Cross-sectional research has demonstrated poorer function and health-related quality of life (HRQOL) in those with multiple sclerosis (MS) but less is known about change over time. The goals of this study were to measure change in HRQOL and identify factors associated with change.

HRQOL was assessed at baseline and annually over two subsequent years using the Multiple Sclerosis Quality of Life Inventory. Function was assessed using the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite. Annualized rate of change was calculated for all twenty outcomes. Mixed effects modeling (univariate followed by multivariate) was used to examine the associations among patient characteristics and the age- and sex-adjusted Physical Component Summary (PCS) and Mental Component Summary (MCS) at study initiation and over the two years of follow-up.

Of 300 participants, 288 (96%) provided at least one assessment and are included in this analysis. Although 14 of the 20 outcomes showed a mean decline, only two (SF-36 physical function, p=0.018 and the EDSS, p<0.001) were statistically significant. The SF-36 social function showed a significant improvement (p=0.031). Only two variables were significantly associated with a decreased rate of decline or improvement over two years, including being female (PCS, p=0.001) and use of visiting nurse services (MCS, p<0.001).

HRQOL is relatively stable over two years of follow-up, particularly for mentally-oriented outcomes. Further research with a longer period of follow-up is needed to provide additional insight into factors associated with change in HRQOL in patients with MS.

Gait apraxia is a gait disorder not attributable to motor, cerebellar, or sensory dysfunction. Gait impairment is common in Multiple Sclerosis (MS), but is mostly attributed to spasticity and ataxia. Impairment ratings scales are designed accordingly and do not separately evaluate apraxia.

To describe 15 patients with gait apraxia resulting from MS as their major functional impairment.

The Mayo Clinic database (1994-2007) was searched for the terms MS and gait apraxia. Inclusion criteria: Definite MS, significant gait apraxia. Exclusion criteria: alternative disorder causing apraxia, predominantly spastic/ataxic gait disorder.

9 (60%) of the patients were women, and 12 (80%) had a progressive MS course. Gait apraxia was evident at a median of 8 years (range 0-34) following MS onset. Median EDSS at recognition of gait apraxia was 6.5 (range 5-8). Cognitive dysfunction was present in 11 (73%) and neurogenic bladder dysfunction in 14 (93%). The commonest MRI findings were confluent periventricular T2 lesions, T1 hypointensity and generalized cerebral atrophy with symmetrical ex vacuo ventricular enlargement.

Gait apraxia can cause significant functional impairment in MS patients, and may be underrecognized. The natural course of the neurological deficit in such patients is unknown, and may differ from that of MS patients with other ambulatory disabilities.

We studied α-B-crystallin, a small heat shock chaperone protein upregulated by various “stresses”, as an immunocytochemical tissue marker of epileptic foci.

We examined 45 resected brain tissues of epileptic patients, 16 months to 23 years. Postmortem brains of 2 epileptic children and 20 normal fetuses and neonates of 10-41 weeks gestation similarly were studied. Immunocytochemical demonstration of α-B-crystallin was supplemented by neuronal, glial and inflammatory cell markers and electron microscopy (EM) in surgical cases. Autopsy brain tissue of children without epilepsy or neurological disease served as controls.

In all resections, α-B-crystallin was overexpressed in astrocytes and oligodendrocytes, including satellite cells adherent to neurons, and occasionally in neurons of neocortex, hippocampus and amygdala. In six cases, reactivity was most intense at or near the epileptic focus, with a diminishing gradient of intensity for 2-3 cm; similar focal expression was seen in autopsy cases. Presence or absence of histological structural lesions was independent of α-B-crystallin expression. Balloon cells and giant atypical cells in tuberous sclerosis were intensely reactive. Reactivity was present in DNETs. No correlation occurred with microglial activation, inflammation or gliosis; no ultrastructural alterations were seen. No expression was seen in fetal brains at any age.

Immunoreactive α-B-crystallin is a reliable tissue marker of epileptic foci, regardless of presence or absence of structural lesions; at times it maps the extent of a focus.

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.

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”.

Video-electroencephalography (VEEG) telemetry is the simultaneous recording of ictal and interictal EEG pattern and paroxysmal behavior to investigate the nature of paroxysmal events.

