A population-based prevalent group of 150 clinical definite patients ascertained on 1 January 1977, in Saskatoon, Saskatchewan, was followed for 30 years.

To outline the clinical characteristics, determine the levels of disability at 15, 25, 35, 40, and 45 years after onset, to estimate the survival after onset and life expectancy.

Clinical records were maintained, and the cohort reviewed each decade for 30 years. The disability levels according to the Kurtzke Extended Disability Status Scale were recorded and survival times were estimated. SPSS and Kaplan-Meier methods were used for analysis.

On prevalence day, 1 January 1977, there were 48(32%) men and 102(68%) women, with an average age of onset of 32.2±10 years and 28.4±8.6 years. The average duration of disease was 15.7 years. On 1 January 2007, 39(26%) patients were living, 105(70%) deceased, and 6(4%) were missing The disability levels recorded in 1977 and 2007, at 15 and 45 years after onset, were mild (EDSS≤2.5), 33.3% and 8.0%; moderate (EDSS3-5.5), 17.3% and 2.7%; severe (EDSS6-7.5), 6.6% and 4.7%; maximum (EDSS8-9.5), 22.7% and 10.7%. The median survival time after onset was 33 (95% CI: 27.3-38.6) years for men and 38 (95% CI: 34.1-41.9) years for women. The median duration of life was 68.9 years for men and 69.5 years for women, and a decreased life expectancy of 7.7 and 12.8 years.

Multiple sclerosis is a progressive neurological disorder and long-term survival is associated with moderate to severe disability and decreased life expectancy.

Pseudoprogression (psPD) is now recognised following radiotherapy with concurrent temozolomide (RT/TMZ) for glioblastoma multiforme (GBM). The aim of this study was to determine the incidence of psPD following RT/TMZ and the effect of psPD on prognosis.

All patients receiving RT/TMZ for newly diagnosed GBM were identified from a prospective database. Clinical and radiographic data were retrospectively reviewed. Early progression was defined as radiological progression (RECIST criteria) during or within eight weeks of completing RT/TMZ. Pseudoprogression was defined as early progression with subsequent disease stabilization, without salvage therapy, for at least six months from completion of RT/TMZ. The primary outcome was overall survival (Kaplan-Meier) and log rank analysis was used to compare groups.

Out of 111 patients analyzed, 104 were evaluable for radiological response. Median age was 58 years and median follow-up 55 weeks. Early progression was confirmed in 26% and within this group 32% had psPD. Median survival for the whole cohort was 56.7 weeks [95% CI (51.0, 71.3)]. Median survival for patients with psPD was significantly higher than for patients with true early progression (124.9 weeks versus 36.0 weeks, p=0.0286).

Approximately one third of patients with early progression were found to have psPD which was associated with a favourable prognosis. Maintenance TMZ should not be abandoned on the basis of seemingly discouraging imaging features identified within the first three months after RT/TMZ.

To determine our institutional adherence to the Brain Trauma Foundation guidelines with respect to intracranial pressure (ICP) monitoring, and examine the relationship between external ventricular drain (EVD) use and mortality.

Retrospective cohort study of 171 patients with severe traumatic brain injury (TBI). Propensity score adjusted logistic regression was used to model the association between EVD use and mortality.

EVDs were inserted in 98 of 171 patients. Of the 73 patients without an EVD, 63 (86%) would have qualified for ICP monitoring under the current guidelines. EVDs were in situ for a median of 8 days (SD 6). In adjusted analyses, EVD use was associated with hospital mortality (OR 2.8, 95% CI: 1.1 - 7.1, p=0.04) and 28-day mortality (OR 2.1, 95% CI: 0.80 - 5.6, p=0.13). We observed significant modification of the association between EVD and 28-day mortality by GCS within 12 hours (p-interaction = 0.04), indicating strong association only among those patients with GCS score of at least 6 (OR 5.0, 95% CI: 1.5 - 16.7, p<0.01).

The association of EVD with 28-day mortality was only apparent among patients with GCS score of ≥ 6. Further research is warranted to further refine which patients may benefit from ICP monitoring.

Specialization is generally independently associated with improved outcomes for most types of surgery. This is the first study comparing the immediate success of outpatient lumbar microdiscectomy with respect to acute complication and conversion to inpatient rate. Long term pain relief is not examined in this study.

Two separate prospective databases (one belonging to a neurosurgeon and brain tumor specialist, not specializing in spine (NS) and one belonging to four spine surgeons (SS)) were retrospectively reviewed. All acute complications as well as admission data of patients scheduled for outpatient lumbar microdiscectomy were extracted.

