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PubMed1990

[Abnormalities of axonal transport as pathogenesis of axonal degeneration in peripheral neuropathy].

Axonal transport is a universal property of nerve cells. Role of axonal transport abnormalities in the pathogenesis of peripheral neuropathies was discussed. Applications of isotope-labeling technique to the study of axonal transport in experimental neuropathy have provided insights into the pathogenesis of axonal degeneration. As a model of dying-back neuropathy, axonal transport has been studied in sciatic motor neurons of rats with neuropathy induced by p-bromophenylacetylurea (BPAU) using this technique. The velocity of rapid anterograde transport was unaffected in this neuropathy and amount of retrograde axonal transport was reduced. The lag time between precursor injection and the onset of transport was shorter in BPAU-treated rats than controls. Whereas, in experimental ethylene oxide (EO) neuropathy rats, rapid transport velocity was markedly reduced in spite of very mild results of morphometric study. Those rapid axonal transport abnormalities may explain some aspects of the pathogenesis of peripheral neuropathies. In BPAU neuropathy model, disturbance of assembly of membrane-limited vesicles in Golgi processing may play a role in turnaround defect which causes dying-back neuropathy. EO neuropathy model suggests the possibility of oxygen utilization disturbance may causes energy dependent rapid transport velocity. Moreover, environments surrounding axon are also important for function of axonal transport. Present information leads to the conclusion that abnormalities in the supply and deposition of transported materials occur in early course of peripheral neuropathy and may contribute to development of the neuropathy.

Animals↗
PubMed2006

Determining whether delayed nonarteritic ischemic optic neuropathy associated with cataract extraction is a true entity.

PURPOSE: To evaluate cases of delayed nonarteritic anterior and posterior ischemic optic neuropathy after cataract extraction and to evaluate the need for centralized prospective reporting of nonarteritic ischemic optic neuropathy after cataract extraction. SETTING: Neuro-ophthalmology Clinics, University of Colorado Health Sciences Center and Denver Veterans Affairs Medical Center, Denver, Colorado, USA. METHODS: A retrospective review of all patients referred to the Neuro-ophthalmology Divisions, University of Colorado Health Sciences Center and Denver Veterans Affairs Medical Center, from January 2001 to October 2005 was performed. All patients with a diagnosis of nonarteritic anterior or posterior ischemic optic neuropathy were identified. Patients with ischemic optic neuropathy that occurred between 2 months and 12 months after cataract extraction were selected for evaluation. RESULTS: Six eyes with nonarteritic ischemic optic neuropathy that occurred 2 to 6 months after cataract extraction in 4 patients (2 bilateral nonarteritic ischemic optic neuropathy) and 1 eye with nonarteritic ischemic optic neuropathy that occurred after 6 months in 1 patient were identified. One patient had nonarteritic ischemic optic neuropathy in 1 eye 3 months after cataract extraction and 4 years later had nonarteritic ischemic optic neuropathy in the fellow eye 5 months after cataract extraction. Follow-up after the last cataract extraction was 1 to 3 years for all patients. CONCLUSIONS: Although an association between cataract extraction and delayed nonarteritic anterior and posterior ischemic optic neuropathy has been suggested, current data do not support a causal relationship. In addition, the window of postoperative susceptibility for delayed ischemic optic neuropathy after cataract extraction is unclear.

Aged↗
PubMed1999

Clinical features and anti-neural reactivity in neuropathy associated with IgG monoclonal gammopathy of undetermined significance.

