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Classification, differential diagnosis, and staging of diabetic peripheral neuropathy.

The peripheral nerve disorders associated with diabetes are complex and probably involve a variety of causative mechanisms. This may give rise to difficulty in the classification of individual cases. A broad separation into rapidly reversible or more persistent phenomena is helpful. The former, which can be categorized as "hyperglycemic neuropathy," include minor sensory symptoms, reduced nerve conduction velocity, and resistance to ischemic conduction failure. From analogy with experimental studies in animals, nerve hypoxia is likely to play a significant role in their origin. Of the more persistent phenomena, a distal symmetric polyneuropathy that predominantly affects sensory and autonomic function is the most common manifestation. A distal axonopathy of dying-back type may represent the underlying pathogenetic basis. Other more persistent phenomena consist of focal and multifocal lesions giving rise to cranial, thoraco-abdominal, and limb neuropathies, including proximal lower limb motor neuropathy (diabetic amyotrophy). Some of these may have an ischemic basis. Multifocal proximal lesions can summate to produce an approximately symmetric diffuse distal neuropathy. Focal lesions at sites of entrapment or external compression may reflect an abnormal susceptibility of diabetic nerve to compressive damage. There is also evidence that focal inflammatory, including vasculitic, lesions may be involved in proximal lower limb neuropathies. Finally, superimposed chronic inflammatory demyelinating polyneuropathy may occur. For the evaluation of possible treatment regimens, it is essential that cases should be correctly classified as to type. Thus, the features falling into the category of hyperglycemic neuropathy should not contaminate the assessment of distal symmetric polyneuropathy. For this type, a widely accepted scheme for staging devised by P. J. Dyck is available. Other schemes are also available for the assessment of such cases, with differing degrees of complexity. Evaluation by serial nerve biopsies has also been proposed.

Diabetes Complications↗

Decreased myocardial perfusion reserve in diabetic autonomic neuropathy.

The pathophysiological mechanisms responsible for increased cardiovascular mortality in diabetic autonomic neuropathy are unknown. To investigate the effect of autonomic neuropathy on myocardial function, we performed dynamic contrast-enhanced magnetic resonance perfusion imaging during baseline conditions and after Dipyridamole-induced vasodilatation in nine type 1 diabetic patients with autonomic neuropathy (AN+), defined by cardiovascular tests, as well as in 10 type 1 diabetic patients without autonomic neuropathy (AN-) and 10 healthy control subjects. Baseline myocardial perfusion index (K(i)) was similar in the three groups (AN+ 88.6 +/- 8.7 ml. 100 g(-1). min(-1), AN- 82.6 +/- 7.2, control subjects 93.7 +/- 9.0) (means +/- SE). K(i) during Dipyridamole vasodilatation was significantly lower in the patients with autonomic neuropathy (P < 0.001) than in the other groups (AN+ 131.1 +/- 13.0 ml. 100 g(-1). min(-1), AN- 177.3 +/- 8.6, control subjects 197.2 +/- 8.9). Mean blood pressure was unchanged during Dipyridamole infusion in AN- and control subjects, whereas a significant blood pressure decrease was found in AN+ (15.6 +/- 2.6 mmHg, P < 0.025). There was a significant correlation between blood pressure response to Dipyridamole and myocardial perfusion reserve index. We conclude that type 1 diabetic patients with autonomic neuropathy have a decreased myocardial perfusion reserve capacity when challenged with a vasodilatator, a finding that may in part be the pathophysiological substrate for the increase in mortality in these patients. The underlying mechanism may be defective myocardial sympathetic vasodilatation, a lack of ability to maintain blood pressure during vasodilatation, or both.

Adult↗

Experimental diabetic neuropathy with spontaneous recovery: is there irreparable damage?

