Comparison between adaptive and fixed stimulus paired-pulse transcranial magnetic stimulation (ppTMS) in normal subjects.

OBJECTIVES: Paired-pulse TMS (ppTMS) examines cortical excitability but may require lengthy test procedures and fine tuning of stimulus parameters due to the inherent variability of the elicited motor evoked potentials (MEPs) and their tendency to exhibit a 'ceiling/floor effects' in inhibition trials. Aiming to overcome some of these limitations, we implemented an 'adaptive' ppTMS protocol and compared the obtained excitability indices with those from 'conventional' fixed-stimulus ppTMS. METHODS: Short- and long interval intracortical inhibition (SICI and LICI) as well as intracortical facilitation (ICF) were examined in 20 healthy subjects by adaptive ppTMS and fixed-stimulus ppTMS. The test stimulus intensity was either adapted to produce 500 µV MEPs (by a maximum likelihood strategy in combination with parameter estimation by sequential testing) or fixed to 120% of resting motor threshold (rMT). The conditioning stimulus was 80% rMT for SICI and ICF and 120% MT for LICI in both tests. RESULTS: There were significant (p < 0.05) intraindividual correlations between the two methods for all excitability measures. There was a clustering of SICI and LICI indices near maximal inhibition ('ceiling effect') in fixed-stimulus ppTMS which was not observed for adaptive SICI and LICI. CONCLUSIONS: Adaptive ppTMS excitability data correlates to those acquired from fixed-stimulus ppTMS. SIGNIFICANCE: Adaptive ppTMS is easy to implement and may serve as a more sensitive method to detect changes in cortical inhibition than fixed stimulus ppTMS. Whether equally confident data are produced by less stimuli with our adaptive approach (as already confirmed for motor threshold estimation) remains to be explored.

Efficacy and safety of lidocaine for treatment of neonatal seizures.

AIM: Treatment of neonatal seizures still relies primarily on phenobarbital, despite an estimated efficacy of less than 50% and concern over neurodegenerative side effects. The objective of this study was to evaluate the efficacy and safety of lidocaine as second-line treatment of neonatal seizures in infants following benzodiazepine treatment but without previous treatment with phenobarbital. METHODS: In a 10-year cohort, a retrospective chart review was conducted for all infants (gestational age ≥ 37 w, age ≤ 28 days) who had received lidocaine as second-line treatment of neonatal seizures prior to treatment with phenobarbital between January 2000 and June 2010. Infants were included if they had electroencephalographic seizures. RESULTS: Cessation of seizure activity was seen in 16 of 30 infants based on clinical and electroencephalographic features, and a probable response was seen in an additional 3 of 30 patients. Suspected adverse effects were seen in only one patient, who developed a transient bradycardia. CONCLUSION: Lidocaine has a moderate efficacy as second-line therapy following benzodiazepines for treating neonatal seizures and is not frequently associated with cardiovascular adverse effects. Lidocaine should therefore be considered in the treatment of seizures in the neonatal period to a higher extent than is the case today.

Clinical, neuroimaging and neurophysiological features in addicts with manganese-ephedrone exposure.

OBJECTIVE: To identify biomarkers supporting the clinical diagnosis of manganism in patients several years after exposure to manganese (Mn). METHODS: Neurophysiological examinations, magnetic resonance imaging (MRI), single-photon emission computed tomography and fluorodeoxyglycose (FDG) positron emission tomography were performed in four former ephedrone addicts with extrapyramidal symptoms. RESULTS: Peripheral nervous system was not affected. No patients had reduced uptake of (123)I Ioflupane in the striatum. MRI signal intensities were slightly changed in the basal ganglia. All patients showed a widespread, but not uniform, pathological pattern of FDG uptake with changes mainly located to the central part of the brain including the basal ganglia and the surrounding white matter. CONCLUSIONS: Presynaptic neurons in the nigrostriatal pathway are intact in Mn-induced parkinsonism after prolonged abstinence from ephedrone. The diagnosis is principally based on clinical signs and the history of drug abuse.

Guidelines for the use of EEG methodology in the diagnosis of epilepsy. International League Against Epilepsy: commission report. Commission on European Affairs: Subcommission on European Guidelines.