Neuropathy has been frequently reported in patients with IgG monoclonal gammopathy of undetermined significance (MGUS) but it is still unclear whether this association has clinical or pathogenetic relevance. In order to clarify the possible role of IgG MGUS in the neuropathy we correlated the clinical and electrophysiological features of the neuropathy with the duration and anti-neural activity of the M-protein in 17 patients with neuropathy and IgG MGUS. Ten patients (59%) had a chronic demyelinating neuropathy clinically indistinguishable from chronic inflammatory demyelinating polyneuropathy (CIDP) while 7 (41%) had a predominantly sensory axonal or mixed neuropathy. In 80% of patients in the CIDP-like and 28% in the sensory group the IgG M-protein became manifest several months to years after onset of the neuropathy. Antibodies to one or more neural antigens (including tubulin, a 35KD P0-like nerve myelin glycoprotein, GD1a, GM1 and chondrotin sulfate C) were found in 40% of patients with CIDP-like and 43% with sensory neuropathy but also in 37% patients with IgG MGUS without neuropathy. Neuropathy associated with IgG MGUS is probably less heterogeneous than previously considered suggesting that this association may not be merely casual. The evidence for primary pathogenetic role of IgG M-proteins in the neuropathy remains however elusive.

Adult↗
PubMed2005

Vascular risk factors and diabetic neuropathy.

BACKGROUND: Other than glycemic control, there are no treatments for diabetic neuropathy. Thus, identifying potentially modifiable risk factors for neuropathy is crucial. We studied risk factors for the development of distal symmetric neuropathy in 1172 patients with type 1 diabetes mellitus from 31 centers participating in the European Diabetes (EURODIAB) Prospective Complications Study. METHODS: Neuropathy was assessed at baseline (1989 to 1991) and at follow-up (1997 to 1999), with a mean (+/-SD) follow-up of 7.3+/-0.6 years. A standardized protocol included clinical evaluation, quantitative sensory testing, and autonomic-function tests. Serum lipids and lipoproteins, glycosylated hemoglobin, and the urinary albumin excretion rate were measured in a central laboratory. RESULTS: At follow-up, neuropathy had developed in 276 of 1172 patients without neuropathy at baseline (23.5 percent). The cumulative incidence of neuropathy was related to the glycosylated hemoglobin value and the duration of diabetes. After adjustment for these factors, we found that higher levels of total and low-density lipoprotein cholesterol and triglycerides, a higher body-mass index, higher von Willebrand factor levels and urinary albumin excretion rate, hypertension, and smoking were all significantly associated with the cumulative incidence of neuropathy. After adjustment for other risk factors and diabetic complications, we found that duration of diabetes, current glycosylated hemoglobin value, change in glycosylated hemoglobin value during the follow-up period, body-mass index, and smoking remained independently associated with the incidence of neuropathy. Cardiovascular disease at baseline was associated with double the risk of neuropathy, independent of cardiovascular risk factors. CONCLUSIONS: This prospective study indicates that, apart from glycemic control, the incidence of neuropathy is associated with potentially modifiable cardiovascular risk factors, including a raised triglyceride level, body-mass index, smoking, and hypertension.

Adult↗
PubMed1990

Unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation: no causal relation with diabetic autonomic neuropathy.

