Objective:To explore the clinical and electrophysiological characteristics of peripheral neuropathy in prediabetic patients.Methods:Subjects aged 20-65 years with high-risk factors of impaired glycemia enrolled in Beijing Tiantan Hospital, Capital Medical University from 2019 to 2022 were recruited to conduct oral glucose tolerance test, after excluding other causes of neuropathy or radiculopathy. Patients with impaired fasting glucose or impaired glucose tolerance were defined by American Diabetes Association criteria. These patients were divided into clinical polyneuropathy (PN) and clinical non-PN groups, according to the 2010 Toronto consensus criteria and the presence of PN symptoms and signs or not. Nerve conduction studies (NCS), F wave, sympathetic skin response (SSR), R-R interval variation (RRIV) and current perception thresholds (CPT) were performed and the abnormal rate was compared between different electrodiagnostic methods and between clinical subgroups.Results:Among the 73 prediabetic patients ultimately enrolled, only 20 (27.4%) can be diagnosed as clinical PN according to the Toronto consensus criteria. The abnormal rate of CPT (68.5%, 50/73) was significantly higher than those of F wave (2.7%, 2/73), lower limb NCS (0, 0/73), upper limb NCS changes of carpal tunnel syndrome (26.0%, 19/73), SSR (6.8%, 5/73) and RRIV (5.5%, 4/73; McNemar test, all P<0.001). With sinusoid-waveform current stimuli at frequencies of 2 000 Hz, 250 Hz and 5 Hz, the CPT device was used to measure cutaneous sensory thresholds of large myelinated, small myelinated and small unmyelinated sensory fibers respectively. CPT revealed a 21.9% (16/73) abnormal rate of unmyelinated C fiber in the hands of prediabetic patients, significantly higher than that of large myelinated Aβ fibers [8.2% (6/73), χ2=5.352, P=0.021]. Both abnormal rates of small myelinated Aδ [42.5% (31/73)] and unmyelinated C fibers [39.7% (29/73)] in the feet of prediabetic patients were significantly higher than that of large myelinated Aβ fibers [11.0% (8/73), χ2=18.508, 15.965, both P<0.001]. Compared with the clinical non-PN group, the abnormal rates of CPT [90.0% (18/20) vs 60.4% (32/53), χ2=5.904, P=0.015] and SSR [20.0% (4/20) vs 1.9% (1/53), P=0.016) were significantly higher in the clinical PN group. Conclusions:Peripheral neuropathies in prediabetic patients are usually asymptomatic or subclinical, and predispose to affect unmyelinated and small myelinated sensory fibers. Selective electrodiagnostic measurements of small fibers help to detect prediabetic neuropathies in the earliest stages of the disease.

Objective:To determine whether there is a correlation between the cross-sectional area (CSA) and the parameters as measured on nerve conduction studies.Methods:Twenty-one patients with neuromuscular diseases in Beijing Tiantan Hospital from March 3, 2022 to May 4, 2023 underwent ultrasound measurement of the CSA of the median nerves and ulnar nerves at the wrist, elbow and the upper arm, followed by nerve conduction studies (NCS). A linear regression model was performed to compare NCS and CSA.Results:A total of 180 sets of motor nerve conduction velocity (MCV) and CSA at the different sites including 102 sets of median nerve and 78 sets of ulnar nerve, 220 sets of compound muscle action potential (CMAP) amplitude and CSA at the different sites including 104 sets of median nerve and 116 sets of ulnar nerve, 60 sets of sensory nerve conduction velocity (SCV) and CSA and sensory nerve action potential (SNAP) amplitude and CSA at the wrist including 32 sets of median nerve and 28 sets of ulnar nerve were recorded. The linear correlation between MCV and CSA was statistically significant both in median nerve ( r2=0.10,adjusted r2=0.09, P=0.001) and in ulnar nerve ( r2=0.18,adjusted r2=0.17, P<0.001).When CSA>10 mm 2, the linear correlation between CMAP amplitude and CSA was statistically significant both in median nerve ( r2=0.09,adjusted r2=0.08, P=0.024) and ulnar nerve ( r2=0.19,adjusted r2=0.17, P=0.004). The correlation between CMAP and CSA was not statistically significant when CSA≤10 mm 2. And the correlations between SCV and CSA and between SNAP and CSA were not statistically significant. Conclusions:CSA can better show the characteristics of changes in motor nerve conduction especially in motor conduction velocity. It is suggested that its application prospect in demyelinating peripheral neuropathy with motor nerve damage may be more extensive.

