Abnormal Sensory Nerve Research Articles

Local keratinocyte-nociceptor interactions enhance obesity-mediated small fiber neuropathy via NGF-TrkA-PI3K signaling axis.

The pathology of diabetic small fiber neuropathy, characterized by neuropathic pain and axon degeneration, develops locally within the skin during the stages of obesity and pre-diabetes. However, the initiation and progression of morphological and functional abnormalities in skin sensory nerves remains elusive. To address this, we utilized ear skin from mice with diet-induced obesity (DIO), the mouse models for obesity and pre-type 2 diabetes. We evaluated pain-associated wiping behavior and conducted ex vivo live Ca2+ imaging of the DIO ear skin to detect sensory hypersensitivity. Our findings reveal sensory hypersensitivity in skin nociceptive axons followed by axon degeneration. Further mechanistic analysis identified keratinocytes as a major source of nerve growth factor (NGF) in DIO skin, which locally sensitizes nociceptors through NGF-mediated signaling. Indeed, the local inactivation of NGF and its receptor TrkA-mediated downstream signaling, including the phosphoinositide 3-kinases (PI3K) pathway, suppresses sensory hypersensitivity in DIO skin. Thus, targeting these local interactions between keratinocytes and nociceptors offers a therapeutic strategy for managing neuropathic pain, avoiding the adverse effects associated with systemic interventions.

Conscious sensations and protective reflexes driven by eye surface nerves in health and disease

The trigeminal primary sensory neurons that innervate the ocular surface, especially the cornea, have been classified in three functional types: polymodal nociceptors, mechano‐nociceptors and cold thermoreceptors. These sensory nerves are responsible for the conscious sensations evoked in response to ocular surface stimulation as well as for the regulation of tearing and blinking, and they are also involved in the trophic maintenance of the ocular tissues.Depending on the transducing channels they express in their membrane, sensory nerves from the ocular surface respond to different types of stimulus and, after this information is processed by the CNS, different conscious sensations are evoked: corneal mechano‐nociceptors' activation led to pricking pain; polymodal nociceptors evoke burning irritation, and cold thermoreceptors' activation may evoke freshness/cold/dryness/pain depending on the subtype of cold thermoreceptor neuron activated by the stimulus. While reflex blinking and tearing are driven by the activation of polymodal nociceptors as the afferent arm of the reflex, basal blinking and tearing rate are under the control of cold thermoreceptors' activity.During inflammation and after injury (such as UV‐induced keratitis, allergic keratoconjunctivitis, corneal surgery, tear‐deficient dry eye) the activity of corneal sensory nerves is modified in both eyes, even when inflammation or damage affects only one eye. The abnormal corneal sensory nerve activity constitutes the basis for the discomfort, dryness and pain sensations experienced under these conditions. Also, protective mechanisms depending on ocular nerve activity such as blinking and tearing become altered.(Supported by PID2020‐115934RB‐I00 from DOI: MCIN/AEI/10.13039/50110001103, and CIPROM/2021/48 from the Generalitat Valenciana, Spain)

Characteristics of Sensory Neuron Dysfunction in Amyotrophic Lateral Sclerosis (ALS): Potential for ALS Therapy.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterised by the progressive degeneration of motor neurons, resulting in muscle weakness, paralysis, and, ultimately, death. Presently, no effective treatment for ALS has been established. Although motor neuron dysfunction is a hallmark of ALS, emerging evidence suggests that sensory neurons are also involved in the disease. In clinical research, 30% of patients with ALS had sensory symptoms and abnormal sensory nerve conduction studies in the lower extremities. Peroneal nerve biopsies show histological abnormalities in 90% of the patients. Preclinical research has reported several genetic abnormalities in the sensory neurons of animal models of ALS, as well as in motor neurons. Furthermore, the aggregation of misfolded proteins like TAR DNA-binding protein 43 has been reported in sensory neurons. This review aims to provide a comprehensive description of ALS-related sensory neuron dysfunction, focusing on its clinical changes and underlying mechanisms. Sensory neuron abnormalities in ALS are not limited to somatosensory issues; proprioceptive sensory neurons, such as MesV and DRG neurons, have been reported to form networks with motor neurons and may be involved in motor control. Despite receiving limited attention, sensory neuron abnormalities in ALS hold potential for new therapies targeting proprioceptive sensory neurons.

