Paediatric epilepsy surgery: Techniques and outcomes.

Epilepsy is a neurological condition characterised by recurrent and persistent seizures. For paediatric patients, achieving early seizure freedom can have positive impacts on cognition, development, social integration and mental health, leading to improved quality of life. In general, one third of patients with epilepsy are refractory to medication; for these patients, epilepsy surgery may offer the only chance for improved seizure control. Epilepsy surgery as a therapeutic intervention has become increasingly accepted in the past few decades, with more diverse options available (including neuromodulatory and minimally invasive techniques). In this context, we discuss here the pre-operative workup for paediatric patients with medically refractory epilepsy and provide an updated review on current and emerging surgical therapies for this condition. We also discuss the clinical, neuropsychological, quality of life and economic impacts of epilepsy surgery.

Resting State BOLD Variability in Alzheimer's Disease: A Marker of Cognitive Decline or Cerebrovascular Status?

Background: Alzheimer's disease (AD) is a neurodegenerative disorder that may benefit from early diagnosis and intervention. Therefore, there is a need to identify early biomarkers of AD using non-invasive techniques such as functional magnetic resonance imaging (fMRI). Recently, novel approaches to the analysis of resting-state fMRI data have been developed that focus on the moment-to-moment variability in the blood oxygen level dependent (BOLD) signal. The objective of the current study was to investigate BOLD variability as a novel early biomarker of AD and its associated psychophysiological correlates. Method: Data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) 2 database from 19 participants with AD and 19 similarly aged controls. For each participant, a map of BOLD signal variability (SDBOLD) was computed as the standard deviation of the BOLD timeseries at each voxel. Group comparisons were performed to examine global differences in resting state SDBOLD in AD versus healthy controls. Correlations were then examined between participant SDBOLD maps and (1) ADNI-derived composite scores of memory and executive function and (2) neuroimaging markers of cerebrovascular status. Results: Between-group comparisons revealed significant (p < 0.05) increases in SDBOLD in patients with AD relative to healthy controls in right-lateralized frontal regions. Lower memory scores and higher WMH burden were associated with greater SDBOLD in the healthy control group (p < 0.1), but not individuals with AD. Conclusion: The current study provides proof of concept of a novel resting state fMRI analysis technique that is non-invasive, easily accessible, and clinically compatible. To further explore the potential of SDBOLD as a biomarker of AD, additional studies in larger, longitudinal samples are needed to better understand the changes in SDBOLD that characterize earlier stages of disease progression and their underlying psychophysiological correlates.

Relationship Between DTI Metrics and Cognitive Function in Alzheimer's Disease.

Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder with a clinical presentation characterized by memory impairment and executive dysfunction. Our group previously demonstrated significant alterations in white matter microstructural metrics in AD compared to healthy older adults. We aimed to further investigate the relationship between white matter microstructure in AD and cognitive function, including memory and executive function. Methods: Diffusion tensor imaging (DTI) and neuropsychological data were downloaded from the AD Neuroimaging Initiative database for 49 individuals with AD and 48 matched healthy older adults. The relationship between whole-brain fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD), radial diffusivity (RD), and composite scores of memory and executive function was examined. We also considered voxel-wise relationships using Tract-Based Spatial Statistics. Results: As expected, individuals with AD had lower composite scores on tests of memory and executive function, as well as disrupted white matter integrity (low FA, high MD, AxD, and RD) relative to healthy older adults in widespread regions, including the hippocampus. When the AD and healthy older adult groups were combined, we found significant relationships between DTI metrics (FA/MD/AxD/RD) and memory scores across widespread regions of the brain, including the medial temporal regions. We also found significant relationships between DTI metrics (FA/MD/AxD/RD) and executive function in widespread regions, including the frontal areas in the combined group. However, when the groups were examined separately, no significant relationships were found between DTI metrics (FA/MD/AxD/RD) and memory performance for either group. Further, we did not find any significant relationships between DTI metrics (FA/MD/AxD/RD) and executive function in the AD group, but we did observe significant relationships between FA/RD, and executive function in healthy older adults. Conclusion: White matter integrity is disrupted in AD. In a mixed sample of AD and healthy elderly persons, associations between measures of white matter microstructure and memory and executive cognitive test performance were evident. However, no significant linear relationship between the degree of white matter disruption and level of cognitive functioning (memory and executive abilities) was found in those with AD. Future longitudinal studies of the relations between DTI metrics and cognitive function in AD are required to determine whether DTI has potential to measure progression of AD and/or treatment efficacy.

