Alcoholic neuropathy: Clinical,electrophysiological, and biopsy findings

Nerve conduction and biopsy findings from the sural nerve in 37 patients with alcohokic neuropathy were compared with findings in 6 patients who had neuropathy associated with postgastrectomy malnutrition. Half the patients with alcoholic neuropathy had both muscle weakness and sensory loss, half had only sensory impairment, but all had electromyographic signs of denervation. Only half the patients, with or without muscle weakness, had signs of malnutrition. In alcoholics, sural nerve conduction velocity was slowed to at most 60% of normal, correlating with loss of large fibers. These findings, together with a marked reduction in amplitude of the sensory potentials, are consistent with axonal loss. Myelinated fiber counts showed loss of small and large fibers in most nerves, retaining a bimodal distribution. Signs of regeneration were rare. Segmental demyelination was found in only 0.3% of teased fibers. Electron microscopy confirmed axonal degeneration of myelinated and unmyelinated fibers. Neuropathy after gastrectomy malnutrition was clinically similar to alcoholic neuropathy. Conduction velocities were slower than expected from the diameter of the largest myelinated fibers, however, and teased fibers showed segmental demyelination. The findings are against alcoholic neuropathy being due to malnutrition and suggest a toxic action on peripheral nerve.     

Alcoholic polyneuropathy. Electrophysiological and clinical findings in 85 patients (author's transl)]

Maximum motor and sensory nerve conduction velocities, amplitudes of muscle action potentials (surface electrodes) and of sensory nerve action potentials, and needle electromyograms were studied in 80 patients with alcoholic neuropathy and in 5 chronic alcoholics without clinical signs of neuropathy. The electrophysiological results were compared to the clinical findings. Neurographic criteria compatible with the diagnosis "alcoholic neuropathy" were defined. Neurographic findings contrary to a diagnosis of alcoholic etiology were demonstrated in 3 patients. Only in a smaller group of patients could a reduction of conduction velocity be found, especially in regions of peripheral nerve entrapment. A decrease in conduction velocity outside of the entrapment sites can be explained in some cases by segmental demyelination in chronic hepatitis or cirrhosis of the liver.     

Corneal confocal microscopy for the diagnosis of diabetic autonomic neuropathy

Introduction: A case series of acute intermittent porphyria (AIP) is described that focuses on the clinical course of the disease with regard to neurological manifestations of the peripheral nervous system. Methods: Eight patients were diagnosed with AIP on the basis of characteristic clinical findings, erythrocyte porphobilinogendeaminase activity, neuropathic patterns, serial changes in nerve conduction studies (NCS), and temporal relationship of central nervous system involvement. Results: Six patients diagnosed with AIP <2 months after symptom onset had neuropathy that was predominantly upper extremity, motor, and proximal. NCS recovery rates were slower in the lower than the upper limbs. Two patients diagnosed >2 months after symptom onset had distal sensorimotor polyneuropathy. Conclusions: The findings from this case series suggest that the peripheral nerves may be differentially and selectively involved in different diagnostic stages of porphyric neuropathy. Muscle Nerve 51 : 363–369, 2015     

Peripheral neuropathy in patients with beta-thalassaemia.

As some patients with beta-thalassaemia manifested neurological signs, clinical and electrophysiological investigations were carried out on 53 thalassaemic patients and 29 healthy control subjects. Twenty per cent of the patients showed clinical and electrophysiological findings of a mild peripheral sensorimotor neuropathy, mainly of the lower limbs. The clinical symptoms were numbness, pins and needles sensations, muscular cramps, myalgia and muscle weakness. The electrophysiological abnormalities were manifested by decreased motor conduction velocity (MCV) and prolonged F-wave latencies of the tibial and the peroneal nerves. Borderline increase in the latencies of the sensory potentials of the median nerve was also observed. The electromyographic findings of the patients with diminished MCVs were compatible with a predominantly motor peripheral neuropathy. This neuropathy appears during the second and third decade of life.     

