Advancing Intraoperative Neurophysiological Monitoring With Human Reflexes.

Human reflexes are simple motor responses that are automatically elicited by various sensory inputs. These reflexes can provide valuable insights into the functioning of the nervous system, particularly the brainstem and spinal cord. Reflexes involving the brainstem, such as the blink reflex, laryngeal adductor reflex, trigeminal hypoglossal reflex, and masseter H reflex, offer immediate information about the cranial-nerve functionality and the overall state of the brainstem. Similarly, spinal reflexes such as the H reflex of the soleus muscle, posterior root muscle reflexes, and sacral reflexes provide crucial information about the functionality of the spinal cord and peripheral nerves. One of the critical benefits of reflex monitoring is that it can provide continuous feedback without disrupting the surgical process due to no movement being induced in the surgical field. These reflexes can be monitored in real time during surgical procedures to assess the integrity of the nervous system and detect potential neurological damage. It is particularly noteworthy that the reflexes provide motor and sensory information on the functional integrity of nerve fibers and nuclei. This article describes the current techniques used for monitoring various human reflexes and their clinical significance in surgery. We also address important methodological considerations and their impact on surgical safety and patient outcomes. Utilizing these methodologies has the potential to advance or even revolutionize the field of intraoperative continuous monitoring, ultimately leading to improved surgical outcomes and enhanced patient care.

Prognostic factors of first-onset optic neuritis based on diagnostic criteria and antibody status: a multicentre analysis of 427 eyes.

BACKGROUND: Optic neuritis (ON) prognosis is influenced by various factors including attack severity, underlying aetiologies, treatments and consequences of previous episodes. This study, conducted on a large cohort of first ON episodes, aimed to identify unique prognostic factors for each ON subtype, while excluding any potential influence from pre-existing sequelae. METHODS: Patients experiencing their first ON episodes, with complete aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibody testing, and clinical data for applying multiple sclerosis (MS) diagnostic criteria, were enrolled. 427 eyes from 355 patients from 10 hospitals were categorised into four subgroups: neuromyelitis optica with AQP4 IgG (NMOSD-ON), MOG antibody-associated disease (MOGAD-ON), ON in MS (MS-ON) or idiopathic ON (ION). Prognostic factors linked to complete recovery (regaining 20/20 visual acuity (VA)) or moderate recovery (regaining 20/40 VA) were assessed through multivariable Cox regression analysis. RESULTS: VA at nadir emerged as a robust prognostic factor for both complete and moderate recovery, spanning all ON subtypes. Early intravenous methylprednisolone (IVMP) was associated with enhanced complete recovery in NMOSD-ON and MOGAD-ON, but not in MS-ON or ION. Interestingly, in NMOSD-ON, even a slight IVMP delay in IVMP by >3 days had a significant negative impact, whereas a moderate delay up to 7-9 days was permissible in MOGAD-ON. Female sex predicted poor recovery in MOGAD-ON, while older age hindered moderate recovery in NMOSD-ON and ION. CONCLUSION: This comprehensive multicentre analysis on first-onset ON unveils subtype-specific prognostic factors. These insights will assist tailored treatment strategies and patient counselling for ON.

Therapeutic Outcomes and Electrophysiological Biomarkers in Anti-Myelin-Associated Glycoprotein Neuropathy: A Multicenter Cohort Study in South Korea.

BACKGROUND AND PURPOSE: Unlike other immune-mediated neuropathies, anti-myelin-associated glycoprotein (MAG) neuropathy is often refractory to immunotherapy. It is necessary to compare the relative efficacies of various immunotherapies and develop objective biomarkers in order to optimize its clinical management. METHODS: This study recruited 91 patients with high anti-MAG antibody titers from 7 tertiary hospitals in South Korea. We analyzed the baseline characteristics, therapeutic outcomes, and nerve conduction study (NCS) findings of 68 patients and excluded 23 false positive cases. RESULTS: The rate of positive responses to treatment was highest using zanubrutinib (50%) and rituximab (36.4%), followed by corticosteroids (16.7%), immunosuppressants (9.5%), intravenous immunoglobulin (5%), and plasma exchange (0%). Disability and weakness were significantly associated with multiple NCS parameters at the time of diagnosis, especially distal compound muscle action potential (CMAP) amplitudes. Moreover, the longitudinal trajectory of the average CMAP amplitudes paralleled the clinical courses, with a 16.2 percentile decrease as an optimal cutoff for predicting a clinical exacerbation (area under the receiver operating characteristic curve=0.792). CONCLUSIONS: Our study supports the use of NCS as an objective marker for estimating disease burden and tracking clinical changes in patients with anti-MAG neuropathy. We have described the beneficial effects of rituximab and a new drug, zanubrutinib, compared with conventional immunotherapies.

