Far lateral lumbar disc herniation part 1: Imaging, neurophysiology and clinical features

Far lateral lumbar disc herniations(FLLDH)represent a separate category of disc pathology which includes both intraforaminal and extraforaminal lumbar disc herniations,that are characterized by a peculiar clinical presentation,diagnostic and treatment modalities as compared to the more frequent median and paramedian disc hernias.Surgical treatment often represents the only effective weapon for the cure of this disease and over the years different approaches have been developed that can reach the region of the foramen or external to it,with different degrees of invasiveness.The diagnosis is more demanding and still underestimated as it requires a more detailed knowledge in the spine anatomy and dedicated radiological studies.Computerized tomography and in particular magnetic resonance imaging are the appropriate tools for the diagnosis of FLLDH.Despite the widespread use of these diagnostic tests,many cases of FLLDH are overlooked due to insufficiently detailed radiological examinations or due to the execution of exams not focused to the foraminal or the extraforaminal region.Neurophysiological studies represent a valid aid in the diagnostic classification of this pathology and in some cases they can facilitate the differential diagnosis with other types of radiculopathies.In the present study,a comprehensive review of the clinical presentation,epidemiology,radiological study and the neurophysiological aspects is presented.

Neurophysiological, histological, and behavioral characterization of animal models of distraction spinal cord injury: a systematic review

Distraction spinal cord injury is caused by some degree of distraction or longitudinal tension on the spinal cord and commonly occurs in patients who undergo corrective operation for severe spinal deformity.With the increased degree and duration of distraction,spinal cord injuries become more serious in terms of their neurophysiology,histology,and behavior.Very few studies have been published on the specific characteristics of distraction spinal cord injury.In this study,we systematically review 22 related studies involving animal models of distraction spinal cord injury,focusing particularly on the neurophysiological,histological,and behavioral characteristics of this disease.In addition,we summarize the mechanisms underlying primary and secondary injuries caused by distraction spinal cord injury and clarify the effects of different degrees and durations of distraction on the primary injuries associated with spinal cord injury.We provide new concepts for the establishment of a model of distraction spinal cord injury and related basic research,and provide reference guidelines for the clinical diagnosis and treatment of this disease.

Stepping up after spinal cord injury:negotiating an obstacle during walking

Every day walking consists of frequent voluntary modifications in the gait pattern to negotiate obstacles.After spinal cord injury,stepping over an obstacle becomes challenging.Stepping over an obstacle requires sensorimotor transformations in several structures of the brain,including the parietal cortex,premotor cortex,and motor cortex.Sensory information and planning are transformed into motor commands,which are sent from the motor cortex to spinal neuronal circuits to alter limb trajectory,coordinate the limbs,and maintain balance.After spinal cord injury,bidirectional communication between the brain and spinal cord is disrupted and animals,including humans,fail to voluntarily modify limb trajectory to step over an obstacle.Therefore,in this review,we discuss the neuromechanical control of stepping over an obstacle,why it fails after spinal cord injury,and how it recovers to a certain extent.

Possible Cortical Spreading Depression Recorded Intraoperatively Following a Generalized Seizure: Illustrative Case

Background: We present a compelling case fitting the phenomenon of cortical spreading depression detected by intraoperative neurophysiological monitoring (IONM) following an intraoperative seizure during a craniotomy for revascularization. Cortical spreading depression (CSD, also called cortical spreading depolarization) is a pathophysiological phenomenon whereby a wave of depolarization is thought to propagate across the cerebral cortex, creating a brief period of relative neuronal inactivity. The relationship between CSD and seizures is unclear, although some literature has made a correlation between seizures and a cortical environment conducive to CSD. Methods: Intraoperative somatosensory evoked potentials (SSEPs) and electroencephalography (EEG) were monitored continuously during the craniotomy procedure utilizing standard montages. Electrophysiological data from pre-ictal, ictal, and post-ictal periods were recorded. Results: During the procedure, intraoperative EEG captured a generalized seizure followed by a stepwise decrease in somatosensory evoked potential cortical amplitudes, compelling for the phenomenon of CSD. The subsequent partial recovery of neuronal function was also captured electrophysiologically. Discussion: While CSD is considered controversial in some aspects, intraoperative neurophysiological monitoring allowed for the unique analysis of a case demonstrating a CSD-like phenomenon. To our knowledge, this is the first published example of this phenomenon in which intraoperative neurophysiological monitoring captured a seizure, along with a stepwise subsequent reduction in SSEP cortical amplitudes not explained by other variables.

