Increase of HCN current in SOD1-associated amyotrophic lateral sclerosis.

The clinical manifestations of sporadic amyotrophic lateral sclerosis (ALS) vary widely. However, the current classification of ALS is mainly based on clinical presentations, while the roles of electrophysiological and biomedical biomarkers remain limited. Herein, we investigated a group of patients with sporadic ALS and an ALS mouse model with superoxide dismutase 1 (SOD1)/G93A transgenes using nerve excitability tests (NET) to investigate axonal membrane properties and chemical precipitation, followed by enzyme-linked immunosorbent assay analysis to measure plasma misfolded protein levels. Six of 19 patients (31.6%) with sporadic ALS had elevated plasma misfolded SOD1 protein levels. In sporadic ALS patients, only those with elevated misfolded SOD1 protein levels showed an increased inward rectification in the current-threshold (I/V) curve and an increased threshold reduction in the hyperpolarizing threshold electrotonus (TE) in the NET study. Two familial ALS patients with SOD1 mutations also exhibited similar electrophysiological patterns of NET. For patients with sporadic ALS showing significantly increased inward rectification in the I/V curve, we noted an elevation in plasma misfolded SOD1 level, but not in total SOD1, misfolded C9orf72, or misfolded phosphorylated TDP43 levels. Computer simulations demonstrated that the aforementioned axonal excitability changes are likely associated with an increase in hyperpolarization-activated cyclic nucleotide-gated (HCN) current. In SOD1/G93A mice, NET also showed an increased inward rectification in the I/V curve, which could be reversed by a single injection of the HCN channel blocker, ZD7288. Daily treatment of SOD1/G93A mice with ZD7288 partially prevented the early motor function decline and spinal motor neuron death. In summary, sporadic ALS patients with elevated plasma misfolded SOD1 exhibited similar patterns of motor axonal excitability changes as familial ALS patients and ALS mice with mutant SOD1 genes, suggesting the existence of SOD1-associated sporadic ALS. The observed NET pattern of increased inward rectification in the I/V curve was attributable to an elevation in the HCN current in SOD1-associated ALS.

An electrophysiological prognostic diagnosis for facial palsy.

Two electrophysiological tests for facial palsy-electroneurography (ENoG) and nerve excitability test (NET)-were reviewed. ENoG has advantages over NET in that it reflects the percentage of degenerated facial nerve fibers and can provide an accurate prognosis. However, as disadvantages, ENoG requires large, expensive equipment, and such supramaximal electrical stimulation can be quite painful for patients. NET is less painful due to weak stimulation with just enough current to meet the threshold, and the required equipment is compact and inexpensive to procure. However, it is impossible to calculate the percentage of degenerated nerve fibers, and NET is inferior to ENoG in terms of accurate prognostic prediction for facial palsy. The appropriate timing for both ENoG and NET is 7 to 10 days after the onset. While ENoG has proven more popular than NET because of its accuracy for prognostic prediction, we should not predict the prognosis of facial palsy based solely on the results of electrophyisiolgical examinations; a comprehensive evaluation including the facial muscle grading system is essential.

Nerve excitability test and lead toxicity: a case-control study.

BACKGROUND: Although conventional electrophysiological parameters have been proposed as clinical indicators for monitoring lead neuropathies, their correlations with blood lead level are weak. In this study, we investigated the applicability of nerve excitability tests (NETs) to evaluate lead intoxication. METHODS: Fourteen workers who were exposed to lead with an elevated blood level ranging from 17.8 to 64.9 µg/dL and 20 healthy controls with similar ages and body heights were enrolled. Both workers and controls underwent nerve conduction studies (NCSs), motor evoked potentials (MEPs) with transcranial magnetic stimulation (TMS), and NETs. RESULTS: NCSs showed prolonged distal latencies and decreased motor nerve conduction velocity of median nerves in the workers but without significant correlation to blood lead level (BLL). Significantly prolonged MEP latency was observed in the workers (+ 6 ms). NETs demonstrated hyperpolarized resting membrane potentials in stimulus-response curves and changes in the property of potassium channels under a hyperpolarized current in threshold electrotonus, implying that lead hyperpolarized nerves by interfering with potassium channels. NETs also showed a better correlation with BLL than conventional electrophysiological parameters. CONCLUSIONS: Axonal hyperpolarization and central conduction delay are more apparently reflecting elevated BLL than NCS. NET may have the potential for early detection of lead neuropathy.

Bell's Palsy: A Review.