Different cutoff value of motor evoked potentials for the postoperative outcome in the ossification of the posterior longitudinal ligament surgery in the cervical and thoracic spine.

BACKGROUND CONTEXT: Transcranial muscle motor evoked potentials (Tc-mMEPs), a key component of intraoperative neurophysiologic monitoring (IONM), effectively reflect the changes in corticospinal tract integrity and are closely related to the occurrence of the postoperative motor deficit (PMD). Most institutions have applied a specified (fixed) alarm criterion for the heterogeneous groups in terms of etiologies or lesion location. However, given the high risk of PMD in ossification of the posterior longitudinal ligament (OPLL) surgery, it is essential to determine a tailored cutoff value for IONM. PURPOSE: We aimed to establish the intraoperative cutoff value of Tc-mMEPs reduction for predicting PMD in OPLL according to lesion levels. DESIGN: Retrospective analysis using a review of electrical medical records. PATIENT SAMPLE: In this study, we included 126 patients diagnosed with OPLL, who underwent surgery and IONM. OUTCOME MEASURES: The occurrence of PMD immediately and 1 year after operation, as well as the decrement of intraoperative Tc-mMEPs amplitude. METHODS: We analyzed OPLL surgery outcomes using Tc-mMEPs monitoring. Limbs with acceptable baseline Tc-mMEPs in the tibialis anterior or abductor hallucis were included in the final set. PMD was defined as a ≥1 decrease in Medical Research Council score in the legs, and it was evaluated immediately and 1year after operation. The reduction ratios of Tc-mMEPs amplitude compared with baseline value were calculated at the two time points: the maximal decrement during surgery and at the end of surgery. Receiver operating characteristic curve analysis was used to determine the cutoff value of Tc-mMEPs amplitude decrement for predicting PMDs. RESULTS: In total, 203 limbs from 102 patients with cervical OPLL and 42 limbs from 24 patients with thoracic OPLL were included. PMD developed more frequently in thoracic lesions than in cervical lesions (immediate, 9.52% vs. 2.46%; 1 year, 4.76% vs. 0.99%). The Tc-mMEPs amplitude cutoff point at the end of surgery for PMD (both immediate and 1-year) was a decrease of 93% in cervical and 50% in thoracic OPLL surgeries. Similarly, the Tc-mMEPs amplitude cutoff point at the maximal decrement during surgery for PMD (both immediate and 1 year) was a reduction of 97% in cervical and 85% in thoracic OPLL surgeries. CONCLUSIONS: The thoracic lesion exhibited a lower cutoff value than the cervical lesion for both immediate and long-term persistent PMD in OPLL surgery (Tc-mMEPs at the end of surgery measuring 93% vs. 50%; and Tc-mMEPs at the maximal decrement measuring 97% vs. 85% for cervical and thoracic lesions, respectively). To enhance the reliability of monitoring, considering the application of tailored alarm criteria for Tc-mMEPs changes based on lesion location in OPLL could be beneficial.

Protein biomarkers in multiple sclerosis.

This review aimed to elucidate protein biomarkers in body fluids, such as blood and cerebrospinal fluid (CSF), to identify those that may be used for early diagnosis of multiple sclerosis (MS), prediction of disease activity, and monitoring of treatment response among MS patients. The potential biomarkers elucidated in this review include neurofilament proteins (NFs), glial fibrillary acidic protein (GFAP), leptin, brain-derived neurotrophic factor (BDNF), chitinase-3-like protein 1 (CHI3L1), C-X-C motif chemokine 13 (CXCL13), and osteopontin (OPN), with each biomarker playing a different role in MS. GFAP, leptin, and CHI3L1 levels were increased in MS patient groups compared to the control group. NFs are the most studied proteins in the MS field, and significant correlations with disease activity, future progression, and treatment outcomes are evident. GFAP CSF level shows a different pattern by MS subtype. Increased concentration of CHI3L1 in the blood/CSF of clinically isolated syndrome (CIS) is an independent predictive factor of conversion to definite MS. BDNF may be affected by chronic progression of MS. CHI3L1 has potential as a biomarker for early diagnosis of MS and prediction of disability progression, while CXCL13 has potential as a biomarker of prognosis of CIS and reflects MS disease activity. OPN was an indicator of disease severity. A periodic detailed patient evaluation should be performed for MS patients, and broadly and easily accessible biomarkers with higher sensitivity and specificity in clinical settings should be identified.