Auditory brainstem functioning in individuals with misophonia

Purpose:Misophonia is not investigated much from an audiological perspective.Our study aims to examine the processing of the auditory retro-cochlear pathways in individuals with misophonia.Methods:A cross-sectional study was conducted among university students who had misophonia.The revised Amsterdam Misophonia Scale was used to determine the severity of misophonia.Participants were divided into mild and moderate-severe misophonia and compared with the healthy control group.Auditory Brainstem Response testing was recorded from all the individuals with misophonia.The absolute latency,amplitude,inter-peak latency difference,and inter-rate latency difference were compared between the groups.Results:One-way ANOVA result showed no significant difference in all the parameters of auditory brainstem response between the groups.These results are suggestive of normal brainstem processing in individuals with misophonia.Conclusions:The study concludes that the auditory pathway up to brainstem areas is intact in individuals with misophonia.Further studies are essential on a larger population for generalizing the results.

On the Hybrid Model of Nerve Pulse: Mathematical Analysis and Numerical Results

Amongst the important phenomena in neurophysiology, nerve pulse generation and propagation is fundamental. Scientists have studied this phenomena using mathematical models based on experimental observations on the physiological processes in the nerve cell. Widely used models include: the Hodgkin-Huxley (H-H) model, which is based entirely on the electrical activity of the nerve cell;and the Heimburg and Jackson (H-J), model based on the thermodynamic activity of the nerve cell. These classes of models do not, individually, give a complete picture of the processes that lead to nerve pulse generation and propagation. Recently, a hybrid model proposed by Mengnjo, Dikandé and Ngwa (M-D-N), takes into consideration both the electrical and thermodynamic activities of the nerve cell. In their work, the first three bound states of the model are analytically computed and they showed great resemblance to some of the experimentally observed pulse profiles. With these bound states, the M-D-N model reduces to an initial value problem of a linear parabolic partial differential equation with variable coefficients. In this work we consider the resulting initial value problem and, using the theory of function spaces, propose and prove conditions under which such equations will admit unique solutions. We then verify that the resulting initial value problem from the M-D-N model satisfies these conditions and so has a unique solution. Given that the derived initial value problem is complex and there are no known analytic techniques that can be deployed to obtain its solution, we designed a numerical experiment to estimate the solutions. The simulations revealed that the unique solution is a stable pulse that propagates in the x-t plane with constant velocity and maintains the shape of the initial profile.

Review: Practical Use of a Neurophysiological Detector and the Protocol for High-Performance Liquid Chromatography

The main aim for discovery and development of the neurophysiological detector was detection of the production’ seats and criminal use of poisons in warfare. Phosphor-organic (PO) substances with acetylcholinesterase-blocking effects are prohibited in warfare by international law (Geneva Protocol. https://www.un.org/disarmament/wmd/bio/1925-geneva-protocol/). Monitoring PO analogs with acetylcholinesterase-blocking effects and their degradation products in water and soil can provide clues to unlawful production sites and the possible use of POs in warfare. Attempts to analyze POs by derivatization have had a low ability to detect them. A neurophysiological detector (NPD)-high-performance liquid chromatography (HPLC) system was developed for specific detection with high detection ability. The first official presentation of our NPD was at the 3rd International Symposium on Separation in BioSciences SBS 2003: A 100 Years of Chromatography, May 13-18, 2003, in Moscow, Russia. The NPD in connection to HPLC was developed 14 years before the presentation at the SBS in 2003. Initially, NPD combined with an HPLC system was developed for intelligence services and only for use in monitoring and espionage against the unlawful production of neuroparalytic agents, as explained in this article. NPD combined with an HPLC system was developed in Umeå, Sweden, in 1987-89;the protocol was further developed in Statens Plantevern Institutt, Ås, Norway, in 1990-92. NPD may have great utility during the current period of active warfare in Europe. The initial challenge was detecting unlawful production and use of PO compounds and their metabolites that can potentially block acetylcholinesterase. The sensor in NPD can detect and monitor substances such as tabun, soman, and modern PO poisons used in military applications. This article describes the history of the development of NPD and its aim as a sensitive sensor in detecting PO substances with acetylcholinesterase-blocking effects.

