literature on the use of noninvasive brain stimulation, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), and of noninvasive peripheral muscle stimulation, as therapeutic strategies for rehabilitation of neglect after acquired brain injury, such as in stroke or in traumatic injuries. The studies were grouped as controlled or uncontrolled studies in each stimulation techniques.RESULTS:Thirty-four studies were identified and 16 on rTMS, 10 on tDCS, and 8 on vibration. All studies were conducted in adult patients who suffered a stroke, except for one that was conducted in a patient suffering traumatic acquired brain injury and another that was conducted in a patient with brain tumor. In spite of significant variability in treatment protocols, patients' features and assessment of neglect, improvement was reported in almost all studies with no side-effects.CONCLUSIONS:Noninvasive brain stimulation and neuromuscular vibration are promising therapeutic neuromodulatory approaches for neglect. Further randomized-controlled studies are needed to corroborate their effectiveness as separate and combined techniques.

McArdle disease is a disorder of muscle glycogen metabolism caused by mutations in the PYGM gene, encoding for the muscle-specific isoform of glycogen phosphorylase (M-GP). The activity of this enzyme is completely lost in patients' muscle biopsies, when measured with a standard biochemical test which, does not allow to determine M-GP protein levels. We aimed to determine M-GP protein levels in the muscle of McArdle patients, by studying biopsies of 40 patients harboring a broad spectrum of PYGM mutations and 22 controls. Lack of M-GP protein was found in muscle in the vast majority (95%) of patients, irrespective of the PYGM genotype, including those carrying missense mutations, with few exceptions. M-GP protein biosynthesis is not being produced by PYGM mutations inducing premature termination codons (PTC), neither by most PYGM missense mutations. These findings explain the lack of PYGM genotype-phenotype correlation and have important implications for the design of molecular-based therapeutic approaches.

McArdle disease is an autosomal recessive condition caused by deficiency of the PYGM gene-encoded muscle isoform of glycogen phosphorylase. Some cases of "manifesting" heterozygotes or carriers (i.e., patients who show some McArdle-like symptoms or signs despite being carriers of only one mutated PYGM allele) have been reported in the literature but there is controversy, with misdiagnosis being a possibility. The purpose of our study was to determine if there are actually "manifesting" heterozygotes of McArdle disease and, if existing, whether statin treatment can trigger such condition. Eighty-one relatives of McArdle patients (among a total of 16 different families) were studied. We determined whether they were carriers of PYGM mutations and also collected information on exercise tests (second wind and modified Wingate anaerobic test) and statin intake. We found 50 carriers and 31 non-carriers of PYGM mutations. Although we found existence of heterozygotes manifesting some exercise-related muscle problems such as exacerbated myalgia or weakness, they only accounted for 14% of the carriers and muscle symptoms were milder than those commonly reported in patients. Further, no carrier (whether reporting symptoms or not) showed the second wind phenomenon or a flat blood lactate response to maximal-intensity exercise, both of which are hallmarks of McArdle disease. On the other hand, statin myotoxicity was not associated with muscle symptom onset.

Valosin-containing protein (VCP) is a ubiquitous protein, being broadly expressed in several human body systems [ [1] Watts G.D.J. Wymer J. Kovach M.J. Mehta S.G. Mumm S. Darvish D. et al. Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nat Genet. 2004 Apr 21; 36 ([Internet]. [cited 2017 May 8]. Available from:): 377-381http://www.nature.com/doifinder/10.1038/ng1332 Crossref PubMed Scopus (1119) Google Scholar ]. More than 45 missense mutations in the VCP gene have been associated with several disease conditions, collectively known as ‘multisystem proteinopathies’: these include early-onset Paget disease of the bone (PDB), myopathy with rimmed vacuoles or inclusion body myopathy (IBM), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS) [ [2] Weihl C.C. Pestronk A. Kimonis V.E. Valosin-containing protein disease: Inclusion body myopathy with Paget?s disease of the bone and fronto-temporal dementia. Neuromuscul Disord. 2009 May; 19 ([Internet]. [Cited 2017 Jun 16]. Available from): 308-315http://www.ncbi.nlm.nih.gov/pubmed/19380227 Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar , [3] Al-Obeidi E. Al-Tahan S. Surampalli A. Goyal N. Wang A.K. Hermann A. et al. Genotype-phenotype study in patients with valosin-containing protein mutations associated with multisystem proteinopathy. Clin. Genet. 2018; 93: 119-125 Crossref PubMed Scopus (63) Google Scholar ]. Myopathy is the most common clinical feature of these conditions, mainly affecting proximal muscles. Here, we report a novel mutation in the VCP gene in two related Spanish patients showing an IBM - PDB phenotype.