Case Report: A Comprehensive Neuropsychological Assessment of a Case of Superficial Siderosis.

OBJECTIVE: Superficial siderosis (SS) is a neurodegenerative condition due to the long-term effects of hemosiderin deposition on the surface of the brain, cerebellum, brainstem, and spinal cord. SS symptoms include sensorineural hearing loss, ataxia and upper motor neuron signs. SS was diagnostically evasive until magnetic resonance imaging (MRI) became available. As the detection of SS improved, case studies have become more prevalent. To our knowledge, however, this is the first report of SS detailing a comprehensive neuropsychological assessment. METHOD: The current study presents a right-handed female in her early 60s, with a university level of education, who was diagnosed with SS. RESULTS: Her neuropsychological profile showed impairment across multiple domains, including memory and executive function, with consistent behavioral findings. The results from a comprehensive neuropsychological assessment include dementia and a cerebellar cognitive affective syndrome. CONCLUSIONS: Neuropsychological evaluation of a patient with new cognitive impairment in combination with unexplained hearing loss, gait disorder, or myelopathy should lead to a referral for MRI that includes techniques sensitive for iron deposition, in order to rule out SS.

Longitudinal Assessment of Health-Related Quality of Life following Adolescent Sports-Related Concussion.

To examine initial and longitudinal health-related quality of life (HRQOL) in adolescent sports-related concussion (SRC) patients, a prospective observational case-series study was conducted among adolescent SRC patients who were evaluated at a multi-disciplinary pediatric concussion program. Health-related quality of life was measured using the child self-report Pediatric Quality of Life Inventory (PedsQL) generic score scale (age 13-18 version) and the PedsQL Cognitive Functioning scale. Initial and longitudinal HRQOL outcomes were compared between patients who did and did not develop post-concussion syndrome (PCS). A total of 63 patients met the inclusion criteria during the study period. The mean age of the cohort was 14.57 years (standard deviation, 1.17) and 61.9% were male. The median time from injury to initial consultation was 6.5 days (interquartile range, 5, 11). At initial consultation, impairments in physical and cognitive HRQOL but not social or emotional HRQOL were observed. Initial symptom burden and length of recovery were associated with greater impairment in physical and cognitive HRQOL. Patients who went on to develop PCS had significantly worse physical and cognitive HRQOL at initial consultation and demonstrated a slower rate of recovery in these domains, compared with those who recovered in less than 30 days. Adolescent SRC was associated with HRQOL impairments that correlated with clinical outcomes. No persistent impairments in HRQOL were detected among patients who achieved physician-documented clinical recovery. Future studies are needed to evaluate the clinical utility of HRQOL measurement in the longitudinal management of adolescent SRC and PCS patients.