New technologies to investigate the brain-gut axis

Functional gastrointestinal disorders are commonly encountered in clinical practice, and pain is their commonest presenting symptom. In addition, patients with these disorders often demonstrate a heightened sensitivity to experimental visceral stimulation, termed visceral pain hypersensitivity that is likely to be important in their pathophysiology. Knowledge of how the brain processes sensory information from visceral structures is still in its infancy. However, our understanding has been propelled by technological imaging advances such as functional Magnetic Resonance Imaging, Positron Emission Tomography, Magnetoencephalography, and Electroencephalography （EEG）. Numerous human studies have non-invasively demonstrated the complexity involved in functional pain processing, and highlighted a number of subcortical and cortical regions involved. This review will focus on the neurophysiological pathways （primary afferents, spinal and supraspinal transmission）, brainimaging techniques and the influence of endogenous and psychological processes in healthy controls and patients suffering from functional gastrointestinal disorders. Special attention will be paid to the newer EEG source analysis techniques. Understanding the phenotypic differences that determine an individual＇s response to injurious stimuli could be the key to understanding why some patients develop pain and hyperalgesia in response to inflammation/injury while others do not. For future studies, an integrated approach is required incorporating an individual＇s psychological, autonomic, neuroendocrine, neurophysiological, and genetic profile to define phenotypic traits that may be at greater risk of developing sensitised states in response to gut inflammation or injury.

Multimodal pain stimulation of the gastrointestinal tract

Understanding and characterization of pain and other sensory symptoms are among the most important issues in the diagnosis and assessment of patient with gastrointestinal disorders. Methods to evoke and assess experimental pain have recently developed into a new area with the possibility for multimodal stimulation （e.g., electrical, mechanical, thermal and chemical stimulation） of different nerves and pain pathways in the human gut. Such methods mimic to a high degree the pain experienced in the clinic. Multimodal pain methods have increased our basic understanding of different peripheral receptors in the gut in health and disease. Together with advanced muscle analysis, the methods have increased our understanding of receptors sensitive to mechanical, chemical and temperature stimuli in diseases, such as systemic sclerosis and diabetes. The methods can also be used to unravel central pain mechanisms, such as those involved in allodynia, hyperalgesia and referred pain. Abnormalities in central pain mechanisms are often seen in patients with chronic gut pain and hence methods relying on multimodal pain stimulation may help to understand the symptoms in these patients. Sex differences have been observed in several diseases of the gut, and differences in central pain processing between males and females have been hypothesized using multimodal pain stimulations. Finally, multimodal methods have recently been used to gain more insight into the effect of drugs against pain in the GI tract. Hence, the multimodal methods undoubtedly represents a major step forward in the future characterization and treatment of patients with various diseases of the gut.

Breath-based meditation: A mechanism to restore the physiological and cognitive reserves for optimal human performance

