Clinical studies in familial VCP myopathy associated with Paget disease of bone and frontotemporal dementia.

Inclusion body myopathy with Paget disease of the bone (PDB) and/or frontotemporal dementia (IBMPFD, OMIM 167320), is a progressive autosomal dominant disorder caused by mutations in the Valousin-containing protein (VCP, p97 or CDC48) gene. IBMPFD can be difficult to diagnose. We assembled data on a large set of families to illustrate the number and type of misdiagnoses that occurred. Clinical analysis of 49 affected individuals in nine families indicated that 42 (87%) of individuals had muscle disease. The majority were erroneously diagnosed with limb girdle muscular dystrophy (LGMD), facioscapular muscular dystrophy, peroneal muscular dystrophy, late adult onset distal myopathy, spinal muscular atrophy, scapuloperoneal muscular dystrophy, or amyotrophic lateral sclerosis (ALS) among others. Muscle biopsies showed rimmed vacuoles characteristic of an inclusion body myopathy in 7 of 18 patients (39%), however, inclusion body myopathy was correctly diagnosed among individuals in only families 5 and 15. Frontotemporal dementia (FTD) was diagnosed in 13 individuals (27%) at a mean age of 57 years (range 48.9-60.2 years); however, several individuals had been diagnosed with Alzheimer disease. Histopathological examination of brains of three affected individuals revealed a pattern of ubiquitin positive neuronal intranuclear inclusions and dystrophic neurites. These families expand the clinical phenotype in IBMPFD, a complex disorder caused by mutations in VCP. The presence of PDB in 28 (57%) individuals suggests that measuring serum alkaline phosphatase (ALP) activity may be a useful screen for IBMPFD in patients with myopathy.

Cost-effectiveness of multilevel hemilaminectomy for lumbar stenosis-associated radiculopathy.

BACKGROUND CONTEXT: Laminectomy for lumbar stenosis-associated radiculopathy is associated with improvement in pain, disability, and quality of life. However, given rising health-care costs, attention has been turned to question the cost-effectiveness of lumbar decompressive procedures. The cost-effectiveness of multilevel hemilaminectomy for radiculopathy remains unclear. PURPOSE: To assess the comprehensive medical and societal costs of multilevel hemilaminectomy at our institution and determine its cost-effectiveness in the treatment of degenerative lumbar stenosis. STUDY DESIGN: Prospective single cohort study. PATIENT SAMPLE: Fifty-four consecutive patients undergoing multilevel hemilaminectomy for lumbar stenosis-associated radiculopathy after at least 6 months of failed conservative therapy were included. OUTCOME MEASURES: Self-reported measures were assessed using an outcomes questionnaire that incorporated total back-related medical resource utilization, missed work, and improvement in leg pain (visual analog scale for leg pain [VAS-LP]), disability (Oswestry Disability Index [ODI]), quality of life (Short Form-12 [SF-12]), and health state values (quality-adjusted life years [QALYs], calculated from EuroQuol 5D [EQ-5D] with US valuation). METHODS: Over a 2-year period, total back-related medical resource utilization, missed work, and improvement in leg pain (VAS-LP), disability (ODI), quality of life (SF-12), and health state values (QALYs, calculated from EQ-5D with US valuation) were assessed. Two-year resource use was multiplied by unit costs based on Medicare national allowable payment amounts (direct cost), and patient and caregiver workday losses were multiplied by the self-reported gross-of-tax wage rate (indirect cost). Mean total 2-year cost per QALY gained after multilevel hemilaminectomy was assessed. RESULTS: Compared with preoperative health states reported after at least 6 months of medical management, a significant improvement in VAS-LP, ODI, and SF-12 (physical and mental components) was observed 2 years after multilevel hemilaminectomy, with a mean 2-year gain of 0.72 QALYs. Mean±standard deviation total 2-year cost of multilevel hemilaminectomy was $24,264±10,319 (surgery cost, $10,220±80.57; outpatient resource utilization cost, $3,592±3,243; and indirect cost, $10,452±9,364). Multilevel hemilaminectomy was associated with a mean 2-year cost per QALY gained of $33,700. CONCLUSIONS: Multilevel hemilaminectomy improved pain, disability, and quality of life in patients with lumbar stenosis-associated radiculopathy. Total cost per QALY gained for multilevel hemilaminectomy was $33,700 when evaluated 2 years after surgery with Medicare fees, suggesting that multilevel hemilaminectomy is a cost-effective treatment of lumbar radiculopathy.