Longitudinal changes in microstructural white matter metrics in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Current avenues of AD research focus on pre-symptomatic biomarkers that will assist with early diagnosis of AD. The majority of magnetic resonance imaging (MRI) based biomarker research to date has focused on neuronal loss in grey matter and there is a paucity of research on white matter. METHODS: Longitudinal DTI data from the Alzheimer's Disease Neuroimaging Initiative 2 database were used to examine 1) the within-group microstructural white matter changes in individuals with AD and healthy controls at baseline and year one; and 2) the between-group microstructural differences in individuals with AD and healthy controls at both time points. RESULTS: 1) Within-group: longitudinal Tract-Based Spatial Statistics revealed that individuals with AD and healthy controls both had widespread reduced fractional anisotropy (FA) and increased mean diffusivity (MD) with changes in the hippocampal cingulum exclusive to the AD group. 2) Between-group: relative to healthy controls, individuals with AD had lower FA and higher MD in the hippocampal cingulum, as well as the corpus callosum, internal and external capsule; corona radiata; posterior thalamic radiation; superior and inferior longitudinal fasciculus; fronto-occipital fasciculus; cingulate gyri; fornix; uncinate fasciculus; and tapetum. CONCLUSION: The current results indicate that sensitivity to white matter microstructure is a promising avenue for AD biomarker research. Additional longitudinal studies on both white and grey matter are warranted to further evaluate potential clinical utility.

Migraine with Aura or Sports-Related Concussion: Case Report, Pathophysiology, and Multidisciplinary Approach to Management.

The evaluation and management of athletes presenting with clinical features of migraine headache with aura in the setting of sports-related head trauma is challenging. We present a case report of a 15-yr-old boy with a history of migraine with visual aura that developed acute visual disturbance and headache after a head injury during an ice hockey game. The patient underwent comprehensive assessment at a multidisciplinary concussion program, including neuro-ophthalmological examination, neurocognitive testing, and graded aerobic treadmill testing. Clinical history and multidisciplinary assessment was consistent with the diagnosis of coexisting sports-related concussion and migraine with brainstem aura. The authors discuss the pearls and pitfalls of managing patients who develop migraine headache with visual aura after sports-related head injury and the value of a comprehensive multidisciplinary approach to this unique patient population.

Googling Concussion Care: A Critical Appraisal of Online Concussion Healthcare Providers and Practices in Canada.

BACKGROUND: Concussion is an emerging public health concern, but care of patients with a concussion is presently unregulated in Canada. METHODS: Independent, blinded Google Internet searches were conducted for the terms "concussion" and "concussion clinic" and each of the Canadian provinces and territories. The first 10 to 15 concussion healthcare providers per province were identified. A critical appraisal of healthcare personnel and services offered on the provider's Web site was conducted. RESULTS: Fifty-eight concussion healthcare providers were identified using this search methodology. Only 40% listed the presence of an on-site medical doctor (M.D.) as a member of the clinical team. Forty-seven percent of concussion healthcare providers advertised access to a concussion clinic, program, or center on their Web site. Professionals designated as team leaders, directors, or presidents among concussion clinics, programs, and centers included a neuropsychologist (15%), sports medicine physician (7%), neurologist (4%), and neurosurgeon (4%). Services offered by providers included baseline testing (67%), physiotherapy (50%), and hyperbaric oxygen therapy (2%). CONCLUSIONS: This study indicates that there are numerous concussion healthcare providers in Canada offering diverse services with clinics operated by professionals with varying levels of training in traumatic brain injury. In some cases, the practices of these concussion clinics do not conform to current expert consensus guidelines.

Googling concussion care in the USA: a critical appraisal of online concussion healthcare providers.

AIM: To examine the online personnel and practice profiles of concussion healthcare providers in the USA. METHODS: We conducted independent, blinded, Google Internet searches for concussion healthcare providers using the terms 'concussion clinic' and 'concussion program' and each American state and completed a critical appraisal of healthcare personnel and services at these websites. RESULTS: A total of 184 concussion healthcare providers were identified. Despite offering care to traumatic brain injury (TBI) patients, access to professionals with expertise in TBI including neuropsychologists (40.8%), neurologists (33.7%) and neurosurgeons (21.7%) was variable across sites. CONCLUSION: Concussion healthcare in the USA is presently delivered by a range of healthcare professionals with varying levels of training in TBI offering a variety of services.

Multidisciplinary Management of Pediatric Sports-Related Concussion.

