Electrical spinal-cord stimulation for painful diabetic peripheral neuropathy

BACKGROUND: Conventional treatment for painful peripheral diabetic neuropathy is largely symptomatic and often ineffective, with unacceptable side-effects. We tested electrical spinal-cord stimulation for the management of chronic neuropathic pain. METHODS: Ten diabetic patients who did not respond to conventional treatment (mean age 51 [SD 9.3] years, six with type II diabetes, mean duration of diabetes 12 [6.3] years, mean duration of neuropathy 5 [2.1] years) were studied. The electrode was implanted in the thoracic/lumbar epidural space. Immediate neuropathic pain relief was assessed by visual analogue scale (VAS) after connecting the electrode, in a random order, to a percutaneous electrical stimulator or to a placebo stimulator. Exercise tolerance was assessed on a treadmill. FINDINGS: Eight subjects had statistically significant pain relief with the electrical stimulator (p < 0.02) and were therefore converted to a permanent system. Statistically significant relief of both background and peak neuropathic pain was achieved at 3 months (n = 7, p = 0.016), at 6 months (n = 7, p = 0.03), and at the end of the study (14 months, n = 7, background pain p = 0.06, peak pain p = 0.03). One patient died 2 months after the start of the study of unrelated cause while continuing to benefit from treatment and another patient ceased to benefit at 4 months. McGill pain questionnaire scores with the stimulator turned off did not change significantly from baseline scores, indicating that the severity of the underlying pain was unaltered. However, with the stimulator turned on, there was a statistically significant (p < 0.05) improvement in all four components of the score, by the end of the study. At the end of the study, six patients continued to gain significant pain relief and used the stimulator as the sole treatment for their neuropathic pain. For example, median background and peak pain scores at the end of study, were, respectively, 77 and 81 with the stimulator off and 23 and 20 with the stimulator on. Exercise tolerance significantly improved at 3 months (n = 7, median % increase 85 [IQR, 62-360], p = 0.015) and at 6 months (n = 6, 163 [61-425], p = 0.0007). Electrophysiological tests, vibration perception-threshold, and glycaemic control were unchanged. INTERPRETATION: Electrical spinal-cord stimulation offers a new and effective way of relieving chronic diabetic neuropathic pain and improves exercise tolerance. The technique should be considered in patients with neuropathic pain who do not respond to conventional treatment.     

Evaluation of the efficacy of thiamine and pyridoxine in the treatment of symptomatic diabetic peripheral neuropathy

Our purpose in this study was to determine the effects of cheilectomy on the mechanics of dorsiflexion of the first metatarsophalangeal (MTP) joint. Ten fresh-frozen cadaver feet were utilized, of which two demonstrated radiographic evidence of hallux rigidus. Each specimen was rigidly mounted on a custom-made slide tray that was articulated with a hinge mechanism designed to dorsiflex the first MTP joint. Range-of-motion measurements were made on the first MTP joint. Cheilectomy of 30% of the metatarsal head diameter was performed. Lateral radiographs with the beam centered on the MTP joint were taken with the joint at neutral, 20 degrees, 40 degrees, and at the limits of dorsiflexion. This process was repeated after a 50% cheilectomy was performed. The radiographs were examined for changes in joint congruence and in patterns of surface motion as the hallux moved from neutral to full dorsiflexion. Instant centers of rotation were determined by a method first described by Rouleaux. We constructed surface velocity vectors to describe patterns of motion of the first MTP joint. The mean dorsiflexion of the first MTP joint was 67.9 degrees and increased to 78.3 degrees after 30% cheilectomy. The increase in dorsiflexion was significantly greater in the two specimens with hallux rigidus (33%) than in the other specimens (12.1%). After both levels of cheilectomy, the proximal phalanx demonstrated pivoting at the resection site on the metatarsal head. This pivoting resulted in abnormal motion patterns across the MTP joint. Normal sliding motion predominated in early dorsiflexion, with compression peaking at the end stage of dorsiflexion, producing jamming of the articular surfaces. Cheilectomy significantly increased dorsiflexion of the MTP joint, but resulted in abnormal motion patterns. The increase in dorsiflexion resulted from pivoting of the proximal phalanx on the metatarsal head, resulting in anomalous velocity vectors and compression across the MTP joint.     

