Benn E. Smith

The Rochester Diabetic Neuropathy Study: Design, criteria for types of neuropathy, selection bias, and reproducibility of neuropathic tests

A cross-sectional survey and subsequent longitudinal study among diabetic residents of Rochester, MN- The Rochester Diabetic Neuropathy Study (RDNS)-is population-based and uses quantitative, validated, and unique end points to detect, classify, and stage neuropathy. Nondiabetic persons, drawn from the same population, serve as controls. For patients 10 to 70 years old, the RDNS cohort is representative of diabetics living in Rochester, MN. We assessed reproducibility of tests used to characterize and quantitate severity of neuropathy in 20 diabetic subjects without neuropathy and with varying severities of neuropathy. Using intraclass correlation coefficient (r1) as a measure of test reproducibility, we found high r1 (usually 0.9 or better) with small confidence intervals for the Neurologic Disability Score (NDS); weakness subset of NDS (W-NDS); vibratory and cooling detection thresholds (using computer-assisted sensory examination [CASE] IV); compound muscle action potentials; sensory nerve action potentials; and motor nerve conduction velocities. There was good agreement among three trained observors for NDS and the W-NDS.

Plasma exchange in polyneuropathy associated with monoclonal gammopathy of undetermined significance

BACKGROUND Polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUS) has been treated with plasma exchange, intravenous immune globulin, and chemotherapy, but the effectiveness of these treatments remains uncertain. METHODS We randomly assigned 39 patients with stable or worsening neuropathy and MGUS of the IgG, IgA, or IgM type to receive either plasma exchange twice weekly for three weeks or sham plasma exchange, in a double-blind trial. The patients who initially underwent sham plasma exchange subsequently underwent plasma exchange in an open trial. RESULTS In the double-blind trial, the average neuropathy disability score improved by 2 points from base line (from 62.5 to 60.5) in the sham-exchange group and by 12 points (from 58.3 to 46.3) in the plasma-exchange group (P = 0.06). A similar difference was observed in the weakness score, a component of the neuropathy disability score (improvement, 1 and 10 points, respectively; P = 0.07). After treatment the summed compound muscle action potentials of motor nerves were 1.2 mV lower (worse) than at base line in the sham-exchange group and 0.4 mV higher (better) in the plasma-exchange group (P = 0.07). The greater degree of improvement with plasma exchange was equal in magnitude to or greater than the difference between not being able to walk on the heels or toes and being able to perform these activities. Changes in the vibratory detection threshold, summed motor-nerve conduction velocity, and sensory-nerve action potentials did not differ significantly between the treatment groups. In the open trial, in which patients who initially underwent sham exchange were treated with plasma exchange, the neuropathy disability score (P = 0.04), weakness score (P = 0.07), and summed compound muscle action potentials (P = 0.07) improved more with plasma exchange than they had with sham exchange. In both the double-blind and the open trial, those with IgG or IgA gammopathy had a better response to plasma exchange than those with IgM gammopathy. CONCLUSIONS Plasma exchange appears to be efficacious in neuropathy associated with MGUS, especially of the IgG or IgA type.

Phase III randomized trial of gabapentin in patients with amyotrophic lateral sclerosis

Background: Preclinical and clinical studies of gabapentin in patients with ALS led the authors to undertake a phase III randomized clinical trial. Methods: Patients were randomly assigned, in a double-blinded fashion, to receive oral gabapentin 3,600 mg or placebo daily for 9 months. The primary outcome measure was the average rate of decline in isometric arm muscle strength for those with two or more evaluations. Results: Two hundred four patients enrolled, 196 had two or more evaluations, and 128 patients completed the study. The mean rate of decline of the arm muscle strength was not significantly different between the groups. Moreover, there was no beneficial effect upon the rate of decline of other secondary measures (vital capacity, survival, ALS functional rating scale, timed walking) nor was there any symptomatic benefit. In fact, analysis of the combined data from the phase II and III trials revealed a significantly more rapid decline of forced vital capacity in patients treated with gabapentin. Conclusion: These data provide no evidence of a beneficial effect of gabapentin on disease progression or symptoms in patients with ALS.

Symptoms of 100 patients with electromyographically verified carpal tunnel syndrome

To determine the symptoms of carpal tunnel syndrome (CTS), screening evaluations were performed in 244 consecutive patients with sensory symptoms in the hand and unequivocal slowing of median nerve conduction at the wrist. This yielded 100 patients thought to have no explanation other than CTS for their upper limb complaints. These patients completed a hand symptom diagram (HSD) and questionnaire (HSQ) about their symptoms. CTS symptoms were most commonly reported in median and ulnar digits, followed by median digits only and a glove distribution. Unusual sensory patterns were reported by some patients. Based on the HSQ, paresthesias or pain proximal to the wrist occurred in 36.5% of hands. The usefulness of the HSD and HSQ for diagnosis was determined by asking three physicians, blinded to the diagnosis, to rate the likelihood of CTS in the patients with CTS and in 50 patients with other causes of upper extremity paresthesia. The sensitivities of the instruments ranged from 54.1% to 85.5%. Combining the HSD and HSQ ratings increased the range of sensitivities to 79.3% to 93.7%.