The Commission of European Affairs of the International League Against Epilepsy published 'Appropriate Standards for Epilepsy Care Across Europe' which contained recommendations for the use of electroencephalography (EEG) in the diagnosis of epilepsy (Brodie et al. Epilepsia 1997; 38:1245). The need for a more specific basic document of EEG methodology was recognized and the Subcommission on European Affairs was asked to produce more detailed guidelines to be used across Europe recognizing the range of practices in EEG laboratories. There are many general guidelines published on EEG methodology but this document focuses on the diagnosis of epilepsy. Details from previously published guidelines are included in references and in an appendix. These guidelines are not meant to be used as minimal standards but recommendations that can be applied to all EEG laboratories despite variations in equipment.

Extracellular amino acid levels measured with intracerebral microdialysis in the model of posttraumatic epilepsy induced by intracortical iron injection.

An iron induced model of posttraumatic chronic focal epilepsy in rats was studied with respect to extracellular amino acids, electrophysiology, and morphology, approx. 6 months after intracortical injection of ferrous chloride. Twenty-six of the twenty-eight (93%) rats developed spontaneous epileptiform EEG-activity and electrical cortical stimulation done in eight animals evoked seizure activity in five animals (62.5%). Epileptic brain tissue displayed significantly higher extracellular interictal levels of aspartate (ASP), compared to normal brain, measured with intracerebral microdialysis. The interictal levels of serine (SER) were significantly higher at the lesion side compared to the contralateral cortex in epileptic animals. Spontaneous elevations of ASP and glutamate (GLU) levels up to 8 times the basal level were found in 4/5 (80%). There was no consistent amino acid pattern following the electrically induced seizures, but in association with more intense seizure activity ASP and GLU were elevated. Histopathologically, the necrotic lesions in the cortex contained small vessels and iron pigment loaded astrocytes. Scattered eosinophilic neurons were found in the hippocampus, bilaterally in 37% of the animals. The results show that a focal epileptiform activity developed in a high percentage of animals that received an intracortical iron injection. The observed amino acid changes in epileptic animals may be involved in the development of seizures in this model of posttraumatic epilepsy.

Decreased cortical levels of astrocytic glutamate transport protein GLT-1 in a rat model of posttraumatic epilepsy.

The extracellular homeostasis of glutamate in the brain is maintained by the efficient uptake into astroglial cells. The high extracellular glutamate levels seen during seizures are therefore probably a result of both an increased synaptic release and a deranged glutamate uptake. In this study we used immuno-blotting technique to measure the cortical levels of the astrocytic glutamate transport protein (GLT-1) and of the glutamate and aspartate transporting protein (GLAST) in an epilepsy model induced by ferrous chloride injection in the cortex of rats. The levels of GLT-1 were lower in epileptic rats than in controls, day 1 and 5 after induction, but not at 3 months. Glial fibrillary protein (GFAP) levels increased with time in the epileptic model, whereas GLAST and beta-tubulin III remained unchanged compared to controls. The results suggest that the transient decrease of GLT-1 could play a role in epileptogenesis, while recurrent seizure activity may be maintained by other mechanisms.

Electric stimulation of a transsected nerve does not seem to prevent loss of sensory neurons: an experimental study in cats.

Injury to a sensory nerve often results in a clinically poor long term outcome, possibly as a result of the extensive loss of neurons within the dorsal root ganglia (DRG), which has been shown in several experimental studies. This loss is possibly caused by interruption of the sensory input and axonal transport in the damaged afferent nerve. To investigate the importance of sensory afferent input into a nerve a pulsed electric stimulation was applied on the proximal part of the superficial radial nerve after transsection and microsurgical repair. The purpose was to simulate nerve impulses and thereby mask the severity of the injury. To test this hypothesis a pilot study was undertaken in eight cats. The neuronal tracer showed that the median neuronal loss was 38% of the neurons of the dorsal root ganglia that received afferents from the nerve investigated, which corresponds to the figure in a previous study in which electric stimulation was not used. Artificial sensory stimulation during regeneration in a transsected and repaired peripheral nerve therefore does not seem to reduce neuronal loss.

Urinary stress incontinence. A urodynamic and quantitative electromyographic study of the perineal muscles.