Objective:To analyze the clinical, electromyographic and tremor characteristics in tremor patients with neuronal intranuclear inclusion disease (NIID).Methods:From May 2018 to April 2023, 34 patients with NIID diagnosed in the Department of Neurology, Beijing Tiantan Hospital of Capital Medical University were retrospectively included. Sixteen patients with tremor of at least one limb and (or) head were in tremor group, and 18 patients without tremor were in control group. The clinical, electromyogram and tremor data of all participants were summarized, the clinical features and electromyogram differences of the 2 groups were compared, and the tremor characteristics of patients with NIID were analyzed.Results:The proportion of female patients in the tremor group was higher than that in the non tremor group (12/16 vs 7/18, P=0.045). The proportion of upper and lower limb peripheral nerve damage in the tremor group was lower than that in the non tremor group (2/16 vs 9/18, P=0.030), with statistical significance. There was no significant difference between the 2 groups in higher cortex and autonomic nervous dysfunction. The amplitude of composite muscle action potential and sensory nerve action potential in all patients was normal or slightly decreased; some patients experienced a decrease in motor and sensory fiber conduction velocity. The proportion of motor and sensory nerve conduction velocity slowing in the non tremor group was higher than that in the tremor group [motor nerve:41.7%(30/72) vs 17.2%(11/64), χ 2=9.64, P=0.002;sensory nerve:38.9% (35/90) vs 20.0%(16/80), χ 2=7.19, P=0.007]. The number of cases of postural tremors in different parts among the 16 patients was as follows: 13 in the upper limbs, 7 in the lower limbs, and 6 in the head; static tremor: 8 cases in the upper limbs, 3 cases in the lower limbs, and 5 cases in the head. At rest, the frequency of tremors in different parts of the body was as follows: upper limb (5.3±1.1) Hz, lower limb (4.2±0.4) Hz, and head (3.9±0.6) Hz. The difference in tremor frequency among the 3 parts was statistically significant ( F=3.92, P=0.047); Pairwise comparison showed that the frequency of head tremor was lower than that of upper limb tremor, with a statistically significant difference ( P=0.020). In a postural state, tremor frequency in different parts was as follows: upper limb (5.4±0.9) Hz, lower limb (5.0±0.7) Hz, head (3.9±0.7) Hz. There was a statistically significant difference in tremor frequency among the 3 parts ( F=6.65, P=0.005). Further pairwise comparison revealed statistically significant differences in tremor frequency between the patient′s head, upper and lower limbs ( P=0.001, P=0.022). Synchronous tremor rhythm was predominant, with occasional alternations or synchronous+alternations. There was no harmonic tremor spectrum was observed. Conclusions:NIID patients with tremors were more common in female patients.The degree of peripheral nerve damage was milder than those without tremors. The site and form of tremor were diverse, with a dominant frequency of 4-6 Hz, mainly synchronous rhythm, and no harmonic spectrum. Postural tremors were common in the limbs.

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a hereditary small vessel disease originated from adult onset, which is caused by the mutation of NOTCH3 gene located in the region of chromosome 19p13. Its clinical features include recurrent ischemic stroke, progressive cognitive impairment, migraine and mental disorders. Recent studies have shown that the mutations in the EGFr region of NOTCH3 gene are associated with the course, clinical manifestations and imaging features of CADASIL. This article reviews the research progress of the NOTCH3 gene EGFr region mutation genotype, clinical phenotype of CADASIL and their correlation, hoping to provide ideas for the early diagnosis and pathogenesis of CADASIL.

