Individual Nerve Research Articles

A biophysical account of multiplication by a single neuron

Nonlinear, multiplication-like operations carried out by individual nerve cells greatly enhance the computational power of a neural system1–3, but our understanding of their biophysical implementation is scant. Here we pursue this problem in the Drosophila melanogaster ON motion vision circuit4,5, in which we record the membrane potentials of direction-selective T4 neurons and of their columnar input elements6,7 in response to visual and pharmacological stimuli in vivo. Our electrophysiological measurements and conductance-based simulations provide evidence for a passive supralinear interaction between two distinct types of synapse on T4 dendrites. We show that this multiplication-like nonlinearity arises from the coincidence of cholinergic excitation and release from glutamatergic inhibition. The latter depends on the expression of the glutamate-gated chloride channel GluClα8,9 in T4 neurons, which sharpens the directional tuning of the cells and shapes the optomotor behaviour of the animals. Interacting pairs of shunting inhibitory and excitatory synapses have long been postulated as an analogue approximation of a multiplication, which is integral to theories of motion detection10,11, sound localization12 and sensorimotor control13.

Pretemporal Transcavernous Approach for Resection of Non-meningeal Tumors of the Cavernous Sinus: Single Center Experience.

ObjectivesTo study the outcomes of the pretemporal transcavernous approach in the treatment of non-meningeal tumors involving cavernous sinus and to investigate the surgical strategy for these lesions.MethodsWe conducted a retrospective study of 45 patients with non-meningeal tumors involving cavernous sinus. All 45 patients received microsurgical resection via the pretemporal transcavernous approach from April 2012 to January 2019 by the same neurosurgeon. We analyzed clinical manifestations, image data, perioperative complications, surgical outcomes, functional outcomes, and follow-up data of these patients.ResultsGross total resection was achieved in 38 cases (84.4%) of the 45 patients. Preoperatively, a total of 64 individual cranial nerves were affected. Postoperatively, 92.2% of 64 impaired cranial nerves completely or partially restored function, 7.8% had worsened function compared with their preoperative statuses, and 5 new cranial nerve deficits (CNV) were observed in five patients during the last follow-up. Seven patients presented transient new cranial nerve deficits (5 CNIII and 2 CNVI), three cases suffered transient worsen cranial nerve deficits (3 CNIII and 1 CNVII). There were no cases of intracranial hematoma, intracranial infection, cerebrospinal fluid leaks, and death. The progression of residual tumor was observed in two patients (1 chordoma and 1 pituitary adenoma).ConclusionsNon-meningeal tumors involving cavernous sinus can be safely and radically removed with less morbidity and mortality. Pretemporal transcavernous approach is an ideal approach to the cavernous sinus and can be tailored individually.

Nerve ultrasound detects abnormally small nerves in patients with spinal and bulbar muscular atrophy.

Sensory impairment secondary to dorsal root ganglion neuronopathy is common, although often subclinical, in X-linked spinal and bulbar muscular atrophy (SBMA). We investigated the hypothesis that nerves of SBMA patients show the same morphological changes on ultrasound as other inherited sensory neuronopathies and that these changes are distinct from those in axonal neuropathy. We compared the ultrasound cross-sectional areas (CSAs) of median, ulnar, sural, and tibial nerves of prospectively recruited SBMA patients with those of patients with acquired axonal neuropathy and healthy controls. We also compared the individual nerve CSAs of SBMA and neuropathy patients with our laboratory reference values. There were 7 SBMA patients, 18 neuropathy patients, and 42 healthy controls. The nerve CSAs of the SBMA patients were significantly smaller than those of patients in the other two groups. The changes were most prominent in the upper limbs (p < .001), with the nerves of the SBMA patients being on average approximately half the size of the controls and a third the size of the neuropathy patients. On individual analysis, the ultrasound abnormality was sufficiently characteristic to be detected in all but one SBMA patient. These ultrasound changes are similar to those reported in other inherited sensory neuronopathies and clearly different from the ultrasound findings in axonal neuropathy. Smaller nerves are possibly a distinctive finding in SBMA that may distinguish it from other motor neuron syndromes. Further studies are warranted to confirm this and determine the optimal sonographic protocol.

