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.

Purpose: To compare patient effective dose resulting from two alternative imaging protocols for pre-coiling assessment of intracranial aneurysms: a series of 2D Digital Subtraction Angiography (DSA) projections, and a 3D rotational angiography (RA) acquisition. Methods: In a retrospective analysis, we investigated 44 patients who underwent endovascular coiling in our institution. Images were acquired on a biplane Image Intensifier system not equipped with dose-area product (DAP) meter. Conventional 2D DSA images were simulated with an anthropomorphic skull phantom. Entrance skin dose was measured with a 60 cc ion chamber, and the PCXMC Monte Carlo based software was used to calculate patient effective dose. For the RA protocol, a 16 cm computed tomography (CT) dosimetry phantom and a 100 mm pencil ion chamber were employed to measure the CT dose index. Patient effective dose was calculated with the ImPACT calculator. An unpaired two-tailed t-test was used to determine the significance of differences between patient doses in each group. Results: Sixteen patients underwent the 2D DSA protocol with multiple projections; their mean number of cine runs was 5.1; the mean effective dose was 2.11 millisievert (mSv) (range 1.69–3.43 mSv). Twenty eight patients were assessed using the 3D RA protocol with the effective dose of 1.29 mSv. The difference between the means of two dose distributions was statistically significant (p=0.00028). Conclusion: Our study demonstrated that the patient effective dose was significantly lower from the 3D RA protocol than that from the 2D DSA protocol used in the planning of coiling of intracranial aneurysm.

Automated analysis of 1p and 19q status in oligodendroglial tumors by fluorescence in-situ hybridization (FISH) can be achieved by image-analysis software present in the majority of institutions using the FISH technique. Despite the widespread availability of this software, there are no specific guidelines in the literature on how to use it.

We studied which green/red (G/R) probe signal combinations are predictive of 1p/19q co-deletion in a retrospective series of 53 oligodendroglial tumours and defined a new algorithm with a reduced sequence of combinations compared to previous studies. This algorithm was then tested and refined on a prospective series of 45 oligodendroglial tumours. The new algorithm scores 24 G/R combinations, which represent less than 50 % of the total observed combinations in our series. This algorithm excludes some previously described combinations and redefines the place of others. G/R combinations of 5/2, 6/2 and 6/3 associate with deletion status combinations, combinations of 1/2 associate with normal chromosome status, and combinations of 3/3 and 4/4 associate with imbalanced chromosome status.

The new algorithm when applied to the combination and ratio methods of signal probe analysis gives a high concordance between manual and automated analysis on examination of 100 tumour cells (91% concordance for 1p and 89% concordance for 19q) and total concordance on examination of 200 tumour cells. This highlights the value of automated analysis to identify cases with imbalanced chromosome status, in which a larger number of tumour cells should be study by manual analysis. Our algorithm can be easily programmed on all existing FISH analysis software platforms and should facilitate multicentric evaluation and standardization of 1p/19q assessment in gliomas.

Background: Recurrence of chronic subdural haematomas (CSDHs) after surgical drainage is a significant problem with rates up to 20%. This study focuses on determining factors predictive of haematoma recurrence and presents a scoring system stratifying recurrence risk for individual patients. Methods: Between the years 2005 and 2009, 331 consecutive patients with CSDHs treated with surgery were included in this study. Univariate and multivariate analyses were performed searching for risk factors of increased post-operative haematoma volume and haematoma recurrence requiring repeat drainage. Results: We found a 12% reoperation rate. CSDH septation (seen on computed tomogram scan) was found to be an independent risk factor for recurrence requiring reoperation (p=0.04). Larger post-operative subdural haematoma volume was also significantly associated with requiring a second drainage procedure (p<0.001). Independent risk factors of larger post-operative haematoma volume included septations within a CSDH (p<0.01), increased pre-operative haematoma volume (p<0.01), and a greater amount of parenchymal atrophy (p=0.04). A simple scoring system for quantifying recurrence risk was created and validated based on patient age (< or ≥80 years), haematoma volume (< or ≥160cc), and presence of septations within the subdural collection (yes or no). Conclusion: Septations within CSDHs are associated with larger post-operative residual haematoma collections requiring repeat drainage. When septations are clearly visible within a CSDH, craniotomy might be more suitable as a primary procedure as it allows greater access to a septated subdural collection. Our proposed scoring system combining haematoma volume, age, and presence of septations might be useful in identifying patients at higher risk for recurrence.

