奥沙利铂所致神经毒性和神经病变进展

The pathophysiology of oxaliplatin-induced neurotoxicity remains unclear, a lthough in vitro studies suggest involvement of voltage- gated Na+ channels. In the present study, clinical assessment was combined with nerve conduction stu dies (NCS) and nerve excitability studies in 16 patients after completion of oxa liplatin therapy. Chronic neuropathic symptoms persisted in 50% of patients. N CS confirmed abnormalities in symptomatic patients: sensory potentials were sign ificantly low, whereas motor studies remained essentially normal. At 12- month follow- up of symptomatic patients, positive sensory symptoms improved but NCS abnormalities persisted. Cumulative oxaliplatin dose was a predictor of neuropat hy, and long- term effects appeared to be minimized by low single- infusion do sages. Nerve excitability measures in symptomatic patients established that axon s were of high threshold. Refractoriness was significantly greater in patients ( symptomatic group, 56.3± 24.9% ; entire patient group, 46.3± 12.5% ; control s, 27.1± 1.9% ; P < 0.05). Thus, although positive sensory symptoms of oxalipl atin- induced neuropathy improved, negative sensory symptoms and abnormalities of sensory nerve conduction persisted. Differences in nerve excitability measure s, particularly refractoriness, support in vitro studies indicating involvement of voltage- gated transient Na+ - channel dysfunction in the development of o xaliplatin- induced neurotoxicity.

胞浆体肌病误认为运动神经元病

Cytoplasmic body myopathy (CBM) is characterized by proteinaceous inclusion bo dies in muscle tissue. A 43 year old woman presented with rapidly progressive weakness and dysphagia. Electromyography (EMG) elsewhere demonstrated lower lim b chronic partial denervation. Muscle biopsy showed fiber size variation without diagnostic features. A diagnosis of possible motor neuron disease was made and the patient was commenced on riluzole. Subsequently, the patients condition st abilized, prompting reassessment. Repeat EMG demonstrated no features of denervation and was more suggestive of a myopathic process. Review of the orig inal muscle biopsy showed cytoplasmic bodies. The case highlights a further diag nostic possibility in the assessment of patients with “possible”motor neuron d isease. The clinical features of CBM are briefly reviewed.

终末期肾病患者运动神经兴奋性的改变

Although multiple toxins have been implicated in the development of uraemic neuropathy, no causative agent has been identified. In the present study, the excitability properties of lower limb motor nerves in patients with end-stage kidney disease treated with haemodialysis were measured before, during and after a standard 5 h haemodialysis session, in an attempt to explore the pathophysiology of uraemic neuropathy. Compound muscle action potentials were recorded from tibialis anterior and extensor digitorum brevis, following stimulation of the common peroneal nerve in 14 patients. Measures of excitability were assessed in relation to changes in serum levels of potential neurotoxins, including potassium, calcium, urea, uric acid, parathyroid hormone and β-2-microglobulin. Before dialysis, measures of nerve excitability were significantly abnormal in the patient group for axons innervating tibialis anterior and extensor digitorum brevis, consistent with axonal depolarization: refractoriness was increased and superexcitability and depolarizing threshold electrotonus were reduced. Pre-dialysis excitability abnormalities were strongly correlated with serum K+. Correlation was also noted between the severity of symptoms and excitability abnormalities. Haemodialysis normalized the majority of nerve excitability parameters. In conclusion, lower limb motor axons in uraemic patients are depolarized before dialysis. The correlation between serum K+and excitability measures indicates that hyperkalaemia is primarily responsible for uraemic depolarization, and a likely contributing factor to the development of neuropathy.

糖尿病性神经病变神经兴奋性的变化

The underlying cause of diabetic neuropathy remains unclear,although pathological studies have suggested an ischaemic basis related to microangiopathy, possibly mediated through effects on the energy-dependent Na+/K+pump. To investigat e the pathophysiology of diabetic neuropathy, axonal excitability techniques wer e undertaken in 20 diabetic patients with neuropathy severity graded through a c ombination of quantitative sensory testing (QST) using a vibratory stimulus, ass essment of symptom severity using the Total Neuropathy Symptom Score (T-NSS) an d measurement of glycosylated haemoglobin as a marker of disease control. To ass ess axonal excitability,compound muscle action potentials were recorded at rest from abductor pollicis brevis following stimulation of the median nerve, and sti mulus-response behaviour, threshold electrotonus,a current-threshold relationship and the recovery of excitability were recorded in each patient. All patients had established neuropathy,with abnormalities of T-NSS present in all patients and QST abnormalities present in 65%. Compared w ith controls,diabetic neuropathy patients had significant reduction in maximal C MAP amplitude (P < 0.0005), accompanied by a‘fanning in’of threshold electroto nus. In addition, the strength-duration time constant was decreased in diabetic neuropathy patients and recovery cycles were altered with reductions in refract oriness,the duration of the relative refractory period, superexcitability and su bexcitability. It is proposed that while the changes in threshold electrotonus w ith supportive findings in the currentthreshold relationship are consistent with axonal depolarization,possibly mediated by a decrease in Na +/K+pump activity , the alterations in the recovery cycle of excitability could be explained on th e basis of a smaller action potential, reflecting a limitation on the nodal driv ing current imposed by a reduction in Na+conductances.