OBJECTIVE: To examine the traditional view that unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation in insulin dependent diabetes mellitus are manifestations of autonomic neuropathy. DESIGN: Perspective assessment of unawareness of hypoglycaemia and detailed assessment of autonomic neuropathy in patients with insulin dependent diabetes according to the adequacy of their hypoglycaemic counterregulation. SETTING: One routine diabetic unit in a university teaching hospital. PATIENTS: 23 Patients aged 21-52 with insulin dependent diabetes mellitus (seven with symptoms suggesting autonomic neuropathy, nine with a serious clinical problem with hypoglycaemia, and seven without symptoms of autonomic neuropathy and without problems with hypoglycaemia) and 10 controls with a similar age distribution, without a personal or family history of diabetes. MAIN OUTCOME MEASURES: Presence of autonomic neuropathy as assessed with a test of the longest sympathetic fibres (acetylcholine sweatspot test), a pupil test, and a battery of seven cardiovascular autonomic function tests; adequacy of hypoglycaemic glucose counterregulation during a 40 mU/kg/h insulin infusion test; history of unawareness of hypoglycaemia; and response of plasma pancreatic polypeptide during hypoglycaemia, which depends on an intact and responding autonomic innervation of the pancreas. RESULTS: There was little evidence of autonomic neuropathy in either the 12 diabetic patients with a history of unawareness of hypoglycaemia or the seven patients with inadequate hypoglycaemic counterregulation. By contrast, in all seven patients with clear evidence of autonomic neuropathy there was no history of unawareness of hypoglycaemia and in six out of seven there was adequate hypoglycaemic counterregulation. Unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation were significantly associated (p less than 0.01). The response of plasma pancreatic polypeptide in the diabetic patients with adequate counterregulation but without autonomic neuropathy was not significantly different from that of the controls (change in plasma pancreatic polypeptide 226.8 v 414 pmol/l). The patients with autonomic neuropathy had a negligible plasma pancreatic polypeptide response (3.7 pmol/l), but this response was also blunted in the patients with inadequate hypoglycaemic counterregulation (72.4 pmol/l) compared with that of the controls (p less than 0.05). CONCLUSIONS: Unawareness of hypoglycaemia and inadequate glucose counterregulation during hypoglycaemia are related to each other but are not due to autonomic neuropathy. The blunted plasma pancreatic polypeptide responses of the patients with inadequate hypoglycaemic counterregulation may reflect diminished autonomic activity consequent upon reduced responsiveness of a central glucoregulatory centre, rather than classical autonomic neuropathy.

Adult↗
PubMed1992

Non-invasive assessment of gastrointestinal motility disorders in diabetic patients with and without cardiovascular signs of autonomic neuropathy.

Twenty six patients with insulin dependent diabetes mellitus underwent a gastric emptying test, a gall bladder contraction test, an orocaecal transit study, and a colon transit test. Eleven patients had signs of cardiovascular autonomic neuropathy, 15 patients were without signs of cardiovascular autonomic neuropathy. Mean gastric clearance of radioopaque markers ingested with a meal averaged 29.5 (2.3) markers per six hours in subjects without cardiovascular autonomic neuropathy compared with 17.8 (2.3) markers per six hours in patients with cardiovascular autonomic neuropathy (p < 0.02). Gall bladder emptying in response to graded CCK8 stimulation was impaired in five of 11 patients with cardiovascular autonomic neuropathy, whereas it was normal in the patients without cardiovascular autonomic neuropathy (p < 0.01). Oral caecal transit times were not significantly different in the two patient groups, whereas colonic transit was slower in the patients with cardiovascular autonomic neuropathy compared with the group without cardiovascular autonomic neuropathy (p < 0.02). There was no correlation between disturbed gastric clearance, impaired gall bladder contraction, and prolonged colonic transit time in the patients with cardiovascular autonomic neuropathy nor was there a correlation between any disturbed motor function and age or duration of diabetes. It is concluded that autonomic neuropathy can affect motor functions throughout the gastro-intestinal tract. Any disturbed motor function in the gut could therefore be one of the numerous expressions of diabetic neuropathy affecting the cardiovascular, the endocrine or the gastrointestinal system.

Adult↗
PubMed1994

Differences in peripheral and autonomic nerve function measurements in painful and painless neuropathy. A clinical study.