Central and peripheral SEP defects in neurologically symptomatic and asymptomatic subjects with low vitamin B12 levels

Somatosensory evoked potentials (SEPs) following median nerve stimulation were abnormal in 7 patients with sensory impairment due to vitamin B12 deficiency. Extensor plantar reflexes indicated a central sensory pathway lesion in 4 cases and absent tendon jerks suggested peripheral neuropathy in 4, but median nerve SEPs indicated a predominantly central lesion without marked peripheral nerve involvement in 6 and an axonal neuropathy without CNS involvement in 1. The latter had evidence of central slowing of conduction in SEPs following posterior tibial nerve stimulation. Consequently, it is suggested that the brunt of sensory pathway involvement usually falls on the CNS, although peripheral neuropathy may occur as the major abnormality in some cases. In 2 patients SEPs showed a marked improvement following treatment with vitamin B12 injections, one consistent with restored central conduction and the other with recovery from peripheral neuropathy. No peripheral or central SEP abnormalities were seen in 18 dairy-produce eating vegetarians with low vitamin B12 levels, although 6 reported mild sensory symptoms suggestive of peripheral neuropathy and 3 had corroborative clinical signs.     

Toxic polyneuropathy of shoe-industry workers. A study of 122 cases.

The toxic polyneuropathy observed in a group of shoe-industry workers in Italy was clinically characterised by a symmetrical prevalently distal motor deficit, with occasional marked weakness of pelvic girdle muscles, and frequently by only subjective sensory symptoms; non-specific disturbances usually preceded neurological signs. Subclinical cases of 'minimal' chronic neuropathy, characterised by alterations of a neurogenic type in the EMG without a reduction of motor nerve conduction velocity, were also observed. Worsening of the clinical picture, with further lowering of nerve conduction velocity, was noted in some cases up to four months after removal from the toxic environment. In the most severe cases clinical recovery took up to three years. The electromyographic and electroneurographic features were consistent with a mixed axonal neuropathy, with clear prevalence of the damage in the distal part of the nerve (dying-back neuropathy). Volatile substances, such as n-hexane and other low boiling point hydrocarbons found in high percentage in solvents and glues, are suggested as the causative agent.     

Electrophysiological studies in diabetic neuropathy

In 30 patients with diabetic neuropathy sensory potentials in the median nerve, motor conduction in the lateral popliteal and median nerves, and electromyographic findings in distal and proximal muscles were compared with the severity of symptoms and signs. All patients had abnormalities in at least one of the electrophysiological parameters. The sensory potentials were the most sensitive indicator of subclinical involvement; abnormalities were found in 24 patients, 12 of whom had no sensory symptoms or signs and five of whom had no other clinical or electrophysiological evidence of neuropathy in the upper extremities. This indicates that sensory nerve fibres may be affected before motor. The next most sensitive parameter was the presence of fibrillation potentials, found in more than half the distal muscles examined. Slowing in motor conduction in the lateral popliteal nerve was the only electrophysiological change correlated to the severity of the neuropathy, and no other electrophysiological parameter was correlated to the duration or the severity of the neuropathy or the diabetes. An onset of neuropathy before or simultaneously with the manifestations of the diabetes, as well as the frequent occurrence of asymptomatic changes in sensory conduction, support the evidence at hand that the neuropathy develops concomitantly with and as an integral part of the metabolic disturbance rather than as a consequence of the vascular complications of diabetes. Of three patients with clinical signs or symptoms of a diabetic amyotrophy, two had asymptomatic electrophysiological abnormalities in distal nerves and muscles, consistent with widespread involvement of the peripheral nerves. The third patient had electromyographic changes in the medial vastus muscles suggestive of a myopathy. Motor and sensory conduction in distal and proximal nerves were normal.     

