Diabetic neuropathy: clinical aspects

The importance of diabetic neuropathy derives from its remarkable frequency and its clinical impact. In view of the varying underlying pathogenetic mechanisms and the resulting diversity of clinical representations, it becomes apparent that there are diabetic neuropathies, rather than a single entity of diabetic neuropathy. The scope of involvement is widespread with virtually every system at risk. Although peripheral neuropathy is by far the most common expression, visceral neuropathy is also highly significant. It may affect every part of the gastrointestinal tract, the genitourinary tract, and sexual function, as well as direct autonomic nerve pathology. Clearly, neuropathy in diabetes offers a specific and important diagnostic challenge to the clinician and plays a definitive role in differential diagnosis. The problem is heightened by the fact that any and all of the diabetic neuropathic syndromes may be the initial clinical manifestation of diabetes in the absence of covert manifestations of carbohydrate metabolic disorder. It is to be stressed that the diagnosis is more than an academic exercise, since each diabetic neuropathic syndrome carries with it some beneficial therapeutic modality to aid the patient.     

Neuropathies associated with malignancy

Patients with malignancy can develop peripheral neuropathies as (1) a direct effect of the cancer by invasion or compression of nerves, (2) a remote or paraneoplastic effect, or (3) an iatrogenic effect of treatment. Focal or multifocal cranial neuropathies, radiculopathies, and plexopathies typically result from tumor infiltration, herpes zoster infection, or radiation-induced injury. Sensorimotor polyneuropathies are the most frequently encountered peripheral nerve syndromes, but motor neuropathies, sensory neuronopathies, polyradiculoneuropathies, and autonomic neuropathies can also occur. Although uncommon, paraneoplastic mechanisms should be considered in a patient with malignancy and an associated peripheral nerve disorder, especially in the setting of small-cell lung cancer or lymphoproliferative cancer. Toxic neuropathies occur with exposure to several chemotherapeutic agents, including the vinca alkaloids, cisplatin, taxanes, and suramin. These neuropathies are usually dose-related, sensory-predominant, and at least partially reversible, with an axonopathic or ganglionopathic mechanism. Suramin is unique in causing subacute, demyelinating polyradiculoneuropathy.     

Common peripheral vascular diseases

Among the most common causes of morbidity and mortality in elderly individuals are the manifestations of the various peripheral vascular diseases. Many chronic degenerative diseases, which begin in middle age, are associated with peripheral vascular disease. Heart disease, hypertension, hyperlipidemia and diabetes are all risk factors for peripheral vascular diseases and also common degenerative conditions in our society. Other risk factors, such as diet, smoking, stress, lack of exercise, and obesity, are also closely associated with peripheral vascular disease. Aging itself is also a risk factor. Appropriate treatment for disease processes such as diabetes and hypertension and control of other preventable risk factors have been shown to reduce the morbidity and mortality seen in peripheral vascular disorders. Our rapidly aging population requires increasing amounts of medical resources, placing an enormous burden on society because the aged population are generally more dependent upon government-sponsored health care services. The podiatric practitioner is in a position as a primary care provider to influence the health practices of our aging population. The implementation of a health practice that stresses prevention and wellness as well as the appropriate management and a referral of patients with peripheral vascular disorders will limit the morbid results of peripheral vascular diseases.     

Constipation: a common problem in patients with neurological abnormalities

Constipation is a frequent complaint among patients with different neurological diseases. This review provides a brief account of the numerous conditions affecting the central, peripheral and intrinsic (enteric) nervous systems in which constipation can be the only clinical manifestation or a component of a complex syndrome. Recent neuropathophysiological acquisitions show that any structural or functional impairment of the intrinsic innervation of the gut, including both developmental (i.e., Hirschsprung's disease and intestinal neuronal dysplasia) and acquired (i.e., either degenerative or inflammatory neuropathies) disorders, can be associated with constipation. Constipation may also arise from derangements of the peripheral nervous system, including diabetes and primary chronic autonomic failure (pandysautonomias). Finally, in the central nervous system, a wide array of disorders (post-traumatic, degenerative, ischaemic or neoplastic) are recognized to determine bowel dysfunction, ultimately leading to constipation. Further understanding of the fine pathophysiological mechanisms through which the intrinsic and extrinsic nerve supplies to the digestive system are involved in idiopathic constipation or in diseases generating this symptom will hopefully lead to a better treatment of this frequent pathological condition.     