OBJECTIVE: To examine the differences in peripheral and autonomic nerve function measurements between diabetic patients without neuropathy (group 1, n = 38, mean age 50.9, range 29-71 years), with painless neuropathy (group 2, n = 32, mean age 49.2, range 30-71 years), and with painful neuropathy (group 3, n = 52, mean age 51.5, range 28-73 years). RESEARCH DESIGN AND METHODS: The evaluation of neuropathy was based on clinical symptoms, signs, and quantitative sensory testing, including current perception threshold (CPT) with a neurometer and electrophysiology. RESULTS: The Neuropathy Symptom Score and the Neuropathy Disability Score were higher in patients with painful neuropathy compared with patients with painless neuropathy (6.8 +/- 2.7 vs. 0.5 +/- 0.8 [mean +/- SD], P < 0.0001, and 12.5 +/- 6.2 vs. 8.6 +/- 6.8, P < 0.01, respectively). In contrast, no differences were found in the quantitative sensory testing, including CPT measurements, the electrophysiological measurements, and the autonomic nerve system function tests in the two groups. Significant differences were found in all the above measurements when groups 2 and 3 were compared with diabetic patients without neuropathy (group 1). When all diabetic patients were considered as one group, significant correlations were found between CPT and the other peripheral nerve function assessments. In particular, peroneal nerve motor conduction velocity correlated with CPT at 2 kHz (r = -0.48, P < 0.001) and vibration perception threshold (r = -0.50, P < 0.001). CONCLUSIONS: We conclude that no difference could be found in the function of small and large nerve fibers between painful and painless diabetic neuropathy using conventional tests currently used. The CPT evaluation failed to quantify painful symptoms, but it compared favorably with other quantitative sensory tests in quantifying peripheral neuropathy.

Adult↗
PubMed2005

Diabetic peripheral neuropathy and depressive symptoms: the association revisited.

OBJECTIVE: We examined the association between severity of diabetic peripheral neuropathy and depressive symptoms and investigated the potential mediators of this association. RESEARCH DESIGN AND METHODS: The Hospital Anxiety and Depression Scale (HADS) was used to assess depressive symptoms in 494 patients (mean age 62 years; 70% male; 72% type 2 diabetic) with diabetic neuropathy diagnosed by the Neuropathy Disability Score (NDS) and the Vibration Perception Threshold (VPT). Diabetic neuropathy symptoms, activities of daily living (ADLs), and social self-perception were measured by the neuropathy and foot ulcer-specific quality-of-life instrument, NeuroQoL; perceptions of diabetic neuropathy symptom unpredictability and the lack of effective treatment were assessed by the revised Illness Perception Questionnaire. RESULTS: Both the NDS and VPT were significantly associated with the HADS after controlling for demographic and disease variables. Although diabetic neuropathy symptoms mediated this association, with unsteadiness being most strongly associated with HADS, the relationship between foot ulceration and depression was nonsignificant. The association between diabetic neuropathy symptoms and HADS was partially mediated by two sets of psychosocial variables: 1) perceptions of diabetic neuropathy symptom unpredictability and the lack of treatment control and 2) restrictions in ADLs and changes in social self-perception. CONCLUSIONS: These findings establish the association between diabetic neuropathy and depressive symptoms and identify potential targets for interventions to alleviate depressive symptoms in persons affected by diabetic peripheral neuropathy.

Activities of Daily Living↗
PubMedDate not supplied

Autonomic nervous function in asymptomatic diabetic patients with signs of peripheral neuropathy.

Fifty-two long-term diabetic patients without symptoms of autonomic neuropathy and 31 age-matched healthy controls were tested for autonomic neuropathy by deep breathing, Valsalva maneuver, and an orthostatic test on tilt table. The deep breathing and the orthostatic tests showed significant parasympathetic impairments in patients with signs of peripheral neuropathy. The Valsalva maneuver, which also mainly reflects parasympathetic function, was disturbed in patients with peripheral neuropathy, but only in those with a very long duration of diabetes. Parasympathetic neuropathy was closely correlated with peripheral neuropathy. However, five patients showed signs of parasympathetic neuropathy but not of peripheral neuropathy. Thus, parasympathetic neuropathy can appear before peripheral neuropathy. On the contrary, sympathetic denervation, as shown from the blood pressure reaction to tilting, only appeared in patients with peripheral neuropathy.

Adult↗
PubMed2000

[Relation between cardiovascular and gastrointestinal neuropathy in diabetics].