Early rituximab treatment reduces long-term disability in aquaporin-4 antibody-positive neuromyelitis optica spectrum.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) causes relapsing inflammatory attacks in the central nervous system, leading to disability. As rituximab, a B-lymphocyte-depleting monoclonal antibody, is an effective in preventing NMOSD relapses, we hypothesised that earlier initiation of rituximab can also reduce long-term disability of patients with NMOSD. METHODS: This multicentre retrospective study involving 19 South Korean referral centres included patients with NMOSD with aquaporin-4 antibodies receiving rituximab treatment. Factors associated with the long-term Expanded Disability Status Scale (EDSS) were assessed using multivariable regression analysis. RESULTS: In total, 145 patients with rituximab treatment (mean age of onset, 39.5 years; 88.3% female; 98.6% on immunosuppressants/oral steroids before rituximab treatment; mean disease duration of 121 months) were included. Multivariable analysis revealed that the EDSS at the last follow-up was associated with time to rituximab initiation (interval from first symptom onset to initiation of rituximab treatment). EDSS at the last follow-up was also associated with maximum EDSS before rituximab treatment. In subgroup analysis, the time to initiation of rituximab was associated with EDSS at last follow-up in patients aged less than 50 years, female and those with a maximum EDSS score ≥6 before rituximab treatment. CONCLUSIONS: Earlier initiation of rituximab treatment may prevent long-term disability worsening in patients with NMOSD, especially among those with early to middle-age onset, female sex and severe attacks.

Intraoperative bulbocavernosus reflex monitoring in posterior lumbar fusion surgery.

OBJECTIVE: To assess the utility of intraoperative bulbocavernosus reflex (BCR) monitoring in posterior lumbar fusion surgery. METHODS: We retrospectively evaluated 153 patients undergoing posterior lumbar fusion with intraoperative BCR monitoring. Voiding function was assessed at discharge and two follow-ups. RESULTS: BCR was preserved in 151 patients and completely disappeared in two patients at the end of surgery. For patients in whom BCR was preserved, voiding difficulties at discharge and 1-month and 6-month follow-ups were noted in 16 (10.6%), 9 (6.0%), and 0 (0.0%) patients, respectively. However, patients with BCR loss experienced voiding difficulties at all three time-points. Statistical analysis showed a significant difference in voiding between those with preserved and disappeared BCRs at 6 months postoperatively. BCR disappeared during surgery but recovered before the end of surgery in six patients. Among these patients, one experienced transient voiding difficulties postoperatively but with good recovery. However, the other five patients did not experience postoperative voiding difficulties. CONCLUSIONS: BCR had low sensitivity for voiding dysfunction at discharge, but had high accuracy at 6-month follow-up examinations. BCR loss was associated with new voiding dysfunction. SIGNIFICANCE: Intraoperative BCR monitoring is a potentially useful tool for enhancing safety during posterior lumbar fusion by predicting postoperative voiding dysfunction.

Safety and efficacy of clonazepam in patients with hemifacial spasm: A double-blind, randomized, placebo-controlled trial.

INTRODUCTION: Hemifacial spasm (HFS) is an involuntary intermittent twitching of the facial muscles. Medical and surgical treatments can be considered for HFS. Among medical treatments, clonazepam is a benzodiazepine used to treat epilepsy, psychiatric symptoms, and movement disorders. This study aimed to investigate the efficacy and safety of clonazepam for the treatment of HFS. METHODS: This randomized double-blind placebo-controlled trial prospectively enrolled patients with HFS aged 20-79 years. The patients were randomly assigned in a 1:1 ratio to receive either clonazepam (0.5 mg twice daily) or a placebo for 4 weeks. All participants underwent clinical assessment and laboratory tests at baseline and visit 2. The primary endpoint was the clinical global impression-improvement (CGI-I) score at visit 2. RESULTS: A total of 34 patients with HFS assessed for eligibility were enrolled between April 2015 and November 2016. Among them, two patients were withdrawn before randomization. Thus, the intention-to-treat analysis included 32 patients with HFS. The median CGI-I scores at visit 2 did not differ significantly between the clonazepam (3; range 1-6) and placebo (3.5; range 3-5) groups. In the safety analysis, only mild or no serious adverse events were observed. CONCLUSION: The results of this study demonstrated the safety of clonazepam in patients with HFS. However, clonazepam did not show a statistically significant effect on HFS. Further studies are needed to provide evidence of the clinical benefits in patients with HFS.