Diagnosis of polyneuropathies

The accurate diagnosis of peripheral neuropathy is important with respect to the therapeutic possibilities and limitations, which are especially relevant in immune-mediated polyneuropathies. These polyneuropathies may be axonal or demyelinating and have an acute or chronic course, and they may be difficult to distinguish from non-treatable neuropathies on clinical grounds. Efforts have been made to establish clinical, neurophysiological, morphological, biochemical, immunological and molecular biological criteria to attain specific diagnosis. This has shown heterogeneity not only within the treatable neuropathies, which may have implications for the treatment. It has also been shown that hereditary or diabetic polyneuropathy may have features which respond to immunosuppressive treatment. Molecular biology studies have revealed markers for the diagnosis of hereditary neuropathy, and have in some instances also delineated the gene product.     

Tumor hypoxia and gene expression--implications for malignant progression and therapy

Neuropathies are infrequent but potentially debilitating complications in surgical patients. Although the most common of these affect the peripheral ulnar and sciatic nerves, more centrally located sets of nerves such as the brachial plexus and lumbosacral nerve roots also can be affected perioperatively. Traditionally, these neuropathies have been considered avoidable and associated with inappropriate patient positioning intraoperatively. Recent epidemiologic and anatomic studies suggest, however, that various factors other than intraoperative positioning may contribute to the development of neuropathies. For example, it is now clear that a large proportion of surgical patients who subsequently have development of ulnar neuropathies are asymptomatic during the first several postoperative days. Further delineation of the epidemiology and causes of the various perioperative neuropathies should lead to innovative interventions and clinical trials of their effectiveness to decrease the frequency and severity of these complications in surgical patients.     

Redox reactivity of the type 1 copper protein amicyanin from Thiobacillus versutus with its physiological partner cytochrome C550 and inter-protein cross-reaction studies

The differential diagnosis of compressive neuropathies in the arms includes syndromes involving the nerve roots and brachial plexus, as well as the peripheral nerves. Often these conditions coexist. Nerve conduction velocity studies as well as electromyography have a role along with the clinical evaluation in differentiating these conditions. Limitations in routine electrodiagnostic testing are present, which necessitate several specialized techniques for identifying compressive neuropathies.     

The cornea in diabetes mellitus

Diabetes mellitus has a significant effect on morphological, metabolic, physiological, and clinical aspects of the cornea. Morphological changes are manifest in the corneal epithelium, epithelial basement membrane and basement membrane complexes, stroma, and endothelium. The homeostasis of these structures can be altered by diabetes in both the non-stressed and the stressed cornea, causing myriad primary and postoperative manifestations. The polyol pathway appears to be involved in some of the pathophysiology mechanisms leading to these clinical entities and appears also to play a role in the treatment of some diabetic pathological processes associated with diabetes mellitus.     

Hereditary motor and sensory neuropathies. Clinical and molecular genetic aspects

Hereditary motor sensory neuropathies are a heterogeneous group of inherited diseases of the peripheral nerves. In this review the clinical and genetic differences between the sub-groups of this disease will be discussed. Since the discovery of a 1.5 mb duplication on chromosome 17 p11.2-12 in most patients with a hereditary motor sensory neuropathy and a variety of different mutations on chromosomes 1 and X in other patients with a similar disease profile, Dycks' clinical classification needs to be re-evaluated. In this review Dycks' taxonomy of heridihary neuropathies will be compared to a new genetic classification and a relevant diagnostic procedure proposed when a hereditary neuropathy is suspected.     

The effects of serial stretch loading on stretch work and stretch-shorten cycle performance in the knee musculature

Diabetes mellitus is associated with an inordinately high risk of virtually all manifestations of cardiovascular-renal disease including atherosclerotic coronary and peripheral vascular disease, congestive heart failure, stroke, nephropathy, and cardiomyopathy unassociated with coronary heart disease. Abnormalities in the renin-angiotensin-aldosterone-kinin (RAAK) cascade have been implicated in the pathogenesis and clinical expression of these cardiovascular-renal sequelae. Thus, pharmacological modulation of the RAAK system is an attractive therapeutic target in diabetes mellitus. Indeed, emerging data from human clinical studies appear to confirm this thesis.     

