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.     

Peripheral polyneuropathy and monoclonal gammopathy of undetermined significance.

The prevalence of peripheral polyneuropathy in patients with monoclonal gammopathy is known to be higher than in the general population. A prevalence as high as that in the series of Osby et al, who found clinical and/or electrophysiological evidence compatible with peripheral polyneuropathy in 15 of 21 patients has not been reported before. These results could not be confirmed in a study in which 19 patients with benign monoclonal gammopathy were investigated. In contrast there were only two patients with questionable evidence of peripheral neuropathy: one had lower limb symptoms and signs only, the other had evidence of a subclinical polyneuropathy with some abnormalities of nerve conduction.     

Electrophysiological study of neuromuscular system involvement in mitochondrial cytopathy.

OBJECTIVES: To define the neuromuscular involvement in 'mitochondrial' patients with clinical evidence of a neuromuscular disorder, and to evaluate if the proposed electrophysiological protocol was suitable to reveal a subclinical neuropathy or myopathy in 'mitochondrial' patients with no clinical sign of a neuromuscular disturbance. METHODS: Quantitative concentric needle electromyography (CNEMG), single fiber electromyography (SFEMG) and nerve conduction studies (NCS) were performed in 33 patients with mitochondrial cytopathies. Lastly, we studied 9 clinically unaffected relatives. RESULTS: NCS were abnormal in 18% of patients, with CNEMG and SFEMG in 58% of cases, but there was not a complete overlapping of the positivity of the different techniques. No asymptomatic relatives showed abnormalities of the electrophysiological studies. CONCLUSIONS: Electrophysiological findings did not correlate with any specific biochemical or genetic defect, but were consistent with clinical diagnosis in almost all of the patients with clinical signs of myopathy and/or neuropathy. Increase of both SFEMG jitter and fiber density was significantly tied to a neuropathic process. CNEMG and SFEMG were altered in about 30% of subjects without clinical signs of myopathy or neuropathy and were therefore able to reveal a subclinical involvement of neuromuscular system in some patients who had external ophthalmoplegia or retinitis only.     

Peripheral neuropathy in myotonic dystrophy type 1

Myotonic dystrophy 1 (DM1) is characterized by a wide range of clinical features. We aimed to verify the presence of peripheral nerve involvement in a large cohort of DM1 patients and to determine clinical consequences. A total of 93 patients underwent detailed neurological examination and nerve conduction studies. Additionally, balance impairment was assessed with the Berg Balance Scale and health status was evaluated with the SF-36 health survey. Sensory symptoms were not reported and mild sensory signs were found in six patients. Electrophysiological abnormalities consistent with a diagnosis of neuropathy were found in 16 patients (17%). Peripheral nerve involvement was significantly associated with decreased muscle strength (p = 0.001) and absence of Achilles-tendon reflexes (p = 0.003), but not with age or duration of neuromuscular symptoms. It had no significant effect on balance, mental or physical health. In conclusion, peripheral nerve involvement may be one of the multisystemic manifestations of DM1, but is usually subclinical. Other causes should be excluded when sensory symptoms or signs are severe.     

Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study

OBJECTIVES: To evaluate neuromuscular signs and symptoms in patients with newly diagnosed hypothyroidism and hyperthyroidism. METHODS: A prospective cohort study was performed in adult patients with newly diagnosed thyroid dysfunction. Patients were evaluated clinically with hand held dynamometry and with electrodiagnosis. The clinical features of weakness and sensory signs and the biochemical data were evaluated during treatment. RESULTS: In hypothyroid patients 79% had neuromuscular complaints, 38% had clinical weakness (manual muscle strength testing) in one or more muscle groups, 42% had signs of sensorimotor axonal neuropathy, and 29% had carpal tunnel syndrome. Serum creatine kinase did not correlate with weakness. After 1 year of treatment 13% of the patients still had weakness. In hyperthyroid patients 67% had neuromuscular symptoms, 62% had clinical weakness in at least one muscle group that correlated with FT4 concentrations, but not with serum CK. Nineteen per cent of the patients had sensory-motor axonal neuropathy and 0% had carpal tunnel syndrome. The neuromuscular signs developed rapidly, early in the course of the disorder and were severe, but resolved rapidly and completely during treatment (average time 3.6 months). CONCLUSIONS: Neuromuscular symptoms and signs were present in most patients. About 40% of the hypothyroid patients and 20% of the hyperthyroid patients had predominantly sensory signs of a sensorimotor axonal neuropathy early in the course of thyroid disease. Weakness in hyperthyroidism evolved rapidly at an early stage of the disorder and resolved completely during treatment, suggesting a functional muscle disorder. Hand held dynamometry is sensitive for the detection of weakness and for the clinical evaluation of treatment effects. Weakness in hypothyroidism is more difficult to treat, suggesting myopathy.     

