Background: and Purpose CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (NOTCH2NLC) has been associated with neuronal intranuclear inclusion disease (NIID) and oculopharyngodistal myopathy type 3 (OPDM3). Few OPDM3 patients have been reported. This report describes two OPDM3 patients with novel imaging findings who presented the typical features of NIID, and reviews all OPDM3 cases available in the literature. Methods: The available clinical, imaging, and pathological information was reviewed and investigated. CGG repeat expansion in the 5'UTR of NOTCH2NLC was tested using the repeatprimed polymerase chain reaction (PCR), followed by the fluorescence amplicon-length PCR to determine the number of CGG repeats. Results: Our two OPDM3 patients and most patients reported in the literature developed the typical clinical characteristics of NIID, including leukoencephalopathy, peripheral neuropathy, cognitive deterioration, pigmentary retinopathy, ataxia, tremor, acute encephalitis-like episodes, pigmentary retinopathy, miosis, and sensorineural hearing loss. In addition to typical imaging findings of NIID, our two patients exhibited diffusion weighted imaging (DWI) hyperintensities in the middle cerebellar peduncles, which have not been described previously. Muscle biopsies revealed rimmed vacuoles and p62-positive intranuclear inclusions in the myofibers in both patients. The skin biopsy performed in one patient detected typical eosinophilic intranuclear inclusions. Genetic analysis identified CGG repeat expansion in NOTCH2NLC as the causative mutation in the two patients. Conclusions Our two patients with OPDM3 had clinical characteristics of NIID and exhibited DWI abnormality in the cerebellum. Our results indicate that OPDM3 is within the spectrum of NIID and that DWI hyperintensities in the cerebellum are helpful for diagnosing NIID or OPDM3.

Background: and Purpose CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (NOTCH2NLC) has been associated with neuronal intranuclear inclusion disease (NIID) and oculopharyngodistal myopathy type 3 (OPDM3). Few OPDM3 patients have been reported. This report describes two OPDM3 patients with novel imaging findings who presented the typical features of NIID, and reviews all OPDM3 cases available in the literature. Methods: The available clinical, imaging, and pathological information was reviewed and investigated. CGG repeat expansion in the 5'UTR of NOTCH2NLC was tested using the repeatprimed polymerase chain reaction (PCR), followed by the fluorescence amplicon-length PCR to determine the number of CGG repeats. Results: Our two OPDM3 patients and most patients reported in the literature developed the typical clinical characteristics of NIID, including leukoencephalopathy, peripheral neuropathy, cognitive deterioration, pigmentary retinopathy, ataxia, tremor, acute encephalitis-like episodes, pigmentary retinopathy, miosis, and sensorineural hearing loss. In addition to typical imaging findings of NIID, our two patients exhibited diffusion weighted imaging (DWI) hyperintensities in the middle cerebellar peduncles, which have not been described previously. Muscle biopsies revealed rimmed vacuoles and p62-positive intranuclear inclusions in the myofibers in both patients. The skin biopsy performed in one patient detected typical eosinophilic intranuclear inclusions. Genetic analysis identified CGG repeat expansion in NOTCH2NLC as the causative mutation in the two patients. Conclusions Our two patients with OPDM3 had clinical characteristics of NIID and exhibited DWI abnormality in the cerebellum. Our results indicate that OPDM3 is within the spectrum of NIID and that DWI hyperintensities in the cerebellum are helpful for diagnosing NIID or OPDM3.

