To evaluate the outcomes of patients with giant pituitary tumours (GPTs) who underwent a purely binasal endoscopic transsphenoidal surgery (BETS) and compare their outcomes with those achieved through craniotomy and microscopic transsphenoidal surgery (MTS).

Seventy-two consecutive patients with GPTs (greater than 10 cm3 in volume) who were treated surgically with BETS, craniotomy, or MTS from October 1994 to July 2009 were reviewed for clinical outcomes, degree of tumor resection, recurrence rates, and surgical complications.

The BETS group had significantly better mean reduction of tumor volume (91%) than the craniotomy (63%, p = 0.001), and the MTS (63%, p = 0.010) groups. Gross total resection rates were also higher for BETS patients than for craniotomy patients (p = 0.010). Improvements in vision and headaches were noted in 96% and 100% of patients in the BETS group, respectively; these rates were similar to those in the craniotomy and MTS groups. Of the four patients with hormone-secreting tumours in the BETS group, three remained in remission. The median length-of-stay (four days) for the BETS group was shorter (p = 0.010), and surgical complications were less frequent (p = 0.037) and less severe compared to the craniotomy group. There were no differences in the recurrence rates: 79% percent of patients in the BETS group, 69% in the craniotomy group, and 79% in the MTS group were recurrence free at last follow-up (p = 0.829).

Treatment of GPT with BETS offers excellent oncologic and clinical outcomes and can frequently obviate the need for craniotomy in these patients.

Neuropathic pain is characterised by spontaneous ongoing or shooting pain and evoked amplified pain responses after noxious or non-noxious stimuli. Neuropathic pain develops as a result of lesions or disease affecting the somatosensory nervous system either in the periphery or centrally. Melanocortin 4 receptor (MC4R) plays an important role in the initiation of neuropathic pain but the underlying mechanisms are still unclear.

Adult male Wistar rats were given chronic constriction injury (CCI) or sham operations. Part of CCI rats were intrathecally treated with HS014 (MC4R antagonist) or SB203580 (p38MAPK inhibitor). On the third, seventh and fourteenth day, the thermal threshold of operated paws was tested. In addition, the MC4R or phosphorylated p38MAPK (p-p38MAPK) levels of lumbar spinal cord were tested with ELISA (enzyme-linked immunosorbent assay), western blot and immunohistochemistry.

Here we demonstrate that (1) both HS014 and SB203580 reduced CCI reduced hyperalgesia (2) p-p38MAPK was increased after CCI with a time course parallel to that of the MC4R change, (3) The p38 activation was prevented by blocking MC4R with an antagonist HS014, but MC4R-IR was not prevented by SB203580. (4) MC4R and p-p38MAPK were located in the same cells.

The mechanisms of neuropathic pain mediated by MC4R is related to the inhibition of p38MAPK activation. P38MAPK may be a downstream of MC4R.

Levodopa-induced dyskinesias (LID) are amongst the most disabling side-effects of levodopa therapy for Parkinson's disease (PD). It has been suggested that that N-Methyl-D-Aspartate (NMDA)-receptor antagonist may reduce peak-dose dyskinesia in PD patients and may lead to motor improvement. In this study, we compared the efficacy of NMDA receptor antagonists versus placebo in the treatment of LID in PD through a meta-analysis of controlled trials.

Electronic search of Pubmed (1990 - 2010), Medline (1966-2010), EMBASE (1974-2010) and other databases for relevant studies were performed. Controlled clinical trials of the effects of NMDA antagonists on LID that fulfill the study protocol were selected. Pooled data from included studies was then used to perform random and fixed effect models meta-analysis.

The search resulted in 11 randomized, placebo controlled clinical trials that involved a total of 253 PD patients with peak-dose LID. The outcome measures were various dyskinesia rating scales and the Unified Parkinson Disease Rating Scale (UPDRS) subscales III and IV. The analysis showed significant reduction in Standard Mean Difference (SMD) for UPDRS IV (SMD -1.45; 95% CI -2.28 to -0.63) and UPDRS III (SMD -0.41; 95% CI -0.69 to -0.12) after treatment with amantadine. Other included drugs did not show significant change in the outcomes measured.

