Implementation of N-Interval fourier transform analysis - Application to compound action potentials.

N-Interval Fourier Transform Analysis (N-FTA) allows for spectral separation of a periodic target signal from uncorrelated background interference. A N-FTA pseudo-code is presented. The spectral resolution is defined by the repetition rate of the near periodic signal. Acceptance criteria for spectral targets were defined such that the probability of accepting false positives is less than 1500. Simulated and recorded neural compound action potentials (CAPs) were investigated. Simulated data allowed for comparison with reference solutions demonstrating the stability of N-FTA at conditions being comparable to real world data. Background activity was assessed with small errors. Evoked target components were assessed down to power spectral density being approximately N times below the background level. Validation was completed investigating a measured CAP. In neurophysiological recordings, this approach allows for accurate separation of near periodic evoked activity from uncorrelated background activities for frequencies below 1kHz.•N-FTA allows for spectral separation of a periodic target signal from uncorrelated interference by analyzing a segment containing N target signal repetitions.•A MATLAB implementation of the algorithm is provided along with simulated and recorded data.•N-FTA was successfully validated using simulated and measured data for CAPs.

Efecto analgésico del baclofeno intratecal a largo plazo sobre el dolor neuropático en pacientes con lesión medular / The long-term analgesic effect of intrathecal baclofen on neuropathic pain in patients with spinal cord injury

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A Lead Field Two-Domain Model for Longitudinal Neural Tracts-Analytical Framework and Implications for Signal Bandwidth.

Somatosensory evoked potentials are a well-established tool for assessing volley conduction in afferent neural pathways. However, from a clinical perspective, recording of spinal signals is still a demanding task due to the low amplitudes compared to relevant noise sources. Computer modeling is a powerful tool for gaining insight into signal genesis and, thus, for promoting future innovations in signal extraction. However, due to the complex structure of neural pathways, modeling is computationally demanding. We present a theoretical framework which allows computing the electric potential generated by a single axon in a body surface lead by the convolution of the neural lead field function with a propagating action potential term. The signal generated by a large cohort of axons was obtained by convoluting a single axonal signal with the statistical distribution of temporal dispersion of individual axonal signals. For establishing the framework, analysis was based on an analytical model. Our approach was further adopted for a numerical computation of body surface neuropotentials employing the lead field theory. Double convolution allowed straightforward analysis in the frequency domain. The highest frequency components occurred at the cellular membrane. A bandpass type spectral shape and a peak frequency of 1800 Hz was observed. The volume conductor transmitting the signal to the recording lead acted as an additional bandpass reducing the axonal peak frequency from 200 Hz to 500 Hz. The superposition of temporally dispersed axonal signals acted as an additional low-pass filter further reducing the compound action potential peak frequency from 90 Hz to 170 Hz. Our results suggest that the bandwidth of spinal evoked potentials might be narrower than the bandwidth requested by current clinical guidelines. The present findings will allow the optimization of noise suppression. Furthermore, our theoretical framework allows the adaptation in numerical methods and application in anatomically realistic geometries in future studies.

Influence of posture on blink reflex prepulse inhibition induced by somatosensory inputs from upper and lower limbs.

BACKGROUND: Prepulse inhibition (PPI) is a neurophysiological phenomenon whereby a weak stimulus modulates the reflex response to a subsequent strong stimulus. Its physiological purpose is to avoid interruption of sensory processing by subsequent disturbing stimuli at the subcortical level, thereby preventing undesired motor reactions. An important hub in the PPI circuit is the pedunculopontine nucleus, which is also involved in the control of posture and sleep/wakefulness. OBJECTIVE: To study the effect of posture (supine versus standing) on PPI, induced by somatosensory prepulses to either upper or lower limb. PPI was measured as the percentage inhibition of the blink reflex response to electrical supraorbital nerve (SON) stimulation. METHODS: Sixteen healthy volunteers underwent bilateral blink reflex recordings following SON stimulation either alone (baseline) or preceded by an electrical prepulse to the median nerve (MN) or sural nerve (SN), both in supine and standing. Stimulus intensity was 8 times sensory threshold for SON, and 2 times sensory threshold for MN and SN, respectively. Eight stimuli were applied in each condition. RESULTS: Baseline blink reflex parameters did not differ significantly between the two postures. Prepulse stimulation to MN and SN caused significant inhibition of R2. In supine but not in standing, R2 was significantly more inhibited by MN than by SN prepulses. In standing, SN stimulation caused significantly more inhibition of R2 than in supine, while the inhibition caused by MN prepulses did not differ significantly between postures. SIGNIFICANCE: PPI induced by lower limb afferent input may contribute to postural control while standing.

