Muscle spindles as pain receptors.

Background: Muscle membranes have a sensation of pain, but within the muscle tissue, the origin of pain is unclear. We present a hypothesis that the pain receptors of the muscle tissue are situated principally in the muscle spindles. A recent report reintroduced that 'end plate spikes' in needle electromyography (EMG) are fusimotor unit potentials of the intrafusal muscle fibres, and thus represent a marker of muscle spindles. Methods: We studied four relaxed muscles with 50 EMG needle insertions in each and mapped the appearance of pain and spontaneous EMG activity. Results: Only 4.0% of the needle insertions in muscle tissue elicited pain. However, needle insertions in local active points showing 'end plate spikes' and, thus, fusimotor unit potentials of the muscle spindles elicited pain in 86% of the insertions, whereas needle insertions in points without 'end plate spikes' elicited pain in only 1.0% of the insertions (p<0.001). Conclusions: Muscle spindles have pain receptors. The extrafusal muscle tissue is practically pain-free for the needle insertions. This demonstrates a scarcity of extrafusal pain receptors. How this observation is put into perspective with the muscle pain syndromes was discussed.

Electromyography of the muscle spindle.

In needle electromyography, there are two spontaneous waveforms, miniature end plate potentials and "end plate spikes", appearing usually together. Miniature end plate potentials are local, non-propagating postsynaptic waves, caused by spontaneous exocytosis of acetylcholine in the neuromuscular junction. The prevailing hypothesis states that "end plate spikes" are propagated postsynaptic action potentials of muscle fibers, caused by presynaptic irritation of the motor nerve or nerve terminal. Using several small concentric needle electrodes in parallel with the muscle fibers, most "end plate spikes" are strictly local or propagating for 2-4 mm. At the end plate zone, there are miniature end plate potentials without "end plate spikes". Local "end plate spikes" are junctional potentials of intrafusal gamma neuromuscular junctions of the nuclear bag fibers, and propagated "end plate spikes" are potentials of nuclear chain muscle fibers of muscle spindles. Miniature end plate potentials without "end plate spikes" at the end plate zone derive from alpha neuromuscular junctions. These findings contrast with the prevailing hypothesis. The history of observations and different hypotheses of the origin of end plate spikes are described.

Muscle activity and acute stress in fibromyalgia.

BACKGROUND: Fibromyalgia (FM) patients are likely to differ from healthy controls in muscle activity and in reactivity to experimental stress. METHODS: We compared psychophysiological reactivity to cognitive stress between 51 female FM patients aged 18 to 65 years and 31 age- and sex-matched healthy controls. They underwent a 20-minute protocol consisting of three phases of relaxation and two phases of cognitive stress. We recorded surface electromyography normalized to maximum voluntary muscle contraction (%EMG), the percentage of time with no muscle activity (EMG rest time), and subjective pain and stress intensities. We compared group reactivity using linear modelling and adjusted for psychological and life-style factors. RESULTS: The FM patients had a significantly higher mean %EMG (2.2 % vs. 1.0 %, p < 0.001), pain intensity (3.6 vs. 0.2, p < 0.001), and perceived stress (3.5 vs. 1.4, p < 0.001) and lower mean EMG rest time (26.7 % vs. 47.2 %, p < 0.001). In the FM patients, compared with controls, the pain intensity increased more during the second stress phase (0.71, p = 0.028), and the %EMG decreased more during the final relaxation phase (-0.29, p = 0.036). Within the FM patients, higher BMI predicted higher %EMG but lower stress. Leisure time physical activity predicted lower %EMG and stress and higher EMG rest time. Higher perceived stress predicted lower EMG rest time, and higher trait anxiety predicted higher pain and stress overall. CONCLUSIONS: Our results suggest that repeated cognitive stress increases pain intensity in FM patients. FM patients also had higher resting muscle activity, but their muscle activity did not increase with pain. Management of stress and anxiety might help control FM flare-ups. TRIAL REGISTRATION: Retrospectively registered on ClinicalTrials.gov ( NCT03300635 ).

