Effects of direct transplantation of multipotent mesenchymal stromal/stem cells into the demyelinated spinal cord.

The adult bone marrow contains a population of multipotent mesenchymal stromal cells (MSCs), defined by plastic adherence, expression of stromal cell surface markers, and differentiation into mesenchymal lineages. There has been much interest in the possible therapeutic use of MSCs in the treatment of demyelinating diseases of the central nervous system. One therapeutic possibility is that these cells may be able to remyelinate when directly injected into the demyelinated spinal cord. Here we examine the effects of direct transplantation of green fluorescent protein (GFP)-labeled MSCs into a model of focal spinal cord demyelination induced by ethidium bromide. We demonstrate that direct intralesional injection of undifferentiated MSCs does not lead to remyelination. Furthermore, we report that transplanted MSCs migrate into areas of normal tissue, deposit collagen, and are associated with axonal damage. These findings support the need for further experimental evaluation of the safety and efficacy of direct parenchymal injection of MSCs into demyelinated lesions and highlight an important issue regarding potential clinical consequences of culture heterogeneity of MSCs between centers.

Long QT syndrome presenting as epileptic seizures in an adult.

A 50 year old woman with a previous diagnosis of epilepsy presented to the emergency department with a generalised seizure. Her admission ECG showed QT prolongation secondary to bradycardia and a subsequent seizure in the department demonstrated that these events were secondary to cerebral hypoperfusion during episodes of torsades de pointes. This case illustrates how long QT syndrome can masquerade convincingly as epilepsy, delaying treatment and exposing the patient to a high risk of sudden cardiac death. Careful ECG analysis is recommended for all patients presenting with seizures.

Early recurrence of benign meningioma correlates with expression of mini-chromosome maintenance-2 protein.

We have investigated the potential utility of monoclonal antibodies against mini-chromosome maintenance-2 protein (Mcm2) in predicting meningioma recurrence. MCM proteins are members of the DNA-binding prereplicative complex and are essential for eukaryotic DNA replication. They are present throughout the cell cycle, but are down-regulated in quiescence and cell differentiation, making them specific markers of proliferating cells. We analysed 10 benign meningiomas that subsequently recurred within a 5-year period, together with 20 matched non-recurrent benign meningiomas. There was no significant correlation between histological subtype, mitotic count or Ki-67 labelling index and tumour recurrence. We observed that whilst the average Mcm2 labelling index (LI) of the tumour section as a whole (LI(Ave)) is not significantly different between recurrent and nonrecurrent meningiomas, the Mcm2 labelling index in the area of highest proliferative activity within the tumour section (LI(Max)) is significantly higher in recurrent meningiomas (p < 0.0001). Seven out of the 10 recurrent meningiomas displayed a Mcm2 LI((Max) greater than 30%, compared to 0 out of 20 for non-recurrent tumours. In conclusion, these results suggest that analysis of Mcm2 expression may facilitate identification of patients with a high risk of meningioma recurrence, for whom adjuvant radiotherapy may be of benefit.