This meta-analysis provides an update on the clinical trials and confirms the short-term benefits of amantadine therapy in the treatment of dyskinesia. The effects of other NMDA receptor antagonists need to be evaluated further in clinical trials.

Postural instability is one of the most disabling features of Parkinson's disease, usually occurring in late and advanced stages. The aim of this study was to investigate the postural performance of early-stage de novo Parkinson's disease patients with no clinical postural instability using computerized dynamic posturography. We sought to understand the relationship between postural sway and disease severity and the relationship between postural instability quantitatively measured by computerized dynamic posturography and cognitive impairment in early-stage Parkinson's disease patients.

Thirty-one subjects with Parkinson's disease and 20 healthy controls were assessed by the computerized dynamic posturography protocol using the sensory organization test and the motor control test. A neuropsychological assessment was also administered.

The mean equilibrium score for sensory organization test and the vestibular input ratio were significantly correlated with Hoehn-Yahr stage. No associations between motor latency for any motor control test condition and Hoehn-Yahr stage were found. The equilibrium score for sensory organization test correlated with the mini-mental status examination scores. There was a significant correlation between motor latency for large backward translation and mini-mental status examination scores. There were significant correlations between visual perception/construction/ memory of the neuropsychological battery test and the equilibrium score for sensory organization test and between verbal word learning test, controlled word association test and motor latency for large backward translation.

These findings showed the postural instability present in early-stage (Hoehn-Yahr stage 2-2.5) Parkinson's disease. We also found a close relationship between postural instability and cognitive function in Parkinson's disease patients.

To investigate the feasibility of Electroencephalogram (EEG) power spectrum analysis as a noninvasive method for monitoring intracranial pressure (ICP).

The EEG signals were recorded in 62 patients (70 cases) with central nervous system (CNS) disorders in our hospital. By using self-designed software, EEG power spectrum analysis was conducted and pressure index (PI) was calculated automatically. Intracranial pressure was measured by lumbar puncture (LP).

We found a significant negative correlation between PI and ICP (r = -0.849, p < 0.01).

The PI obtained from EEG analysis is correlated with ICP. Analysis of specific parameters from EEG power spectrum might reflect the ICP.

Neuromyelitis optica (NMO) and multiple sclerosis (MS) are autoimmune diseases of the central nervous system with complex pathogeneses. NMO was once considered to be a severe variant of MS. There has been more evidence that a non-synonymous exchange (rs763361/Gly307Ser) in the gene for CD226 is linked to several autoimmune diseases including multiple sclerosis (MS). However, no studies have investigated the role of rs763361 in the pathogenesis of NMO.

The goal of our study is to evaluate the role of CD226 Gly307Ser in neuromyelitis optica (NMO) in Southern Han Chinese.

Eight-nine NMO patients, 93 relapsing-remitting multiple sclerosis (RRMS) patients, and 122 controls (CTLs) were enrolled. The rs763361 alleles of the subjects were determined by sequencing-based typing.

The results strongly support that the TT genotypes are associated with NMO but are not significantly correlated with susceptibility for MS.

CD226 Gly307Ser may correlate with risk of NMO in Southern Han Chinese.

To quantify and compare T2 signal and apparent diffusion coefficient (ADC) in pilocytic and pilomyxoid astrocytoma (PA and PMA) and correlate results with myxoid content.

Echo-planar diffusion weighted images (DWI) and standard magnetic resonance imaging (MRI) findings were reviewed retrospectively in patients with PA (n=34) and PMA (n=8). Regions of interest (ROIs) were drawn on ADC maps within tumor parts with lowest ADC values. Apparent diffusion coefficient values in tumor were normalized to those in cerebrospinal fluid (ADC/CSF). The ratio of T2 signal intensity in solid tumor parts to CSF (T2/CSF) was registered. Myxoid matrix was histologically quantified retrospectively in 8 PMAs and 17 PAs and correlated with imaging findings.

