Einar Wilder-Smith

Automatic EEG Artifact Removal: A Weighted Support Vector Machine Approach With Error Correction

An automatic electroencephalogram (EEG) artifact removal method is presented in this paper. Compared to past methods, it has two unique features: 1) a weighted version of support vector machine formulation that handles the inherent unbalanced nature of component classification and 2) the ability to accommodate structural information typically found in component classification. The advantages of the proposed method are demonstrated on real-life EEG recordings with comparisons made to several benchmark methods. Results show that the proposed method is preferable to the other methods in the context of artifact removal by achieving a better tradeoff between removing artifacts and preserving inherent brain activities. Qualitative evaluation of the reconstructed EEG epochs also demonstrates that after artifact removal inherent brain activities are largely preserved.

Dural puncture and activated protein C resistance: risk factors for cerebral venous sinus thrombosis

OBJECTIVES Dural puncture is regarded a safe procedure when contraindications are carefully excluded and has so far not been recognised as a risk factor for cerebral venous sinus thrombosis (CVST). Five patients are described with CVST after dural puncture in the presence of additional risk factors. METHODS In four out of five patients complete investigations for thrombophilia were performed at least one month after withdrawal of oral anticoagulation. RESULTS In three out of four patients tested, activated protein C (APC) resistance due to heterozygous coagulation factor V R506Q mutation (factor V Leiden) was found. One patient was using oral contraceptives as a circumstantial risk factor and three had had spinal anaesthesia for surgical procedures. Family history of venous thromboembolism was negative in all patients. Retrospective evaluation of 66 patients with CVST disclosed that dural puncture was the fourth most common risk factor (8%) possibly contributing to thrombosis. CONCLUSION Dural puncture may constitute an additional risk factor for CVST especially in patients with APC resistance or surgery. In such patients a thrombophilia screen is indicated.

Early Diagnosis of Neuropathy in Leprosy—Comparing Diagnostic Tests in a Large Prospective Study (the INFIR Cohort Study)

Background Leprosy is the most frequent treatable neuromuscular disease. Yet, every year, thousands of patients develop permanent peripheral nerve damage as a result of leprosy. Since early detection and treatment of neuropathy in leprosy has strong preventive potential, we conducted a cohort study to determine which test detects this neuropathy earliest. Methods and Findings One hundred and eighty-eight multibacillary (MB) leprosy patients were selected from a cohort of 303 and followed for 2 years after diagnosis. Nerve function was evaluated at each visit using nerve conduction (NC), quantitative thermal sensory testing and vibrometry, dynamometry, monofilament testing (MFT), and voluntary muscle testing (VMT). Study outcomes were sensory and motor impairment detected by MFT or VMT. Seventy-four of 188 patients (39%) had a reaction, neuritis, or new nerve function impairment (NFI) event during a 2-year follow-up. Sub-clinical neuropathy was extensive (20%–50%), even in patients who did not develop an outcome event. Sensory nerve action potential (SNAP) amplitudes, compound motor action potential (CMAP) velocities, and warm detection thresholds (WDT) were most frequently affected, with SNAP impairment frequencies ranging from 30% (median) to 69% (sural). Velocity was impaired in up to 43% of motor nerves. WDTs were more frequently affected than cold detection thresholds (29% versus 13%, ulnar nerve). Impairment of SNC and warm perception often preceded deterioration in MF or VMT scores by 12 weeks or more. Conclusions A large proportion of leprosy patients have subclinical neuropathy that was not evident when only MFT and VMT were used. SNC was the most frequently and earliest affected test, closely followed by WDT. They are promising tests for improving early detection of neuropathy, as they often became abnormal 12 weeks or more before an abnormal monofilament test. Changes in MFT and VMT score mirrored changes in neurophysiology, confirming their validity as screening tests.