BACKGROUND: Neurophysiological techniques are increasingly used in examination of urinary incontinence. The purpose was to measure the activity in the perineal muscles in women with urinary stress incontinence and compare with normal subjects by using quantitative EMG methods. METHODS: Twenty-four incontinent women and seven normal subjects were evaluated urodynamically and with quantitative EMG analysis of interference pattern and single fiber measurements. The recordings were made in the pubo rectal and the external anal sphincter muscle with empty urinary bladder at rest and maximal voluntary contraction as well as during cystometry. RESULTS: The incontinent women had a denser interference pattern in the anal sphincter at rest but no differences at maximal activation compared to the reference group. No differences in interference pattern were noted between the two groups in the pubo rectal muscle. Fiber density in the external anal sphincter muscle was increased in the patient group (2.01 compared to 1.33, p<0.01). The urethral pressures at rest and activation were higher in the normal subjects (p<0.05). The normal subjects showed a denser interference pattern in the external anal sphincter muscle during cystometry (p<0.05). CONCLUSIONS: Quantitative analysis of the interference pattern and fiber density in the perineal muscles in incontinent women showed a denser interference pattern at rest and increased fiber density. Both observations indicate a peripheral nerve lesion. Furthermore, the interference pattern showed signs of reduced central activation in the incontinent women during cystometry.

Interference pattern in the urethral sphincter: a quantitative electromyographic study in patients before and after radical retropubic prostatectomy.

OBJECTIVE: Radical retropubic prostatectomy (RRP) involves removal of the bladder neck where the proximal urethral sphincter is located. Assuming that this sphincter participates in urinary continence mechanisms, removal of this sphincter might increase the interference pattern in the distal urethral sphincter as a compensatory mechanism. MATERIAL AND METHODS: We examined the distal (striated) urethral sphincter before and after surgery with quantitative EMG techniques in ten patients. RESULTS: No compensatory activity was demonstrated, but tendencies towards a decreased number of turns at rest (41 pre-op/27 post-op) and an increased mean amplitude at maximal activation (334 microV pre-op/408 microV post-op) in the interference pattern in the muscle were recorded using the turns/amplitude (T/A) analysis. The fibre density was 1.71 before and 1.96 after surgery (p = 0.08), indicating a peripheral nerve lesion. CONCLUSIONS: The numerical reduction of turns during rest can be explained by disturbed feedback, indicating that not only efferent, but also sensory afferent nerve fibres can be involved in an iatrogen lesion during prostatic surgery. The increased mean amplitude at maximal activation was probably due to reinnervated motor units with increased amplitudes.

Long-term neurological dysfunction and neonatal hypoglycaemia after diabetic pregnancy.

AIM: To determine if children born to mothers with diabetes mellitus during pregnancy, who subsequently developed neonatal hypoglycaemia, experienced long-term neurological dysfunction. METHODS: Thirteen children with, and 15 without, neonatal hypoglycaemia (blood glucose < 1.5 mmol/l) were randomly selected from a larger cohort and investigated at the age of 8 years. They were also compared with 28 age matched healthy controls. RESULTS: Children with neonatal hypoglycaemia had significantly more difficulties in a validated screening test for minimal brain dysfunction than controls and were also more often reported to be hyperactive, impulsive, and easily distracted. On psychological assessment, they had a lower total development score than normoglycaemic children born to diabetic mothers, and control children. CONCLUSIONS: Neonatal hypoglycaemia in diabetic pregnancy was associated with long-term neurological dysfunction related to minimal brain dysfunction/deficits in attention, motor control, and perception.

Interference pattern in perineal muscles: a quantitative electromyographic study in patients before and after transurethral surgery of the prostate.

The study aimed at assessing alterations in muscular activity in the external urethral sphincter when the internal sphincter located at the bladder neck was resected during TUR-P, and at determining whether activity in the external urethral sphincter increased to compensate for the loss of the internal sphincter. Perineal muscles were examined with quantitative EMG recordings, including interference pattern and fiber density before and after surgery. Fiber density increased in the external urethral sphincter after surgery. This indicates a reinnervation in the muscle, probably due to a peripheral nerve lesion that occurs during TUR-P, and may also explain the reduction in penile erectibility observed after surgery. The lack of compensatory activity in the external urethral sphincter expressed as unchanged number of turns may be explained as a disturbed feedback mechanism and a decreased central activation or to the lithotomy position at examination. The internal part of the external sphincter not available for measurement may compensate for the loss in bladder-neck sphincter function.

Clinical neurophysiological methods for investigating the lower urinary tract in patients with micturition disorders.

METHODS: Different clinical neurophysiological methods used in the investigation of patients with micturition disorders are summarized in a short critical review. The techniques of measuring nerve conduction velocities, sacral reflex latencies, cortical evoked potentials, sensory thresholds, concentric needle EMG and single fibre EMG are described and the clinical applications of the different methods are reported. CONCLUSION: It is concluded that the neurophysiological tests are mainly useful in establishing the integrity of the peripheral innervation of the pelvic floor and in case of neurogenic lesions, the combination of different methods might show the level of the lesion.