A case of hereditary neuropathy with liability to pressure palsies (HNPP) with diabetes mellitus

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant neuropathy recently reported to be associated with deletion of the peripheral myelin protein-22 (PMP-22) gene. We report a 39-year-old man with recurrent brachial plexopathy and foot drop complicated by uncontrolled diabetes mellitus (DM). Right foot drop occurred at 31 years of the age and the patient subsequently experienced difficulty in raising his right arm. Neurological examination revealed weakness of the right deltoid, biceps muscles and tibialis anterior muscles. Deep tendon reflexes were generally absent. Sensory nerve conduction velocities in th ulnar, median and sural nerves were prolonged. Serum glucose and HB Alc levels were elevated to 468 mg/dl and 12.5%, respectively. Initially, it was difficult to diagnose the neuropathy as HNPP because the patient had poorly controlled diabetes mellitus and was unaware of similar disease in his family. In addition, focal asymmetric motor neuropathy and good recovery can develop in diabetes mellitus, occasionally with recurrence. We were able to make a final diagnosis of HNPP by detecting deletion of the PMP-22 gene region. After the diagnosis was confirmed, we examined the patient's family and found that his father experienced recurrent episodes of bilateral foot drop. This case suggests that gene analysis is sometimes essential in the differential diagnosis of hereditary peripheral neuropathies.     

The management of diabetes in the elderly

It appears inevitable that with increased longevity, the management of the elderly diabetic will place even greater demands on hospital services. It seems reasonable to adopt a more liberal attitude to the regulation of control of diabetes in the elderly than in younger patients. However, the view that diabetes in the elderly is always mild can be dangerously misleading. A significant number of elderly diabetics develop ketoacidosis or other serious forms of metabolic disturbance, and in these patients the mortality is high. Cardiovascular disease and peripheral vascular disease are major problems in the elderly, the former being the main cause of death. For best results, it is desirable that management of diabetes not be isolated from management of other, coexisting disorders, but rather that it be considered as part of the overall patient problem. As Malins pointed out, we should think in terms of diabetics rather than diabetes.     

Electrodiagnostic evaluation of the foot

Focal entrapment neuropathies in the foot, as compared to those of the hand, represent a daunting diagnostic challenge to many electromyographers. This article emphasizes an understanding of the anatomy of the foot as a fundamental key to its electrodiagnostic evaluation. The anatomic course of specific nerves will be described in terms of entrapment sites, and the clinical and electrophysiologic manifestations of each nerve entrapment will be discussed.     

Metabolic neuropathies

A large epidemiological study has documented that one-third of diabetic patients have peripheral neuropathy. Diabetes duration, poor glycaemic control, smoking and hypertension are all independent predictors of the incidence of diabetic polyneuropathy. High prevalence of autonomic dysfunctions, both sympathetic and parasympathetic, has been found in patients with nonalcoholic chronic liver disease. The pathogenesis of metabolic neuropathy is unclear; even immunologic factors might play a role in the development of diabetic autonomic neuropathy. No specific treatments are available for these neuropathies. Correction of metabolic derangement is fundamental, as shown by the amelioration of peripheral nerve function obtained after successful simultaneous pancreas-kidney transplantation. The therapeuthic potentials of neurotrophins for the prevention and treatment of diabetic neuropathy have to be confirmed in future studies.     

A model psychosocial screening program for children and youth with newly diagnosed Type 1 diabetes: Implications for psychologists across contexts of care.

Psychosocial factors are strongly associated with long-term medical and mental health outcomes for children with Type 1 diabetes. As a result, current national and international guidelines now call for psychosocial screening at or near the time of diabetes diagnosis. Despite this recommendation, there are no published protocols to provide guidance to psychologists attempting to screen and identify at-risk patients and their families and prevent the emergence of secondary psychological and medical complications. In this article, the authors describe a model psychosocial screening program that was designed to minimize barriers to implementation and that can potentially be adapted for use by psychologists in different settings. Preliminary findings from the pilot phase of program development suggest that the screening is effective at identifying patients at risk for subsequent problems with diabetes management. The screening was able to identify specific, modifiable risk factors that provide targets for efforts at preventive intervention using treatment approaches familiar to most psychologists. The authors conclude with a discussion of the importance of screening and knowledge of diabetes risk factors for psychologists working in different treatment settings. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Injuries in young female players in European team handball

