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David Mathieu, Mathieu Beaudry, René Martin, Hans McLelland, Bruno Robert and Brendan Kenny

Object. The authors conducted a double-blind prospective randomized study to determine whether infiltration of Mayfield skull-pin sites with 0.5% bupivacaine, compared with placebo, would prevent hemodynamic stimulation, thus allowing for a reduction in the quantity of anesthetic agents required.

Methods. Thirty patients were randomized into two groups. There was a significant increase in blood pressure (mean systolic blood pressure 10 mm Hg, p = 0.003) in patients in the placebo group compared with that in patients in the bupivacaine group 1 minute after securing the head holder.

Conclusions. The local administration of bupivacaine for anesthetic purposes before skull-pin application may prevent potentially hazardous hemodynamic stimulation.

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Nadia Veilleux, Philippe Goffaux, Marie Boudrias, David Mathieu, Kathya Daigle and David Fortin

Object

Due partly to therapeutic improvements and prolonged patient survival, the field of neurooncology is gradually undergoing a philosophical shift, progressively moving toward a more functional approach to patient welfare. This shift includes, as one of its defining objectives, the promotion of elevated levels of quality of life (QOL) and quality of health (QOH) for patients of all ages. Unfortunately, an adult life-stage perspective has never been used to study the long-lasting impact of age on well-being in neurooncology patients.

Methods

In this study, the authors assessed and compared the QOL and QOH scores of 42 younger adults (≤ 40 years of age) and 88 older adults (> 40 years of age) presenting with a primary supratentorial tumor.

Results

After having controlled for biomedical and treatment-related factors, the authors discovered that older adults reported lower functional well-being and poorer neurocognitive functioning than younger adults. This age difference appeared earlier than expected (developing as early as middle age), suggesting an accelerated effect of disease on the aging process. Importantly, it was also found that the variables that predict QOL and QOH differed depending on patient age. For example, support from friends was a significant predictor of QOL for younger adults, whereas the capacity to continue enjoying life was a significant predictor for older adults. Moreover, the presence of a high-grade tumor and increased physical pain had a negative impact on the QOH of younger adults, whereas increased difficulty with concentration negatively impacted the QOH of older adults.

Conclusions

These age differences clearly warn against consolidating the QOL or QOH scores of younger and older adults, and instead suggest that age at diagnosis is essential when considering patient perspective, and when establishing tailored support programs.

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Nicolas Dea, Martin Borduas, Brendan Kenny, David Fortin and David Mathieu

Object

Brain metastases are the most frequently occurring cerebral tumors. Tumors that are located in eloquent cerebral parenchyma can cause considerable morbidity and may pose a significant challenge during surgery. Gamma Knife surgery (GKS) is a recognized treatment modality for brain metastases. This study was undertaken to assess the safety and efficacy of GKS, specifically for brain metastases in eloquent locations.

Methods

Charts of patients harboring brain metastases that were treated by GKS at the Centre Hospitalier Universitaire de Sherbrooke between August 2004 and April 2008 were reviewed. Planning images were assessed by an independent neurosurgeon to assess tumor location. Eloquent locations included the primary motor, somatosensory, speech, and visual cortices; the basal ganglia; the thalamus; and the brainstem. Data on survival, tumor response, and complications were analyzed and compared with data published on surgical treatment of these lesions.

Results

During the study period, 650 metastases in 295 patients were treated with GKS; of these, 164 metastases in 95 patients were located in eloquent areas. In this subgroup, the median age of patients was 59 years and women constituted 57.9% of the population. The median Karnofsky Performance Scale score was 80% (range 50%–100%). Patients were categorized according to their recursive partitioning analysis class: Class 1, 22.1%; Class 2, 70.5%; and Class 3, 7.4% of patients. Non–small cell lung cancer was the most common primary tumor (63.2% of metastases), followed by small cell lung (8.4%), breast (7.4%), colorectal (5.3%), and renal cell (4.2%) cancers, as well as melanoma (4.2%). The median dose to the tumor margin was 18 Gy (range 14–24 Gy). The median duration of survival after GKS was 8.2 months. The recursive partitioning analysis class was the most significant variable affecting survival (p < 0.0001). Immediate control was achieved in 92.9% of tumors, and 68.6% of tumors were still controlled at the last follow-up. The median time to tumor progression was 16 months. Higher margin dose (p = 0.002), the absence of edema (p = 0.009), and the non–small cell lung cancer tissue type (p = 0.035) positively affected response rates. Steroid medications were no longer used in 46% of patients after GKS. New neurological deficits occurred in 5.7% of patients and seizures in 5.7%. All these deficits were transient and patients completely recovered in response to a temporary course of steroids. Imaging studies showed that new edema occurred in 8.6% of treated metastases and biopsy-proven radiation necrosis in 1.4%.

