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Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial.

OBJECTIVE: The aim of this trial was to evaluate the effects of alpha-lipoic acid (ALA) on positive sensory symptoms and neuropathic deficits in diabetic patients with distal symmetric polyneuropathy (DSP). RESEARCH DESIGN AND METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, 181 diabetic patients in Russia and Israel received once-daily oral doses of 600 mg (n = 45) (ALA600), 1,200 mg (n = 47) (ALA1200), and 1,800 mg (ALA1800) of ALA (n = 46) or placebo (n = 43) for 5 weeks after a 1-week placebo run-in period. The primary outcome measure was the change from baseline of the Total Symptom Score (TSS), including stabbing pain, burning pain, paresthesia, and asleep numbness of the feet. Secondary end points included individual symptoms of TSS, Neuropathy Symptoms and Change (NSC) score, Neuropathy Impairment Score (NIS), and patients' global assessment of efficacy. RESULTS: Mean TSS did not differ significantly at baseline among the treatment groups and on average decreased by 4.9 points (51%) in ALA600, 4.5 (48%) in ALA1200, and 4.7 (52%) in ALA1800 compared with 2.9 points (32%) in the placebo group (all P < 0.05 vs. placebo). The corresponding response rates (>/=50% reduction in TSS) were 62, 50, 56, and 26%, respectively. Significant improvements favoring all three ALA groups were also noted for stabbing and burning pain, the NSC score, and the patients' global assessment of efficacy. The NIS was numerically reduced. Safety analysis showed a dose-dependent increase in nausea, vomiting, and vertigo. CONCLUSIONS: Oral treatment with ALA for 5 weeks improved neuropathic symptoms and deficits in patients with DSP. An oral dose of 600 mg once daily appears to provide the optimum risk-to-benefit ratio.

Administration, Oral↗

Clinical efficacy of fidarestat, a novel aldose reductase inhibitor, for diabetic peripheral neuropathy: a 52-week multicenter placebo-controlled double-blind parallel group study.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of fidarestat, a novel aldose reductase (AR) inhibitor, in a double-blind placebo controlled study in patients with type 1 and type 2 diabetes and associated peripheral neuropathy. RESEARCH DESIGN AND METHODS: A total of 279 patients with diabetic neuropathy were treated with placebo or fidarestat at a daily dose of 1 mg for 52 weeks. The efficacy evaluation was based on change in electrophysiological measurements of median and tibial motor nerve conduction velocity, F-wave minimum latency, F-wave conduction velocity (FCV), and median sensory nerve conduction velocity (forearm and distal), as well as an assessment of subjective symptoms. RESULTS: Over the course of the study, five of the eight electrophysiological measures assessed showed significant improvement from baseline in the fidarestat-treated group, whereas no measure showed significant deterioration. In contrast, in the placebo group, no electrophysiological measure was improved, and one measure significantly deteriorated (i.e., median nerve FCV). At the study conclusion, the fidarestat-treated group was significantly improved compared with the placebo group in two electrophysiological measures (i.e., median nerve FCV and minimal latency). Subjective symptoms (including numbness, spontaneous pain, sensation of rigidity, paresthesia in the sole upon walking, heaviness in the foot, and hypesthesia) benefited from fidarestat treatment, and all were significantly improved in the treated versus placebo group at the study conclusion. At the dose used, fidarestat was well tolerated, with an adverse event profile that did not significantly differ from that seen in the placebo group. CONCLUSIONS: The effects of fidarestat-treatment on nerve conduction and the subjective symptoms of diabetic neuropathy provide evidence that this treatment alters the progression of diabetic neuropathy.

Aldehyde Reductase↗

Pronator syndrome and other nerve compressions that mimic carpal tunnel syndrome.

