Repeat CyberKnife Radiosurgery for Trigeminal Neuralgia: Outcomes and Complications.

BACKGROUND: CyberKnife radiosurgery (RS), as an initial first treatment, is recognized as an efficient and safe modality for trigeminal neuralgia (TN). However, knowledge on repeat CyberKnife RS in refractory cases is limited. The objective was to evaluate the clinical outcomes of repeat CyberKnife RS for TN. METHODS: A retrospective review of 33 patients with refractory TN treated a second time with CyberKnife RS from 2009 to 2021. The median follow-up period after the second RS was 26.0 months (range 0.3-115.8). The median dose for the repeat RS was 60 Gy (range 60.0-70.0). Pain relief after the intervention was assessed using the Barrow Neurological Institute scale for pain (I-V). Scores I to IIIb were classified as an adequate pain relief and scores IV-V were classified as a treatment failure. RESULTS: After the second RS, initial adequate pain relief was achieved in 87.9% of cases. The actuarial probabilities of maintaining an adequate pain relief at 6, 12, 24, and 36 months were 92.1%, 74.0%, 58.2%, and 58.2%, respectively. Regarding sustained pain relief, there was no significant difference between the first and the second RS. Sensory toxicity after the first RS was predictive of a better outcome following the second RS. The onset of hypesthesia rate was the same after the first or the second RS (21%). CONCLUSION: Repeat RS is an effective and safe method for the treatment of refractory TN.

CyberKnife radiosurgery for trigeminal neuralgia: a retrospective review of 168 cases.

OBJECTIVE: Gamma Knife radiosurgery is recognized as an efficient intervention for the treatment of refractory trigeminal neuralgia (TN). The CyberKnife, a more recent frameless and nonisocentric radiosurgery alternative, has not been studied as extensively for this condition. This study aims to evaluate the clinical outcomes of a first CyberKnife radiosurgery (CKRS) treatment in patients with medically refractory TN. METHODS: A retrospective cohort study of 166 patients (168 procedures) with refractory TN treated from 2009 to 2021 at the Centre Hospitalier de l'Université de Montréal was conducted. The treatment was performed using a CyberKnife (model G4, VSI, or M6). The treatment median maximum dose was 80 (range 70.0-88.9) Gy. RESULTS: Adequate pain relief, evaluated using Barrow Neurological Institute pain scale scores (I-IIIb), was achieved in 146 cases (86.9%). The median latency period before adequate pain relief was 35 (range 0-202) days. The median duration of pain relief for cases with a recurrence of pain was 8.3 (range 0.6-85.0) months. The actuarial rates of maintaining adequate pain relief at 12, 36, and 60 months from the treatment date were 77.0%, 62.5%, and 50.2%, respectively. There was new onset or aggravation of facial numbness in 44 cases (26.2%). This facial numbness was predictive of better maintenance of pain relief (p < 0.001). The maintenance of adequate pain relief was sustained longer in idiopathic cases compared with cases associated with multiple sclerosis (MS; p < 0.001). CONCLUSIONS: In the authors' experience, CKRS for refractory TN is efficient and safe. The onset or aggravation of facial hypoesthesia after treatment was predictive of a more sustained pain relief, and idiopathic cases had more sustained pain relief in comparison with MS-related cases.

Levodopa-responsive dystonia caused by biallelic PRKN exon inversion invisible to exome sequencing.

Biallelic pathogenic variants in PRKN (PARK2), encoding the E3 ubiquitin ligase parkin, lead to early-onset Parkinson's disease. Structural variants, including duplications or deletions, are common in PRKN due to their location within the fragile site FRA6E. These variants are readily detectable by copy number variation analysis. We studied four siblings with levodopa-responsive dystonia by exome sequencing followed by genome sequencing. Affected individuals developed juvenile levodopa-responsive dystonia with subsequent appearance of parkinsonism and motor fluctuations that improved by subthalamic stimulation. Exome sequencing and copy number variation analysis were not diagnostic, yet revealed a shared homozygous block including PRKN. Genome sequencing revealed an inversion within PRKN, with intronic breakpoints flanking exon 5. Breakpoint junction analysis implicated non-homologous end joining and possibly replicative mechanisms as the repair pathways involved. Analysis of cDNA indicated skipping of exon 5 (84 bp) that was replaced by 93 bp of retained intronic sequence, preserving the reading frame yet altering a significant number of residues. Balanced copy number inversions in PRKN are associated with a severe phenotype. Such structural variants, undetected by exome analysis and by copy number variation analysis, should be considered in the relevant clinical setting. These findings raise the possibility that PRKN structural variants are more common than currently estimated.

