Surgical management of nervus intermedius neuralgia: A report of 4 cases and literature review.

BACKGROUND: Nervus intermedius neuralgia (NIN) is characterized by paroxysmal episodes of sharp, lancinating pain in the deep ear. Unfortunately, only a few studies exist in the literature on this pain syndrome, its pathology and postoperative outcomes. METHOD: We conducted a retrospective review of four cases diagnosed with NIN who underwent a neurosurgical intervention at our center from January 2015 to January 2023. Detailed information on their MRI examinations, intraoperative findings and other clinical presentations were obtained, and the glossopharyngeal and vagus nerves were isolated for immunohistochemistry examination. RESULTS: A total of 4 NIN patients who underwent a microsurgical intervention at our institution were included in this report. The NI was sectioned in all patients and 3 of them underwent a microvascular decompression. Of these 4 patients, 1 had a concomitant trigeminal neuralgia (TN), and 1 a concomitant glossopharyngeal neuralgia (GPN). Three patients underwent treatment for TN and 2 for GPN. Follow-up assessments ranged from 8 to 99 months. Three patients reported complete pain relief immediately after the surgery until last follow-up, while in the remaining patient the preoperative pain gradually resolved over the 3 month period. Immunohistochemistry revealed that a greater amount of CD4+ and CD8+ T cells had infiltrated the glossopharyngeal versus vagus nerve. CONCLUSIONS: NIN is an extremely rare condition showing a high degree of overlap with TN/GPN. An in depth neurosurgical intervention is effective to completely relieve NIN pain, without any serious complications. It appears that T cells may play regulatory role in the pathophysiology of CN neuralgia.

Application of AI in biological age prediction.

The development of anti-aging interventions requires quantitative measurement of biological age. Machine learning models, known as "aging clocks," are built by leveraging diverse aging biomarkers that vary across lifespan to predict biological age. In addition to traditional aging clocks harnessing epigenetic signatures derived from bulk samples, emerging technologies allow the biological age estimating at single-cell level to dissect cellular diversity in aging tissues. Moreover, imaging-based aging clocks are increasingly employed with the advantage of non-invasive measurement, making it suitable for large-scale human cohort studies. To fully capture the features in the ever-growing multi-modal and high-dimensional aging-related data and uncover disease associations, deep-learning based approaches, which are effective to learn complex and non-linear relationships without relying on pre-defined features, are increasingly applied. The use of big data and AI-based aging clocks has achieved high accuracy, interpretability and generalizability, guiding clinical applications to delay age-related diseases and extend healthy lifespans.

A molecular brake that modulates spliceosome pausing at detained introns contributes to neurodegeneration.

Emerging evidence suggests that intron-detaining transcripts (IDTs) are a nucleus-detained and polyadenylated mRNA pool for cell to quickly and effectively respond to environmental stimuli and stress. However, the underlying mechanisms of detained intron (DI) splicing are still largely unknown. Here, we suggest that post-transcriptional DI splicing is paused at the Bact state, an active spliceosome but not catalytically primed, which depends on Smad Nuclear Interacting Protein 1 (SNIP1) and RNPS1 (a serine-rich RNA binding protein) interaction. RNPS1 and Bact components preferentially dock at DIs and the RNPS1 docking is sufficient to trigger spliceosome pausing. Haploinsufficiency of Snip1 attenuates neurodegeneration and globally rescues IDT accumulation caused by a previously reported mutant U2 snRNA, a basal spliceosomal component. Snip1 conditional knockout in the cerebellum decreases DI splicing efficiency and causes neurodegeneration. Therefore, we suggest that SNIP1 and RNPS1 form a molecular brake to promote spliceosome pausing, and that its misregulation contributes to neurodegeneration.

Comparation of the structural characteristics and biological activities of chondroitin sulfates extracted from notochord and backbone of Chinese sturgeon (Acipenser sinensis).

