Friedreich's ataxia (FRDA) is an inherited recessive disorder characterized by progressive neurological disability and heart abnormalities. A deficiency in the protein frataxin causes this disease. Frataxin deficiency leads to progressive iron accumulation in mitochondria, excessive free radical production and dysfunction of respiratory chain complexes. The expansion (GAA) repeat in the first intron causes decreased frataxin expression by interfering with transcription.

Activity of mitochondrial respiratory chain complex I (measured as NADH ferricyanide reductase) and intracellular ATP measurement was performed on lymphocyte of FRDA patients (n=12) and control subjects (n=25).

Our findings showed that complex I activity and intracellular ATP were significantly reduced (P=0.001) in patients compared with controls and we found strong correlation between complex I activity and intracellular ATP content in FRDA patients (r = 0.93; P<0.002). 8.6 and 9.0 kb deletion in mtDNA was detected in 9 patients out of 12 (75%) by multiplex polymerase chain reaction (PCR) and Southern blot analysis.

This study suggested that a biochemical defect in complex I activity and ATP production, which may be due to iron accumulation in mitochondria, can be involved in age of onset of FRDA.

Intravenous tissue plasminogen activator (IV tPA) has been studied primarily in patients over age 50. We sought to describe baseline differences in adult patients ≤50 years-old taken from a large prospective cohort of acute stroke patients treated with intravenous tPA (IV tPA) and to determine whether outcomes differed for this population.

Data (n = 1120) prospectively collected from the Canadian Alteplase for Stroke Effectiveness Study (CASES) were reviewed and patients aged ≤50 years-old (n=99) were compared with those aged >50 years (n=1021) with regards to baseline characteristics, symptomatic intracerebral haemorrhage (sICH), functional outcome at 90 days and death.

Nine percent of patients were ≤50 years-old. Among patients aged ≤50 years, 40.4% were women and median age was 42 ± 6.1 years (range 20 to 50). They had significantly more current cigarette use but fewer other vascular risk factors than older patients (p<0.05) and their baseline median NIHSS score was lower (13 versus 15, P=0.001). Although this group was more likely to have a favourable 90-day outcome, multivariable regression confirmed that age ≤50 years, while independently associated with a decreased risk of death (RR 0.36, 95% CI 0.14 to 0.95), was not itself predictive of favourable 90-day outcome or decreased risk of sICH.

Adult patients ≤50 years-old had fewer medical co-morbidities and a modestly lower baseline median NIHSS score than their older counterparts. Age ≤50 years was independently associated with a decreased risk of death but not with favourable outcome or risk of sICH.

Assessing the impact of glioma location on prognosis remains elusive. We approached the problem using multivoxel proton magnetic resonance spectroscopic imaging (1H-MRSI) to define a tumor “metabolic epicenter”, and examined the relationship of metabolic epicenter location to survival and histopathological grade.

We studied 54 consecutive patients with a supratentorial glioma (astrocytoma or oligodendroglioma, WHO grades II-IV). The metabolic epicenter in each tumor was defined as the 1H-MRSI voxel containing maximum intra-tumoral choline on preoperative imaging. Tumor location was considered the X-Y-Z coordinate position, in a standardized stereotactic space, of the metabolic epicenter. Correlation between epicenter location and survival or grade was assessed.

Metabolic epicenter location correlated significantly with patient survival for all tumors (r2 = 0.30, p = 0.0002) and astrocytomas alone (r2 = 0.32, p = 0.005). A predictive model based on both metabolic epicenter location and histopathological grade accounted for 70% of the variability in survival, substantially improving on histology alone to predict survival. Location also correlated significantly with grade (r2 = 0.25, p = 0.001): higher grade tumors had a metabolic epicenter closer to the midpoint of the brain.

The concept of the metabolic epicenter eliminates several problems related to existing methods of classifying glioma location. The location of the metabolic epicenter is strongly correlated with overall survival and histopathological grade, suggesting that it reflects biological factors underlying glioma growth and malignant dedifferentiation. These findings may be clinically relevant to predicting patterns of local glioma recurrence, and in planning resective surgery or radiotherapy.