Mean ADC/CSF for PA and PMA was 0.53±0.10 and 0.69±0.10 (p<0.01). Mean T2/CSF for PA and PMA was 0.78±0.19 and 0.93±0.09 (p<0.01). Mean proportion of myxoid tumor matrix in PA was 50% (range, 10-100%) and 93% (range, 90-100%) in PMA (p=0.004). Eight patients (32%; all PA) had less than 50% myxoid content and 17 (68%; 8 PA; 9 PMA) had more. There was positive correlation of ADC/CSF, T2/CSF and ADC (r2=0.61, 0.65 and 0.60 respectively) and significant difference between the groups with more and less than 50% myxoid content (p=0.01 for ADC/CSF and T2/CSF and p=0.02 for ADC).

General imaging features of PA and PMA are non-specific, ADC values and T2 signal intensity are generally higher in the latter, reflecting the proportion of myxoid matrix in these tumors.

Lack of additional utility over non-contract computed tomography (NCCT) in decision making and delay in door to needle time are arguments used against routine computed tomographic angiography (CTA) use in acute ischemic stroke management. We compare interval times during a CTA based acute ischemic stroke protocol with an earlier non-CTA based protocol at our center.

We reviewed 850 stroke thrombolysis patients in a university hospital in Canada from April 1996 to December 2009. Time to treatment was divided into the following interval times: onset-to-door, door-to-needle and onset-to-needle. Patients were categorized into: Group 1 (April 1996-Dec 2002) (Non-contrast CT Scan based thrombolysis) n=297, Group 2 (Jan 2004-Dec 2009) (CTA based thrombolysis) n=504. The period from Jan to Dec 2003 (n=49) was considered a washout period as we had started the CTA protocol that year. Interval times were compared between the two groups.

Interval times in Group 1 and Group 2 were: median onset-to-door times in Group 1 [55 minutes (IQR 48),] and Group 2 [61 minutes (IQR 57)] (p=0.019); median door-to-needle times in Group 1 [67 minutes(IQR 43)] and Group 2 [62.5 minutes (IQR 52)] (p=0.519); median onset-to-needle times in Group 1 (139 minutes (IQR 73)] and Group 2 (141.5 min (IQR 109.5) (p=0.468). In multivariable linear regression analysis, age and onset-to-door time influenced the door-to-needle time. For every decade of age, door-to-needle times were 5.4 minutes faster.

CTA based thrombolytic approach for acute ischemic stroke does not significantly delay thrombolysis in routine clinical practice.

To assess the relationship between carotid flow velocity and cognitive impairment in patients with mild-moderate (<50%) carotid artery disease.

We studied 407 participants with available carotid ultrasound and cognitive measures. We related peak systolic velocity (PSV) and end diastolic velocity (EDV) of internal carotid artery (ICA) and common carotid artery (CCA) and intimal medial thickness (IMT) to Mini Mental State Examination (MMSE), Clock Draw Test (CDT), Activities of Daily Living Scale (ADL)and Montreal Cognitive Assessment (MoCA).

EDV of CCA was significantly different in higher and lower MoCA (MMSE) groups. Multiple regression analysis demonstrated that lower EDV was significantly associated with lower MoCA (+0.459 per standard deviation (SD), p<0. 01 for the left; +0.539 per SD, p<0. 01 for the right) and CDT (odds ratio (OR) 0.093, p< 0.05 for the left; OR) 0.120, p<0. 01 for the right) scores. PSV of left CCA (-0.205 per SD, p<0.05) and IMT (+42.536 per SD, p< 0.001) were associated with ADL. PSV of right CCA was associated with MMSE (+0.081 per SD, p<0.001). No significant relationship between ICA flow velocity and cognitive performance was observed.