Sedative drugs modulate the neuronal activity in the subthalamic nucleus of parkinsonian patients.

Microelectrode recording (MER) is often used to identify electrode location which is critical for the success of deep brain stimulation (DBS) treatment of Parkinson's disease. The usage of anesthesia and its' impact on MER quality and electrode placement is controversial. We recorded neuronal activity at a single depth inside the Subthalamic Nucleus (STN) before, during, and after remifentanil infusion. The root mean square (RMS) of the 250-6000 Hz band-passed signal was used to evaluate the regional spiking activity, the power spectrum to evaluate the oscillatory activity and the coherence to evaluate synchrony between two microelectrodes. We compare those to new frequency domain (spectral) analysis of previously obtained data during propofol sedation. Results showed Remifentanil decreased the normalized RMS by 9% (P < 0.001), a smaller decrease compared to propofol. Regarding the beta range oscillatory activity, remifentanil depressed oscillations (drop from 25 to 5% of oscillatory electrodes), while propofol did not (increase from 33.3 to 41.7% of oscillatory electrodes). In the cases of simultaneously recorded oscillatory electrodes, propofol did not change the synchronization while remifentanil depressed it. In conclusion, remifentanil interferes with the identification of the dorsolateral oscillatory region, whereas propofol interferes with RMS identification of the STN borders. Thus, both have undesired effect during the MER procedure.Trial registration: NCT00355927 and NCT00588926.

Role of CB2 Receptor in the Recovery of Mice after Traumatic Brain Injury.

Cannabis is one of the most widely used plant drugs in the world today. In spite of the large number of scientific reports on medical marijuana, there still exists much controversy surrounding its use and the potential for abuse due to the undesirable psychotropic effects. However, recent developments in medicinal chemistry of novel non-psychoactive synthetic cannabinoids have indicated that it is possible to separate some of the therapeutic effects from the psychoactivity. We have previously shown that treatment with the endocannabinoid 2-AG, which binds to both CB1 and CB2 receptors 1 h after traumatic brain injury in mice, attenuates neurological deficits, edema formation, infarct volume, blood-brain barrier permeability, neuronal cell loss at the CA3 hippocampal region, and neuroinflammation. Recently, we synthesized a set of camphor-resorcinol derivatives, which represent a novel series of CB2 receptor selective ligands. Most of the novel compounds exhibited potent binding and agonistic properties at the CB2 receptors with very low affinity for the CB1 receptor, and some were highly anti-inflammatory. This selective binding correlated with their intrinsic activities. HU-910 and HU-914 were selected in the present study to evaluate their potential effect in the pathophysiology of traumatic brain injury (TBI). In mice and rats subjected to closed-head injury and treated with these novel compounds, we showed enhanced neurobehavioral recovery, inhibition of tumor necrosis factor α production, increased synaptogenesis, and partial recovery of the cortical spinal tract. We propose these CB2 agonists as potential drugs for development of novel therapeutic modality to TBI.

[Comparison between unipolar and bipolar depression: review of functional neuroimaging studies].

Bipolar and unipolar depression are two common mental conditions. The depressive manifestation in both disorders is identical. However, bipolar and unipolar depression require different psychopharmacological treatment. Currently, all patients with depression who have not undergone a manic condition will be diagnosed as suffering from unipolar depression and treated accordingly. This will pose a risk of inducing a manic episode in bipolar depressed subjects. Therefore, establishing a diagnosis of bipolar depression prior to the expression of a manic episode would be highly beneficial. Technological advances in functional neuroimaging have enabled shedding light on the mechanisms underlying affective disorders. In this review, we present a comparison of functional neuroimaging findings between patients who suffer from unipolar and bipolar depression during both symptomatic and euthymic phases of their disease. Most studies focused on two core domains of depression - emotion processing and executive control, and on associated anatomical structures in the limbic system and the prefrontal cortex, respectively. The long-term goal of research on this topic has been to find objective state and trait neuroimaging markers that can be used to improve diagnostic reliability regarding these two subtypes of depression that currently cannot be teased apart clinically.