Progressive diabetic neuropathy has hitherto been irreversible in humans. New approaches raise the question of whether islet cell reconstitution rendering euglycemia can reverse specific features of neuropathy. We evaluated physiological and structural features of experimental neuropathy in a long-term murine model of diabetes induced by streptozotocin. By serendipity, a subset of these diabetic mice spontaneously regained islet function and attained near-euglycemia. Our hypotheses were that this model might better reflect axon loss observed in human disease and that spontaneous recovery from diabetes might identify the features of neuropathy that are reversible. In this model, experimental neuropathy closely modeled that in humans in most critical aspects: declines in motor conduction velocities, attenuation of compound muscle (M waves) and nerve action potentials, axon atrophy, myelin thinning, loss of epidermal axons, and loss of sweat gland innervation. Overt sensory neuron loss in dorsal root ganglia was a feature of this model. In mice with recovery, there was robust electrophysiological improvement, less myelin thinning, and remarkable epidermal and sweat gland reinnervation. There was, however, no recovery of populations of lost sensory neurons. Our findings identify a robust model of human diabetic neuropathy and indicate that overt, irretrievable loss of sensory neurons is one of its features, despite collateral reinnervation of target organs. Sensory neurons deserve unique protective strategies irrespective of islet cell reconstitution.

Action Potentials↗

Complications: neuropathy, pathogenetic considerations.

The most common form of neuropathy associated with diabetes mellitus is distal symmetric sensorimotor polyneuropathy, often accompanied by autonomic neuropathy. This disorder is characterized by striking atrophy and loss of myelinated and unmyelinated fibers accompanied by Wallerian degeneration, segmental, and paranodal demyelination and blunted nerve fiber regeneration. In both humans and laboratory animals, this progressive nerve fiber damage and loss parallels the degree and/or duration of hyperglycemia. Several metabolic mechanisms have been proposed to explain the relationship between the extent and severity of hyperglycemia and the development of diabetic neuropathy. One mechanism, activation of the polyol pathway by glucose via AR, is a prominent metabolic feature of diabetic rat peripheral nerve, where it promotes sorbitol and fructose accumulation, myo-inositol depletion, and slowing of nerve conduction by alteration of neural Na(+)-K(+)-ATPase activity or perturbation of normal physiological osmoregulatory mechanisms. ARIs, which normalize nerve myo-inositol and nerve conduction slowing, are currently the focus of clinical trials. Other specific metabolic abnormalities that may play a role in the pathogenesis of diabetic neuropathy include abnormal lipid or amino acid metabolism, superoxide radical formation, protein glycation, or potential blunting of normal neurotrophic responses. Metabolic dysfunction in diabetic nerve is accompanied by vascular insufficiency and nerve hypoxia that may contribute to nerve fiber loss and damage. Although major questions about the pathogenesis of diabetic neuropathy remain unanswered and require further intense investigation, significant recent progress is pushing us into the future and likely constitutes only the first of many therapies directed against one or more elements of the complex pathogenetic process responsible for diabetic neuropathy.

Animals↗

Microalbuminuria associated with diabetic neuropathy.

OBJECTIVE: To test the hypothesis that microalbuminuria may show an independent statistical association with diabetic neuropathy. RESEARCH DESIGN AND METHODS: An observational study of a prospectively identified cohort was conducted at the University Medical Center. The cohort consisted of 78 consecutive diabetic patients who fulfilled the criteria of having diabetes for greater than 10 yr, a normal serum creatinine, urine negative for macroalbuminuria by a commonly used dipstick method, a blood glucose less than 13.8 mM (less than 250 mg/dl), and an HbA1 less than 11% (normal range 5.5-8.5%). Medical record review established the presence of chronic complications of diabetes. Urine albumin level was measured by radioimmunoassay. Albumin concn greater than or equal to 15 mg/L was used as a cutoff value for microalbuminuria. RESULTS: Twenty-five of 78 patients (32%) showed microalbuminuria. Of these, 51% had neuropathy, 39% had retinopathy, 35% arterial hypertension, 17% peripheral vascular disease, and 15% ischemic heart disease. After adjusting for age, sex, and type and duration of diabetes, diabetic neuropathy and hypertension showed a significant association with microalbuminuria. After adjusting for other diabetic complications, diabetic neuropathy showed a significant association with microalbuminuria. CONCLUSIONS: Microalbuminuria is independently associated with diabetic neuropathy. This association lends support to the theory of a vascular etiology for diabetic distal symmetrical neuropathy.

Albuminuria↗

The forefoot-to-rearfoot plantar pressure ratio is increased in severe diabetic neuropathy and can predict foot ulceration.

