Spinal manifestations of CLN1 disease start during the early postnatal period.

AIM: To understand the progression of CLN1 disease and develop effective therapies we need to characterize early sites of pathology. Therefore, we performed a comprehensive evaluation of the nature and timing of early CLN1 disease pathology in the spinal cord, which appears especially vulnerable, and how this may affect behaviour. METHODS: We measured the spinal volume and neuronal number, and quantified glial activation, lymphocyte infiltration and oligodendrocyte maturation, as well as cytokine profile analysis during the early stages of pathology in Ppt1-deficient (Ppt1-/- ) mouse spinal cords. We then performed quantitative gait analysis and open-field behaviour tests to investigate the behavioural correlates during this period. RESULTS: We detected significant microglial activation in Ppt1-/- spinal cords at 1 month. This was followed by astrocytosis, selective interneuron loss, altered spinal volumes and oligodendrocyte maturation at 2 months, before significant storage material accumulation and lymphocyte infiltration at 3 months. The same time course was apparent for inflammatory cytokine expression that was altered as early as one month. There was a transient early period at 2 months when Ppt1-/- mice had a significantly altered gait that resembles the presentation in children with CLN1 disease. This occurred before an anticipated decline in overall locomotor performance across all ages. CONCLUSION: These data reveal disease onset 2 months (25% of life-span) earlier than expected, while spinal maturation is still ongoing. Our multi-disciplinary data provide new insights into the spatio-temporal staging of CLN1 pathogenesis during ongoing postnatal maturation, and highlight the need to deliver therapies during the presymptomatic period.

Core features of frontotemporal dementia recapitulated in progranulin knockout mice.

Frontotemporal dementia (FTD) is typified by behavioral and cognitive changes manifested as altered social comportment and impaired memory performance. To investigate the neurodegenerative consequences of progranulin gene (GRN) mutations, which cause an inherited form of FTD, we used previously generated progranulin knockout mice (Grn-/-). Specifically, we characterized two cohorts of early and later middle-aged wild type and knockout mice using a battery of tests to assess neurological integrity and behavioral phenotypes analogous to FTD. The Grn-/- mice exhibited reduced social engagement and learning and memory deficits. Immunohistochemical approaches were used to demonstrate the presence of lesions characteristic of frontotemporal lobar degeneration (FTLD) with GRN mutation including ubiquitination, microgliosis, and reactive astrocytosis, the pathological substrate of FTD. Importantly, Grn-/- mice also have decreased overall survival compared to Grn+/+ mice. These data suggest that the Grn-/- mouse reproduces some core features of FTD with respect to behavior, pathology, and survival. This murine model may serve as a valuable in vivo model of FTLD with GRN mutation through which molecular mechanisms underlying the disease can be further dissected.

Acetabular revision after failed total hip arthroplasty in patients with congenital hip dislocation and dysplasia. Results after a mean of 8.6 years.