BACKGROUND: The presence of autonomic neuropathy impairs the quality of life (orthostatic hypotension, impotence, gastroparesis) or endangers the life of diabetics (sudden death, unawareness of hypoglycemia). The purpose of the investigation was: 1. To assess the presence of the autonomic neuropathy of the cardiovascular and the gastrointestinal systems and their mutual relationship. 2. To assess the relationship of found autonomic neuropathy and the subjective symptoms which are typical to affected particular systems (cardiovascular, gastrointestinal, genitourinary, sudomotor systems and the syndrome of unawareness of hypoglycemia). METHODS AND RESULTS: The group comprised of 25 type 1 diabetic patients (12 women and 13 men) mean age 40.5 +/- 11.6 (range 21-57 years) with a mean duration of diabetes of 17.8 +/- 7.9 (range 4-35 years), treated with intensified insulin regimens. The cardiovascular autonomic neuropathy was automatically examined by the VariaPulse TF 3 computer system. Scintigraphy was used to investigate the gastric emptying time of 99mTc labelled rice. The information about the subjective symptoms we collected from the questionnaire. For statistic analysis we used Spearmen correlations and ANOVA. RESULTS: 1. A statistically significant correlation was found between the presence of the autonomic neuropathy of cardiovascular and gastrointestinal systems (r = 0.634, p < 0.0007). 2. We didn't find any relation among the cardiovascular autonomic neuropathy and the subjective symptoms of cardiovascular system, respectively the gastrointestinal neuropathy (impair gastric emptying) and the subjective symptoms of gastrointestinal system. We found a significant correlation between cardiovascular and gastrointestinal neuropathy and erectile dysfunction (r = 0.48, p < 0.0078), (r = 0.42, p < 0.0388) and with the syndrome of hypoglycemia unawareness (r = 0.49, p < 0.0057), (r = 0.52, p < 0.0075). CONCLUSIONS: The evidence of the cardiovascular autonomic neuropathy is warning signal for the affected autonomic neuropathy in other systems which are more complicated for diagnostic. The subjective symptoms don't correlate with the presence of the visceral neuropathy.

Adult↗
PubMed2006

Spectrum of peripheral neuropathy in eastern India.

Peripheral neuropathies constitute an important group of disorders in neurological practice. Very few systematic studies on peripheral neuropathies are available from India. Hence we conducted a prospective study in two large hospitals from Kolkata, the biggest city of eastern India in order to find out the spectrum of peripheral neuropathy. This prospective study was carried out from June 1998 to January 2003 on admitted patients with symptoms and signs of peripheral neuropathy. Two hundred and twenty-five patients were evaluated (one hundred and twenty-five from an industrial hospital and one hundred from an academic tertiary care institution at Kolkata). Result showed that most of the cases of peripheral neuropathy belonged to fourth decade with men dominance. Common varieties of neuropathy were Guillain-Barré syndrome, diabetes mellitus, hereditary motor sensory neuropathy, chronic inflammatory demyelinating neuropathy, drugs and toxin related. Unusual varieties were Isaacs's syndrome and X-linked hereditary motor-sensory neuropathy. One case of neuropathy due to Plasmodium vivax has received intravenous immunoglobulin therapy. The type of peripheral neuropathy in hospital-based patients in eastern India was similar to other parts of country excepting some sporadic types due to infective or genetic causes and a large number of cases of undetermined aetiology exist despite detailed investigations.

Adolescent↗
PubMed1991

[Comparison of ischemic pain threshold and reactive hyperemia in autonomic diabetic neuropathy and silent myocardial ischemia].

