Mild phenotype in a male with pyruvate dehydrogenase complex deficiency associated with novel hemizygous in-frame duplication of the E1α subunit gene (PDHA1).

Pyruvate dehydrogenase complex (PDHC) deficiency is an inborn error of metabolism that occurs most commonly due to mutations in the X-linked E1α subunit gene (PDHA1). We report a novel duplication of PDHA1 associated with a mild phenotype in a 15-year-old boy who was diagnosed with PDHC deficiency at 4 years of age following a history of seizures and lactic acidosis. The novel c.1087_1119 mutation in exon 11 resulted in an in-frame duplication of 11 amino acids. Measurements of PDHC activity in cultured skin fibroblasts were low, corresponding to 18.6 and 11.6% of the mean with respect to prior controls, whereas the E1 PDH component was absent. He has borderline intellectual functioning and maintains normal lactate levels on a ketogenic diet in between relapses due to illness. Review of the literature reveals wide variation of clinical phenotype in patients with mutations of the E1α subunit gene (PDHA1). There appears to be a higher incidence of normal or borderline intellectual ability in individuals who have insertions or deletions that are in-frame versus those that are out-of-frame. Furthermore, there is no correlation between mean residual PDH activity and phenotype in these patients.

A Repurposing Programme Evaluating Transdermal Oestradiol Patches for the Treatment of Prostate Cancer Within the PATCH and STAMPEDE Trials: Current Results and Adapting Trial Design.

AIMS: Androgen deprivation therapy (ADT), usually achieved with luteinising hormone releasing hormone analogues (LHRHa), is central to prostate cancer management. LHRHa reduce both testosterone and oestrogen and are associated with significant long-term toxicity. Previous use of oral oestrogens as ADT was curtailed because of cardiovascular toxicity. Transdermal oestrogen (tE2) patches are a potential alternative ADT, supressing testosterone without the associated oestrogen-depletion toxicities (osteoporosis, hot flushes, metabolic abnormalities) and avoiding cardiovascular toxicity, and we here describe their evaluation in men with prostate cancer. MATERIALS AND METHODS: The PATCH (NCT00303784) adaptive trials programme (incorporating recruitment through the STAMPEDE [NCT00268476] platform) is evaluating the safety and efficacy of tE2 patches as ADT for men with prostate cancer. An initial randomised (LHRHa versus tE2) phase II study (n = 251) with cardiovascular toxicity as the primary outcome measure has expanded into a phase III evaluation. Those with locally advanced (M0) or metastatic (M1) prostate cancer are eligible. To reflect changes in both management and prognosis, the PATCH programme is now evaluating these cohorts separately. RESULTS: Recruitment is complete, with 1362 and 1128 in the M0 and M1 cohorts, respectively. Rates of androgen suppression with tE2 were equivalent to LHRHa, with improved metabolic parameters, quality of life and bone health indices (mean absolute change in lumbar spine bone mineral density of -3.0% for LHRHa and +7.9% for tE2 with an estimated difference between arms of 9.3% (95% confidence interval 5.3-13.4). Importantly, rates of cardiovascular events were not significantly different between the two arms and the time to first cardiovascular event did not differ between treatment groups (hazard ratio 1.11, 95% confidence interval 0.80-1.53; P = 0.54). Oncological outcomes are awaited. FUTURE: Efficacy results for the M0 cohort (primary outcome measure metastases-free survival) are expected in the final quarter of 2023. For M1 patients (primary outcome measure - overall survival), analysis using restricted mean survival time is being explored. Allied translational work on longitudinal samples is underway.

Pituicytoma: diagnostic features on selective carotid angiography and MR imaging.

We report a case of pituicytoma, a rare primary tumor of the neurohypophysis. A 64-year-old man presented with progressive visual complaints, bitemporal hemianopsia, and headache. Imaging studies revealed distinctive features of a mass lesion that thickened the pituitary stalk with a bilobed protrusion extending into the hypothalamus. Angiography demonstrated tumor vascular supply from the superior hypophyseal arteries representing the diencephalic branches of the internal carotid arteries. We discuss the imaging and pathology of this unusual tumor.

Cerebral vasoconstriction in toxemia.