OBJECTIVES: To summarize the clinical characteristics and outcomes of pediatric sports-related concussion (SRC) patients who were evaluated and managed at a multidisciplinary pediatric concussion program and examine the healthcare resources and personnel required to meet the needs of this patient population. METHODS: We conducted a retrospective review of all pediatric SRC patients referred to the Pan Am Concussion Program from September 1st, 2013 to May 25th, 2015. Initial assessments and diagnoses were carried out by a single neurosurgeon. Return-to-Play decision-making was carried out by the multidisciplinary team. RESULTS: 604 patients, including 423 pediatric SRC patients were evaluated at the Pan Am Concussion Program during the study period. The mean age of study patients was 14.30 years (SD: 2.32, range 7-19 years); 252 (59.57%) were males. Hockey (182; 43.03%) and soccer (60; 14.18%) were the most commonly played sports at the time of injury. Overall, 294 (69.50%) of SRC patients met the clinical criteria for concussion recovery, while 75 (17.73%) were lost to follow-up, and 53 (12.53%) remained in active treatment at the end of the study period. The median duration of symptoms among the 261 acute SRC patients with complete follow-up was 23 days (IQR: 15, 36). Overall, 25.30% of pediatric SRC patients underwent at least one diagnostic imaging test and 32.62% received referral to another member of our multidisciplinary clinical team. CONCLUSION: Comprehensive care of pediatric SRC patients requires access to appropriate diagnostic resources and the multidisciplinary collaboration of experts with national and provincially-recognized training in TBI.

Graded aerobic treadmill testing in pediatric sports-related concussion: safety, clinical use, and patient outcomes.

OBJECTIVE The objectives of this study were 2-fold: 1) to evaluate the safety, tolerability, and clinical use of graded aerobic treadmill testing in pediatric patients with sports-related concussion (SRC), and 2) to evaluate the clinical outcomes of treatment with a submaximal aerobic exercise program in patients with physiological post-concussion disorder (PCD). METHODS The authors conducted a retrospective chart review of pediatric patients (age < 20 years) with SRC who were referred to a multidisciplinary pediatric concussion program and underwent graded aerobic treadmill testing between October 9, 2014, and February 11, 2016. Clinical assessments were carried out by a single neurosurgeon and included clinical history taking, physical examination, and recording specific patient-reported concussion-related symptoms using the Post-Concussion Symptom Scale (PCSS). Graded aerobic treadmill testing using a modified Balke protocol for incremental increases in intensity was used as a diagnostic tool to assess physiological recovery, classify post-concussion syndrome (PCS) subtype, and reassess patients following treatment. Patients with a symptom-limited threshold on treadmill testing (physiological PCD) were treated with an individually tailored submaximal exercise prescription and multidisciplinary targeted therapies. RESULTS One hundred six patients (mean age 15.1 years, range 11-19 years) with SRC underwent a total of 141 treadmill tests. There were no serious complications related to treadmill testing in this study. Overall, 138 (97.9%) of 141 tests were well tolerated and contributed valuable clinical information. Treadmill testing confirmed physiological recovery in 63 (96.9%) of 65 patients tested, allowing successful return to play in 61 (93.8%). Treadmill testing was used to diagnose physiological PCD in 58 patients and cervicogenic PCD in 1 patient. Of the 41 patients with physiological PCD who had complete follow-up and were treated with tailored submaximal exercise prescription, 37 (90.2%) were classified as clinically improved and 33 (80.5%) successfully returned to sporting activities. Patients who did not respond or experienced an incomplete response to submaximal aerobic exercise treatment included 7 patients with migraine headaches and 1 patient with a postinjury psychiatric disorder. CONCLUSIONS Graded aerobic treadmill testing is a safe, tolerable, and clinically valuable tool that can assist in the evaluation and management of pediatric SRC. Future research is needed to confirm the clinical value of this tool in return-to-play decision making. Studies are also needed to understand the pathophysiology of physiological PCD and the effects of targeted treatment.