The History of Neuroscience 5: Discovery of the Neuron and Its Connections

Thanks to the invention of the microscope equipped with an achromatic lens, research on the histology of the nervous system flourished during the 19th century. Jan Evangelista Purkinje, together with Gabriel Valentin, first depicted individual nerve cells. Robert Remak, one of the most remarkable microscopists of the 19th century, made the pivotal discovery that the cell body (globule) and fibers arising from the globule formed a single unit. In addition to improvements in microscopes, a new method of visualizing nervous tissue was developed—namely, the silver staining method introduced by Camillo Golgi. Golgi could identify the types and delicate branches of axons. However, he believed that axons always directly merged with other axons, which was the basis of the reticular or nerve net theory. Santiago Ramón y Cajal, the founder of modern neuroscience, finally established the cornerstone of the neuron doctrine, according to which the nerve cell is the basic unit of the nervous system and information flows from unit to unit without direct fusion. This structure is called the synapse. Key words: Achromatic lens; Histology; Silver staining; Neuron doctrine; Synapses.

Intertruncal versus classical approach to the ultrasound-guided supraclavicular brachial plexus block for upper extremity surgery: study protocol for a randomized non-inferiority trial

BackgroundUltrasound-guided intertruncal approach (IA) to the supraclavicular block (SB) is recently proposed as a new approach for local anesthetic (LA) injection in terms of the classical approach (CA) at the level of the first rib. The CA-SB has been proven to result in satisfying sensorimotor block, but associate with a high risk of intraneural injection. The aim of this randomized non-inferiority study is to explore whether IA-SB can obtain similar block dynamics, as the CA-SB, but avoiding an intraneural injection during the whole nerve block procedure.MethodsThe total 122 patients undergoing elective upper extremity surgery will be randomly allocated to receive either an IA-SB or a CA-SB using a double-injection (DI) technique. In the IA-SB group, a portion of LA (15 mL) is injected accurately to the intertruncal plane between the middle and lower trunks under real-time ultrasound guidance; then, the remaining volume (10 mL) is carefully distributed to the other intertruncal plane between the upper and middle trunks. In the CA-SB group, the DI technique will be carried out as described in Tran’s study. The primary outcome is the percentage of patients with a complete sensory blockade at 20 min with a predefined non-inferiority margin of − 5%. The secondary outcomes include the sensory-motor blockade of all 4 terminal nerves, onset times of the individual nerves within 30 min, block-related variables, and adverse events.DiscussionThe results will provide sensory-motor blockade-related parameters and safety of the ultrasound-guided intertruncal approach to the supraclavicular block, thereby promoting clinical practice.Trial registrationChinese Clinical Trial Registry ChiCTR2000040199. Registered on 25 November 2020

The Structure of the Brachial Plexus of the Djungarian Hamster (Phodopus sungorus)

Hamsters are often chosen as companion animals but are also a group of animals frequently subjected to laboratory tests. As there are no scientific publications providing information on the anatomical architecture of the brachial plexus of the Djungarian hamster, this study analyses the structure of this part of the nervous system of this species. It is important to know the details of this structure not only for cognitive reasons, but also due to the increasing clinical significance of rodents, which are often used in scientific research. The study was conducted on 55 specimens. Like in humans, the brachial plexus of the Djungarian hamster has three trunks. The following individual nerves innervating the thoracic limb of the Djungarian hamster: the radial nerve, median nerve, ulnar nerve, musculocutaneous nerve, axillary nerve, suprascapular nerve, thoracodorsal nerve, cranial pectoral nerves, caudal pectoral nerve, lateral thoracic nerve, long thoracic nerve, and subscapular nerves. Similarly to other mammals of this order, the brachial plexus of the Djungarian hamster ranges widely (C5-T1). However, its nerves are formed from different ventral branches of the spinal nerves than in other mammals.