Altered N100-potential associates with working memory impairment in Parkinson's disease.

The diagnosis of cognitive impairment and dementia often occurring with Parkinson's disease (PD) is still based on the clinical picture and neuropsychological examination. Ancillary methods to detect cognitive decline in these patients are, therefore, needed. Alterations in the latencies and amplitudes of evoked response potential (ERP) components N100 and P200 have been described in PD. Due to limited number of studies their relation to cognitive deficits in PD remains obscure. The present study was designed to examine if alterations in the N100- and P200-potentials associate with neuropsychological impairment in PD. EEG-ERP was conducted to 18 PD patients and 24 healthy controls. The patients underwent a thorough neuropsychological evaluation. The controls were screened for cognitive impairment with Consortium to Establish Alzheimer's disease (CERAD)-testing and a normal result were required to be included in the study. The N100-latency was prolonged in the patients compared to the controls (p = 0.05). In the patients, the N100 latency correlated significantly with a visual working memory task (p = 0.01). Also N100 latency was prolonged and N100 amplitude habituation diminished in the patients achieving poorly in this task. We conclude that prolonged N100-latency and diminished amplitude habituation associate with visual working memory impairment in PD.

Three cases of acute distal demyelinating neuropathy with recovery.

Guillain-Barré syndrome (GBS) may present as distal acute inflammatory demyelinating polyradiculoneuropathy (AIDP), with severe distal demyelination of the peripheral nerves in the absence of radiculitis. Clinical course is benign, and prognosis seems favorable, but nerve conduction studies (NCS) findings at nadir may resemble some chronic forms of polyneuropathy, so close follow-up during recovery is needed.

Epileptic Electroencephalography Profile Associates with Attention Problems in Children with Fragile X Syndrome: Review and Case Series.

Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and a variant of autism spectrum disorder (ASD). The FXS population is quite heterogeneous with respect to comorbidities, which implies the need for a personalized medicine approach, relying on biomarkers or endophenotypes to guide treatment. There is evidence that quantitative electroencephalography (EEG) endophenotype-guided treatments can support increased clinical benefit by considering the patient's neurophysiological profile. We describe a case series of 11 children diagnosed with FXS, aged one to 14 years, mean 4.6 years. Case data are based on longitudinal clinically-observed reports by attending physicians for comorbid symptoms including awake and asleep EEG profiles. We tabulate the comorbid EEG symptoms in this case series, and relate them to the literature on EEG endophenotypes and associated treatment options. The two most common endophenotypes in the data were diffuse slow oscillations and epileptiform EEG, which have been associated with attention and epilepsy respectively. This observation agrees with reported prevalence of comorbid behavioral symptoms for FXS. In this sample of FXS children, attention problems were found in 37% (4 of 11), and epileptic seizures in 45% (5 of 11). Attention problems were found to associate with the epilepsy endophenotype. From the synthesis of this case series and literature review, we argue that the evidence-based personalized treatment approach, exemplified by neurofeedback, could benefit FXS children by focusing on observable, specific characteristics of comorbid disease symptoms.

Optimal digital filters for analyzing the mid-latency auditory P50 event-related potential in patients with Alzheimer's disease.

BACKGROUND: Filtering is an effective pre-processing technique for improving the signal-to-noise ratio of ERP waveforms. Filters can, however, introduce substantial distortions into the time-domain representations of ERP waveforms. Inappropriate filter parameters may lead to the presence of statistically significant but artificial effects, whereas true effects may appear as insignificant. NEW METHOD: The present study aimed to determine the optimal digital filters for analyzing the auditory P50 component in patients with Alzheimer's disease. To provide evidence of the optimal filter settings, different high-pass and low-pass filters were applied to ERP waveforms obtained from a conditioning-testing paradigm. The results facilitate practical recommendations for selection of filters that maximize the signal-to-noise ratio of the P50 components without introducing significant distortions. RESULTS: The present study confirms that filter parameters have a significant effect on the amplitude and gating measures of the P50 component. Setting the high-pass cut-off at 0.1Hz and the low-pass cut-off at 90Hz (or above) is recommended for P50 component analyses. COMPARISON WITH EXISTING METHODS: The majority of ERP studies on sensory gating report using high-pass filters with 10-Hz cut-offs to measure P50 suppression. Such a high cut-off appeared to induce significant distortions into the ERP waveforms; thus, the authors advise against using these excessive high-pass cut-offs. CONCLUSIONS: Filtering broadband signals, such as ERP signals, necessary results in time-domain distortions. However, by adjusting the filter parameters carefully according to the components of interest, it is possible to minimize filter artifacts and obtain more easily interpretable ERP waveforms.