Conclusions

Gamma Knife surgery is safe and effective for brain metastases located in eloquent areas.

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David Mathieu, Khaled Effendi, Jocelyn Blanchard and Mario Séguin

Object

Among patients with multiple sclerosis (MS) there is a high incidence of trigeminal neuralgia (TN), and outcomes after treatment seem inferior to those in patients suffering from idiopathic TN. The goal of this study was to evaluate clinical outcomes in patients with MS-related TN after Gamma Knife surgery (GKS) and compare them with those obtained using percutaneous retrogasserian glycerol rhizotomy (PRGR).

Methods

The authors retrospectively reviewed the charts of 45 patients with MS-related TN. The first procedure undertaken was GKS in 27 patients and PRGR in 18 patients. Pain had been present for a median of 60 months (range 12–276 months) in patients who underwent GKS and 48 months (range 12–240 months) in patients who underwent PRGR. The following outcome measures were assessed in both groups of patients: pain relief (using the Barrow Neurological Institute [BNI] Pain Scale), procedure-related morbidity, time to pain relief and recurrence, and subsequent procedures that were performed.

Results

The median duration of follow-up was 39 months (range 13–69 months) in the GKS group and 38 months (range 2–75 months) in the PRGR group. Reasonable pain control (BNI Pain Scale Scores I–IIIb) was noted in 22 patients (81.5%) who underwent GKS and in 18 patients (100%) who underwent PRGR. For patients who underwent GKS, the median time to pain relief was 6 months; for those who underwent PRGR, pain relief was immediate. In the GKS group12 patients required subsequent procedures (3 patients for absence of response and 9 patients for pain recurrence), whereas in the PRGR group 6 patients required subsequent procedures (all for pain recurrence). As of the last follow-up, complete or reasonable pain control was finally achieved in 23 patients (85.2%) in the GKS group and in 16 patients (88.9%) in the PRGR group. The morbidity rate was 22.2% in the GKS group (all due to sensory loss and paresthesia) and 66.7% in the PRGR group (mostly hypalgesia, with 2 patients having corneal reflex loss and 1 patient suffering from meningitis).

Conclusions

Both GKS and PRGR are satisfactory strategies for treating MS-related TN. Gamma Knife surgery has a lower rate of sensory and overall morbidity than PRGR, but requires a delay before pain relief occurs. The authors propose that patients with extreme pain in need of fast relief should undergo PRGR. For other patients, both management strategies can lead to satisfactory pain relief, and the choice should be made based on patient preference and expectations.

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Veronica L. Chiang, Samuel T. Chao, Constantin Tuleasca, Matthew C. Foote, Cheng-chia Lee, David Mathieu, Hany Soliman and Arjun Sahgal

In order to determine what areas of research are a clinical priority, a small group of young Gamma Knife investigators was invited to attend a workshop discussion at the 19th International Leksell Gamma Knife Society Meeting. Two areas of interest and the need for future radiosurgical research involving multiple institutions were identified by the young investigators working group: 1) the development of additional imaging sequences to guide the understanding, treatment, and outcome tracking of diseases such as tremor, radiation necrosis, and AVM; and 2) trials to clarify the role of hypofractionation versus single-fraction radiosurgery in the treatment of large lesions such as brain metastases, postoperative cavities, and meningiomas.