Focus on the pedunculopontine nucleus. Consensus review from the May 2018 brainstem society meeting in Washington, DC, USA.

The pedunculopontine nucleus (PPN) is located in the mesopontine tegmentum and is best delimited by a group of large cholinergic neurons adjacent to the decussation of the superior cerebellar peduncle. This part of the brain, populated by many other neuronal groups, is a crossroads for many important functions. Good evidence relates the PPN to control of reflex reactions, sleep-wake cycles, posture and gait. However, the precise role of the PPN in all these functions has been controversial and there still are uncertainties in the functional anatomy and physiology of the nucleus. It is difficult to grasp the extent of the influence of the PPN, not only because of its varied functions and projections, but also because of the controversies arising from them. One controversy is its relationship to the mesencephalic locomotor region (MLR). In this regard, the PPN has become a new target for deep brain stimulation (DBS) for the treatment of parkinsonian gait disorders, including freezing of gait. This review is intended to indicate what is currently known, shed some light on the controversies that have arisen, and to provide a framework for future research.

Early thrombosis prophylaxis with enoxaparin is not associated with hematoma expansion in patients with spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Early pharmacological deep vein thrombosis (DVT) prophylaxis is recommended by guidelines, but rarely started within 48 h. We aimed to analyze the effect of early (within 48 h) versus late (>48 h) DVT prophylaxis on hematoma expansion (HE) and outcome in patients with spontaneous intracerebral hemorrhage (ICH). METHODS: We analyzed 134 consecutive patients admitted to a tertiary neurointensive care unit with diagnosed spontaneous ICH, without previous anticoagulation, severe coagulopathy, hematoma evacuation, early withdrawal of therapy or ineligibility for DVT prophylaxis according to our institutional protocol. Significant late HE was defined as ≥6 mL increase of hematoma volume between neuroimaging within 48 h and day 3-6. Multivariate analysis was performed to identify risk factors for late HE, poor 3-month outcome (modified Rankin Scale score ≥ 4) and mortality. RESULTS: Patients had a median Glasgow Coma Scale score of 14 [interquartile range (IQR), 10-15], ICH volume of 11 (IQR, 5-24) mL and were 71 (IQR, 61-76) years old. A total of 56% (n = 76) received early DVT prophylaxis, 37% (n = 50) received late DVT prophylaxis and 8 (6%) had unknown bleeding onset. Patients with early DVT prophylaxis had smaller ICH volume [9.5 (IQR, 4-18.5) vs. 17.5 (IQR, 8-29) mL, P = 0.038] and were more often comatose (26% vs. 10%, P = 0.025). Significant late HE [n = 5/134 (3.7%)] was associated with larger initial ICH volume (P = 0.02) and lower thrombocyte count (P = 0.03) but not with early DVT prophylaxis (P = 0.36). Early DVT prophylaxis was not associated with worse outcome. CONCLUSION: Significant late HE is uncommon and DVT prophylaxis within 48 h of symptom onset may be safe in selected patients with ICH.

[Voiding disorders in geriatric patients : Correlation with age-related functional impairments]. / Blasenentleerungsstörungen bei geriatrischen Patient(inn)en : Korrelation mit altersassoziierten funktionellen Defiziten.