In total, 269 patients were in the NS group and 137 patients were in the SS group. The NS group averaged 24 cases per year while the SS group averaged 50 cases per year. Chi-square tests revealed no difference in acute complication rate [NS(6.7%), SS(7.3%)] (p>0.5) and admission rate [NS(4.1%), SS(5.8%)] (p=0.4) while the SS group had a significantly higher proportion of patients undergoing repeat microdiscectomy [NS(4.1%), SS(37.2%)] (p<0.0001). Excluding revision operations, there was no statistically significant difference in acute complication [NS(5.4%), SS(1.2%)] (p=0.09) and conversion to inpatient [NS(4.3%), SS(4.6%)] (p>0.5) rate. The combined acute complication and conversion to inpatient rate was 6.9% and 4.7% respectively.

Based on this limited study, outpatient lumbar microdiscectomy can be apparently performed safely with similar immediate complication rates by both non-spine specialized neurosurgeons and spine surgeons, even though the trend favored the latter group for both outcome measures.

The purpose of this study was to evaluate Canadian amyotrophic lateral sclerosis (ALS) centres with respect to: 1) the prevalence of Non-invasive positive pressure ventilation (NIPPV) and invasive mechanical ventilation via tracheostomy (TV) utilization, 2) the approach to NIPPV use, focusing upon the currently employed initiation criteria and 3) the barriers influencing NIPPV administration.

A descriptive survey research design aimed to obtain quantitative data and open-ended responses from an active physician at each of the 15 multidisciplinary Canadian ALS centres.

The principal findings of this study were: 1) NIPPV and TV are used in 18.3% and 1.5% of patients at Canadian ALS centres, respectively, 2) symptoms of respiratory insufficiency, namely orthopnea (clinical significance rated at 9.00/10 ± 1.48), dyspnea (8.27 ± 1.95) and morning headache (7.55 ± 1.21) are the most significant indicators for NIPPV initiation, 3) the primary barriers to NIPPV utilization are patient intolerance (70% of centres) and inaccessibility of respirologists and ventilation technologists (50% of centres).

Variability in NIPPV use has an impact upon the management of Canadian ALS patients. The establishment of more definitive NIPPV initiation criteria, emphasizing respiratory symptoms, and the attenuation of barriers to NIPPV use should be targeted so as to ensure optimal care for all ALS patients.

To examine predictive factors associated with onset of depression among individuals diagnosed with Parkinson's disease (PD).

Depression may precede or follow symptomatic parkinsonism in PD. It is frequently treatable but often overlooked.

The clinical series comprised 685 individuals who were diagnosed with PD and followed by one neurologist (RJU) from 1994 to 2007. The primary outcome was time to depression following the onset of PD. Diagnosis of depression was based on clinical assessment of depressive symptoms from patients (and spouse/family/caregiver) and antidepressant usage. A number of demographic, historical and clinical predictive factors were examined, including gender, age at symptomatic onset, disease duration, onset characteristics, clinical ratings, antiparkinsonian medications, cognitive status, depression history, and familial history of PD and other neurodegenerative disorders.

Seventy-two percent of patients developed depression within ten years of symptomatic PD onset, and the mean time to depression was 7.9 years (median: 5.7 years). Factors associated with depression included longer PD duration, greater impairment in activities of daily living, and positive family history of motor neuron disease (MND).

A high rate of individuals with PD develop depressive symptoms during the course of the disease. Based on first clinic visit characteristics, most factors examined were not helpful in identifying individuals with an increased risk of depression. However, disease duration, functional limitations and family history of MND should lead clinicians to an increased vigilance for identifying depression.

According to a recent proposal for revised diagnostic criteria for Alzheimer disease, the diagnosis could be made even in the absence of impairment of social function or daily life activities, provided positivity of one or more abnormal biomarkers. The use of the new proposed diagnostic criteria raises ethical issues and needs to be carefully evaluated.

We describe two clinical cases of prodromal Alzheimer's disease and discuss the diagnosis disclosure, taking into consideration several issues: (i) the issue of the boundary between well founded research procedures and clinical practice, (ii) the issue of the fuzziness of the concepts of scientific evidence and scientific uncertainty, (iii) the issue of patient's autonomy and patient's best interest, and (iv) the issue of the patients' specific personal and social context.

The degree of informativeness of the proposed diagnostic criteria for the single patient is already such as to deserve high regard in making the diagnosis and in the diagnosis disclosure process. During the disclosure process, the physician needs to take into account both what is known and what it is not sufficiently known. The patient's personal and environmental conditions should drive the physician to partial or full diagnostic disclosure, or delay communication.

We proposed two different diagnosis disclosure processes, on the basis of the common neurological features and of the different global clinical situations, socio-personal contexts and attitudes towards the communication of the diagnosis.