The purpose of this clinical commentary is to provide a comprehensive review of compressive neuropathies that may mimic carpal tunnel syndrome, provide the clinician with information to differentially diagnose these median nerve compression sites, and provide an evidence-based opinion regarding conservative intervention techniques for the various compression syndromes. While rare in comparison to carpal tunnel syndrome, pronator syndrome and anterior interosseous nerve syndrome are proximal median nerve compressions that may be suspected if a patient with carpal tunnel syndrome fails to respond to conservative or surgical intervention. Differential diagnosis is based largely on the symptoms, patterns of paresthesia, and specific patterns of muscle weakness. Due to the relative rarity of pronator syndrome and anterior interosseous nerve syndrome, few controlled studies exist to determine the most effective treatment techniques. Based on sound anatomical and biomechanical considerations, anecdotal experience, and available research, however, treatment strategies for pronator syndrome and anterior interosseous nerve syndrome compression neuropathies can be divided into 4 major categories: (1) rest/immobilization, (2) modalities, (3) nerve gliding, and (4) nonconservative treatment.

Carpal Tunnel Syndrome↗

Diagnosis of a rare source of upper extremity symptoms in a healthy woman after weight lifting.

STUDY DESIGN: Resident's case problem. BACKGROUND: The popularity of weight training has increased dramatically during the past 20 years. With the increase in popularity of weight training, the rate of injury has also increased dramatically. The types of injuries range from benign to life threatening. DIAGNOSIS: The patient was a 21-year-old woman originally referred for pelvic pain who presented with new complaints of right upper extremity swelling, discomfort, and cyanosis after recently beginning a comprehensive weight-lifting program. Additional signs, including paresthesias decreased pulses, and venous distension, warranted a timely referral by the physical therapist bavk to the referring physician. DISCUSSION: The primary injury in this case report was hypothesized to have been induced by the recent start of a weight-lifting program, with no other significant contributing risk factors. A comprehensive examination by the physical therapist revealed clinical signs of an upper extremity deep vein thrombosis, leading to a same-day referral back to the referring physician. Further research, resulting in a clinical decision rule for upper extremity deep vein thrombosis or estimates of diagnostic accuracy of clinical signs and symptoms, would improve the diagnostic process.

Adult↗

Neurophysiologic studies of patients with Crohn's disease on long-term treatment with metronidazole.

Fifty-three patients with Crohn's disease were chosen for this study. They were divided into three groups: the first group (19 patients) was treated with metronidazole and had been receiving the drug for at least 1 year; the second group (13 patients) had previously had the same type of long-term treatment but had been off the drug for at least 3 months before entering the study; the third group (21 patients) had never received treatment with metronidazole. The maximum daily dose of metronidazole used was 800 mg. All patients were examined with a broad set of neurophysiologic investigations devised to reveal signs of peripheral neuropathy. No significant difference was found between the three groups. The conclusion was that a daily dose of metronidazole not exceeding 800 mg is well tolerated by patients with Crohn's disease with regard to objective signs of neurotoxicity. A few patients from all three groups showed a raised perception threshold for changes of temperature in the feet (as compared with the department's normal standard). The results of the test were almost identical in the three groups and thus not connected with the metronidazole treatment. During the study, patients were asked about subjective neurologic symptoms such as tingling and numbness. A few patients from all three groups reported such paresthesias from time to time, but they were of a transient nature, not perpetual, and, in patients taking metronidazole, not aggravated despite continuing treatment with unchanged dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Neurotoxicological effects and the mode of action of pyrethroid insecticides.

Neuroexcitatory symptoms of acute poisoning of vertebrates by pyrethroids are related to the ability of these insecticides to modify electrical activity in various parts of the nervous system. Repetitive nerve activity, particularly in the sensory nervous system, membrane depolarization, and enhanced neurotransmitter release, eventually followed by block of excitation, result from a prolongation of the sodium current during membrane excitation. This effect is caused by a stereoselective and structure-related interaction with voltage-dependent sodium channels, the primary target site of the pyrethroids. Near-lethal doses of pyrethroids cause sparse axonal damage that is reversed in surviving animals. After prolonged exposure to lower doses of pyrethroids axonal damage is not observed. Occupational exposure to pyrethroids frequently leads to paresthesia and respiratory irritation, which are probably due to repetitive firing of sensory nerve endings. Massive exposure may lead to severe human poisoning symptoms, which are generally treated well by symptomatic and supportive measures.

Animals↗

Thallium poisoning from maliciously contaminated food.