Stress can be associated with many physiologicalchanges resulting in significant decrements in human performance.Due to growing interests in alternative and complementary medicine by Westerners,many of the traditions and holistic yogic breathing practices today are being utilized as a measure for healthier lifestyles.These state-of-the-art practices can have a significant impact on common mental health conditions such as depression and generalized anxiety disorder.However,the potential of yogic breathing on optimizing human performance and overall well-being is not well known.Breathing techniques such as alternate nostril,Sudarshan Kriya and bhastrika utilizes rhythmic breathing to guide practitioners into a deep meditative state of relaxation and promote self-awareness.Furthermore,yogic breathing is physiologically stimulating and can be described as a natural"technological"solution to optimize human performance which can be categorized into:(1)cognitive function(i.e.,mind,vigilance);and(2)physical performance(i.e.,cardiorespiratory,metabolism,exercise,whole body).Based on previous studies,we postulate that daily practice of breathing meditation techniques play a significant role in preserving the compensatory mechanisms available to sustain physiological function.This preservation of physiological function may help to offset the time associated with reaching a threshold for clinical expression of chronic state(i.e.,hypertension,depression,dementia)or acute state(i.e.,massive hemorrhage,panic attic)of medical conditions.However,additional rigorous biomedical research is needed to evaluate the physiological mechanisms of various forms of meditation(i.e.,breath-based,mantra,mindfulness)on human performance.These efforts will help to define how compensatory reserve mechanisms of cardiovascular and immune systems are modulated by breath-based meditation.While it has been suggested that breath-based meditation is easier for beginning practitioners when compared to other forms of meditation more research is needed to elucidate these observations.A breath-based meditation sequence suchas Sudarshan Kriya has the potential to help develop an individual’s self-awareness and support better integration of the brain(i.e.,mind)with other organ systems(i.e.,body)for enhanced human performance.

Neuroprotective effect of interleukin-6 regulation of voltage-gated Na^+ channels of cortical neurons is time-and dose-dependent

Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour expo-sure of interleukin-6 on cortical neurons at various concentrations （0.1, 1, 5 and 10 ng/mL） and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations （2, 4, 8, 24 and 48 hours） by studying voltage-gated Na＋ channels using a patch-clamp technique. Volt-age-clamp recording results demonstrated that interleukin-6 suppressed Na＋ currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na＋channels in rat corti-cal neurons by interleukin-6 is time- and dose-dependent.

Sensory testing of the human gastrointestinal tract

The objective of this appraisal is to shed light on the various approaches to screen sensory information in the human gut. Understanding and characterization of sensory symptoms in gastrointestinal disorders is poor. Experimental methods allowing the investigator to control stimulus intensity and modality, as well as using validated methods for assessing sensory response have contributed to the understanding of pain mechanisms. Mechanical stimulation based on impedance planimetry allows direct recordings of luminal cross-sectional areas, and combined with ultrasound and magnetic resonance imaging, the contribution of different gut layers can be estimated. Electrical stimulation depolarizes free nerve endings non-selectively. Consequently, the stimulation paradigm （single, train, tetanic） influences the involved sensory nerves. Visual controlled electrical stimulation combines the probes with an endoscopic approach, which allows the investigator to inspect and obtain small biopsies from the stimulation site. Thermal stimulation （cold or warm） activates selectively mucosal receptors, and chemical substances such as acid and capsaicin （either alone or in combination） are used to evoke pain and sensitization. The possibility of multimodal （e.g. mechanical, electrical, thermal and chemical） stimulation in different gut segments has developed visceral pain research. The major advantage is involvement of distinctive receptors, various sensory nerves and different pain pathways mimicking clinical pain that favors investigation of central pain mechanisms involved in allodynia, hyperalgesia and referred pain. As impairment of descending control mechanisms partly underlies the pathogenesis in chronic pain, a cold pressor test that indirectly stimulates such control mechanisms can be added. Hence, the methods undoubtedly represent a major step forward in the future characterization and treatment of patients with various diseases of the gut, which provides knowledge to dinicians about the underlying symptoms and treatment of these patients.

Attenuated inhibition of medium spiny neurons participates in the pathogenesis of childhood depression

Accumulating evidence suggests that the nucleus accumbens, which is involved in mechanisms of reward and addiction, plays a role in the pathogenesis of depression and in the action of anti-depressants. In the current study, intraperitoneal injection of nomifensine, a dopamine reuptake inhibitor, decreased depression-like behaviors in the Wistar Kyoto rat model of depression in the sucrose-preference and forced swim tests. Nomifensine also reduced membrane excitability in medium spiny neurons in the core of the nucleus accumbens in the childhood Wistar Kyoto rats as evaluated by electrophysiological recording. In addition, the expression of dopamine D2-like receptor mRNA was downregulated in the nucleus accumbens, striatum and hippocampus of nomifensine-treated childhood Wistar Kyoto rats. These experimental ifndings indicate that impaired inhibition of medium spiny neurons, mediated by dopamine D2-like receptors, may be involved in the formation of depression-like behavior in childhood Wistar Kyoto rats, and that nomifensine can alleviate depressive behaviors by reducing medium spiny neuron membrane excitability.

