Honokiol alleviated neurodegeneration by reducing oxidative stress and improving mitochondrial function in mutant SOD1 cellular and mouse models of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment.

Clinical utility of bedside electromyography in critical ill with suspected neuromuscular diseases / 中华神经科杂志

Objective To investigate the utility of bedside electromyography (EMG) in diagnosis and management of critical illness patients with suspected neuromuscular diseases.Methods Bedside EMG was performed in 34 critical illness patients with weakness and respiratory involvement,including segmental motor nerve conduction studies,sensory nerve conduction studies,F waves,concentric needle EMG and repetitive nerve stimulation.The clinical manifestations and clinical utility of bedside EMG in critical illness patients with suspected neuromuscular diseases were analyzed. Results EMG was normal in 5 patients.Low-frequency repetitive nerve stimulation showed decrement response of compound muscle action potential (CMAP) in 4 of 8 patients.Motor nerve conduction studies showed CMAP amplitude decreased in 73.3％(22/30) patients,and demyelinating changes was detected in 20.0％ (6/30)patients.F-wave persistence was 0 in 55.0％ (11/20) patients.Amplitude of sensory nerve action potential decreased in 28.6％ (6/21)patients.Bedside EMG could help to confirm or exclude diagnoses and guide the management in 82.4％(28/34) patients,confirm the diagnoses of peripheral neuropathy but have no effect on management in 11.8％ (4/34) patients,and bedside EMG was inconclusive in 2 patients.Conclusions Bedside EMG is useful for the diagnosis and management of critical ill with suspected neuromuscular diseases,while motor nerve conduction studies and repetitive nerve stimulation are more valuable.Individualized protocol for EMG studies should be made on the basis of clinical problem.

Correlation between muscle strength and electromyography with blood potassium level after exercise test in patients with hypokalemic periodic paralysis / 中华神经科杂志

Objective To assess the correlations between muscle strength and amplitude of compound muscle action potential(CMAP)with blood potassium level in hypokalemic periodic paralysis after long exercise test(ET).Methods ET of abductor digiti minimi(ADM)was performed on 78 patients with hypokalemic periodic paralysis.Ulnar and median CMAP amplitude,blood potassium level,muscle strength of ADM,palmar interossei muscle and abductor pollicis brevis were measured before and 120 minutes after exercise.The correlations of muscle strength,CMAP amplitude and blood potassium level were analyzed.Results Ulnar CMAP amplitude was(4.6 ±2.7)mV after ET and(9.6 ±3.2)mV before ET(t =16.047,P =0.000)in 78 patients with hypokalemic periodic paralysis,respectively.Median CMAP amplitude was(10.9 ± 4.2)mV after ET and(11.2 ± 3.9)mV before ET(t =0.673,P =0.822),respectively.After ET,muscle strength of ADM decreased in 76 patients,score on MRC was less than Ⅲ in ADM but V in palmar interossei muscle and abductor pollicis brevis in 41 patients,the blood potassium level was tested in 10 of them,which was(3.8 ±0.3)mmol/L before ET and(3.9 ±0.4)mmol/L after ET(t =0.395,P =0.702).Conclusion In patients with hypokalemic periodic paralysis,blood potassium level is not the key factor affecting muscle strength and CMAP amplitude after ET.

Nerve conduction studies in 205 patients with amyotrophic lateral sclerosis / 中华神经科杂志