Background: KCNQ2 abnormalities were described in infants with benign familial neonatal seizures (BFNS) and epileptic encephalopathy (EE). Associated features possibly include abnormal neuroimaging findings such as hypomyelination and/or T2 high signal of basal ganglia. Methods: This report describes 4 infants carrying different heterozygous KCNQ2 variants and 2 infants with 20q13.33 deletions encompassing KCNQ2 gene. Results: The different KCNQ2 mutations led to EE in 3 patients and included a novel de novo missense variant, p.Arg201Cys/c.601C>T, in an infant with severe EE and global developmental delay, hyperkinetic movement disorder, autonomic dysfunction with chronic hypoventilation, apnea, low GABA levels in CSF, and hypomyelination. She died at age 3 years of respiratory failure. One patient with BFNS and normal MRI has a previously reported c.508delG frame shift mutation in KCNQ2. Of the two de novo 22q13.33 deletions (1.2Mb versus 254.1 Kb) the larger caused a more severe phenotype, including focal epilepsy from infancy until 4 years, moderate developmental delay and diffuse brain volume loss. Conclusions: Along with varied epilepsy phenotypes and neuroimaging findings KCNQ abnormalities were associated with severe autonomic dysfunction and reduced CSF GABA levels. This might have further treatment implications, besides that the altered potassium channel function itself presents a therapeutic target.

Background: Polymorphisms in the endothelial nitric oxide synthase (eNOS) and in the plasminogen activator inhibitor -1 (PAI-1) genes have been implicated in stroke pathogenesis but results are still controversial. The aim of this study was to examine the possible contribution of Glu298Asp in the eNOS and 4G/5G in the PAI-1polymorphisms with ischemic stroke in a young Mexican population. Materials and Methods: In a case-control study, conducted between January 2006 and June 2010, 204 patients ≤45 years of age with ischemic stroke and 204 controls matched by age and gender, were recruited. The Glu298Asp and 4G/5G polymorphisms were determined in all participants by polymerase chain reaction-restriction fragment length polymorphism. Results: There was a significant difference in the Glu298Asp genotype distribution (P=0.001) and allele frequency between the two groups (P=0.001). The 4G/5G genotype distribution (P=0.40) and the allele frequency was similar between groups; (P=0.13). There were independent factors for ischemic stroke: Asp carriage (GluAsp+AspAsp) (P=0.02); smoking (P=0.01); hypertension (P=0.03), and familial history of atherothrombotic disease (P=0.04). Conclusions: The Asp allele from the Gu298Asp gene represents an independent risk factor for ischemic stroke in a young Mexican population. In contrast, the 4G/5G was not associated with an increased risk for this disease in the same group of patients, as previously has been demonstrated in other populations.

Background: Patients with acute cardio-embolic stroke from atrial fibrillation (AF) are at risk for recurrence with up to 50% of recurrent stroke occurring within two weeks of the index event. Anti-coagulation with heparinoids within 48 hours of stroke has been shown to increase risk of symptomatic intracranial hemorrhage (ICH) with no clear benefit on early stroke recurrence. Methods: This study was a retrospective chart review of consecutive patients who were admitted to the stroke service at the Foothills Medical Centre between 2009 and 2011. All patients with an acute stroke with a cardio-embolic etiology and a diagnosis of atrial fibrillation were reviewed. We hypothesized that anti-coagulation within two weeks of stroke, appropriately begun because of a diagnosis of AF, decreased rates of recurrent stroke without causing an increase in rates of symptomatic ICH. Results: Between 2009-2011, 324 patients were identified with cardio-embolic stroke secondary to AF. Within two weeks of stroke onset 61.4% (199/324) of patients were therapeutic on anti-coagulation. Patients who were anti-coagulated had a smaller median index stroke volume (3.2 ml vs 18.4 ml). Three (0.9%) patients suffered a clinically significant ICH. Recurrent stroke occurred in 11 patients (3.4%) within the two-week period. Therapeutic anti-coagulation within two weeks of initial stroke was associated with a decreased risk of recurrent stroke (RR 0.1, 95% CI 0.03-0.64). Conclusions: Anti-coagulation within two weeks of acute stroke in patients with AF appears to be safe among patients with smaller infarcts and prevents early recurrent infarction.