Current ‘standard of care’ for patients presenting with a ‘high-risk’ TIA varies, with use of several outpatient and inpatient approaches. We describe the clinical outcomes and costs for high risk TIA patients who received care in a ‘rapid evaluation unit’, and compare these to a historical ‘high-risk’ cohort.

The study cohort was comprised of patients with TIA admitted to a ‘rapid evaluation unit’ during the period March 2002 to April 2003. The comparison cohort was established by screening Calgary Health Region ER discharge records to identify all patients presenting with a diagnosis of TIA during the year 2000. A ‘high-risk standard care cohort’ was then identified based on the clinical admission criteria used to select patients for the rapid evaluation unit. Outcomes (stroke within 90 days, death) and costs were identified using chart review and provincial administrative data.

The early risk of stroke in the high risk standard care group (392 patients) was 9.7%, compared to 4.7% in the rapid evaluation cohort (189 patients) (p=0.05). Median 1-year costs post TIA were CAN$8360 for patients in the rapid evaluation cohort, compared with CAN$4820 for patients in the high risk standard care group (p<0.001).

The risk of early stroke was lower for patients in the rapid evaluation cohort compared to the high risk standard care cohort, suggesting that the use of rapid evaluation programs in patients with TIA at high risk of stroke may be beneficial, but incur greater costs over the course of the first year.

Patients with low grade astrocytomas generally have good prognosis when total resection can be achieved, but surveillance neuroimaging is commonly performed to detect recurrence or progression. This study evaluated the utility and yield of such strategy for pilocytic and non-pilocytic cerebellar astrocytomas.

A 20-year retrospective review was performed of patients undergoing resection of cerebellar astrocytoma at a single institution. A negative MRI string (NMS) ratio was computed as the fraction of total follow-up period over which surveillance neuroimaging was negative for recurrence or progression. Chi-squared analysis differentiated NMS ratio by resection extent and lesion histopathology.

Twenty-eight patients with pilocytic (n=15) and non-pilocytic (n=13) astrocytoma underwent 34 craniotomies, with total resection in 19 cases. Surveillance MRIs (n=167) among total resection patients were uniformly negative for recurrent disease at average seven years follow-up (NMS ratio = 1.0). The 43 surveillance MRIs among subtotal resection patients revealed disease progression in two patients within six months of operation (NMS ratio = 0.78, p<0.05). No differences in NMS ratio were observed between pilocytic and non-pilocytic astrocytoma subtypes.

This study illustrates pediatric patients with low-grade cerebellar astrocytomas undergoing total resection may not benefit from routine surveillance neuroimaging, primarily because of low recurrence likelihood. Patients with subtotal resection may benefit from surveillance of residual disease, with further work aimed at exploring the schedule of such follow-up.

To assess the clinical features of several members of the same family diagnosed with both hot water epilepsy (HWE) and cerebral lesions.

Age at onset and types of seizure, precipitating factors, EEG findings, and neuroimages were evaluated.

The family consisted of six generations, including one consanguineous parent. Of eight family members diagnosed with epilepsy, seven suffered from HWE. Age at onset of seizures ranged within childhood. Seven patients with HWE experienced complex partial seizures, with or without secondary generalization; one experienced simple partial seizures as well as complex partial seizures. Three patients experienced spontaneous seizures as well as HWE. Interictal EEG revealed abnormalities in two patients. Magnetic resonance imaging revealed cerebral lesions in one patient, probably attributable to ischemic changes. Magnetic resonance images were consistent with findings of ischemic gliosis in two patients, and either demyelinating or ischemic gliosis in one patient.

Descriptions of HWE families with different ethnic backgrounds may permit more definite conclusions regarding the mechanisms epileptogenesis, and the genetic defects that underlie this disease.

Recently a high prevalence of asystole was found in individuals with refractory epilepsy.

To measure the prevalence and characterize the pattern of ictal bradycardia (IB) in our cohort.

We analyzed ictal heart rate (HR) and seizure localization in 69 consecutive individuals with intractable epilepsy. Ictal bradycardia was defined by HR less than 60 beat per min (bpm) and a fall of more than 30 bpm.

Ictal bradycardia was observed in 1.9% of seizures and in five individuals (7.2%), who presented IB in 5.7% of their seizures. Four of them had also relative IB (a decrease of HR of more than10 bpm) in the majority of their seizures. Four additional individuals showed relative IB.