Childhood thalidomide neuropathy: a clinical and neurophysiologic study

Thalidomide was recently reintroduced to treat several immune-mediated pathologies. Peripheral neuropathy is a significant side effect limiting its clinical use. Our aims include: (1) describing and identifying the incidence of clinical or electrophysiologic peripheral neuropathy in children, (2) determining whether peripheral neuropathy correlates with cumulative dose of thalidomide and with age, and (3) defining its reversibility rate. We studied 13 children manifesting immune-mediated pathologies treated with thalidomide at doses ranging from 25-100 mg/day. Clinical and neurophysiologic evaluation was performed before and after starting treatment. Seven children (53.8%) showed neurophysiologic signs of sensory peripheral axonal polyneuropathy. Five presented associated clinical symptoms, while the other two only presented subclinical, neurophysiologic signs of peripheral neuropathy. We found a significant correlation between the incidence of peripheral neuropathy and thalidomide cumulative dose (P = 0.02). We observed a lower incidence of peripheral neuropathy at a cumulative dose <20 gm, and a correlation with age (P < 0.01). The clinical and electrophysiologic recovery rate was 40%, and clinical improvement alone was observed in another 40%. Thalidomide induces dose-dependent and age-dependent peripheral neuropathy at a significant frequency in childhood (53.8%). In our experience a cumulative dosage at >20 gm and long-term administration for >10 months seem to increase the risk of peripheral neuropathy. We propose clinical and neurophysiologic follow-up every 3 months to identify and monitor possible side effects.     

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.     

Absence of sensory neuropathy among workers with occupational exposure to chlorpyrifos

Several studies have reported the occurrence of sensory neuropathy with exposure to chlorpyrifos and other organophosphorus insecticides, at levels not associated with overt toxicity. We evaluated 113 chemical workers, including 53 of 66 (80%) eligible chlorpyrifos workers and 60 of 74 (81%) randomly selected referent workers, to identify evidence of sensory neuropathy or subclinical neuropathy. Compared to referents, chlorpyrifos subjects had significantly longer duration of work in chlorpyrifos-exposed areas (9.72 vs. 0.01 years; P < 0.0001), greater cumulative chlorpyrifos exposure (64.16 vs. 0.69 mg/m(3). day; P < 0.0001), higher urine 3,5,6-trichloro-2-pyridinol (TCP) excretion (108.6 vs. 4.3 microg/g creatinine; P < 0.0001), and lower plasma butyrylcholinesterase (BuChE) activity (7281 vs. 8176 mU/ml; P = 0.003). Despite exposures among chlorpyrifos subjects to levels at which well-described physiological effects on B-esterases exist, the frequency of symptoms or signs of neuropathy did not differ significantly between groups, and the only 2 subjects fulfilling criteria for confirmed neuropathy were both in the referent group. Mean nerve conduction study results were comparable to established control values and did not differ significantly between groups. We found no evidence of sensory neuropathy or isolated peripheral abnormalities among subjects with long-term chlorpyrifos exposure at levels known to be associated with the manufacturing process.     

Human diabetic endoneurial sorbitol,fructose, and myo-inositol related to sural nerve morphometry

Fascicles of the sural nerve from each of 20 diabetic patients, mostly with maturity-onset diabetes, were studied by biochemical and pathological techniques, and results were compared to values found in nerve specimens from 15 healthy persons. The sorbitol and fructose content was much more variable in diabetic than in healthy nerves. More than one-third of the diabetic nerves had sorbitol and fructose values above the highest levels for controls. myo-Inositol and scyllo-inositol content was not reduced in diabetic nerves. The sorbitol, fructose, and inositol concentrations could not be related to clinical, neurophysiological, or pathological severity of neuropathy. A comparison of scored symptoms and signs and clinical neurophysiological studies against morphometric and teased fiber studies of sural nerve demonstrated that the former three provide sensitive and reliable measures of severity of neuropathy that can be used for controlled clinical trials of diabetic neuropathy. The presence and type of teased fiber abnormalities could be related to the duration of diabetes and to symptoms of neuropathy. In untreated diabetics without symptoms of neuropathy, a higher than normal frequency of teased fibers showing segmental demyelination and remyelination was found. Untreated diabetics with symptomatic neuropathy showed two kinds of abnormalities: fibers with segmental demyelination and remyelination and fibers undergoing axonal degeneration. In treated diabetics, who often had longstanding neuropathy, the most common abnormalities were fibers undergoing axonal degeneration.     