OBJECTIVE: We have previously demonstrated that high plantar pressures can predict foot ulceration in diabetic patients. The aim of the present study was to evaluate both the relationship between forefoot and rearfoot plantar pressure in diabetic patients with different degrees of peripheral neuropathy and their role in ulcer development. RESEARCH DESIGN AND METHODS: Diabetic patients of a 30-month prospective study were classified according to the neuropathy disability score: scores of 0, 1-5, 6-16, and 17-28 are defined as absent (n = 20), mild (n = 66), moderate (n = 95), and severe (n = 57) neuropathy, respectively. The F-Scan mat system was used to measure dynamic plantar pressures. The peak pressures under the forefoot and the rearfoot were selectively measured for each foot, and the forefoot-to-rearfoot ratio (F/R ratio) was calculated. RESULTS: Foot ulcers developed in 73 (19%) feet. The peak pressures were increased in the forefoot of the severe and moderate neuropathic groups compared with the mild neuropathic and non-neuropathic groups (6.2 +/- 4.5 and 3.8 +/- 2.7 vs. 3.0 +/- 2.1 and 3.3 +/- 2.1 kg/cm(2) [mean +/- SD], respectively; P < 0.0001). The rearfoot pressures were also higher in the severe and moderate neuropathic groups compared with the mild neuropathic and non-neuropathic groups (3.2 +/- 2.0 and 3.2 +/- 1.9 vs. 2.5 +/- 1.3 and 2.3 +/- 1.0, respectively; P < 0.0001). The F/R ratio was increased only in the severe group compared with the moderate and mild neuropathic and non-neuropathic groups (2.3 +/- 2.4 vs. 1.5 +/- 1.2, 1.3 +/- 0.9, and 1.6 +/- 1.0, respectively; P < 0.0001). In a logistic regression analysis, both forefoot pressure (odds ratio 1.19 [95% CI 1.11-1.28], P < 0.0001) and the F/R ratio (1.37 [1.16-1.61], P < 0.0001) were related to risk of foot ulceration, whereas rearfoot pressure was not. CONCLUSIONS: Both the rearfoot and forefoot pressures are increased in the diabetic neuropathic foot, whereas the F/R ratio is increased only in severe diabetic neuropathy, indicating an imbalance in pressure distribution with increasing degrees of neuropathy. This may lend further evidence toward the concept that equinus develops in the latest stages of peripheral neuropathy and may play an important role in the etiology of diabetic foot ulceration.

Adult↗

The LDIflare: a novel test of C-fiber function demonstrates early neuropathy in type 2 diabetes.

OBJECTIVE: The aim of this study was to evaluate a novel method for assessing the axon reflex and to determine its value in detecting neuropathy in type 2 diabetes. RESEARCH DESIGN AND METHODS: The neurogenic flare response to nociceptive stimuli is mediated by an axon reflex involving small unmyelinated C-fibers. We developed a method to assess this reflex involving skin heating to 44 degrees C to evoke the flare followed by scanning the site using a laser Doppler imager (LDI) to measure the area; we termed this method LDIflare. To confirm its neurogenic nature, we examined the LDIflare in eight healthy subjects before and after topical administration of anesthesia. We used this technique to detect C-fiber neuropathy in people with type 2 diabetes. A total of 36 subjects were studied: 12 subjects with neuropathy (group DN), 12 subjects without neuropathy (group DC), and 12 age- and sex-matched control subjects (group NC). For comparison, small-fiber function was also assessed using the Computer Aided Sensory Evaluator-IV (CASE IV) (WR Medical Electronics, Stillwater, MN). RESULTS: In the eight healthy control subjects, LDIflare was markedly reduced after topical administration of anesthesia (1.62 [1.45-1.72] vs. 5.2 cm2 [3.9-5.9], P <0.0001), confirming its neurogenic nature. Similarly, in neuropathic subjects, LDIflare was significantly smaller compared with normal and diabetic control subjects (LDIflare area: DN 1.3 cm2 [0.9-1.8], NC 5.5 cm2 [3.9-5.8], and DC 2.8 cm2 [2.5-3.8]; P <0.0001 and P=0.01, respectively). The group without neuropathy (DC) also demonstrated a reduced flare compared with the NC group (P=0.01). In contrast, C-fiber function assessed by evaluating the quantitative thermal thresholds (CASE IV) did not detect a difference between the latter two groups. CONCLUSIONS: This study confirms the neurogenic nature of the LDIflare and clearly demonstrates loss of C-fiber function in neuropathic subjects with type 2 diabetes. Moreover, it demonstrates C-fiber dysfunction before its detection by other currently available methods, including CASE IV. The LDIflare seems to be a simple objective method to detect early neuropathy and may be of value in assessing therapeutic interventions aimed at preventing or reversing C-fiber dysfunction.