INTRODUCTION: Voiding disorders are a common problem in elderly people. The highest incidence and prevalence occurs in female patients with a high level of dependency and cognitive impairments. AIM: The aim of the study was to define the correlation between the presence of voiding disorders and age-related functional deficits in hospitalized elderly patients within the framework of a comprehensive geriatric assessment. This is of utmost importance for planning adequate further diagnostic and therapeutic measures. METHODS: This study involved a retrospective cross-sectional assessment of data from 7487 hospitalized patients (74.1 % females, 25.9 % males, mean age 78.9 ± 7.2 years) evaluated by a multidimensional geriatric assessment. Items tested were symptoms of voiding disorders, activities of daily living, cognitive and emotional status, mobility, handgrip strength, need for walking aids, pain, nutritional status and visual function. Data were evaluated with respect to the prevalence of voiding disorders, patient functional status and to the relationship between these findings. RESULTS: Among all patients 4494 (60.0 %) presented with voiding disorders. Of these 95.8 % showed additional relevant functional deficits in three or more test items. Voiding disorders were positively correlated to patient age, dependency in activities of daily living and pain scores and were negatively correlated to cognitive and emotional status, mobility, hand grip strength, nutritional status and visual function. The functional deficits were associated with the severity of voiding disorders. Female patients were more often affected by voiding disorders as well as by functional impairments in comparison to male patients. DISCUSSION: The results showed that more than half of the elderly hospitalized patients suffered from voiding disorders. The high prevalence and correlation between the presence of voiding disorders and functional deficits indicate the need to clearly define and plan diagnostic and therapeutic measures (e. g. bladder diaries and bladder retraining) for these patients, taking the individual functional status into consideration. CONCLUSION: In older patients with voiding disorders, high levels of functional impairment should be considered before planning diagnostic and therapeutic measures in order to ensure the quality of implementation.

Acyclovir resistance in herpes simplex virus type I encephalitis: a case report.

Acyclovir resistance is rarely seen in herpes simplex virus (HSV) type I encephalitis. Prevalence rates vary between 0.5 % in immunocompetent patients (Christophers et al. 1998; Fife et al. 1994) and 3.5-10 % in immunocompromised patients (Stranska et al. 2005). We report a 45-year-old, immunocompetent (negative HIV antigen/antibody testing), female patient, without previous illness who developed-after a febrile prodromal stage-aphasia and psychomotor slowing. Cerebral magnetic resonance imaging (cMRI) showed right temporal and insular T2-hyperintense lesions with spreading to the contralateral temporal lobe. Cerebrospinal fluid (CSF) analysis yielded lymphocytic pleocytosis and elevated protein level. Polymerase chain reaction testing for HSV type I showed a positive result in repeat lumbar puncture. HSV type I encephalitis was diagnosed and intravenous acyclovir treatment was initiated (750 mg t.i.d.). Acyclovir treatment was intensified to 1000 mg t.i.d., due to clinical deterioration, ongoing pleocytosis and progression on cMRI 5 days after initiation of antiviral therapy. In parallel, acyclovir resistance testing showed mutation of thymidine kinase gene at position A156V prompting foscarnet therapy (60 mg t.i.d.). Patient's condition improved dramatically over 2 weeks. Acyclovir resistance is rare but should be considered in case of clinical worsening of patient's condition. To our knowledge, this is the first report of acyclovir resistance in HSV type I encephalitis of an immunocompetent and previously healthy patient in Austria.

Effect of intrathecal baclofen on evoked pain perception: an evoked potentials and quantitative thermal testing study.