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     

Vibratory and thermal thresholds in diabetics with and without clinical neuropathy

Vibration and thermal detection threshold and heat pain threshold were determined in 34 diabetics scrutinized for clinical neuropathy using a standardized questionnaire and examination form. On the basis of the clinical grading patients were classified as having either no neuropathy or a neuropathy of increasing severity. As expected thermal and vibratory detection threshold increased with increasing severity of neuropathy. Comparison between diabetics without symptoms and signs of neuropathy and a corresponding non-diabetic control group showed that a warm sensibility index (WSI = the range in which non-noxious heat is perceived) was significantly lower on feet in diabetics than in their matched non-diabetic controls. The findings show that quantitative assessment of thermal sensitivity may be of value to detect early small nerve fiber dysfunction even in patients without symptoms or signs of a clinical neuropathy.     

Subclinical inorganic mercury neuropathy: neurophysiological investigations in 17 occupationally exposed subjects

17 workers in a thermometer factory exposed to mercury for periods ranging from 1 to 40 years all had high urine and blood mercury levels on undergoing electromyographic examination. All were clinically free from central and peripheral nervous symptoms. 88% had subclinical neuropathy, mainly distal and axonal. There was no correlation between severity of the neuropathy and blood and urine mercury levels or between severity of neuropathy and duration of exposure to mercury. The presence of a subclinical neuropathy in symptomless workers exposed to mercury is perhaps the most reliable index for the detection of the early toxic effects of mercury on the peripheral nerve fiber when it is probably still reversible.     

Electromyogram and nerve conduction in patients with acute intermittent porphyria

Summary Diminished activity of uroporphyrinogen I-synthetase in the liver and other tissues may be regarded to be the primary genetic deficiency of acute intermittent porphyria (AIP). Increased production and renal excretion of delta-aminolevulinic acid (ALA) und porphobilinogen (PBG) are secondary phenomena. The neuropsychiatric symptomatology of AIP consists of neuropathy, vegetative crises and exogenous psychoses.In this study electromyographic and neurographic investigations were performed on 20 persons with AIP. 16 patients had experienced attacks of AIP, 10 of them including neuropathy. 4 persons showed the biochemical findings of AIP but had not yet had symptoms.In cases with persistent pareses following porphyric neuropathy denervation signs or sequelae were still present. In patients without clinical symptoms and in latent cases there were normal or borderline findings. Motor nerve conduction velocity was mostly decreased in combination with denervation signs and in a range that indicated a primarily axonal nerve lesion and consequent myelin damage rather than primary demyelinization. The mean motor conduction velocity of n. tibialis was somewhat lower in patients with porphyric crises without neuropathy than in latent cases without any clinical crises. The differences were not significant in other nerves. The findings are discussed under consideration of the electrodiagnostic results of other investigations and of neuropathological and clinical data.Herrn Prof. Dr. Richard Jung zum 65. Geburtstag gewidmet     

Histology and ultrastructure of alterations in neuropathy

Histologic findings are described in nerves from men exposed to lead, from patients with discrete clinical signs of peripheral neuropathy, and from controls. Every nerve from control subjects showed an abnormality (paranodal remyelination, segmental remyelination, or regeneration) in teased fibers. The only histologic alteration in eight lead-exposed males without signs or symptoms of neuropathy was a slightly increased incidence of paranodal remyelination. Sixteen patients with discrete neurologic symptoms and signs had a loss of large myelinated fibers and an increased incidence of regenerated fibers among teased fibers. Electron microscopy of unmyelinated fibers showed an increased occurrence of Schwann-cell processes, of fibers undergoing degeneration, and of Schwann-cell subunits with many profiles as the earliest signs of abnormality. Clinically mild neuropathies may exhibit advanced regeneration in the case of unmyelinated fibers. The earliest sign of degeneration in myelinated fibers was a diminution in the number of axonal organelles.     

