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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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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, 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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Alexandrine Gagnon, Mathieu Laroche, David Williamson, Marc Giroux, Jean-François Giguère, and Francis Bernard

OBJECTIVE

After craniectomy, although intracranial pressure (ICP) is controlled, episodes of brain hypoxia might still occur. Cerebral hypoxia is an indicator of poor outcome independently of ICP and cerebral perfusion pressure. No study has systematically evaluated the incidence and characteristics of brain hypoxia after craniectomy. The authors’ objective was to describe the incidence and characteristics of brain hypoxia after craniectomy.

METHODS

The authors included 25 consecutive patients who underwent a craniectomy after traumatic brain injury or intracerebral hemorrhage and who were monitored afterward with a brain tissue oxygen pressure monitor.

RESULTS

The frequency of hypoxic values after surgery was 14.6% despite ICP being controlled. Patients had a mean of 18 ± 23 hypoxic episodes. Endotracheal (ET) secretions (17.4%), low cerebral perfusion pressure (10.3%), and mobilizing the patient (8.6%) were the most common causes identified. Elevated ICP was rarely identified as the cause of hypoxia (4%). No cause of cerebral hypoxia could be determined 31.2% of the time. Effective treatments that were mainly used included sedation/analgesia (20.8%), ET secretion suctioning (15.4%), and increase in fraction of inspired oxygen or positive end-expiratory pressure (14.1%).

CONCLUSIONS

Cerebral hypoxia is common after craniectomy, despite ICP being controlled. ET secretion and patient mobilization are common causes that are easily treatable and often not identified by standard monitoring. These results suggest that monitoring should be pursued even if ICP is controlled. The authors’ findings might provide a hypothesis to explain the poor functional outcome in the recent randomized controlled trials on craniectomy after traumatic brain injury where in which brain tissue oxygen pressure was not measured.

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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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Roman Mounier, Ron Birnbaum, Fabrice Cook, Paul-Henri Jost, Mathieu Martin, Bouziane Aït-Mamar, Biba Nebbad, Séverine Couffin, Françoise Tomberli, Ryad Djedid, Gilles Dhonneur, and David Lobo

OBJECTIVE

The authors aimed to describe the natural history of ventriculostomy-related infections (VRIs) under appropriate treatment and to assess risk factors for poor outcome.

METHODS

All patients older than 18 years in whom an external ventricular drain (EVD) had been implanted and who had developed a VRI requiring treatment were included in this retrospective study. D0 was defined as the first day of antibiotic administration. Clinical and biological parameters were compared each day beginning with D1 and ending with D10 to those of D0. The authors defined D0 in a control group as the day a CSF culture came back positive, without any sign of infection. The authors then searched for poor prognostic factors in the VRI group.

RESULTS

Among 567 patients requiring an EVD between January 2007 and October 2017, 39 developed a VRI. Most were monomicrobial infections, and 47 microbes were responsible (45% were gram-positive cocci). Clinical parameters differed significantly from the control group during the first 2 days and then returned to baseline. The CSF parameters differed significantly from the control group for a longer period, returning to baseline after 5 days. CSF sterilization occurred in a median time of 2 days. An intrathecal route or EVD exchange was not associated with a poor outcome. No clinical or biological parameter between D3 and D5 was linked to outcome.

CONCLUSIONS

Clinical status improved faster than CSF parameters (before and after D5, respectively). Some CSF parameters remained abnormal until D10. Body temperature and microbiological cultures normalized faster than other parameters.

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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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Ching-Jen Chen, Kathryn N. Kearns, Dale Ding, Hideyuki Kano, David Mathieu, Douglas Kondziolka, Caleb Feliciano, Rafael Rodriguez-Mercado, Inga S. Grills, Gene H. Barnett, L. Dade Lunsford, and Jason P. Sheehan

OBJECTIVE

Arteriovenous malformations (AVMs) of the basal ganglia (BG) and thalamus are associated with elevated risks of both hemorrhage if left untreated and neurological morbidity after resection. Therefore, stereotactic radiosurgery (SRS) has become a mainstay in the management of these lesions, although its safety and efficacy remain incompletely understood. The aim of this retrospective multicenter cohort study was to evaluate the outcomes of SRS for BG and thalamic AVMs and determine predictors of successful endpoints and adverse radiation effects.

METHODS

The authors retrospectively reviewed data on patients with BG or thalamic AVMs who had undergone SRS at eight institutions participating in the International Gamma Knife Research Foundation (IGKRF) from 1987 to 2014. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs). Multivariable models were developed to identify independent predictors of outcome.

RESULTS

The study cohort comprised 363 patients with BG or thalamic AVMs. The mean AVM volume and SRS margin dose were 3.8 cm3 and 20.7 Gy, respectively. The mean follow-up duration was 86.5 months. Favorable outcome was achieved in 58.5% of patients, including obliteration in 64.8%, with rates of post-SRS hemorrhage and permanent RIC in 11.3% and 5.6% of patients, respectively. Independent predictors of favorable outcome were no prior AVM embolization (p = 0.011), a higher margin dose (p = 0.008), and fewer isocenters (p = 0.044).

CONCLUSIONS

SRS is the preferred intervention for the majority of BG and thalamic AVMs. Patients with morphologically compact AVMs that have not been previously embolized are more likely to have a favorable outcome, which may be related to the use of a higher margin dose.