Corticospinal excitability during motor imagery is diminished by continuous repetition-induced fatigue

Application of continuous repetition of motor imagery can improve the performance of exercise tasks.However,there is a lack of more detailed neurophysiological evidence to support the formulation of clear standards for interventions using motor imagery.Moreover,identification of motor imagery intervention time is necessary because it exhibits possible central fatigue.Therefore,the purpose of this study was to elucidate the development of fatigue during continuous repetition of motor imagery through objective and subjective evaluation.The study involved two experiments.In experiment 1,14 healthy young volunteers were required to imagine grasping and lifting a 1.5-L plastic bottle using the whole hand.Each participant performed the motor imagery task 100 times under each condition with 48 hours interval between two conditions:500 mL or 1500 mL of water in the bottle during the demonstration phase.Mental fatigue and a decrease in pinch power appeared under the 1500-mL condition.There were changes in concentration ability or corticospinal excitability,as assessed by motor evoked potentials,between each set with continuous repetition of motor imagery also under the 1500-mL condition.Therefore,in experiment 2,12 healthy volunteers were required to perform the motor imagery task 200 times under the 1500-mL condition.Both concentration ability and corticospinal excitability decreased.This is the first study to show that continuous repetition of motor imagery can decrease corticospinal excitability in addition to producing mental fatigue.This study was approved by the Institutional Ethics Committee at the Nagasaki University Graduate School of Biomedical and Health Sciences(approval No.18121302)on January 30,2019.

Clinical characteristics,neurophysiological grade and outcome of patients with carpal tunnel syndrome A retrospective study

BACKGROUND： Carpal tunnel syndrome （CTS） is diagnosed mainly according to clinical symptoms, physical sign and neurodiagnostic laboratory examination. The therapeutic effect of conservative management and surgical operation in treating CTS need to be further observed and evaluated. OBJECTIVE： To analyze the clinical characteristics, neurophysiological grade and outcome in patients with CTS. DESIGN： Retrospective case-analysis. SETTING： Department of Neurology, First Affiliated Hospital, Medical College, Xi＇an Jiaotong University. PARTICIPANTS： Totally 161 patients with suspected CTS from National Neuroscience Institute of Singapore referred to the Neurodiagnostic Laboratory for the confirmatory testing between January and September 2002. The involved patients, 137 male and 24 female, were aged 21 - 85 years. METHODS： ①The condition of diabetes mellitus complicated by abnormal thyroid function was observed.② The effect on predominant hand, and paraesthesia were observed. ③Neuroelectrophysiological studies were performed and the results were graded into mild, moderate and severe CTS according to the American Association of Electrodiagnostic Medicine （AAEM） criteria.④ Conservative management and surgical intervention were followed up 3 months later, and symptoms and physical sign basically disappeared, and function was basically recovered, which indicated that disease condition improved. MAIN OUTCOME MEASURES： ①Condition of CTS complicated by metabolic disease; ②Effects on predominant hand and paraesthesia; ③Electrophysiological grading; ④Prognosis. RESULTS： Totally 161 patients participated in the final analysis. ①Condition of CTS complicated by metabolic disease： Among 161 patients, 17.4% （28/161） were documented to have diabetes mellitus and 7（4.3%） had hypothyroidism. ②Effects on predominant hand and paraesthesia： Dominant hand involvement was present in 134 patients （83.2%） and more than 75% had onset of symptoms in the dominant hand. Sensory symptoms like numbness and paresthesias were the predominant symptoms, accounting for 89.1% （134/161）, this discomfort was felt in all 5 digits of the hand in 47.6%, and lateral three and half digits in 21.4%. The noctural symptoms were present in 30.4% （49/161） patients. ③Electrophysiological typing： The most frequent abnormality was that of the prolonged mid-palm median and ulnar latency difference in 146（54.7%） hands; 103（38.6%） hands had prolonged median motor distal latency. Absent response from thenar muscle was present in 35 （13.1%） hands. Nerve conduction study showed bilateral CTS in 105 （65.2%） patients and unilateral CTS in 56 （34.8%） patients. Sixteen patients with bilateral CTS had symptoms in one hand only. Overall, 36.8% had mild, 49.2 % had moderate and 13.9 % had severe CTS, with median duration of symptoms of 6, 9 and 14 months, respectively. ④Delay in diagnosis： 37（22.9%） patients delayed in diagnosis from 1-4 months, 16（43.2%） were misdiagnosed as cervical spondylosis; 6（16.2%） were ignored due to their condition by busy work; 15（40.5%） were unware of their symptoms. ⑤Prognosis： Follow up data was available for only 72.7% （117/161） patients. Conservative management was conducted in 73.5% （86/117）. Clinical symptoms were resolved or improved in 65.1% （56/86） patients with 17 mild CTS, 29 moderate CTS, and 10 severe CTS. 26.5% （31/117） patients underwent surgery for CTS release, and clinical symptoms were improved in 12（38.7%） with moderate CTS and 2 （6.5%） with severe CTS at 3 months of follow up. CONCLUSION： ①Sensory symptoms in CTS are more in severe and common in dominant hand. ②Conservative management showed resolution or improvement for mild and moderate CTS. Surgical intervention shows either resolution or improvement in clinical symptoms in moderate CTS. ③The common reasons for delay in diagnosis were due to misdiagnosis as cervical spondylosis and lack of awareness of the condition.④Assessment on severity of CTS by electrophysiological grade is of important significance for determining therapeutic mean.