BACKGROUND AND OBJECTIVES: Somatic antinociceptive effects of baclofen have been demonstrated in animal models. We hypothesized that if enhanced thermal or pain sensitivity is produced by loss of gamma-aminobutyric acid (GABA)-ergic tone in the central nervous system, spinal administration of GABA agonists might be predicted to be effective in thermal and/or pain perception changes and pain-related evoked potentials in candidates for intrathecal baclofen (ITB) treatment. METHODS: Eleven patients with severe spinal cord injury (SCI) who suffered from severe spasticity were evaluated during a 50-µg ITB bolus test. Warm and heat pain thresholds, evoked heat pain perception, and contact heat-evoked potentials (CHEPs) were determined above SCI level from the right and left sides. Nine age- and gender-matched healthy volunteers undergoing repeat testing without any placebo injection served as control group. RESULT: In patients, heat pain perception threshold increased, and evoked pain perception and amplitude of CHEPs decreased significantly after ITB bolus application in comparison with baseline (p < 0.005), with no change in warm perception threshold. In controls, no significant changes were observed in repeat testing over time. CONCLUSION: Our findings indicate that ITB modulates heat pain perception threshold, evoked heat pain perception and heat pain-related evoked potentials without inducing warm perception threshold changes in SCI patients. This phenomenon should be taken into account in the clinical evaluation and management of pain in patients receiving baclofen.

Cutaneous silent periods are not affected by the antihistaminic drug cetirizine.

OBJECTIVE: Noxious digital nerve stimulation leads to transient suppression of the electromyographic activity in isometrically contracted hand muscles, known as the "cutaneous silent period" (CSP). To date, neurotransmitters potentially involved in mediating this electromyographic (EMG) suppression remain unknown. Anecdotal observation lead to the hypothesis that antihistaminic medication may counteract nociceptive EMG suppression, as CSPs in one male subject who was accustomed to CSP recordings were temporarily lost following ingestion of an antihistaminic drug for acute rhinitis. A second otherwise healthy male subject, who was on long-term cetirizine for allergic rhinitis, presented without clearly defined CSPs when volunteering for normal values. METHODS: We undertook a systematic study in five healthy subjects (including the one with temporarily lost CSPs) who underwent serial CSP testing after ingestion of 10 mg cetirizine. CSPs were elicited in thenar muscles following digit II and digit V stimulation (20 times sensory threshold, 100 sweeps rectified and averaged) before and 90, 180, and 360 min following intake of medication. RESULTS: CSP onset latency, CSP end latency and CSP duration, as well as the index of suppression did not change significantly following ingestion of 10 mg cetirizine. Repeat study in the subject with no clearly defined CSPs on long-term treatment revealed persistently absent CSPs after a 5-week withdrawal from cetirizine. CONCLUSION: CSPs are not affected by therapeutic doses of the H1 antihistaminic cetirizine. SIGNIFICANCE: Our findings suggest that histamine plays no major role as a neurotransmitter of CSPs.

The effect of a prepulse stimulus on the EMG rebound following the cutaneous silent period.

The cutaneous silent period (CSP) is a spinal inhibitory reflex mediated by Adelta fibres. The postinhibitory rebound of electromyographic (EMG) activity following the CSP has been mainly attributed to resynchronization of motoneurons, but the possibility of startle reflex activity contributing to the EMG burst has also been suggested. Several types of reflexes may be suppressed by a preceding weak stimulus--a phenomenon called prepulse inhibition (PPI). Our aim was to study whether PPI would diminish the EMG rebound, thereby providing further evidence for excitatory reflex activity contained within the postinhibitory EMG rebound following the CSP. Ten healthy subjects underwent CSP testing following noxious digit II stimulation in two conditions, with and without a prepulse applied to digit III. Rectified surface EMG recordings were obtained from right orbicularis oculi, sternocleidomastoid and thenar muscles of the dominant hand during thumb abduction with 25% of maximum force. The area of the EMG rebound and the EMG reflex responses in orbicularis oculi and sternocleidomastoid were significantly smaller in recordings where a prepulse stimulus was applied 100 ms before the stimulus as compared to control responses without prepulse. CSP onset and end latency, CSP duration, and the degree of EMG suppression were not influenced. Prepulses significantly reduced subjective discomfort as based on visual analog scale scores. Inhibition of the EMG rebound by prepulse stimulation supports the hypothesis that the excitatory EMG activity following the CSP contains not only resynchronization of motoneuronal firing, but also an excitatory reflex component. The most probable type of reflex seems to be a somatosensory startle reflex, a defence reaction which is generated in structures located in the caudal brainstem following an unexpected intense stimulus. Reduction of the discomfort associated with high-intensity electrical fingertip stimulation by a prepulse without affecting CSP parameters underlines the utility of PPI in the context of CSP testing.