The virtual peripheral nerve academy: education for the identification and treatment of peripheral nerve disorders

Millions of people around the globe suffer peripheral nerve injuries caused by trauma and medical disorders. However, medical school curricula are profoundly deficient in peripheral nerve education. This lack of knowledge within the healthcare profession may cause inadequate patient care. We developed the Virtual Peripheral Nerve Academy (VPNA) as a reusable virtual learning environment to provide medical students with detailed education on the peripheral nervous system (PNS). Students are introduced to the PNS through virtual 3D rendering of the human body, wherein they visualize individual nerves through dissection and observe normal motor and sensory function associated with each nerve. PNS structures that are absent from traditional texts are included in this visualization, ranging from the innervation of joints to the normal anatomic variation required for differential diagnosis of pain after an injury. Detailed modules on peripheral nerve disorders allow students to observe pathophysiological mechanisms, associated symptomatology, and appropriate treatments. Students are briefed on a patient clinical case, then interact with a patient avatar to learn the appropriate diagnostics, including physical exam maneuvers and electrodiagnostic testing. Interactive modules on peripheral nerve surgeries detail surgical techniques. The VPNA data and analytics dashboards allow medical students and course instructors to assess skill improvement and identify specific learning needs. The built-in learner management system and availability on both computer-based and virtual reality platforms facilitate integration into any existing medical school curricula. Ultimately, this immersive technology enables every medical student to learn about the peripheral nervous system and gain competency in treating real-life nerve pathologies.

Supraclavicular versus Infraclavicular Approach to Brachial Plexus Block under Ultrasound Guidance for Elective Surgeries of the Upper Limb: A Randomised Controlled Trial

Introduction: Ultrasonography has revived the infraclavicular approach to brachial plexus block resulting in many studies available in the literature. However, very few studies have assessed the sensory block characteristics of individual nerve territories by this approach. Aim: To compare the supraclavicular with the infraclavicular approach with special emphasis on the assessment of block characteristics of each nerve domain. Materials and Methods: This randomised controlled trial was conducted on 40 patients of American Society of Anesthesiologists (ASA) physical status I and II, aged between 20-60 years of age undergoing elective surgical procedures of the upper limb. They were randomly allocated into either group Supraclavicular (SC group) or Infraclavicular (IC group). Ultrasound-guided block was performed using 30 mL of 0.25% bupivacaine. The primary outcome measure was the efficacy of block, and the secondary outcome was the time taken for performance of block. Categorical variables were compared with the Chi-square test or Fisher’s-exact test. Continuous variables were analysed using the unpaired t-test. The p-value &lt;0.05 was considered significant. Results: Sensory block was complete in radial, median, and musculocutaneous nerve territories in both groups. All patients in the IC group had a complete sensory block in the ulnar nerve territory, compared to 80% patients in the SC group (p=0.036). Patients in the IC group had higher motor block scores in the shoulder joint (p=0.016), elbow, and wrist joints (p=0.036) and finger joints (p= 0.038). Block performance time was significantly longer in the IC group (p&lt;0.001). Conclusion: Infraclavicular approach provides better motor block and more complete sensory block of the upper limb. However, the time taken for performing the block was longer.

Accuracy of ultrasonography predicting spread location following intraneural and subparaneural injections: a scoping review.

Ultrasonography is useful for detecting intraneural injections. However, the reliability of the sonographic findings of intraneural and subparaneural injections in terms of true spread location and their association with intrafascicular deposits has not been systematically evaluated. Our objectives were: 1) to explore the reliability of sonographic findings of intraneural and subparaneural injections when validated with tests of true spread such as histology, dissection, or imaging; and 2) to evaluate their association with intrafascicular deposits. A scoping review was conducted according to Joanna Briggs guidelines. Cinahl, PubMed, ProQuest, ScienceDirect, Scopus and Cochrane databases were searched for studies on adults, cadavers, and animal models. Pediatric studies were excluded. The search strategy found 598 citations. Following screening, 19 studies were selected. Intraneural injections occurred in the brachial plexus, sciatic, femoral, and median nerves. Subparaneural injections in popliteal, supraclavicular and interscalene blocks. Sixteen different ultrasound findings were used to label injection location. Subepineural deposits within individual nerves occurred occasionally following subparaneural injections, regardless of nerve expansion. Overall, five studies reported intrafascicular deposits, two of which frequently, following intraneural and subparaneural injections. None of the currently used ultrasound findings was predictive of intrafascicular deposits. Our results suggest that sonographic parameters of intraneural and subparaneural injections are reliable in terms of detecting spread location. Intrafascicular injectate deposition may occur, albeit infrequently, particularly in the proximal brachial plexus. Our findings support the judicious interrogation of sonographic parameters suggestive of incipient intraneural injection.