Mechanism of Action of Low Dose Preparations from <i>Coffea arabica</i>, <i>Gelsemium</i>and <i>Veratrum</i>Based on <i>in Vivo</i>and <i>in Vitro</i>Neurophysiological Findings

Low dose remedies are widely administered in medicine. We used Tele-Stereo-EEG and the hippocampal slice preparation to measure physiological effects of orally given Coffea D6 (40 mg/kg), Gelsemium D4 (10 mg/kg) and Veratrum D6 (30 mg/kg) in rats. Adult rats were implanted with electrodes positioned stereotactically into four brain regions. Changes in field potentials were transmitted wirelessly. After frequency analysis data from 6 - 8 animals were averaged. For in vitro testing, preparations were superfused directly on hippocampal slices. Stimulation of Schaffer Collaterals by single stimuli (SS) or theta burst stimulation (TBS) resulted in stable population spike amplitudes. All three low dose preparations produced decreases of spectral power. Statistically significant changes were observed in delta, theta and alpha2 spectral power. In the hippocampal slice preparation Coffea facilitated signal transfer presumably by enhancing glutamate AMPA receptor transmission. Gelsemium showed a similar effect, but only after single shock stimulation. Opposite to this, attenuation of the electric pathway was recognized after theta burst stimulation due to AMPA receptor and glutamate metabotropic II receptor mediated transmission. Veratrum was able to attenuate glutamatergic due to receptor-mediated signalling sensitive to AMPA and NMDA. The results strongly speak in favour of the existence of biologically active molecules in these low dose preparations.

Mental Activity of the Brain and Emotional Stress

The article considers the biological nature and origins of emotional stress. Emotional stress is primarily formed in the mental activity of the brain in the form of pronounced long-term negative emotions and is secondarily manifested in neurophysiological mechanisms and somatovegetative processes. However, all studies of the development of emotional stress are focused on the study of central neurophysiological mechanisms, excluding the possibility of analysis for the “sources” of emotional stress, which is primarily formed in the subjective sphere of brain activity, i.e., in the mechanisms of emotions. In our studies, we propose a fundamentally new methodology for studying the mental activity of the human brain and, in particular, the mechanisms of emotions. Thereby, modern methods of psychophysiology make it possible to come closer to understanding the nature of emotional stress.