Introduction: The mortality of Parkinson’s disease (PD) and its associated risk factors among clinically definite PD patients in China has been rarely investigated. Our study aimed to identify the mortality rates and predictors of death in PD patients in China. Methods: 157 consecutive, clinically definite PD patients from the urban area of Shanghai were recruited from a central hospital based movement disorder clinic in 2006. All patients were regularly followed up at the clinic until December 31, 2011, or death. Mortality and associations with baseline demographics, health and medical factors were then determined within the cohort. Results: After 5 years, 11(7%) patients had died. The standardised mortality ratio was 0.62 (95% CI 0.32 to 1.07, P=0.104). The main causes of death were pneumonia (54.5%, 6/11) and digestive disorders (18.2%, 2/11), respectively. Age at onset, independent living, the mini mental state examination score, the Parkinson’s disease sleep scale score and the Epworth sleepiness scale score at baseline were statistically significantly different between the survival group and the deceased group (P<0.05). Across all participants, risk factors for death included low mini mental state examination score, and high Epworth sleepiness scale score according to a binary variable logistic regression analysis. Conclusions: This study confirms the similar survival of patients with PD to the control population up to a follow-up of 5 years. Interventions tailored to potential risk factors associated with death may offer further benefits.

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: Essential tremor (ET) is the most common tremor disorder in adults. In addition to upper limbs, the tremor in ET may also involve head, jaw, voice, tongue, and trunk. Though head tremor (HT) is commonly present in patients with ET, large comparative studies of ET patients with HT (HT+) and without HT (HT−) are few. Methods: To determine whether ET with HT is a distinct clinical subtype by comparing ET patients with and without HT, a chart review of 234 consecutive patients with ET attending the neurology clinics of the National Institute of Mental Health and Neurosciences, India, was done. A movement disorder specialist confirmed the diagnosis of ET in all patients using the National Institutes of Health collaborative genetic criteria. Results: HT was present in 44.4% of the patients. Comparison between HT+ and HT− showed that the HT+ group patients: (1) were older, (2) had later onset of tremor, (3) had unimodal distribution of age at onset with a single peak in the fifth decade, (4) had more frequent voice tremor, and (5) were more likely to have mild cervical dystonia. HT was part of presenting symptoms in nearly two thirds of the ET patients and in the rest it was detected during clinical examination. Conclusions: Several demographic and clinical variables suggest that ET patients with HT have a distinct clinical phenotype.

Background: Recurrence after intracranial aneurysm coiling is a highly prevalent outcome, yet to be understood. We investigated clinical, radiological and procedural factors associated with major recurrence of coiled intracranial aneurysms. Methods: We retrospectively analyzed prospectively collected coiling data (2003-12). We recorded characteristics of aneurysms, patients and interventional techniques, pre-discharge and angiographic follow-up occlusion. The Raymond-Roy classification was used; major recurrence was a change from class I or II to class III, increase in class III remnant, and any recurrence requiring any type of retreatment. Identification of risk factors associated with major recurrence used univariate Cox Proportional Hazards Model followed by multivariate regression analysis of covariates with P<0.1. Results: A total of 467 aneurysms were treated in 435 patients: 283(65%) harboring acutely ruptured aneurysms, 44(10.1%) patients died before discharge and 33(7.6%) were lost to follow-up. A total of 1367 angiographic follow-up studies (range: 1-108 months, Median [interquartile ranges (IQR)]: 37[14-62]) was performed in 384(82.2%) aneurysms. The major recurrence rate was 98(21%) after 6(3.5-22.5) months. Multivariate analysis (358 patients with 384 aneurysms) revealed the risk factors for major recurrence: age>65 y (hazard ratio (HR): 1.61; P=0.04), male sex (HR: 2.13; P<0.01), hypercholesterolemia (HR: 1.65; P=0.03), neck size ≥4 mm (HR: 1.79; P=0.01), dome size ≥7 mm (HR: 2.44; P<0.01), non-stent-assisted coiling (HR: 2.87; P=0.01), and baseline class III (HR: 2.18; P<0.01). Conclusion: Approximately one fifth of the intracranial aneurysms resulted in major recurrence. Modifiable factors for major recurrence were choice of stent-assisted technique and confirmation of adequate baseline occlusion (Class I/II) in the first coiling procedure.

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.