Four young adults presented two days after one of them had received marzipan balls packaged in a box from an expensive candy manufacturer. Two ate one candy ball, while two others shared a third. The next day, variable gastrointestinal symptoms developed. On the third day, two patients developed painful paresthesiae of the hands and feet, an early but nonspecific clinical marker of thallium poisoning. A tentative diagnosis of thallium poisoning was made based on symptoms, and treatment was initiated. The remaining candies were radiographed. Metallic densities in the candies supported the diagnosis, and atomic absorption spectroscopy was used to quantitate thallium content. Each candy contained a potentially fatal dose. Five to seven days later, hypertension and tachycardia developed in the two patients who had ingested an entire candy. All patients developed alopecia but recovered without overt neurologic or other sequelae. While the diagnosis of thallium poisoning is often delayed until alopecia develops, an early diagnosis favors an effective treatment strategy.

Adult↗

Anterior transposition of the ulnar nerve.

Twenty-four patients with 26 ulnar neuropathies in the elbow region were treated by anterior transposition of the ulnar nerve. The dominant arm was involved in 14 of these patients. Improvement of paresthesia was found in 17 out of 21 (75 per cent) in this series of patients; 10 out of 18 (55 per cent) had improvement of sensation; 7 out of 14 (50 per cent) had less pain; 10 out of 14 (71 per cent) showed an increase in motor power, but only 2 out of 12 patients (16 per cent) with long-standing muscle atrophy showed any improvement in their condition. Electromyographic studies (EMG) were carried out before and after operation. The postoperative studies revealed increased motor conduction velocity within the elbow segment of the ulnar nerve in 15 patients. Slowing in ulnar nerve conduction velocity was found in 3 patients, and in 8 the EMG remained unchanged. Our EMG series indicated that patients with a conduction velocity of less than 40 m/s will certainly benefit more from anterior transposition of the ulnar nerve than will patients whose measurements are within the normal range.

Adult↗

Hemorrhage of cavernous malformations during pregnancy and in the peripartum period: causal or coincidence? Case report and review of the literature.

There is growing evidence to suggest that pregnancy may increase the risk of hemorrhage from cavernous malformations (CMs). In the present case, a 21-year-old primigravida was admitted to the authors' neurosurgical service after a cesarean section. Three weeks before admission she had experienced rapidly progressive bilateral lower-extremity paresthesias. Spinal magnetic resonance (MR) imaging revealed the presence of an intramedullary thoracic lesion. On T2-weighted MR images, heterogeneous signal intensity with a rim of decreased intensity was demonstrated in the spine. The mass was successfully resected, and 1 year later the patient's symptoms had resolved completely. This is the fourth reported case of a spinal intramedullary CM that became symptomatic during pregnancy. The pathogenesis and management of this entity are reviewed.

Adult↗

Combined epidural and peripheral nerve stimulation for relief of pain. Description of technique and preliminary results.

A technique is described that combines percutaneous epidural with peripheral nerve stimulation to provide limited paresthesia to a lower extremity. The peripheral electrode is placed percutaneously and positioned along the course of the anterior division fo the spinal nerve anterolateral to the vertebral bodies. This is accomplished by a modified epidural tap. Combined stimulation was carried out in 23 patients with intractable leg pain. Sixteen patients proceeded to chronic autostimulation; follow-up time extended to 18 months. The procedure proved simple; there were no perioperative and only few minor late complications. Results were similar to those from conventional epidural stimulator implantation. It is concluded that combined epidural-peripheral nerve stimulation constitutes a valid therapeutic alternative for patients with unilateral lower extremity pain.

Adult↗

Endoscopic treatment of carpal tunnel syndrome: a critical review.

OBJECT: The goal of this paper is to present a critical review of the endoscopic procedures currently in use for the treatment of carpal tunnel syndrome. Endoscopic techniques and outcomes are discussed. METHODS: An extensive review of published articles on the subject of endoscopic carpal tunnel release surgery is presented, encompassing six endoscopic techniques used to treat carpal tunnel syndrome. Since the first report in 1987, 7091 patients have undergone 8068 operations. The overall success rate has been 96.52%, with a complication rate of 2.67% and a failure rate of 2.61%. The mean time to return to work in patients not receiving Workers' Compensation was 17.8 days, ranging between 10.8 and 22.3 days. The most common complications were transient paresthesias of the ulnar and median nerves. Other complications included superficial palmar arch injuries, reflex sympathetic dystrophy, flexor tendon lacerations, and incomplete transverse carpal ligament division. In many studies in which open and endoscopic techniques were compared, it was reported that patients in the the latter group experienced significantly less pain and returned to work and activities of daily living earlier. CONCLUSIONS: Success and complication rates of endoscopic carpal tunnel release surgery are similar to those for standard open procedures.