The thermodynamic theory of action potential propagation: a sound basis for unification of the physics of nerve impulses.

The thermodynamic theory of action potential propagation challenges the conventional understanding of the nerve signal as an exclusively electrical phenomenon. Often misunderstood as to its basic tenets and predictions, the thermodynamic theory is virtually ignored in mainstream neuroscience. Addressing a broad audience of neuroscientists, we here attempt to stimulate interest in the theory. We do this by providing a concise overview of its background, discussion of its intimate connection to Albert Einstein's treatment of the thermodynamics of interfaces and outlining its potential contribution to the building of a physical brain theory firmly grounded in first principles and the biophysical reality of individual nerve cells. As such, the paper does not attempt to advocate the superiority of the thermodynamic theory over any other approach to model the nerve impulse, but is meant as an open invitation totheneuroscience community to experimentally test the assumptions and predictions of the theory on their validity.

Presynaptic Mitochondrial Volume and Packing Density Scale with Presynaptic Power Demand.

Stable neural function requires an energy supply that can meet the intense episodic power demands of neuronal activity. Neurons have presumably optimized the volume of their bioenergetic machinery to ensure these power demands are met, but the relationship between presynaptic power demands and the volume available to the bioenergetic machinery has never been quantified. Here, we estimated the power demands of six motor nerve terminals in female Drosophila larvae through direct measurements of neurotransmitter release and Ca2+ entry, and via theoretical estimates of Na+ entry and power demands at rest. Electron microscopy revealed that terminals with the highest power demands contained the greatest volume of mitochondria, indicating that mitochondria are allocated according to presynaptic power demands. In addition, terminals with the greatest power demand-to-volume ratio (∼66 nmol·min-1·µl-1) harbor the largest mitochondria packed at the greatest density. If we assume sequential and complete oxidation of glucose by glycolysis and oxidative phosphorylation, then these mitochondria are required to produce ATP at a rate of 52 nmol·min-1·µl-1 at rest, rising to 963 during activity. Glycolysis would contribute ATP at 0.24 nmol·min-1·µl-1 of cytosol at rest, rising to 4.36 during activity. These data provide a quantitative framework for presynaptic bioenergetics in situ, and reveal that, beyond an immediate capacity to accelerate ATP output from glycolysis and oxidative phosphorylation, over longer time periods presynaptic terminals optimize mitochondrial volume and density to meet power demand.SIGNIFICANCE STATEMENT The remarkable energy demands of the brain are supported by the complete oxidation of its fuel but debate continues regarding a division of labor between glycolysis and oxidative phosphorylation across different cell types. Here, we exploit the neuromuscular synapse, a model for studying neurophysiology, to elucidate fundamental aspects of neuronal energy metabolism that ultimately constrain rates of neural processing. We quantified energy production rates required to sustain activity at individual nerve terminals and compared these with the volume capable of oxidative phosphorylation (mitochondria) and glycolysis (cytosol). We find strong support for oxidative phosphorylation playing a primary role in presynaptic terminals and provide the first in vivo estimates of energy production rates per unit volume of presynaptic mitochondria and cytosol.

Scatterometry Measurements With Scattered Light Imaging Enable New Insights Into the Nerve Fiber Architecture of the Brain