Cyclosporine A Decreases Dryness-Induced Hyperexcitability of Corneal Cold-Sensitive Nerve Terminals.

Cyclosporine A (CsA) is used for the treatment of dry eye (DE) with good clinical results, improving tear secretion and decreasing subjective symptoms. These effects are attributed to the improved tear film dynamics, but there are no data on the effect of CsA on the abnormal sensory nerve activity characteristic in DE. Our purpose was to evaluate the CsA effect on the enhanced activity of corneal cold thermoreceptors in a tear-deficient DE animal model using in vitro extracellular recording of cold thermoreceptors nerve terminal impulses (NTIs) before and in the presence of CsA. NTI shape was also analyzed. Blinking frequency and tearing rate were also measured in awake animals before and after topical CsA. CsA increased the tearing and blinking of treated animals. CsA significantly decreased the peak response to cold of cold thermoreceptors. Neither their spontaneous NTIs discharge rate nor their cooling threshold were modified. CsA also seemed to reverse some of the changes in NTI shape induced by tear deficiency. These data suggest that, at least in part, the beneficial clinical effects of CsA in DE can be attributed to a direct effect on sensory nerve endings, although the precise mechanisms underlying this effect need further studies to be fully clarified.

A multicenter, randomized, double blind, placebo-controlled clinical trial of dl-3-butylphthalide in treatment of amyotrophic lateral sclerosis.

A multicenter, randomized, double blind, placebo-controlled clinical trial of dl-3-butylphthalide in treatment of amyotrophic lateral sclerosis.

Therapeutic efficacy of programmed spatial anatomy of the myopectineal orifice in total extraperitoneal hernioplasty: a retrospective study

This study aimed to investigate the therapeutic efficacy of programmed spatial anatomy of myopectineal orifice technique in laparoscopic total extraperitoneal hernioplasty (TEP) surgery. A total of 121 adult male patients with unilateral inguinal hernias who underwent TEP in the Department of General Surgery, Wujin Hospital, affiliated with Jiangsu University, from January 2019 to December 2020 were selected. Patients were divided into the procedural (63 cases) and traditional groups (58 cases) according to the surgical methods adopted. The procedural group underwent programmed spatial anatomy of the myopectineal orifice combined with TEP, and the traditional group underwent traditional TEP. The perioperative evaluation indicators and postoperative complications were observed and compared between the two groups. Compared with the traditional group, the time of handling hernia, the intraoperative operation time, intraoperative blood loss, postoperative ambulation time, and postoperative hospital stay in the procedural group were significantly reduced (P < 0.05). The incidence of postoperative complications such as sensory nerve abnormalities and chronic pain was significantly decreased (P < 0.05), and the total incidence of complications in the procedural group was significantly lower than that in the traditional group (P < 0.05). While there was no significant difference in postoperative incision infection (P > 0.05). The programmed spatial anatomy of the myopectineal orifice can significantly improve the treatment outcome of TEP, significantly improve the patients' intraoperative and postoperative indicators, and reduce the incidence of postoperative complications. It is worthy of being promoted among young physicians and basic hospitals.

P.219 Novel clinical phenotype of early-onset amyotrophic lateral sclerosis and frontotemporal dementia with SNCB mutation

The continuum between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is well known spectrum of disease and genetic variability in this overlap has been previously reported. We report a novel clinical phenotype of early-onset ALS and FTD with a previously reported <i>SNCB</i> (β synuclein) mutation with Lewi body dementia. 45-year-old woman presented to our department complaining of progressive quadriparesis and dysphagia, which had started with right hemiparesis 4 months ago. She had a history of hypothyroidism but denied neurological family history. Neurologic examination revealed Hoffmann sign positive bilaterally and hyperreflexia of both knees. Nerve conduction study and electromyography showed low complex motor action potentials and widespread denervation in four limbs and thoracic paraspinal muscles without abnormal sensory nerve action potentials. CSF study was unremarkable. Diagnosis of probable ALS was established and riluzole 100mg daily was administered. Three months later, she reported a cognitive decline. In the neuropsychologic assessment battery, her language, memory, and frontal/executive function were below the first percentile for her age with relatively intact attention and visuospatial function. Brain MRI showed bilateral temporal atrophy, especially in the left anterior temporal area. SPECT revealed hypoperfusion in both frontal, temporal, and parietal cortices. Targeted next generation sequencing was conducted for ALS and FTD, and we found heterozygous c.208G>A mutation in <i>SNCB</i>. Despite tremendous research elucidating ALS-FTD, early onset case is rare. With this case, we report a new clinical phenotype of ALS-FTD with <i>SNCB</i> mutation, which has been only reported in few cases of Lewy body dementia and is being investigated recently. This case implies <i>SNCB,</i> which is assumed to contribute to neurodegeneration, can be a new candidate of ALS-FTD, especially in young age.