To compare the structural properties and biological activities of chondroitin sulfate (CS) in two different tissues of Chinese sturgeon (Acipenser sinensis) and Russian sturgeon (Acipenser gueldenstaedti), we extracted their backbone cartilage CS (Cart-CS) and notochord CS (Noto-CS), and analyzed the CS structural properties using chromatographic and spectroscopic methods. The molecular weights of Chinese sturgeon Cart-CS and Noto-CS were 54.7 and 25.4 kDa, respectively, and the molecular weights of Russian sturgeon were 50.0 and 38.4 kDa, respectively. The disaccharide composition results showed that Cart-CS was mainly composed of CS-C, while Noto-CS was almost composed of pure CS-A. The antioxidant activity of sturgeon CS and its effect on collagen fibril formation were discussed. Sturgeon CS exhibited higher antioxidant activity than shark and bovine CSs. Sturgeon CS inhibited the self-assemble of type I collagen into fibrils. The inhibition effect of Cart-CS was higher than that of Noto-CS. The high value-added utilization of Cart-CS and Noto-CS will increase the value of sturgeon by-products. Furthermore, the disaccharide composition of CS in sturgeon depends on tissues of origin, but not on species. It means that the CS of Chinese sturgeon can be substituted by the CS of other commercial sturgeon. That will contribute to the protection of endangered species of Chinese sturgeon from illegal fishing and increase the value of commercial sturgeon by-products.

Optimizing the Optical Absorption of Poly(heptazine imide) by the n → π* Electron Transition for Improved Photocatalytic H2 Evolution.

Poly(heptazine imide) (abbreviated as PHI), a heptazine-based crystalline carbon nitride photocatalyst, has attracted widespread attention in the photocatalytic H2 evolution benefiting from its high crystallinity. Nevertheless, the optical absorption range of the directly synthesized PHI is generally narrow, which severely hinders the utilization of visible light. Much research aimed to extend the optical absorption range of PHI; however, either the optimization degree was insufficient or the synthesis process was cumbersome. Herein, red PHI (RPHI) for improving the photocatalytic H2 evolution was facilely synthesized by the one step method. The optimal RPHI sample possesses an obvious new absorption band of the n → π* electron transition and exhibits a significantly enhanced photocatalytic H2 evolution rate of 169 µmol h-1 (λ > 510 nm) and 46 µmol h-1 (λ > 600 nm), which is about 5 times (λ > 510 nm) and 7.7 times (λ > 600 nm) that of pristine PHI and surpasses most reported RPHIs. This work may promote the development of the PHI photocatalyst for near-infrared photocatalytic H2 production.

Dual-gRNA approach with limited off-target effect corrects C9ORF72 repeat expansion in vivo.

C9ORF72 GGGGCC repeat expansion is the most common genetic cause for amyotrophic lateral sclerosis and frontotemporal dementia, which generates abnormal DNA and RNA structures and produces toxic proteins. Recently, efficacy of CRISPR/Cas9-mediated editing has been proven in treatment of disease. However, DNA low complexity surrounding C9ORF72 expansion increases the off-target risks. Here we provide a dual-gRNA design outside of the low complexity region which enables us to remove the repeat DNA in a 'cutting-deletion-fusion' manner with a high fusion efficiency (50%). Our dual-gRNA design limits off-target effect and does not significantly affect C9ORF72 expression. In neurons carrying patient C9ORF72 expansion, our approach removes the repeat DNA and corrects the RNA foci in vitro and in vivo. Therefore, we conclude that our proof-of-concept design correct C9ORF72 repeat expansion, which may have potential therapeutic value for the patients.

ROS1-mediated decrease in DNA methylation and increase in expression of defense genes and stress response genes in Arabidopsis thaliana due to abiotic stresses.

BACKGROUND: Small interfering RNAs (siRNAs) target homologous genomic DNA sequences for cytosine methylation, known as RNA-directed DNA methylation (RdDM), plays an important role in transposon control and regulation of gene expression in plants. Repressor of silencing 1 (ROS1) can negatively regulate the RdDM pathway. RESULTS: In this paper, we investigated the molecular mechanisms by which an upstream regulator ACD6 in the salicylic acid (SA) defense pathway, an ABA pathway-related gene ACO3, and GSTF14, an endogenous gene of the glutathione S-transferase superfamily, were induced by various abiotic stresses. The results demonstrated that abiotic stresses, including water deficit, cold, and salt stresses, induced demethylation of the repeats in the promoters of ACD6, ACO3, and GSTF14 and transcriptionally activated their expression. Furthermore, our results revealed that ROS1-mediated DNA demethylation plays an important role in the process of transcriptional activation of ACD6 and GSTF14 when Arabidopsis plants are subjected to cold stress. CONCLUSIONS: This study revealed that ROS1 plays an important role in the molecular mechanisms associated with genes involved in defense pathways in response to abiotic stresses.

The Clinical Characteristics and Surgical Treatment of Glossopharyngeal Neuralgia With Pain Radiating to the Innervated Area of the Trigeminal Nerve.