Sonography versus Nerve Conduction Studies in Patients Referred with a Clinical Diagnosis of Carpal Tunnel Syndrome

To compare the diagnostic value of high‐resolution ultrasound (US) with nerve conduction studies (NCS) in patients with clinically defined carpal tunnel syndrome (CTS).

High dose of simvastatin induces hyperlocomotive and anxiolytic-like activities: The association with the up-regulation of NMDA receptor binding in the rat brain

Statins are widely being used for the treatment of a variety of conditions beyond their original indication for lowering cholesterol. We have previously reported that simvastatin affected the dopaminergic system in the rat brain. This study aims to investigate locomotor and anxiety effects along with the regional changes of N-methyl-d-aspartate (NMDA) receptors in the rat brain after 4-week administration of simvastatin. Hyperlocomotive and anxiolytic-like activities in the rat were observed after chronic administration of high dose simvastatin (10 mg/kg/day). Distributions and alterations of NMDA receptors in the post-mortem rat brain were detected by [(3)H] MK-801 binding autoradiography. Simvastatin increased [(3)H] MK-801 binding, predominantly in the prefrontal cortex (20%, p=0.003), primary motor cortex (20%, p<0.001), cingulate cortex (28%, p<0.001), hippocampus (41%, p<0.001), caudate putamen (30%, p=0.029), nucleus accumbens (27%, p=0.035) and amygdala (45%, p<0.001) compared to controls. Significant positive correlations were identified between hyperlocomotive as well as anxiolytic-like activities and the upregulation of NMDA receptors in different brain regions. Our results also provide strong evidence that chronic high dose simvastatin administration is to exhibit NMDA antagonist-like effects, which would partially explain the anxiolytic and hyperlocomotor activities. These findings contribute to a better understanding of the critical roles of simvastatin in modulating psycho-neurodegenerative disorders, via NMDA receptors.

Feature selection via sensitivity analysis of SVM probabilistic outputs

Abstract Feature selection is an important aspect of solving data-mining and machine-learning problems. This paper proposes a feature-selection method for the Support Vector Machine (SVM) learning. Like most feature-selection methods, the proposed method ranks all features in decreasing order of importance so that more relevant features can be identified. It uses a novel criterion based on the probabilistic outputs of SVM. This criterion, termed Feature-based Sensitivity of Posterior Probabilities (FSPP), evaluates the importance of a specific feature by computing the aggregate value, over the feature space, of the absolute difference of the probabilistic outputs of SVM with and without the feature. The exact form of this criterion is not easily computable and approximation is needed. Four approximations, FSPP1-FSPP4, are proposed for this purpose. The first two approximations evaluate the criterion by randomly permuting the values of the feature among samples of the training data. They differ in their choices of the mapping function from standard SVM output to its probabilistic output: FSPP1 uses a simple threshold function while FSPP2 uses a sigmoid function. The second two directly approximate the criterion but differ in the smoothness assumptions of criterion with respect to the features. The performance of these approximations, used in an overall feature-selection scheme, is then evaluated on various artificial problems and real-world problems, including datasets from the recent Neural Information Processing Systems (NIPS) feature selection competition. FSPP1-3 show good performance consistently with FSPP2 being the best overall by a slight margin. The performance of FSPP2 is competitive with some of the best performing feature-selection methods in the literature on the datasets that we have tested. Its associated computations are modest and hence it is suitable as a feature-selection method for SVM applications.

Diagnosing carpal tunnel syndrome--clinical criteria and ancillary tests.

Damage to the median nerve within the carpal tunnel gives rise to carpal tunnel syndrome (CTS), which is associated with a wide spectrum of symptoms. The predominant classic symptoms are nocturnal pain of the hand, and sensory disturbances within the distribution of the median nerve, both of which are characteristically relieved by hand movements. Ancillary tests, including nerve conduction studies (NCS) and imaging techniques, are mainly indicated when the classic defining features are absent. NCS are less accurate in the early stages of CTS, and in younger patients. Imaging tests (ultrasound and MRI), while still having a lower diagnostic accuracy than NCS, are proving to be useful for explaining persistence of symptoms following surgical relief. Supplementary tests of small nerve fiber function and measurement of intracarpal pressure might, in the future, improve early recognition of CTS, especially in the absence of well-defined symptoms.