This is a prospective study performed to asses the safety and yield of early discontinuation of antiepileptic drugs (AEDs) in the telemetry unit. Over a 2.5-year period, 50 patients that met the indications for VEEG monitoring were admitted by an epileptologist to neuro-observation units with continuous monitoring, nursing coverage and EEG technicians support during working hours and on-call thereafter. In most cases AEDs (except Phenobarbital) were discontinued in 24h. We prospectively assessed the yield and safety of the telemetry investigation as well as epilepsy surgery outcomes.

Our monitoring answered the study question in 88% of the patients. The question was not answered in 12% of cases due to the lack of recorded events. Our results changed the management in 74% of cases and potentially improved quality of life by decreasing the AEDs consumption and number of seizures per month. Over all, 22% received epilepsy surgery and became either seizure free or their seizures became non-disabling. Our method significantly decreased the duration of hospital admission for monitoring and minimal complications occurred only in 8% of patients.

In conclusion, our method for short VEEG monitoring has a high yield for diagnosis, minimal complications and is cost effective. These qualities, together with good surgery results validate our method for the investigation and treatment of refractory seizure cases.

To evaluate the results of intracranial electrical stimulation (ICES) as a pre-surgical tool in order to select the side of the operation in bitemporal lobe epilepsy (BTLE) patients who underwent depth electrode (DE) implantation.

We reviewed the files of 77 medically intractable BTLE patients who underwent ICES with positive results through implanted DEs and then were under surgical treatment. One year or more after surgery, we evaluated the outcome. ICES was performed through: 1) Square-wave bipolar stimulation with symmetrical pulses of 60 Hz for 0.5 ms was delivered by a constant current Nuclear Chicago stimulator; 2) An initial intensity of 0.5 mA, and subsequently progressively stronger currents at 1-2 and occasionally 3 or 4 mA; 3) The duration of a single stimulation was usually 5 seconds; 4) The volume of tissue effectively stimulated did not exceed 5 mm.

We obtained habitual auras or seizures (clinical responses, CRs) in 74 patients and after-discharges, ADs in 61 of them, according to Engel's classification for post surgery outcomes. If CRs or ADs were obtained by stimulation of only one temporal lobe the result of epilepsy surgery tended to be better (Engel classes I or II) when the operation was done on the same side of positive CRs (15 cases) or ADs (14 cases), and tended to be worse (Engel classes III or IV) when the ICES had provoked bilateral responses or when the side operated on was contra-lateral to positive CRs (33 cases) or ADs (28 cases). Statistical analyses were performed in order to test these results and we found better post-operative results when the resection took place in the same side of positive responses to ICES (CRs: χ2 4.74 and p=0.0295; ADs: χ2 7.57 and p=0.0059).

In addition to other methods (PET, MRI and neuropsychology) presurgical ICES can provide useful data in the process of identifying the temporal lobe to be targeted for resection in BTLE patients.

To evaluate the performance of a one-minute screening test measured against a validated 10-minute screening test for mild cognitive impairment (MCI) in detecting CI in patients aged ≥ 65 years with two or more vascular risk factors (VRF).

Patients (n=1523) aged 65 years or older without documented CI symptoms or dementia with two or more VRF participated in this study set in Canadian primary care practice. Baseline data was collected, followed by the 1-minute animal fluency (AF) test and the 10-minute Montreal Cognitive Assessment (MoCA). Physicians (n=122) completed case reports during patient interviews and reported their diagnostic impression. AF test sensitivity, specificity, and accuracy in predicting a positive MoCA was assessed.

Study sample mean age was 79.7 years, 55% were female, 97.6% were Caucasian and 75% had ≤ 12 years of education. The AF test and MoCA detected CI in 52 and 56 percent of the study population, respectively. The AF test demonstrated sensitivity, specificity, and accuracy in predicting a positive MoCA of 67 percent each. Physicians diagnostic impression of MCI was reported for 37% of patients, and of dementia for 6%.

In an elderly population with at least two VRF, using AF can be useful in detecting previously unknown symptoms of CI or dementia. Screening for CI in this high risk population is warranted to assist physician recognition of early CI. The short AF administration time favours its incorporation into clinical practice.

This descriptive study seeks to identify the incidence rates of head injuries in a large Canadian province, given incident cases for a ten year period. It describes cases in terms of age standardized rates, demographics, and health care utilization.

The analyses were done using descriptive statistics. Incidence rates were calculated using the direct method. The indicators of hospital resource utilization were: mean length of hospital stay, number of intensive care unit (ICU) stays, and mean length of stay in an ICU.

