Pregabalin relieves symptoms of painful diabetic neuropathy: a randomized controlled trial.

OBJECTIVE: Pregabalin, an alpha2-delta ligand with analgesic, anxiolytic, and anticonvulsant activity, has been evaluated for treatment of neuropathic pain. The authors assessed the efficacy and tolerability of pregabalin (75, 300, 600 mg/day) vs placebo in patients with diabetic peripheral neuropathy (DPN). METHODS: Patients with a 1- to 5-year history of DPN and average weekly pain score of > or =4 on an 11-point numeric pain-rating scale were enrolled in a 5-week, double-blind, multicenter, placebo-controlled study. Patients (n = 338) were randomized to receive one of three doses of pregabalin or placebo TID. Pregabalin 600 mg/day was titrated over 6 days; lower doses were initiated on day 1. RESULTS: Patients in the 300- and 600-mg/day pregabalin groups showed improvements in endpoint mean pain score (primary efficacy measure) vs placebo (p = 0.0001). Improvements were also seen in weekly pain score, sleep interference score, patient global impression of change, clinical global impression of change, SF-McGill Pain Questionnaire, and multiple domains of the SF-36 Health Survey. Improvements in pain and sleep were seen as early as week 1 and were sustained throughout the 5 weeks. Responders (patients with > or =50% reduction in pain compared to baseline) were 46% (300 mg/day), 48% (600 mg/day), and 18% (placebo). Pregabalin was well tolerated with a low discontinuation rate. The most common adverse events were dizziness and somnolence. CONCLUSIONS: In patients with diabetic peripheral neuropathy, pregabalin demonstrated early and sustained improvement in pain and a beneficial effect on sleep, which were confirmed by positive patient global impression. Pregabalin was well tolerated at all doses.

Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of pregabalin in the treatment of postherpetic neuralgia (PHN). METHODS: The authors conducted a multicenter, parallel-group, double-blind, placebo-controlled, 8-week, randomized clinical trial in PHN, defined as pain for 3 or more months following herpes zoster rash healing. Patients (n = 173) were randomized to treatment with pregabalin or placebo. Patients randomized to pregabalin received either 600 mg/day (creatinine clearance > 60 mL/min) or 300 mg/day (creatinine clearance 30 to 60 mL/min). The primary efficacy measure was the mean of the last seven daily pain ratings. Secondary endpoints included additional pain ratings, sleep interference, quality of life, mood, and patient and clinician ratings of global improvement. RESULTS: Pregabalin-treated patients had greater decreases in pain than patients treated with placebo (endpoint mean scores 3.60 vs 5.29, p = 0.0001). Pain was significantly reduced in the pregabalin-treated patients after the first full day of treatment and throughout the study, and significant improvement on the McGill Pain Questionnaire total, sensory, and affective pain scores was also found. The proportions of patients with >or=30% and >or=50% decreases in mean pain scores were greater in the pregabalin than in the placebo group (63% vs 25% and 50% vs 20%, p = 0.001). Sleep also improved in patients treated with pregabalin compared to placebo (p = 0.0001). Both patients and clinicians were more likely to report global improvement with pregabalin than placebo (p = 0.001). Given the maximal dosage studied, pregabalin had acceptable tolerability compared to placebo despite a greater incidence of side effects, which were generally mild to moderate in intensity. CONCLUSIONS: Treatment of PHN with pregabalin is safe, efficacious in relieving pain and sleep interference, and associated with greater global improvement than treatment with placebo.

Frequency and severity of asymptomatic coronary disease in patients with different causes of stroke.