Retirement-from-sport considerations following pediatric sports-related concussion: case illustrations and institutional approach.

The decision to advise an athlete to retire from sports following sports-related concussion (SRC) remains a persistent challenge for physicians. In the absence of strong empirical evidence to support recommendations, clinical decision making must be individualized and should involve a multidisciplinary team of experts in concussion and traumatic brain injury. Although previous authors have advocated for a more conservative approach to these issues in child and adolescent athletes, there are few reports outlining considerations for this process among this unique population. Here, the authors use multiple case illustrations to discuss 3 subgroups of clinical considerations for sports retirement among pediatric SRC patients including the following: those with structural brain abnormalities identified on neuroimaging, those presenting with focal neurological deficits and abnormalities on physical examination, and those in whom the cumulative or prolonged effects of concussion are suspected or demonstrated. The authors' evolving multidisciplinary institutional approach to return-to-play and retirement decision making in pediatric SRC is also presented.

Traumatic Optic Neuropathy: A Potentially Unrecognized Diagnosis after Sports-Related Concussion.

Traumatic optic neuropathy is a rare cause of visual disturbance after head injury that can be difficult to distinguish from coexisting vestibulo-ocular dysfunction because of the overlap in presenting symptoms in patients with these conditions. We present a case report of a 13-year-old girl who sustained a head injury during a ringette game leading to blurred vision and diplopia persisting 5 months after injury. Clinical history and physical examination findings were consistent with a traumatic optic neuropathy, convergence insufficiency, and postconcussion syndrome. Neuroimaging was normal. The patient was managed using a multidisciplinary approach. At 6 months of follow-up, neuro-ophthalmological examination demonstrated evidence of permanent partial optic nerve injury, and formal neuropsychological testing fell primarily within normal limits. The patient was advised to retire from collision sports. The authors discuss the value of a comprehensive multidisciplinary approach to the evaluation and management of concussion patients presenting with persistent visual symptoms.

Psychiatric outcomes after pediatric sports-related concussion.

OBJECT: The objectives of this study were twofold: (1) to examine the prevalence of emotional symptoms among children and adolescents with a sports-related concussion (SRC) who were referred to a multidisciplinary pediatric concussion program and (2) to examine the prevalence, clinical features, risk factors, and management of postinjury psychiatric outcomes among those in this clinical population. METHODS: The authors conducted a retrospective chart review of all patients with SRC referred to a multidisciplinary pediatric concussion program between September 2013 and October 2014. Clinical assessments carried out by a single neurosurgeon included clinical history, physical examination, and Post-Concussion Symptom Scale (PCSS) scoring. Postinjury psychiatric outcomes were defined as a subjective worsening of symptoms of a preinjury psychiatric disorder or new and isolated suicidal ideation or diagnosis of a novel psychiatric disorder (NPD). An NPD was defined as a newly diagnosed psychiatric disorder that occurred in a patient with or without a lifetime preinjury psychiatric disorder after a concussion. Clinical resources, therapeutic interventions, and clinical and return-to-play outcomes are summarized. RESULTS: One hundred seventy-four patients (mean age 14.2 years, 61.5% male) were included in the study. At least 1 emotional symptom was reported in 49.4% of the patients, and the median emotional PCSS subscore was 4 (interquartile range 1-8) among those who reported at least 1 emotional symptom. Overall, 20 (11.5%) of the patients met the study criteria for a postinjury psychiatric outcome, including 14 patients with an NPD, 2 patients with isolated suicidal ideation, and 4 patients with worsening symptoms of a preinjury psychiatric disorder. Female sex, a higher initial PCSS score, a higher emotional PCSS subscore, presence of a preinjury psychiatric history, and presence of a family history of psychiatric illness were significantly associated with postinjury psychiatric outcomes. Interventions for patients with postinjury psychiatric outcomes included pharmacological therapy alone in 2 patients (10%), cognitive behavioral therapy alone in 4 (20%), multimodal therapy in 9 (45%), and no treatment in 5 (25%). Overall, 5 (25%) of the patients with postinjury psychiatric disorders were medically cleared to return to full sports participation, whereas 5 (25%) were lost to follow-up and 9 (45%) remained in treatment by the multidisciplinary concussion program at the end of the study period. One patient who was asymptomatic at the time of initial consultation committed suicide. CONCLUSIONS: Emotional symptoms were commonly reported among pediatric patients with SRC referred to a multidisciplinary pediatric concussion program. In some cases, these symptoms contributed to the development of an NPD, isolated suicidal ideation, and worsening symptoms of a preexisting psychiatric disorder. Future research is needed to clarify the prevalence, pathophysiology, risk factors, and evidence-based management of postinjury psychiatric outcomes after pediatric SRC. Successful management of these patients requires prompt recognition and multidisciplinary care by experts with clinical training and experience in concussion and psychiatry.