Ictal bradycardia occurs more frequently than previously thought in individuals with refractory epilepsy. Recognition of individuals with small to moderate ictal HR decrease may help to identify those at greatest risk for asystole.

To present our experience with the endovascular management of intracranial dural arteriovenous fistulas with direct cortical venous drainage by trans-arterial embolisation using Onyx.

Between January 2004 and April 2008, 12 consecutive high grade intracranial dural arteriovenous fistulas (Cognard type III (eight patients) or IV (three patients)) were treated by trans-arterial embolisation with Onyx. The majority of cases were treated by Onyx embolisation alone. One case had additional embolisation with n-butyl-2-cyanoacrylate at the same session. Imaging follow-up was obtained in all but one patient (mean 3.6 months).

Nine patients had a technical success at the end of the embolisation procedure with complete angiographic exclusion of the fistula. Two patients had a small residual fistula at the end of embolisation, one of which had residual mild cortical venous drainage. Both were stable at follow-up angiography. One patient had a residual fistula supplied by the ophthalmic artery, which was thought to be unsafe to embolise and was sent for surgery, which was curative. In one patient the microcatheter ruptured, with a fragment of the distal microcatheter left in the occipital artery. No clinical complications were observed in this series at clinical follow-up (mean 3.3 months). Two patients were noted to have significant radiation dose.

Endovascular management of intracranial dural arteriovenous fistulas with direct venous cortical drainage by trans-arterial Onyx embolisation is a safe and effective treatment according to our experience. Fluoroscopy times and radiation dose may be a concern.

The computed tomogram angiography (CTA) ‘spot sign’ describes foci of intralesional enhancement associated with hematoma expansion in primary intracerebral hemorrhage patients. A consistent radiological definition is required for two proposed recombinant Factor VIIa trials planning patient dichotomization according to ‘spot sign’ presence or absence. We propose radiological criteria for diagnosis of the CTA ‘spot sign’ and describe different morphological patterns.

A prospective cohort of 36 consecutive patients presenting with primary intracerebral hemorrhage (ICH) were enrolled in a multicenter collaborative study, and have been included for the present analysis. Three reviewers analyzed the CTA studies in a blinded protocol. Analysis of specific ICH and ‘spot sign’ features was performed including prevalence, number, size, location, morphology and Hounsfield unit density.

Twelve of thirty-six patients (33%) demonstrated a total of 19 enhancing foci consistent with the CTA ‘spot sign’. Mean maximal axial ‘spot sign’ dimension was 3.7±2.2 mm and mean density was 216±57.7 HU. No significant differences in age or blood pressure (p=0.7), glucose (p=0.9), INR/PTT (p=0.3 and 0.4) or hematoma location (p=0.3) were demonstrated between patients with or without the ‘spot sign’. Consensus definition and classification criteria for the CTA ‘spot sign’ are proposed.

The ‘spot sign’ is defined as spot-like and/or serpiginous foci of enhancement, within the margin of a parenchymal hematoma without connection to outside vessels. The ‘spot sign’ is greater than 1.5 mm in maximal dimension and has a Hounsfield unit density at least double that of background hematoma density.

To compare the efficacy of computed tomographic angiography (CTA) to that of digital subtraction angiography (DSA) in the detection of secondary causes of intracerebral hemorrhage (ICH).

Between January 2001 and February 2007 there were 286 patients that had both CTA and DSA for intracranial hemorrhage of all types. Those with primarily subarachnoid hemorrhage or recent trauma were excluded. Fifty-five patients formed the study cohort. Three reviewers independently analyzed the CTAs in a blinded protocol and classified them based on presence or absence of a secondary etiology. Results were compared with the reference standard DSA and kappa values determined for interobserver variability.

The overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CTA were 89%, 92%, 91%, 91% and 91%, respectively. Kappa value for interobserver agreement ranged from 0.78 to 0.89. Two of four dural arteriovenous fistulas (dAVF) were missed on CTA by all three reviewers.

CTA is nearly as effective as DSA at determining the cause of secondary intracerebral hemorrhage, but with a lower sensitivity for dAVFs. This supports the use of CTA as the first screening test in patients presenting with spontaneous ICH.