31 patients with coronary artery disease (11 patients with diabetes mellitus and autonomic neuropathy. 10 patients with diabetes without neuropathy, and 10 patients with asymptomatic myocardial ischemia) participated in a study designed to investigate whether there is a difference in forearm skeletal muscle ischemia and pain threshold. The degree of ischemia was determined by plethysmographically measured reactive hyperemia. There was no difference in maximum reactive hyperemia after passive forearm ischemia of 5-min duration in the three groups. After symptom-limited ischemic work, there was significantly more reactive hyperemia in patients with silent myocardial ischemia as compared to diabetic patients. Exercise time was longer in patients with silent myocardial ischemia (153 +/- 51 s) than in patients with diabetic neuropathy (139 +/- 45 s) and diabetics without neuropathy (120 +/- 45 s). Pain as a cause of termination of symptom-limited ischemic forearm exercise occurred less frequently in patients with diabetic neuropathy (2/11) and patients with silent myocardial ischemia (3/10) as compared to patients with diabetes without neuropathy. Patients with silent myocardial ischemia had a higher ischemic tolerance in the ischemic working forearm than did diabetic patients with and without neuropathy. In patients with neuropathy, however, ischemic pain occurred less frequently at the same ischemic work level compared to diabetics without neuropathy. Therefore, diabetic neuropathy appears to facilitate the occurrence of silent myocardial ischemia. The data presented here suggest that there is a qualitative difference in ischemic tolerance between patients with silent myocardial ischemia and patients with diabetic neuropathy.

Angina Pectoris↗
PubMed1994

[Association of autonomic neuropathies and gastrointestinal peptides in non-insulin dependent diabetics].

Basal and postprandial levels of gastrin, somatostatin, vasoactive intestinal polypeptide (VIP) and pancreatic polypeptide (PP) were followed up in 105 patients with non insulin dependent diabetes mellitus (20 with autonomic neuropathy only, 35 with peripheric neuropathy only, 30 with autonomic and peripheric neuropathy simultaneously and 20 without any sign of neuropathy) and in the control group of 40 individuals. Serum levels of gastrin, somatostatin, VIP and PP are determined by a RIA (used kits of Prof. SR Bloom, Hammersmith Hospital, London). The results of investigation showed significantly higher basal and postprandial levels of gastrin and VIP in patients with autonomic neuropathy in comparison with the group without neuropathy and with the control group (p < 0.001). The serum levels of somatostatin did not differ significantly between the groups of diabetics with and without neuropathy. Basal level of PP was significantly lower and postprandial PP levels remained low in patients with autonomic neuropathy in comparison with the group without neuropathy (p < 0.001). We postulate that basal and postprandial gastrin and VIP levels raised secondary to partial vagotomy in diabetics with autonomic neuropathy. Measuring PP serum levels in diabetics after a protein rich meal can be useful to check vagus nerve function in the gastrointestinal tract in order to detect autonomic neuropathy.

Adult↗
PubMed1998

[Diabetic neuropathy: epidemiologic and predictive data].

Neuropathy is a classical complication of diabetes mellitus, to the same extent as micro- and macroangiopathy. Diabetic neuropathy can be schematically divided into peripheral neuropathy, especially in the lower limbs (distal polyneuropathy), and autonomic neuropathy, present in all systems (cardiovascular, gastrointestinal, urogenital and even pulmonary abnormalities). Detection should be based on an oriented anamnesis and a careful physical examination. Complementary exams may be performed in order to confirm the diagnosis and assess the severity of the neuropathy. While the diagnosis of peripheral neuropathy is essentially based on clinical examination, that of autonomic neuropathy has been markedly facilitated by simple standardised tests for early detection of cardiac autonomic neuropathy. Depending on the terminology, the diagnostic criteria and the characteristics of the population, the prevalence of diabetic neuropathy can range from 15 to 100%. However, all studies agree that prevalence is important in both types of diabetes (Type 1 and Type 2), that it increases with age and disease duration, and that it is inversely related to the quality of glycaemic control. Detection of neuropathy is an essential step in the clinical approach to diabetic patients, mainly because of the prognosis linked to such a diagnosis, at both an early and late stage of the disease. Once neuropathy is diagnosed, the physician should provide specific advice to diabetic patients in order to prevent possible dramatic complications.

Diabetic Angiopathies↗
PubMed2003

Peripheral neuropathy in patients with the 3243A>G mutation in mitochondrial DNA.