[ARMOR: an electromechanical robot for upper limb training following stroke. A prospective randomised controlled pilot study]. / ARMOR: Elektromechanischer Roboter für das Bewegungstraining der oberen Extremität nach Schlaganfall. Prospektive randomisierte kontrollierte Pilotstudie.

PURPOSE: Due to the complexity of the upper motor neuron syndrome, functional improvement in the paretic upper limb after stroke continues to be a challenge in neurorehabilitation. Robot-assisted training has been shown to be useful in relearning gait. In order to achieve similar results in the upper limb, an electromechanical arm robot (ARMOR), capable of moving all joints through complex patterns, has been developed. MATERIAL AND METHOD: Eight patients following stroke of different etiologies were included in a clinical AB-BA cross-over study comparing ARMOR training with EMG-triggered neuromuscular electrical stimulation (EMG-NMES). Chedoke-McMaster Stroke Assessment, modified Ashworth Scale, goniometry (Neutral-0-Method), dynamometry and Functional Dexterity Test served as outcome measures. RESULTS: ARMOR training resulted in more improvement of muscle tone (p = 0.004), range of movement (ROM) (p = 0.005) and dexterity, but less improvement of strength, than EMG-NMES. Chedoke-McMaster Stroke Assessment showed improvement of at least one point in shoulder pain and arm and hand activity during ARMOR training, while these values did not change with EMG-NMS. Better results of ARMOR training were achieved in the earlier phase (A1) than in the later phase (A2). CONCLUSION: This study demonstrates the positive effect of automatised training with a new electromechanical arm robot (ARMOR), and documents its clinical applicability in the rehabilitation of the paretic upper extremity in stroke patients.

[TSE surveillance in small ruminants and pigs: a pilot study]. / Uberwachung von TSE bei kleinen Wiederkäuern und Schweinen: Eine Pilotstudie.

Switzerland is controlling Transmissible Spongiform Encephalopathies (TSE) in cattle (BSE) and small ruminants (scrapie). Since BSE is potentially transmissible to sheep, goats or pigs through feeding of contaminated meat and bone meal, implementation of an active surveillance programme for TSE in these species is discussed. The aim of this pilot study was to obtain preliminary data on the prevalence ofTSE and other neurological disorders in these populations. For that purpose, a total of 398 perished and 825 slaughtered adult small ruminants and pigs was examined for the presence of neuropathological changes. None of these animals revealed positive for TSE. However, the investigations demonstrated that perished sheep and goats exhibited a higher prevalence of relevant neuropathological changes when compared with slaughtered animals. From these results, it is concluded that perished small ruminants are probably a risk population for TSE and should be considered as target populations for an active surveillance programme.

Brain natriuretic peptide (BNP) in patients undergoing coronary artery bypass grafting.

BACKGROUND: This study was designed to examine plasma concentrations of BNP and its relation to hemodynamic parameters in patients (pts.) with coronary artery disease (CAD) undergoing coronary artery bypass grafting (CABG). METHODS: 21 pts. with CAD undergoing CABG were examined. The pts. were divided into two groups. Group I: normal left ventricular function (LVF); Group II: reduced LVF. Pre-, intra- and postoperative BNP and hemodynamic parameters were measured. The perioperative administration of inotropic drugs was documented. RESULTS: In both groups postoperative BNP increased to a peak 24 h postoperatively; although BNP concentrations were high 24 h postoperatively hemodynamic parameters were improved in both groups. In Group I the BNP peak did not correlate with any hemodynamic parameter nor with the use of inotropic drugs. In Group II the BNP peak was inversely correlated with CO and CI and positively correlated with the PCWP. There was no correlation with inotropic support. CONCLUSION: Postoperative peak of BNP after 24 h does not reflect a state of acute perioperative heart failure or myocardial damage. These results suggest that the gene expression, metabolism and biological activity of BNP may be altered after extracorporeal circulation. Further studies are warranted to reveal the actual triggers for BNP increase early after CABG.