Our main objective was to use videoconferencing as a primary means to: a) assist in launching an epilepsy surgery program in Pakistan; 2) participate in case conferences on complex epilepsy patients in each country.

Extensive testing using both point to point and bridged integrated service digital network (ISDN) and internet protocol (IP) connections was carried out using bandwidths of 384-768 kilobits per second (kbps). Videoconferences between sites were arranged two to three weeks in advance and connections were tested a day prior to the scheduled conference. Sharing of PowerPoint presentations, neuroimaging and video-EEG was available to all sites. Discussions centered on patients with medically refractory epilepsy.

Between July 2006 and June 2008, 17 sessions were booked. Five of these conferences bridged in specialists from West Virginia University. Most successful connections occurred using IP point to point calls or a bridge connecting end points through IP at 512 kbps. We conducted three surgeries for medically refractory temporal lobe epilepsy in Pakistan. At follow-up in January 2009, two patients have been seizure free and one had two breakthrough seizures after sudden unsupervised discontinuation of Levetiracetam.

Our international tele-epilepsy collaboration has proven feasible and valuable to all participants. Our experience suggests considerable thought and preparation are needed before a teleconference to ensure its success. We provide a recipe to set-up similar telemedicine collaborations. Considerations include time zone differences, equipment type, interoperability between endpoints, connection capabilities, bandwidth availability, and backup plans for unsuccessful connections. Telemedicine can facilitate epilepsy care around the world, identifying with the concept of a “Global Health Village”.

Chiari type II malformation (CII) is a developmental deformity of the hindbrain. We have previously reported that many patients with CII have impaired smooth pursuit, while few make inaccurate saccades or have an abnormal vestibuloocular reflex. In contrast, saccadic adaptation and visual fixation are normal. In this report, we correlate results from several eye movement studies with neuroimaging in CII. We present a model for structural changes within the cerebellum in CII.

Saccades, smooth pursuit, the vestibulo-ocular reflex, and visual fixation were recorded in 21 patients with CII, aged 8-19 years and 39 age-matched controls, using an infrared eye tracker. Qualitative and quantitative MRI data were correlated with eye movements in 19 CII patients and 28 controls.

Nine patients with CII had abnormal eye movements. Smooth pursuit gain was subnormal in eight, saccadic accuracy abnormal in four, and vestibulo-ocular reflex gain abnormal in three. None had fixation instability. Patients with CII had a significantly smaller cerebellar volume than controls, and those with normal eye motion had an expanded midsagittal vermis compared to controls. However, patients with abnormal eye movements had a smaller (non-expanded) midsagittal vermis area, posterior fossa area and medial cerebellar volumes than CII patients with normal eye movements.

The deformity of CII affects the structure and function of the cerebellum selectively and differently in those with abnormal eye movements. We propose that the vermis can expand when compressed within a small posterior fossa in some CII patients, thus sparing its ocular motor functions.

Most estimates of the prevalence of seizure disorders in Canada derive from national surveys which differ in sampling and case-finding methods. This study used health care utilization data to make a population-based estimate of the prevalence of epileptic seizures and of epilepsy in children in British Columbia (BC).

All BC residents between 0-19 years-of-age in 2002-3 enrolled in the Medical Services Plan were included. Epileptic seizures were defined using ICD-9 codes; health care utilization data was obtained from BC Linked Health Database. The period prevalence of epileptic seizures and of epilepsy was determined by age, urban/rural region and socioeconomic status.

8,125 of 1,013,816 children were identified as having an epileptic seizure of which 5,621 were classified as epilepsy - 5.5 per 1,000 children (95% CI: 5.4-5.7). The prevalence of epilepsy in infants and preschoolers was higher than that reported in the literature. A higher prevalence of epilepsy was observed also among those with low socioeconomic status. A higher prevalence of epilepsy was observed in those health regions with a higher proportion of First Nations and a lower prevalence was observed in health regions with a higher proportion of visible minorities.

Age-specific prevalence rates in BC children for epilepsy, determined from population-based administrative records, were similar to published data except in children under five years. We found a gradient of increased prevalence with decreased level of income. Prevalence rates based on utilization data have the potential to guide program planning for children with epileptic seizures.

To investigate the use of computed tomography (CT) scans in patients with suspected acute mild traumatic brain injury (mTBI) presenting to emergency departments.