Body Mass Index↗

Intraepidermal nerve fibers are indicators of small-fiber neuropathy in both diabetic and nondiabetic patients.

OBJECTIVE: Small-fiber neuropathies may be symptomatic yet escape detection by standard tests. We hypothesized that morphologic changes in intraepidermal nerves would correlate with clinical measures of small-fiber neuropathy. RESEARCH DESIGN AND METHODS: We studied 25 diabetic and 23 nondiabetic patients with neuropathy defined by signs, symptoms, and quantitative testing and 20 control subjects. Skin biopsies were obtained from forearm, thigh, proximal leg, and distal leg, and nerves identified using immunofluorescence with antibody to protein gene product (PGP) 9.5. RESULTS: Mean dendritic length (MDL) (P < 0.01) and intraepidermal nerve fiber density (IENF) (P < 0.001) progressively decreased from proximal to distal sites only in patients with neuropathy. There was a significant reduction in IENF when comparing control subjects and patient groups in the distal leg (P < 0.001). MDL was significantly decreased in the thigh (P < 0.005) and in the proximal (P < 0.01) and distal (P < 0.002) leg in patients compared with control subjects. IENF was not significantly altered in diabetic patients of <5 years' duration, but significantly decreased in patients with >5 years' duration. MDL showed a linear decrease with increasing duration of diabetes. Distal leg IENF showed significant negative correlations with warm (P < 0.02) and cold (P < 0.05) thermal threshold, heat pain (P < 0.05), pressure sense (P < 0.05), and neurological disability score total sensory (P < 0.03) and total neuropathy (P < 0.03) values. CONCLUSIONS: IENF was not significantly altered in these patients at <5 years' duration of diabetes, but fell significantly after 5 years of diabetes. MDL exhibited a linear loss with time, suggesting a different mechanism of change. MDL and IENF together may prove a useful end point in therapeutic trials for neuropathy.

Adult↗

Botanicals and dietary supplements in diabetic peripheral neuropathy.

BACKGROUND: Many persons use botanicals and dietary supplements for chronic conditions that do not respond to traditional Western medications. Tricyclic antidepressants, a common treatment option for diabetic neuropathy, can have many side effects and are a poor choice in certain populations (eg, the elderly). As such, patients might turn to botanicals and dietary supplements, not realizing that these products are not well regulated. METHODS: This article reviews botanicals and dietary supplements that have been involved in randomized controlled trials (RCTs) for diabetic neuropathy. We searched MEDLINE for English-language literature dating from 1966 to April 2001 using the following subject headings: (1) diabetes and botanical, herb, and supplement, (2) neuropathy and botanical, herb, and supplement, and (3) diabetic neuropathy and botanical, herb, and supplement. RESULTS: Our search found agents that might improve symptoms of neuropathy (eg, evening primrose oil, alpha-lipoic acid, capsaicin) without affecting glucose control. Botanicals and dietary supplements involved in only one RCT or associated with little clinical benefit were reviewed in brief. CONCLUSIONS: Evening primrose oil, alpha-lipoic acid, and capsaicin have received the greatest attention for their use in diabetic neuropathy, but further studies are needed to confirm their efficacy. Patients using these products need to be informed of potential drug interactions and side effects.

Antioxidants↗

Colonic transit time in diabetic patients--comparison with healthy subjects and the effect of autonomic neuropathy.

Constipation and the use of laxatives are relatively common in patients with diabetes mellitus. However, the mechanisms responsible for the constipation are unclear. Even though autonomic neuropathy is regarded as one of the important mechanisms of constipation, it requires further clarification. In addition, the colonic function in diabetic patients requires further investigation. The aim of this study was to compare the colonic transit time between patients with diabetes mellitus and healthy subjects, and correlate it to the presence of cardiovascular autonomic neuropathy. The colonic transit time was measured by a noninvasive, radio-opaque marker method, and the presence of cardiovascular autonomic neuropathy was evaluated by the beat-to-beat variation and the orthostatic hypotension. Constipation was defined by the Rome II criteria. The mean total colonic transit time of the 28 diabetic patients (34.9 +/- 29.6 h, mean +/- S.D.) was significantly longer than that of the 28 healthy subjects (20.4 +/- 15.6 h, p < 0.05). Among the diabetic patients, 9/28 (32%) had constipation and 14/28 (50%) had cardiovascular autonomic neuropathy. The diabetic patients with constipation showed longer total, left and recto-sigmoid colonic transit times than those without constipation. However, the mean colonic transit time of diabetic patients with and those without cardiovascular autonomic neuropathy was similar. In conclusion, other mechanisms than the mere presence of cardiovascular autonomic neuropathy might be more relevant to the development of constipation in patients with diabetes mellitus.