Diagnostic accuracy of nerve ultrasonography for the detection of peripheral neuropathy in type 2 diabetes.

Nerve conduction studies (NCS) are the current objective measure for diagnosis of peripheral neuropathy in type 2 diabetes but do not assess nerve structure. This study investigated the utility of peripheral nerve ultrasound as a marker of the presence and severity of peripheral neuropathy in type 2 diabetes. A total of 156 patients were recruited, and nerve ultrasound was undertaken on distal tibial and distal median nerves. Neuropathy severity was graded using the modified Toronto Clinical Neuropathy Scale (mTCNS) and Total Neuropathy Score (TNS). Studies were undertaken by a single ultrasonographer blinded to nerve conduction results. A stepwise increase in tibial nerve cross-sectional area (CSA) was noted with increasing TNS grade (p&lt; 0.001) and each mTCNS quartile (p&lt; 0.001). Regression analysis demonstrated a correlation between tibial nerve CSA and neuropathy severity (p&lt; 0.001). Using receiver operator curve analysis, tibial nerve CSA of &gt;12.88 mm yielded a sensitivity of 70.5% and specificity of 85.7% for neuropathy detection. Binary logistic regression revealed that tibial nerve CSA was a predictor of abnormal sural sensory nerve action potential amplitude (odds ratio=1.239, 95% confidence interval [CI]=1.142-1.345) and abnormal neuropathy score (odds ratio=1.537, 95% confidence interval [CI]=1.286-1.838). Tibial nerve ultrasound has good specificity and sensitivity for neuropathy diagnosis in type 2 diabetes. The study demonstrates that tibial nerve CSA correlates with neuropathy severity. Future serial studies using both ultrasound and NCS may be useful in determining whether changes in ultrasound occur prior to development of nerve conduction abnormalities and neuropathic symptoms.

Clinical features of Guillain-Barré syndrome with anti-neurofascin 155 antibody.

Anti-neurofascin 155 (NF155) antibody has been discovered in chronic demyelinating conditions. However, the positive rate and clinical description were insufficient in acute demyelinating conditions, such as Guillain-Barré syndrome (GBS). This study aimed to explore the positive rate of anti-NF155 antibody in GBS patients and determine whether there were unique clinical characteristics in these patients. Serum anti-NF155 antibody was detected from 94 GBS patients and 50 sex- and age-matched healthy controls using cell-based assay and tissue-based assay with immunostaining of mouse teased sciatic nerve fibers. Clinical characteristics, laboratory data, and electrophysiology examinations were retrospectively collected. Seven of 94 (7.45%) GBS patients were positive for anti-NF155 antibody, and the main IgG subclass was IgG1. Compared with anti-NF155 antibody-negative GBS patients, anti-NF155 antibody-positive GBS patients had a higher GBS disability score at nadirs (p=.010), higher modified Erasmus GBS outcome score (p=.022), higher rate of abnormal compound motor action potential (CMAP) amplitude (p=.002), higher frequency of prolonged F-wave latency (p < .001), lower frequency of abnormal sensory conduction velocity (p < .001) and sensory nerve action potential amplitude (p < .001), more axonal type (p=.040), and poorer therapeutic effect (p=.017). Anti-NF155 antibody exists in a small portion of GBS patients. Anti-NF155 antibody-positive GBS patients possibly have a more severe clinical course, less sensory nerves involved, higher proportion of axonal type, poorer therapeutic effect, and worse prognosis, but the pathogenicity of the anti-NF155 antibody in GBS needs further study.