Peripheral neuropathy is one of the clinical manifestations of the MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) syndrome, but its frequency and phenotypic variability have not been properly characterised. We therefore studied the clinical and electrophysiological features of peripheral neuropathy in 32 patients with the 3243A > G mutation in mitochondrial DNA by using clinical examination, assessment of Neuropathy Symptom Score, Neuropathy Disability Score, and electrophysiological examinations. Seven patients (22 %; 95 % confidence interval, 9-40 %) fulfilled the electrodiagnostic criteria for polyneuropathy. Mixed axon loss and demyelinating sensorimotor neuropathy was the most common type of polyneuropathy, while one patient presented with uniform demyelinating sensorimotor polyneuropathy. Sensory more than motor neuropathy was diagnosed in four patients. Clinically and electrophysiologically confirmed carpal tunnel syndrome (CTS) occurred in three patients (9.4 %), suggesting a higher prevalence than in the general population. Patients with neuropathy were in general more severely affected than those without neuropathy, although no correlation was found between the presence of neuropathy and the degree of mutant heteroplasmy in muscle. Higher age and male gender were associated with an increased risk of neuropathy. Our results show that peripheral neuropathy is not uncommon in patients with the 3243A > G mutation, and they also may have an increased risk of CTS.

Action Potentials↗
PubMed1999

Relation of peripheral neuropathy to HIV treatment in four randomized clinical trials including didanosine.

Peripheral neuropathy has been recognized as a dose-limiting adverse effect in Phase I studies of didanosine (ddI) therapy for HIV infection. To study the effect of the currently recommended lower dose of ddI, the databases of 4 randomized, controlled trials were used to assess the frequency of dose-limiting peripheral neuropathy during treatment with ddI 500 or 750 mg/d, compared with zidovudine (ZDV) monotherapy or combination therapy with ddI/ZDV or zalcitabine/ZDV. No between-group differences in risk factors for neuropathy (eg, infectious and metabolic factors, malignancy, concurrent medications) were observed in the individual trials, and the presence of these risk factors appeared to have no increased treatment effect on the occurrence of neuropathy. No significant between-group differences were observed in the individual studies with regard to the incidence or time to onset of peripheral neuropathy. Analysis of the combined results by treatment regimen showed no significant difference in the incidence of neuropathy between recipients of ddI 500 mg/d, ddI 750 mg/d, or ZDV and no significant difference in the cumulative dose received until the onset of neuropathy between the ddI 500- and 750-mg regimens. Entry CD4+ cell counts were significantly predictive of neuropathy, with each 100-cell/microL decrement associated with a 17% increase in risk (P = 0.002); a CD4+ cell count of <50 cells/microL was highly predictive of neuropathy (P = 0.0001). In summary, the risk for peripheral neuropathy was not increased by treatment with ddI versus comparator regimens or by treatment with ddI at the dosages used in studies conducted more recently than the Phase I trials. Peripheral neuropathy seems more likely to be associated with advanced HIV infection and lower CD4+ cell counts (particularly counts <50 cells/microL) than with ddI therapy at the currently recommended dose.

Adolescent↗
PubMed2000

Incidence of neuropathy in HIV-infected patients on monotherapy versus those on combination therapy with didanosine, stavudine and hydroxyurea.