Ephaptic transmission from type ii afferents to static γ and ß efferents causes complex repetitive discharge: An hypothesis.

INTRODUCTION: Complex repetitive discharges (CRDs) are thought to result from depolarization of a single denervated muscle fiber, followed by ephaptic spread to adjacent fibers. This leads to cyclic spread of the depolarization to produce a recurrent discharge. Another explanation is suggested. METHODS: CRDs were recorded with single and multiple electromyographic needles longitudinal to muscle fibers in 39 neuropathy patients. RESULTS: The mean frequency of CRDs was 26 Hz, mean number of negative spikes was 5.4, and blocking of spikes occurred in 53% of CRDs. In multi-needle recordings most CRDs were local, but propagation of the discharge was sometimes observed. CONCLUSIONS: The prevailing hypothesis of CRDs cannot explain local CRDs. Type II afferents of bag2 and chain fibers branch widely in the juxtaequatorial region of muscle spindles where they may intermingle with motor terminals. Ephaptic transmission from type II afferents to static γ and ß efferents may cause CRDs and fix the CRD frequency.

Myotonia in ion channel diseases of muscle.

Ion channel dysfunctions of the muscular cell membrane are usually inheritable, rare diseases. They may become manifest as relatively mild symptoms of muscle stiffness and pain, myotonia or paralysis. We describe two young patients who had an inherited ion channel disease of the muscular cell membrane with mild symptoms. The first patient had a chloride channel dysfunction of the muscular cell membrane, the second one a sodium channel dysfunction. In electromyography findings typical of the respective ion channel disease were detected in both patients. Closer examination of the patients' myotonic sequences occurring in electromyography of the relaxed muscle revealed differences that already enable the evaluation of the type of ion channel disease.

Truncated HSPB1 causes axonal neuropathy and impairs tolerance to unfolded protein stress.

BACKGROUND: HSPB1 belongs to the family of small heat shock proteins (sHSP) that have importance in protection against unfolded protein stress, in cancer cells for escaping drug toxicity stress and in neurons for suppression of protein aggregates. sHSPs have a conserved α-crystalline domain (ACD), flanked by variable N- and C-termini, whose functions are not fully understood. Dominant missense variants in HSPB1, locating mostly to the ACD, have been linked to inherited neuropathy. METHODS: Patients underwent detailed clinical and neurophysiologic characterization. Disease causing variants were identified by exome or gene panel sequencing. Primary patient fibroblasts were used to investigate the effects of the dominant defective HSPB1 proteins. RESULTS: Frameshift variant predicting ablation of the entire C-terminus p.(Met169Cfs2*) of HSPB1 and a missense variant p.(Arg127Leu) were identified in patients with dominantly inherited motor-predominant axonal Charcot-Marie-Tooth neuropathy. We show that the truncated protein is stable and binds wild type HSPB1. Both mutations impaired the heat stress tolerance of the fibroblasts. This effect was particularly pronounced for the cells with the truncating variant, independent of heat-induced nuclear translocation and induction of global transcriptional heat response. Furthermore, the truncated HSPB1 increased cellular sensitivity to protein misfolding. CONCLUSION: Our results suggest that truncation of the non-conserved C-terminus impairs the function of HSPB1 in cellular stress response. GENERAL SIGNIFICANCE: sHSPs have important roles in prevention of protein aggregates that induce toxicity. We showed that C-terminal part of HSPB1 is critical for tolerance of unfolded protein stress, and when lacking causes axonal neuropathy in patients.

