Findings from the individualized management of a patient with Acyl-CoA Oxidase-1 (ACOX1) deficiency: A bedside-to-bench-to-bedside strategy.

Acyl-CoA Oxidase-1 (ACOX1) deficiency (MIM 264470) is an autosomal recessive disease characterized by impairments in the desaturation of acyl-CoAs to 2-trans-enoyl-CoAs, which is the first step in the catalysis of the ß-oxidative breakdown of very long chain fatty acids (VLCFA) occuring in peroxisomes. The deleterious accumulation of VLCFA in several organs, including the brain, is a key biochemical feature of this disease which has devastating neurological consequences. ACOX1 deficiency is ultra-rare; as such, few studies have been conducted to determine the leading causes of symptoms or uncover new therapeutics. When confronted with one such case, we decided to bring drug discovery tools to the patient's bedside in an attempt to identify a cure. A skin biopsy was performed on a young patient with ACOX1 deficiency, following which screening technologies and mass spectrometry analysis techniques were applied to design a cellular assay that enabled the direct measurement of the effect of small molecules on the patient's primary fibroblasts. This approach is particularly well adapted to inherited metabolic disorders such as ACOX1 deficiency. Through the evaluation of a proprietary library of repurposable drugs, we found that the anthelmintic drug niclosamide led to a significant reduction in VLCFA in vitro. This drug was subsequently administered to the patient for more than six years. This study outlines the screening and drug selection processes. Additionally, we present our comprehensive clinical and biochemical findings that aided in understanding the patient's natural history and analysis of the progression of the patient's symptoms throughout the treatment period. Although the patient's overall lifespan was extended compared to the average age at death in severe early onset cases of ACOX1 deficiency, we did not observe any definitive evidence of clinical or biochemical improvement during niclosamide treatment. Nonetheless, our study shows a good safety profile of long-term niclosamide administration in a child with a rare neurodegenerative disease, and illustrates the potential of individualized therapeutic strategies in the management of inherited metabolic disorders, which could benefit both patients and the broader scientific and medical communities.

Ventriculomegaly in the Elderly: Who Needs a Shunt? A MRI Study on 90 Patients.

OBJECTIVE: In the case of ventriculomegaly in the elderly, it is often difficult to differentiate between communicating chronic hydrocephalus (CCH) and brain atrophy. The aim of this study is to describe the MRI criteria of CCH, defined by a symptomatic patient with ventriculomegaly and that improved after shunt placement. MATERIALS AND METHODS: Magnetic resonance imaging was prospectively evaluated in 90 patients with ventriculomegaly. Patients were classified into three groups: patients without clinical signs of CCH (control, n = 47), patients with CCH treated by shunt placement with clinical improvement (responders, n = 36), and patients with CCH treated using a shunt without clinical improvement (nonresponders, n = 7). MRI parameters of the two groups of interest (responders vs. controls) were compared. RESULTS: Compared with controls, Evans' index (p = 0.029), ventricular area (p < 0.01), and volume (p = 0.0001) were higher in the responders. In this group, the callosal angle was smaller (p ≤ 0.0001) and the aqueductal stroke volume (SVa) of CSF was higher (p ≤ 0.0001) than in controls. On the ROC curves, the optimal cut-off values for differentiating between responders and controls were a ventricular area >33.5 cm2, a callosal angle <90.8° and a SVa > 136.5 µL/R-R. In multivariate analysis, responders remained associated with SVa and callosal angle, with a c-statistic of 0.90 (95%CI, 0.83-0.98). CONCLUSION: On suspicion of CCH, a large ventricular area, a small callosal angle, and an increased aqueductal stroke volume are important MRI arguments that can be associated with the clinical evaluation and dynamic testing of CSF to confirm the indication for a shunt.

An unusual ectopic thyroid tissue location & review of literature.

Ectopic thyroid is well-known pathology for several decades. Many locations have been described. Nowadays, only three cases of skull base location have been described in literature. In our case, we reported a single case of a 39-year-old male presenting with a supra-sellar and suprachiasmatic location. He presented no clinical symptoms, no endocrine alteration on biology and no skull base invasion which make this case unique compared to actual literature. Such diagnosis should always be an exclusion diagnosis as secondary neoplastic should be first ruled out.

MR imaging in the diagnosis of desmoplastic infantile tumor: retrospective study of six cases.

BACKGROUND AND PURPOSE: Desmoplastic infantile tumors (DITs) are rare supratentorial tumors of infancy with a favorable prognosis. Radiologic and histologic features of DIT are misleading, and DIT may be misinterpreted as a malignant lesion. We have studied the usefulness of MR imaging in the diagnosis of these tumors. METHODS: Between 1995 and 2002, six DITs were diagnosed in young children at our institution. Neuroimaging, age at diagnosis, sex, clinical presentation, symptoms duration, follow-up, and development were studied retrospectively. Contrast-enhanced CT and MR images were available. MR study included T1-, T2-, and postgadolinium T1-weighted sequences in the axial, sagittal, and coronal planes. RESULTS: These tumors were massive and predominantly cystic, with preferential frontal and parietal involvement. Typically, a DIT appears as a hypointense cystic mass with an isointense peripheral solid component on T1-weighted MR images. The peripheral solid component enhances after gadolinium administration. On T2-weighted MR images, the cystic component is hyperintense and the solid portion isointense or heterogeneous. The cystic portion is usually located deep inside the lesion, whereas its solid portion is peripheral. Meningeal enhancement and thickening adjacent to the solid portion of the tumor, calcifications, bone abnormalities adjacent to the tumor consisting of thinning and deformation were noted in 50% of our cases. Edema was usually absent or moderate. Median follow-up was 32 months, and no recurrence was noted except for one atypical case with incomplete excision, which led to the patient's death. CONCLUSION: Despite their malignant appearance, MR imaging features of DIT may help in the diagnosis and obviate unnecessary chemotherapy or radiation therapy.