Faculty Bibliography

INTRODUCTION: Saphenous mononeuropathy has been a well recognized consequence of lower extremity surgery. However, this complication has not been previously described with popliteal vein aneurysm repair. CASE PRESENTATION: We report the case of a 42-year-old woman with a saphenous mononeuropathy after popliteal vein aneurysm repair. Her saphenous neuropathy was confirmed by nerve conduction studies. Her case gives us an opportunity to review saphenous mononeuropathy and its many different etiologies. We also review the role of electrodiagnostic studies in the diagnosis of saphenous mononeuropathy. CONCLUSIONS: Though this particular iatrogenic injury has not previously been described, both neurologists and surgeons should be aware of this complication following popliteal vein aneurysm resection with saphenous vein interposition.

A patient with primary (AL) systemic amyloidosis developed mononeuropathy multiplex complicated by diaphragmatic failure. High dose melphalan and autologous stem cell transplantation did not ameliorate neuropathy or diaphragm dysfunction. Nocturnal non-invasive ventilation lowered arterial carbon dioxide levels and improved daytime dyspnea. This is the first case associating AL amyloid-induced neuropathy with diaphragm dysfunction.

BACKGROUND: AL amyloidosis is a fatal disease resulting from tissue deposition of amyloid fibrils derived from monoclonal immunoglobulin light chains. Treatment with oral chemotherapy is minimally effective. OBJECTIVE: To test survival and organ response in a large sample of patients treated with high-dose intravenous melphalan (100 to 200 mg/m2) and autologous blood stem-cell transplantation. DESIGN: 8-year longitudinal analysis of clinical effectiveness. SETTING: University-affiliated specialty referral clinic. PATIENTS: 701 consecutive new patients with AL amyloidosis. INTERVENTION: High-dose chemotherapy and autologous stem-cell transplantation for patients who met eligibility requirements based on organ involvement and clinical status. MEASUREMENTS: Survival analysis of all patients evaluated and a detailed analysis of treatment outcome in the subgroup that received high-dose melphalan and stem-cell transplantation. RESULTS: Among 701 patients with AL amyloidosis, 394 (56%) were eligible for high-dose melphalan and stem-cell transplantation; 82 did not proceed with treatment because of patient choice or disease progression. Median survival of the 312 patients who initiated treatment was 4.6 years. A complete hematologic response, defined as no evidence of an underlying plasma cell dyscrasia 1 year after treatment, was achieved in 40% of patients and was associated with prolonged survival. Statistically significant improvements occurred in end-organ disease and were greater in patients with a complete hematologic response. Mortality rate within 100 days of treatment with high-dose melphalan and stem-cell transplantation was 13%; patients with cardiomyopathy had the highest mortality rates. CONCLUSIONS: Treatment of selected patients with AL amyloidosis by using high-dose melphalan and stem-cell transplantation resulted in hematologic remission, improved 5-year survival, and reversal of amyloid-related disease in a substantial proportion.

Thalidomide is an effective therapy for multiple myeloma, although its mechanisms of action remain unclear. Light chain-associated (AL) amyloidosis is a plasma cell disorder related to multiple myeloma, but in AL amyloidosis, fibrillar tissue deposits of clonal immunoglobulin light chains produce organ dysfunction. To test the toxicity and efficacy of thalidomide in AL amyloidosis we initiated a phase I/II trial for patients with AL amyloidosis, most of whom had failed prior therapy with high-dose melphalan and autologous stem cell transplantation. This trial was designed as an individualized 6-month dose-escalation study with reevaluation of bone marrow plasmacytosis and serum and urine monoclonal proteins after 3 and 6 months. Sixteen patients were enrolled in the study with a median age of 62 years (range, 37-70 years). Fourteen patients had renal involvement, 4 had cardiac involvement, 4 had liver involvement, and 2 had predominant soft tissue or lymph node involvement. The median maximum tolerated dose was 300 mg, with fatigue and other central nervous system side effects being the major dose-limiting toxicities. Side effects not frequently reported for other patient populations included exacerbation of peripheral and pulmonary edema and worsening azotemia. In all, 50% of patients experienced grade 3/4 toxicity, and 25% had to discontinue the study drug. No complete hematologic responses were seen, but 25% of patients had a significant reduction in Bence-Jones proteinuria. Thus, while thalidomide has activity in AL amyloidosis, it also has significant toxicity in this patient population.