850 potential mTBI cases were identified through reviews of three months of health records from nine selected emergency departments across the province of Ontario. Records for review were selected using the International Classification of Disease, 9th revision, Clinical Modification codes and Injury codes.

Patients who received head CT were significantly older (p<0.01), had documented loss-of-consciousness (LOC) &/or Post-TraumaticAmnesia (PTA) (p<0.001), documented nausea (p<0.01), documented vomiting (p<0.001), abnormal neurological exam results (p<0.01), had visited an urban center (p<0.001), and/or arrived by ambulance (p<0.001). The significant predictors of CT scan prescription (in a forward stepwise logistic regression) were urban location of hospital (OR=5.14; p≤0.001), LOC &/or PTA (OR=4.83; p≤0.001), vomiting (OR=2.56; p≤0.01), arrival by ambulance (OR=2.15; p≤0.001), nausea (OR=1.92; p=≤0.02) and older age (OR=1.02; p≤0.01).

These data extend our knowledge regarding the use of CT during acute diagnosis and management of suspected mTBI patients. In addition to confirming previously reported risk factors of intracranial complication, geographical location of hospital and arrival mode were found to be significant predictors of CT use. The results suggest that the management patterns for acute mTBI are inconsistent. The implications of this are discussed.

The onset of progressive cerebellar ataxia in early childhood is considered a key feature of ataxiatelangiectasia (A-T), accompanied by ocular apraxia, telangiectasias, immunodeficiency, cancer susceptibility and hypersensitivity to ionizing radiation.

We describe the clinical features and course of three Mennonite children who were diagnosed with A-T following the completion of therapy for lymphoid malignancies.

Prior to cancer therapy, all had non-progressive atypical neurological abnormalities, with onset by age 30 months, including dysarthria, dyskinesia, hypotonia and/or dystonia, without telangiectasias. Cerebellar ataxia was noted in only one of the children and was mild until his death at age eight years. None had severe infections. All three children were “cured” of their lymphoid malignancies, but experienced severe adverse effects from the treatments administered. The two children who received cranial irradiation developed supratentorial primitive neuroectodermal tumors of the brain, an association not previously described, with fatal outcomes.

The range of neurological presentations of A-T is broad. Ataxia and telangiectasias may be minimal or absent and the course seemingly non-progressive. The diagnosis of A-T should be considered in all children with neuromotor dysfunction or peripheral neuropathy, particularly those who develop lymphoid malignancies. The consequences of missing the diagnosis may be dire. Radiation therapy and radiomimetic drugs should be avoided in individuals with A-T.

Younger patients, aged below 45 years, usually lack the conventional risk factors of stroke whereas infections, especially in developing countries, may play a role. There have been many reports in the last decade about the association of Chlamydia pneumoniae (C.pneumoniae) and atherosclerosis involving cerebral vessels.

To investigate the seroprevalence of C.pneumoniae IgG and IgA antibodies in patients aged below 45 years with acute ischemic stroke.

This study was done at a tertiary care hospital in South India between January 2004 and December 2006 where we recruited consecutive patients aged less than 45years with acute ischemic stroke. Age and sex matched controls were recruited from the outpatient department with non stroke diagnosis. All stroke patients underwent CT (Computerized Tomography), MRI (Magnetic Resonance Image), MRA (Magnetic Resonance Angiography), Transthoracic Echocardiography and Carotid Doppler for stroke sub group diagnosis. We measured C.pneumoniae antibodies IgG and IgA by microimmunofluorescence technique in all patients and controls.

A total of 120 patients and 120 controls were studied over a period of two years. We found C.pneumoniae antibodies in 29.1% (35/120) stroke patients and in 12.5% (15/120) control subjects (p=0.002). C.pneumoniae IgG antibodies were found in 27.5 % (33/120) of stroke patients and 12.5% (15/120) of controls (p=0.006). IgAantibodies were observed in 5 % (6/120) of strokes and none in control group (p=0.03). After adjustment of all risk factors C.pneumoniae IgG seropositivity showed odds ratio of 2.6; 95% Confidence Interval 1.2-5.6.

C.pneumoniae IgG antibodies were found to be associated with ischemic stroke in young.