BACKGROUND AND PURPOSE: We sought (1) to compare the frequency and severity of asymptomatic coronary artery disease (CAD) in patients with different causes of brain ischemia and (2) to determine profiles of patients with brain ischemia who are at highest risk of asymptomatic CAD. METHODS: Sixty-nine patients with transient ischemic attack or stroke and without overt CAD underwent a cardiac stress test and a diagnostic evaluation to determine the cause of brain ischemia. The frequency of abnormal cardiac stress tests was compared in patients with large-artery cerebrovascular disease versus other causes of brain ischemia (90% of whom had penetrating artery disease or cryptogenic stroke). Additionally, the frequencies of vascular risk factors, resting electrocardiographic abnormalities, and cause of stroke (large-artery disease versus other causes) were compared in patients with abnormal stress tests versus patients with normal stress tests. RESULTS: The frequency of abnormal stress tests was 50% (15 of 30) in patients with large-artery cerebrovascular disease versus 23% (9 of 39) in patients with other causes of brain ischemia (P = .04). Moreover, 60% of abnormal stress tests (9 of 15) in patients with large-artery cerebrovascular disease suggested severe underlying CAD that was confirmed in 7 of 7 patients who underwent coronary angiography. On the other hand, less than 25% of abnormal stress tests (2 of 9) in patients with other causes of brain ischemia suggested severe underlying CAD. Features that were more common in patients with abnormal stress tests were smoking (P = .006), large-artery cerebrovascular disease (P = .02), veteran status (P = .02), and left ventricular hypertrophy (P = .07). CONCLUSIONS: Patients with penetrating artery disease or cryptogenic stroke have a significantly lower frequency of asymptomatic CAD than patients with large-artery cerebrovascular disease. Large-artery cerebrovascular disease, smoking, veteran status, and possibly left ventricular hypertrophy may be useful features for identifying patients with transient ischemic attack or stroke who are at highest risk of harboring asymptomatic CAD.

Motor neuron disease and angiotropic lymphoma.

BACKGROUND: The number of patients with motor neuron disease (MND) and a concomitant hematologic disorder appears to be overrepresented. Angiotropic large cell lymphoma, a rare and aggressive type of lymphoma, has been associated with MND only once (to our knowledge) prior to this report. There are more than 35 cases of MND associated with lymphoma or monoclonal gammopathy reported in the literature. The nature of this association remains disputable. OBJECTIVE: To investigate whether the association between some MNDs and certain hematologic disorders is coincidental or pathogenetically related. CASE PRESENTATION: We describe the clinical and neuropathologic findings in a case involving a 70-year-old man with a rapidly progressive lower MND who at autopsy also exhibited angiotropic large cell lymphoma without ischemic lesions in the nervous system. CONCLUSIONS: This case supports the notion that the association between some MNDs and certain hematologic disorders is not coincidental but pathogenetically related. A 2-hit hypothesis is proposed in which an initial abnormal glycosylation in motoneurons would require the production of an appropriate autoantibody for disease expression.

Ischemic stroke and TIA: clinical clues to common causes.

Establishing the cause of a transient ischemic attack (TIA) or minor stroke enables you to institute effective therapy to prevent major stroke. Clinical and radiologic features that help to clarify the cause of cerebrovascular ischemia include characteristics of prior TIAs, temporal progression and nature of the neurologic deficit, and appearance of infarction on CT and MRI of the brain. Carotid and transcranial Doppler ultrasound, magnetic resonance angiography, arterial angiography, and echocardiography are used to confirm the cause of cerebral ischemia. We provide three case studies to illustrate our approach to stroke diagnosis.

Hereditary neuropathy with liability to pressure palsies masquerading as slowly progressive polyneuropathy.

Hereditary neuropathy with liability to pressure palsies (HNLPP) is a peripheral nerve disorder in which recurrent pressure palsies are associated with pathological swelling ('tomacula') of myelinated nerve internodes. We report a patient with a slowly progressive polyneuropathy associated with substantial slowing of conduction velocities initially suggestive of an acquired or hereditary demyelinating polyneuropathy. However, repeat electrodiagnostic studies demonstrated that conduction slowing and partial conduction block were localized primarily to common sites of nerve compression and entrapment. Sural nerve biopsy revealed multiple tomacula consistent with the diagnosis of HNLPP.