Multimodal event-related potentials in occupational chronic solvent encephalopathy.

The aim of this study was to test a multimodal event-related potential (ERP) paradigm in chronic solvent encephalopathy (CSE) to develop a sensitive method for the clinical diagnostics to CSE. The study comprised 11 CSE patients and 13 healthy controls. We used three tasks: an auditory odd-ball (AUD), a visual detection (VIS), and a recognition memory (MEM) task. The auditory and visual stimuli were presented in single- and dual-task conditions. The auditory P300 amplitude in single-task condition was smaller in the patient group than in the control group at the parietal (Pz) but not at the frontal midline electrode location. The auditory P300 response in the dual task condition AUD+VIS was unrecognizable in 8 of 11 patients and in 1 of 13 controls and in the AUD+MEM condition in 10 of 11 patients and in 4 of 13 controls. In the AUD+MEM condition, the auditory P300 amplitude at Pz was smaller in the patient group than in the control group. Reaction time for auditory stimuli in both dual conditions as well as for visual stimuli in AUD+VIS condition were in the patient group prolonged. The ERP results indicate that CSE patients present with slowed performance speed and difficulties in allocation of attention. Based on ERP results, the disturbance in brain activity in CSE seems to affect posterior aspects of the frontoparietal continuity. The multimodal paradigm seems promising as a tool for the clinical diagnostics of CSE.

[Anemization, recurring bouts of fever and cardiac insufficiency in a young woman]. / Nuoren naisen anemisoituminen, kuumeilu ja sydämen vajaatoiminta.

A young woman having undergone surgery for aortic coarctation in childhood developed severe cardiac insufficiency after being ill for a few months. The clinical picture turned out to be compatible with subacute endocarditis. The patient received antibiotic treatment with vague effect on hemodynamics and the aortic valve was replaced. However, after valvular replacement a refractory myocardial insufficiency developed. A heart transplantation was performed. Thereafter the patient has been well.

[Myofascial pain syndrome--fascial muscle pain]. / Myofaskiaalinen kipuoireyhtymä--lihasjuostekipu.

Symptoms of myofascial pain syndrome, i.e. fascial muscle pain may occur in several areas of the body, particularly in the neck-shoulder region. The muscle pain symptom in the neck-shoulder region is commonly termed tension neck pain or nonspecific neck pain, but myofascial pain syndrome can also be distinguished into its own diagnosis. This review deals with the clinical picture of myofascial pain syndrome along with pathophysiological hypotheses and treatment options.

Myofascial syndrome and pain: A neurophysiological approach.

It has been debated whether muscle spindles have a role in myofascial pain or not. We present a number of arguments for the former hypothesis. It was hypothesized that firing of intrafusal muscle fibres, i.e. fusimotor activity can be observed as "end plate spikes" (EPSs) in electromyography (EMG). The EPSs may be found in local active spots of muscle, often associated with miniature end plate potentials (MEPPs). Insertion of EMG needle electrodes into an active spot is painful, indicating nociception in the muscle spindle. Myofascial syndrome patients have taut bands with active trigger points (TrPs) in painful muscles. End plate activity (EPSs and MEPPs) is a significantly more common finding in TrPs of myofascial pain than in control points of the muscle, indicating the presence of muscle spindles. However, some control sites may show EPSs of normal muscle spindles. Increased amount of inflammatory metabolites have been observed in active TrPs. Muscle spindle is a capsulated gel-filled container, where inflammatory and contraction metabolites may be heavily concentrated during sustained fusimotor activation. Thus the intrafusal chemosensitive pain mediating III- and IV-afferents are sensitized and activated. Intrafusal inflammation causes further reflex activation of the fusimotor and skeletofusimotor systems via sensitized III- and IV-afferents. The taut band itself may be a contracture (rigor) of local skeletofusimotor (beta) units caused by sustained reflex drive by the given muscle spindles. In EMG this may be seen as complex repetitive discharges. We conclude that TrPs of myofascial pain are related to painful muscle spindles in taut bands.

