To help investigators decide if new therapies for glioma warrant definitive evaluation in randomized studies we have been developing a method for assessing the degree to which patient selection may have enhanced the results of uncontrolled treatment trials. In this study, we analyzed the impact of case selection on the survival of patients with malignant glioma receiving adjuvant stereotactic radiosurgery, a promising therapy reserved for those with small tumors and good performance status.

Following published eligibility criteria we simulated the patient selection process for stereotactic radiosurgery given as a boost at the conclusion of conventional radiotherapy. Eligible patients were culled from a pre-existing clinical/imaging database of 101 consecutive conventionally-treated patients with biopsy-proven malignant glioma and known survival times. Median durations of survival and 2- and 3-year survival rates were determined for those judged eligible or ineligible for stereotactic radiosurgery.

Twenty-seven percent of patients were deemed eligible for stereotactic radiosurgery, eligible patients had more favorable prognostic factors and significantly longer median survival than ineligible patients (23.4 vs. 8.6 months; 2-year rate, 48% vs. 15%; 3-year rate, 30% vs. 7%); eligible patients also had a longer median survival than the entire group of unselected patients (23.4 vs. 11.4 months). Radiosurgery-eligible, conventionally-treated patients with glioblastoma multiforme and a group of radiosurgery-treated patients at a special referral center had similar median survival times (16.4 vs. 19.7 months).

We provide additional evidence for selection bias in uncontrolled trials of stereotactic radiosurgery and by simulating the selection process accurately have detected a larger bias effect than noted previously. Judging from experience with interstitial radiation and intraarterial chemotherapy where substantial selection bias also occurred and randomized controlled trials proved disappointing, we conclude that a phase III study of stereotactic radiosurgery for malignant glioma is unlikely to yield a positive result and may not be necessary.

A reliable marker for tumor oligodendroglial cells is not yet available, so that the histological recognition of the tumor still encounters uncertainties. There is no general agreement also on prognostic factors in oligodendroglioma. The inconsistency concerns mainly the histopathological factors. The aim of the study was recognition of prognostic factors in oligodendroglioma.

In a series of ninety-eight oligodendrogliomas, including twenty mixed oligoastrocytomas, clinical [sex, age at surgery, tumor location, symptoms at presentation], therapeutic [extent of resection, year of surgery, post-operative Karnofsky score, post-operative radiotherapy, post-operative chemotherapy], histological [cell density, nuclear pleomorphism, vascular endothelial proliferation, necrosis, microcysts, mitoses, mitotic index (MI), apoptosis, apoptotic index (AI)] and immunohistochemical parameters [MIB-1 and PCNA Labeling Indexes (Lis), staining for GFAP, positivity for p53] were correlated with survival in uni- and multivariate analysis in order to identify their prognostic significance.

Age at surgery, extent of surgical resection, year of surgery, postoperative Karnofsky score and MIB-1 LI were associated with survival in both uni- and multivariate analysis. Location, symptoms at presentation, mitoses, MI, AI, and PCNA LI showed a significant correlation with survival in uni- but not in multivariate analysis. The twenty cases of oligoastrocytomas did not show any difference in survival from pure oligodendrogliomas.

Some clinical and therapeutic factors together with MIB-1 LI play a prognostic role. MIB-1 LI is prognostic with a cutoff of 8%. Histology gives a limited contribution to the prognosis. Oligoastrocytomas had the same outcome and prognostic factors as pure oligodendrogliomas.

The assessment of thalamocortical function in comatose patients in the intensive care unit (ICU) can be difficult to determine. Since the electroencephalogram (EEG) affords such assessment, we have developed an EEG classification for comatose patients in our general ICU.

One hundred EEGs were classified in a blinded fashion by two EEGers, using our method and that of Synek. Interobserver agreement was assessed using kappa score determination.

Kappa scores were 0.90 for our system and 0.75 for the Synek system. (The Kappa score represents the inter-rater agreement that is beyond chance; 0.90 is almost perfect agreement, while 0.75 is substantial agreement).

Our system for classifying EEGs in comatose patients has a higher interobserver reliability than one that was previously published. This EEG classification scheme should be useful in clinical electrophysiological research involving ICU patients, allowing for internal consistency and comparisons among centres.

The Saguenay-Lac-Saint-Jean (SLSJ) region is a geographically isolated area (population 285,955) located in the Northeastern part of the Province of Quebec, Canada. Using a population-based register, the genealogical reconstruction of 502 individuals with ruptured intracranial aneurysm (RIA) showed a familial aggregation (the presence of aneurysm in two or more first- to third-degree relatives) for 144 (28.7%) of them; this proportion is much higher than reported elsewhere.

In order to assess the genetic predisposition to RIA in the SLSJ population, the objective of the present study is to compare familial and non-familial cases and to provide an estimate of the recurrence risk ratio for siblings.

