Pure Progressive Ataxia and Palatal Tremor (PAPT) Associated with a New Polymerase Gamma (<Emphasis Type="Italic">POLG</Emphasis>) Mutation

Progressive ataxia with palatal tremor (PAPT) is a syndrome caused by cerebellar and brainstem lesions involving the dentato-rubro-olivary tract and associated with hypertrophic olivary degeneration. Etiologies include acquired posterior fossa lesions (e.g. tumors, superficial siderosis, and inflammatory diseases) and genetic disorders, such as glial fibrillary acidic protein (GFAP) and polymerase gamma (POLG) mutations. We describe the case of a 52-year-old man who developed pure progressive ataxia and palatal tremor. Genetic analysis has shown that he is compound heterozygote for a known pathogenic (W748S) and a novel POLG variant (I1185N). Patients with POLG recessive mutations usually manifest a more complex clinical picture, including polyneuropathy and epilepsy; our case emphasizes the need to consider a genetic origin in a seemingly sporadic and pure PAPT.     

Oncogenic osteomalacia: two case reports with surprisingly different outcomes

Oncogenic osteomalacia is a rare paraneoplastic syndrome of acquired hypophosphatemic osteomalacia, resulting from a deficit in renal tubular phosphate reabsorption, in which fibroblast growth factor 23 (FGF23) seems to be implicated. This condition is usually associated with a phosphaturic mesenchymal tumor of mixed connective tissue located in the bone or soft tissue. The clinical and the radiologic findings are the same as those seen in osteomalacia, and the biochemical features include renal phosphate loss, low serum phosphate and 1,25-(OH)₂ vitD₃ levels, increased alkaline phosphatase, and normal calcium, PTH, calcitonin, 25-OH-vitD₃ and 25,25-(OH)₂ vitD₃. We present two cases of oncogenic osteomalacia associated with phosphaturic mesenchymal tumors, which were histologically similar, but presented a completely different evolution. In the first patient, the tumor developed on the sole of the foot. Following removal of the mass, the symptoms resolved and biochemical and radiological parameters returned to normal. However, in the second patient, a liver tumor developed and resection did not resolve the disease. Multiple lesions appeared in several locations during follow-up. This disease usually remits with complete tumor resection. Nevertheless, if this is not possible, oral treatment with phosphate, calcium and calcitriol can improve the symptoms. If scintigraphy of the tumor shows octreotide receptors, patients may respond partially to therapy with somatostatin analogs, with stabilization of the lesion.     

Whole-body MRI for the detection of bone marrow involvement in lymphoma: prospective study in 116 patients and comparison with FDG-PET

Objective

To assess and compare the value of whole-body MRI with FDG-PET for detecting bone marrow involvement in lymphoma.

Methods

A total of 116 patients with newly diagnosed lymphoma prospectively underwent whole-body MRI and blind bone marrow biopsy (BMB) of the posterior iliac crest. Of 116 patients, 80 also underwent FDG-PET. Patient-based sensitivities of whole-body MRI for detecting bone marrow involvement were calculated using BMB as reference standard and compared with FDG-PET in aggressive and indolent lymphomas separately.

Results

Sensitivity of whole-body MRI in all lymphomas was 45.5 % [95 % confidence interval (CI): 29.8–62.0 %]. Sensitivity of whole-body MRI in aggressive lymphoma [88.9 % (95 % CI: 54.3–100 %)] was significantly higher (P?=?0.0029) than that in indolent lymphoma [23.5 % (95 % CI: 9.1–47.8 %)]. Sensitivity of FDG-PET in aggressive lymphoma [83.3 % (95 % CI: 41.8–98.9 %)] was also significantly higher (P?=?0.026) than that in indolent lymphoma [12.5 % (95 % CI: 0–49.2 %)]. There were no significant differences in sensitivity between whole-body MRI and FDG-PET (P?=?1.00)

Conclusion

Sensitivity of whole-body MRI for detecting lymphomatous bone marrow involvement is too low to (partially) replace BMB. Sensitivity of whole-body MRI is significantly higher in aggressive lymphoma than in indolent lymphoma and is equal to FDG-PET in both entities.