Objective:To investigate the electrophysiological features of patients with anti-neurofascin 155 (NF155) IgG4 antibodies positive chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).Methods:The electrophysiological data of 6 anti-NF155 IgG4 antibodies positive CIDP patients in Beijing Tiantan Hospital, Capital Medical University from September 2018 to May 2021 were retrospectively analyzed. Parameters studies included standard motor and sensory nerve conduction studies, electromyography (EMG) and F waves studies. Correlation analysis was made to explore the relationships between clinical indicators and electrophysiological data.Results:There was statistically significant difference in the motor nerve conduction study on abnormal rate of tibial nerve (χ 2=11.08, P=0.011). Motor nerve conduction abnormalities were presented in a majority of patients with decreased motor conduction velocity (MCV) and prolonged distal motor latency (DML). There was no statistically significant difference in the overall abnormal rate between lower limbs and upper limbs (30/32, 93.8% vs 22/22, 100.0%; χ 2=1.43, P=0.508), sensory nerve conduction and motor nerve conduction (52/54, 96.3% vs 42/42, 100.0%; χ 2=1.59, P=0.503). There was statistically significant difference in the overall abnormal rate in median nerve, ulnar nerve and sural nerve (χ 2=14.96, P=0.001;χ 2=10.00, P=0.007; χ 2=9.95, P=0.008),and absent sensory nerve action potential was the most common abnormality in sensory nerve conduction abnormalities. The abnormal rate of EMG was 9/14, which was constituted by upper limbs (4/8) and lower limbs (5/6), and the spontaneous activity accompanied with prolonged duration and increased amplitude of motor unit action potential was common. Significant negative correlations were established between disease duration and compound muscle action potential (CMAP) amplitude and negative area of ulnar nerve ( r=-0.84, P=0.036; r =-0.76, P=0.011), and the correlations between age and MCV of median nerve and ulnar nerve were also found ( r=0.89, P=0.019; r=0.95, P=0.003). The DML of median nerve was negatively correlated with CMAP amplitude ( r=-0.63, P=0.049). Moreover, the correlation analysis revealed associations of the F wave latency with the DML, CMAP amplitude and MCV of tibial nerve ( r= 0.90, P=0.039; r=-0.96, P=0.012; r=-0.96, P=0.010). Conclusions:The motor nerve and sensory nerve, the myelin sheath and axon of peripheral nerves in anti-NF155 IgG4 CIDP patients were largely affected. The CMAP amplitude and negative area of ulnar nerve might be of certain clinical value in reflecting the disease duration.The younger the patients, the more severe the demyelination degree of the upper limbs. The F wave latency of tibial nerve not only reflected the abnormal proximal conduction, but also the distal damage degree of myelin sheath and axon.

  Objective  Adrenoleukodystrophy (ALD) is the most common peroxisomal diseases with high clinical and genetic heterogeneity. Our study is to analyze the phenotype and genotype characteristics of adult patients with ALD.  Methods  A total of 18 adult patients with ALD admitted to Beijing Tiantan Hospital from May 2016 to April 2021 were recruited, and their clinical manifestations, imaging features, and genetic results were comprehensively analyzed.  Results  Among 18 patients, 6(33%) patients were diagnosed as adrenomyeloneuropathy (AMN), 2(11%) were cerebral AMN, 5(28%) were adult cerebral ALD (ACALD), 2(11%) were childhood cerebral ALD (CCALD), 1(6%) were adolescent cerebral ALD (AdolALD), and 2(11%) were cerebellar variant of ALD. AMN patients presented with adult-onset stiffness and weakness of lower limbs as the initial and main symptoms, and can developed additional cerebral demyelination; In the case of cerebral ALD, ACALD is more common than CCALD and AdolALD. The prominent manifestations were psychiatric disorders, cognitive, and motor impairment. The imaging features were predominantly occipitoparietal involvement or predominantly frontal involvement with or without contrast enhancement marginal to the demyelinated areas; cerebellar ataxia is the main manifestation in patients with cerebellar variant, and the imaging feature was symmetrical involvement of the cerebellar dentate nucleus. Genetically, the most common mutation type was missense mutation (10/18, 55.6%), followed by frameshift mutation (7/18, 38.9%), and splice site mutation (1/18, 5.6%). Moreover, we found five novo mutations, all of which were frameshift mutations.  Conclusions  AMN is the most common subtype of adult patients with ALD. ACALD is common among the cerebral ALD. The proportion of cerebellar variant might have been underestimated.