OBJECTIVE: The aim of this study was to investigate the clinical characteristics and surgical outcome of microvascular decompression (MVD) with or without glossopharyngeal nerve and partial vagus nerve rhizotomy for treating glossopharyngeal neuralgia (GPN) patients with pain radiating to the area innervated by the trigeminal nerve. METHODS: A retrospective review was performed to collect the clinical data from GPN patients who had pain in the area innervated by the glossopharyngeal and vagus nerves and radiating to the innervated area of the trigeminal nerve. All patients underwent surgical treatment. The immediate and long-term outcomes were investigated to show the efficacy and safety of the treatment. Information on pain recurrence and complications was collected. RESULTS: Fourteen patients were recruited. The pain area radiated to the trigeminal nerve distribution, including the anterior auricle (57.1%), temple (50%), cheek (28.6%), mandibular gingiva (42.9%), and anterior part of the tongue (14.3%). Swallowing was the most common trigger (85.7%) in these patients. Seven patients underwent MVD of the offending vessel at the root entry zone (REZ) of the glossopharyngeal and vagus nerves. Seven patients underwent MVD plus glossopharyngeal nerve rhizotomy with or without partial vagus nerve rhizotomy. Thirteen patients experienced complete pain relief during the follow-up (mean 49.3 months). CONCLUSIONS: GPN patients with pain radiating to the area innervated by the trigeminal nerve could be successfully treated solely by management of the glossopharyngeal and vagus nerves. In these GPN patients, differential diagnosis is extremely important to identify the true diagnosis, which would reduce the occurrence of iatrogenic injury of the trigeminal nerve during treatment.

In vivo stress granule misprocessing evidenced in a FUS knock-in ALS mouse model.

Many RNA-binding proteins, including TDP-43, FUS, and TIA1, are stress granule components, dysfunction of which causes amyotrophic lateral sclerosis (ALS). However, whether a mutant RNA-binding protein disrupts stress granule processing in vivo in pathogenesis is unknown. Here we establish a FUS ALS mutation, p.R521C, knock-in mouse model that carries impaired motor ability and late-onset motor neuron loss. In disease-susceptible neurons, stress induces mislocalization of mutant FUS into stress granules and upregulation of ubiquitin, two hallmarks of disease pathology. Additionally, stress aggravates motor performance decline in the mutant mouse. By using two-photon imaging in TIA1-EGFP transduced animals, we document more intensely TIA1-EGFP-positive granules formed hours but cleared weeks after stress challenge in neurons in the mutant cortex. Moreover, neurons with severe granule misprocessing die days after stress challenge. Therefore, we argue that stress granule misprocessing is pathogenic in ALS, and the model we provide here is sound for further disease mechanistic study.

The viral suppressor HCPro decreases DNA methylation and activates auxin biosynthesis genes.

Auxin has profound effects on plant growth and development. In addition to participating in plant growth and development, the auxin signaling pathway is involved in plant defense against pathogens. In this study, we investigated the molecular mechanism by which helper-component protease (HCPro) encoded by the Tobacco vein banding mosaic virus (TVBMV) activates auxin biosynthesis genes (YUCs) and interferes with the auxin signaling pathway. Our results demonstrated that the viral suppressor HCPro decreased the DNA methylation of dispersed repeats (DRs) within the promoters of YUC1, YUC5 and YUC10 and transcriptional activated these YUC genes targeted by RNA-directed DNA methylation (RdDM), leading to an increase in auxin accumulation in plants. Furthermore, we found that the induction of these YUCs by HCPro was attenuated in ros1 mutant plants, suggesting that HCPro-mediated transcriptional activation of the genes was partly dependent on ROS1-mediated DNA demethylation.

N-terminal truncated carboxypeptidase E represses E-cadherin expression in lung cancer by stabilizing the Snail-HDAC complex.

The N-terminal truncated carboxypeptidase E (CPEΔN) protein, an alternative splicing product of the carboxypeptidase E gene, has recently been recognized as an independent predictor for the recurrence and metastasis of lung adenocarcinoma. In this study, we showed that CPEΔN may accelerate lung cancer invasion via an E-cadherin-dependent mechanism. In vitro experiments and in vivo bioluminescence imaging assay revealed CPEΔN promoted the mobility and invasion of human lung cancer cells by suppressing endogenous expression of E-cadherin, a critical regulator for epithelial tissue homeostasis. Further mechanistic analyses revealed that CPEΔN directly interacted with and stabilized the Snail/HDAC1/HDAC3 complex within the promoter region of the E-cadherin-encoding CDH1 gene. CPEΔN overexpression led to a reduction of histone H3K9 acetylation and an increase of H3K9 and H3K27 trimethylation in the CHD1 gene promoter and ultimately inhibited E-cadherin transcription. In addition, correlations among CPEΔN, E-cadherin expression and tumor progression in 195 cases of lung adenocarcinoma patients were analyzed. Higher nuclear expression of CPEΔN was detected in patients with advanced stage of lung adenocarcinoma. Nuclear expression of CPEΔN was negatively correlated with the cell membrane expression of E-cadherin. Collectively, our findings illustrated that CPEΔN was involved in the transcriptional regulation of the epithelial-mesenchymal transition-related gene CDH1 and provide novel insights into CPEΔN-associated lung cancer metastasis.