In the ten year period, British Columbia saw 48,753 admissions due to an incident head injury. The most common head injury diagnosis was an “Intracranial” injury. The year with the highest total age standardized rate was 1991/92 (174.18/100 000). The mean length of hospital stay was 7.4 days. Ten percent had an ICU stay and the mean length of stay was 4.4 days (± 4.8). The diagnosis with the longest mean length of stay was a “Fractured Skull” while of the top five E-code categories; “Motor Vehicle Traffic” had the highest mean length of stay with 12.2 days.

Our study provides a much needed analysis of the incidence of head injuries in British Columbia. These rates can be compared to other provinces using the 2001 Canadian population as the standardized population. Our results indicate that there are certain “at risk” groups that warrant attention, in particular, younger men with lower socioeconomic standing. Indicators of health care utilization presented in the study should generate policy discussions.

As has been shown previously, S-100β levels in serum can be a useful predictor of brain damage after head trauma. This pilot study was designed to investigate whether urine samples, which are much easier to obtain, could be used for the same purpose instead of serum samples.

Ninety-six consecutive patients admitted with head trauma were recruited in the study. After exclusion of 54 patients, mostly because of significant additional trauma, S-100β levels were analyzed in serum and urine of 42 patients using a luminometric assay. A range for normal values was established based on samples from ten healthy volunteers.

S-100β serum levels increased proportional to the severity of the head trauma, as had been previously shown by several other groups. In many patients, initial increases in urine S-100β levels were seen later than in serum, after which the kinetics of S-100β levels in urine seemed to follow that established for serum levels. S-100β values in urine were on average about 54% lower in urine than in serum.

S-100β levels in urine obtained on admission to the hospital are not a good indicator for the extent of brain damage. However, urine S-100β levels obtained at later time points might be a useful indicator for the development of secondary brain injury.

Chemoradiotherapy followed by monthly temozolomide (TMZ) is the standard of care for patients with glioblastoma multiforme (GBM). Case reports have identified GBM patients who experienced transient radiological deterioration after concurrent chemoradiotherapy which stabilized or resolved after additional cycles of adjuvant TMZ, a phenomenon known as radiographic pseudoprogression. Little is known about the natural history of radiographic pseudoprogression.

We retrospectively evaluated the incidence of radiographic pseudoprogression in a population-based cohort of GBM patients and determined its relationship with outcome and MGMT promoter methylation status.

Out of 43 evaluable patients, 25 (58%) exhibited radiographic progression on the first MRI after concurrent treatment. Twenty of these went on to receive adjuvant TMZ, and subsequent investigation demonstrated radiographic pseudoprogression in 10 cases (50%). Median survival (MS) was better in patients with pseudoprogression (MS 14.5 months) compared to those with true radiologic progression (MS 9.1 months, p=0.025). The MS of patients with pseudoprogression was similar to those who stabilized/responded during concurrent treatment (p=0.31). Neither the extent of the initial resection nor dexamethasone dosing was associated with pseudoprogression.

These data suggest that physicians should continue adjuvant TMZ in GBM patients when early MRI scans show evidence of progression following concurrent chemoradiotherapy, as up to 50% of these patients will experience radiologic stability or improvement in subsequent treatment cycles.

Larger intracranial tumors require extended operating times and may be associated with increased perioperative complications. There are few reports describing the experience of resecting large meningiomas ≥5cm in a variety of locations. As a group, it remains largely unknown whether these relatively rare lesions are amenable to radical resection, and what factors influence their resectability.

Sixty-seven patients undergoing surgery for a large intracranial meningioma (≥5cm in the longest dimension) between 1998 and 2004 were retrospectively reviewed. The surgeries were performed at a single institution University of California at San Francisco. Predictors of resectability were assessed via multivariate logistical regression analysis.

Thirty-nine (58%) patients underwent gross total resection (GTR) (Simpson grades I/II). There were no cases of perioperative mortality. At last follow-up, symptoms improved in 39 (58%) patients, remained unchanged in 20 (30%), and were aggravated in 8 (12%). In the multivariate model for all large meningiomas, age>45 years [OR(95%CI);0.127 (0.026-0.616),p=0.01] and superior sagittal sinus involvement [OR(95%CI);0.160 (0.026-0.976),p=0.05] were negative predictors of GTR, while preoperative embolization [OR(95%CI);8.087(1.719-38.044),p=0.008] was positively associated with GTR. For only supratentorial meningiomas, superior sagittal sinus involvement [OR (95%CI);0.077 (0.010-0.571),p=0.01] and preoperative embolization [OR(95%CI);10.492(1.961-56.135),p=0.006] were independently associated with GTR.

