Léo Cantin

Bilateral stereotactic anterior capsulotomy for obsessive-compulsive disorder: long-term follow-up

Background and purpose Psychosurgery, such as anterior capsulotomy, is a therapeutic option for treatment-resistant obsessive-compulsive disorder (OCD). In this paper, we present a prospective, long-term follow-up study aimed at evaluating both the efficacy and the safety of anterior capsulotomy for the treatment of severe, refractory OCD. Methods Twenty-four patients were surgically treated in our centre between 1997 and 2009, 19 of whom were included in this study. Patients were assessed at 3, 6, 12, and 24 months and last follow-up (mean of 7 years) was carried out by phone. OCD symptom severity was evaluated using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). A patient with an improvement rate of over 35% in the Y-BOCS score was considered a responder, while a patient with a 25% improvement was considered a partial responder. Results With a mean improvement of 31% in the Y-BOCS score at long-term follow-up, 36.8% of the patients responded fully to the procedure and 10.5% were considered partial responders, for an overall response rate of 47.3% of patients. At the end of the study, 3/19 patients had recovered (Y-BOCS score <8) and 3/19 were in remission (Y-BOCS score <16). No cases of mortality were reported and the overall adverse event rate was 57.9%. Only 2 patients had permanent surgical complications. Conclusions Anterior capsulotomy is an effective and safe technique for the treatment of severe refractory OCD in patients who have no other alternative to improve their symptoms.

Gap junctions in human glioblastomas: implications for suicide gene therapy.

Glioblastoma is a very aggressive astrocytic tumor and most patients have 1-year survival time after diagnosis. A promising therapeutic strategy is the local delivery of the herpes simplex virus thymidine kinase gene in the tumor bed followed by ganciclovir treatment. The presence of functional gap junctions is highly relevant for the success of suicide gene therapy. Connexins are expressed in practically all tissues and form gap junctions that allow intercellular communication. Connexin 43 (Cx43) is the major connexin member being expressed in astrocytes but its status in glioblastoma is not well defined. We have investigated by immunofluorescence the presence of Cx43 in 74 human glioblastoma samples; its expression was detected in 77% of the samples analyzed. We report here that glioblastoma is a heterogenous disease as regards Cx43 expression with presentations, in which Cx43 expression is unaltered, reduced or totally lost. A predominant Cx43 cytoplasmic localization was observed in four out of eight primary glioblastoma cultures that we have established. This aberrant localization reduced gap junctionnal intercellular communication by 50 to 75% as compared with primary cell cultures displaying gap junctional plaques. However, the bystander effect evaluated after lentiviral delivery of the herpes simplex virus thymidine kinase gene and ganciclovir treatment was detected in all Cx43-positive primary cell cultures, and it was independant of the Cx43 localization. These findings may have important clinical implications for the design of anticancer cytotoxic therapies that rely on the gap junction-mediated bystander effect for their success.

Intrathecal Morphine Therapy‐Related Granulomas: Faster to Grow than Thought

Complications of intrathecal drug delivery are relatively rare. Of these, infections, cutaneous erosion, and granulomas account for the most common complications. The latter is often noticed when the patient shows signs of sedation and/or reduced pain relief. Granulomas have always been considered to develop over a long period of time, usually calculated in months. Here, we present a case where a catheter‐tip granuloma formed within 5 weeks of intrathecal morphine. The patient was carrying an intrathecal pump for 3 months when it was diagnosed. Probable causes of the formation are discussed.

Epidemiological study of ruptured intracranial aneurysms in the Saguenay-Lac-Saint-Jean region (Quebec, Canada)

BACKGROUND Using a population-based register of the Saguenay-Lac-Saint-Jean region (Quebec, Canada), the genealogical reconstruction of 533 individuals with intracranial aneurysm (IA) showed a familial aggregation (the presence of aneurysm in two or more first- to third-degree relatives) for 159 (29.8%) of them; this proportion is much higher than reported elsewhere. OBJECTIVE As part of an ongoing project to assess a genetic predisposition to intracranial aneurysms in the Saguenay-Lac-Saint-Jean population, the objective of the present study was to determine whether age-specific rates of reputed cerebral aneurysms were higher than in other populations. DESIGN A retrospective study of cases of proven ruptured IAs which were hospitalized during the 1973 to 1992 period was conducted. Age-adjusted rates were computed and compared to those reported in the Helsinki population. RESULTS We identified 412 cases of ruptured aneurysms. The age-adjusted incidence rate was 7.2/100,000/year (6.2 for men, 8.1 for women), which is similar to the incidence rates reported in other studies. Although the mean age at time of rupture was younger (46.6 years +/- 13.8) than usually reported, no increase in age-specific incidence rates was detected. CONCLUSIONS The results of this epidemiological study neither support nor reject the hypothesis of a genetic predisposition to intracranial aneurysms in the Saguenay-Lac-Saint-Jean population.

Changes in Vowel Articulation with Subthalamic Nucleus Deep Brain Stimulation in Dysarthric Speakers with Parkinson's Disease

Purpose. To investigate changes in vowel articulation with the electrical deep brain stimulation (DBS) of the subthalamic nucleus (STN) in dysarthric speakers with Parkinsons disease (PD). Methods. Eight Quebec-French speakers diagnosed with idiopathic PD who had undergone STN DBS were evaluated ON-stimulation and OFF-stimulation (1 hour after DBS was turned off). Vowel articulation was compared ON-simulation versus OFF-stimulation using acoustic vowel space and formant centralization ratio, calculated with the first (F1) and second formant (F2) of the vowels /i/, /u/, and /a/. The impact of the preceding consonant context on articulation, which represents a measure of coarticulation, was also analyzed as a function of the stimulation state. Results. Maximum vowel articulation increased during ON-stimulation. Analyses also indicate that vowel articulation was modulated by the consonant context but this relationship did not change with STN DBS. Conclusions. Results suggest that STN DBS may improve articulation in dysarthric speakers with PD, in terms of range of movement. Optimization of the electrical parameters for each patient is important and may lead to improvement in speech fine motor control. However, the impact on overall speech intelligibility may still be small. Clinical considerations are discussed and new research avenues are suggested.