Objective: The radiological and clinical significance of a dilated Virchow-Robin space (dVRS) in the striatum (STR) remains unclear. We investigated the role of dVRS in STR on parkinsonism and dopamine transporter positron emission tomography (DaT-PET) findings. Methods: Patients with parkinsonism who underwent both brain magnetic resonance imaging and DaT-PET were included. Clinical status was evaluated by Hoehn and Yahr (HY) stage, Korean-Mini Mental Status Examination (K-MMSE), Montreal Cognitive Assessment Korea (MoCA-K), and Frontal Assessment Battery (FAB). dVRS was assessed by semi-quantitative and quantitative scales in each of the three segments of STR (caudate nuclei, anterior and posterior putamen) and was expressed as a dVRS score. DaT-PET was qualitatively assessed as either normal or abnormal in each segment. The relationship between dVRS and DaT-PET abnormality (ab-DaT-PET) was designated in each segment as either concordant or discordant. A concordant segment was defined by the presence of dVRS with ab-DaT-PET [Concordance rate (CR)=number of concordant segments/number of concordant and discordant segments]. Results: Eleven patients were included. There was no significant correlation between the presence of dVRS and ab-DaT-PET. The mean CR was 0.39. CR was not significantly correlated with any clinical or neuroimaging scales. The dVRS score was significantly correlated with K-MMSE, MoCA-K, and FAB (r=−0.675, −0.847, and −0.868, respectively) but not with HY stage. Conclusion: dVRS in STR played no significant role on dopaminergic innervation revealed by DaT-PET and made little contribution to clinical parkinsonism; however, it was correlated with cognitive impairment.

Proteoglycans are components of the extracellular matrix and have roles in brain development and responses to injury. Connective tissue components are known to be major inhibitors of remyelination in mouse models of demyelination and are found at the border of active demyelinating lesions in Multiple Sclerosis. Surfen (bis 2-methyl, 4- amino, 6-quinolyl amide) is a small molecule antagonist previously shown to bind preferentially to heparan sulfate and related proteoglycans.

We have previously reported that surfen reduces T cell proliferation in vivo and in vitro. Here we report the effects of surfen on an in vivo model of demyelination and its effects on macrophage function in vitro. Demyelination was induced by injecting the detergent lysolecithin into the spinal cord dorsal columns of adult C57Bl/6 mice. Relative to vehicle treated mice, co-injection of surfen (100 μM) with lysolecithin reduced total lesion area seven days post-injection. Because macrophages dominate these lesions and influence remyelination, murine bone marrow derived macrophages were assessed using assays of chemotaxis and phagocytosis. Macrophages chemotaxis was increased in response to surfen (10 μM) relative to vehicle by approximately 15% (p<0.05). Phagocytosis of E. coli was not affected by surfen.

These effects of surfen on experimental demyelination and macrophage function suggest that proteoglycan binding may promote aspects of myelin repair relevant to Multiple Sclerosis.

Background: Perinatal stroke causes hemiparetic cerebral palsy. Constraint therapy (CIMT) improves function in congenital hemiparesis and adult stroke. Repetitive transcranial magnetic stimulation (rTMS) may improve function in adult stroke. The two have not been tested in perinatal stroke. Methods: PLASTIC CHAMPS (www.clinicaltrials.gov/NCT01189058) was a controlled factorial trial of rTMS and CIMT in perinatal-stroke hemiparesis. Children 6-18 years participated in a 2 week peer-supported motor learning camp, randomized to daily inhibitory rTMS (1200 stimulations, contralesional M1), CIMT, both or neither. Primary outcomes were Assisting Hand Assessment (AHA) and Canadian Occupational Performance Measure (COPM) at 1, 8, and 24 weeks. Quality-of-life, safety and tolerability were evaluated. Change was assessed across treatment groups over time (linear mixed effects model). Results: All forty-five subjects completed the trial (median 11.4yrs). COPM scores increased >100% with maximal gains at 6 months (p<0.002). Addition of rTMS and/or CIMT doubled the chances of clinically significant gains. Combined rTMS+CIMT resulted in larger AHA gains at all time points (6 months p=0.006). CIMT or rTMS alone had more modest effects. Neither treatment decreased function in either hand. Procedures were well tolerated. Conclusions: Children with hemiparesis participating in intensive, psychosocial rehabilitation programs perceive marked increases in function. Non-invasive brain stimulation may enhance motor learning therapy in perinatal stroke hemiparesis.