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David Mathieu, Charles Deacon, Catherine-Andrée Pinard, Brendan Kenny and Julie Duval

Object

Hypothalamic hamartomas (HHs) are congenital lesions typically presenting with medically refractory epilepsy. Open or endoscopic surgical procedures to remove or disconnect the hamartoma have been reported to be effective but are associated with significant morbidity. The authors of studies on Gamma Knife surgery for HHs have reported an encouraging rate of epilepsy resolution with minimal side effects. At the Centre Hospitalier Universitaire de Sherbrooke, the authors have undertaken a prospective observational study of the outcomes of patients who underwent radiosurgery for HHs.

Methods

Patients were included in the study if they had an HH, refractory epilepsy, and no other suspected seizure focus. After radiosurgery, seizure status was assessed every 3 months and reported using the Engel Classification. Quality of life evaluation was performed annually using a standardized questionnaire, and neuropsychological evaluation was performed after 2 years.

Results

Nine patients were included in the study. They ranged in age from 12 to 57 years. Epilepsy began in infancy in all cases and was refractory to standard antiepileptic drugs. The patients received an average of 2 antiepileptic drugs before undergoing radiosurgery. Using the Régis Classification, 6 patients had smaller hamartomas (Grade I–III) and underwent treatment of the entire lesion, using a margin dose of 14–20 Gy. Treatment volume ranged from 0.3 to 1.0 ml. Three patients had larger lesions (Grade IV–VI) for which a radiosurgical disconnection was attempted, targeting the area of attachment to the hypothalamus. For those patients, the margin dose was 15 or 16 Gy, with treatment volume ranging from 0.8 to 1.8 ml. In all patients, the radiation dose received by the optic pathways was kept below 10 Gy. Disconnection led to no improvement in epilepsy (Engel Class IV). Four patients in whom the entire lesion was treated are now seizure free (Engel Class I), with another having only rare seizures (Engel Class II). Quality of life and verbal memory were improved in those patients with more than 3 years of follow-up. No adverse event occurred after radiosurgery.

Conclusions

Radiosurgery safely and effectively controlled the epileptic disorder in patients with HHs when the entire lesion could be targeted. Radiosurgical disconnection is ineffective and cannot be recommended.

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Douglas Kondziolka, Ricky Madhok, L. Dade Lunsford, David Mathieu, Juan J. Martin, Ajay Niranjan and John C. Flickinger

Object

Meningiomas of the cerebral convexity are often surgically curable because both the mass and involved dura mater can be removed. Stereotactic radiosurgery has become an important primary or adjuvant treatment for patients with intracranial meningiomas. The authors evaluated clinical and imaging outcomes in patients with convexity meningiomas after radiosurgery.

Methods

The patient cohort consisted of 125 patients with convexity meningiomas managed using radiosurgery at some point during an 18-year period. The patient series included 76 women, 55 patients who had undergone prior resection, and 6 patients with neurofibromatosis Type 2. Tumors were located in frontal (80 patients), parietal (24 patients), temporal (12 patients), and occipital (9 patients) areas. The WHO tumor grades in patients with prior resections were Grade I in 34 patients, Grade II in 15 patients, and Grade III in 6 patients. Seventy patients underwent primary radiosurgery and therefore had no prior histological tumor diagnosis. The mean tumor volume was 7.6 ml. Radiosurgery was performed using the Leksell Gamma Knife with a mean tumor margin dose of 14.2 Gy.

Results

Serial imaging was evaluated in 115 patients (92%). After primary radiosurgery, the tumor control rate was 92%. After adjuvant radiosurgery, the control rate was 97% for Grade I tumors. The actuarial tumor control rates at 3 and 5 years for the entire series were 86.1 ± 3.8% and 71.6 ± 8.6%, respectively. For patients with benign tumors (Grade I) and those without prior surgery, the actuarial tumor control rate was 95.3 ± 2.3% and 85.8 ± 9.3%, respectively. Delayed resection after radiosurgery was performed in 9 patients (7%) at an average of 35 months. No patient developed a subsequent radiation-induced tumor. The overall morbidity rate was 9.6%. Symptomatic peritumoral imaging changes compatible with edema or adverse radiation effects developed in 5%, at a mean of 8 months.