Somatosensory evoked potentials by median nerve stimulation in children during thiopental/sevoflurane anesthesia and the additive effects of ketoprofen and fentanyl.

BACKGROUND: Somatosensory evoked potentials (SEPs) are used to determine the spinal cord and brain function during surgical procedures. In general, SEPs are sensitive to volatile anesthetics, but little is known about the effects of anesthesia maintenance with sevoflurane on SEPs in children. Analgesics are often provided during anesthesia, and supplementary drugs may also affect the SEPs. In this prospective clinical trial of 27 healthy, 3- to 8-yr-old children, we evaluated the effects of sevoflurane anesthesia after IV induction with benzodiazepine and barbiturate on median nerve SEP. In addition, the effects of two analgesics (ketoprofen and fentanyl) on SEPs were evaluated. METHODS: Median nerve SEPs were recorded before premedication with midazolam 0.1 mg/kg IV, and at three separate times during anesthesia maintenance with sevoflurane 2% end-tidal concentration in air/oxygen (after 15 min of sevoflurane inhalation), supplemented with/without ketoprofen 1 mg/kg (after 25 min) and fentanyl 1 microg/kg (after 35 min). RESULTS: Compared with baseline measurements, an increase both in N20 latency (P = 0.015) and in central conduction time (P = 0.001) was noted during anesthesia maintenance with sevoflurane. The administration of analgesics did not have an influence on the N20 latency or central conduction time. In children 5 to 8 yr of age, the mean cortical N20-P25 amplitude was decreased (P = 0.008). In addition, in older children, the N20-P25 amplitude decreased after the co-administration of ketoprofen and fentanyl compared with the values measured before the analgesics (P = 0.03). These decreases were not seen in the younger children. DISCUSSION: In children, anesthesia maintenance with 2% sevoflurane prolongs median SEP latencies in a manner that is similar to those reported for other volatile anesthetics. However, SEP monitoring can be done with sevoflurane inhalation, but the dosage should be adjusted due to interindividual variability. Co-administration of ketoprofen, and fentanyl did not affect the SEP latencies, but post hoc analysis suggested that older children had a decrease in cortical amplitudes.

Compound nerve conduction velocity- a reflection of proprioceptive afferents?

OBJECTIVE: To gather the required sample size to compare compound nerve conduction velocities (CV) to cutaneous sensory CVs and motor CVs to find out if there are statistically significant differences between these nerve fibre populations. METHODS: We report age, height, and temperature standardized CVs for cutaneous sensory, motor, and compound nerve fibres measured by electroneuromyography (ENMG) for 109 median nerves in 74 people from different age groups with no known neuropathy (age 50.4, median 49, range 21-87). RESULTS: In the region of the forearm, mean CVs were 63.6m/s (CI=62.6-64.7) for compound nerve fibres, 61.3m/s (CI=60.1-62.5) for cutaneous sensory fibres, and 56.3m/s (CI=55.1-57.6) for motor fibres (for all p<0.001). Age explained most of the variation of CVs (Pearson's coefficients -0.394, -0,538, and -0.443, respectively, for all p

Nascent body ego: metapsychological and neurophysiological aspects.

For Freud, body ego was the organizing basis of the structural theory. He defined it as a psychic projection of the body surface. Isakower's and Lewin's classical findings suggest that the body surface experiences of nursing provide the infant with sensory-affective stimulation that initiates a projection of sensory processes towards the psychic realm. During nursing, somato-sensory, gustatory and olfactory modalities merge with a primitive somatic affect of satiation, whereas auditory modality is involved more indirectly and visual contact more gradually. Repeated regularly, such nascent experiences are likely to play a part in the organization of the primitive protosymbolic mental experience. In support of this hypothesis, the authors review findings from a neurophysiological study of infants before, during and after nursing. Nursing is associated with a significant amplitude change in the newborn electroencephalogram (EEG), which wanes before the age of 3 months, and is transformed at the age of 6 months into rhythmic 3-5 Hz hedonic theta-activity. Sucking requires active physiological work, which is shown in a regular rise in heart rate. The hypothesis of a sensory-affective organization of the nascent body ego, enhanced by nursing and active sucking, seems concordant with neurophysiological phenomena related to nursing.