Background: and Purpose CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (NOTCH2NLC) has been associated with neuronal intranuclear inclusion disease (NIID) and oculopharyngodistal myopathy type 3 (OPDM3). Few OPDM3 patients have been reported. This report describes two OPDM3 patients with novel imaging findings who presented the typical features of NIID, and reviews all OPDM3 cases available in the literature. Methods: The available clinical, imaging, and pathological information was reviewed and investigated. CGG repeat expansion in the 5'UTR of NOTCH2NLC was tested using the repeatprimed polymerase chain reaction (PCR), followed by the fluorescence amplicon-length PCR to determine the number of CGG repeats. Results: Our two OPDM3 patients and most patients reported in the literature developed the typical clinical characteristics of NIID, including leukoencephalopathy, peripheral neuropathy, cognitive deterioration, pigmentary retinopathy, ataxia, tremor, acute encephalitis-like episodes, pigmentary retinopathy, miosis, and sensorineural hearing loss. In addition to typical imaging findings of NIID, our two patients exhibited diffusion weighted imaging (DWI) hyperintensities in the middle cerebellar peduncles, which have not been described previously. Muscle biopsies revealed rimmed vacuoles and p62-positive intranuclear inclusions in the myofibers in both patients. The skin biopsy performed in one patient detected typical eosinophilic intranuclear inclusions. Genetic analysis identified CGG repeat expansion in NOTCH2NLC as the causative mutation in the two patients. Conclusions Our two patients with OPDM3 had clinical characteristics of NIID and exhibited DWI abnormality in the cerebellum. Our results indicate that OPDM3 is within the spectrum of NIID and that DWI hyperintensities in the cerebellum are helpful for diagnosing NIID or OPDM3.

Objective:To describe the clinical features of a patient of anti-neurofascin 186 (NF186) antibody associated acute immune sensory polyradiculopathy (AISP), and enhance understanding of AISP/chronic immune sensory polyradiculopathy (CISP).Methods:The clinical characteristics, diagnosis and treatment of a domestic AISP patient with NF186 antibody positive admitted to the First Hospital of Shanxi Medical University in December 2021 were summarized, and the previously reported cases of AISP/CISP were systematically reviewed.Results:The patient was a 62-year-old male with acute onset. The clinical manifestations included severe sensory ataxia, increased protein in cerebrospinal fluid, no response to stimulation of the central segment of somatosensory evoked potentials (SEP), normal sensory and motor nerve conduction, and positive serum anti-NF186 antibody (1∶32). After glucocorticoid treatment, the clinical symptoms and SEP were significantly improved. The drug was stopped for 2 months, and there was no recurrence. There were 23 cases of AISP and CISP with complete data reported in the literature (including this patient). The age of onset was (54.7±17.7) years, and the ratio of male to female was 1.88. Three patients with acute onset were classified as AISP. A total of 95.7% (22/23) of patients showed sensory ataxia without limb weakness, 95.0% (19/20) of patients showed prolonged cortical potential latency or even no response, and 95.5% (21/22) of patients showed increased cerebrospinal fluid protein in varying degrees, and nerve root thickening or abnormal enhancement was not common. All 10 patients receiving immunotherapy responded to corticosteroids or intravenous immune globulin. Only 6 AISP/CISP articles reported screening for anti-ganglioside antibodies or Ranvier′s node-paranodal region-related antibodies, and no positive NF186 antibodies were reported. All the 3 patients with AISP had some characteristics of CISP/chronic inflammatory demyelinating polyradiculoneuropathy, and there was no significant difference between AISP and CISP patients in clinical features except the mode of onset.Conclusions:NF186 antibody could cause AISP, which presents as acute onset sensory ataxia. AISP is responsive to glucocorticoid therapy. Except for the mode of onset, AISP and CISP are difficult to distinguish from clinical, electrophysiological, pathological aspects and pathogenic antibodies, so they may be two different manifestations of the same disease.

Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots, which is usually triggered by infections. It is characterized by rapidly progressive, symmetrical weakness of the extremities. Some patients develop respiratory insufficiency and many show signs of autonomic dysfunction. Diagnosis can usually be made on clinical grounds, but lumbar puncture and electrophysiological studies can help to substantiate the diagnosis and to differentiate demyelinating from axonal subtypes of GBS. Molecular mimicry of pathogen-borne antigens, leading to generation of crossreactive antibodies that also target gangliosides, is generally accepted pathogenesis of GBS. The treatment of GBS is intravenous immunoglobulin or plasma exchange with general clinical treatment. Most patients have a good prognosis and basically recover within weeks to months. A few patients have persistent neurological dysfunction or even death.