Adult↗

Cardiac denervation in diabetic neuropathy.

Measurement of heart rate variation during deep breathing has been used as a diagnostic test of autonomic function. Normal subjects have considerable heart rate variation that is accentuated during deep breathing; this variation is diminished or sometimes absent in diabetics with autonomic neuropathy. Recording heart rate variation during deep breathing is a good method for establishing the presence of autonomic neuropathy: All normal subjects have a score greater than 9, and autonomic neuropathy is probably absent if the score is greater than 12. The optimal breathing rate for this test is six breaths per minute in nondiabetics but is usually less in diabetics with autonomic neuropathy. The use of six breaths per minute as a standard, however, enhances the ability of the test to discriminate normal from neuropathic patients. Imparied heart rate variation can be the earliest sign of diabetic neuropathy and may precede the appearance of autonomic symptoms by several years. Severe autonomic neuropathy may be responsible for spontaneous respiratory arrest and unexplained sudden deaths, which are not rare among these patients.

Adult↗

Diabetic autonomic neuropathy causing gall bladder dysfunction.

OBJECTIVE: The objective of the study was to study gall bladder volume in fasting and 45 minutes post-prandial, by real time ultrasound in healthy controls and diabetic patients with and without autonomic neuropathy and to compare them. METHOD: Age, Sex and body mass index (BMI) matched 50 healthy subjects and 10 patients with insulin dependent diabetes mellitus and 40 patients with noninsulin dependent diabetes mellitus were evaluated according to National diabetes Data Group of National Institute of Health (1979) criteria: 1. Fasting (overnight) venous plasma glucose concentration of > 140 mg/dl on two separate occasions. 2. Following ingestion of 75 gms of glucose, venous plasma glucose concentration of > 200 mg/dl at second hour and at one other occasion during two hour test. Autonomic neuropathy was assessed by the presence of symptoms like dysphagia, abdominal fullness, nausea, vomiting, diarrhea +/- nocturnal, faecal incontinence or constipation, dysuria, urinary incontinence, the gustatory sweating, impotence etc. and were confirmed by standing test for orthostatic hypotension, hand grip test, Valsalva test and deep breaths test. RESULT: The study showed that: 1. Patients of diabetes mellitus had statistically significant larger fasting gall bladder volumes and these values were highly significant amongst patients with autonomic neuropathy. 2. Patients of diabetes mellitus and statistically significant larger post fatty meal gall bladder volume and these values were highly significant in patients with autonomic neuropathy. CONCLUSIONS: We therefore conclude that impaired gall bladder contraction was found amongst patients of diabetes mellitus with autonomic neuropathy. The mechanism responsible for cholecystoparesis is attributed to vagal neuropathy. Incomplete gall bladder emptying leads to sequestration of cholesterol and nidus formation. Therefore gall bladder functions should be evaluated routinely in such patients and early intervention is recommended.

Adult↗

Diabetic neuropathies.

Diabetes mellitus is a systemic disorder with a significant impact on the peripheral nervous system. Over half of the 15 million patients with diabetes mellitus in the United States have some form of diabetic neuropathy. Individuals with diabetes may develop acute or subacute painful polyneuropathy, proximal motor neuropathy, autonomic neuropathy, compression neuropathy, focal neuropathy, and chronic polyneuropathy. Studies have shown that optimizing diabetic control provides the greatest likelihood of either preventing or slowing the development of diabetic neuropathy.

Diabetic Neuropathies↗

[Risk factors involved in symmetrical distal diabetic neuropathy].