Sensory nerve conduction in the upper limbs at various stages of diabetic neuropathy

In 59 diabetic patients, sensory nerve potentials were recorded at various sites along the course of the median nerve. Pathological responses were characterized by reduced amplitude, desynchronization and decreased conduction velocity (CV). Four groups of patients with increasingly severe nerve dysfunction were distinguished. The presence and severity of clinical neuropathy in the upper limbs could be related to decreased maximal sensory nerve CV in the proximal segment of the limbs. When maximal sensory nerve CV was normal above the wrist, neuropathy usually remained latent. In severe cases where no sensory nerve potentials could be recorded, the cerebral evoked potentials nonetheless permitted a precise evaluation of the somatosensory conduction. In these cases, maximal sensory nerve CV was very low. In five patients with a so-called diabetic mononeuropathy, abnormal nerve potentials were recorded in the median nerve, although no clinical signs could be seen in the corresponding territory. It is proposed that the diabetic nature of a mononeuropathy can be assessed by the finding of latent abnormalities in seemingly normal nerve.     

Peripheral neuropathy in essential mixed cryoglobulinemia

Sixteen patients with essential mixed cryoglobulinemia were studied and followed up clinically and electrophysiologically for 4.2 years. Peripheral neuropathy was diagnosed in seven cases. Five of these patients had distal symmetrical sensorimotor polyneuropathy. Nerve conduction velocities were normal and therefore indicative of pure axonal neuropathy. Sural nerve biopsy showed moderate loss of myelinated axons in two patients and severe loss in one. This patient also had necrotizing arteritis. The remaining two had both clinical and electrophysiologic signs of overlapping mononeuritis multiplex with severe denervation in the territory of the involved nerves, but normal conduction velocities. Sural nerve biopsy in one of these two patients showed marked loss of myelinated fibers and signs of vasculitis. Two types of neuropathy were noted: (1) a mild distal neuropathy with relatively minor neurologic deficit, probably due to vasa nervorum microcirculation occlusion caused by intravascular deposits of cryoglobulins and (2) a severe distal symmetrical sensorimotor neuropathy or overlapping mononeuritis multiplex, associated with necrotizing vasculitis.     

Peripheral neuropathy associated with polycythemia vera

Nerve conduction studies were performed on 26 patients with polycythemia vera, 11 of whom had sensory symptoms in the extremities and 3 of whom had clinical signs of peripheral neuropathy. There was significant impairment of sensory conduction in the ulnar and sural nerves and mild slowing of motor conduction in the lateral popliteal nerve. Sural nerve biopsies were performed on three patients. The pathological findings, including teased fiber studies, were consistent with mild chronic axonal degeneration. There is an association between polycythemia vera and peripheral neuropathy.     

Porphyric neuropathies in an acute intermittent porphyria family

The objective of this study was to investigate two patients with porphyric neuropathy in a family with acute intermittent porphyria. Molecular analysis of the porphobilinogen deaminase (PBGD) gene was performed. We analyzed the clinical course of peripheral neuropathy and serial changes in nerve conduction studies (NCS) of the two patients. We also examined the pathological findings of sural nerve biopsy in one patient. Molecular analysis of the PBGD gene revealed a missense mutation (Arg26His) in exon 2 for two patients and their family members. Distal polyneuropathy was noted in the patients with chronic porphyric neuropathy. In the follow‐up NCS, recovery was relatively poor in the lower limb in one patient with severe polyneuropathy, and NCS evidence of deterioration was found following frequent hormone‐related porphyric attacks in another patient. The sural nerve biopsy showed marked loss of myelinated and unmyelinated fibers in one patient with chronic porphyric neuropathy. In contrast to radial and fibular motor nerves in acute porphyric neuropathy, the sural nerve is vulnerable to involvement in chronic porphyric neuropathy following repeated porphyric attack as seen in the NCS.     

Hypoglycemic polyneuropathy: report of a case with insulinoma

A case of a young man who presented symptoms and clinical signs of polyneuropathy that occurred in connection with recurrent hypoglycemic episodes is reported. The hypoglycemia was probably caused by a pancreatic islet tumor. There were symmetric weakness and wasting of hands and feet, absent tendon reflexes and 'glove and stocking' loss of sensation. Electromyographic studies showed denervation potentials with slight reduction of nerve conduction velocities. Sural nerve biopsy studied by optic and electronic microscopy showed axonal degeneration without signs of demyelination or remyelination. There are only 30 similar cases reported in the literature. According to experimental findings, the authors believe that glucopenia is the mechanism responsible for the development of the neuropathy, and that at present time there is no evidence for a direct insulin effect.     