BACKGROUND: Revision of a total hip arthroplasty in a patient who has had congenital hip dysplasia or dislocation is often more difficult than a standard revision operation. The purpose of this study was to assess the efficacy and complications of use of a cementless hemispherical acetabular component for revision of an acetabular component of a failed total hip replacement in patients whose initial problem was arthritis secondary to congenital dislocation or dysplasia. The mean duration of follow-up was approximately eight years. METHODS: We reviewed a consecutive series of sixty-one hips in fifty-three patients who underwent a cementless acetabular revision with use of a hemispherical acetabular component, with or without concurrent femoral revision. Data were collected prospectively. The mean age of the patients at the time of the index operation was fifty-six years. A mean of 1.9 ipsilateral hip operations had been performed previously. Thirty-nine hips (64 percent) had a so-called high hip center prior to the index revision. With one exception, the uncemented acetabular component was fixed with screws. Fifty-one acetabular components were placed with so-called line-to-line fit, and ten were oversized by one to three millimeters. In thirty-eight hips, the femoral component was revised as well. Twenty-nine femora were reconstructed with use of a cemented device, and nine were revised with an uncemented patch-porous-coated femoral stem (a stem on which the porous coating appears in patches). RESULTS: Four patients (five hips) died prior to the five-year minimum follow-up interval. With the exception of one hip treated with resection arthroplasty because of deep infection, none of the hips in these deceased patients had been revised or had a loose component. One living patient (one hip) had a resection arthroplasty, and one additional patient (two hips) had both stable acetabular components rerevised at the time of femoral rerevision at another institution because of loosening and osteolysis. One patient refused to return for follow-up, but the components had not been revised. The remaining fifty-two hips in forty-six patients were followed for a mean of 8.6 years (range, 5.0 to 12.7 years). The mean Harris hip score was 80 points (range, 56 to 100 points) at the time of the latest follow-up. No acetabular component had been revised, although two had migrated. No other acetabular component was loose according to our radiographic criteria. Thus, the mechanical failure rate on the acetabular side was 3 percent (two of sixty-one) for the entire series and 4 percent (two of fifty-two) for the patients who had been followed for a mean of 8.6 years. On the femoral side, the mechanical failure rate was 3 percent (one of twenty-nine) for the cemented stems and six of nine for the uncemented patch-porous-coated stems. CONCLUSIONS: Of the approaches used in this difficult series of patients requiring revision, the hybrid arthroplasty (a cementless acetabular component and a cemented femoral component) yielded overall good results after an intermediate duration of follow-up.

Acetabular revision arthroplasty using so-called jumbo cementless components: an average 7-year follow-up study.

The optimal technique for acetabular revision surgery in the face of major bone stock deficiency remains controversial. One subset of these problem cases consists of hips that are amenable to reconstruction using a large, hemispherical cementless acetabular component, the so-called jumbo acetabular component. We report the intermediate-term experience of 24 hips in 24 patients who underwent an uncemented acetabular revision using a hemispherical acetabular component of > or = 66 mm diameter. In 16 hips, the femoral component was replaced as well. Of the 18 hips in patients alive after 5 years, 15 were assessed at a mean follow-up of 7.0 years (range, 5.0-10.3 years). The mean final Harris Hip Score was 86 points (range, 45-100 points). No acetabular component had been revised, and none were loose radiographically. In this difficult group, a bimodal distribution resulted. The complication rate was high. In those without infection, the results were excellent.

Thromboembolic complications after major thoracolumbar spine surgery.

STUDY DESIGN: Adult spinal surgery patients were studied prospectively to determine the incidence of subclinical deep venous thrombosis. An overlapping group of patients was reviewed retrospectively for symptomatic thromboembolism. OBJECTIVES: To determine the incidence of symptomatic and asymptomatic thromboembolism in spinal surgery patients. SUMMARY OF BACKGROUND DATA: Although thromboembolic complications are known to occur after spinal operations, there are limited published data on the incidence of pulmonary embolus or deep venous thrombosis after major spinal surgery. METHODS: One hundred sixteen adult spinal surgery patients were examined with duplex ultrasound to determine the incidence of deep venous thrombosis. Seventy-three of these patients also underwent lung perfusion scans to look for subclinical pulmonary embolism. A retrospective review was conducted of symptomatic thromboembolic complications occurring in a 2-year period at the authors' center. Three hundred and eighteen major spinal reconstructive procedures were performed during the period reviewed, which included the period of the prospective study and therefore the patients of the prospective group. Thigh-length compression stockings and pneumatic compression leggings were used for prophylaxis in all patients. RESULTS: One patient had an asymptomatic iliac vein thrombosis, and seven patients had symptomatic pulmonary embolism (2.2%). Six of the symptomatic pulmonary emboli occurred after combined anterior/posterior spinal fusions (6%), whereas only one occurred after posterior decompression and fusion (0.5%). CONCLUSIONS: Duplex ultrasound appeared insensitive for diagnosing clots before embolization in this patient group. Simple mechanical prophylaxis for thromboembolism, which may be adequate for patients undergoing posterior procedures, may not be as protective for patients undergoing combined anterior/posterior spine surgery.

