This systematic review examines the role of chemotherapy following surgery and external beam radiotherapy for adults with newly diagnosed malignant glioma.

MEDLINE, EMBASE, and the Cochrane Library databases were searched to August 2006 to identify relevant randomized controlled trials (RCTs) and meta-analyses. Proceedings from the 1997 to 2006 annual meetings of the American Society of Clinical Oncology were also searched.

Two RCTs reported a survival advantage in favour of radiotherapy with concomitant and adjuvant temozolomide compared with radiotherapy alone in patients with anaplastic astrocytoma or glioblastoma. Twenty-six RCTs and two meta-analyses detected either no advantage or a small survival advantage in favour of adjuvant chemotherapy.

Concomitant temozolomide during radiotherapy and post-radiation adjuvant temozolomide is recommended for all patients ages 18-70 with newly diagnosed glioblastoma multiforme who are fit for radical therapy (ECOG 0-1). Temozolomide may be considered in other situations (i.e., ECOG 2, biopsy only, age >70, intermediate grade glioma), but there is no high-level evidence to support this decision. Moreover, there are few data on long-term toxicities or quality of life with temozolomide. Adjuvant chemotherapy may be an option for younger patients with anaplastic (grade 3) astrocytoma and patients with pure or mixed oligodendroglioma. However, there is no evidence of a survival advantage from adjuvant chemotherapy in these patients, and treatment-related adverse effects and their impact upon quality of life are poorly studied. The combination of procarbazine, lomustine, and vincristine (PCV) is not recommended for patients with anaplastic oligodendroglioma and oligoastrocytoma.

Randomized trials demonstrate that intravenous tissue plasminogen activator (tPA) improves outcome in acute ischemic stroke (AIS). To assess translation of this efficacy into effectiveness in routine clinical practice we performed a case-control study of tPA treatment for AIS in a single hospital.

151 tPA-treated AIS patients (1996-2005) were matched 1:1 with blinding to outcome to controls from a prospective registry based on age, gender, pre-stroke Oxford handicap scale (OHS), stroke severity, and subtype. The outcomes were in-hospital death, symptomatic intracranial hemorrhage (SICH), length-of-stay (LOS), discharge OHS and long-term survival.

In-hospital mortality (23% vs. 24%) or long-term survival (median follow-up of 2 years) was not different between cases and controls (p=0.83). SICH occurred in 7.8% (95% CI 4.2-13.5%) of tPA-treated patients. Median LOS was non-significantly shorter for cases (13 [7-29] vs. 16 [8-32] days, p=0.14) but significantly shorter in tPA-treated vs. non-treated women (14 [7-28] vs. 20 [11-34] days, p=0.04). At discharge 6.6% (95% CI 1.1-12.0%) more tPA-treated patients than controls had no disability (OHS ≤1, p=0.02). However, there was no difference in discharge independence rates or proportion discharged home.

We demonstrate minor improvements in early recovery after stroke with tPA but the impact is less dramatic than that reported in randomized trials. This may relate to timing of treatment and the type of patients treated.

Complications of intravenous (IV) thrombolysis with tissue plasminogen activator (t-PA) for acute stroke are commonly related to hemorrhage, anaphylaxis, or arterial re-occlusion. Embolic complications of t-PA are beginning to be recognized with increased use of t-PA for acute ischemic stroke. We hypothesize that disruption of intra-cardiac thrombus may result in myocardial infarction (MI) after use of t-PA for acute ischemic stroke.

We describe three cases of acute MI immediately following IV t-PA infusion for acute stroke. In patient #1 apical thrombus was visualized on cardiac echocardiogram accounting for the MI after t-PA for acute stroke. Patient #2 had fresh thrombus seen on cardiac catherization after use of t-PA for acute stroke. Patient #3 developed a significant troponin rise 15 hours after the t-PA for stroke infusion with an echocardiogram revealing new wall motion abnormalities. Patient # 1 and #2 died secondary to multi-organ failure.

Acute MI immediately following t-PA treatment for stroke is a rare but serious complication. The disruption of intra-cardiac thrombus and subsequent embolization to the coronary arteries may be an important mechanism in the development of MI after t-PA treatment for acute ischemic stroke.

The gene encoding the ganglioside-induced-differentiation-associated protein 1 (GDAP1) has been associated with both axonal and demyelinating neuropathy. Up to date, 25 mutations in the GDAP1 gene have been reported in patients from different origins.

Three Moroccan families with early onset ARCMT1 and autosomal recessive inheritance were genotyped to test linkage to 8q21.3 and their GDAP1 gene coding exons screened for mutations.

