Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease which leads to systemic disease, including progressive neurodegeneration, mental retardation and death before the age of 10 years. MPS I results from deficiency of α-L-iduronidase (laronidase, IDUA) in lysosomes and subsequent accumulation of glycosaminoglycans (GAG). Clinical enzyme replacement therapy (ERT) with intravenous laronidase reverses some aspects of MPS I disease (e.g., hepatomegaly, splenomegaly, glycosaminoglycanuria) and ameliorates others (e.g., pulmonary function, cardiac disease, arthropathy, exercise tolerance). However, neurologic benefits are thought to be negligible because the blood-brain barrier (BBB) blocks enzyme from reaching the central nervous system (CNS). We considered the possibility that a very high dose of intravenous laronidase might be able to transit across the BBB in small quantities, and provide some metabolic correction in the brain. To address this question, we administered high-dose laronidase (11.6 mg/kg, once per week, 4 weeks) to adult MPS I mice. IDUA enzyme activity in cortex of injected mice increased to 97% of that in wild type mice (p<0.01). GAG levels in cortex were reduced by 63% of that from untreated MPS I mice (p<0.05). Further, immunohistochemical analysis showed that the treatment reduced secondary storage material GM3-ganglioside in treated MPS I mice. Water T-maze tests showed that the learning abnormality in MPS I mice was surprisingly reduced (p<0.0001). In summary, these results indicated that repeated, high-dose ERT facilitated IDUA transit across the BBB, reduced GAG accumulation within the CNS, and rescued cognitive impairment.

Background En bloc resection for treatment of sacral tumors is the approach of choice for patients with resectable tumors who are well enough to undergo surgery, and studies describe patient survival, postoperative complications, and recurrence rates associated with this treatment. However, most of these studies do not provide patient-reported functional outcomes other than binary metrics for bowel and bladder function postresection. Questions/purposes The purpose of this study was to use validated patient-reported outcomes tools to compare quality of life based on level of sacral resection in terms of (1) physical and mental health; (2) pain; (3) mobility; and (4) incontinence and sexual function. Methods Our analysis included 33 patients (19 men, 14 women) who had a mean age of 53 years (range, 22-72 years) with a quality-of-life survey administered at a mean postoperative followup of 41 months (range, 6-123 months). The majority of patient-reported quality-of-life outcome surveys for this study were taken from the National Institute of Health's Patient Reported Outcome Measurement Information System (PROMIS) system. To assess physical and mental health, the PROMIS Global Items Survey with physical and mental subscores, Anxiety, and Depression scores were used. Pain outcomes were assessed using PROMIS Pain Intensity and Pain Interference surveys. Patient-reported lower extremity function was assessed using the PROMIS Mobility Survey. Patientreported quality of life for sexual function was assessed using the PROMIS Sex Interest and Orgasm survey, One-way analysis of variance tests on means or ranks were used to conduct statistical analysis between levels. Results Patients with more caudal resections had higher physical health (95% confidence interval [CI] total sacrectomy 36-42 versus S4 50-64, p \ 0.001), less intense pain (95% CI total sacrectomy 47-60 versus S4 28-37, p \ 0.001), less interference resulting from pain (95% CI total sacrectomy 58-69 versus S4 36-51, p = 0.004), higher mobility (95% CI total sacrectomy 24-46 versus S4 59-59, p = 0.002), and were more functionally able to achieve orgasm (95% CI S1 1-1 versus S4 2.2-5.3, p = 0.043).

Overgrowth of epidural fat, known as spinal epidural lipomatosis (SEL), can cause symptomatic compression of the spinal cord, conus medullaris, or cauda equina. Suggested predisposing factors such as obesity, steroid use, and diabetes mellitus have been based on a few reported cases, many of which were not surgically confirmed. There is a paucity of epidemiological data in surgically confirmed cases for this disorder. The purpose of this independently reviewed, retrospective, matched cohort analysis was to compare the demographics and incidence of comorbidities of patients who underwent lumbar decompression for SEL vs degenerative stenosis without SEL. Two surgeons' databases were reviewed to identify patients older than 18 years who underwent decompression surgery for magnetic resonance imaging-verified, symptomatic lumbar SEL. A matched control group comprised an equal number of patients with degenerative stenosis (n=14). Demographic data, body mass index, symptom type/duration, comorbidities, complications, treatment history, and associated pathology were collected from medical records. Previously suggested risk factors, such as obesity, endocrinopathy, and epidural steroid injections, were not significantly different between the SEL and control groups. Furthermore, there were no differences in operative times, complications, or blood loss. The only noted difference between the 2 groups was the preoperative duration of symptoms, on average double in patients with SEL. This series represents the largest of its kind reported to date. Because symptom duration was the only difference noted, it is postulated to be the result of lack of awareness of SEL. Future prospective study in a larger group of patients is warranted. [Orthopedics. 2016; 39(3):163-168.].

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