Combined Doppler and B-mode sonography in carpal tunnel syndrome

An intraoperatively enlarged engorged median nerve has been described as typical of patients with carpal tunnel syndrome (CTS). Although many studies of CTS have addressed median nerve enlargement, little is known about the usefulness of Doppler methods in detecting median nerve engorgement combined with nerve cross-sectional area (CSA). In a retrospective study of hands referred for evaluation of possible CTS, patients were clinically graded into Highly-likely or Indeterminate CTS. Nerve conduction studies (NCS), CSA, and Doppler analysis were compared. Median nerve blood flow was detected in 29 of 30 Highly-likely CTS hands (mean 13.3m/s (8.2) SD) and in 25 of 30 with Indeterminate CTS (mean 8.5m/s (4.5) SD). These were significantly higher than our laboratory normal values (mean 1.9 m/s (2.8) SD). Raised intraneural blood flow showed the highest test sensitivity in diagnosing Highly-likely carpal tunnel syndrome (83%) and combined with CSA reached 90%. NCS sensitivity was 83%. In the group of Indeterminate CTS, combined blood flow and CSA showed abnormality in 77% and NCS 47%. All nerve conduction parameters and median nerve cross sectional area showed linear correlation to intraneural blood flow velocity (P<0.05; Spearmans r=0.362 to 0.264). This study suggests that adding measures of intraneural blood flow to CSA further improves the sonographic evaluation of CTS and may be of particular use in patients with negative NCS.

Electroencephalographic changes and seizures in familial hemiplegic migraine patients with the CACNA1A gene S218L mutation.

The S218L CACNA1A mutation has been previously described in two families with familial hemiplegic migraine. We present three siblings with the mutation with the novel association of childhood seizures, and highlight the dynamic changes seen on electroencephalography during hemiplegic migraine attacks. Depressed activity contralateral to the hemiparesis was seen on electroencephalography during acute hemiplegic migraine attacks, which may be due to changes to calcium channels caused by the S218L mutation. Both parents were asymptomatic and did not carry the S218L mutation in their blood. This suggests the presence of mosaicism in the transmitting parent.

Frequency-domain EEG source analysis for acute tonic cold pain perception

OBJECTIVE To investigate electrocortical responses to tonic cold pain by frequency-domain electroencephalogram (EEG) source analysis, and to identify potential electrocortical indices of acute tonic pain. METHODS Scalp EEG data were recorded from 26 healthy subjects under tonic cold pain (CP) and no-pain control (NP) conditions. EEG power spectra and the standardized low-resolution brain electromagnetic tomography (sLORETA) localized EEG cortical sources were compared between the two conditions in five frequency bands: 1-4 Hz, 4-8 Hz, 8-12 Hz, 12-18 Hz and 18-30 Hz. RESULTS In line with the EEG power spectral results, the source power significantly differed between the CP and NP conditions in 8-12 Hz (CPNP) in extensive brain regions. Besides, there were also significantly different 4-8 Hz and 12-18 Hz source activities between the two conditions. Among the significant source activities, the left medial frontal and left superior frontal 4-8 Hz activities, the anterior cingulate 8-12 Hz activity and the posterior cingulate 12-18 Hz activity showed significant negative correlations with subjective pain ratings. CONCLUSIONS The brains perception of tonic cold pain was characterized by cortical source power changes across different frequency bands in multiple brain regions. Oscillatory activities that significantly correlated with subjective pain ratings were found in the prefrontal and cingulate regions. SIGNIFICANCE These findings may offer useful measures for objective pain assessment and provide a basis for pain treatment by modulation of neural oscillations at specific frequencies in specific brain regions.