MRI in Multiple Sclerosis: What’s Inside the Toolbox?

Magnetic resonance imaging (MRI) has played a central role in the diagnosis and management of multiple sclerosis (MS). In addition, MRI metrics have become key supportive outcome measures to explore drug efficacy in clinical trials. Conventional MRI measures have contributed to the understanding of MS pathophysiology at the macroscopic level yet have failed to provide a complete picture of underlying MS pathology. They also show relatively weak relationships to clinical status such as predictive strength for clinical progression. Advanced quantitative MRI measures such as magnetization transfer, spectroscopy, diffusion imaging, and relaxometry techniques are somewhat more specific and sensitive for underlying pathology. These measures are particularly useful in revealing diffuse damage in cerebral white and gray matter and therefore may help resolve the dissociation between clinical and conventional MRI findings. In this article, we provide an overview of the array of tools available with brain and spinal cord MRI technology as it is applied to MS. We review the most recent data regarding the role of conventional and advanced MRI techniques in the assessment of MS. We focus on the most relevant pathologic and clinical correlation studies relevant to these measures.     

Regulation of dimethylnitrosamine metabolism by androgenic hormones

Hormonal regulation of dimethylnitrosamine (DMN) metabolism by mouse kidney microsomes was investigated using an in vitro mutagenesis system that detects bioactive metabolites of this procarcinogen by measuring reverse mutation in Salmonella typhimurium his auxotrophs. Induction of microsomal DMN metabolizing enzymes was androgen-specific. Testosterone and medroxyprogesterone acetate were active inducers, d/1 norgestrel was less active, while epitestosterone, estradiol, and progesterone were ineffective. The response to testosterone and medroxyprogesterone acetate was time- and dose-dependent. Eleven strains of inbred mice were screened for their response to exogenous testosterone. DMN metabolism was stimulated in all mouse strains except for RF/J mice. Other androgenic end points were responsive in the latter strain, however. These observations suggest that induction of renal microsomal DMN metabolising enzymes is androgen-specific and probably mediated via the androgen receptor. The insensitivity of RF/J mice may be due to a mutation affecting a key step in the enzymatic activation of DMN.     

Tamoxifen citrate loaded solid lipid nanoparticles (SLN): preparation, characterization, in vitro drug release, and pharmacokinetic evaluation

Solid lipid nanoparticles (SLN) were prepared by emulsification and high pressure homogenization technique and characterized by size analysis and differential scanning calorimetry. The influence of experimental factors such as homogenization pressure, time, and surfactant concentration on the nanoparticle size and distribution were investigated to optimize the formulation. Homogenization at 15,000 psi for 3 cycles was found to be optimum and resulted in smaller sized nanoparticles. In case of tristearin SLN (TSSLN), tripalmitin SLN (TPSLN), and glycerol behenate SLN (GBSLN), the relatively smaller sized nanoparticles were obtained with 3% sodium tauroglycocholate. The SLN were loaded with an anticancer agent, tamoxifen citrate (TC). The TC-loaded TSSLN shown lower entrapment efficiency (78.78%) compared to the TPSLN (86.75%) and GBSLN (98.64%). Short term stability studies indicated a significant increase in size of nanoparticles when stored at 500C, compared to those stored at 30 degrees C and 4 degrees C. The particle destabilization upon storage in case of all the types of nanoparticles studied was in the order of day light > artificial light > dark. An ultraviolet (UV) spectrophotometric method of estimation of tamoxifen in rat plasma was developed and validated. The TC-loaded TSSLN was administered to the rats intravenously and the pharmacokinetic parameters in the plasma were determined. The t(1/2) and mean residence time of TC-loaded TSSLN in plasma was about 3.5-fold (p < 0.001) and 3-fold (p < 0.001) higher, respectively, than the free tamoxifen, indicating the potential of TC-loaded TSSLN as a long circulating system in blood. Thus the above mentioned solid lipid nanoparticles can be a beneficial system to deliver tamoxifen to cancer tissues through enhanced permeability and retention (EPR) effect.     

Successful complete regression of isolated intramedullary spinal cord metastases from epithelial ovarian carcinoma with chemotherapy and radiotherapy

Advances in the management of ovarian cancer by use of aggressive surgery and effective platinum-based chemotherapy have prolonged survival; this may have resulted in an alteration of the metastatic pattern of the disease and spread to unusual sites (e.g, CNS) has become more common. Also, with the availability of more sensitive imaging techniques, these tumors are being diagnosed with increasing frequency. Intramedullary spinal cord metastasis is rare. We report one such case treated successfully with chemotherapy and radiotherapy with long-term survival.     

Doxorubicin hydrochloride (Adriamycin) cardiotoxicity evaluated by sequential radionuclide angiocardiography

A prospective study was carried out to evaluate the role of radionuclide angiocardiography (CEF) in accessing subclinical cardiotoxicity secondary to Adriamycin (doxorubicin) therapy in 73 women with gynecologic malignancies. Based on the findings of this study, the authors conclude that all patients should have an initial CEF before Adriamycin therapy. In patients with an initial CEF of greater than or equal to 55, frequent determinations are not necessary unless there is a significant decrease from the initial CEF. Patients with low normal initial CEF or significant difference between the initial CEF and minimum CEF should have CEF studies performed at more frequent intervals. Patients who develop below normal CEF should have Adriamycin withheld and CEF should be repeated at more frequent intervals. If the CEF returns to normal Adriamycin therapy can be reinstated. Patients requiring continuation of Adriamycin past 550 mg/m2, can safely do so as long as the CEF values remain normal.     

Unusual phenobarbitone sensitivity

Summary A case is reported of an unusual, near fatal sensitization reaction to phenobarbital consisting of fever, oral ulceration, generalised lymphadenopathy, hepatomegaly and exfoliative dermatitis in an 8-year-old girl. From the Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, 11.     

An Unusual Presentation of Foreign Body in the Common Carotid Artery

Penetrating trauma to neck resulting in arteriovenous (AV) fistula and aneurysms involving the carotid system are uncommon injuries with life-threatening consequences. We report here a case of a young factory worker who developed a traumatic AV fistula with false aneurysm, with however, no other complications. He was successfully operated when he presented to us two months after the injury and is doing well in follow-up.