Bell's palsy, also known as "acute facial palsy of unknown cause", is a common cranial neuropathy leading to facial muscle paresis or complete paralysis characteristically on one side, occurring suddenly and may progress over 48 hours. It results from facial nerve dysfunction due to trauma or inflammation of the 7th cranial nerve or facial nerve or its branches along its course, primarily in the bony canal. Both sexes are equally affected, and though no age is immune, its incidence rises with increasing age. The risk is high in diabetics, hypertensives, women who are pregnant, obese, and people with upper respiratory tract infections. It is considered chiefly idiopathic and is diagnosed by the exclusion of other causes. Bell's palsy can cause physical and psychological complications and negatively impact patients and their relatives. Thus, early diagnosis and quick cause determination are prime roles in proper treatment. However, the exact etiology of Bell's palsy is unknown, affecting its treatment. Still, determining probable causative and risk factors is critical for employing a targeted treatment approach and requires a comprehensive examination and a complete history. Although the majority of patients recover spontaneously in less than three weeks even if they are not treated. But there is always a risk of residual paresis after treatment or recovery, which may require medical help. This review aims to furnish the most thorough understanding of Bell's palsy, focusing on anatomy, etiology, clinical features, diagnosis, clinical consequences,and preferred therapy approaches.

Recurrent facial palsy: The prognostic value of electrophysiological tests according to recurrence interval.

OBJECTIVE: The prognostic value of nerve excitability tests (NET) and electroneurography (ENoG) for recurrent peripheral facial palsy is poorly understood. This study aimed to evaluate the association between NET/ENoG results for the current palsy and recovery. METHODS: We extracted data on patients who were referred to our hospital (2005-2017). Adult patients with recurrent peripheral facial palsy who underwent NET and ENoG within 3 weeks of onset were retrospectively analyzed (n = 26). Favorable recovery was defined as the achievement of either House-Brackmann grade I/II or the same level of facial movement as before the current palsy. We evaluated the predictive NET/ENoG results by making comparison between the favorable recovery group and the unfavorable recovery group, which were subdivided based on the length of time after the previous palsy. RESULTS: In terms of patients with a >4-year recurrent interval, 8 out of 12 patients achieved favorable recovery. Compared to the favorable recovery group, the unfavorable recovery group had significantly higher NET results (9.03 mA vs. -1.08 mA, p = 0.017). Also, the unfavorable recovery group had significantly higher NET results in patients with a >2-year recurrent interval (9.03 mA vs. 1.06 mA, p = 0.036). However, other test results (NET in ≤4-year recurrent interval/all 26 patients, and ENoG in >4-year recurrent interval/≤4-year recurrent interval/all 26 patients) did not differ significantly between patients with favorable and unfavorable recovery. CONCLUSION: NET might be a useful prediction method in patients with at least a few years interval between the previous and the current palsy.

Elucidating Unique Axonal Dysfunction Between Nitrous Oxide Abuse and Vitamin B12 Deficiency.

Introduction: Abuse of nitrous oxide (N2O) has an unusually high lifetime prevalence in developed countries and represents a serious concern worldwide. Myeloneuropathy following the inhalant abuse is commonly attributed to the disturbance of vitamin B12 metabolism, with severe motor deficits are often noted. The present study aims to elucidate its underlying pathophysiology. Methods: Eighteen patients with N2O abuse or vitamin B12 deficiency were recruited. Comprehensive central and peripheral neuro-diagnostic tests were performed, including whole spine MRI, and thermal quantitative sensory testing (QST). Specifically, paired motor and sensory nerve excitability tests were performed in order to obtain a complete picture of the sensorimotor axonal damage. Results: The mean duration of N2O exposure for the N2O abuse patients was 17.13 ± 7.23 months. MRI revealed T2 hyperintensity in 87.5% of the N2O abuse patients and 50% of the vitamin B12 deficiency patients. In N2O abuse patients, the motor nerve excitability test showed decreased in peak response (7.08 ± 0.87 mV, P = 0.05), increased latency (7.09 ± 0.28 ms, P < 0.01), increased superexcitability (-32.95 ± 1.74%, P < 0.05), and decreased accommodation to depolarizing current [TEd (40-60 ms) 56.53 ± 0.70%, P < 0.05]; the sensory test showed only decreased peak response (30.54 ± 5.98 µV, P < 0.05). Meanwhile, motor test in vitamin B12 deficiency patients showed only decreased accommodation to depolarizing current [TEd (40-60 ms) 55.72 ± 1.60%, P < 0.01]; the sensory test showed decreased peak response (25.86 ± 3.44 µV, P < 0.05) increased superexcitability (-28.58 ± 3.71%, P < 0.001), increased subexcitability (8.31 ± 1.64%, P < 0.05), and decreased accommodation to depolarizing current [TEd (peak) 67.31 ± 3.35%, P < 0.001]. Conclusion: Compared to vitamin B12 deficiency, N2O abuse patients showed prominent motor superexcitability changes and less prominent sensory superexcitability changes, hinting a unique pathological process different from that of vitamin B12 deficiency. N2O abuse might cause axonal dysfunction not only by blocking methionine metabolism but also by toxicity affecting the paranodal region.

IH activity is increased in populations of slow versus fast motor axons of the rat.

