Changes of tau protein in cerebrospinal fluid of sporadic Creutzfeldt-Jakob disease / 中华神经科杂志

Objective@#To evaluate the value of cerebrospinal fluid markers expecially total-tau protein (T-tau), phosphorylated-tau protein (P-tau) in diagnosis and differentiation of sporadic Creutzfeldt-Jakob disease (sCJD).@*Methods@#sCJD (according to 2009 Brain criteria, 2018 Neurology amended criteria), Alzheimer's disease (AD; the National Institute on Aging at National Institutes of Health and the Alzheimer's Association revised guidelines 2011 criteria) and other patients without cognitive impairment, matched for sex and age, in the Department of Neurology, Peking Union Medical College Hospital from 2018 to 2019 were enrolled. Twelve sCJD patients, 49 AD patients and 14 normal controls were enrolled. Cerebrospinal fluid (CSF) specimens were collected through gravity dropping directly, and further stored in -80 ℃ and disposed according to widely used standards. The levels of T-tau and P-tau were measured by ELISA. The data on electroencephalogram and neuroimaging findings of sCJD patients were recorded. Moreover, specimens of sCJD patients were sent to the Chinese Center for Disease Control and Prevention to test 14-3-3 protein and PRNP genotype.@*Results@#Using Mann-Whitney U test, T-tau concentrations were found higher in patients with sCJD (1 211(448, 2 227) pg/ml) than in AD patients (549(314, 1 078) pg/ml; U=178, P=0.034 9), and both groups had higher T-tau than the control group (127(79, 192) pg/ml; U=20, 73, P<0.01). The level of P-tau was significantly increased in AD patients (72(58,109) pg/ml) compared to the control group (27(15, 42) pg/ml; U=82, P<0.01), but not in sCJD patients (32(24, 47) pg/ml). The T-tau/P-tau ratio was higher in sCJD patients (29.77(20.01, 54.53)) than in AD patients (7.45(4.79, 10.43); U=87, P<0.01). Twelve sCJD patients had cotical hyperintensity on diffusion weighted imaging and five had periodic three-phase waves on electroencephalogram. Nine sCJD patients, whose CSF samples were tested in the Chinese Center for Disease Control and Prevention, carried an M/M genotype at codon 129 and E/E at codon 219.@*Conclusion@#The CSF tau level and T-tau/P-tau ratio are significantly increased in sCJD, which may promote the diagnosis and differentiation of sCJD in routine clinical setting.

Changes of tau protein in cerebrospinal fluid of sporadic Creutzfeldt-Jakob disease / 中华神经科杂志

protein (T-tau),phosphorylated-tau protein (P-tau) in diagnosis and differentiation of sporadic Creutzfeldt-Jakob disease (sCJD).Methods sCJD (according to 2009 Brain criteria,2018 Neurology amended criteria),Alzheimer's disease (AD;the National Institute on Aging at National Institutes of Health and the Alzheimer's Association revised guidelines 2011 criteria) and other patients without cognitive impairment,matched for sex and age,in the Department of Neurology,Peking Union Medical College Hospital from 2018 to 2019 were enrolled.Twelve sCJD patients,49 AD patients and 14 normal controls were enrolled.Cerebrospinal fluid (CSF) specimens were collected through gravity dropping directly,and further stored in-80℃ and disposed according to widely used standards.The levels of T-tau and P-tau were measured by ELISA.The data on electroencephalogram and neuroimaging findings of sCJD patients were recorded.Moreover,specimens of sCJD patients were sent to the Chinese Center for Disease Control and Prevention to test 14-3-3 protein and PRNP genotype.Results Using Mann-Whitney U test,T-tau concentrations were found higher in patients with sCJD (1 211(448,2 227) pg/ml) than in AD patients (549(314,1 078) pg/ml;U=178,P=0.0349),and both groups had higher T-tau than the control group (127(79,192) pg/ml;U=20,73,P＜0.01).The level of P-tau was significantly increased in AD patients (72(58,109) pg/ml) compared to the control group (27(15,42) pg/ml;U=82,P＜0.01),but not in sCJD patients (32(24,47) pg/ml).The T-tau/P-tau ratio was higher in sCJD patients (29.77(20.01,54.53)) than in AD patients (7.45(4.79,10.43);U=87,P＜0.01).Twelve sCJD patients had cotical hyperintensity on diffusion weighted imaging and five had periodic three-phase waves on electroencephalogram.Nine sCJD patients,whose CSF samples were tested in the Chinese Center for Disease Control and Prevention,carried an M/M genotype at codon 129 and E/E at codon 219.Conclusion The CSF tau level and T-tau/P-tau ratio are significantly increased in sCJD,which may promote the diagnosis and differentiation of sCJD in routine clinical setting.