The correct reconstruction of individual (crossing) nerve fibers is a prerequisite when constructing a detailed network model of the brain. The recently developed technique Scattered Light Imaging (SLI) allows the reconstruction of crossing nerve fiber pathways in whole brain tissue samples with micrometer resolution: the individual fiber orientations are determined by illuminating unstained histological brain sections from different directions, measuring the transmitted scattered light under normal incidence, and studying the light intensity profiles of each pixel in the resulting image series. So far, SLI measurements were performed with a fixed polar angle of illumination and a small number of illumination directions, providing only an estimate of the nerve fiber directions and limited information about the underlying tissue structure. Here, we use a display with individually controllable light-emitting diodes to measure the full distribution of scattered light behind the sample (scattering pattern) for each image pixel at once, enabling scatterometry measurements of whole brain tissue samples. We compare our results to coherent Fourier scatterometry (raster-scanning the sample with a non-focused laser beam) and previous SLI measurements with fixed polar angle of illumination, using sections from a vervet monkey brain and human optic tracts. Finally, we present SLI scatterometry measurements of a human brain section with 3 μm in-plane resolution, demonstrating that the technique is a powerful approach to gain new insights into the nerve fiber architecture of the human brain.

Prednisone combined with antiviral agents for the treatment of early idiopathic brachial plexus neuritis: report of five cases

&lt;p&gt;&lt;strong&gt;Background and Objective: &lt;/strong&gt;The aim of this study was to report the short-term outcomes of early idiopathic brachial plexus neuritis after low-dose corticosteroid combined with antiviral agent.&lt;/p&gt;&#x0D; &lt;p&gt;&lt;strong&gt;Methods:&lt;/strong&gt; Five patients with early brachial plexus neuritis presenting from April to June 2019 were included in this study. According to individual patient conditions, electromyography (EMG), nerve B-ultrasound and/or brachial plexus magnetic resonance imaging (MRI) were performed. After the diagnosis was confirmed, modified conservative treatments were initiated, including low-dose corticosteroid therapy and antiviral therapy for 2 weeks each while neurotrophic therapy for 4 weeks.&lt;/p&gt;&#x0D; &lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of the five patients, only two patients had symptoms of pain at onset, and three patients had sensory disturbances. Two patients reported a common cold before onset. The lesion involved the upper trunk of the brachial plexus in two patients. MRI showed slightly intense signals, of which one patient also had supraclavicular lymph node augmentation. The other three patients suffered ipsilateral radial nerve (RN) palsy. At 1 month of modified treatment, four patients recovered well with almost complete shoulder and hand movements; however, their muscle strength was still weaker comparing with the contralateral side. One patient restored full range of motion after surgery in 2 months.&lt;/p&gt;&#x0D; &lt;p&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; Early treatment is the key to good prognosis in patients with brachial plexus neuritis. Antiviral therapy combined with lowdose corticosteroid therapy may be superior to traditional treatment alone. In terms of early diagnosis, the clinical value of imaging examinations such as ultrasound and MRI is more specific as compared to that of EMG.&lt;/p&gt;

SP7.2.6 Where is the nerve? Review of operation note documentation practice for inguinal hernia repair

Abstract Introduction Careful identification and management of inguinal nerves during inguinal hernia repair is important to avoid iatrogenic injury. Documentation of this practice informs postoperative clinical management. We set out to investigate how often surgeons identify inguinal nerves and document findings and management in operation notes. Methods Retrospective review of operation notes at single District General Hospital (DGH). Operation notes analysed for documentation of identification and intraoperative management (preservation vs sacrifice) of the inguinal nerves: iliohypogastric, ilioinguinal and genital branch of genitofemoral nerve. Data including baseline characteristics of each patient, hernia characteristics, and primary operating surgeon ascertained for subgroup analysis. Results A total of 100 patients were included in the analysis. Identification of any of the inguinal nerves (generic - “nerve”) was documented in 17% of operation notes. Documentation of named individual nerves in operation notes was limited. No documentation of intraoperative management of inguinal nerves found in 83% of operation notes. Preservation of the inguinal nerves (generic - “nerve”) was recorded in 8% and sacrifice recorded in 9% of cases. Subgroup analysis revealed similar incidence of documentation of identification and management of inguinal nerves across grades of primary surgeon, with overall incidence low for all grades. Conclusion This study has revealed a lack of appreciation of the importance of documentation of identification and intraoperative management of inguinal nerves in operation notes. Further consideration of the potential implications of poor documentation would be beneficial to improve standards.

Focused Neuromuscular Ultrasound Approach for the Diagnosis of Chronic Inflammatory Demyelinating Polyneuropathy.