Increased number of febrile seizures in children born very preterm: relation of neonatal, febrile and epileptic seizures and neurological dysfunction to seizure outcome at 16 years of age.

PURPOSE: In prematurely born population, a cascade of events from initial injury in the developing brain to morbidity may be followed. The aim of our study was to assess seizures in prematurely born children from birth up to 16 years and to evaluate the contribution of different seizures, and of neurological dysfunction to the seizure outcome. METHODS: Pre- and neonatal data and data from neurodevelopmental examination at 5 years of 60 prospectively followed children born at or before 32 weeks of gestation, and of 60 matched term controls from the 2 year birth cohort were available from earlier phases of the study. Later seizure data were obtained from questionnaires at 5, 9, and 16 years, and from hospital records and parent interviews. RESULTS: In the preterm group, 16 children (27%) exhibited neonatal seizures, 10 children (17%) had seizures during febrile illness and 5 children had epilepsy. Eight children had only febrile seizures, and 3 of these had both multiple simple and complex febrile seizures and neurodevelopmental dysfunction. None of the 8 children had experienced neonatal seizures, 6 had a positive family history of seizures, but none developed epilepsy. The children with epilepsy had CP and neurocognitive problems, and all but one had experienced neonatal seizures; two of them had also had fever-induced epileptic seizures. In controls 3 children (5%) had simple febrile seizures. CONCLUSION: Children born very preterm have increased rate of febrile seizures compared to the controls. However, no cascade from initial injury via febrile seizures to epilepsy could be shown during the follow-up of 16 years. Symptomatic epilepsy in prematurely born children is characterised by neonatal seizures, major neurological disabilities and early onset of epilepsy.

The effect of small doses of botulinum toxin a on neck-shoulder myofascial pain syndrome: a double-blind, randomized, and controlled crossover trial.

OBJECTIVES: Myofascial pain syndrome is a common cause of muscular pain in the shoulder-neck region. Injections of large amounts of botulinum toxin A have been found to be beneficial for the alleviation of myofascial pain, but large doses of this toxin may cause paresis of the muscle and other adverse events. The aim of this work was to determine the effect of small doses (5 U) of botulinum toxin A (BTA) injected directly into the painful trigger points of the muscles, using a double-blind crossover technique. METHODS: On the basis of the empirical criteria proposed for diagnosis of myofascial pain syndrome, 31 patients suffering from myofascial pain in the neck-shoulder region were studied. The patients received either botulinum toxin A or physiological saline injections on 2 occasions 4 weeks apart. The total dose varied from 15 to 35 U of botulinum toxin A [28+/- 6 U (mean+/- SD)]. The follow-up measurements were carried out at 4 weeks after each treatment. Neck pain and result of treatment were assessed with questionnaires. The pressure pain threshold was determined using a dolorimeter. RESULTS: Neck pain values decreased from 4.3+/- 2.4 to 3.3+/- 2.0 after saline injections and from 4.1+/- 2.1 to 3.3+/- 2.2 after botulinum toxin A. The pressure pain threshold values increased from 5.2+/-1.6 to 5.9+/-1.5 and from 5.7+/-1.6 to 5.9+/-1.6 after injections with saline and botulinum toxin A, respectively. No statistically significant changes in the neck pain and pressure pain threshold values occurred between the botulinum toxin A and saline groups. After the first injections, the subjective result of treatment was significantly (P=0.008) in favor of botulinum toxin A, and after the second injections, the subjective result was better for saline, but the difference was not statistically significant (P=0.098). There was no significant difference in the prevalence of side effects between saline and botulinum toxin A. CONCLUSIONS: Our study shows that there was no difference between the effect of small doses of botulinum toxin A and those of physiological saline in the treatment of myofascial pain syndrome.