Motor nerve conduction and clinical characteristics of POEMS syndrome / 中华神经科杂志

Objective@#To summarize the clinical characteristics and nerve conduction damage in patients with early POEMS syndrome, and to explore the value of segment nerve conduction velocity in the diagnosis of POEMS syndrome. @*Methods@#A total of 73 patients with POEMS syndrome and 27 healthy controls in Peking Union Medical College Hospital from September 2009 to June 2019 were recruited in this study. The motor and sensory nerve conduction characteristics of median, ulnar, tibial, and peroneal nerves and the clinical features of the participants were analyzed. The analysis parameters included: (1) distal motor latency (DML), compound muscle action potential (CMAP); (2) the median velocity from elbow to wrist, the median velocity from axillary to elbow, the ulnar velocity from the site below elbow to wrist, the ulnar velocity from the site above elbow to below elbow, the ulnar velocity from axillary to the site above elbow, the tibial velocity from ankle to knee, the peroneal velocity from ankle to fibulae capitulum; (3) sensory nerve conduction velocity and amplitude of these nerves; (4) terminal latency indices (TLI) of median; (5) motor nerve conduction blocks. @*Results@#Peripheral nerve damages were the initial symptoms in thirty-two patients in this group, accounting for 43.8% (32/73), and 81.3% (26/32) of these patients only showed numbness in lower extremities. All POEMS syndrome patients with numbness had abnormal sensory nerve conduction, and 9.5% (7/73) of patients without sensory symptoms also had abnormal sensory nerve conduction. On the other hand, the decrease of CMAP amplitude corresponded to clinical muscle strength decline and motor dysfunction. In the patients with POEMS syndrome, motor nerve conduction in the lower limbs were more likely to be affected and the damages were more severe than in the upper limbs: the proportion of CMAP disappearance in the lower limbs and upper limbs was 47.6% (112/235) vs 2.8% (7/252; χ2=133.698, P<0.01). Sensory nerve conduction damage was more severe than motor nerve conduction: the proportion of amplitude disappearance in sensory and motor conduction was 43.0% (141/328) vs 24.4% (119/487; χ2=133.698, P<0.01). The slowing of motor nerve conduction velocity was more common than the decrease of CMAP amplitude: the rate of slowing down of motor nerve conduction was 88.7% (432/487), and the rate of decrease of amplitude was 52.8% (257/487; χ2=151.905, P<0.01). The DML of median and ulnar nerve in the POEMS syndrome group was longer than that in the control group (median nerve: 4.4 (3.7, 5.0) ms vs 3.2 (3.0, 3.5) ms, U=854.000, P<0.01; ulnar nerve: 3.1 (2.7, 3.8) ms vs 2.5 (2.2, 2.7) ms, U=1 077.500, P<0.01). The TLI of median nerve in patients with POEMS syndrome was significantly higher than that of healthy controls (0.40±0.11 vs 0.35±0.06, t=3.466, P=0.001). There was no statistically significant difference in nerve conduction velocity between the forearm segment and the upper arm segment in the POEMS group. @*Conclusions@#Neurological damages were common in patients with POEMS syndrome with sensory nerve damage often being the initial clinical manifestation. In patients with POEMS syndrome, the nerve damage in the lower limbs was more severe than in the upper limbs, and sensory nerve damage was more severe than motor nerve damage. Segmental motor nerve conduction results suggested that demyelination damage occurred earlier than axonal damage, and proximal lesions were slightly heavier than distal lesions. No conduction block was detected in these patients. These characteristics of segmental nerve conduction can provide more evidence for clinical diagnosis of POEMS syndrome.

Clinical Diagnosis and Treatment Recommendations for Adverse Reaction in the Nervous System Related to Immunocheckpoint Inhibitor / 中国肺癌杂志

Immune checkpoint inhibitors (ICIs) can cause adverse reactions in the nervous system, with the incidence rate ranging from 0.1% to 12%, and 80% occurring within the first 4 months of ICI application. It can cause lesions in various parts of the nervous system, including aseptic meningitis, meningoencephalitis, necrotizing encephalitis, brainstem encephalitis, transverse myelitis and other central nervous system diseases. It can also cause cranial peripheral neuropathy, multifocal radicular neuropathy, Guillain-Barre syndrome, spinal radicular neuropathy and myasthenia gravis, myopathy, etc. For these complications of the nervous system, diagnosis could be made by sufficient collection of disease manifestations combined with imaging, cerebrospinal fluid examinations, electro-encephalogram or electro myography to exclude infection or tumor progression. In the treatment of severe cases, ICIs should be discontinued and treated with high doses of glucocorticoid or gamma globulin with systemic support. After neurological adverse reactions, the prognosis of severe cases is poor.