Objective To investigate the F-wave and nerve conduction in patients with amyotrophic lateral sclerosis (ALS) and explore the correlation between these parameters and muscle strength, disease duration and onset site.Methods The data of outpatients and inpatients diagnosed with ALS were collected in Peking Union Medical College Hospital from January 1997 to May 2008.Standard sensory and motor nerve conduction study of the median nerve, ulnar nerve and tibial nerve was performed in 205 patients with ALS.F-wave velocity and frequency was measured in median nerve.Parameters for analyses included sensory conduction velocity and amplitude, distal motor latency (DML), and compound muscle action potential (CMAP) amplitude.Correlation between muscle strength and DML, CMAP amplitude or F-wave frequency were also explored.Results Delayed DML of the median nerve, ulnar nerve and tibial nerve were found in 24.9% (48/193), 15.3% (25/163), 21.2% (7/33) of patients respectively.Decreased CMAP amplitudes were found in 57.0% (110/193), 49.7% (81/163), 39.4% (13/33) of patients respectively.Decreased F-wave frequency of the median nerve was found in 68.9% (122/177) of patients.The abnormality of DML,CMAP amplitude and F-wave frequency of median nerve were increased in weaker muscles.Decreased median nerve CMAP amplitude (81.5% (53/65)) and F-wave abnormality (decreased persistence 70.9%(44/62), absent responses 45.1% (28/62)) in spinal onset groups were significantly higher than those in bulbar onset groups (CMAP 32.4% (11/34); F-wave: decreased persistence 38.2% (13/34), absent responses 14.7% (5/34); x2 = 23.629, 9.753, 9.029,all P <0.01).Compared with the bulbar onset group,the abnormality of DML in spinal onset group was higher, but not reach statistical significance.Logistic regression revealed a strong direct association between decreased CMAP amplitudes and upperextremity muscles strength, disease duration and onset symptom.Abnormality of F-wave frequency was associated with upper-extremity muscles strength and onset symptom.Conclusions Delayed DML and decreased amplitude of CMAP are found in ALS patients.CMAP amplitude is a sensitive parameter related to the severity of ALS.F-wave velocity is relatively normal while F-wave frequency of the median nerve is correlated with muscle strength.Decreasing CMAP amplitude and F-wave frequency are correlated strongly with muscle weakening,disease duration and symptom onset over limbs.

Difference of segmental motor nerve conduction study between chronic inflammatory demyelinating polyradiculoneuropathy and Clarcot-Marie-Tooth type 1 / 中华神经科杂志

Objective to assess the utility of segmental motor nerve conduction study in differential diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy(CIDP)and Charcot-Marie-Tooth type 1(CMT1).Methods A segmental motor nerve conduction study was performed on 16 patients with CIDP and 13 patients with CMT1.Distal motor latency,motor nerve conduction velocity,the changes of amplitude,area and duration of compound motor action potential over conventional segment were compared between the groups.ResultsDistal motor latency was (5.6±3.4) ms in CIDP and (9.3±2.1) ms in CMT1(t=5.347 P=0.000),motor nerve conduction velocity was (31.1±14.3) m/s in CIDP and(22.2±5.8)m/s(t=6.369,P=0.000),M50 of the decrease in amplitude over conventional segment was 29.7% in CIDP and 4.9% in CMT1 (Z=7.141,P=0.000).Distal motor latency was normal in 40.3% (25/62) nerves and motor nerve conduction velocity was normal in 18.1% (26/44)of segments in CIDP,while distal motor latency and motor nerve conduction velocity were abnormal in all nerves in CMT1.Motor nerve conduction block or abnormal temporal dispersion was detected in 29.2% segments in CIDP and 3.0% in CMT1 (x2=20.829,P=0.000).Conclusions The segmental motor nerve conduction study can help separate CIDP and CMT1.When motor nerve conduction block or abnormal temporal dispersion is detected,the motor nerve conduction velocity is distinctly various in different segments,the diagnosis of CIDP but not CMT1 should be considered.

Progress of MRI study on amyotrophic lateral sclerosis / 中国实用内科杂志

ALS is a progressive neurodegenerative disease affecting both lower and upper motor neurons,including the pyramidal tract.There have been no objective and effective method to evaluate the lesions of upper motor neurons.With non-invasive,sensitive and macroscopic advantages,the application of Regular MR,MRS,DWI,function MR and VBM on ALS will undoubtedly have great potentials in the diagnosis,disease monitor and therapy of ALS.