ATP activates damage-sensing neurons (nociceptors) and can evoke a sensation of pain. The ATP receptor P2X3 is selectively expressed by nociceptors and is one of seven ATP-gated, cation-selective ion channels. Here we demonstrate that ablation of the P2X3 gene results in the loss of rapidly desensitizing ATP-gated cation currents in dorsal root ganglion neurons, and that the responses of nodose ganglion neurons to ATP show altered kinetics and pharmacology resulting from the loss of expression of P2X(2/3) heteromultimers. Null mutants have normal sensorimotor function. Behavioural responses to noxious mechanical and thermal stimuli are also normal, although formalin-induced pain behaviour is reduced. In contrast, deletion of the P2X3 receptor causes enhanced thermal hyperalgesia in chronic inflammation. Notably, although dorsal-horn neuronal responses to mechanical and noxious heat application are normal, P2X3-null mice are unable to code the intensity of non-noxious 'warming' stimuli.

Limbic encephalitis (LE) is often associated with lung, thymic, or testicular tumours and antibodies to Hu, CV2, or Ma2 (Ta) antigens. In these cases, it generally has a poor prognosis. Here we describe two patients with symptoms of LE, negative for typical paraneoplastic antibodies, in whom antibodies to voltage-gated potassium channels (VGKC) were detected retrospectively in serial serum samples. Patient 1 had a thymoma recurrence, but in patient 2 no tumour has been detected in the years following presentation. Plasma exchange was effective in reducing VGKC antibody levels, with substantial improvement in mental symptoms in patient 1. In patient 2, the VGKC antibodies fell spontaneously over two years, with almost complete recovery of mental function. Although neither patient had obvious neuromyotonia at presentation, both showed excessive secretions. We suggest that patients with limbic symptoms and excessive secretions should be tested for VGKC antibodies, and, if they are present, prompt and effective immunosuppressive treatment should be considered.

Across a large, treatment-resistant population, add-on perampanel was retained for ≥1 year by 48% of individuals, and 9% were seizure-free for ≥6 months. TEAEs were in line with previous reports in routine clinical use, and less frequent than in the clinical trial setting. No new or unexpected TEAEs were seen. Despite the limitations of observational studies, our data indicate that some individuals may derive a marked benefit from the use of perampanel.

In the healthy human brain, evidence for dissociable memory networks along the anterior-posterior axis of the hippocampus suggests that this structure may not function as a unitary entity. Failure to consider these functional divisions may explain diverging results among studies of memory adaptation in disease. Using task-based and resting functional MRI, we show that chronic seizures disrupting the anterior medial temporal lobe (MTL) preserve anterior and posterior hippocampal-cortical dissociations, but alter signaling between these and other key brain regions. During performance of a memory encoding task, we found reduced neural activity in human patients with unilateral temporal lobe epilepsy relative to age-matched healthy controls, but no upregulation of fMRI signal in unaffected hippocampal subregions. Instead, patients showed aberrant resting fMRI connectivity within anterior and posterior hippocampal-cortical networks, which was associated with memory decline, distinguishing memory-intact from memory-impaired patients. Our results highlight a critical role for intact hippocampo-cortical functional communication in memory and provide evidence that chronic injuryinduced functional reorganization in the diseased MTL is behavioral inefficient.

Right hemisphere activation during functional imaging studies of language has frequently been reported following left hemisphere injury. Few studies have anatomically characterized the specific right hemisphere structures engaged. We used functional MRI (fMRI) with verbal fluency tasks in 12 right-handed patients with left temporal lobe epilepsy (LTLE) and 12 right-handed healthy controls to localize language-related activity in the right inferior frontal gyrus (RIFG). During the phonemic task, LTLE patients activated a significantly more posterior region of the right anterior insula/frontal operculum than healthy controls (P = 0.02). Activation of the left inferior frontal gyrus (LIFG) did not differ significantly between the two groups. This suggests that, following left hemisphere injury, language-related processing in the right hemisphere differs from that with a functionally normal left hemisphere. The localization of activation in the left and right inferior frontal gyri was determined with respect to the anatomical sub-regions pars opercularis (Pop), pars triangularis (Ptr) and pars orbitalis (Por). In the LIFG, both healthy controls (8 out of 12) and LTLE patients (9 out of 12) engaged primarily Pop during phonemic fluency. Activations in the RIFG, however, were located mostly in the anterior insula/frontal operculum in both healthy controls (8 out of 12) and LTLE patients (8 out of 12), albeit in distinct regions. Mapping the locations of peak voxels in relation to previously obtained cytoarchitectonic maps of Broca's area confirmed lack of homology between activation regions in the left and right IFG. Verbal fluency-related activation in the RIFG was not anatomically homologous to LIFG activation in either patients or controls. To test more directly whether RIFG activation shifts in a potentially adaptive manner after left hemisphere injury, fMRI studies were performed in a patient prior to and following anatomical left hemispherectomy for the treatment of Rasmussen's encephalitis. An increase in activation magnitude and posterior shift in location were found in the RIFG after hemispherectomy for both phonemic and semantic tasks. Together, these results suggest that left temporal lobe injury is associated with potentially adaptive changes in right inferior frontal lobe functions in processing related to expressive language.