Advances in Intraoperative Neurophysiology During Microvascular Decompression Surgery for Hemifacial Spasm.

Microvascular decompression (MVD) is a widely used surgical intervention to relieve the abnormal compression of a facial nerve caused by an artery or vein that results in hemifacial spasm (HFS). Various intraoperative neurophysiologic monitoring (ION) and mapping methodologies have been used since the 1980s, including brainstem auditory evoked potentials, lateral-spread responses, Z-L responses, facial corticobulbar motor evoked potentials, and blink reflexes. These methods have been applied to detect neuronal damage, to optimize the successful decompression of a facial nerve, to predict clinical outcomes, and to identify changes in the excitability of a facial nerve and its nucleus during MVD. This has resulted in multiple studies continuously investigating the clinical application of ION during MVD in patients with HFS. In this study we aimed to review the specific advances in methodologies and clinical research related to ION techniques used in MVD surgery for HFS over the last decade. These advances have enabled clinicians to improve the efficacy and surgical outcomes of MVD, and they provide deeper insight into the pathophysiology of the disease.

Transcriptome-based variant calling and aberrant mRNA discovery enhance diagnostic efficiency for neuromuscular diseases.

BACKGROUND: Whole-exome sequencing-based diagnosis of rare diseases typically yields 40%-50% of success rate. Precise diagnosis of the patients with neuromuscular disorders (NMDs) has been hampered by locus heterogeneity or phenotypic heterogeneity. We evaluated the utility of transcriptome sequencing as an independent approach in diagnosing NMDs. METHODS: The RNA sequencing (RNA-Seq) of muscle tissues from 117 Korean patients with suspected Mendelian NMD was performed to evaluate the ability to detect pathogenic variants. Aberrant splicing and CNVs were inspected to identify additional causal genetic factors for NMD. Aberrant splicing events in Dystrophin (DMD) were investigated by using antisense oligonucleotides (ASOs). A non-negative matrix factorisation analysis of the transcriptome data followed by cell type deconvolution was performed to cluster samples by expression-based signatures and identify cluster-specific gene ontologies. RESULTS: Our pipeline called 38.1% of pathogenic variants exclusively from the muscle transcriptomes, demonstrating a higher diagnostic rate than that achieved via exome analysis (34.9%). The discovery of variants causing aberrant splicing allowed the application of ASOs to the patient-derived cells, providing a therapeutic approach tailored to individual patients. RNA-Seq data further enabled sample clustering by distinct gene expression profiles that corresponded to clinical parameters, conferring additional advantages over exome sequencing. CONCLUSION: The RNA-Seq-based diagnosis of NMDs achieves an increased diagnostic rate and provided pathogenic status information, which is not easily accessible through exome analysis.

The utility of intraoperative neurophysiological monitoring in surgical treatment for spinal arteriovenous malformations: A historical control study.

OBJECTIVE: This study sought to investigate the utility of intraoperative neurophysiological monitoring (IONM) in the surgical treatment for spinal arteriovenous malformations (SAVMs). METHODS: We retrospectively reviewed the data of 39 patients who underwent surgical treatment for SAVMs. Twenty-eight patients who received multimodal IONM (transcranial electrical motor-evoked potentials [MEPs], somatosensory-evoked potentials, continuous electromyography, and bulbocavernosus reflex [BCR]) between 2011 and 2020 were compared to 11 historical controls between 2003 and 2011. The rates of postoperative neurological deficits (PNDs), neurophysiological warnings, and their characteristics were analyzed. RESULTS: PNDs were developed in 10.7% and 54.5% of patients in the IONM and historical control (non-IONM) groups, respectively (p = 0.008). Moreover, not applying IONM was the only significant risk factor for the development of PNDs in the logistic regression analysis (odds ratio 10.0, p = 0.007). In the IONM group, a total of three electrophysiological warnings were observed, and two of these were true positives; one patient complained of leg motor weakness after surgery with loss of the abductor halluces MEPs. The other patient experienced disappearance of the BCR during surgery and newly developed urinary retention. Overall, the sensitivity, specificity, positive predictive value, and negative predictive value of IONM warnings for detecting PNDs were 66.7%, 96.0%, 66.7%, and 96.0%, respectively. CONCLUSIONS: The neurological outcome of the IONM group was significantly better than that of the historical control group in the surgical treatments for SAVMs. SIGNIFICANCE: Multimodal IONM could be a useful tool to detect neurological damage with relatively high accuracy in this type of surgery.