Key Points

? Bone marrow involvement in lymphoma has prognostic and therapeutic implications. ? Blind bone marrow biopsy (BMB) is standard for bone marrow assessment. ? Neither whole-body MRI nor FDG-PET can yet replace BMB. ? Both techniques have higher sensitivity in aggressive than in indolent lymphoma. ? Both imaging techniques are complementary to BMB.     

Switch from ritonavir-boosted to unboosted atazanavir guided by therapeutic drug monitoring

Plasma concentration of atazanavir (ATV) may be reduced when coadministered with tenofovir (TDF) or proton pump inhibitors. Boosting ATV exposure with ritonavir (r) may make it possible to overcome these drug interactions. However, jaundice and loss of the metabolic advantages of ATV are more frequent using ATV/r than ATV alone. Herein, we assessed whether therapeutic drug monitoring (TDM) could make it possible to identify the subset of patients in whom removal of ritonavir could be attempted without risk of suboptimal plasma ATV exposure and subsequent virological failure. A total of 56 patients with undetectable plasma HIV-RNA under a stable triple regimen containing ATV 300/100 mg qd were switched to ATV 400 mg qd. Plasma ATV concentrations were measured using a reliable high-performance liquid chromatography method. Median plasma ATV C(min) fell from 880 to 283 ng/ml (p = 0.03) after removal of ritonavir. While all patients on ATV/r showed ATV plasma concentrations within therapeutic values (IC(min) above 150 ng/ml) before switching, four patients (7%) fell below this threshold after switching to ATV 400 mg qd. However, only one of this group experienced virological failure at week 24 of follow-up. TDF was part of the antiretroviral regimen in all four cases. From a total of 29 (52%) patients on ATV/r showing grade 3-4 hyperbilirubinemia, only 7 (12%) remained on it upon switching to ATV 400 mg qd (p < 0.001). Patients with complete viral suppression under ATV/r 300/100 mg qd may benefit from switching to ATV 400 mg qd guided by TDM, which may make it possible to minimize adverse events without compromising antiviral efficacy in most cases.     

Cost and quality-of-life impacts of community treatment orders (CTOs) for patients with psychosis: economic evaluation of the OCTET trial

Purpose

Current RCT and meta-analyses have not found any effect of community treatment orders (CTOs) on hospital or social outcomes. Assumed positive impacts of CTOs on quality-of-life outcomes and reduced hospital costs are potentially in conflict with patient autonomy. Therefore, an analysis of the cost and quality-of-life consequences of CTOs was conducted within the OCTET trial.

Methods

The economic evaluation was carried out comparing patients (n = 328) with psychosis discharged from involuntary hospitalisation either to treatment under a CTO (CTO group) or voluntary status via Section 17 leave (non-CTO group) from the health and social care and broader societal perspectives (including cost implication of informal family care and legal procedures). Differences in costs and outcomes defined as quality-adjusted life years (QALYs) based on the EQ-5D-3L or capability-weighted life years (CWLYs) based on the OxCAP-MH were assessed over 12 months (£, 2012/13 tariffs).

Results

Mean total costs from the health and social care perspective [CTO: £35,595 (SD: £44,886); non-CTO: £36,003 (SD: £41,406)] were not statistically significantly different in any of the analyses or cost categories. Mental health hospitalisation costs contributed to more than 85% of annual health and social care costs. Informal care costs were significantly higher in the CTO group, in which there were also significantly more manager hearings and tribunals. No difference in health-related quality of life or capability wellbeing was found between the groups.

Conclusion

CTOs are unlikely to be cost-effective. No evidence supports the hypothesis that CTOs decrease hospitalisation costs or improve quality of life. Future decisions should consider impacts outside the healthcare sector such as higher informal care costs and legal procedure burden of CTOs.

     

Environmental reduplicative paramnesia in a case of atypical Alzheimer’s disease

A 79-year-old patient with neuropathologically confirmed Alzheimer’s disease (AD) presented with a selective environmental reduplicative paramnesia (RP), the belief that one or more environments exist simultaneously in two or more physical locations. Clinical presentation and neuropathological examination revealed an atypical form of AD. High neurofibrillary tangle densities were observed in the frontal and temporal association cortex, whereas the parietal and entorhinal cortex, as well as the hippocampus, were nearly spared. These findings are compared to those reported in frontal and frontotemporal variants of AD and discussed in the light of current anatomoclinical models for environmental RP.