No benefit derived from repetitive transcranial magnetic stimulation in depression: a prospective, single centre, randomised, double blind, sham controlled "add on" trial.

Repetitive transcranial magnetic stimulation (rTMS) has been reported to demonstrate slight effects in the treatment of depression. Hence, a novel bilateral versus unilateral and sham stimulation design was applied to further assess rTMS' antidepressant effects. Forty one medication free patients with major depression, admitted to a psychiatric unit specialising in affective disorders, were consecutively randomised into 3 groups. Group A1 (n = 12) received unilateral active stimulation consisting of high frequency (hf) rTMS over the left dorsolateral prefrontal cortex (LDLPC) and subsequent sham low frequency (lf) rTMS over the right dorsolateral prefrontal cortex (RDLPC). Group A2 (n = 13) received simultaneous bilateral active stimulation consisting of hf-rTMS over the LDLPC and lf-rTMS over the RDLPC. Group C (n = 13) received bilateral sham stimulation. Stimulation was performed on 10 consecutive workdays. All patients received antidepressant medication on the first day of stimulation, which was continued during and after the stimulation period. As no significant difference in antidepressant outcome between group A1 and A2 was found, the two groups were pooled. The time course of the outcome variables Hamilton depression rating scale (HDRS(21)) and Beck depression inventory (days 0, 7, 14, 28) by repeated measures analysis of variance revealed no significant group differences (in terms of a group by time interaction), whereas there was a significant effect of time on all three outcome variables in all groups. The results suggest that rTMS as an "add on" strategy, applied in a unilateral and a bilateral stimulation paradigm, does not exert an additional antidepressant effect.

The erythrocyte adhesiveness/aggregation test for the detection of an acute phase response and for the assessment of its intensity.

We have developed a simple slide test and image analysis to reveal the state of erythrocyte adhesiveness/aggregation in the peripheral blood of patients with various degrees of the humoral acute phase response. The significant correlation between the results of the erythrocyte adhesiveness/aggregation test (EAAT), the erythrocyte sedimentation rate and fibrinogen concentration support the notion that it is possible to use the EAAT as a marker for the intensity of the acute phase response. Within a group of 860 individuals, we were able to differentiate effectively between groups of patients with a different intensity of humoral acute phase response. The present study confirms previous observations that support the applicability of the EAAT to routine clinical practice.

Influence of gender on auditory startle responses.

The auditory startle reaction is considered a brainstem reflex in response to an unexpected loud stimulus. It may be abnormal in various neurological conditions. However, the influence of gender on physiological characteristics of auditory startle responses (ASRs) in humans has to date been studied only in orbicularis oculi muscle. We investigated 54 healthy adult subjects (27 males, 27 females). ASRs were elicited by binaural high-intensity auditory stimuli which differed randomly in tonal frequency and intensity (250 Hz-90 db; 500 Hz-105 dB; 750 Hz-110 db, 1000 Hz-110 dB nHL), presented through tubal insert phones. Reflex electromyographic activity was simultaneously recorded with surface electrodes from masseter, orbicularis oculi, sternocleidomastoid, biceps brachii, abductor pollicis brevis, rectus femoris, tibialis anterior, and soleus muscles. ASR probability was significantly lower, and ASR area under the curve was significantly smaller, in men versus women. Median onset latencies did not differ significantly, but tended to be shorter in the lower extremities of men despite greater body height. Habituation, measured as a reduction in response probability with repeated stimulation, was significant in all muscles except orbicularis oculi in both men and women. Our data provide evidence for a significant influence of gender on ASR characteristics. The observed differences are likely due to gender-specific variations of central processing in the brainstem centers involved in ASR generation, and should be taken into account when testing ASRs in health and disease.