Mannitol enhances delivery of marrow stromal cells to the brain after experimental intracerebral hemorrhage.

Previous studies show that intravascular injection of human bone marrow stromal cells (hBMSCs) significantly improves neurological functional recovery in a rat model of intracerebral hemorrhage (ICH). In the present study, we tested the hypothesis that mannitol improves the efficiency of intraarterial MSC delivery (i.e., fewer injected cells required for therapeutic efficacy) after ICH. There were four post-ICH groups (N=9): group 1, negative control with only intraarterial injection of 1 million human fibroblasts in phosphate-buffered saline (PBS); group 2, intravenous injection of mannitol alone in PBS (1.5 g/kg); group 3, intraarterial injection of 1 million hBMSCs alone in PBS; and group 4, intravenous injection of mannitol (1.5 g/kg) in PBS followed by intraarterial injection of 1 million hBMSCs in PBS. Group 4 exhibited significantly improved neurological functional outcome as assessed by neurological severity score (NSS) and corner test scores. Immunohistochemical staining of group 4 suggested increased synaptogenesis, proliferating immature neurons, and neuronal migration. The number of hBMSCs recruited to the injured region increased strikingly in group 4. Tissue loss was notably reduced in group 4. In summary, the beneficial effects of intraarterial infusion of MSCs are amplified with intravenous injection of mannitol. Preadministration of mannitol significantly increases the number of hBMSCs located in the ICH region, improves histochemical parameters of neural regeneration, and reduces the anatomical and pathological consequences of ICH.

Postoperative radiosurgery for malignant spinal tumors.

OBJECTIVE: Although, as a primary therapy, radiosurgery for spinal tumors is becoming more common in clinical practice and is associated with encouraging clinical results, we wanted to evaluate outcomes after radiosurgery in a series of postoperative patients. METHODS: We examined the medical records of 18 postoperative patients who received radiosurgical treatment to their residual spinal tumors: metastatic carcinoma (10), sarcoma (3), multiple myeloma/plasmacytoma (4), and giant cell tumor (1). Marginal radiosurgical doses ranged from 6 to 16 Gy (mean, 11.4 Gy) prescribed to the 90% isodose line. All regions of the spine received treatment: 2 cervical, 15 thoracic, and 1 lumbosacral. The volume of irradiated spinal elements receiving 30, 50, and 80% of the total dose ranged from 0.51 to 11.05, 0.19 to 6.34, and 0.06 to 1.73 cm, respectively. Treatment sessions (i.e., patient in to patient out of the room) varied between 20 and 40 minutes. Follow-up ranged from 4 to 36 months (median, 7 mo). RESULTS: Even though significant doses of radiation were delivered to all regions of the spinal cord and nerve roots coincidentally involved in the treatments, only one patient in this series developed progressive symptoms possibly attributable to a toxic effect of the radiosurgery. Of those patients initially presenting with neurological deficits, 92% either remained neurologically stable or improved. CONCLUSION: Our observations suggest that radiosurgery as prescribed in this series of postoperative patients with residual spinal tumor is well-tolerated and associated with little to no significant morbidity.

Livedo reticularis and migraine: a marker for stroke risk?

BACKGROUND AND PURPOSE: Livedo reticularis is a dermatopathy characterized by an irregular, violaceous, netlike pattern which spares the face. Associated with a variety of conditions, it occurs consequent to pathological or physiological narrowing of small and medium arteries at the dermis-subcutis border. Sneddon syndrome refers to the idiopathic coupling of livedo reticularis and stroke in the absence of traditional vascular risk factors. Over 50% of persons with Sneddon syndrome describe a history of headache. We undertook this study to determine the frequency of livedo reticularis in our headache clinic. METHODS: We performed a retrospective chart review of consecutive patients attending a headache clinic over a period of 6 months. The patients had all been seen by one physician (G.E.T.) who noted the presence or absence of livedo reticularis. The charts were reviewed for age, sex, and vascular risk factors, including current use of oral contraceptives, and history of smoking, coronary artery disease, hypertension, diabetes mellitus, stroke, or arthritis. RESULTS: Charts from 133 patients with headache were reviewed (24 men [18%], 109 women [82%]; mean age, 42 +/- 13 years). Livedo reticularis was observed in 29 patients (22%) and in a similar proportion in men (25%) and women (21%). When we stratified the migraine population by presence or absence of livedo, we found no significant difference in age (44.5 versus 41.7 years, P =.16). There was a higher frequency of stroke diagnosis in the cohort with livedo reticularis (28%[8 of 29] versus 7%[7 of 104], P =.005), but we found no significant differences in frequency of hypertension, oral contraceptive use, diabetes mellitus, coronary artery disease, arthritis, or cigarette smoking. CONCLUSIONS: In our headache clinic, livedo reticularis is present in more than one fifth of patients. A history of stroke is more frequent in this subset of migraineurs, raising the possibility that livedo reticularis can be used as a clinical marker to identify those migraineurs with an increased risk of stroke.