Previous ultrasonographic studies of individuals with chronic inflammatory demyelinating polyneuropathy (CIDP) have shown nerve enlargement at several sites. This prospective study compares only the bilateral median and ulnar nerves of individuals with CIDP with reference values to determine the clinical usefulness of this focused approach as a diagnostic tool. The cross-sectional area, echogenicity, and vascularity of the bilateral median and ulnar nerves of 25 subjects with CIDP were measured using ultrasound. Nineteen had typical CIDP based on the European Federation of Neurological Societies and the Peripheral Nerve Society guidelines, whereas six had atypical CIDP and were diagnosed based on clinical impression. Focal nerve enlargement was found in at least one segment in all subjects. Subjects with typical CIDP had larger cross-sectional areas compared with subjects with atypical CIDP. A focused ultrasound study, involving only the median and ulnar nerves, is sensitive for the detection of nerve enlargement in CIDP. Measuring the cross-sectional area of the median and ulnar nerves is clinically feasible and may help establish the diagnosis of CIDP.

Ultrasound-guided costoclavicular vs. axillary brachial plexus block: A randomized clinical study.

Background and Aims:Brachial plexus is in a very compact state at the costoclavicular space (CCS) when compared to the axilla, where the individual nerves are separate. This study aimed to test the hypothesis that brachial plexus block (BPB) at the CCS would result in a faster onset of block as compared to the axillary approach of BPB.Material and Methods:Fifty patients who underwent surgeries below the level of mid-arm under ultrasound-guided BPB were randomly allocated to any one of the two study groups. Thirty milliliters of local anesthetic (LA), a mixture of 10-mL 2% lidocaine with 5-μg/mL adrenaline and 20-mL 0.5% bupivacaine, was deposited around the axillary artery (25-mL LA) and the musculocutaneous nerve (5-mL LA) or at the CCS, and performance time was noted. Observer blinded to the block procedure recorded the block onset time and success rate.Results:The mean (SD) onset times were comparable between the costoclavicular (CC) and axillary (AX) groups (12.0 ± 3.2 vs. 11.2 ± 2.9 min, respectively; P = 0.367). Group CC demonstrated a reduction in performance time compared to group AX (5.3 ± 1.9 vs. 8.0 ± 3 min, respectively; P < 0.05). All blocks were successful in both groups without any complications except for one patient in group AX who required a rescue block for radial nerve.Conclusion:Costoclavicular and axillary ultrasound-guided BPBs resulted in similar onset times. However, the block performance time was longer for AX group compared to CC group. There were no intergroup differences found in terms of success rates.

Spatial modeling of epidermal nerve fiber patterns.

Peripheral neuropathy is a condition associated with poor nerve functionality. Epidermal nerve fiber (ENF) counts per epidermal surface are dramatically reduced and the two-dimensional (2D) spatial structure of ENFs tends to become more clustered as neuropathy progresses. Therefore, studying the spatial structure of ENFs is essential to fully understand the mechanisms that guide those morphological changes. In this article, we compare ENF patterns of healthy controls and subjects suffering from mild diabetic neuropathy by using suction skin blister specimens obtained from the right foot. Previous analysis of these data has focused on the analysis and modeling of the spatial ENF patterns consisting of the points where the nerves enter the epidermis, base points, and the points where the nerve fibers terminate, end points, projected on a 2D plane, regarding the patterns as realizations of spatial point processes. Here, we include the first branching points, the points where the nerve trees branch for the first time, and model the three-dimensional (3D) patterns consisting of these three types of points. To analyze the patterns, spatial summary statistics are used and a new epidermal active territory that measures the volume in the epidermis that is covered by the individual nerve fibers is constructed. We developed a model for both the 2D and the 3D patterns including the branching points. Also, possible competitive behavior between individual nerves is examined. Our results indicate that changes in the ENFs spatial structure can more easily be detected in the later parts of the ENFs.

Progression and regression of nerve fibre pathology and dysfunction early in diabetes over 5 years.