The basis for treatment of lipid disorders in patients with non-insulin-dependent diabetes mellitus is weight reduction by diet and exercise, and additional control of glycaemic condition with oral antidiabetics, alone or in combination with insulin. Hypercholesterolaemic, mildly hypertriglyceridaemic non-insulin-dependent diabetes mellitus patients respond to cholesterol malabsorption caused by dietary sitostanol ester margarine, while long-term statin treatment of respective coronary patients significantly lowers the recurrence of coronary events, in addition to improving the lipid disorder. However, no information is available concerning the preventive effect of long-term improvement of lipid disorders in non-insulin-dependent diabetes mellitus patients without coronary heart disease, or in patients with the 'classical' type of diabetic lipid disorder, that is, hypertriglyceridaemia with low HDL and normal-low LDL-cholesterol levels. In this group of patients, beneficial lipid effects can be obtained (although perhaps not normalization) with fibrates alone or, especially, in combination with current statins.     

Systemic calciphylaxis revisited

A syndrome characterized by rapidly progressive ischemic necrosis involving large areas of the skin and muscle, and by peripheral gangrene associated with extensive vascular calcifications was observed in a patient with end-stage renal failure on chronic hemodialysis. In an effort to control the disease, parathyroidectomy was performed which resulted in rapid improvement of tissue perfusion. However, the patient eventually died from sepsis within 2 months after admission. This case presents the typical features of the syndrome of systemic calciphylaxis. The literature is reviewed searching for similar cases of this poorly recognized, but life-threatening, clinical syndrome. The pathogenesis, clinical manifestations, and therapy of this unusual and rapidly progressive, but potentially reversible, condition are reviewed with emphasis on its prompt recognition and appropriate management.     

Promoting psychology in diabetes primary care.

Better diabetes management can be achieved by adding an explicit psychological component to diabetes treatment. Three cases are presented that illustrate how integrated assessment and psychotherapy can improve glucose control through three mechanisms: increasing patient acceptance of a disease state, enabling behavior change for self-care, and removing psychological barriers to disease control. Guidelines are suggested for standardized integration of psychology into diabetes care. The explicit treatment of psychological barriers to diabetes self-management would enhance standard medical practice, which normally relies on education to overcome treatment adherence problems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Peripheral neuropathies associated with monoclonal proteins

Peripheral neuropathies associated with monoclonal proteins have received considerable attention as a clinically important group of chronic late-onset neuropathies. When a monoclonal protein is found in patients with peripheral neuropathy of unknown cause, as occurs in 10% of such cases, usually no associated disease is discovered; hence MGUS. Less often, disorders such as multiple myeloma, AL amyloidosis, Waldenstr?m's macroglobulinemia, osteosclerotic myeloma, and lymphoma are found. Demyelinating neuropathies associated with MGUS of all classes, but particularly IgM, Waldenstr?m's macroglobulinemia, and osteosclerotic myeloma typically follow an indolently progressive course, and frequently respond to treatments aimed at interfering with putative underlying immune mechanisms. By contrast, axonal neuropathies associated with MGUS, multiple myeloma, and AL amyloidosis have generally shown no response to therapy. Recently, IgM monoclonal and polyclonal antibodies directed against human peripheral nerve antigens including MAG and various glycolipids such as GM1 ganglioside have been found in patients with specific neuropathy syndromes. Anti-MAG antibodies occur in predominantly sensory demyelinating neuropathies, whereas elevated titers of anti-GM1 ganglioside antibodies are associated with lower motor neuron syndromes with multifocal motor conduction block. Although the evidence for autoimmune mechanisms in some monoclonal protein-associated neuropathies is mounting, a causal connection between monoclonal proteins and these neurologic syndromes has yet to be established.     

Idiopathic hypoparathyroidism--a rare disease?

Five patients with nonfamilial idiopathic hypoparathyroidism were observed in a peripheral hospital. There was no association with other autoimmune disorders such as hypothyroidism, adrenal insufficiency or pernicious anemia. Only in one patient with tetany was the diagnosis clinically obvious; all the others presented with unusual clinical symptoms. These manifestations of chronic hypocalcemia are presented, as well as the diagnostic workup and therapeutic management. We suggest that idiopathic hypoparathyroidism is not a very rare disease, but one which is often missed because of the unusual clinical picture.