Absenteeism↗

Cavernous sinus syndrome during balloon test occlusion of the cervical internal carotid artery. Report of two cases.

The authors report the occurrence of ipsilateral transient cavernous sinus syndrome during balloon test occlusion (BTO) of the cervical internal carotid artery (ICA) and discuss the involved pathomechanisms. The authors reviewed their series of 129 BTOs of the ICA performed between 1989 and 1996. Two patients developed facial paresthesias and transient palsies of the third through sixth cranial nerves during test occlusion of the cervical ICA. The tests were performed prior to planned permanent carotid artery occlusion for the treatment of a neck sarcoma in one patient and a giant cavernous carotid artery aneurysm in the other. The patients' symptoms resolved with deflation of the balloon. When the balloon was subsequently inflated above the inferior cavernous sinus artery (ICSA), one of the patients complained of mild facial discomfort. There was no contralateral weakness or mental status change during test occlusion in either patient. Angiography demonstrated good filling of the ipsilateral intracranial circulation via collateral vessels of the circle of Willis. In these two cases, the cranial nerves in the cavernous sinus were likely supplied by the ICA via the meningohypophyseal trunk and the ICSA. In each case, there was excellent blood supply to the ipsilateral cerebral hemisphere; however, there was probably inadequate retrograde filling of the cranial nerve collateral vessels located where the meningohypophyseal trunk and ICSA originated. These cases emphasize the importance of a patent external carotid artery-ICA connection for successful cervical carotid artery occlusion. Neurological examination during BTO was critical to interpret the clinical manifestations caused by the hemodynamic changes.

Abducens Nerve↗

[Subacute combined degeneration of the spinal cord caused by vitamin B12 deficiency. Report of 11 cases].

BACKGROUND: Subacute combined degeneration is a clinical manifestation of vitamin B12 deficiency, that we observe with unusual frequency. AIM: To report a series of eleven patients with subacute combined degeneration. PATIENTS AND METHODS: Retrospective analysis of 11 patients hospitalized in a public hospital in Santiago, between March 2001 and February 2003. All had a myelopathy of more than three weeks of evolution with serum vitamin B12 levels of less than 200 pg/ml. RESULTS: A risk factor was identified in 10 cases and the most common was an age over 60 years old. The main presenting symptom was the presence of paresthesias. On admission, sphincter dysfunction, posterior column and pyramidal syndromes coexisted in nine patients. A level of sensitive deficit was detected in six. Ten patients had macrocytosis and eight were anemic. Serum vitamin B12 was measured in ten and in nine, it was below 200 pg/ml. The mean lapse between onset of symptoms and treatment was eight months. All received intramuscular vitamin B12 in doses on 1,000 to 10,000 IU/day. Sphincter dysfunction and propioception were the first symptoms to improve. CONCLUSIONS: Subacute combined degeneration must be suspected in patients older than 60 years with a subacute myelopathic syndrome and low serum vitamin B12 levels.

Acute Disease↗

Vibration syndrome among Finnish forest workers, a follow-up from 1972 to 1983.

A longitudinal survey on the prevalence of vibration syndrome among professional forest workers was conducted from 1972 (118 workers) to 1983 (206 workers). The prevalence of vibration-induced white finger (VWF) was 40% among the workers in 1972; it gradually declined to 5% in 1983. Three new workers developed VWF symptoms during the follow-up period. They had only used saws equipped with antivibration handles. The prevalence of VWF has decreased mainly due to the reduction of chain-saw vibration. The prevalence of paresthesias of the hands and arms declined from 78% in 1972 to 37% in 1976, and then increased to 51% in 1983. The recent increase was thought to be due to static muscle load and the ageing of the workers. No correlation was found between the severity of VWF and peripheral nerve symptoms. No significant changes in muscle fatigue occurred during the follow-up period; it was present in about 10-15% of the workers. The forest workers subjectively assessed musculoskeletal load and strain as being more harmful than the symptoms of vibration syndrome. The preventive measures aimed at reducing chain-saw vibration, implemented since 1970, have been beneficial and explain the decreased prevalence of VWF.