Three patients with toxemia developed acute neurologic deterioration postpartum. In all, cerebral angiography revealed widespread arterial vasoconstriction. Cerebral vasoconstriction may be an important cause of neurologic complications in toxemia.

CT number characteristics of malpositioned TMJ menisci. Diagnosis with CT number highlighting (blinkmode).

The use of computed tomography (CT) number highlighting ("blinkmode") for diagnosing malpositioned temporomandibular joint menisci was investigated. By determining the average CT number, standard deviation, and range for specific periarticular tissues, it is possible to tell how much their attenuation values overlap and, therefore, whether there is a sound basis for distinguishing the disc from adjacent tissues. Fresh and fresh-frozen cadaver specimens, were scanned in axial and direct sagittal planes with 1.5-mm thick overlapping soft-tissue sections. CT number measurements were made for tendon, muscle, fat, and meniscus. Patients also were scanned with overlapping 1.5-mm thick axial soft-tissue sections in order to compare the range of CT numbers in cadavers with that in living subjects. Cadaver joints were cryosectioned at 0.5-mm intervals in the same planes as their CT sections, and the tissue sections were compared with their respective CT highlighted sections. For patients the average CT numbers in Hounsfield units were 88 for tendon, 67 for muscle, -25 for fat, and 100 for meniscus. Fresh unembalmed cadavers showed a higher CT average number for tendon and a lower average CT number for fat. The anatomic sections confirmed the meniscal position seen in the highlighted sections in nine of ten joints (90%) and was equivocal in one. Misshapen and malpositioned discs are seen readily with the blinker function; thinned and normal discs are not. The tendinous insertion of the lateral pterygoid muscle may be confused for meniscus in the medial aspect of the TMJ.(ABSTRACT TRUNCATED AT 250 WORDS)

Large optic nerve glioma with normal vision.

When the diagnosis of optic glioma is made, the visual loss is most often mildly or profoundly impaired. We report the details of the unusual situation where central visual acuity, visual fields, and color vision were normal at the time a large optic nerve glioma was demonstrated in a young boy. To our knowledge, this is the first case report containing ophthalmologic, neuroradiologic, surgical, and histologic details illustrating the rare association of normal vision and an optic glioma.

Hyperventilation-induced cerebral ischemia in patients with acute brain lesions: demonstration by xenon-enhanced CT.

PURPOSE: To examine the possibility that hyperventilation, commonly used to prevent or treat increased intracranial pressure in patients with acute brain lesions, may induce significant cerebral ischemia. METHODS: Local cerebral blood flow and vascular reactivity were measured before and after hyperventilation using xenon-enhanced CT in 12 patients with acute brain lesions. RESULTS: Five patients showed "paradoxical" reactivity (increased cerebral blood flow during hyperventilation) within the lesions. In five patients, hyperventilation induced ischemia in apparently normal regions of brain. In three patients, areas of luxury perfusion became ischemic during hyperventilation, while in three patients, lesions with moderate ischemia became more ischemic. Most patients showed more than one type of reactivity. CONCLUSIONS: These findings document hyperventilation-induced ischemia in acute brain lesions, and demonstrate that this phenomenon affects both injured and apparently intact areas of the brain. Further studies are required to determine the clinical significance of these pathophysiologic changes.

CT scanning phantom for normalization of infant brain attenuation.

The x-ray attenuation values of brain studied with computed tomography (CT) are strikingly affected by the ages of the subjects. Premature neonates, for example, may have brain attenuation values 20-30 H below adult values. These lower attenuation values for developing compared with adult brain can be ascribed partly to machine-related effects (beam-hardening, adult algorithms, scanning geometry, etc.). A scanning phantom made from aluminum was developed that can be used to develop a nomogram for any particular scanner from which normalized brain attenuation may be derived for any small head size. Using this nomogram, predicted neonatal attenuations are still 10-15 H higher than those actually observed in scanning neonates. The model predicts that, at the most, 3-4 H of this discrepancy can be accounted for by less beam-hardening from the lower bone attenuation of the thinner developing skull. Presumably, the rest is from a lower brain density in neonates (higher water content). By normalizing to cerebrospinal fluid (water) with special care to avoid partial-volume artifacts, one can predict attenuation values for developing brain more accurately.