Peripheral neuropathy in chronic respiratory insufficiency

Peripheral neuropathy commonly occurs in patients with chronic obstructive lung disease (COPD). We report the presence of peripheral neuropathy in 19 of our 30 COPD patients (63.3%): 7 patients had clinical signs of a symmetric motor and sensory polyneuropathy, 12 patients had only subclinical evidence of peripheral nervous system involvement. Neurophysiological studies showed low amplitude compound muscle action potentials (CMAP) and sensory action potentials (SAP) with only slight reduction of nerve conduction velocity in affected patients: these data confirm an axonal polyneuropathy. The severity of the peripheral nervous system involvement in COPD patients was correlated with hypercapnia, the degree of disability and thus with the severity of COPD. Hypoxia, age and duration of the disease were not related with the presence of polyneuropathy. Improvement of respiratory function produced slight but progressive improvement of neurological symptoms. Within one year, also neurophysiological studies revealed a progressive and statistically significant improvement in CMAP and SAP amplitude and motor and sensory conduction velocity and, in some cases, normal electromyography.     

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.     

Subclinical diabetic polyneuropathy: early detection of involvement of different nerve fibre types.

Nerve conduction studies, tests of autonomic function and terminal nerve branches, and soleus muscle H reflexes were applied to 60 patients with insulin dependent diabetes mellitus who had no clinical symptoms but abnormal vibratory or temperature perception thresholds indicating subclinical neuropathy. In most patients neurophysiological examination yielded a broad spectrum of neural dysfunction. The perception threshold for cold stimuli was sometimes selectively impaired and abnormal pupillometry results were common, suggesting that small fibres are vulnerable in the early stage of diabetic neuropathy. The arms were less frequently and less severely affected than the legs, an effect that may be related to nerve length. The neurophysiological test results did not change in 30 patients followed up for one year.     

Inflammatory sensory polyganglionopathies.

The inflammatory sensory polyganglionopathies are a group of uncommon neurologic disorders primarily affecting dorsal root ganglion cells and their processes. Subdivided into malignant and nonmalignant inflammatory sensory polyganglionopathy, these conditions are important in the differential diagnosis of sensory neuropathy. The clinical significance of malignant inflammatory sensory polyganglionopathy, a paraneoplastic syndrome, rests in the discovery of subclinical cancer, which may produce antineuronal nuclear antibodies directed against the dorsal root ganglion cell and other neurons resulting in characteristic neurologic deficits. Prompt recognition of these distinctive signs and symptoms may result in early diagnosis and improved patient survival and lead to a better understanding of immune-mediated neurologic disease.     

Increased neurotoxicity of arsenic in methylenetetrahydrofolate reductase deficiency

A 16-year-old girl from Surinam presented with mental deterioration and severe paraparesis with areflexia and bilateral Babinski signs. Laboratory examination showed a hyperhomocysteinemia that was caused by 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency. In addition, urine samples contained large amounts of arsenic. An open bag with the pesticide copper acetate arsenite was found to be the source of exposure. In remethylation defects such as MTHFR deficiency, the concentration of methyldonors is severely reduced. As arsenic is detoxified by methylation, we suggest that the MTHFR deficiency in this girl might explain the fact that of all family members exposed to arsenic, only she developed severe clinical signs and symptoms of arsenic poisoning.     

Subclinical diabetic neuropathy with normal conventional electrophysiological study

Background For early detection and prevention of diabetic neuropathy, it is important to identify subclinical diabetic neuropathy. Routine nerve conduction study often fails to detect early stage of neuropathy. Objectives The purpose of this study is to evaluate the clinical usefulness of electrophysiological indexes in detecting early diabetic neuropathy with no objective clinical or electrophysiological abnormalities. Materials and Methods Nerve conduction study of upper/lower limbs was investigated in 31 subclinical diabetic neuropathy patients with normal nerve conduction studies(group I), 38 clinical diabetic neuropathy patients with normal nerve conduction studies(group II) and 31 normal controls. Residual latency (RL), terminal latency index (TLI) and modified F raito (MFR) were calculated and compared among groups. Results Compared with controls, MFR of lower limbs and TLI of both upper/lower limbs were significantly decreased in both group I and II (p<0.05). RL was increased in both groups, but the difference was not statistically significant. Comparing the indexes between group I and II, there was no significant difference. Conclusions RL, TLI and MFR, which reflect distal conduction slowing, may be useful indexes to identify subclinical diabetic neuropathy. The results also suggest that electrophysiological changes that are obscured in routine nerve conduction study are present before the clinical manifestation. Presented at the American Academy of Neurology annual meeting, Miami, Florida, April 13, 2005. Received in revised form: 22 March 2006