Cross-Sectional Studies↗

Neurologic manifestations of essential thrombocythemia.

Essential thrombocythemia is a clonal myeloproliferative disorder, characterized predominantly by a markedly elevated platelet count without known cause. We report a case that was recognized during investigation of a transient ischemic attack, and review the neurologic findings in 33 patients with unequivocal essential thrombocythemia under prospective study by the Polycythemia Vera Study Group. Twenty-one patients had neurologic manifestations at some point during their course, including headache (13 patients), paresthesiae (10), posterior cerebral circulatory ischemia (9), anterior cerebral circulatory ischemia (6), visual disturbances (6) and epileptic seizures (2). All patients with neurologic symptoms responded satisfactorily to treatment, although continuous or repeated treatment was often required. Therapeutic recommendations include plateletpheresis for major thrombo-hemorrhagic phenomena, or megakaryocyte suppression with radioactive phosphorus, alkylating agents (such as melphalan), or hydroxyurea; minor symptoms may respond to platelet antiaggregating agents.

Adult↗

[Gliomatosis cerebri].

A 64 years old woman presented with weakness, vertigo, paresthesia, dementia, which progressed to coma in a three-month-long period. The autopsy revealed pulmonary thrombosis and infarction, gastric erosions, peptic ulcer in the duodenum, leiomyoma in the esophagus, fibrosis of the pancreas and mild atherosclerosis. On macroscopic examination, the 1440 g brain did not show any bleeding, infarction or tumor. The histologic examination revealed gliomatosis cerebri of the white matter of the cerebral hemispheres.

Autopsy↗

Lateralization of the inferior alveolar nerve with simultaneous implant placement: surgical techniques.

In the event of moderate to severe mandibular bone resorption posterior to the mental foramen, repositioning of the inferior alveolar nerve provides a greater amount of available bone for implant placement and reduces the risk of nerve injury. While neural paresthesia may initially occur, this altered sensation generally resolves spontaneously. Alveolar nerve repositioning may be possible in cases in which other procedures cannot be performed due to the extent of atrophy of the posterior mandibular alveolar crest. This article presents the surgical technique to achieve this objective.

Dental Implantation, Endosseous↗

[A study of peripheral neural conduction, motor and sensory, in diabetic patients treated with hyperbaric oxygenation].

INTRODUCTION: There are some occlusive disorders in the vasa nervorum and metabolic changes disminishing oxygen liberation by erytrocites at the capillary blood vessels, and these disturbances lead to endoneural microhypoxia. Hyperbaric oxygen reverts hypoxia in the diabetic neuropathy. OBJECTIVE: We studied motor and sensitive peripheric neuroconduction in nine diabetic patients, with distal symmetrical polyneuropathy, during normoglycemia. Four of them were insulin dependent and five were non insulin dependent. PATIENTS AND METHODS: The electrophysiological studies were done before treatment with hyperbaric oxygen, in a week, three and six months later. The abnormal electrophysiological parameters detected in diabetics were terminal latencies (enlarged), velocities of conduction (slowed) and distal amplitudes of compound action potentials (reduced). RESULTS: Neither distal latencies nor distal amplitudes and conduction velocities in peroneal nerve showed significative changes in the statistical analysis. We observed slower conduction velocities in the motor fibers of the median nerve in the examination performed six months after treatment. There was an increase of distal latency and retardation of the velocity of conduction six months later after treatment in the sensitive fibers of median nerve, whereas the amplitudes of sensitive action potentials decreased progressively. These changes suggest large diameter peripheral fibers didn't receive benefit with hyperbaric oxygen treatment. CONCLUSIONS: In all patients disappeared all symptoms of dysesthesias, paresthesias, distal pains and cramps in the legs and arms, suggesting functional changes in small unmyelinated fibers which we can't test with conventional techniques to prove it.

Adult↗