This manuscript served as a companion piece for the original article “Pregabalin for the Management of Cervicogenic Headache; A Double Blind Study” by Guy P. Boudreau and Luc Marchand, which was published in the September 2014 issue of The Canadian Journal of Neurological Sciences.1

The role of fludeoxyglucose F 18 positron emission tomography (PET) in the presurgical evaluation of patients with medically intractable epilepsy continues to be refined. The purpose of this study was to systematically review the literature to assess the diagnostic accuracy and utility of PET in this setting. Thirty-nine studies were identified through MEDLINE and EMBASE databases that met the inclusion criteria. In adult patients, PET hypometabolism showed a 56 to 90% agreement with seizure onset localized by intracranial electroencephalogram (pediatric: 21 to 86%). In temporal lobe epilepsy patients with good surgical outcome, PET displayed moderate to high sensitivity in localizing the seizure focus (range: 71 to 89%). The sensitivity increased by 8 to 23% when PET results were combined with magnetic resonance imaging or electroencephalogram. PET has been shown to affect patient management by improving the guidance of intracranial electrodes placement, altering the decision to perform surgery, or excluding patients from further evaluation.

Objective: To replicate a previous finding that the trajectory of the Neuropsychiatric Inventory (NPI) shifts in the sixth year of behavioural variant frontotemporal dementia (bvFTD). We evaluated longitudinal tracking with both the Frontal Behavioural Inventory (FBI) and NPI, comparing bvFTD against other dementias.Methods: Chart reviews over two to five years for patients with bvFTD (n=30), primary progressive aphasia (PPA, n=13) and Alzheimer’s disease (AD, n=118) at an urban Canadian tertiary clinic specializing in dementia. Linear regressions of the longitudinal data tested predictors of annualized rates of change (ROC) in NPI and FBI total and subscales for apathy and disinhibition among dementia groups. Results: The mode of the overall sample for the most advanced duration of illness observed was 5 years, with the median at 7 years. We did not find a crescendo-decrescendo pattern in scores although, for bvFTD and AD, high initial scores correlated with ensuing downward ROCs on the NPI and FBI. Educational level showed an influence on disinhibition ROCs. The FBI was no more revealing than the NPI for apathy and disinhibition scores in these dementias. Conclusions: A cognitive reserve effect on behavioural disturbance was supported but it may take longer than our 4 years of observing the clinical sample to record inflection points in the behavioural and psychiatric symptoms seen in bvFTD. The current data only imply that both apathy and disinhibition will diminish over the course of dementia.

Background: Dysphagia is a common symptom and an important prognostic factor in Parkinson’s disease (PD). Although cognitive and motor dysfunctions may contribute to dysphagia in patients with PD, any specific association between such problems and swallowing functions is unclear. Here, we examined the potential relationship between cognitive/motor components and swallowing functions in PD. We evaluated the contributions of cognition and motor function to the components of swallowing via video fluoroscopic swallowing (VFS) experiments. Methods: We prospectively enrolled 56 patients without dementia having PD. Parkinson’s disease severity was assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS). All participants received neuropsychological tests covering general mental status, visuospatial function, attention, language, learning and memory, and frontal executive function. The well-validated “modified barium swallow impairment profile” scoring system was applied during VFS studies to quantify swallowing impairments. Finally, correlations between neuropsychological or motor functions and impairment in swallowing components were calculated. Results: The most significant correlations were found between the frontal/executive or learning/memory domains and the oral phase of swallowing, though a minor component of the pharyngeal phase correlated with frontal function as well. Bradykinesia and the UPDRS total score were associated with both the pharyngeal and oral phases. Conclusions: Our findings suggest that cognitive dysfunctions are associated with the oral phase of swallowing in patients with early stage PD while the severity of motor symptoms may be associated with overall swallowing function.

Background: Chronic motor cortex stimulation (MCS) has been used to treat medically refractory neuropathic pain over the past 20 years. We investigated this procedure using a prospective multicentre randomized blinded crossover trial. Methods: Twelve subjects with three different neuropathic pain syndromes had placement of MCS systems after which they were randomized to receive low (“subtherapeutic”) or high (“therapeutic”) stimulation for 12 weeks, followed by a crossover to the other treatment group for 12 weeks. The primary outcome measure was the pain visual analogue scale (VAS). Secondary outcome measures included McGill Pain Questionnaire (MPQ), Beck Depression Inventory-II, medication log, work status, global impression of change, and SF-36 quality of life scale. Results: The trial was halted early due to lack of efficacy. One subject withdrew early due to protocol violation and five subjects withdrew early due to transient adverse events. Six subjects with upper extremity pain completed the study. There was no significant change in VAS with low or high stimulation and no significant improvement in any of the outcome measures from low to high stimulation. SF-36 role physical and mental health scores were worse with high compared to low stimulation (p=0.024, p=0.005). Conclusions: We failed to show that MCS is an effective treatment for refractory upper extremity neuropathic pain and suggest that previous studies may have been skewed by placebo effects, or ours by nocebo. We suggest that a healthy degree of skepticism is warranted when considering this invasive therapy for upper extremity pain syndromes.