QS63. Severity of Neuropathic Pain, Sensorimotor Impairments, and Sensory Neuron Abnormalities in Rat Model of Radiation Induced Neuropathy is Dose Dependent

Purpose: Radiation therapy (XRT) is one of the mainstays of cancer treatment, with approximately 50% of cancer patients requiring XRT as part of their treatment regimen. Of these patients, almost 31% subsequently suffer from debilitating neuropathic pain and sensory nerve abnormalities. XRT induced peripheral neuropathy results in progressive, intractable, and often irreversible nerve pain which can have a devastating effect on patients’ quality of life and potentially reduce the overall benefit of the therapy itself. We have previously established a novel rodent model of radiation induced peripheral neuropathy. The purpose of the present study was to assess neuropathic pain, sensorimotor impairments, and sensory neuron abnormalities in both clinically relevant and clinically high dose radiated animals. Methods: Eighteen male Lewis rats were randomly assigned to one of three experimental groups: (1) radiation of 35 Gray (Gy) divided into 5 daily doses of 7 Gy/day; (2) radiation of 70 Gray divided into 5 daily doses of 14 Gy/day, and (3) sham-radiated controls. All animals were tested at baseline in both pain and sensorimotor behavioral tests. Pain related measures included mechanical allodynia (von Frey test), cold allodynia (Acetone test), and thermal allodynia (Hargreaves test). Sensorimotor testing consisted of evaluation of overground locomotion using walkings tracks with calculation of the Sciatic Functional Index (SFI). Animals were tested serially over an 8 week period. At study endpoint, we performed nerve conduction analysis, electromyography (EMG), muscle force measurements, and all sciatic nerves were taken for histological/histomorphometrical analysis. In a separate cohort of animals, retrograde labeling was conducted in order to assess the level of sensory neuron death following radiation. Results: All animals that underwent radiation displayed significantly greater hypersensitivity to mechanical stimulation as compared to sham-radiated animals, indicative of chronic neuropathic pain. SFI values indicated sensorimotor impairments in radiated animals, and significantly lower twitch and tetanic muscle forces. Sensory neuron abnormalities and cell death were greater in radiated animals, with the high dose group displaying the most severe decrease. Conclusion: Results from this study demonstrate that neuropathic pain, sensorimotor behavioral impairment, and sensory neuron abnormalities vary as a function of radiation dose administered. Ongoing research is currently assessing novel therapeutic compounds to attenuate debilitating radiation induced sequelae, with the goal of improving the quality of life for cancer patients undergoing XRT.

Sural-sparing pattern: A study against electrodiagnostic subtypes of Guillain–Barre syndrome

ObjectiveTo study sural-sparing pattern in Guillain–Barre syndrome (GBS) and compare it among GBS’s electrodiagnostic subtypes, classified by two recent criteria. MethodsThis study retrospectively reviewed clinical data and electrodiagnostic studies (EDXs) of 88 GBS patients diagnosed in a tertiary care hospital (2010–2019). ResultsOverall, 79/88 (89.8%) and 36/45 (80%) patients had bilateral sensory nerve conduction studies (NCS) in the first EDX and follow-up EDX, respectively. Sural-sparing occurred in all subtypes (50% overall occurrence rate), most commonly in demyelination. There was no statistically significant difference in sural-sparing occurrence rates between demyelinating and axonal GBS; however, sural-sparing in axonal GBS tended to show a lower number of abnormal upper-limb sensory nerve action potentials (SNAPs) than demyelinating GBS. Shifting between sural-sparing and no sural-sparing occurred in approximately-one-fourth of patients receiving serial studies. Follow-up EDX additionally discovered 20% of all sural-sparing. Unilateral EDX could have omitted up to 30% of sural-sparing. ConclusionsSural-sparing is less obviously manifested in axonal than demyelinating GBS, with respect to the number of affected upper-limb SNAPs. Extended sensory NCS is worth in detecting sural-sparing as a supportive electrodiagnostic GBS feature. SignificanceThis report showed one different character of sural-sparing (number of affected upper-limb SNAPs) between demyelinating and axonal GBS.

Variability in electrodiagnostic findings associated with neurogenic thoracic outlet syndrome.

