Bowel Ischemia in Refractory Status Epilepticus: Report of Two Cases and Review of the Literature.

BACKGROUND: Bowel ischemia is a rare life threatening complication seen in patients with refractory status epilepticus (RSE). The few reported cases of bowel ischemia in this setting have been associated with the use continuous barbiturate infusions. We report two patients with RSE in the absence of barbiturate infusion and without clear structural, infectious, anatomic, vascular, or autoimmune etiology. We review the clinical details of the cases and potential factors involved in the development of non-occlusive bowel ischemia in patients with RSE. METHODS: The following is a retrospective review of two cases of non-occlusive mesenteric ischemia that occurred during the management of RSE. The clinical data and the details of pathological examination of the infarcted segments of bowel are presented in both cases. RESULTS: In both cases, the bowel ischemia occurred in the absence of barbiturate infusion or evidence of clear thrombosis, infection, or autoimmune etiology. Case 1 had extensive ischemic necrosis of the small bowel with secondary pseudomembrane formation, and case 2 had full thickness infarction of both the large and small bowel. CONCLUSIONS: The mechanism of bowel infarction in these cases is likely multifactorial and was not associated with barbiturate use. Likely contributors to ischemia include RSE itself, systemic hypotension, vasopressor use, general anesthesia, and abnormal cardiac function. During the management of RSE, every effort must be made to avoid the secondary complications such as bowel ischemia.

Mefloquine in the treatment of progressive multifocal leukoencephalopathy.

Mefloquine, an antimalarial medication with efficacy against JC virus, was used to treat progressive multifocal leukoencephalopathy. A 54-year-old woman with sarcoidosis presented with a progressive cerebellar syndrome. MRI showed lesions affecting the right cerebellum that progressed over time to the brainstem. JC virus was found in the cerebrospinal fluid (CSF), and brain biopsy confirmed the diagnosis of progressive multifocal leukoencephalopathy. Mefloquine 1000 mg/week was initiated 6 months after symptom onset. Clinical progression stopped immediately, and JC virus became undetectable in the CSF. No clinical or imaging evidence of disease progression has occurred over 20 months of follow-up. This is the first report of successful treatment of progressive multifocal leukoencephalopathy with mefloquine.

Challenges facing palliative neurology practice: A qualitative analysis.

PURPOSE: This study aimed to develop a conceptual understanding of the specific characteristics of palliative care in neurology and the challenges of providing palliative care in the setting of neurological illness. METHOD: The study was conducted at London Health Sciences Centre in Canada using grounded theory methodology. Qualitative thematic analysis was applied to focus group (health care providers physicians, nursing, allied health, trainees) and semi-structured interview (patient-caregiver dyads) data to explore challenges facing the delivery of palliative care in neurology. RESULTS: Specific characteristics of neurological disease that affect palliative care in neurology were identified: 1) timelines of disease progression, 2) barriers to communication arising from neurologic disease, 3) variability across disease progression, and 4) threat to personhood arising from functional and cognitive impairments related to neurologic disease. Moreover, three key challenges that shaped and complicated palliative care in neurology were identified: 1) uncertainty with respect to prognosis, support availability and disease trajectory, 2) inconsistency in information, attitudes and skills among care providers, care teams, caregivers and families, and 3) existential distress specific to neurological disease, including emotional, psychological and spiritual distress resulting from loss of function, autonomy and death. These challenges were experienced across groups, but manifested themselves in different ways for each group. CONCLUSIONS: Further research regarding prognosis, improved identification of patients with palliative care needs, developing an approach to palliative care delivery within neurology and the creation of more robust educational resources for teaching palliative neurology are expected to improve neurologists' comfort with palliative care, thereby enhancing care delivery in neurology.

Nitric oxide-mediated regulation of chemosensitivity in cancer cells.

BACKGROUND: Hypoxia in tumors is associated with malignant progression, metastatic spread, and increased resistance to radiotherapy and chemotherapy. Molecular O(2) is required for the cellular production of nitric oxide (NO) by the enzyme NO synthase (NOS), and NO may block components of the adaptive response to hypoxia. Hence, we hypothesized that hypoxia increases drug resistance in tumor cells by inhibiting endogenous NO production. METHODS: Human breast carcinoma (MDA-MB-231) and mouse melanoma (B16F10) cells were pre-exposed to 20% O(2), 5% O(2), or 1% O(2), incubated with a pharmacologic inhibitor of endogenous NO production, and then treated with chemotherapeutic agents. Resistance was assessed by colony-formation assays, and western blot analysis was used to measure NOS protein levels. All P values were two-sided. RESULTS: Incubation of MDA-MB-231 tumor cells in 1% O(2) maximally increased their resistance to doxorubicin and 5-fluorouracil by 8.5-fold (P =.002) and 2.3-fold (P =.002), respectively, compared with incubation in 20% O(2). B16F10 mouse melanoma cells preincubated in 1% O(2) (versus 20% O(2)) for 12 hours exhibited a twofold increase in resistance to doxorubicin (P<.001). The rapid acquisition of drug resistance after exposure to 1% O(2) could be mimicked by incubating the MDA-MB-231 cells for 12 hours with the NOS inhibitor N(G)-monomethyl-Larginine (fivefold increase; P<.001). Conversely, replacement of NO activity by use of the NO-mimetic glyceryl trinitrate (GTN) and diethylenetriamine NO adduct produced statistically significant attenuations in the development of resistance of 59% (P<.001) and 40% (P<.001), respectively, in MDA-MB-231 cells. Treatment of B16F10 cells with GTN produced a 58% reduction in resistance (P<.001). MDA-MB-231 cells expressed all three isoforms of the NOS enzyme at levels that were not altered by exposure to hypoxia. CONCLUSIONS: NO mediates chemosensitivity in tumor cells, and hypoxia-induced drug resistance appears to result, in part, from downstream suppression of endogenous NO production. These results raise the possibility that administration of small doses of NO mimetics could be used as an adjuvant in chemotherapy.