Radiodense dural sinuses: new CT sign in patients at risk for hypoxemic insult.

The observation of apparent dural sinus opacification in a polycythemic patient with cerebral infarction prompted a review of 300 computed tomographic scans for the significance of dense dural sinuses. Fifteen patients including 11 neonates, were identified; each of them had dense dural sinuses and elevated hematocrit or red blood cell indices or both. With only one exception, computed tomography also showed various low attenuation parenchymal abnormalities. A typical cerebral infarction pattern was seen in six and parenchymal hemorrhage in one. Nonthrombotic dural sinus opacification is a sign of increased blood viscosity in patients with congenital heart disease, hemoconcentration states, polycythemia of the newborn, and polycythemia rubra vera. These patients are at high risk for hypoxemic cerebral insult, which can be detected by cranial computed tomography.

The bright choroid plexus on MR: CT and pathologic correlation.

Fourteen patients studied with MR imaging were found, incidentally, to have unusually bright, large choroid plexus glomera on T2-weighted sequences. A group of 167 patients was then examined retrospectively for size and intensity of the choroid plexus glomera on T2-weighted images. In the latter group of 167 patients, 66 (39.5%) had bright choroid plexus glomera. Of those who had bright choroid plexus glomera, eight of the 14 initial group and 11 of the 66 patients studied retrospectively had previous CT scans. The typical CT appearance of these bright glomera consisted of nonenhancing central regions of low (but not negative) attenuation with peripheral calcifications in the majority. The remainder showed noncalcified glomera. Fifty-two glomera were obtained at autopsy and examined retrospectively. Eight showed small, variably sized masses with lipid deposits, neuroepithelial microcysts, and peripheral psammoma body calcifications. One patient who died had a bright choroid plexus glomus on MR, and his glomera showed the same pathologic findings. The autopsy findings were believed to be typical pathologically for early xanthogranulomata formation. These early xanthogranulomatous changes appear to be of little clinical significance but must be differentiated from other lesions that can produce bright or enlarged choroid plexus glomera on MR.

Cystic acoustic schwannomas: MR characteristics.

PURPOSE: To evaluate the spectrum of MR characteristics of cystic acoustic schwannoma and to investigate its incidence. METHODS: We retrospectively reviewed the MR findings and clinical records of 16 patients with cystic acoustic schwannomas. In addition, the MR examinations of 411 consecutive patients referred for clinical suspicion of acoustic schwannomas were reviewed retrospectively to assess the incidence of acoustic schwannomas with cystic lesions arising from the internal auditory canal. RESULTS: Of the 16 acoustic schwannomas with MR evidence of intramural cysts, 11 tumors had single small cysts, and five had multiple intramural cysts of variable size. Intramural cysts in 11 of the 16 tumors exhibited higher signal intensity than that of cerebrospinal fluid; the remainder were isointense to cerebrospinal fluid on both T1- and T2-weighted images. All intramural cysts showed circumferential enhancement after contrast administration. Nine of the 16 cystic acoustic schwannomas also had MR evidence of extramural/arachnoid cysts. Six of the extramural/arachnoid cysts had epicenters away from the dural interface, and the other three cysts were broadly based against the dura. The incidence of cystic acoustic schwannomas was 11.3% and association with extramural/arachnoid cysts 7.5%. CONCLUSION: Our series suggests that cystic changes in acoustic schwannomas and the association with extramural/arachnoid cysts are not as rare as previously reported by other diagnostic methods. The high signal intensity of intramural cysts is probably related to necrotic material, blood, or colloid-rich fluid. The difference in the MR characteristics of extramural/arachnoid cysts associated with acoustic schwannomas and those of typical arachnoid cysts not associated with neoplasia may be related to higher protein and/or colloid contents secreted by the tumor. Most extramural/arachnoid cysts had epicenters between the tumor and brain, suggesting that the most likely mechanism of formation is peritumoral adhesions. It creates a pseudo-duplication caused by the trapping of fluid between the leptomeninges and the mass, resulting in an acquired type of arachnoid cyst.

Therapeutic embolization for vascular trauma of the head and neck.