Introduction/AimsNeurogenic thoracic outlet syndrome (NTOS) is a heterogeneous and often disputed entity. An electrodiagnostic pattern of T1 > C8 axon involvement is considered characteristic for the diagnosis of NTOS. However, since the advent of high‐resolution nerve ultrasound (US) imaging, we have encountered several patients with a proven entrapment of the lower brachial plexus who showed a different, variable electrodiagnostic pattern.MethodsIn this retrospective case series, 14 patients with an NTOS diagnosis with a verified source of compression of the lower brachial plexus and abnormal findings on their electrodiagnostic testing were included. Their medical records were reviewed to obtain clinical, imaging, and electrodiagnostic data.ResultsSeven patients showed results consistent with the “classic” T1 axon > C8 pattern of involvement. Less typical findings included equally severe involvement of T1 and C8 axons, more severe C8 involvement, pure motor abnormalities, neurogenic changes on needle electromyography in the flexor carpi radialis and biceps brachii muscles, and one patient with an abnormal sensory nerve action potential (SNAP) amplitude for the median sensory response recorded from the third digit. Patients with atypical findings on electrodiagnostic testing underwent nerve imaging more often compared to patients with classic findings (seven of seven patients vs. five of seven respectively), especially nerve ultrasound.DiscussionWhen there is a clinical suspicion of NTOS, an electrodiagnostic finding other than the classic T1 > C8 pattern of involvement does not rule out the diagnosis. High resolution nerve imaging is valuable to diagnose additional patients with this treatable condition.

Baseline extended zone retinal vascular calibres associate with sensory nerve abnormalities in adolescents with type 1 diabetes: A prospective longitudinal study.

The relationship between retinal vascular calibres (RVCs) and diabetic neuropathy is unclear. We investigated associations between RVCs and sensory nerve abnormality in adolescents with type 1 diabetes. In a prospective longitudinal study of 889 adolescents with type 1 diabetes with baseline mean (±SD) age 14.1±1.5years and HbA1c IFCC 69.4±14.1mmol/mol (8.6±1.3%), RVCs were assessed from baseline retinal photographs: 'central zone' calibres, summarized as central retinal arteriolar (CRAE) and venular equivalents (CRVE) and 'extended zone' calibres: mean width of arterioles (MWa) and venules (MWv). Sensory nerve abnormality was defined as at least one abnormal sensory quantitative testing from two thermal and two vibration threshold tests measured at foot every 1-2years. Associations between baseline RVC and sensory nerve function were examined using generalized estimating equations and cumulative risk by Cox regression analyses. During a median study follow-up of 6.2 [IQR 3.7-10.4] years, sensory nerve abnormality was found in 27% of adolescents. Narrower extended zone calibre quartiles but not CRAE or CRVE quartiles were independently associated with sensory nerve abnormality: MWa (Q1 vs. Q2-4: OR 1.35 (95% CI 1.02, 1.61) and MWv (Q1 vs. Q2-4: 1.31 (1.03, 1.7)), after adjusting for HbA1c , duration and blood pressure. Similarly, in Cox regression, the narrowest quartiles were associated with sensory nerve abnormality: MWa hazard ratio (HR) 1.5 (1.3, 1.8) and MWv 1.6 (1.4, 1.9). Narrower extended zone retinal calibres were associated with sensory nerve abnormality in adolescents with type 1 diabetes and may present useful biomarkers to understand the pathophysiology of neuropathy.

CANVAS: A New Genetic Entity in the Otorhinolaryngologist’s Differential Diagnosis

The biallelic inheritance of an expanded intronic pentamer (AAGGG)exp in the gene encoding replication factor C subunit 1 (RFC1) has been found to be a cause of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). This study describes clinical and genetic features of our patients with clinical suspicion of the syndrome. A retrospective descriptive study from an ataxia database comprising 500 patients. The study was performed at the Otorhinolaryngology Department of a hospital in the north of Spain. Specific genetic testing for CANVAS was performed in 13 patients with clinical suspicion of complete or incomplete syndrome. The clinical diagnosis was supported by quantitative vestibular hypofunction, cerebellar atrophy, and abnormal sensory nerve conduction testing. Nine of 13 (69%) patients met clinical diagnostic criteria for definite CANVAS disease. The first manifestation of the syndrome was lower limb dysesthesia in 8 of 13 patients and gait imbalance in 5 of 13. Eleven of 13 (85%) patients were carriers of the biallelic (AAGGG)exp in RFC1. A genetic cause of CANVAS has recently been discovered. We propose genetic screening for biallelic expansions of the AAGGG pentamer of RFC1 in all patients with clinical suspicion of CANVAS, since accurate early diagnosis could improve the quality of life of these patients.