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

Objective:To identify anti-dipeptidyl-peptidase-like protein 6 (DPPX) antibody in patients with encephalitis of unknown etiology and describe the clinical features of anti-DPPX antibody-associated encephalitis in Chinese patients.Methods:For patients registered in the Peking Union Medical College Hospital Encephalitis and Paraneoplastic Syndrome Registration Project from 2016 to 2019 with negative findings in autoimmune encephalitis routine antibody profile and paraneoplastic antibody profile, but with positive tissue-based assay (TBA) results, further tests for rare antibodies, including cell-based assay (CBA) of anti-DPPX antibody, were performed. Patients positive for anti-DPPX antibody were enrolled and the clinical data were collected.Results:Two patients with anti-DPPX antibody-associated encephalitis were found from 2016 to 2019 among about 15 000 patients. Both were females, aged 46 and 75 years. One patient had diarrhea, cachexia, cognitive dysfunction, agitation, myoclonus, tremor, and seizures. The other had cognitive impairment, restlessness, memory loss, disorientation, and sleep disturbance. The second patient had medical history of systemic lupus erythematosus and secondary Sj?gren′s syndrome.Conclusions:TBA should be combined with CBA in identification of anti-DPPX antibody to confirm the diagnosis. Anti-DPPX antibody-associated encephalitis has clinical manifestations of encephalopathy with diarrhea and cachexia, and can coexist with systemic lupus erythematosus.

Objective:To report the clinical, pathological, electrophysiological and genic characteristics of a patient with familial amyloidosis Finnish type.Methods:The clinical characteristic of a 60-year-old female who admitted to Beijing Tiantan Hospital, Capital Medical University in June 2020 was analyzed. Meanwhile, the patient underwent electrophysiological examination, biopsy of labial gland, rectum and skin and gene sequencing analysis.Results:The patient presented left facial paralysis at the age of 50, right facial paralysis and thickening of lips at the age of 55, dysarthria and dysphagia at the age of 56. Physical examination of the patient showed signs of cranial nerves involvement and skin thinning and smoothness. Slit lamp showed corneal lattice dystrophy. Electrophysiological findings of the patient suggested bilateral carpal tunnel syndrome. Latencies were prolonged in bilateral visual evoked potential P100. The deep sensory conduction pathways in bilateral C 7 to biparietal and T 12 to biparietal cortex were abnormal. Pathology of the three biopsies of the patient showed the presence of amyloid deposition in the basement membrane around the glands. The heterozygous mutation of c.654 G>T in exon 4 of gelsolin (GSN) gene in the patient resulted in Asp187 Tyr mutation (p.D187Y). Conclusions:The patient with familial amyloidosis Finnish type was characterized by slowly progressive multiple group cranial neuropathy accompanied by corneal lattice dystrophy and skin changes. Optic nerve and spinal cord posterior funiculus sensory conduction pathway and D187Y mutation of GSN gene were involved.

Objective: To investigate the ultrastructural features of muscle in patients with mitochondrial encephalomyopathy for its diagnosis and differential diagnosis. Methods: The clinical data of 27 mitochondrial encephalomyopathy patients who underwent left or right biceps brachii muscle biopsy at Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University from July 2006 to August 2017 were analyzed retrospectively. The muscle biopsy specimens were examined underlight microscope and transmission electron microscope. Results: There were 27 patients (17 males, 10 females) with an age range of 12 to 62 years (mean 29 years). The age of onset ranged from 3 to 38 years. The course of disease ranged from 1 month to 24 years. Twenty-two cases presented with lactic acidosis and stroke-like episodes (MELAS) syndrome, four with myoclonic epilepsy with ragged red fibers (MERRF) syndrome, and one with chronic progressive paralysis of extraocular muscle (CPEO) syndrome. Skeletal muscle biopsy showed abundant ragged red fibers and strongly SDH-reactive vessel. Genetic studies showed 17 of 22 cases of MELAS syndrome had A3243G mutation, and the other 5 cases had no abnormality. A8344G mutation was found in 3 of 4 cases of MERRF syndrome. No single or multiple mtDNA mutations were found in the single case of CPEO. Transmission electron microscopy of all 27 cases showed diffuse proliferation of mitochondria between the myofibrils and beneath the sarcolemma, with increased spacing between muscle cells. Seven cases showed numerous glycogen and four showed subsarcolemmal lipid droplets, 13 cases showed unusual mitochondrial morphology, including mitochondrial electron-dense substances and paracrystal line inclusions ("parking lot" change)in eight cases. Conclusions Transmission electron microscopy shows significant differences in ultrastructural pathological changes among different patients with mitochondrial encephalomyopathy. Some patients with mild clinical symptoms have increased mitochondrial number, increased metabolism of glycogen and lipid droplets, while others with severe clinical symptoms have abnormal mitochondrial morphology. Typical crystalloid inclusions are found in mitochondria, which are of great value in the diagnosis of this disease.