Electrophysiological evidence of “nerve entrapment syndromes” and subclinical peripheral neuropathy in progressive systemic sclerosis (scleroderma)

We report the electrophysiological findings and the management of 5 subjects with progressive systemic sclerosis (PSS) and clinical evidence of nerve entrapment. Three had carpal tunnel syndrome (CTS), 1 bilateral CTS and right tarsal tunnel syndrome (TTS) and 1 Guyon's canal syndrome. Only 1 patient (with CTS) showed significant clinical improvement after surgical decompression; the other 4 demonstrated a slight recovery of conduction without lasting clinical relief after conventional treatment. To explain these failures we hypothesized that these entrapment syndromes were the clinical expression of underlying diffuse damage to the peripheral nervous system (PNS). The conduction values of nerves unaffected by entrapment syndromes were within normal limits, but almost all distal velocities were below the mean of controls. Such subclinical distal peripheral neuropathy was also verified in a selected sample of 17 patients with PSS, without clinical symptoms or signs of PNS involvement. In these 17 cases the mean distal sensory and motor conduction findings of the median, ulnar, sural and tibial nerves were significantly lower than those of a control group, while no significant differences were found in the more proximal tracts of the same nerves. Furthermore, 3 of the 17 patients showed classical electrophysiological evidence of TCS and TTS without any clinical symptoms. We concluded that the subjects with PSS had subclinical polyneuropathy which may become plain polyneuropathy or nerve entrapment syndromes perhaps induced by other risk factors.     

Peripheral nerve findings in hereditary coproporphyria

Summary In spite of several cases reported in the literature, the exact pathogenetic mechanism of neuropathic changes in porphyric neuropathy remains uncertain. Various authors have ascribed the neuropathologic findings to either a dying-back axonal degeneration or segmental demyelination. In recent years, the hypothesis of an axonal and myelinic disorder has received support by the demonstration of a combined and simultaneous involvement of both these structures. Such different opinions are also a consequence of the reduced number of detailed bioptic observations in the different forms of acute porphyria not only during acute phases but also between attacks. In this paper we report the results of light- and electronmicroscopic examination of two sural nerve biopsies from subjects with hereditary coproporphyria. The first was performed 6 months after an acute attack, the second specimen was obtained from a patient without acute attacks, who had clinical and electrophysiologic signs of a chronic progressive neuropathy. In both cases a dying-back axonal degeneration is considered the primary change. The pathogenetic mechanism of peripheral nerve lesions in porphyric neuropathy will be discussed finally.     

Comparison of IgM-MGUS and IgG-MGUS polyneuropathy

Objective – To compare the clinical and electrodiagnostic features and response to treatment in patients with IgM-MGUS and IgG-MGUS associated polyneuropathy. Material and methods – Retrospective review of 34 consecutive patients with MGUS associated neuropathy evaluated over 5 years. Results – There were 19 patients with IgM-MGUS and 15 with IgG-MGUS. There were no differences in age, duration of symptoms, or distribution of motor and sensory symptoms or signs. IgM-MGUS patients had prolonged distal latencies of the median and ulnar motor potentials, greater slowing of the peroneal nerve conduction velocity and more often absent ulnar sensory potentials. Half of the patients in both groups improved following immunotherapy. Conclusion – IgM-MGUS patients had more severe dernyelination on the nerve conduction studies, but there were no clinical features that differentiated the 2 groups. IgM and IgG-MGUS patients improved with plasma exchange and other immune therapies. Anti-MAG antibodies failed to distinguish a subgroup of patients with IgM-MGUS neuropathy     

Autonomic dysfunction in diphtheritic neuropathy.

Sympathetic and parasympathetic function and somatic nerve conduction were assessed in ten patients with diphtheritic neuropathy and 28 controls. None of the patients had postural hypotension. The Valsalva ratio was abnormal in two patients who also had myocarditis, but it was normal in five cases. Cardiac vagal dysfunction was found in five patients. One case showed cardiac parasympathetic denervation despite normal conduction velocity in the limbs.     