Reproducibility of different methods for diagnosing and monitoring diabetic neuropathy

The subspecialty of allergy and immunology, like all medical specialties, has been dramatically impacted by the managed care revolution. Many of the changes that have been imposed by our environment are likely to persist, including increased emphasis on efficiency of practice and cost-effectiveness of treatment modalities. It is predicted that these changes will decrease the involvement of allergists and immunologists in the primary treatment of patients with allergic rhinitis and mild asthma, in favor of management by generalists with subspecialty consultation. Conversely, outcomes studies demonstrate the cost-effectiveness of management of moderate to severe asthma by an allergy and immunology subspecialist. It is thought probable that HMOs will recognize this fact and implement it as a pattern of practice. The allergist and immunologist will continue to offer, uniquely, expertise in allergic history taking, patient education, environmental control, and management of allergic inflammation. He or she will also be afforded an opportunity for practice expansion, particularly as an expert consultant, into other areas of immune inflammation, such as autoimmunity and graft rejection. Potentially new and increasingly specific products of the pharmaceutical and biotechnology industries will enhance these opportunities for practice expansion by physicians who combine intellectual understanding with practical expertise in patient management. Realization of these new opportunities will require us to work together as teachers and role models to communicate the excitement of our subspecialty to new physicians. Allergy and immunology is a subspecialty with a bright future, provided that we have the will and the insight to deal effectively with our challenges and to master opportunities that our science presents to us.     

Guidelines for management of the jaundiced term and near-term infant

Factors believed to have contributed to the reemergence of kernicterus in the United States during the 1990's are discussed: these include decreased concern about toxicity of bilirubin in term and near-term infants, increased prevalence of breastfeeding, and increasingly shortened postnatal hospital stays. The rationale for a universal predischarge bilirubin measurement at the time of the routine predischarge metabolic screen is presented: the hour-specific level of bilirubin at discharge, plotted on an Hour-Specific Bilirubin Nomogram, improves prediction of risk of excessive jaundice postdischarge and facilitates safe, cost-effective follow-up. This minimizes repeat bilirubin measurements and maximizes recognition of confounding variables and risk of hyperbilirubinemia so that timely, minimally invasive, preventive therapy can be instituted if needed.     

Pathophysiology and treatment of painful diabetic neuropathy of the lower extremity

BACKGROUND: Symptomatic peripheral neuropathy is the most common complication of diabetes mellitus, affecting up to 62% of Americans with diabetes. METHODS: We reviewed the literature using the National Library of Medicine's MEDLINE search service. In total, we reviewed 54 articles. RESULTS: Hyperglycemia leads to increased activity in the polyol pathway in nerve cells; this ultimately results in abnormal nerve function. Numerous pharmacologic agents have been used to treat symptomatic peripheral neuropathy, but all of these drugs can be associated with adverse side effects. Recent work has indicated that subsensory electrical stimulation may be preferred to pharmacotherapy, since it is equally effective and has a more favorable safety profile. CONCLUSION: Although the pathophysiology of diabetic neuropathy is well understood, treatment of the symptoms associated with this condition can be challenging. Additional research is needed to reveal a safe and effective treatment for this debilitating sequela of diabetes mellitus.     

Guidelines for the diagnosis and treatment of chronic obstructive lung disease--effective and necessary

The independent practice of the art of medicine which doctors took for granted in the past has ended. With almost revolutionary speed, insurers, administrators and politicians have distributed the unique relationship between doctors and their patients. Treatment and diagnostic guidelines in different clinical entities have been based on the pillars of medicine - controlled studies and/or a common consensus among specialists and practitioners. These dynamic activities have enriched our knowledge and practice of medicine. However, only the continuing direct collaboration of physicians at all levels and constant adjustment to changing conditions make these guidelines applicable to the ever changing world of medicine. Chronic obstructive lung disease is one such clinical entity that requires uniform guidelines. Issues that have to be addressed are not only who belongs in this category but also what interventions, such as lateral chest radiographs, CT scans and sleep lab investigations, should be performed as well as the indications for costly therapies such as long-term home oxygen, alpha-1-protease inhibitor augmentation therapy and lung transplantations. Instead of looking at guidelines at straitjackets that limit excellence in the practice of medicine, medical associations should treat them as an opportunity to define their own quality standards. By doing so, the medical community would eliminate the influence of administrative directions or gatekeeper decisions, while patients and the whole population would greatly benefit.     