Diffusion tensor imaging studies of amyotrophic lateral sclerosis patients with various levels of cognitive impairment / 中华神经科杂志

Objective To characterize the brain microstructure changes of amyotrophic lateral sclerosis (ALS) patients with various levels of cognitive impairment as measured by diffusion tensor imaging (DTI).Methods A total of 55 ALS patients and 20 healthy controls (HC) were enrolled in the Department of Neurology of Peking Union Medical College Hospital From September 2013 to March 2017,and all participants underwent neuropsychological assessments and DTI scans.According to their cognitive performance,ALS patients were further subclassified into ALS with normal cognition (ALS-Cn,n =27),ALS with cognitive impairment (ALS-Ci,n =17) and ALS-frontotemporal dementia (ALS-FTD,n =11)subgroups.Comparisons of voxel-based and atlas-based fractional anisotropy (FA) and mean diffusivity (MD) data were conducted among the four subgroups.Results In the voxel-based analyses,the FA showed significant differences in cingulate gyms,corpus callosum,brain stem and cerebellum,and MD showed significant differences in bilateral frontal lobe,temporal lobe,cingulate gyms,corpus callosum,and cerebellum among the four subgroups.Besides,when compared to ALS-Ci,ALS-Cn and HC groups in the order,the areas of involvement were larger and differences were more significant in ALS-FTD group.In the atlas-based analyses,the FA and MD of the corticospinal tracts revealed no difference within the patients groups,but decreased FA and increased MD were found compared to HC group.The ALS-IFD patients manifested widespread white matter fiber integrity damage and microstructure impairment in the extramotor areas compared to other three groups.Conclusion The brain white matter structural patterns of ALS patients correlate with their cognitive function,and there is a gradient of alterations across the ALS-Cn,ALS-Ci and ALS-FTD continuum.

Initial exploration on clinical application of resting-state functional magnetic resonance imaging amplitude of low-frequency fluctuation method on cognitive impairment in amyotrophic lateral sclerosis / 中华神经科杂志

Objective To explore diagnostic value of amplitude of low-frequency fluctuation ( ALFF) on cognitive impairment in amyotrophic lateral sclerosis ( ALS ) using resting-state functional magnetic resonance imaging ( MRI ) .Methods Sixteen ALS patients from neurological clinic in Peking Union Medical College Hospital were enrolled between November 2013 and April 2015.The patients were divided into two groups by the presence (ALSi, n=7) or absence (ALSu, n=9) of cognitive impairment. Routine MRI structural images and resting-state functional MRI were collected for comparison between groups through voxel-based morphometry ( VBM ) and ALFF.Results ( 1 ) Neuropsychological analysis showed significant differences in Montreal Cognitive Assessment score (22.9 ±2.0 vs 25.8 ±2.3, t=2.622, P=0.020), Frontal Assessment Battery score (12.4 ±1.6 vs 15.1 ±1.4, t=3.600, P=0.003), animal listing test (13.6 ±1.8 vs 16.7 ±2.9, t=2.482, P=0.026), naming test (2(1) vs 0(1), Z=-2.746, P=0.006), similarity test (7.9 ±3.7 vs 17.3 ±2.8, t=5.846, P=0.000) and clock drawing test (2(2) vs 3(0), Z=2.516, P=0.012).(2) VBM analysis showed no significant differences in both gray matter and white matter density between the two groups .(3) ALFF analysis showed significantly increased signals in widespread areas of bilateral cerebrum and cerebellum in ALSi group compared to ALSu group . Conclusion ALFF value has the potential to provide more valuable imaging basis for early diagnosis on cognitive impairment in ALS.

Rural environment, pesticide exposure and the risk of amyotrophic lateral sclerosis: a meta analysis / 中华神经科杂志

Objective To explore the relationship between the risk of amyotrophic lateral sclerosis (ALS) and exposure to rural environments and pesticide.Methods Studies relevant to rural residence,farmer occupation,pesticide exposure and ALS were identified from the databases including Embase,Ovid Medline,Pubmed,Cochrane Library,Wanfang data,Chinese BioMedical Literature Database,Chinese National Knowledge Infrastructure,China Science and Technology Journal Database up to March 2015.Quality of studies was assessed according to the Newcastle-Ottawa Scale (NOS).Analysis of data and publication bias was performed with software Revman 5.3.Results A total of 24 case-control studies and 3 cohort studies were included into the analysis.The NOS scores of all studies were ≥6.The risk of ALS was associated with pesticide exposure (OR =1.41,95％ CI 1.28-1.56) and farmer occupation (OR =1.42,95％ CI 1.29-1.57),but not associated with rural residence (OR =1.21,95％ CI 0.97-1.51).Subgroup analysis of pesticide exposure and ALS revealed that males (OR =1.75,95％ CI 1.39-2.21) had a higher risk than females (OR =1.53,95％ CI 1.13-2.08),and the risk estimate was higher in studies using E1 Escorial standard (OR =1.68,95％ CI 1.45-1.95) than studies not (OR =1.23,95％ CI 1.08-1.40).The meta analysis had a slight publication bias.Conclusions Our findings support pesticide exposure might increase the risk of ALS.Given that farmers always have high levels of pesticide exposure in their work,they should decrease their exposure level or take proper precautions to lower the risk of ALS.