INTRODUCTION: Diabetic neuropathy is a common neurological complication in patients with diabetes mellitus which affects their quality of life. The risk factors involved in this are not completely clear. OBJECTIVE: To determine the frequency of symmetrical distal diabetic neuropathy and the risk factors associated with its occurrence in the group studied. PATIENTS AND METHODS: A transversal study was made in the Hospital Clinico Quirurgico Hermanos Ameijeiras of Ciudad de la Habana (Cuba), in 200 patients diagnosed as having type 1 or type 2 diabetes mellitus, between January 1997 and December 1999. A clinical neurological examination and neurophysiological investigations were done on all patients to make a diagnosis of diabetic neuropathy. Subsequently, we compared those with diabetic neuropathy and those without in relation to the risk factors. Statistical analysis included the chi squared test and estimation of the relative risk. RESULTS. The frequency of symmetrical distal diabetic neuropathy was 30.0%. Related risk factors were: smoking (p= 0.00, RR= 2.59), raised serum cholesterol (p= 0.00, RR= 4.12), poor metabolic control of diabetes mellitus (p= 0.00, RR= 4.13), associated disorders (p= 0.00, RR= 5.31) including arterial hypertension (p= 0.03, RR= 1.90) and duration of diabetes mellitus (p= 0.00, RR= 2.01). CONCLUSIONS: In our study symmetrical distal diabetic neuropathy was a common complication of diabetes mellitus associated with various risk factors.

Administration, Oral↗

Intravenous immunoglobulin G is remarkably beneficial in chronic immune dysschwannian/dysneuronal polyneuropathy, diabetes-2 neuropathy, and potentially in severe acute respiratory syndrome.

Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy is an autoimmune peripheral-nerve and/or nerve-root disorder known to usually respond to intravenous immunoglobulin-G treatment. Benefit can involve any combination of motor-nerve fibers and large and small sensory-nerve fibers responsible for a progressively crippling, unbalancing, discomforting or painful disorder. "Diabetic neuropathy" is commonly considered untreatable. However, 81% of my 48 recently-summarized type-2 diabetes patients with polyneuropathy, adequately-treated with intravenous immunoglobulin-G, off-label, were relieved, sometimes completely, of various motor and sensory symptoms, including pain, thereby resembling Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy. Spinal fluid protein in them is often elevated, higher values seeming to auger a better intravenous immunoglobulin-G response. Continuing the improvement requires continuing the intravenous immunoglobulin-G treatment, indicating both intravenous immunoglobulin-G responsiveness and dependency. The intravenous immunoglobulin-G responsive type-2 diabetes polyneuropathy usually is dysschwannian, sometimes mainly dysneuronal intravenous immunoglobulin-G, the most beneficial and safest treatment, is costly, but if intravenous immunoglobulin-G-treatability of a dysimmune component of type-2 diabetes neuropathy is overlooked, dismissed or rejected, as commonly happens, other costs are high regarding the patient's worsening morbidity and disability, and resultant need for increased medical care. A novel intravenous immunoglobulin-G regimen effective for fragile patients is Two Non-Consecutive-Days Every Week, using 0.4 gm/kg body wt/day. Possible molecular mechanisms of intravenous immunoglobulin-G benefit are discussed. I propose that a) there is a higher incidence of Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy-like neuropathy in type-2 diabetes patients and in patients with a strong family history of type-2 diabetes, and b) the intravenous immunoglobulin-G-treatable neuropathy in type-2 diabetes can be brought on by the genetico-diabetoid-2 state. The genetic-metabolic milieu (but not necessarily glucose dysmetabolism per se.) of type-2 diabetes putatively predisposes to the presumably-dysimmune intravenous immunoglobulin-G-responsive polyneuropathy. In some of our patients, especially ones having a strong type-2 diabetes genetic background, the intravenous immunoglobulin-G-responsive neuropathy preceded the diagnosis of type-2 diabetes by 5-10 years. Accordingly, Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy patients having a strong type-2 diabetes genetic background are designated "genetico-diabetoid-2 neuropathy" prior to their manifesting type-2 diabetes. Intravenous immunoglobulin-G is herein suggested as a treatment for Severe Acute Respiratory Syndrome, a recent, and feared-repetitive, pandemic with many fatalities caused by a highly-contagious mutant coronavirus, for which there is no definitive treatment. Intravenous immunoglobulin-G might: a) combat a dysimmune component of Severe Acute Respiratory Syndrome, including the reactive cytokine-chemokine storm against respiratory tissues; b) contain some antibodies effective against the coronavirus non-specific components of Severe Acute Respiratory Syndrome; c) block host-cell receptors for the virus; and d) counteract secondary infections.