A novel C233T transversion at codon 78 (P78L) was detected in 6 patients from 3 unrelated families. The mutation was found to be homozygous in two families and compound heterozygous in association with the already reported S194X mutation in one family. The P78L mutation was associated with a common haplotype suggesting a Moroccan founder mutation. The patients had symptoms within the two first years of life and developed common phenotype of CMT4A with evident hoarse-voice in two cases with the longer disease duration.

P78L mutation was associated with a common haplotype suggesting a common ancestor.

Survivors of acute respiratory distress syndrome (ARDS) report generalized weakness and reduced exercise tolerance up to two years following discharge from the intensive care unit (ICU). Persistent neuromuscular complications of ARDS may contribute to the functional disability observed in these patients.

Sixteen ARDS survivors underwent comprehensive neurological evaluation and standardized electrodiagnostic testing 6 to 24 months after ICU discharge. Four of these patients agreed to open muscle biopsy.

Seven of sixteen patients had clinically significant focal compressive mononeuropathies. Electrodiagnostic testing failed to reveal any changes attributable to critical illness polyneuropathy or myopathy. All four muscle biopsies were abnormal, and although the pathological features were structurally non-specific, the presence of an acquired myopathy remains possible. Four patients had persistent mixed sensory complaints but had normal electrodiagnostic evaluation.

The high frequency of mononeuropathies highlights the need for vigilance in daily ICU care. The findings also suggest that complaints of weakness and reduced exercise capacity in ARDS survivors may be related to combined effects of compressive neuropathies and generalized longstanding structural changes in muscle and may support an organic basis for longterm functional disability.

Visual processing deficits involving temporal characteristics are typically not captured by the widely used outcome measures (i.e., Expanded Disability Status Scale, Multiple Sclerosis Functional Composite) in multiple sclerosis (MS). Visual temporal thresholds (i.e., measurements of the temporal aspects in visual processing) are typically significantly higher (i.e., prolonged) in MS patients when compared to controls. The test-retest reliability of these thresholds was examined in patients with MS.

Visual temporal thresholds were measured in 21 stable MS patients during two separate test sessions. Test-retest reliability and the standard error of measurement were calculated. The threshold of change in visual temporal thresholds in MS patients that would correspond to real change beyond measurement error with 95% certainty was also calculated. For comparisons, a control group (n = 10) was included.

The test-retest reliability of this measure of visual temporal thresholds was 0.97. The threshold indicating change beyond chance or measurement error with 95% certainty was 11 ms. Higher thresholds were significantly correlated with longer durations of disease.

This measure of visual temporal thresholds has excellent test-retest reliability and a change of greater than 11 ms is highly likely to represent real change in MS patients. The findings indicate that these measurements may provide useful clinical information about functional changes regarding the temporal aspects of the visual system, which is currently not captured by the Extended Disability Status Scale.

Current Health Canada instructions for use of the dopamine agonists (DA), pramipexole and ropinirole, state that Parkinson's disease (PD) patients should be told not to drive. The objective was to assess neurologists' actual clinical practice concerning driving advice they give to PD patients starting a DA.

An online survey was created consisting of 4 items regarding demographics, 5 regarding PD and driving, and 9 regarding DA use and driving. The survey was distributed to 563 neurologists.

In total 96 neurologists (17.9%) responded. 4.4% tell patients with PD not to drive, solely because they are taking a DA. Respondents assess the patient's tendency for excessive daytime sleepiness and sleep attacks after starting a DA more frequently than after starting other dopaminergic drugs (p<0.001).

A minor proportion of the clinicians responding to our survey advise PD patients not to drive, solely because they use a DA. Such being the case, we propose that current Health Canada guidelines need revision.

We reviewed our experience in 96 consecutive patients exhibiting periodic lateralized epileptiform discharges (PLEDs) on EEG.

EEG reports from January 1, 1999 to September 30, 2006 were screened for the term ‘PLEDs’ and its variants. A retrospective chart review, including examination of neuroimaging and other investigations, was conducted on each patient identified.

Acute stroke, tumor and central nervous system infection were the most common etiologies, accounting for 26%, 12% and 12% of cases respectively. Acute hemorrhage and traumatic brain injury combined accounted for another 12%. Previously unreported etiologies included posterior reversible encephalopathy syndrome (PRES), familial hemiplegic migraine and cerebral amyloidosis. There were 9 cases of chronic PLEDs attributable to underlying cortical dysplasia or severe remote cerebral injury, all with an accompanying partial seizure disorder. A prominent role for alcohol withdrawal was noted, and in 6 cases was the sole etiological factor. Fever was present as a potential contributing factor in 40% of cases, and significant metabolic abnormalities in 35%. Seizure activity occurred in 85% of patients overall, but in 100% of patients with PLEDs Plus and BiPLEDs Plus. The overall mortality rate was 27%. Mortality among patients with BiPLEDs however was almost twice that, at 52%.