Advances in the genetics of peripheral neuropathy in childhood

Pneumocystis carinii pneumonia (PCP) occurs commonly in immunocompromised patients. Sulfamethoxazole-trimethoprim (SMX-TMP) is effective prophylaxis, although PCP may still occur despite apparently adequate use. We report three cases of PCP which highlight some of the pitfalls of prophylaxis.     

Approach to the diagnosis and therapy of vascular neuropathy

Peripheral neuropathy is a very common clinical manifestation of vasculitis syndromes which may present as an early sign of such neuropathy or else may be the only such sign as in the case of non-systemic vascular neuropathy. The clinical affectation of the neuropathy depends on the extent and course of the ischaemic changes brought on by vasculitis, with multineuritis being the most usual presenting form of vascular neuropathy. Neurophysiological studies show the extent and severity of the neuropathy and often identify subclinical affectation representing a mixed pattern of affectation with axomal predominance. Nerve biopsy is a prerequisite for diagnosis, noting any infiltration by inflammatory cells and/or necrosis at perivascular and transmural levels together with vessel thrombosis or rechanneling. Using immunofluorescent techniques, immune deposits of IgG, IgM and components may be noted. Vasculitis neuropathy treatment is fundamentally carried out at the expense of corticosteroids and immunosuppressive which may be administered individually or in combination. In vasculitis neuropathy bad prognostic factors would include old age, the presence of kidney disease and delayed diagnosis and treatment.     

Gastroplasty for morbid obesity. Guidelines for post-operative management

Morbid obesity is a very difficult condition to treat. Any operation intended to help the patient Jose weight is no more than a beginning, and must be combined with rigorous postoperative care or it will surely fail.     

p75 neurotrophin receptor induction and macrophage infiltration in peripheral nerve during experimental diabetic neuropathy: possible relevance on regeneration

In this study we examined the expression of the neurotrophin receptor p75 (p75NTR) and the activation of macrophages in the sciatic nerve of rats at different time points after the induction of diabetes with streptozotocin (STZ). Northern blot and immunocytochemical analysis showed that p75NTR was not detectable in the sciatic nerve by Week 2 after STZ treatment. At this time, single nerve fiber immunostaining using ED1 monoclonal antibody revealed that active macrophages were infiltrating the endoneurium, which had a normal morphological aspect. By Weeks 5 and 15 p75NTR mRNA and protein were induced in the endoneurium of diabetic animals. Immunocytochemical analysis of teased single nerve fibers showed that p75NTR protein was distributed uniformly along isolated fibers with no pathological evidence of axonal degeneration or myelin disruption. At this time, cells of the phagocyte lineage had already disappeared from the nerve. These data show that during experimental diabetic neuropathy, the endoneurial induction of p75NTR is localized along isolated nerve fibers showing no morphological alterations, and in time, follows the recruitment of active macrophages in the nerve, suggesting that these cells, directly or through their products, can influence p75NTR induction. This process might play an important role in STZ diabetic neuropathy, as a response to decreased levels of neurotrophins such as NGF and promoting nerve regeneration in the early phases of the disease.     

HIV-infected subjects with the E4 allele for APOE have excess dementia and peripheral neuropathy

HIV produces a chronic viral infection of the central nervous system that elicits chronic glial activation and overexpression of glial cytokines that are also implicated in Alzheimer disease (AD) pathogenesis. A genetic risk factor for AD is the E4 isoform for apolipoprotein E (APOE). Here we compare the frequency of neurologic symptoms for subjects with and without the E4 isoform (E4(+)and E4(-), respectively) in an HIV cohort. Compared with E4(-) subjects, twice as many E4(+) subjects were demented (30% compared with 15%) or had peripheral neuropathy (70% compared with 39%) at least once, and they had threefold more symptomatic examinations (13% compared with 3% and 42% compared with 14%, respectively)(P < 0.0001). Thus, neurologic symptoms for HIV-infection and AD are linked through an etiologic risk factor. Long-term survivors of HIV infection with E4 may be at high risk for AD; conversely, gene-viral interactions may speed AD pathogenesis.