A Case of Pelvic Migraine

A 62-year-old woman presented with an 8-year history of chronic persisting pelvic pain. She described constant throbbing, stabbing vaginal pain. A pelvic floor neurophysiological assessment of the pudendal nerve was performed by performing a needle EMG to the left and right external anal sphincter assessing for insertional activity and recruitment pattern. A quantitative assessment of the motor unit action potentials [MUAPs] was also performed. Tests confirmed a left pudendal neuropathy with chronic denervation in the left external anal sphincter, with reasonable muscle function, with a recruitment pattern of 65% - 70% of normal. The CAR showed an elevated sensory threshold with a normal distal latency. All other conventional pudendal nerve treatments including oral antiepileptic medication, neuromodulation and pudendal nerve blocking injections had failed, and the patient was exacerbated by the persisting pain and discomfort. In this case, 30 international units (iu) of botulinum toxin type A in 10 divided doses of 3 iu were injected along the nerve. Four days later the patient reported a significant improvement in the pain symptoms. She was reviewed 3 weeks later and for the first time in 8 years had made the 70 mile journey to the clinic as a passenger in her husband’s car. This case highlights a new therapeutic option of botulinum toxin type A injection, along the nerve length, for this common painful condition. It seems to have clinical veracity as unlike other therapeutic option the affect lasts for 3 or 4 months.

Opposite Neurophysiological Findings Induced by Sideritis scardica and Sideritis euboa Extract in the Rat

Psychophysiological effects of Sideritis herba extracts depend on biologically active ingredients, which might be different for several botanical types of this plant. The present investigation aimed at the characterization of extracts from Sideritis scardica and Sideritis euboa in vivo and in vitro. Construction of electropharmacograms on the base of recording of electrical field potentials from four different brain regions was used to compare the possible pharmacological effects to a database of reference drugs with known clinical indications. Whereas Sideritis scardica produced decreases of spectral power in line with stimulatory frequency patterns as observed in the presence of Ginkgo biloba extract, administration of Sideritis euboa produced opposite effects. Electrical stimulation of the Schaffer Collaterals was used to elicit a pyramidal cell response called population spike in vitro. The amplitude of this spike was determined in the presence of single as well as theta burst stimuli. Direct exposure of brain matter to Sideritis scardica extract led to concentration dependent increases of the population spike amplitude under both stimulation patterns in the range from 12.5 to 100 mg/L. On the opposite, extract from Sideritis euboa did not change the electric response up to 50 mg/L. Higher concentrations of this extract attenuated the signal amplitude. A 1:1 blend of both gave intermediate results. The in vitro results are in line with the in vivo EEG recordings, where both extracts induced opposite changes of the electric power with respect to electric frequency patterns. The results from both models suggest a stimulatory and/or memory-enhancing action for the extract from Sideritis scardica but not for Sideritis euboa extract, where a more tranquillizing effect like that observed in the presence of Humulus cone extract may be expected.

Novel Multimodal Evaluation Technology for Symptom Characterization in GI Functional Diseases and Pharmacological Testing of Drugs

Characterizations of pain and other sensory symptoms are very important for diagnosis and assessment of patient with gastrointestinal disorders. Methods to evoke and assess experimental pain have developed into a new area for multimodal assessment with electrical, mechanical, thermal and chemical stimulation of pain pathways in the human gut. Stimulation with this technology mimics to a large degree the pain experienced by patients seeking the health system for treatment. Multimodal methods have increased our understanding of peripheral receptors in the gut in health and disease. Combined with advanced muscle analysis, the methods have increased our understanding of receptors sensitive to mechanical, chemical and temperature stimuli in diseases such as systemic sclerosis and diabetes. Multimodal technology can also be used to unravel central pain mechanisms involved in allodynia, hyperalgesia and referred pain. Abnormalities in central pain mechanisms are often found in patients with chronic gut pain. Hence methods relying on multimodal pain stimulation may help to understand symptoms in these patients. In addition, multimodal methods have been used to gain more insight into the drug effects against pain. It is expected that multimodal methods represent a maj or step forward in the future characterization and treatment of patients with various gastrointestinal diseases.