Left atrial spontaneous echo contrast is highly associated with previous stroke in patients with atrial fibrillation or mitral stenosis.

BACKGROUND AND PURPOSE: Spontaneous echo contrast is a dynamic smokelike signal that is detected by transesophageal echocardiography in patients with stasis of blood in the left atrium. We designed this study to determine if spontaneous echo contrast is associated with an increased risk of previous stroke or peripheral embolism. METHODS: Forty-two patients with spontaneous echo contrast were identified (34 had atrial fibrillation or mitral stenosis; 8 had neither). Control subjects comprised 40 patients randomly selected from patients with atrial fibrillation or mitral stenosis who did not have spontaneous echo contrast at transesophageal echocardiography. The frequency of vascular risk factors, echocardiographic features, and stroke or peripheral embolism within 1 year of echocardiography were compared in the two groups. RESULTS: The frequency of traditional risk factors for stroke were the same in both groups, yet 9 of 42 patients with spontaneous contrast had stroke or peripheral embolism compared with only 1 of 40 control subjects (P < .02; relative risk, 10.6; 95% confidence interval, 1.3 to 88.4). In patients with nonvalvular atrial fibrillation, 6 of 12 patients with spontaneous contrast had a stroke or peripheral embolism compared with 1 of 28 patients without spontaneous contrast (P < .001; relative risk, 27.0; 95% confidence interval, 2.7 to 267.8). CONCLUSIONS: Spontaneous echo contrast is highly associated with previous stroke or peripheral embolism in patients with atrial fibrillation or mitral stenosis. Transesophageal echocardiography may enable stratification of cardioembolic risk in patients with nonvalvular atrial fibrillation.

Prevention and treatment of overuse tendon injuries.

Overuse injuries are common in recreational and competitive sports as well as in day-to-day activities. The musculotendinous unit comprises the tissue most frequently involved: structural damage to the tendon occurs from repetitive strain and loading, from either endurance or skill activities that require technique and power. The potential for injury is enhanced by a great variety of predisposing intrinsic or extrinsic factors. Tendinous tissue will become fatigued as its basal reparative ability is overwhelmed by repetitive dysfunctional and microtraumatic processes. Tendinitis is the earliest recognisable manifestation of overuse injury: as damage progresses, partial tears and complete ruptures may ensue. The diagnosis of overuse injury rests with identification not only of the affected tendinous unit, but also of the underlying predisposing condition or conditions. Treatment can then proceed with elimination or correction, if possible, of these conditions, together with control of inflammation and programmes of modalities designed to restore the structural and functional integrity of the tendon. Knowledge of overuse problems has grown exponentially in the past 3 decades, as evidenced by the outpouring of scientific and medical literature. Sophisticated analytical techniques, supplementing a sound history and physical examination, have greatly facilitated the diagnosis of overuse problems and allowed the application of scientific therapeutic principles. As the number of participants in recreational activities continues to grow, the application of these techniques in ever more innovative ways holds the greatest promise for the prevention of overuse tendon injuries.

Proctitis and fatal septicemia caused by Plesiomonas shigelloides in a bisexual man.

A case of proctitis and fatal septicemia caused by Plesiomonas shigelloides in a 42-year-old bisexual male is reported. The medical history of the patient was significant for an aortic valve replacement 3 years before but was otherwise unremarkable. A serum specimen obtained at autopsy was negative for antibody to human immunodeficiency virus by Western blot (immunoblot) analysis. P. shigelloides isolated from blood was susceptible to all antibiotics tested, agglutinated in Shigella group D antiserum, possessed a greater than 100-megadalton plasmid, and was noninvasive in a HeLa cell invasion assay. The previous reports of Plesiomonas bacteremic infections are reviewed, and possible pathogenic mechanisms are discussed.

The chronically inflamed tendon.

The cause, diagnosis, and treatment of some of the chronic tendonitides are discussed in this article. Most tendon injuries are "overuse syndromes" and treatment involves the use of combined modalities and exercise. Preventive measures are emphasized.