The frequency of carpal tunnel syndrome in computer users at a medical facility.

A survey was done of employees who were identified as frequent computer users. Although 29.6% of the employees reported hand paresthesias, only 27 employees (10.5%) met clinical criteria for carpal tunnel syndrome, and in 9 (3.5%) the syndrome was confirmed by nerve conduction studies. Affected and unaffected employees had similar occupations, years using a computer, and time using the computer during the day. The frequency of carpal tunnel syndrome in computer users is similar to that in the general population.

A miniature confocal Raman probe for endoscopic use

Raman spectroscopy is a powerful tool for studying biochemical changes in the human body. We describe a miniature, confocal fibre optic probe intended to fit within the instrument channel of a standard medical endoscope. This probe has been optimized for the study of the carcinogenesis process of oesophageal malignancy. The optical design and fabrication of this probe is described including the anisotropic wet etching technique used to make silicon motherboards and jigs. Example spectra of PTFE reference samples are shown. Spectra with acquisition times as low as 2 s from resected oesophageal tissue are presented showing identifiable biochemical changes from various pathologies.

Primary lateral sclerosis A neuropsychological study

Nine patients with clinically diagnosed, radiologically supported primary lateral sclerosis underwent cognitive testing. None was demented, but eight had mild cognitive impairment. Performances were most consistently impaired on neuropsychological tests sensitive to frontal lobe functions, followed by tests sensitive to memory. Cognitive testing may be useful in helping to establish a cortical localization in patients with the syndrome of progressive spasticity. There are potential nosologic relations between primary lateral sclerosis and other degenerative frontal lobe syndromes, such as frontal lobe dementia and progressive spasticity with dementia.

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, Waldenströms macroglobulinemia, osteosclerotic myeloma, and lymphoma are found. Demyelinating neuropathies associated with MGUS of all classes, but particularly IgM, Waldenströms 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.

Peripheral neuropathy in the eosinophilia‐myalgia syndrome associated with l‐tryptophan ingestion

Eosinophilia, brawny induration, and tenderness of the skin and deeper tissues, and eosinophilic and lymphocytic infiltration of skin, deep fascia, and muscle characterize the acute eosinophilia-myalgia syndrome associated with ingestion of l-tryptophan. Many patients have a florid inflammatory myopathy. We evaluated 10 patients with this syndrome in whom peripheral neuropathy was a prominent or the only presenting feature. Two of these patients with severe neuromuscular disease required mechanical ventilation, and 1 died. Clinical severity appeared to be positively associated with the total dose of l-tryptophan ingested. Although the inflammation is generally thought to be more severe in skin, fascia, and muscle, inflammation, especially in the epineurium of sural nerve, was sometimes striking and often accompanied by vasculopathy and angioneogenesis. These cases draw attention to a new preventable syndrome with peripheral nerve involvement, emphasize the value of tissue biopsy for its diagnosis, and raise issues related to pathogenesis.

Impact of a computerized physician order-entry system.

BACKGROUND The Institute of Medicine has urged the adoption of electronic prescribing systems in all health-care organizations by 2010. Accordingly, computerized physician order entry (CPOE) warrants detailed evaluation. Mixed results have been reported about the benefit of this system. No review of its application in surgical patients has been reported to date. We present the implementation of CPOE in the management of surgical patients within an academic multispecialty practice. STUDY DESIGN Retrospective and prospective analyses of patient-safety measures were done pre- and post-CPOE institution, respectively. Other metrics evaluated included medication errors, order-implementation times, efficiencies, personnel requirements, and physician time. Sampling of time span for the order placement process was assessed with direct hidden observation of the provider. RESULTS A total of 15 (0.22%) medication errors were discovered in 6,815 surgical procedures performed during the 6 months before CPOE use. After implementation, 10 medication errors were found (5,963 surgical procedures [0.16%]) in the initial 6 months and 13 (0.21%) in the second 6 months (6,106 surgical procedures) (p = NS). Mean total time from placement of order to nurse receipt before implementation was 41.2 minutes per order (2.05 minutes finding chart, 0.72 minutes writing order, 38.4 minutes for unit secretary transcription) compared with 27 seconds per order using CPOE (p < 0.01). Four additional informational technology specialists were temporarily required for assistance in implementing CPOE. After CPOE adoption, 11 of 56 (19.6%) ancillary personnel positions were eliminated related to order-entry efficiencies. CONCLUSIONS Present CPOE technology can allow major efficiency gains, but refinements will be required for improvements in patient safety.