Myelin Oligodendrocyte Glycoprotein-Immunoglobulin G in the CSF: Clinical Implication of Testing and Association With Disability.

BACKGROUND AND OBJECTIVE: To investigate the clinical relevance of CSF myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) testing in a large multicenter cohort. METHODS: In this multicenter cohort study, paired serum-CSF samples from 474 patients with suspected inflammatory demyelinating disease (IDD) from 11 referral hospitals were included. After serum screening, patients were grouped into seropositive myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD, 31), aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG + NMOSD, 60), other IDDs (217), multiple sclerosis (MS, 45), and non-IDDs (121). We then screened CSF for MOG-IgG and compared the clinical and serologic characteristics of patients uniquely positive for MOG-IgG in the CSF to seropositive patients with MOGAD. RESULTS: Nineteen patients with seropositive MOGAD (61.3%), 9 with other IDDs (CSF MOG + IDD, 4.1%), 4 with MS (8.9%), but none with AQP4-IgG + NMOSD nor with non-IDDs tested positive in the CSF for MOG-IgG. The clinical, pathologic, and prognostic features of patients uniquely positive for CSF MOG-IgG, with a non-MS phenotype, were comparable with those of seropositive MOGAD. Intrathecal MOG-IgG synthesis, observed from the onset of disease, was shown in 12 patients: 4 of 28 who were seropositive and 8 who were uniquely CSF positive, all of whom had involvement of either brain or spinal cord. Both CSF MOG-IgG titer and corrected CSF/serum MOG-IgG index, but not serum MOG-IgG titer, were associated with disability, CSF pleocytosis, and level of CSF proteins. DISCUSSION: CSF MOG-IgG is found in IDD other than MS and also in MS. In IDD other than MS, the CSF MOG-IgG positivity can support the diagnosis of MOGAD. The synthesis of MOG-IgG in the CNS of patients with MOGAD can be detected from the onset of the disease and is associated with the severity of the disease. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the presence of CSF MOG-IgG can improve the diagnosis of MOGAD in the absence of an MS phenotype, and intrathecal synthesis of MOG-IgG was associated with increased disability.

Efficacy of intraoperative bulbocavernosus reflex monitoring for the prediction of postoperative voiding function in adult patients with lumbosacral spinal tumor.

Lumbosacral spinal tumor surgery is associated with a relatively high risk of postoperative voiding dysfunction. This study aimed to investigate the correlation between intraoperative bulbocavernosus reflex (BCR) changes and postoperative voiding function in adult patients with lumbosacral spinal tumors. We retrospectively reviewed 63 patients who underwent intradural conus and cauda equina tumor surgeries with intraoperative BCR monitoring. We evaluated patients' voiding functions for 6 months postoperatively. BCR was maintained in 60 patients and disappeared in 3 patients at the end of the surgery. Among the patients in whom BCR was maintained, examinations conducted at discharge and at 1- and 6-month follow-ups revealed that 7 (11.7%), 4 (6.7%), and zero (0.0%) patients experienced voiding difficulty, respectively. However, all 3 (100%) patients without BCR experienced voiding difficulty at the three corresponding follow-ups. Data analysis indicated no significant difference in voiding between the maintained and disappeared BCR groups 6-months postoperatively. The sensitivity, specificity, positive predictive, and negative predictive values of intraoperative BCR monitoring for detecting new and worsening difficulty in voiding were all 100% 6 months postoperatively. Our results shows that intraoperative BCR monitoring is a reliable predictor of voiding function following surgery in adult patients undergoing lumbosacral spinal tumor surgery. Intraoperative BCR monitoring can be useful for assessing and monitoring the integrity of the voiding function during lumbosacral spinal tumor surgery.