Conclusions

Stereotactic radiosurgery provides satisfactory control rates either after resection or as an alternate to resection, particularly for histologically benign meningiomas. Its role is most valuable for patients whose tumors affect critical neurological regions and who are poor candidates for resection. Both temporary and permanent morbidity are related to brain location and tumor volume.

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Hideyuki Kano, Jason Sheehan, Penny K. Sneed, Heyoung L. McBride, Byron Young, Christopher Duma, David Mathieu, Zachary Seymour, Michael W. McDermott, Douglas Kondziolka, Aditya Iyer and L. Dade Lunsford

OBJECT

Stereotactic radiosurgery (SRS) is a potentially important option for patients with skull base chondrosarcomas. The object of this study was to analyze the outcomes of SRS for chondrosarcoma patients who underwent this treatment as a part of multimodality management.

METHODS

Seven participating centers of the North American Gamma Knife Consortium (NAGKC) identified 46 patients who underwent SRS for skull base chondrosarcomas. Thirty-six patients had previously undergone tumor resections and 5 had been treated with fractionated radiation therapy (RT). The median tumor volume was 8.0 cm3 (range 0.9–28.2 cm3), and the median margin dose was 15 Gy (range 10.5–20 Gy). Kaplan-Meier analysis was used to calculate progression-free and overall survival rates.

RESULTS

At a median follow-up of 75 months after SRS, 8 patients were dead. The actuarial overall survival after SRS was 89% at 3 years, 86% at 5 years, and 76% at 10 years. Local tumor progression occurred in 10 patients. The rate of progression-free survival (PFS) after SRS was 88% at 3 years, 85% at 5 years, and 70% at 10 years. Prior RT was significantly associated with shorter PFS. Eight patients required salvage resection, and 3 patients (7%) developed adverse radiation effects. Cranial nerve deficits improved in 22 (56%) of the 39 patients who deficits before SRS. Clinical improvement after SRS was noted in patients with abducens nerve paralysis (61%), oculomotor nerve paralysis (50%), lower cranial nerve dysfunction (50%), optic neuropathy (43%), facial neuropathy (38%), trochlear nerve paralysis (33%), trigeminal neuropathy (12%), and hearing loss (10%).

CONCLUSIONS

Stereotactic radiosurgery for skull base chondrosarcomas is an important adjuvant option for the treatment of these rare tumors, as part of a team approach that includes initial surgical removal of symptomatic larger tumors.

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Hideyuki Kano, Dusan Urgosik, Roman Liscak, Bruce E. Pollock, Or Cohen-Inbar, Jason P. Sheehan, Mayur Sharma, Danilo Silva, Gene H. Barnett, David Mathieu, Nathaniel D. Sisterson and L. Dade Lunsford

OBJECTIVE

The goal of this study was to evaluate the outcomes of Gamma Knife stereotactic radiosurgery (SRS) when used for patients with intractable idiopathic glossopharyngeal neuralgia.

METHODS

Six participating centers of the International Gamma Knife Research Foundation identified 22 patients who underwent SRS for intractable glossopharyngeal neuralgia between 1998 and 2015. The median patient age was 60 years (range 34–83 years). The median duration of symptoms before SRS was 46 months (range 1–240 months). Three patients had unsuccessful prior surgical procedures, including microvascular decompression (MVD) (n = 2) and balloon compression (n = 1). The radiosurgical target was the glossopharyngeal meatus. The median maximum dose was 80 Gy.