Conductivity ratios of the scalp-skull-brain head model in estimating equivalent dipole sources in human brain.

The dipole tracing (DT) method estimates the position and vector dipole moment of an equivalent current dipole by minimizing the mean squared error of the dipole potentials at the surface electrode positions. In the scalp-skull-brain/DT (SSB/DT) method, which we have developed, the head model consists of three compartments of uniform conductors corresponding to the scalp, skull and brain. The accuracy of the calculations are mainly dependent on the ratios of the conductivities of the three compartments. The best result was obtained with the conductivity ratios of 1:1/80:1 for the scalp, skull and brain compartments, respectively.

Location of electric current sources in the human brain estimated by the dipole tracing method of the scalp-skull-brain (SSB) head model.

Using a realistic, 3-shell head model including the scalp (S), skull (S) and brain (B) with conductivity ratios of 1:1/80:1, respectively, the electrical activity in the human brain recorded by conventional electroencephalography was approximated by 1 or 2 equivalent current dipoles. The dipole locations and vector moments were estimated by minimizing the squared difference between the potentials actually recorded from the scalp and those theoretically calculated from the equivalent dipoles. The validity of this dipole tracing method (the DT of the SSB head model) was tested in patients with focal epileptic seizures undergoing presurgical evaluation with intracranial subdural strip electrodes. Weak currents were passed through 1 or 2 pairs of subdural electrodes to create artificial dipoles. The dipole estimations correctly distinguished between single and double generator sources, but there were certain dislocations of the calculated dipoles. The average error of dislocation was found to be 8.5 mm for the 1-dipole model. That for the 2-dipole model was 6 mm for one of the components and 18 mm for the other. It was concluded that the DT method of the SSB head model can be a valuable clinical tool in 3-dimensional localization of focal epileptic discharges in the human brain.

Epileptic seizure activity in the acute phase following cortical impact trauma in rat.

The aim of this investigation was to determine the incidence of seizure activity in the acute phase following traumatic brain injury. Compression contusion trauma was produced in the right parietal cortex in 19 artificially ventilated rats. Electroencephalographic recordings were carried out in 17 of the animals for 2 h following the impact. The extracellular levels of neuroactive amino acids were simultaneously monitored in 9 of the experiments using microdialysis. In 14 of the 17 animals a generalized seizure activity with an average duration of 59 s (range 30-101 s) was recorded. The mean time lag between trauma and seizure onset was 67 s (range 26-90 s). The seizure activity was consistently followed by post-ictal depression. The trauma was accompanied by a transient increase of aspartate, taurine, glutamate and glycine, in decreasing rank order. The seizure activity occurred when the levels of these neuroactive amino acids were elevated. It is concluded that the high incidence of seizure activity observed may be an important factor contributing to secondary ischemia after traumatic brain injury. Aspartate and glutamate, potentiated by glycine, may play a role in post-traumatic seizure activity.

Interference pattern in perineal muscles. A quantitative electromyographic study in patients with faecal incontinence.

The aim of this study was to investigate the possibility of neuromuscular dysfunction in patients with faecal incontinence by measuring interference patterns in the external anal sphincter and puborectalis muscles with quantitative electromyography. The design was an open study including 20 patients with faecal incontinence; in 14 the aetiology was idiopathic and 6 had rupture of the external anal sphincter. Electromyographic interference patterns (turns/amplitude analysis) measured at rest and during maximum voluntary contraction in all patients were recorded together with fibre density measured by single fibre electromyography (n = 10) and anal pressure measured at rest and at maximum contraction (n = 17). A comparison was made with results of a previously published series of reference values taken from normal volunteers. The density of the interference pattern on maximum contraction of the puborectalis muscle was significantly lower among the patients with idiopathic faecal incontinence than among the reference group (137 compared with 241 turns/second, p < 0.01). There was also a significant difference on maximum contraction of the anal sphincter muscle among the group in whom it was ruptured compared with the reference group (76 compared with 165 turns/second, p < 0.05). Fibre density increased with age and was significantly higher among those with idiopathic incontinence (1.64 (0.2) compared with 1.33 (0.1) in the reference group, p < 0.01). There were no significant differences in anal manometry measurements between the groups. In conclusion, in patients with faecal incontinence the role of central activation of the perineal muscles is important, though other factors may play a part.