High placement of an acetabular component inserted without cement in a revision total hip arthroplasty. Results after a mean of ten years.

BACKGROUND: Revision of an acetabular component in a patient who has severe periacetabular bone loss is a complex problem, particularly when there is not enough bone stock to allow placement of an acetabular component near the normal anatomical hip center. A valuable option for revision in such a situation is placement of a hemispherical shell, fixed with screws and without cement, against the superior margin of the acetabular defect. The resulting hip center is more proximal than that seen following a typical primary total hip replacement. METHODS: Forty-six hips in forty-four patients were treated consecutively, between July 1984 and February 1988, with a revision in which a hemispherical acetabular component was fixed with screws and without cement. All shells but one were placed with a so-called line-to-line fit. The procedures resulted in a so-called high hip center--that is, the center of rotation of the revised hip was located at least thirty-five millimeters proximal to the interteardrop line. The mean age of the patients at the time of the index procedure was fifty-two years (range, twenty-five to eighty-one years). The most common diagnosis for which the original arthroplasty was performed was osteoarthritis secondary to congenital hip dysplasia or dislocation (twenty-two hips). Thirty-four hips had had a high hip center before the index revision, and most patients had had a substantial limb-length discrepancy, with a mean of 1.6 centimeters of shortening on the side of the operation. In thirty-three hips, the femoral component was replaced as well, with a long-neck or calcar-replacement stem used when necessary to maintain or increase the length of the limb. RESULTS: Six patients (six hips) died before the minimum eight-year follow-up interval; none had had another revision or loosening of the revised acetabular component. Of the remaining patients, four (four hips) had the implant removed. One of them had a resection arthroplasty and one of them had a hip disarticulation because of infection after a subsequent femoral reoperation. Another had a hip disarticulation because of late infection. The fourth implant was removed because it had displaced into the pelvis at approximately six years; this was the only reoperation for aseptic loosening in the series. The remaining thirty-six hips (thirty-four patients) were followed for a mean of 10.4 years (range, 8.5 to 12.7 years). One acetabular component migrated medially and was scheduled for revision. No other acetabular component was loose or had been revised. The mean Harris hip score was 81 points (range, 56 to 100 points) at the time of the most recent follow-up. Despite the use of a high hip center, the prevalence of a positive Trendelenburg sign was reduced from 98 percent (forty-five of forty-six hips) preoperatively to 44 percent (sixteen of thirty-six hips) at the time of the most recent follow-up. The short limbs were lengthened a mean of seven millimeters (range, five millimeters of shortening to forty millimeters of lengthening). CONCLUSIONS: In this study of acetabular revisions with use of a high hip center in patients who had major periacetabular bone loss, mechanical failure occurred in 4 percent (two) of the forty-six hips in the entire series and in 6 percent (two) of the thirty-six hips in patients who were alive and still had the implant in place after a mean of 10.4 years of follow-up. The use of a high hip center did not adversely affect function of the abductor muscles, and the mean limb-length discrepancy was reduced by the femoral reconstruction.

Postoperative mortality after total hip arthroplasty. An analysis of deaths after two thousand seven hundred and thirty-six procedures.