The effects of subthalamic deep brain stimulation on metaphor comprehension and language abilities in Parkinson’s disease

The effects of subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinsons disease (PD) on different language abilities are still controversial and its impact on high-level language abilities such as metaphor comprehension has been overlooked. The aim of this study was to determine the effects of STN electrical stimulation on metaphor comprehension and language abilities such as lexical and semantic capacities. Eight PD individuals with bilateral STN-DBS were first evaluated OFF-DBS and, at least seven weeks later, ON-DBS. Performance on metaphor comprehension, lexical decision, word association and verbal fluency tasks were compared ON and OFF-DBS in addition to motor symptoms evaluation. STN stimulation had a significant beneficial effect on motor symptoms in PD. However, this stimulation did not have any effect on metaphor comprehension or any other cognitive ability evaluated in this study. These outcomes suggest that STN stimulation may have dissociable effects on motor and language functions.

Transient executive dysfunction following STNDBS in Parkinson's disease.

Deep brain stimulation (DBS) is an alternative treatment for patients with advanced Parkinson’s disease (PD) inadequately or insufficiently controlled with pharmacological treatments. It consists of implanting an electrode in a specific subcortical region to modulate its electrical activity. The structure most often targeted in PD is the subthalamic nucleus (STN). Chronic high frequency stimulation of the STN helps to reduce tremor, dyskynesia and medication doses, and its effectiveness is now well established1. However, there is also a risk that STN-DBS could lead to cognitive side effects but evidence of this is scarce and controversial. Some studies showed minimal influence of STN-DBS on cognition2, while others reported decline3,4 in cognitive efficiency in similar (verbal fluency, executive functions and working memory) or different domains (e.g. improved vs. reduced performance on procedural and declarative memory respectively5). The purpose of this study was to characterize the cognitive performance of PD subjects having undergone bilateral STNDBS and to identify shortand longer-term effects on various domains of cognition.

Articulatory Changes in Vowel Production following STN DBS and Levodopa Intake in Parkinson’s Disease

Purpose. To investigate the impact of deep brain stimulation of the subthalamic nucleus (STN DBS) and levodopa intake on vowel articulation in dysarthric speakers with Parkinsons disease (PD). Methods. Vowel articulation was assessed in seven Quebec French speakers diagnosed with idiopathic PD who underwent STN DBS. Assessments were conducted on- and off-medication, first prior to surgery and then 1 year later. All recordings were made on-stimulation. Vowel articulation was measured using acoustic vowel space and formant centralization ratio. Results. Compared to the period before surgery, vowel articulation was reduced after surgery when patients were off-medication, while it was better on-medication. The impact of levodopa intake on vowel articulation changed with STN DBS: before surgery, levodopa impaired articulation, while it no longer had a negative effect after surgery. Conclusions. These results indicate that while STN DBS could lead to a direct deterioration in articulation, it may indirectly improve it by reducing the levodopa dose required to manage motor symptoms. These findings suggest that, with respect to speech production, STN DBS and levodopa intake cannot be investigated separately because the two are intrinsically linked. Along with motor symptoms, speech production should be considered when optimizing therapeutic management of patients with PD.

Familial Intracranial Aneurysms: Recurrence Risk and Accidental Aggregation Study

BACKGROUND The Saguenay-Lac-Saint-Jean (SLSJ) region is a geographically isolated area (population 285,955) located in the Northeastern part of the Province of Quebec, Canada. Using a population-based register, the genealogical reconstruction of 502 individuals with ruptured intracranial aneurysm (RIA) showed a familial aggregation (the presence of aneurysm in two or more first- to third-degree relatives) for 144 (28.7%) of them; this proportion is much higher than reported elsewhere. OBJECTIVE In order to assess the genetic predisposition to RIA in the SLSJ population, the objective of the present study is to compare familial and non-familial cases and to provide an estimate of the recurrence risk ratio for siblings. RESULTS The age at the time of rupture, the number of intracranial aneurysms for each patient and the location of RIAs were not statistically different in the familial versus the non-familial group. Of the 3449 siblings, 20 (0.58%) had suffered a RIA. The recurrence risk ratio calculated for siblings (defined as the risk of disease among siblings divided by the estimated population prevalence) is 1.6 (CI 95% 1.0-2.4). In other respects, we observed very large kinships in the SLSJ population, with an average number of siblings of 7.2 (SD +/- 3.4), ranging from 0 to 17 individuals. With such large families and on the basis of chance alone, we expected 31.3% of the patients to have at least one first- to third-degree relative with RIA. CONCLUSION These data show that siblings of patients with RIA in the SLSJ population have a greater risk of RIA than the general population. Nevertheless, the largest part of the familial occurrence observed in the SLSJ region can be explained by accidental aggregation, due to large kinships. We propose that, in this population, an underlying genetic predisposition must be suspected only when three or more cases of RIA are identified among first- to third-degree relatives.

Corrigendum to “Changes in Vowel Articulation with Subthalamic Nucleus Deep Brain Stimulation in Dysarthric Speakers with Parkinson’s Disease”

[This corrects the article DOI: 10.1155/2014/487035.].