Effects of phosphate ion concentration on in-vitro fibrillogenesis of sturgeon type I collagen.

Nonmammalian collagens have attracted significant attention owing to their potential for use as a source of cell scaffolds for tissue engineering. Since the morphology of collagen fibrils controls cell proliferation and differentiation, its regulation is essential for fabricating scaffolds with desirable characteristics. In this study, we evaluated the effects of the phosphate ion (Pi) concentration on the characteristics of fibrils formed from swim bladder type I collagen (SBC) and skin type I collagen (SC) from the Bester sturgeon. An increase in the Pi concentration decreased the fibril formation rate, promoted the formation of thick fibrils, and increased the thermal stability of the fibrils for both SBC and SC. However, the SBC and SC fibrils exhibited different fibril formation rates, degrees of fibrillogenesis, morphologies, and denaturation temperatures for the same reaction conditions. Finally, by regulating the Pi concentration, various types of SBC and SC fibrils could be coated on cell culture wells, and fibroblasts could be cultured on them. The results showed that thin fibrils enhance fibroblast extension and proliferation, whereas thick fibrils restrain fibroblast extension but orient them in the same direction. The results of this study suggest that SBC fibrils, which exhibit diverse morphologies, are suitable for use as a novel scaffold material, whose characteristics can be tailored readily by varying the Pi concentration.

Silencing MicroRNA-134 Alleviates Hippocampal Damage and Occurrence of Spontaneous Seizures After Intraventricular Kainic Acid-Induced Status Epilepticus in Rats.

Epilepsy is a disorder of abnormal brain activity typified by spontaneous and recurrent seizures. MicroRNAs (miRNAs) are short non-coding RNAs, critical for the post-transcriptional regulation of gene expression. MiRNA dysregulation has previously been implicated in the induction of epilepsy. In this study, we examined the effect of silencing miR-134 against status epilepticus (SE). Our results showed that level of miR-134 was significantly up-regulated in rat brain after Kainic acid (KA)-induced SE. TUNEL staining showed that silencing miR-134 alleviated seizure-induced neuronal apoptosis in the CA3 subfield of the hippocampus. Western blot showed that a miR-134 antagonist suppressed lesion-induced endoplasmic reticulum (ER) stress and apoptosis related expression of CHOP, Bim and Cytochrome C, while facilitated the expression of CREB at 24 h post KA-induced lesion in the hippocampus. Consistently, silencing miR-134 significantly diminished loss of CA3 pyramidal neurons using Nissl staining as well as reducing aberrant mossy fiber sprouting (MFS) in a rat epileptic model. In addition, the results of EEG and behavior analyses showed seizures were alleviated by miR-134 antagonist in our experimental models. These results suggest that silencing miR-134 modulates the epileptic phenotype by upregulating its target gene, CREB. This in turn attenuates oxidative and ER stress, inhibits apoptosis, and decreases MFS long term. This indicates that silencing miR-134 might be a promising intervention for the treatment of epilepsy.

The effect of alkaline pretreatment on the biochemical characteristics and fibril-forming abilities of types I and II collagen extracted from bester sturgeon by-products.

Non-mammalian collagens have attracted increasing attention for industrial and biomedical use. We have therefore evaluated extraction conditions and the biochemical properties of collagens from aquacultured sturgeon. Pepsin-soluble type I and type II collagen were respectively extracted from the skin and notochord of bester sturgeon by-products, with yields of 63.9 ±â€¯0.19% and 35.5 ±â€¯0.68%. Collagen extraction efficiency was improved by an alkaline pretreatment of the skin and notochord (fewer extraction cycles were required), but the final yields decreased to 56.2 ±â€¯0.84% for type I and 31.8 ±â€¯1.13% for type II. Alkaline pretreatment did not affect the thermal stability or triple-helical structure of both types of collagen. Types I and II collagen formed re-assembled fibril structures in vitro, under different conditions. Alkaline pretreatment slowed down the formation of type I collagen fibrils and specifically inhibited the formation of thick fibril-bundle structures. In contrast, alkaline pretreatment did not change type II collagen fibril formation. In conclusion, alkaline pretreatment of sturgeon skin and notochord is an effective method to accelerate collagen extraction process of types I and II collagen without changing their biochemical properties. However, it decreases the yield of both collagens and specifically changes the fibril-forming ability of type I collagen.