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease, characterized by eosinophilic transparent inclusions in the central and peripheral nervous systems, and internal organs. NIID clinical characteristics are varied, including cognitive impairment, muscle weakness, episodic symptoms, movement disorders and autonomic dysfunction. This article reports a patient with NIID who manifested with episodes of aphasia, dysgraphia and dyslexia without fever, headache, nausea and vomiting confirmed by genetic testing. The patient was a 62-year-old female with acute onset who was diagnosed with transient ischemic attack. This article aims to improve the knowledge of NIID with stroke-like onset by this case presentation and avoid misdiagnosis.

Objective:To explore the correlation and mechanism between thalamic network abnormality and cognitive decline in patients with temporal lobe epilepsy (TLE).Methods:A total of 53 patients with unilateral TLE were consecutively enrolled through the epilepsy clinic of the First Affiliated Hospital of Guangxi Medical University from December 2018 to February 2020. During the same recruitment interval, 37 health controls(HC) with matching demographic characteristic were recruited. All subjects were received the Montreal cognitive assessment(MoCA) test and multimodal MRI scanning. Voxel-based morphometry method was used to study the changes of thalamic gray matter volume in patients with unilateral TLE. The structural covariance network and functional connectivity network based on seed points were used to analyze the changes of thalamic network in TLE patients. In addition, the correlations among abnormal thalamic structure, thalamic network and cognitive function score were analyzed. SPSS 22.0 software was used for statistical analysis. Independent sample t-test and Mann Whitney U test were used for inter group comparison. In order to explore the relationship between thalamus and thalamic network and cognitive performance in TLE patients, thalamic volume and gray matter volume and functional connection value of brain areas with abnormal synergistic changes were extracted and correlated with MoCA score. Results:The total score of MoCA in TLE patients (27.0(25.0, 29.0)) was significantly decreased compared with HC (29.0(28.0, 30.0))( Z=-4.601, P<0.001). Whole brain gray matter volume analysis showed that compared with HCTLE patients showed significant volume reduction in left cerebellum, right temporal pole, right fusiform gyrus, straight gyrus, bilateral middle temporal gyrus, thalamus, medial and paracingulate gyrus (GRF adjusted, voxel-level P<0.001 and cluster-level P<0.05). The thalamus-associated structural covariance network analysis revealed that compared with healthy controls, TLE patients exhibited decreased connectivity in right fusiform gyrus (MNI: x=28.5, y=-15.0, z=-34.5), left insula (MNI: x=-33.0, y=-18.0, z=-1.5), right middle temporal gyrus (MNI: x=55.5, y=-51.0, z=9.0), left complementary motor area (MNI: x=-10.5, y=1.5, z=57.0) and right posterior central gyrus (MNI: x=31.5, y=-33.0, z=51.0) ( P<0.001, cluster > 100). The thalamus-associated functional connectivity network analysis revealed that TLE patients exhibited decreased connectivity in left insula (MNI: x=-38, y=-7, z=-7), left lingual gyrus (MNI: x=-6, y=-81, z=-12), right lingual gyrus (MNI: x=15, y=-105, z=0) and left triangular inferior frontal gyrus (MNI: x=-39, y=36, z=-6) (GRF correction, voxel-level P<0.001 and cluster-level P<0.05). Volume of left insula which had decreased structural connectivity with thalamus were positively correlated with the MoCA score in TLE patients( r=0.279, P=0.043). Volume of left complementary motor area which had decreased structural connectivity with thalamus was positively correalated with the MoCA score and language score in TLE patients( r=0.323, P=0.018; r=0.334, P=0.015). Volume of left lingual gyrus which had decreased functional connectivity with thalamus was negatively correalated with the memory score in TLE patients ( r=-0.331, P=0.016). Conclusion:Thalamic volume, thalamic structural covariant network and functional connection network are changed in TLE patients. The abnormality of thalamic network is associated with cognitive performance in TLE patients, which may be the neural mechanism of thalamus participating in the cognitive impairment of TLE patients.