Development of EQ-6, a Novel Analogue of Ethoxyquin to Prevent Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and often dose-limiting side effect of many cancer drugs. Because the onset of neuronal injury is known, it is an ideal clinical target to develop neuroprotective strategies. Several years ago, we had identified ethoxyquin as a potent neuroprotective drug against CIPN through a phenotypic drug screening and demonstrated a novel mechanism of action, inhibition of chaperone domain of heat shock protein 90. To improve its drug-like properties we synthesized a novel analogue of ethoxyquin and named it EQ-6 (6-(5-amino)-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline hydrochloride). Here we show that EQ-6 prevents axon degeneration in primary dorsal root ganglion neurons in vitro, and this axon protection is associated with preserved levels of nicotinamide adenine dinucleotide, a key metabolite in programmed axon degeneration pathway. We also found that EQ-6 prevents loss of epidermal nerve fibers in a mouse model of CIPN induced by paclitaxel and that doses of EQ-6 that provide neuroprotection are associated with reduced tissue levels of SF3B2, a potential biomarker of target engagement. Furthermore, we show that EQ-6 is safe in vitro and in mice with daily administration for a month. We found that oral bioavailability is about 10%, partly due to rapid metabolism in liver, but EQ-6 appears to be concentrated in neural tissues. Given these findings, we propose EQ-6 as a first-in-class drug to prevent CIPN.

Neurophysiological monitoring during anterior cervical discectomy and fusion for ossification of the posterior longitudinal ligament.

OBJECTIVE: This study aimed to investigate the value of intraoperative neurophysiological monitoring (IONM) in anterior cervical spine discectomy with fusion (ACDF) for ossification of the posterior longitudinal ligament (OPLL). METHODS: Patients who underwent multimodal IONM (transcranial electrical motor-evoked potentials [tcMEP], somatosensory-evoked potentials, and continuous electromyography) for ACDF from 2009 to 2019 were compared to historical controls from 2003 to 2009. The rates of postoperative neurological deficits, neurophysiological warnings, and their characteristics were analyzed. RESULTS: Among 196 patients, postoperative neurological deficit rates were 3.79% and 14.06% in the IONM and historical control (non-IONM) groups, respectively (p < 0.05). The use of IONM (OR: 0.139, p = 0.003) and presence of myelopathy (OR: 8.240, p = 0.013) were associated with postoperative neurological complications on multivariate regression. In total, 23 warnings were observed during IONM (17 tcMEP and/or electromyography; six electromyography). Sensitivity and specificity of IONM warnings for detecting neurological complications were 84.2% and 93.7%, respectively. CONCLUSIONS: IONM, especially multimodal IONM, may be a useful tool to detect neurological damage in ACDF for high-risk conditions such as OPLL with pre-existing myelopathy. SIGNIFICANCE: The utility of IONM in ACDF for OPLL has not been evaluated due to its rarity. This study supports the use of IONM in cervical OPLL with myelopathy.

HyperCKemia in Guillain-Barré Syndrome.

The aim of the present study was to investigate the frequency and clinical features of Guillain-Barré syndrome (GBS) with hyperCKemia. We retrospectively identified 139 patients with GBS at 2 teaching hospitals in South Korea. We excluded patients with Miller-Fisher syndrome (n = 19), acute bulbar palsy (n = 3), and those whose serum creatine kinase (CK) levels were not measured (n = 45). Twelve of 72 patients (16.7%) had transient hyperCKemia, defined as serum CK ≥300 IU/L. The frequency of male sex and non-demyelinating electrodiagnostic features were higher in patients with hyperCKemia than those without. Transient hyperCKemia, occasionally seen in patients with GBS may be associated with the non-demyelinating subtype.

Predictive value of intraoperative blink reflex monitoring for surgical outcome during microvascular decompression for hemifacial spasm.

