The right thalamic ventral posterolateral nucleus seems to be determinant for macrosomatognosia: a case report.

BACKGROUND: Macrosomatognosiais the illusory sensation of a substantially enlarged body part. This disorder of the body schema, also called "Alice in wonderland syndrome" is still poorly understood and requires careful documentation and analysis of cases. The patient presented here is unique owing to his unusual macrosomatognosia phenomenology, but also given the unreported localization of his most significant lesion in the right thalamus that allowed consistent anatomo-clinical analysis. CASE PRESENTATION: This 45-years old man presented mainly with long-lasting and quasi-delusional macrosomatognosia associated to sensory deficits, both involving the left upper-body, in the context of a right thalamic ischemic lesion most presumably located in the ventral posterolateral nucleus. Fine-grained probabilistic and deterministic tractography revealed the most eloquent targets of the lesion projections to be the ipsilateral precuneus, superior parietal lobule,but also the right primary somatosensory cortex and, to a lesser extent, the right primary motor cortex. Under stationary neurorehabilitation, the patient slowly improved his symptoms and could be discharged back home and, later on, partially return to work. CONCLUSION: We discuss deficient neural processing and integration of sensory inputs within the right ventral posterolateral nucleus lesion as possible mechanisms underlying macrosomatognosia in light of observed anatomo-clinical correlations. On the other hand, difficulty to classify this unique constellation of Alice in wonderland syndrome calls for an alternative taxonomy of cognitive and psychic aspects of illusory body-size perceptions.

Identification of GSK-3 as a Potential Therapeutic Entry Point for Epilepsy.

In view of the clinical need for new antiseizure drugs (ASDs) with novel modes of action, we used a zebrafish seizure model to screen the anticonvulsant activity of medicinal plants used by traditional healers in the Congo for the treatment of epilepsy, and identified a crude plant extract that inhibited pentylenetetrazol (PTZ)-induced seizures in zebrafish larvae. Zebrafish bioassay-guided fractionation of this anticonvulsant Fabaceae species, Indigofera arrecta, identified indirubin, a compound with known inhibitory activity of glycogen synthase kinase (GSK)-3, as the bioactive component. Indirubin, as well as the more potent and selective GSK-3 inhibitor 6-bromoindirubin-3'-oxime (BIO-acetoxime) were tested in zebrafish and rodent seizure assays. Both compounds revealed anticonvulsant activity in PTZ-treated zebrafish larvae, with electroencephalographic recordings revealing reduction of epileptiform discharges. Both indirubin and BIO-acetoxime also showed anticonvulsant activity in the pilocarpine rat model for limbic seizures and in the 6-Hz refractory seizure mouse model. Most interestingly, BIO-acetoxime also exhibited anticonvulsant actions in 6-Hz fully kindled mice. Our findings thus provide the first evidence for anticonvulsant activity of GSK-3 inhibition, thereby implicating GSK-3 as a potential therapeutic entry point for epilepsy. Our results also support the use of zebrafish bioassay-guided fractionation of antiepileptic medicinal plant extracts as an effective strategy for the discovery of new ASDs with novel mechanisms of action.