Objective:To investigate longitudinal alterations of brain functional complex network by rest-stage functional magnetic resonance imaging (rs-fMRI) and graph theory in patients with temporal lobe epilepsy (TLE).Methods:A total of 13 TLE patients (TLE baseline group) and 13 healthy controls (healthy control group) were enrolled to observe alterations in complex functional network. The subjects were recruited in the Epilepsy Clinic of the First Affiliated Hospital of Guangxi Medical University from January 2015 to April 2018. For longitudinal analysis, TLE patients were followed-up for three years (TLE follow-up group). All participants underwent rs-fMRI and attention network test (ANT). Finally, a cross-sectional study was conducted by comparing the area under the curve (AUC) between the TLE baseline group and the healthy control group, and a longitudinal analysis was conducted by comparing the AUC between the TLE baseline group and the TLE follow-up group.Results:Cross-sectional analysis showed that the alerting function of the TLE baseline group was declined [The tonic alertness reaction time, phasic alertness reaction time and alertness were (727.00±126.07) ms, (692.85±132.37) ms, and (34.15±23.50) ms, respectively in the TLE baseline group, which were (639.87±81.41) ms, (589.50±80.59) ms, and (50.37±14.71) ms, respectively in the healthy control group, with statistically significant differences between the two groups ( t=-2.09, P=0.047; t=-2.41, P=0.024; t=2.11, P=0.045)]; the TLE baseline group demonstrated decreased clustering coefficient in left supplementary motor area (SMA.L)(AUC was 0.162±0.044, 0.189±0.021, respectively; t=-4.14, P=4.67E-04) and left inferior parietal supramarginal angular gyri (AUC was 0.178±0.021, 0.202±0.026, respectively; t=-2.42, P=0.024), and decreased nodal local efficiency in SMA.L (AUC was 0.239±0.045, 0.260±0.022, respectively; t=-4.13, P=4.77E-04) and left inferior temporal gyrus (AUC was 0.233±0.036, 0.253±0.027, respectively; t=-3.03, P=0.006) compared with the healthy control group, and both SMA.L clustering coefficient and nodal local efficiency were positively correlated with TLE patients′ duration ( r=0.652, P<0.05; r=0.611, P<0.05). Longitudinal analysis showed that the global network efficiency of the TLE follow-up group decreased (The AUC of the TLE baseline group was 0.182±0.008, and the AUC of the TLE follow-up group was 0.169±0.015, t=2.73, P=0.017), which was negatively correlated with alertness ( r=-0.617, P<0.05). Conclusions:TLE patients show impairment of topological properties of brain functional network. SMA.L is a significant node in network. Alterations of brain functional network associate with duration. The decline in global network efficiency may be a characteristic of progressive deficit to TLE.

Objective:To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients.Methods:The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed.Results:The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively ( P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively ( P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm 3, the median survival time of SIB and No-SIB group was 34.7 and 30.3 months ( P=0.155), respectively. In the patients whose GTV volume>50 cm 3, the median survival time of SIB and No-SIB group was 16.1 and 20.1 months ( P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group ( P<0.001). Conclusions:The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.

Objective:To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients.Methods:The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed.Results:The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively ( P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively ( P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm 3, the median survival time of SIB and No-SIB group was 34.7 and 30.3 months ( P=0.155), respectively. In the patients whose GTV volume>50 cm 3, the median survival time of SIB and No-SIB group was 16.1 and 20.1 months ( P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group ( P<0.001). Conclusions:The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.