Anterior nucleus of thalamus stimulation inhibited abnormal mossy fiber sprouting in kainic acid-induced epileptic rats.

BACKGROUND: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) has demonstrated antiepileptic efficacy, especially for mesial temporal lobe epilepsy (MTLE). Mossy fiber sprouting (MFS) is involved in the pathogenesis of MTLE, and Sema-3A and GAP-43 are pivotal regulators of MFS. This study investigated the effects of ANT-DBS on MFS and expression levels of Sema-3A and GAP-43 as a possible mechanism for seizure suppression. METHODS: Adult male Sprague-Dawley rats were randomly divided into four groups: (1) control (saline injection), (2) KA (kainic acid injection), (3) KA + Sham-DBS (electrode implantation without stimulation), and (4) KA + DBS (electrode implantation with stimulation). Video electroencephalography (EEG) was used to ensure model establishment and monitor seizure frequency, latency, and severity (Racine stage). Chronic ANT stimulation was conducted for 35 days in the KA + DBS group, and MFS compared to the other groups by quantitative Timm staining. Sema-3A and GAP-43 expression levels in the hippocampal formation were evaluated in all groups with western blot. RESULTS: The latency period was significantly prolonged and spontaneous seizure frequency reduced in the KA + DBS group compared to KA and KA + Sham-DBS groups. Staining scores for MFS in CA3 and dentate gyrus (DG) were significantly lower in the KA + DBS group. The KA + DBS group also exhibited decreased GAP-43 expression and increased Sema-3A expression compared to KA and KA + Sham-DBS groups. CONCLUSION: These results suggest that ANT-DBS extends the latent period following epileptogenic stimulation by impeding MFS through modulation of GAP-43 and Sema-3A expression.

Solution Growth of Two-Dimensional Bi2Se3 Nanosheets for Two-Color All-Optical Switching.

Two-dimensional Bi2Se3 nanosheets with hexagonal shape are synthesized by a solution synthetic route. The Bi2Se3 nanosheets are 120 nm in edge width and 7 nm in thickness. The size of the Bi2Se3 nanosheets can be controlled by choosing different kinds of reducing agents including hydroxylamine and ethylenediamine. Subsequently, we demonstrate a configuration of two-color all-optical switching based on plasma channels effect using the as-synthesized Bi2Se3 nanosheets as an optical media. The signal light can be modulated as two states including dot and ring shape by changing the intensity of control light. The modulated signal light exhibits excellent spatial propagation properties. As a type of interesting optical material, ultrathin two-dimensional Bi2Se3 nanosheets might provide an effective option for photoelectric applications.

Antagomirs Targeting MicroRNA-134 Increase Limk1 Levels After Experimental Seizures in Vitro and in Vivo.

BACKGROUND: MiR-134 is enriched in dendrites of hippocampal neurons and plays crucial roles in the progress of epilepsy. The present study aims to investigate the effects of antagomirs targeting miroRNA-134 (Ant-134) on limk1 expression and the binding of miR-134 and limk1 in experimental seizure. METHODS: Status epilepticus (SE) rat model was established by lithium chloride-pilocarpine injection and was treated with Ant-134 by intracerebroventricular injection. Low Mg2+-exposed primary neurons were used as an in vitro model of SE. The expression of miR-134 was determined using real-time PCR. Protein expressions of limk1 and cofilin were determined by Western blotting. Luciferase reporter assay was used to examine the binding between miR-134 and limk1 3'-untranslated region. RESULTS: The expression of miR-134 was markedly enhanced in hippocampus of the SE rats and low Mg2+-exposed neurons. Ant-134 increased the expression of limk1 and reduced the expression of cofilin in the SE hippocampus and Low Mg2+-exposed neurons. In addition, luciferase reporter assay confirmed that miR-134 bound limk1 3'-UTR. MiR-134 overexpression inhibited limk1 mRNA and protein expressions in neurons. CONCLUSION: Blockage of miR-134 upregulates limk1 expression and downregulated cofilin expression in hippocampus of the SE rats. This mechanism may contribute to the neuroprotective effects of Ant-134.

