Psoas muscle disorders: MR imaging

Nineteen patients with evidence of psoas and iliopsoas abnormalities on computed tomographic (CT) scans (12 with metastases, three with lymphoma, two with hematoma, and two with abscess) were examined with magnetic resonance (MR) imaging. The abnormal psoas could be identified on both T1- and T2-weighted spin-echo images, although T2-weighted sequences provided better contrast. The psoas muscle can be affected by one of three mechanisms: total replacement, lateral displacement, or medial displacement. In four patients in whom the CT study showed apparent enlargement of a psoas muscle, subsequent MR imaging examinations demonstrated that the psoas muscle was compressed and displaced laterally by a paraspinal mass. MR images provided better contrast between the normal and abnormal psoas than CT scans in nine cases; MR images were inferior to CT scans in two cases because calcifications (one case) and air bubbles within an abscess (one case) were not detectable.     

Is ACTH a key to understanding anticonvulsant action?

Adrenocorticotrophin hormone (ACTH) has been used as an anticonvulsant for many years. In this paper, the use of ACTH in 23 children with intractable epilepsies is described. It was found that ACTH worked most effectively when the EEG showed benzodiazepine sensitivity. A mechanism of action of ACTH is proposed.     

Hepatic metastases studied with MR and CT

Examinations of the liver using magnetic resonance (MR) and computed tomography (CT) were performed on 50 patients with hepatic metastases. MR and CT were comparable in their ability to detect metastases, which generally appeared hypointense compared with normal liver parenchyma on T1-weighted MR images and hyperintense on T2-weighted images. The MR imaging techniques that were most reliable in detecting metastases were inversion recovery and a relatively T2-weighted, spin-echo technique (TR = 1,500 msec, TE = 60 msec). We conclude that CT, because of its shorter imaging time, greater spatial resolution, and lower cost, should remain the preferred screening test for hepatic metastases. MR imaging should be reserved for patients with equivocal CT findings and for patients in whom there is persistent clinical suspicion of hepatic metastases despite a negative CT examination.     

Clinical and experimental vasogenic edema: in vivo sodium MR imaging. Work in progress

To investigate the sodium magnetic resonance (MR) imaging characteristics of acute vasogenic edema, an experimental canine model was developed. Vasogenic edema was produced in the hemisphere of the dogs by the intraarterial infusion of hypertonic mannitol (25%). This solution opens the blood-brain barrier, allowing the influx of water, electrolytes, and proteins into the brain. The main advantage of this model over the established "cold injury" model is the lack of associated brain necrosis. Two patients with chronic vasogenic edema secondary to well-circumscribed meningiomas also underwent MR imaging. The sodium signal was markedly elevated in both clinical and experimental studies of vasogenic edema fluid compared with signal in healthy brain tissue. Extracellular sodium associated with vasogenic edema displayed MR imaging characteristics similar to that of sodium in serum. There was a trend toward a shortened T2 in edema fluid secondary to the presence of serum macromolecules.     

Intra-articular glucocorticoids in early juvenile chronic arthritis

The efficacy of intra-articular glucocorticoid injections in the early phase of knee joint synovitis was studied in 79 children with juvenile chronic arthritis (42 girls and 37 boys). Half of the injections were given within the first six months from the onset of the disease. The probability of a patient staying in remission was much higher in triamcinolone-treated patients than in patients receiving methylprcdni-solone ( p <0.0005, Breslow statistics). Using multivariate analysis there was a significant association between the length of remission and the synovial fluid polymorphonuclcar leucocyte proportion (SF-PMN%. Patients with a high SF-PMN% tended to have shorter remissions than those with a low SF-PMN% (improvement of the fit in stcpwise model: chi-square = 8.81, p <0.005). The difference between triamcinolone and methylprednisolone groups was still clearly evident two years after injection.     