Our preliminary data show that common carotid artery flow velocity was associated with cognitive performance.

This study aims to assess current practices of Canadian physicians providing botulinum toxin-A (BoNT-A) treatments for children with hypertonia and to contrast these with international “best practice” recommendations, in order to identify practice variability and opportunities for knowledge translation.

Thirteen Canadian physicians assembled to develop and analyze results of a cross-sectional electronic survey, sent to 50 physicians across Canada.

Seventy-eight percent (39/50) of physicians completed the survey. The most frequently identified assessment tools were Gross Motor Function Classification System, Modified Tardieu Scale and neurological examination. Goal-setting tools were infrequently utilized. Common indications for BoNT-A injections and the muscles injected were identified. Significant variability was identified in using BoNT-A for hip displacement associated with hypertonia. The most frequent adverse event reported was localized weakness; 54% reporting this “occasionally“ and 15% “frequently”. Generalized weakness, fatigue, ptosis, diplopia, dysphagia, aspiration, respiratory distress, dysphonia and urinary incontinence were reported rarely or never. For dosage, 52% identified 16 Units/kg body weight of Botox® as maximum. A majority (64%) reported a maximum 400 Units for injection at one time. For localization, electrical stimulation and ultrasound were used infrequently (38% and 19% respectively). Distraction was the most frequently used pain-management technique (64%).

Canadian physicians generally adhere to international best practices when using BoNT-A to treat paediatric hypertonia. Two knowledge-translation opportunities were identified: use of individualized goal setting prior to BoNT-A and enhancing localization techniques. Physicians reported a good safety profile of BoNT-A in children.

Pyridoxine dependent epilepsy (PDE) is characterized by neonatal epileptic encepahalopathy responsive to pharmacological doses of vitamin B6. Recently an autosomal recessive deficiency in Antiquitin (ALDH7A1), a gene involved in the catabolism of lysine has been identified as the underlying cause.

In 21 and 23 year-old sisters, who had presented with neonatal / early infantile onset seizures, PDE was confirmed by elevated urinary alpha aminoadipic- 6- semialdehyde (α-AASA) excretion and compound heterozygosity for two known ALDH7A1 missense mutations. Although epilepsy was well controlled upon treatment with pyridoxine, thiamine, phenytoin and carbamazepine since early infancy, both had developmental delay with prominent speech delay as children. As adults, despite the same genetic background and early treatment with pyridoxine, their degree of intellectual disability (ID) differed widely. While the older sister's cognitive functions were in the moderate ID range and she was not able to live unattended, the younger sister had only mild ID and was able to live independently.

Although seizures are a defining feature of PDE, other disease manifestations can vary widely even within the same family. Adult neurologists should be aware that the diagnosis of PDE can be delayed and PDE should be considered in the differential diagnosis of adults with seizure disorders dating from childhood.

Progressive external ophthalmoplegia (PEO) is a mitochondrial myopathy of ocular muscles. Diagnostic investigation usually involves limb skeletal muscle biopsy and molecular genetic studies, although diagnostic yield tends to be low. The purpose of this study was to evaluate the diagnostic yield obtained by analysis of levator palpebrae (LP) muscle tissue.

This is a clinicopathologic study of 8 patients with a diagnosis of PEO, who had LP muscle biopsies as part of oculoplastic procedures. Six of these patients also had limb muscle biopsies. Histopathology, electron microscopy and genetic studies were performed.

Diagnostic histopathologic findings were present in 4/6 quadriceps biopsies, and 7/8 LP biopsies. Genetic testing on DNA extracted from LP muscle revealed abnormalities in 4 patients.

In patients whose LP muscle demonstrate both genetic defects and histopathological abnormalities, the diagnosis of PEO can be confirmed without limb muscle biopsy. Patients having LP resection during oculoplastics procedures for treatment of ptosis may therefore be able to avoid a separate procedure for limb muscle biopsy. Further study is required to determine the specificity of these findings.