This study evaluated a subset of large intracranial meningiomas ≥5cm. The results indicate that GTR can be achieved in the majority of cases with limited morbidity and mortality, where symptoms will likely improve and recurrences seldom occur. This study may provide useful insights for patients undergoing surgery for large intracranial meningiomas.

Surgical resection and adjuvant radiation are mainstays of medulloblastoma (MB) patient management. We utilized a novel 3-dimensional assay to identify how (a) radiation, (b) excision of the primary tumour aggregate, and (c) both treatments combined influence MB cell invasiveness.

Five MB cell lines (UW228-1, 2 and 3; Daoy, and Madsen) were implanted onto a 3-dimensional, type I collagen gel assay to assess tumour invasion distance over five days, in response to (1) needle-assisted excision of the central cell aggregate; (2) pre-exposure to single-dose and fractionated dose irradiation in doses from 6-25 and 8-24 Gy, respectively; and (3) excision plus either single-dose or fractionated radiation.

Within hours, individual MB cells detached from the surface of the cell aggregates and invaded the collagen matrix, to distances up to 1200 μm and at rates up to 300 μm daily. The UW228-1 cell line was less invasive than the other cell lines and was dropped from further analysis. In the four remaining lines, a dose-dependent decline in tumour invasiveness was identified, both for single-dose and fractionated radiation, which achieved statistically decreased invasion distances at higher doses, especially of fractionated irradiation. Excision of the central tumour aggregate tended towards exerting a late effect on cell invasion, but exerted no significant influence on the radio-sensitivity of residual cells.

Both single-dose and fractionated dose irradiation appear to inhibit MB cell invasiveness in a dose-dependent manner, whereas excision of the central cell aggregate exerts no effect on residual invading cells.

Perimesencephalic subarachnoid hemorrhage (PSH) is a relatively benign clinical entity with a low risk of recurrent bleeding. The precise etiology of PSH has not yet been determined. We report here three cases of PSH with clinical and radiological features that support a venous system as a cause.

The first patient, a 72-year-old woman, had PSH and venous hemorrhagic infarct in the left thalamus on non-contrast CT. Subsequent cerebral angiography revealed widespread thrombosis in the cerebral venous system, a potential cause for reflux overflow hemorrhage. The second patient, a 55-year-old man with an established diagnosis of neuro-Behçet's disease, a well-known cause for cerebral venulitis, presented with PSH one year later. The third patient, a 39-year-old female, with incomplete Behçet's disease was admitted with PSH.

Current concepts on the anatomic origin and the possible pathophysiologic mechanism leading to PSH are discussed. The underlying pathological conditions in the venous system in our cases provide theoretical clues to the anatomic origin of PSH in general.

To predict success of endoscopic third ventriculostomy (ETV) in patients with obstructive hydrocephalus, we evaluated pre- and post- operative phase-contrast cine magnetic resonance images (PC MRI) on cerebrospinal fluid (CSF), cine flow in basal cisterns around the brain stem, and cervical medullar junction (CMJ) retrospectively.

The study involved 102 patients with mean age of 36.74±23.25, and F/M = 1.55. All patients had PC MRI taken both pre- and post-operatively. A dynamic MRI video of PC MRI was reviewed at sagittal, axial, and coronal sections to determine cistern flows around the brain stem and CMJ. For quantitative analysis, quadrants were divided around midbrain axially to evaluate interpeduncular, quadrageminal, and ambient cisterns of both sides using scores of 0 to 60. Pre- and post- pontine and CMJ flows were shown in sagittal view and scored 0 to 20, and lateral cerebellopontine cisterns of both sides were measured on coronal image and scored 0 to 20.

No significant difference in CSF flow was seen from three individual views and total cine score, or between ETV success and failure groups by multivariate analysis of variance. Kaplan-Meier Analysis and Spearman's Correlation Test produced no relationship between MRI cine flow scores and interval period after surgery to ETV failure.

PC MRI cine flow failed to demonstrate significant differences between successful and failed ETV groups. This indicates in addition to achieving an adequate fenestration, CSF pathways beyond the basal cisterns around the brain stem and CMJ may play an essential role in achieving ETV success.