Chronic Disease↗

Alpha-lipoic acid in the treatment of autonomic diabetic neuropathy (controlled, randomized, open-label study).

AIM: to evaluate the effect of alpha-lipoic acid in autonomic diabetic neuropathy in a controlled, randomized, open-label study. MATERIAL AND METHODS: 46 patients with type 1 diabetes and different forms of autonomic neuropathy, of mean age 38.1 +/- 12.5 years and mean duration of diabetes 16.8 +/- 8.9 years were treated with alpha-lipoic acid for 10 days 600mg daily iv, thereafter one film tablet of 600mg daily for 50 days. 29 type 1 diabetic patients with autonomic diabetic neuropathy, of mean age 40.2 +/- 9.3 years and mean duration of diabetes 15.4 +/- 7.9 years served as a control group. We have followed-up patients' complaints, Ewing's tests, laboratory parameters of oxidative stress. RESULTS: There was a significant improvement after treatment in the score for severity of cardiovascular autonomic neuropathy--from 6.43 +/- 0.9 to 4.24 +/- 1.8 (p<0.001), while in the control group it worsened from 6.18 +/- 1.3 to 6.52 +/- 0.9 (p>0.1). We found improvement in the Valsalva manoeuvre after treatment - from 1.05 +/- 0.04 to 1.13 +/- 0.08 (p<0.001); in the deep-breathing test -from 3.4 +/- 2.8 to 10.4 +/- 5.7 (p<0.001); and in the lying-to-standing test--from 0.99 +/- 0.01 to 1.01 +/- 0.02 (p>0.1), while in the control group there was no improvement. There was a beneficial effect of treatment on the change of systolic blood pressure at the lying-to-standing test--from 22.7 +/- 11.5 to 9.8 +/- 7.9 (p<0.001), while in the control group the change was 20.5 +/- 11.1 mmHg and 19.7 +/- 12.9 mmHg (p>0.1), respectively. We found improvement in diabetic enteropathy in six patients; in the complaints of dizziness, instability upon standing in six patients; in neuropathic edema of the lower extremities in four patients and in erectile dysfunction in four patients after treatment, while in the control group no change was reported in the symptoms and signs of autonomic neuropathy by the end of the follow-up period. There were changes in the laboratory parameters of oxidative stress after therapy--total serum antioxidant capacity increased from 20.42 +/- 1.8 to 22.96 +/- 2.3 microgH2O2/ml/min (p<0.05), serum SOD activity - from 269.8 +/- 31.1 to 319.8 +/- 29.IU/l (p=0.02) and erythrocyte SOD--from 0.89 +/- 0.10 to 1.11 +/- 0.09 U/gHb (p=0.04). CONCLUSION: Our results demonstrate that alpha-lipoic acid (Thiogamma) appears to be an effective drug in the treatment of the different forms of autonomic diabetic neuropathy.

Adult↗

The evaluation of peripheral neuropathy. Part II: Identifying common clinical syndromes.

The first of this 3-part series on the diagnosis and management of peripheral neuropathy focused on the recognition of neuropathy and its clinical and laboratory characterization as essential to determining etiology. This approach allows for the construction of a differential diagnosis that can be narrowed by subsequent diagnostic testing. This installment, along with the final one, will focus on recognition and management of common neuropathies likely to be seen by the average practitioner. Neuropathies covered in this second part include diabetic, autoimmune and inflammatory, toxic, neuropathies associated with plasma cell dyscrasias, and paraneoplastic neuropathies.

Adult↗

The influence of autonomic neuropathy on mortality in insulin-dependent diabetes.

Five-year survival was investigated in 506 randomly selected patients with insulin-dependent diabetes mellitus screened for autonomic neuropathy with a series of cardiac autonomic function tests. Of the 484 diabetics traced, 44 (9 per cent) had died. The cumulative 5-year mortality rate was increased more than five-fold in those with autonomic neuropathy: 27 per cent vs. 5 per cent in those with normal autonomic function. Discriminant analysis of survivors and non-survivors showed that autonomic neuropathy was the most important independent predictor of death. Among those who died, autonomic neuropathy was associated with an increased frequency of retinopathy and peripheral neuropathy and a slightly lower frequency of macrovascular disease. Autonomic neuropathy was associated with an increased mortality rate from renal failure, but not from any other causes.

Adolescent↗