We retrospectively determined the prevalence and nature of mortality as many as ninety days after 2736 primary and revision total hip arthroplasties performed in 2002 patients by one surgeon at a teaching hospital between January 1969 and December 1996. All but seventy-one of the patients had received prophylaxis against venous thromboembolic disease. There were no intraoperative deaths, and no events during the operation could be linked directly to postoperative mortality. Eight deaths (mortality rate, 0.3 per cent) occurred within ninety days after the 2736 procedures. Four deaths (mortality rate, 0.15 per cent) occurred during the initial hospitalization. The cause of seven of the deaths was determined. Three patients died as a result of preexisting disease (severe hepatorenal disease, metastatic esophageal cancer, or severe cardiac disease), and one patient died from sepsis with a gram-negative organism during a thoracotomy eight days postoperatively. A bleeding complication that occurred while the patient was receiving warfarin therapy led to the death of two other patients; one of these deaths occurred in 1974 and the other, in 1982. At the time that these patients were managed, the desired prothrombin time was considered to be twice the control value. The remaining patient, who had had a clip placed on the inferior vena cava after a pulmonary embolus occurred in 1970, died secondary to acute, severe thrombosis of this vessel after a total hip arthroplasty in 1971. The patient for whom the cause of death was not determined had had an artificial aortic valve and had been receiving chronic warfarin therapy. She died suddenly eighty-nine days postoperatively; no autopsy was performed. No patient died as the direct result of a known pulmonary embolus. No deaths related to venous thromboembolic disease or its prophylaxis or treatment occurred after 1982 (1458 operations). We attribute this, in part, to reduced levels of warfarin prophylaxis and improved management with warfarin. The ninety-day postoperative mortality rate after 2736 procedures performed over nearly three decades was low (0.3 per cent). This span of time included the period before the introduction of many current improvements in perioperative care, such as routine intubation of patients under general anesthesia, continuous monitoring of the electrocardiogram intraoperatively, and blood-gas determinations. When the patients who died as a result of known, severe preexisting disease were excluded, the mortality rate was 0.18 per cent (five of 2733).

Arthopor 2 acetabular component with screw fixation in primary hip arthroplasty: a 7- to 9-year follow-up study.

The first 100 consecutive primary hip arthroplasties with the Arthopor 2 acetabular component (Joint Medical Products, Stamford, CT) with supplemental screw fixation performed by the senior author were prospectively studied. The mean patient age was 57 years. Seventy-seven cemented and 23 cementless stems were placed, with 32-mm femoral heads used in most of the patients. Eighty-six hips were reviewed at 7-8.8 years (mean, 7.8 years). The mean Harris hip score at final follow-up evaluation was 94 points. No cups have been revised, although 2 cups in patients with radiation osteonecrosis were loose radiographically. One patient underwent revision of a severely worn liner. Despite a relatively high mean linear wear rate of 0.27 mm/y (range, 0.13-0.57 mm/y), no radiographic evidence of pelvic osteolysis was seen. The Arthopor 2 cup performed well with respect to pelvic osteolysis, despite the presence of substantial polyethylene debris. The relatively high polyethylene wear rate is attributed in part to the younger patient population and the use of 32-mm femoral heads paired with thin polyethylene liners.

The evaluation and initial management of arthritis.

This article reviews the appropriate workup of the patient presenting with complaints referable to a joint, including the important information to be obtained during the interview and physical examination, as well as from laboratory and imaging studies. The clinical presentation of osteoarthritis, rheumatoid arthritis, gout, and joint sepsis are discussed, and the treatment approach for each is outlined. The specific indications for surgical intervention in the course of arthritis also are detailed.

Medial compartment arthrosis of the knee.

When the resultant forces on the tibial plateau are displaced medially, compressive stresses cause apposition of bony tissue, thus thickening the dense subchondral bone underlying the medial plateau. Loss of the articular cartilage and an increase in subchondral bone density facilitate the progression of osteoarthrosis. Surgical management is dependent on the presence of a varus deformity; patients with medial compartment disease and varus alignment should be considered for high tibial osteotomy (HTO) or unicondylar or total knee arthroplasty (TKA), depending on their age and activity level. Patients without varus deformity and with mechanical symptoms, only mild joint-space narrowing, and pain less than 1 year are likely to benefit from arthroscopic débridement. Patients without varus alignment but with chronic pain associated with loading and more pronounced joint-space loss should be considered for HTO, or unicondylar or TKA.