Despite optimal medical therapy, a sizeable number of patients continue to have persistent seizures. We evaluated the association of pretreatment and treatment variables with unfavorable seizure outcome.

Patients with follow-up over 12 years in the Nepal Epilepsy Association were evaluated. Patients having seizures for at least a year and already on polytherapy after failure of two monotherapy trials were considered having unfavourable outcome. Variables under study were: age, sex, duration and frequency of seizures prior to treatment, type of seizure, neurological status, Computed Tomography (CT) finding, and failure of first anti-epileptic drug (AED). Bivariate analysis was done with Chi-square and Fisher exact tests. Potential interaction between variables was studied with a logistic regression analysis.

Out of a total 529 consecutive patients, 490 were included in the study. Unfavorable seizure outcome was seen in 26.8% of patients. Among 284 patients who remained viable for analysis, bivariate analysis showed significant association of unfavorable outcome with frequency of seizure (p 0.01), abnormal neurological status (p 0.01) and failure of first AED (p 0.00), while no significant association was seen with age at onset (p 0.45), sex (p 0.47), duration of seizure (p 0.43), type of seizure (p 0.12), and presence of CT abnormality (p 0.46). The fitted regression model portended an unfavorable prognosis with failure of first AED and abnormal neurological status, however, failed to show significant association with frequency of seizure.

Failure of first AED trial and associated neurological deficits are significant predictors of unfavorable seizure outcome.

In Parkinson's disease, most of current therapies only provide symptomatic treatment and so far there is no drug which directly affects the disease process.

To investigate the neuroprotective effects of minocycline against long-term rotenone toxicity in primary dopaminergic cell cultures.

Embryonic mice of 14-days-old were used for preparation of primary dopaminergic cell cultures. On the 6th day in vitro, prepared cultures were treated both with minocycline alone (1, 5, 10 and 20 μM) and concomitantly with rotenone (5 and 20 nM) and minocycline. Cultures were incubated at 37°C for six consecutive days. On Day 12 in vitro culture medium was aspirated and used for measuring lactate dehydrogenase. Cultured cells were fixed in 4% paraformaldhyde and stained immunohistochemically against tyrosine hydroxylase.

Treatment of cultures with 5 and 20 nM of rotenone significantly decreased the survival of tyrosine hydroxylase immunoreactive neurons by 27 and 31% and increased the release of lactate dehydrogenase into the culture medium by 31 and 236%, respectively compared to untreated controls. Minocycline (1, 5, 10 μM) significantly protected tyrosine hydroxylase immunoreactive neurons by 17, 15 and 19% and 13, 22 and 23% against 5 and 20 nM of rotenone, respectively compared to rotenone-treated cultures. Minocycline (only at 10 μM) significantly decreased the release of lactate dehydrogenase by 79% and 133% against 5 and 20 nM of rotenone, respectively.

Minocycline has neuroprotective potential against the progressive loss of tyrosine hydroxylase immunoreactive neurons induced by long-term rotenone toxicity in primary dopaminergic cultures.

Neuropsychiatric symptoms are increasingly recognised as a significant problem in patients with Parkinson's disease (PD). These symptoms may be due to ‘sensitisation’ following repeated levodopa treatment or a direct effect of dopamine on the disease state. The levodopa-treated MPTP-lesioned marmoset was used as a model of neuropsychiatric symptoms in PD patients. Here we compare the time course of levodopa-induced motor fluctuations and neuropsychiatric-like behaviors to determine the relationship between duration of treatment and onset of symptoms.

Marmosets were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (2.0 mg/kg s.c.) for five days, resulting in stable parkinsonism. Levodopa (15 mg/kg and benserazide, 3.75 mg/kg) p.o. b.i.d. was administered for 30 days. Animals were evaluated for parkinsonian disability, dyskinesia and on-time (motor fluctuations) and neuropsychiatric-like behaviors on Day 0 (prior to levodopa) and on Days 1, 7, 13, 27 and 30 of treatment using post hoc DVD analysis by a trained rater, blind to the treatment day.

The neuropsychiatric-like behavior rating scale demonstrated high interrater reliability between three trained raters of differing professional backgrounds. As anticipated, animals exhibited a progressive increase in levodopa-induced motor fluctuations, dyskinesia and wearing-off, that correlated with the duration of levodopa therapy. In contrast, levodopa-induced neuropsychiatric-like behaviors were present on Day 1 of levodopa treatment and their severity did not correlate with duration of treatment.

The data suggest that neuropsychiatric disorders in PD are more likely an interaction between levodopa and the disease state than a consequence of sensitisation to repeated dopaminergic therapy.