Neuropathy and myopathy in primary Sjögren''s syndrome: neurophysiological, immunological and muscle biopsy results

Seventeen consecutive patients with primary Sjögren's syndrome (PSS) received neurophysiological examination, analysis of antibodies against peripheral nerve-myelin (PNM) and muscle biopsy, to show the prevalence and characteristics of peripheral neuropathy (PN) and myopathy; 3 PSS cases showed a clinical mild sensorimotor polyneuropathy, 1 of them had been treated with cytostatic drugs; 1 had mononeuropathia multiplex; and 1 clinical carpal tunnel syndrome. In these 5 patients neurophysiological investigation verified the clinical diagnosis of peripheral nerve involvement; 2 with PN had serum-antibodies against PNM; 1 of IgM-, and 1 of IgA-isotype. Muscle biopsies were taken from 15 PSS patients; 11 showed inflammatory myositis or inflammatory perivascular infiltrates and 3 showed signs of denervation. A combination of inflammation and morphological signs of myopathy, compatible with the biopsy diagnosis of polymyositis, was seen in 4, 1 of whom showed clinical signs of polymyositis. We conclude that the peripheral nervous and muscular systems are often involved in PSS, but commonly with relatively mild symptoms and laboratory findings. The common findings of inflammatory myopathy indicate an immune reaction in muscles in addition to other autoimmune manifestations of the disease.     

Peripheral neuropathy in arsenic smelter workers.

We conducted a double-blind controlled study of individuals exposed to arsenic trioxide in a copper-smelting factory. Subjects fell into three categories of peripheral neuropathy: none, subclinical, and clinical. The subclinical group had no symptoms or signs of numbness or reduced reflexes, but did have reduced nerve conduction velocity and amplitude measurements. Clinical neuropathy groups had signs and symptoms of neuropathy and electrophysiologic abnormalities. The clinical and subclinical groups correlated with increased content of arsenic in urine, hair and nails. The incidence of subclinical and clinical neuropathy was greater in arsenic workers than in unexposed controls.     

Peripheral neuropathy following a single exposure to arsenic. Clincal course in four patients with electrophysiological and histological studies.

Four patients are described who developed a peripheral neuropathy 10 days to 3 weeks after ingestion of a single dose of arsenic. All improved slowly, but after 6 to 8 years 3 of them still had abnormal neurological symptoms and signs. Electrophysiological studies showed reduction of motor conduction velocity and marked abnormalities of sensory nerve action potentials. The findings suggest that conduction is abnormal in at least some surviving nerve fibres. Sural nerve biopsies from 2 patients showed axonal degeneration, which was at an early stage in some fibres, even 10 weeks after intoxication.     

感觉轴索神经病的临床与神经生理特点

目的探讨感觉轴索神经病的临床和神经生理特点。方法选择24例感觉轴索神经 病患者及88名年龄匹配的健康人,电生理检查用皮肤表面电极超强刺激,表面电极记录,测试尺神 经、正中神经和胫神经不同节段的运动潜伏期、运动传导速度及其CMAP波幅、时限,感觉传导速度及其波幅等。结果22例患者表现为肢体麻木和感觉性共济失调,18例患者远端的痛觉和(或)音叉振动觉减退或消失,17例以下肢为著,所有患者均不伴肌无力和肌束震颤。病因包括肺癌、糖尿病、遗传性脊髓小脑共济失调、酒精中毒和药物中毒等。神经传导显示感觉神经动作电位波幅明显下降,感觉神经传导速度减慢,两者与年龄匹配的健康人相比,差异有非常显著性意义(P<0.001、0.01);运动神经传导速度和波幅两组差异没有显著性意义(P>0.05)。结论感觉轴索神经病是一类多因素造成的临床综合征,以感觉纤维轴索损害为主,临床表现为以下肢为著的感觉症状体征,神经传导检测主要的改变是感觉神经动作电位(SNAP)波幅的减低或消失、伴或不伴感觉传导速度的改变,其常见病因有肿瘤、中毒、代谢性疾病、神经系统遗传病等。