Therapeutic embolization is an effective and relatively safe method for managing many cases of head and neck trauma. In the last 5 years, 78 traumatic vascular lesions--10 arterial transections and 68 arteriovenous fistula--were treated by intravascular embolization at four medical centers. Selection of embolic materials is discussed and different types of lesions are illustrated. Treatment was successful in every instance. Complications were limited to one case of cerebral infarction and two cases of temporary oculomotor weakness. The indications for embolization have widened beyond life-threatening hemorrhage alone, and continued improvement in techniques and embolic agents should see an increased use of this form of treatment.

CT of tumors and tumor-like conditions of the paranasal sinuses.

High-resolution CT is an ideal technique for evaluating tumors of the paranasal sinuses. It offers excellent detail of both bony and soft tissue structures. CT can demonstrate a tumor in its early stage and can reveal the exact extent of a lesion for optimal staging prior to treatment. It is important in follow-up and can be used to document residual or recurrent tumor with a high degree of accuracy.

The temporomandibular joint.

MRI is the procedure of choice for diagnosing most internal derangements. MRI provides images that not only demonstrate bony detail but show excellent representation of soft tissues in both anatomic and semifunctional relationships. MRI does not use ionizing radiation and has no known adverse effects. Multiplanar imaging allows a three-dimensional analysis of the TMJ, providing a more complete assessment of the condyle, articular disc, fossa relationships. Whenever capsular adhesions or disc perforations are suspected and are not demonstrated with MRI, then arthrography should be performed.

Adult extra-axial brain tumors.

Magnetic resonance imaging is the preferred cross-sectional imaging study for the evaluation of nearly all extra-axial brain tumors in adults. This article outlines the neoplasms by their pathology. The discussion covers the neoplasms originating from central neuroglial cells, meninges, and cranial nerves. In addition, developmental tumors and cysts and secondary extra-axial tumors are discussed.

Magnetic resonance imaging of the paranasal sinuses and nasal cavities.

Magnetic resonance imaging has proven to be a useful tool for imaging the paranasal sinuses and nasal cavities. Of particular interest in this region is the ability to distinguish between lesions that are highly cellular with little free water (neoplasms) and lesions that have significant amounts of serous and mucinous secretions and thus contain predominantly free water (infections).

Magnetic resonance imaging of the pharynx and larynx.

Imaging of the pharynx and larynx has been a difficult challenge for many years. The advent of magnetic resonance imaging (MRI) with its superior soft tissue contrast resolution and multiplanar capabilities has allowed the imaging specialist to examine these structures with unparalleled precision. The recent developments in MRI can also aid the oncologist, surgeon, and radiation therapist in developing a more comprehensive treatment plan for patients with pharyngeal and laryngeal neoplasms. This article describes the important advances in MRI of the pharynx and larynx.

Magnetic resonance imaging of the oral cavity and tongue.

The oral cavity is the oral portion of the upper aerodigestive tract separated from the oropharynx by the soft palate, anterior tonsillar pillars, and circumvallate papillae. The anatomy of the components of the oral cavity, including the oral tongue, the floor of the mouth, the retromolar trigone, the hard and soft palates, the buccal mucosa, and the gingiva, are described. The pathology discussion includes both malignant (predominantly squamous cell carcinomas) and benign disease entities commonly detected in this region.

Magnetic resonance imaging of soft tissues of the neck.

Magnetic resonance imaging (MRI) has proven to be an ideal examination for evaluating a variety of soft tissue lesions in the extracranial head and neck. In this article we will describe the MRI characteristics of a variety of the soft tissue lesions found in the neck. Pathophysiology, clinical presentation, treatment, and prognosis are also discussed.

Magnetic resonance imaging of the skull base.

Magnetic resonance (MR) imaging has made it possible to evaluate the skull base in one primary screening examination. In most cases, MR imaging also serves as the definitive imaging study. In some traumatic or congenital lesions or both, computed tomography (CT) and conventional radiographs may be preferred or may be needed to supplement the MR imaging examination. This article discusses the pathology of the skull base, particularly in the evaluation of suspected neoplasms. Optimal imaging of the skull base requires a minimum of two planes of section, typically with and without gadolinium contrast enhancement.