Antagomirs Targeting MiroRNA-134 Attenuates Epilepsy in Rats through Regulation of Oxidative Stress, Mitochondrial Functions and Autophagy.

The effects of the existing anti-epileptic drugs are unsatisfactory to almost one third of epileptic patients. MiR-134 antagomirs prevent pilocarpine-induced status epilepticus. In this study, a lithium chloride-pilocarpine-induced status epilepticus model was established and treated with intracerebroventricular injection of antagomirs targeting miR-134 (Ant-134). The Ant-134 treatment significantly improved the performance of rats in Morris water maze tests, inhibited mossy fiber sprouting in the dentate gyrus, and increased the survival neurons in the hippocampal CA1 region. Silencing of miR-134 remarkably decreased malonaldehyde and 4-hydroxynonenal levels and increased superoxide dismutase activity in the hippocampus. The Ant-134 treatment also significantly increased the production of ATP and the activities of mitochondrial respiratory enzyme complexes and significantly decreased the reactive oxygen species generation in the hippocampus compared with the status epilepticus rats. Finally, the Ant-134 treatment remarkably downregulated the hippocampal expressions of autophagy-associated proteins Atg5, beclin-1 and light chain 3B. In conclusion, Ant-134 attenuates epilepsy via inhibiting oxidative stress, improving mitochondrial functions and regulating autophagy in the hippocampus.

Stereoelectroencephalography based on the Leksell stereotactic frame and Neurotech operation planning software.

This study aimed to introduce a new stereoelectroencephalography (SEEG) system based on Leksell stereotactic frame (L-SEEG) as well as Neurotech operation planning software, and to investigate its safety, applicability, and reliability.L-SEEG, without the help of navigation, includes SEEG operation planning software (Neurotech), Leksell stereotactic frame, and corresponding surgical instruments. Neurotech operation planning software can be used to display three-dimensional images of the cortex and cortical vessels and to plan the intracranial electrode implantation. In 44 refractory epilepsy patients, 364 intracranial electrodes were implanted through the L-SEEG system, and the postoperative complications such as bleeding, cerebral spinal fluid (CSF) leakage, infection, and electrode-related problems were also investigated.All electrodes were implanted accurately as preoperatively planned shown by postoperative lamina computed tomography and preoperative lamina magnetic resonance imaging. There was no severe complication after intracranial electrode implantation through the L-SEEG system. There were no electrode-related problems, no CSF leakage and no infection after surgery. All the patients recovered favorably after SEEG electrode implantation, and only 1 patient had asymptomatic frontal lateral ventricle hematoma (3 mL).The L-SEEG system with Neurotech operation planning software can be used for safe, accurate, and reliable intracranial electrode implantation for SEEG.

Epileptic Zone Resection for Magnetic Resonance Imaging-Negative Refractory Epilepsy Originating from the Primary Motor Cortex.

OBJECTIVE: Because of the balance between achieving complete seizure freedom and minimizing the postoperative neurologic deficits, surgery for refractory epilepsy originating from the primary motor cortex is difficult. Here, we report the outcomes of surgery for magnetic resonance imaging-negative refractory epilepsy originating from the primary motor cortex in a case series. METHODS: Nine patients with refractory epilepsy originating from the primary motor cortex underwent intracranial electrodes implantation after preoperative evaluation. Subdural grid electrodes and depth electrodes were implanted through craniotomy assisted by stereotactic technique. We delineated the epileptic zone and executed tailored resection according to results of intracranial electroencephalography and mapping. The patients were followed up for at least 1 year. Muscle strength was evaluated at different postoperative times (day 1, 2 weeks, and 1 year). RESULTS: Regarding seizure outcome at the last follow-up, Engel class I outcome was achieved in 5 patients, class II was achieved in 3 patients, and class III was achieved in 1 patient. All cases had postoperative hemiparesis of different degree on the first day after operation. Three patients experienced distal muscle strength of single limb with grade 3 or lower and had obvious dysfunction at 1 year after operation. Six patients experienced distal muscle strength of grade 4 or 5 (Medical Research Council 6-point scale) and had no obvious dysfunction at that time. CONCLUSIONS: Most patients of refractory epilepsy originating from the primary motor cortex were seizure free and had no obvious neurologic deficits at follow-up. Epileptogenic zone resection may not always be contraindicated for patients with nonlesional refractory epilepsy originating from the primary motor cortex.