It has traditionally been suggested that the early development of diabetic sensorimotor polyneuropathy (DSPN) is characterized by predominant and progressive injury to small nerve fibres followed by large fibre impairment. We alternatively hypothesized that small and large fibre damage due to DSPN in type 1 and type 2 diabetes could develop in parallel and may not only be progressive but also reversible. Participants from the German Diabetes Study baseline cohort with recent-onset type 1/type 2 diabetes (n = 350/570) and age-matched glucose-tolerant control individuals (Control 1/Control 2: n = 114/190) were assessed using nerve conduction studies, thermal detection thresholds, vibration perception thresholds, neuropathy symptom scores, neuropathy disability scores and intraepidermal nerve fibre density (IENFD) in skin biopsies (type 1/type 2 diabetes: n = 102/226; Control 1/Control 2: n = 109/208). Subsets of participants with type 1/type 2 diabetes were followed for 5 years (n = 184/307; IENFD subset: n = 18/69). DSPN was defined by the Toronto Consensus criteria. At baseline, DSPN was present in 8.1% and 13.3% of the type 1 and type 2 diabetes groups, respectively. The most frequently abnormal tests in the lower limbs below or above the 2.5th and 97.5th centiles of the controls were the IENFD (13.7%) and individual nerve conduction studies (up to 9.4%) in type 1 diabetes participants and IENFD (21.8%), malleolar vibration perception thresholds (17.5%), and individual nerve conduction studies (up to 11.8%) in those with type 2 diabetes, whereas thermal detection threshold abnormalities did not differ between the control and diabetes groups. After 5 years, the highest progression rates from the normal to the abnormal range in type 2 diabetes participants were found for IENFD (18.8%) by -4.1 ± 2.8 fibres/mm, malleolar vibration perception threshold (18.6%) by 9.1 ± 20.2 µm and nerve conduction studies (15.0%) by 3.7 ± 1.5 points, while vice versa the highest regression rates were observed for neuropathy disability scores (11.2%) by -3.1 ± 1.3 points, sural nerve amplitudes (9.1%) by 4.7 ± 3.0 µV, IENFD (8.7%) by 1.4 ± 1.3 fibres/mm, and neuropathy symptom scores (8.2%) by -5.8 ± 1.6 points. In type 1 diabetes participants, no major progression was seen after 5 years, but subclinical DSPN regressed in 10.3%. These findings point to early parallel damage to both small and large nerve fibres in well-controlled recent-onset type 2 and, to a lesser extent, type 1 diabetes. After 5 years, peripheral nerve morphology and function and clinical measures progress to the abnormal range in type 2 diabetes, but initial nerve alterations are also reversible to a meaningful degree.

Psychological stress induced bladder overactivity in female mice is associated with enhanced afferent nerve activity

Psychological stress has been linked to the development and exacerbation of overactive bladder symptoms, as well as afferent sensitisation in other organ systems. Therefore, we aimed to investigate the effects of water avoidance stress on bladder afferent nerve activity in response to bladder filling and pharmaceutical stimulation with carbachol and ATP in mice. Adult female C57BL/6J mice were exposed to either water avoidance stress (WAS) for 1 h/day for 10 days or normal housing conditions. Voiding behaviour was measured before starting and 24-h after final stress exposure and then animals were euthanised to measure afferent nerve activity in association with bladder compliance, spontaneous phasic activity, contractile responses, as well as release of urothelial mediators. WAS caused increased urinary frequency without affecting urine production. The afferent nerve activity at low bladder pressures (4–7 mmHg), relevant to normal physiological filling, was significantly increased after stress. Both low and high threshold nerves demonstrated enhanced activity at physiological bladder pressures. Urothelial ATP and acetylcholine release and bladder compliance were unaffected by stress as was the detrusor response to ATP (1 mM) and carbachol (1 µM). WAS caused enhanced activity of individual afferent nerve fibres in response bladder distension. The enhanced activity was seen in both low and high threshold nerves suggesting that stressed animals may experience enhanced bladder filling sensations at lower bladder volumes as well as increased pain sensations, both potentially contributing to the increased urinary frequency seen after stress.

Pathological and anatomical changes in the peripheral nervous system in typhus. Morgenstern (Journal of Psychol., Neur. and Psychiatry, 1922)

The author found that in typhus there is, and with regard to the severity of the lesions, a parallelism between the central nervous system and the peripheral. There is no such correspondence between the individual nerves.