OBJECTIVE: To investigate the prognostic and predictive value of intraoperative blink reflex (BR) monitoring during microvascular decompression (MVD) for hemifacial spasm (HFS). METHODS: We retrospectively reviewed 41 patients with HFS undergoing MVD with intraoperative BR and lateral spread response (LSR) monitoring. Facial spasm was evaluated for six months postoperatively. RESULTS: The BR resolved in 38 patients and persisted in three after MVD. For patients who exhibited BR resolution, 1-day, 1-month, and 6-month follow-ups revealed that 35 (92.1%), 35 (92.1%), and 38 (100%) patients had spasm resolution, respectively. However, of the three patients with persistent BR, one (33.3%), one (33.3%), and zero (0%) patients exhibited spasm resolution at the three corresponding follow-ups. We found a statistically significant difference in spasm resolution between the persistent and resolved BR groups at six months postoperatively. A comparison between intraoperative BR and LSR monitoring revealed that BR was a better predictor of clinical outcomes. CONCLUSIONS: Intraoperative BR monitoring is a potentially useful tool to help facilitate an adequate decompression and is a reliable prognostic predictor of surgical outcome. SIGNIFICANCE: This study is the first to document the relationship between intraoperative BR monitoring and surgical outcome in patients with HFS.

Repeated low-dose rituximab treatment based on the assessment of circulating B cells in patients with refractory myasthenia gravis.

BACKGROUND: The objective of this study was to evaluate the efficacy and safety of repeated low-dose rituximab treatment guided by monitoring circulating CD19+ B cells in patients with refractory myasthenia gravis (MG). METHODS: Patients with refractory MG who had received rituximab treatment at two teaching hospitals between September 2013 and January 2017 were reviewed retrospectively. The treatment protocol consisted of an induction treatment with low-dose rituximab (375 mg/m2 twice with a 2-week interval), followed by retreatment (375 mg/m2 once). Retreatment was based on either circulating CD19+ B-cell repopulation or clinical relapse. Outcome measures included the MG Foundation of America (MGFA) clinical classification and postintervention status, prednisolone dose, CD19+ B-cell counts, clinical relapse, and adverse effects. RESULTS: Of 17 patients, 11 (65%) achieved the primary endpoint, defined as the minimal manifestation or better status with prednisolone ⩽5 mg/day, after median 7.6 months (range, 2-17 months) following rituximab treatment. Over a median follow up of 24 months (range, 7-49 months), a total of 30 retreatments were undertaken due to clinical relapse without B-cell repopulation (n = 6), on the basis of B-cell repopulation alone (n = 16) and both (n = 8). B-cell recovery appeared to be in parallel with clinical relapse on the group level, although the individual-level association appeared to be modest, with B-cell repopulation observed only at 57% (8/14) of clinical relapses. CONCLUSIONS: The repeated low-dose rituximab treatment based on the assessment of circulating B-cell depletion could be a cost-effective therapeutic option for refractory MG. Further studies are needed to verify the potentially better cost-effectiveness of low-dose rituximab, and to identify biomarkers that help optimize treatment in MG patients.

Pathological Modification of TDP-43 in Amyotrophic Lateral Sclerosis with SOD1 Mutations.

Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset, progressive neurodegenerative disorder with no known cure. Cu/Zn-superoxide dismutase (SOD1) was the first identified protein associated with familial ALS (fALS). Recently, TAR DNA-binding protein 43 (TDP-43) has been found to be a principal component of ubiquitinated cytoplasmic inclusions in neurons and glia in ALS. However, it remains unclear whether these ALS-linked proteins partly have a shared pathogenesis. Here, we determine the association between mutant SOD1 and the modification of TDP-43 and the relationship of pathologic TDP-43 to neuronal cytotoxicity in SOD1 ALS. In this work, using animal model, human tissue, and cell models, we provide the evidence that the association between the TDP-43 modification and the pathogenesis of SOD1 fALS. We demonstrated an age-dependent increase in TDP-43 C-terminal fragments and phosphorylation in motor neurons and glia of SOD1 mice and SOD1G85S ALS patient. Cytoplasmic TDP-43 was also observed in iPSC-derived motor neurons from SOD1G17S ALS patient. Moreover, we observed that mutant SOD1 interacts with TDP-43 in co-immunoprecipitation assays with G93A hSOD1-transfected cell lines. Mutant SOD1 overexpression led to an increase in TDP-43 modification in the detergent-insoluble fraction in the spinal cord of SOD1 mice and fALS patient. Additionally, we showed cellular apoptosis in response to the interaction of mutant SOD1 and fragment forms of TDP-43. These findings suggest that mutant SOD1 could affect the solubility/insolubility of TDP-43 through physical interactions and the resulting pathological modifications of TDP-43 may be involved in motor neuron death in SOD1 fALS.