This case series demonstrates the wide variety of potential PLED etiologies. It also emphasizes that despite advances in neurocritical care, the morbidity and mortality associated with PLEDs has changed little since their recognition four decades ago.

Routine histopathological examination of intervertebral disc specimens is commonly performed in North American hospitals, but recent studies have questioned the utility of this practice in cases where the indication for surgery is a benign process such as degenerative disc disease. In this study, we have performed a cost-benefit analysis of this practice.

We performed a cost-benefit analysis of routine histopathological examination of 1775 routine (non-neoplastic and non-infectious indications for surgery) and 70 non-routine (suspected neoplastic or infectious indications for surgery) discectomy specimens obtained over an eight-year period (1996 and 2004). Chart reviews were used to determine if any histopathology findings were clinically significant (i.e., affected subsequent patient care). Total costs were calculated. A literature review was conducted to compare our results with other published series.

We found four unexpected histopathology results among 1775 specimens obtained from routine cases, one of which was clinically significant. We calculated costs of $42,165.25 per unexpected histopathological finding and $168,625 per clinically significant histopathological finding. For non-routine surgeries, the cost per abnormal pathological finding was $116.67.

In routine cases, histopathological examination of disc specimens is not justified. The decision to send specimens for pathological examination should be based on the surgeon's judgment.

Occipital condyle syndrome is characterized by severe, unilateral, occipital headache and ipsilateral twelfth-nerve palsy. It is associated with skull-base metastasis.

We identified two patients with sub-acute onset of severe, unilateral, occipital headache and ipsilateral tongue paralysis. The first patient was a 58-year-old woman with a history of limited stage small-cell lung cancer in clinical remission. The second patient was an otherwise healthy 36-year-old man. Neither patient had any other findings on general medical or neurological examination. One patient had only equivocal findings on initial magnetic resonance imaging (MRI), and the other patient's MRI was normal. Although initial work-up for metastatic disease was normal, the first patient developed severe bone pain over the next few months, and follow-up investigations demonstrated metastases to her spine, tibia, skull base and brain. The second patient improved initially, but was admitted to hospital three months later with constitutional symptoms and pancytopenia. Bone marrow and lymph node biopsies were consistent with Stage IVB Hodgkin's lymphoma.

Occipital condyle syndrome can be the first presentation of disseminated malignancy. Initial imaging of the brain and skull base may be normal, and recognition of this syndrome warrants thorough investigation and close follow-up.

Endovascular therapy (ET) is infrequently used in the setting of acute penetrating intracranial trauma.

We report a case where ET was used immediately prior to and following removal of an embedded intracranial knife, which was found to be disrupting the anterior cerebral artery.

The proximal vessel was coiled and angiographically occluded and then the knife was removed with the microcatheter in place. Immediate angiography allowed us to see and quickly treat the contrast extravasation with further coiling. Despite full medical management, the patient died of elevated intracranial pressure.

In this severely injured patient, endovascular therapy represented the most suitable means to attempt safe removal of the knife.

Reversible Cerebral Vasoconstriction Syndrome (RCVS) may present as thunderclap headache (TCH), accompanied by reversible cerebral vasospasm and focal neurological deficits, often without a clear precipitant. RCVS may be mistaken for Primary Angiitis of the Central Nervous System (PACNS) due to the presence of similar angiographic features of segmental narrowing of cerebral arteries. We discuss the clinical features of a young female migraine patient who developed TCH and was found to have RCVS following initial treatment with corticosteroids for PACNS, in the context of a systematic review of the available medical literature.

A Medline™ search was performed to identify all case reports since 1966 describing RCVS and PACNS that provide sufficient clinical detail to permit diagnostic classification according to published criteria. RCVS included case studies in which there was angiographic or transcranial Doppler ultrasound evidence of near-to-complete resolution of cerebral vasoconstriction in the absence of a well-recognized secondary cause. PACNS included reports of histologically confirmed PACNS either through biopsy or necropsy.

Reversible Cerebral Vasoconstriction Syndrome occurs primarily in females and is characterized by sudden, severe headache at onset, normal CSF analysis, vasoconstriction involving the Circle of Willis and its immediate branches, and angiographic or TCD ultrasound evidence of near-to-complete vasospastic resolution within 1-4 weeks. It occurs typically in the context of vasoconstrictive drug use, the peripartum period, bathing, and physical exertion.

Initial and follow-up (within 4 weeks) non-invasive angiographic studies are indicated in patients who present with TCH or who have clinical presentations that could be consistent with RCVS or PACNS in the absence of a well-recognized secondary cause, such as subarachnoid haemorrhage. Early reversibility of cerebral vasospasm is the key neuroradiological feature that supports the clinical diagnosis of RCVS.