Background: When patients with cranial glioblastoma develop weakness, a rare differential diagnosis is spinal metastases. Methods: Chart and literature reviews were performed. Results: The reported patient had delayed onset spinal drop metastasis that was only detected by magnetic resonance imaging (MRI). A 48-year-old patient had supratentorial glioblastoma, treated with radiotherapy (RT) and concurrent temozolomide followed by six cycles of adjuvant temozolomide. Four years after completion of all treatments (62 months from initial presentation), he developed low backache and weakness in both legs. Positron emission tomography/computed tomography scans demonstrated intracranial recurrence only. Spinal drop metastases were detected only by MRI scan. Local spinal RT 40 Gy in 20 fractions with concurrent and maintenance temozolomide were given. Because of disease progression after nine cycles of temozolomide, systemic therapy was changed to bevacizumab, which greatly improved his symptoms for 4 months before deterioration of mental status. He is still alive with disease at 22 months after diagnosis of spinal metastases (84 months from initial glioblastoma diagnosis). Conclusions: MRI is the diagnostic imaging of choice for spinal metastases. This illustrative case of delayed-onset spinal metastases shows unusual slow progression. Local RT, temozolomide, and targeted therapy may improve survival. This illustrative case is the first report of bevacizumab as a second-line therapy in drop metastasis of glioblastoma.

Background: The emphasis regarding intracranial neuroendoscopy has been traditionally advocated and focused on the role in pediatric patients, although a significant usage has developed in adult patients. In this study, we examine and contrast the role of predominantly intracranial neuroendoscopy in both a pediatric and adult population with a minimum postprocedure follow-up of 5 years. Methods: A retrospective review was conducted for patients in the two hospitals that manage neurosurgical care for Southern Alberta, Canada, undergoing neuroendoscopic surgery between 1994 and 2008. The pediatric group was defined as age ≤17 years and the adult group as age ≥18 years. Results: A total of 273 patients who underwent a total of 330 procedures with a mean postprocedure follow-up of 12.9 years were identified. There were 161 adult and 112 pediatric patients, and both groups underwent surgery by the same surgeons. The most common procedure was endoscopic third ventriculostomy, accounting for 55% of procedures. One postoperative death occurred in an adult patient. Endoscopic third ventriculostomy success 1-year postprocedure was 81%, with only three late-term failures. Postoperative infection was the most common serious complication (two pediatric/four adult patients). Adult and pediatric patients had similar major complication rates (4.2% vs 5.7%, p=0.547). Conclusions: Neuroendoscopy overall had a similar role in both pediatric and adult neurosurgical populations, with the most commonly associated complication being infection. Neuroendoscopy is an important therapeutic modality in the management of appropriate adult patients.

Background: Although current pain-evoked electroencephalographic (EEG) studies provide valuable information regarding human brain regions involved in pain, they have mostly considered neuronal responses which oscillate in phase following a painful event. In many instances, cortical neurons respond by generating bursts of activity that are slightly out of phase from trial-to-trial. These types of activity bursts are known as induced brain responses. The significance of induced brain responses to pain is still unknown. Methods: In this study, 23 healthy subjects were given both non-painful and painful transcutaneous electrical stimulations in separate testing blocks (stimulation strength was kept constant within blocks). Subjective intensity was rated using a numerical rating scale, while cerebral activity tied to each stimulation was measured using EEG recordings. Induced brain responses were identified using a time frequency wavelet transform applied to average-removed single trials. Results: Results showed a pain-specific burst of induced theta activity occurring between 180 and 500 ms post-shock onset. Source current density estimations located this activity within the dorsolateral prefrontal cortex (DLPFC, bilaterally), however, only right DLPFC activity predicted a decrease in subjective pain as testing progressed. Conclusion: This finding suggests that non-phase locked neuronal responses in the right DLPFC contribute to the endogenous attenuation of pain through time. Perspective: This article presents neuroimaging findings demonstrating that, in response to pain, non-phase locked bursts of theta activity located in the right dorsolateral prefrontal cortex are associated with a progressive decrease in subjective pain intensity, which has potentially important implications regarding how humans endogenously control their experiences of pain.

On February 11, 2015, the Canadian Food Inspection Agency announced that a cow born and raised in Alberta had tested positive for bovine spongiform encephalopathy (BSE), commonly known as mad cow disease. BSE is a prion disease of cattle that, when transmitted to humans, produces a fatal neurodegenerative disease known as variant Creutzfeldt-Jakob disease. We believe that this latest case of BSE in Canadian cattle suggests the timeliness of a review of the management of BSE in Canada from a historically and scientifically informed perspective. In this article, we ask: how did the Canadian management of BSE between 1990 and 2014 engage with the contemporary understanding of BSE’s human health implications? We propose that Canadian policies largely ignored the implicit medical nature of BSE, treating it as a purely agricultural and veterinary issue. In this way, policies to protect Canadians were often delayed and incomplete, in a manner disturbingly reminiscent of Britain’s failed management of BSE. Despite assurances to the contrary, it is premature to conclude that BSE (and with it the risk of variant Creutzfeldt-Jakob disease) is a thing of Canada’s past: BSE remains very much an issue in Canada’s present.