Brachial plexopathy as a rare presenting manifestation of scorpion envenomation.

We report a patient who experienced a rare manifestation of an acute, severe brachial plexopathy as the initial complication of scorpion (presumed Hemiscorpius lepturus species) envenomation. Features suggesting conduction block, due to either proximal demyelination or ion channel dysfunction, along with axonal loss were seen on serial electrophysiological studies. Possible mechanisms of the brachial plexopathy include direct compression from tissue edema or a toxic effect on the membrane channels along the nerve.

The peripheral neuropathy evaluation in an office-based neurology setting.

Peripheral neuropathy is the most common neuromuscular disorder encountered in a neurologic practice. The evaluation of patients with suspected peripheral neuropathy can be a challenging endeavor for the neurologist. Determining the pattern of clinical involvement and the nerve modalities affected can help to generate a differential diagnosis and design an approach to determine a potential cause. The combination of clinical features, electrodiagnostic testing, and ancillary laboratory studies may be used to determine the etiology. As the most common acquired etiology of peripheral neuropathy is diabetes, careful testing for impaired glucose metabolism is an important part of any diagnostic evaluation.

FUNDUS FINDINGS IN A PATIENT WITH α-METHLYACYL-COA RACEMASE DEFICIENCY.

PURPOSE: To describe the ocular findings in a patient with α-methylacyl-CoA racemase deficiency. METHODS: Case report. RESULTS: A 45-year-old white man presented with seizures, hemiparesis, and altered mental status. As a part of an extensive investigation, an ophthalmic evaluation was performed. Funduscopic examination of both eyes showed a bull's-eye pattern pigmentary maculopathy. Fluorescein angiography demonstrated a prominent choroidal circulation without dye leakage. Optical coherence tomography showed a significant thinning of the macula with moderate nerve fiber layer loss. Serum pristanic levels were significantly elevated, and α-methylacyl-CoA racemase deficiency was confirmed by urine and bile analysis. The patient's clinical condition improved after plasma exchange and dietary restriction of fatty acids. CONCLUSION: α-Methylacyl-CoA racemase deficiency is a rare peroxisomal enzyme disorder previously described in only six patients, two of whom had pigmentary retinopathies. This article describes the third patient with retinopathy and the first with published fundus findings.

An adult onset case of alpha-methyl-acyl-CoA racemase deficiency.

α-Methyl-acyl-CoA-racemase (AMACR) deficiency (OMIM 604489) is a rare peroxisomal disorder with a variable age of onset from infancy to late adulthood. We describe a 45-year-old male with a history of seizures who presented with relapsing encephalopathy. Laboratory studies revealed an elevated serum pristanic acid concentration, an elevated pristanic/phytanic acid ratio, as well as the previously described homozygous mutation in the AMACR gene, c.154T>C, consistent with AMACR deficiency. This homozygous mutation is associated with a variable phenotype ranging from neonatal cholestasis to late-onset sensorimotor neuropathy. Dietary pristanic acid restriction was attempted to improve clinical status and the patient has remained in remission for more than 16 months.

Efflux of drugs and solutes from brain: the interactive roles of diffusional transcapillary transport, bulk flow and capillary transporters.

We examined the roles of diffusion, convection and capillary transporters in solute removal from extracellular space (ECS) of the brain. Radiolabeled solutes (eight with passive distribution and four with capillary or cell transporters) were injected into the brains of rats (n=497) and multiple-time point experiments measured the amount remaining in brain as a function of time. For passively distributed compounds, there was a relationship between lipid:water solubility and total brain efflux:diffusional efflux, which dominated when k(p), the transcapillary efflux rate constant, was >10(0) h(-1); when 10(-1)

Isolation of drug delivery from drug effect: problems of optimizing drug delivery parameters.

A recurring question in the treatment of malignant brain tumors has been whether treatment failure is due to inadequate delivery or ineffective drugs. To isolate these issues, we tested a paradigm in which the "therapeutic" agent was a toxin about which there could be no question of efficacy, provided it was delivered in adequate amounts; we used 10% formalin. We infused 10% formalin into 5- to 8-mm subcutaneous RG-2 and D54-MG gliomas at increasing rates until we achieved 100% tumor cell kill. In RG-2 gliomas, infusions of 10 microl/h x 7 days, and 2, 4, 6, and 8 microl/min x 2 h failed to kill tumors, although growth was delayed, while infusion rates of 12 microl/min x 60 min and 48 microl/min x 15 min produced 100% tumor kill. In D54-MG tumors, infusions of 4, 8, and 24 microl/min produced 100% tumor kill. 14C-Formalin autoradiographs showed a heterogeneous distribution after infusions of 2 microl/min x 2 h, whereas infusions of 48 microl/min x 15 min showed a homogeneous distribution within the tumor, but more than 95% of tissue radioactivity was found in tissue surrounding tumor. Drug delivery remains a major issue in brain tumor treatment: Distribution inhomogeneity, rapid efflux, and consequent treatment failures are likely due to high interstitial fluid pressure. Because the infusion rates being used in the treatment of human brain tumors are low and the tumors are larger, treatment failures can be expected on the basis of inadequate drug delivery alone, regardless of the effectiveness of the drug.

Comparative pharmacokinetics of 14C-sucrose in RG-2 rat gliomas after intravenous and convection-enhanced delivery.

We compared tissue and plasma pharmacokinetics of 14C-sucrose in subcutaneous RG-2 rat gliomas after administration by 3 routes, intravenous bolus (i.v.-B; 50 microCi over 30 s), continuous i.v. infusion (i.v.-C, 50 microCi at a constant rate), and convection-enhanced delivery (CED, 5 microCi infused at a rate of 0.5 microl/min), and for 3 experimental durations, 0.5, 2, and 4 h. Plasma, tumor, and other tissue samples were obtained to measure tissue radioactivity. Plasma radioactivity in the CED group increased exponentially and lagged only slightly behind the IV-C group. After 90 min, plasma values were similar in all. Mean tumor radioactivity was 100 to 500 times higher in the CED group at each time point than in the i.v.-B and i.v.-C groups. Tumor radioactivity was homogeneous in the i.v. groups at 0.5 h and inhomogeneous at 1 and 2 h. In CED, radioactivity distribution was inhomogeneous at all 3 time points; highest concentrations were in tissue around tumor and in necrosis, while viable tumor contained the lowest and sometimes negligible amounts of isotope. Systemic tissue radioactivity values were similar in all groups. Efflux of 14C-sucrose from tumors was evaluated in intracerebral tumors (at 0.5, 1, 2, and 4 h) and subcutaneous tumors (at 0 to 0.5 h). Less than 5% of 14C activity remained in intracerebral tumors at each time point. The efflux half-time from the subcutaneous tumors was 7.3 +/- 0.7 min. These results indicate rapid efflux of drug from brain tumor and marked heterogeneity of drug distribution within tumor after CED administration, both of which may be potentially limiting factors in drug delivery by this method.