The age at the time of rupture, the number of intracranial aneurysms for each patient and the location of RIAs were not statistically different in the familial versus the non-familial group. Of the 3449 siblings, 20 (0.58%) had suffered a RIA. The recurrence risk ratio calculated for siblings (defined as the risk of disease among siblings divided by the estimated population prevalence) is 1.6 (CI 95% 1.0 - 2.4). In other respects, we observed very large kinships in the SLSJ population, with an average number of siblings of 7.2 (SD ± 3.4), ranging from 0 to 17 individuals. With such large families and on the basis of chance alone, we expected 31.3% of the patients to have at least one first- to third-degree relative with RIA.

These data show that siblings of patients with RIA in the SLSJ population have a greater risk of RIA than the general population. Nevertheless, the largest part of the familial occurrence observed in the SLSJ region can be explained by accidental aggregation, due to large kinships. We propose that, in this population, an underlying genetic predisposition must be suspected only when three or more cases of RIA are identified among first- to third-degree relatives.

To investigate the mechanisms underlying disability in multiple sclerosis (MS), 40 patients with the relapsing-remitting form of the disease and 13 patients with secondary progressive MS underwent multimodal evoked potential (EP), motor evoked potential (MEP), and spinal motor conduction time evaluation. Clinical disability was evaluated by the expanded disability status scale (EDSS) and functional system scales. In secondary progressive MS patients, magnetic resonance imaging (MRI) was used to obtain a semiquantitative estimate of the total lesion load of the brain.

Spinal motor conduction time was significantly longer in secondary progressive MS patients than controls (p < 0.001) and relapsing-remitting MS patients (p < 0.05), but did not differ between relapsing-remitting patients and controls. Spinal motor conduction times also correlated directly with EDSS scores (p < 0.001) and pyramidal functional system scores (p < 0.001). Brain lesion load (4960.3 ± 3719.0 mm2) and the total number of lesions (67.7 ± 37.0) in secondary progressive MS did not correlate with disability scores. For the following EPs, the frequencies of abnormalities were significantly higher in secondary progressive MS patients than relapsing-remitting patients: visual evoked potentials (p < 0.05), somatosensory evoked potentials and upper limb motor evoked potentials (p < 0.01), and brainstem auditory evoked potentials, lower limb somatosensory evoked potentials and lower limb motor evoked potentials (p < 0.001).

These findings suggest that disability in secondary progressive MS patients is mainly due to progressive involvement of corticospinal tract in the spinal cord.

Patients with carpal tunnel syndrome (CTS) sometimes report sensory symptoms outside the median nerve distribution. This study was designed to provide a more detailed assessment of these symptoms.

Patients with clinical suspicion of upper limb neuromuscular lesions were divided into those with electrodiagnostic (EDX) evidence of CTS, and those without. CTS patients with superimposed nerve abnormalities were excluded. Motor and sensory symptoms were assessed in the exclusive CTS patients.

Over 50% of patients with exclusive CTS reported tingling or numbness over the whole hand, ulnar or radial nerve distributions. Some patients reported symptoms proximal to the wrist. Sensory signs did not extend beyond the median nerve distribution. Numbness and nocturnal pain were predictive of positive EDX evidence of CTS.

Sensory symptoms outside the distribution of the median nerve are common in CTS. For enhanced sensitivity in diagnosis it is useful to be aware of these “atypical” symptoms. Reports of numbness and nocturnal pain are strong indicators of CTS.

CSF shunting procedures are generally considered the fundamental therapy of syphilitic hydrocephalus.

We followed up with CSF analysis and MR imaging a patient with progressive mental and gait disturbances and tetraventricular hydrocephalus due to tertiary syphilis who was treated for 14 days with high dose intravenous penicillin alone.

Clinical and CSF abnormalities resolved within a few months, whereas the hydrocephalus disappeared only 30 months after therapy.

Before consideration of a CSF shunting procedure, a trial of high dose intravenous penicillin is warranted for patients with syphilitic hydrocephalus.

A seizure is the most common cause of loss of driving privileges for medical reasons but there is variability in how physicians and the authorities who regulate driving approach this issue.

A questionnaire regarding epilepsy and driving was sent to all adult neurologists in Canada (n = 494).

Of 289 (59%) neurologists responding, 50% usually report patients with seizures to the department of motor vehicles compared to only 4% for stroke/TIA, 26% for dementia and 8% for other neurologic disorders (p < 0.0001). In the five provinces with mandatory reporting laws, seizures were reported most of the time by 84% compared to only 19% in the five provinces with discretionary reporting (p < 0.0001). Nationwide, 44% agreed with mandatory reporting but this also differed in provinces with and without mandatory reporting legislation (63% vs. 37%, p < 0.0001). Only 49% agreed with the current recommendation of at least one year seizure free interval before resuming driving.

Seizures are disproportionately reported compared to other neurological conditions. Many neurologists disagree with the recommended Canadian standards for duration of driving restriction after seizures. Variability in the attitude and practice of neurologists in regard to reporting of seizures is confirmed.