Clinical decision trees for predicting conversion from cognitive impairment no dementia (CIND) to dementia in a longitudinal population-based study.

The lack of gold standard diagnostic criteria for cognitive impairment in the absence of dementia has resulted in variable nomenclature, case definitions, outcomes, risk factors, and prognostic utilities. Our objective was to elucidate the clinical correlates of conversion to dementia in a longitudinal population-based sample. Using data from the Canadian Study of Health and Aging, a machine learning algorithm was used to identify symptoms that best differentiated converting from nonconverting cognitively impaired not demented participants. Poor retrieval was the sole predictor of conversion to dementia over 5 years. This finding suggests that patients with impaired retrieval are at greater risk for progression to dementia at follow-up. Employing significant predictors as markers for ongoing monitoring and assessment, rather than as clinical markers of conversion, is recommended given the less than optimal specificity of the predictive algorithms.

Patterns of cognitive decline, conversion rates, and predictive validity for 3 models of MCI.

Our objective was to compare the predictive ability of different models of mild cognitive impairment (MCI) as a marker of incipient dementia in a longitudinal population-based Canadian sample. We examined the use of existing, well-documented MCI criteria using data from persons who underwent a clinical examination in the second wave of the Canadian Study of Health and Aging (CSHA). Demographic characteristics, average neuropsychological test performance, and sample frequencies and conversion rates were calculated for each classification. Receiver operating characteristic (ROC) analyses were employed to assess the predictive power of each cognitive classification. The highest sample frequencies and conversion rates were associated with case definitions of multiple-domain MCI. The only diagnostic criteria to significantly predict dementia 5 years later was the cognitive impairment no dementia (CIND)-2 case definition. More restrictive MCI case definitions fail to address the varying temporal increases in decline across different cognitive domains in the progression from normal cognitive functioning and dementia.

Neuropsychiatric impairments as predictors of mild cognitive impairment, dementia, and Alzheimer's disease.

In this study, the relations between cognitive status and neuropsychiatric impairments in nondemented older adults in cross section and over time is examined. Using data from the Canadian Study of Health and Aging (CSHA), a longitudinal, nation-wide study in which data were collected 3 times (ie, CSHA-1, CSHA-2, CSHA-3) at 5-year intervals, individuals were classified with (n = 240) and without (n = 386) cognitive impairment at CSHA-2. Loss of interest, changes in personality and mood, and depression were reported by a knowledgeable informant (ie, family or friends) more frequently for those with cognitive impairment than for those without cognitive impairment. After controlling for initial cognitive status, loss of interest and depression contributed significantly to the prediction of mild cognitive impairment, dementia, and Alzheimer's disease over time. These findings suggest that these neuropsychiatric impairments play significant roles throughout the course of cognitive decline and should be taken into consideration even before cognitive impairment is evident.