Anterior cruciate ligament tears: MR imaging compared with arthroscopy and clinical tests

Seventy-nine magnetic resonance (MR) studies of the knee were reviewed in an evaluation of the ability of MR imaging to demonstrate arthroscopically proved anterior cruciate ligament (ACL) tears. MR findings were also compared with the findings of two commonly applied clinical tests of ACL instability: the Lachman test and the anterior drawer test. The sensitivity of MR imaging was 94% (17 of 18), compared with 78% (14 of 18) for the anterior drawer test and 89% (16 of 18) for the Lachman test. The specificity was 100% for all three. Three MR criteria were applied: irregularity or a wavy contour of the anterior margin of the ligament, high-signal-intensity change within the substance of the ligament on T2-weighted images, and discontinuity of that substance. The sagittal T2-weighted image was especially helpful, producing an "arthrographic" effect, in which the anterior margin of the ACL is outlined by high-signal-intensity joint fluid. By demonstrating ACL and other extrameniscal lesions, MR imaging may help clarify the mechanisms of knee injury.     

Novel delivery system enhances efficacy of antiretroviral therapy in animal model for HIV-1 encephalitis.

Most potent antiretroviral drugs (e.g., HIV-1 protease inhibitors) poorly penetrate the blood-brain barrier. Brain distribution can be limited by the efflux transporter, P-glycoprotein (P-gp). The ability of a novel drug delivery system (block co-polymer P85) that inhibits P-gp, to increase the efficacy of antiretroviral drugs in brain was examined using a severe combined immunodeficiency (SCID) mouse model of HIV-1 encephalitis (HIVE). Severe combined immunodeficiency mice inoculated with HIV-1 infected human monocyte-derived macrophages (MDM) into the basal ganglia were treated with P85, antiretroviral therapy (ART) (zidovudine, lamivudine and nelfinavir (NEL)), or P85 and ART. Mice were killed on days 7 and 14, and brains were evaluated for levels of viral infection. Antiviral effects of NEL, P85, or their combination were evaluated in vitro using HIV-1 infected MDM and showed antiretroviral effects of P85 alone. In SCID mice injected with virus-infected MDM, the combination of ART-P85 and ART alone showed a significant decrease of HIV-1 p24 expressing MDM (25% and 33% of controls, respectively) at day 7 while P85 alone group was not different from control. At day 14, all treatment groups showed a significant decrease in percentage of HIV-1 infected MDM as compared with control. P85 alone and combined ART-P85 groups showed the most significant reduction in percentage of HIV-1 p24 expressing MDM (8% to 22% of control) that were superior to the ART alone group (38% of control). Our findings indicate major antiretroviral effects of P85 and enhanced in vivo efficacy of antiretroviral drugs when combined with P85 in a SCID mouse model of HIVE.     

Familial cerebral cavernous haemangioma diagnosed in an infant with a rapidly growing cerebral lesion

Cavernous haemangiomas of the central nervous system are vascular malformations best imaged by MRI. They may present at any age, but to our knowledge only 39 cases in the first year of life have previously been reported. A familial form has been described and some of the underlying genetic mutations have recently been discovered. We present the clinical features and serial MRI findings of an 8‐week‐old boy who presented with subacute intracranial haemorrhage followed by rapid growth of a surgically proven cavernous haemangioma, mimicking a tumour. He also developed new lesions. A strong family history of neurological disease was elucidated. A familial form of cavernous haemangioma was confirmed by identification of a KRIT 1 gene mutation and cavernous haemangiomas in the patient and other family members. We stress the importance of considering cavernous haemangiomas in the context of intracerebral haemorrhage and in the differential diagnosis of rapidly growing lesions in this age group. The family history is also important in screening for familial disease.     

Unsanctifying the sanctuary: challenges and opportunities with brain metastases

While the use of targeted therapies, particularly radiosurgery, has broadened therapeutic options for CNS metastases, patients respond minimally and prognosis remains poor. The inability of many systemic chemotherapeutic agents to penetrate the blood-brain barrier (BBB) has limited their use and allowed brain metastases to become a burgeoning clinical challenge. Adequate preclinical models that appropriately mimic the metastatic process, the BBB, and blood-tumor barriers (BTB) are needed to better evaluate therapies that have the ability to enhance delivery through or penetrate into these barriers and to understand the mechanisms of resistance to therapy. The heterogeneity among and within different solid tumors and subtypes of solid tumors further adds to the difficulties in determining the most appropriate treatment approaches and methods of laboratory and clinical studies. This review article discusses therapies focused on prevention and treatment of CNS metastases, particularly regarding the BBB, and the challenges and opportunities these therapies present.