Faculty Bibliography

Background: Trigeminal neuralgia (TN) is a recognized pain condition the treatment of which can be very challenging. Various surgical interventions can be applied in cases of therapy-resistance to drug treatments. The central lateral thalamotomy (CLT) against neurogenic (or neuropathic) pain is based on multiarchitectonic histological as well as physiopathological studies, and integrates the nucleus in a large thalamocortical (TC) and corticocortical network responsible for the sensory, cognitive and affective/emotional components of pain. The advent of the magnetic resonance imaging guided high intensity focused ultrasound (MRgFUS) brought a strong reduction in morbidity and increase in accuracy compared to penetration techniques. Objective: This study was aimed at analyzing the outcome of bilateral MRgFUS CLT for chronic therapy-resistant trigeminal pain, all performed in one single center. Methods: Patients were categorized in Classical, Idiopathic and Secondary TN. By definition, paroxysms lasted for seconds up to 2 min. All patients were screened for trigeminal neurovascular conflict. In case of classical TN, microvascular decompression was proposed. Therapy-resistance and thus indication for MRgFUS CLT was based on the lack of efficacy and/or side effects of antiepileptic and antidepressant drugs. Good outcome was defined by a pain relief ≥50%. Results: Eight patients suffering from chronic therapy-resistant trigeminal neuralgia were treated. All suffered from pain with paroxysmal character. Six patients reported additionally continuous pain. Mean follow-up was 53 months (range: 12-92, median: 60 months). The mean pain relief assessed by patients was 51% (median: 58%, range: 0-90%) at 3 months, 71% (median: 65%, range: 40-100%) at 1 year and 78% (median: 75%, range: 50-100%) at their longest follow-up. This represents 63% good outcomes at 3 months, 88% at 1 year and 100% at last follow-up. Frequency of the mean pain paroxysms decreased from 84 per day preoperative to 3.9 at 1 year postoperatively. There were no serious adverse events in this series. Conclusion: Our study provides preliminary support for the safety and efficacy of MRgFUS CLT, a histologically and pathophysiologically based medial thalamotomy against chronic therapy-resistant trigeminal neuralgia.

Animals are capable of detecting odorants in a single sniff, at extremely low concentrations. This ability is crucial for survival, yet it is unknown how the olfactory system supports detection at the perceptual limit. In the mouse olfactory bulb, inhalation of different odors leads to changes in the set of neurons activated, as well as when neurons are activated relative to each other (synchrony), and the onset of inhalation (latency). A key question is which features of stimulus evoked activity (e.g. rate, synchrony, or latency) are used to guide detection behavior? Here, we probed the sensitivity of mice to perturbations across each stimulus dimension using holographic two-photon (2P) optogenetic stimulation of olfactory bulb neurons, with cellular and single action potential resolution and millisecond precision. We found that mice can detect single action potentials evoked synchronously across <20 olfactory bulb neurons. Mice exhibited this sensitivity for artificial ensembles of mitral cells, as well as mixed ensembles of mitral and granule cells. Further, we discovered that detection depends strongly on the synchrony of activation across neurons, with detectability falling to near-chance levels with an imposed stimulus spread 3 30 ms, while detection performance was minimally perturbed by changes in the latency of activation relative to inhalation. These results reveal that mice are acutely attuned to single neurons and action potentials in olfactory circuits, and that synchrony across neurons may be a critical feature supporting the perceptibility of sparse ensemble activity signals

Background: Our previous study showed that PH without a transplant (tx) had worse HRQoL compared to the US Standard Population and worsened with increased stone frequency. We now show the first longitudinal HRQoL profiles for PH patients with transplants.
Method(s): PH participants were enrolled from the Rare Kidney Stone Consortium registry. HRQoL was measured with a generic non-disease specific instrument (SF-36v2). Results were calculated as norm-based scores (NBS) based on US Standard Population (Mean domain score = 50). We created three groups based on the time of last stone event (<= 30 days, 31 - 365 days, >;366 days). The study compared HRQoL for participants with a kidney and/or liver transplant over 5 different time points.
Result(s): This sub-sample included 100 surveys of 32 PH participants (16 males and 16 females) with a tx. The mean age was 47 years for both males and females. This subsample includes 24 participants with liver/kidney tx (75%) and 8 with kidney tx only (25%). Participants with only a kidney tx reported significantly more stone events within a year (26% vs 13%, X2 =0.028). Two way ANOVA did not find a change in HRQoL profiles over time for PH participants with kidney or kidney/liver tx (figure). Most mean domain scores are 50 or above, except for the domain of General Health which was less. Participants with only a kidney tx scored significantly lower in role physical, bodily pain, general health, social function, and physical component score (data not shown) than participants with kidney/liver tx. There was no difference between male and female participants over time.
Conclusion(s): PH participants with kidney/liver tx achieve better HRQoL, measured with a non-disease specific generic instrument, than those with kidney alone; both are better when compared to the US Standard Population. The majority of PH participants with a tx are stone-free, with a direct beneficial impact on their HRQoL