RESULTS

The median follow-up was 45 months after SRS (range 6–120 months). Twelve patients (55%) had < 4 years of follow-up. Thirteen patients (59%) had initial complete pain relief at a median of 12 days after SRS (range 1–60 days). Three patients (14%) had partial pain relief at a median of 70 days after SRS (range 60–90 days). Six patients (27%) had no pain relief. Among 16 patients with initial pain relief, 5 maintained complete pain relief without medication (Barrow Neurological Institute [BNI] pain intensity score Grade I), 1 maintained occasional pain relief without medication (BNI Grade II), 3 maintained complete pain relief with medication (BNI Grade IIIb), and 7 patients had pain recurrence at a median of 20 months after SRS (range 6–120 months). The rates of maintenance of adequate pain relief (BNI Grades I–IIIb) were 63% at 1 year, 49% at 2 years, 38% at 3 years, 38% at 5 years, and 28% at 7 years. When 7 patients without pain recurrence within 4 years of follow-up were excluded, the rates of maintenance of adequate pain relief were 38% at 5 years and 28% at 7 years. Ten patients required additional procedures (MVD, n = 4; repeat SRS, n = 5; glossopharyngeal nerve block, n = 1). Four of 5 patients who underwent repeat SRS maintained pain relief (BNI Grade I, n = 3; and BNI Grade IIIb, n = 1). No adverse effects of radiation were observed after a single SRS. Two patients developed hyperesthesia in the palatoglossal arch 5 and 8 months after repeat SRS, respectively.

CONCLUSIONS

Stereotactic radiosurgery for intractable, medically refractory glossopharyngeal neuralgia provided lasting pain reduction in 55% of patients after 1 or 2 SRS procedures. Patients who had a poor response or pain recurrence may require additional procedures such as repeat SRS, MVD, nerve blocks, or nerve section. No patient developed changes in vocal cord function or swallowing disorders after SRS in this study.

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Christian Iorio-Morin, Laurence Masson-Côté, Youssef Ezahr, Jocelyn Blanchard, Annie Ebacher and David Mathieu

Object

Optimal case management after surgical removal of brain metastasis remains controversial. Although postoperative whole-brain radiation therapy (WBRT) has been shown to prevent local recurrence and decrease deaths, this modality can substantially decrease neurocognitive function and quality of life. Stereotactic radiosurgery (SRS) can theoretically achieve the same level of local control with fewer side effects, although studies conclusively demonstrating such outcomes are lacking. To assess the effectiveness and safety profile of tumor bed SRS after resection of brain metastasis, the authors performed a retrospective analysis of 110 patients who had received such treatment at the Centre Hospitalier Universitaire de Sherbrooke. They designed the study to identify risk factors for local recurrence and placed special emphasis on factors that could potentially be addressed.

Methods

Patients who had received treatment from 2004 through 2013 were included if they had undergone surgical removal of 1 or more brain metastases and if the tumor bed was treated by SRS regardless of the extent of resection or prior WBRT. All cases were retrospectively analyzed for patient and tumor-specific factors, treatment protocol, adverse outcomes, cavity outcomes, and survival for as long as follow-up was available. Univariate and multivariate Cox regression analyses were performed to identify risk factors for local recurrence and predictors of increased survival times.

Results

Median patient age at first SRS treatment was 58 years (range 37–84 years). The most frequently diagnosed primary tumor was non–small cell lung cancer. The rate of gross-total resection was 81%. The median Karnofsky Performance Scale score was 90%. Tumor bed SRS was performed at a median of 3 weeks after surgery. Median follow-up and survival times were 10 and 11 months, respectively. Actuarial local control of the cavity at 12 months was 73%; median time to recurrence was 6 months. According to multivariate analysis, risk factors for recurrence were a longer surgery-to-SRS delay (HR 1.625, p = 0.003) and a lower maximum radiation dose delivered to the cavity (HR 0.817, p = 0.006). Factors not associated with increased recurrence were subtotal or piecemeal resections, prior WBRT, histology of the primary tumor, and larger cavity volume. No factors predictive of survival were identified. Symptomatic radiation-induced enhancement occurred in 6% of patients and leptomeningeal dissemination in 11%. Pathologically confirmed radiation-induced necrosis occurred in 1 (0.9%) patient.

Conclusions

Adjuvant tumor bed SRS after the resection of brain metastasis is a valuable alternative to adjuvant WBRT. Risk factors for local recurrence are lower maximum radiation dose and a surgery-to-SRS delay longer than 3 weeks. Outcomes were not worse for patients who had undergone prior WBRT and subtotal or piecemeal resections. Pending the results of prospective randomized controlled trials, the authors' study supports the safety and efficacy of adjuvant SRS after resection of brain metastasis. SRS should be performed as early as possible, ideally within 3 weeks of the surgery.