BACKGROUND: Sensory neuropathy is a common adverse effect of the nucleoside analogue anti-retroviral drugs didanosine (ddl) and stauvudine (d4T). These drugs are increasingly being used in combination, and it is not currently known whether the incidence of neuropathy is higher with combination compared to individual drug use. It is also not known if hydroxyurea, used to potentiate the antiviral efficacy of these drugs, may also increase the risk of neuropathy. The purpose of this analysis is to investigate if the combination of ddl and d4T, with or without hydroxyurea, has a higher incidence of neuropathy than a single drug regimen. METHODS: Data were obtained from patients followed longitudinally by the Johns Hopkins AIDS Services. Incidence rates of development of neuropathy were calculated for each of five regimens: ddl (+/- hydroxyurea), ddl + d4T (+/- hydroxyurea), and d4T. Cox proportional hazard regression was used to compare the relative risk of neuropathy for each regimen adjusting for CD4 cell count, other drugs received, and time on therapy. RESULTS: A total of 1116 patients received at least one of the five regimens. There were 117 cases of neuropathy. The crude incidence rate of neuropathy ranged from 6.8 cases per 100 person-years for ddl to 28.6 cases per 100 person-years for ddl + d4T + hydroxyurea. Compared with ddl alone, and adjusting for CD4 cell counts and other variables, the relative risk of neuropathy was 1.39 [95% confidence interval (CI): 0.84-2.32] for d4T alone, 2.35 (95% CI: 0.69-8.07) for ddl + hydroxyurea, 3.50 (95% CI: 1.81-6.77) for ddl + d4T, and 7.80 (95% CI: 3.92-15.5) for ddl + d4T + hydroxyurea. CONCLUSIONS: Based on the data, the risk of neuropathy is additive or even synergistic for ddl + d4T + hydroxyurea compared with ddl or d4T alone. The combination of ddl + d4T also increases the risk of neuropathy but less than when hydroxyurea is included.

Adult↗
PubMed1991

Hemodynamic effects of octreotide in patients with autonomic neuropathy.

BACKGROUND: The somatostatin analogue, ectrootide, is being used to treat postprandial hypotension in patients with autonomic neuropathy. Although the therapeutic effect of the drug is presumably secondary to a splanchnic vasoconstrictor action, its effect on splanchnic hemodynamics has never been characterized in patients with autonomic neuropathy. Moreover, it is unknown whether octreotide acts on other vascular beds in this group of patients or whether it affects cardiac output. We, therefore, measured splanchnic, forearm, and systemic vascular resistance and cardiac output before and after administering octreotide (0.4 microgram/kg s.c.) to patients with idiopathic autonomic neuropathy and diabetic autonomic neuropathy. METHODS AND RESULTS: Splanchnic blood flow was determined from the clearance of indocyanine green in seven patients. We observed that octreotide decreased splanchnic blood flow (from 850 +/- 77 to 664 +/- 48 ml/min, p less than 0.005), increased mean blood pressure (from 97 +/- 6 to 115 +/- 3 mm Hg, p less than 0.005), and increased splanchnic vascular resistance (from 0.118 +/- 0.012 to 0.18 +/- 0.018 mm Hg/ml/min, p less than 0.005). Forearm blood flow was measured by plethysmography in 13 patients. Octreotide increased forearm vascular resistance in patients with idiopathic autonomic neuropathy (n = 8) from 19.1 +/- 1.0 to 27.2 +/- 3.8 mm Hg/ml/min/100 ml forearm volume (p less than 0.01) and from 25.2 +/- 3.9 to 41.0 +/- 6.8 mm Hg/ml/min/100 ml (p less than 0.01) in patients with diabetic autonomic neuropathy (n = 5). Cardiac output was measured by two-dimensional echocardiography. Octreotide administration increased cardiac output in five of six patients with idiopathic autonomic neuropathy (from 4.4 +/- 0.4 to 5.0 +/- 0.5 l/min, p less than 0.02) and five of five patients with diabetic autonomic neuropathy (from 3.8 +/- 0.4 to 5.1 +/- 0.4 l/min, p less than 0.02). Systemic vascular resistance increased in patients with idiopathic autonomic neuropathy from 21.2 +/- 2 to 24.9 +/- 2.6 (p less than 0.05) but did not change in patients with diabetic autonomic neuropathy. CONCLUSION: The pressor effect of octreotide in patients with autonomic neuropathy is associated with increased splanchnic and forearm vascular resistance and with increased cardiac output.

Adolescent↗