Much is known about the electrophysiological variation in motoneuron somata across different motor units. However, comparatively less is known about electrophysiological variation in motor axons and how this could impact function or electrodiagnosis in healthy or diseased states. We performed nerve excitability testing on two groups of motor axons in Sprague-Dawley rats that are known to differ significantly in their chronic daily activity patterns and in the relative proportion of motor unit types: one group innervating the soleus ("slow motor axons") and the other group innervating the tibialis anterior ("fast motor axons") muscles. We found that slow motor axons have significantly larger accommodation compared to fast motor axons upon application of a 100 ms hyperpolarizing conditioning stimulus that is 40% of axon threshold (Z = 3.24, p = 0.001) or 20% of axon threshold (Z = 2.67, p = 0.008). Slow motor axons had larger accommodation to hyperpolarizing currents in the current-threshold measurement (-80% Z = 3.07, p = 0.002; -90% Z = 2.98, p = 0.003). In addition, we found that slow motor axons have a significantly smaller rheobase than fast motor axons (Z = -1.99, p = 0.047) accompanied by a lower threshold in stimulus-response curves. The results provide evidence that slow motor axons have greater activity of the hyperpolarization-activated inwardly rectifying cation conductance (IH) than fast motor axons. It is possible that this difference between fast and slow axons is caused by an adaptation to their chronic differences in daily activity patterns, and that this adaptation might have a functional effect on the motor unit. Moreover, these findings indicate that slow and fast motor axons may react differently to pathological conditions.

Peripheral nerve axon involvement in myotonic dystrophy type 1, measured using the automated nerve excitability test.

BACKGROUND AND PURPOSE: Primary involvement of the peripheral nerves in myotonic dystrophy type I (MyD1) is controversial. We investigated whether the involvement of peripheral nerves is a primary event of MyD1 or secondary to another complication such as diabetes mellitus (DM). METHODS: The subjects comprised 12 patients with MyD1, 12 with DM and no peripheral nerve involvement, and 25 healthy volunteers. We measured multiple excitability indices in the median motor axons. The strength-duration time constant was calculated from the duration-charge curve, the threshold electrotonus and current-threshold relationships were calculated from the sequential subthreshold current, and the recovery cycle was derived from double suprathreshold stimulation. RESULTS: The depolarizing and hyperpolarizing threshold electrotonus were significantly reduced and exhibited increased refractoriness in the MyD1 group compared with the DM and control groups. The SDTC, superexcitability, and subexcitability were not significantly altered in the MyD1 group. CONCLUSIONS: The MyD1 group exhibited a depolarized axonal membrane potential. The significant differences in peripheral nerve excitability between the MyD1 group and the DM and normal control groups suggest that peripheral neuropathy is a primary event in MyD1 rather than a secondary complication of DM.

Peripheral Nerve Axon Involvement in Myotonic Dystrophy Type 1, Measured Using the Automated Nerve Excitability Test

BACKGROUND AND PURPOSE: Primary involvement of the peripheral nerves in myotonic dystrophy type I (MyD1) is controversial. We investigated whether the involvement of peripheral nerves is a primary event of MyD1 or secondary to another complication such as diabetes mellitus (DM). METHODS: The subjects comprised 12 patients with MyD1, 12 with DM and no peripheral nerve involvement, and 25 healthy volunteers. We measured multiple excitability indices in the median motor axons. The strength-duration time constant was calculated from the duration-charge curve, the threshold electrotonus and current-threshold relationships were calculated from the sequential subthreshold current, and the recovery cycle was derived from double suprathreshold stimulation. RESULTS: The depolarizing and hyperpolarizing threshold electrotonus were significantly reduced and exhibited increased refractoriness in the MyD1 group compared with the DM and control groups. The SDTC, superexcitability, and subexcitability were not significantly altered in the MyD1 group. CONCLUSIONS: The MyD1 group exhibited a depolarized axonal membrane potential. The significant differences in peripheral nerve excitability between the MyD1 group and the DM and normal control groups suggest that peripheral neuropathy is a primary event in MyD1 rather than a secondary complication of DM.

Correlation study on syndrome type and effect of TCM and facial nerve excited threshold in facial paralysis patients / 中华中医药杂志

0.05).Conclusions:Facial nerve excited threshold detection was a simple and effective method of conjecturing TCM syndrome and severity and prognosis of facial paralysis patients.

Analysis of Nerve Excitability Test and Stapedial Reflex on the Prognosis of Facial Nerve Paralysis / 听力学及言语疾病杂志

Objective To evaluate the clinical application of nerve excitability test and stapedial reflex on the prognosis of facial nerve paralysis. Methods The threshold of excitability of the branches of facial nerves in both sides and stapedial reflex were tested in 50 patients.Results 34 patients out of 42 with differences of nerve excited threshold less than 3.5 mA showed complete recovery (81%),while only 2 patients out of 8 with the differences of nerve excited threshokd more than 3.5 mA showed recovery (25%), 32 patients out of 36 with positive response of stapedial reflex showed recovery (88.9%), but only 3 patients out of 14 recovered (21.4%) in non-response group.Conclusion The difference of nerve excited threshold of both sides less than 3.5 mA and positive response of stapedial refles showed a better prognosis, suggesting no severe injury to facial nerve and both nerve excitability test and stapedial reflex were useful chinical parameters to predict the prognosis of facial paralysis.