Evaluation of axonal loss in ulnar sensory nerve fibers recorded from ring and little fingers secondary to idiopathic carpal tunnel syndrome in Egyptian patients

BackgroundThe association between carpal tunnel syndrome (CTS) and ulnar nerve entrapment is unclear, and the extra-median paresthesia in the ulnar nerve territory innervation in CTS is unexplained. Our purpose is to evaluate the neurophysiologic changes in ulnar nerve sensory fibers secondary to idiopathic CTS in comparison to normal subjects, and their relation to the severity of CTS.ResultsThe difference between CTS and control hands regarding all parameters of ulnar motor nerve conduction studies (MNCS) was not statistically significant (p > 0.05). There was a statistically significant difference in all parameters of median sensory conduction study (SCS) and MNCS between CTS and control hands (p < 0.0001) except for conduction velocity and in all parameters of median and ulnar SCS recording digit 4 (D4) (p < 0.05). The mean value of abnormalities of ulnar SCS recording D4 and digit 5 (D5) was significantly higher in moderate and severe CTS hands (p < 0.05). There were significant negative correlations between median motor and sensory latency and ulnar sensory amplitude recording D4 and D5.ConclusionUlnar sensory nerve abnormalities exist among CTS patients, which were more in moderate and severe grades. The drop in amplitude of ulnar nerve sensory response argues in favor of the possible impact of CTS on the ulnar nerve and did not indicate axonal deterioration of the ulnar nerve.

Clinical features of Guillain\u2013Barr\xe9 syndrome patients with elevated serum creatine kinase levels

BackgroundIt is not well defined whether Guillain–Barré syndrome (GBS) patients with elevated serum creatine kinase (CK) levels have characteristic clinical features and are related to the subgroups of GBS.MethodsWe retrospectively studied 51 consecutive patients with GBS, who visited our hospital, and compared clinical, laboratory and electrophysiological findings between patients with and without elevated CK levels.ResultsOf 51 patients, 14 patients (27%) showed an elevation of serum CK levels. When compared with patients with the normal CK levels, the ratios of male, antecedent infections, and anti-GM1 antibody positivity were significantly higher in patients with elevated CK levels. The ratios of hypoesthesia, cranial nerve involvement, and urinary retention were significantly less in patients with elevated CK levels. There were no significant differences in disability at peak between two groups. In the electrophysiological examination, sensory nerve abnormalities were not observed. Although some patients with elevated CK levels showed prolongation of distal motor latencies (DMLs) and increase of durations in the initial examination, development of the prolongation of DMLs and increase of durations was not observed in the follow-up examinations. The findings were consistent with acute motor axonal neuropathy (AMAN) with reversible conduction failure (RCF) but not acute inflammatory demyelinating polyneuropathy (AIDP).ConclusionsThe results suggest that the GBS patients with elevated CK levels represent not a group of AIDP but a group of AMAN with axonal degeneration or RCF even though the initial electrophysiological examination shows AIDP pattern.

Sciatic neuropathy with preserved sensory nerve action potentials, a case series

Background: Sciatic neuropathy is differentiated from lumbosacral radiculopathy based on the finding of abnormal sensory nerve action potentials (SNAPs). Cases of sciatic neuropathy with intact SNAPS have not been well described.&#x0D; Methods: A retrospective analysis of 12 patients with sciatic neuropathy in a single institution.&#x0D; Results: We describe 12 patients in whom a sciatic neuropathy was diagnosed based on a combination of history, physical exam, radiological and electrodiagnostic (EDX) findings. Lower extremity SNAPs were found to be within normal range in all patients, although SNAP amplitude asymmetry between both sides was observed in 3. Included patients were young (mean age of 40.3 years) and mostly female (9 patients).&#x0D; Conclusions: Sciatic neuropathy may occur with a relative sparing of sensory fibers. Recognition of this group of patients should help to avoid making a misdiagnosis of lumbosacral radiculopathy.

Transient global amnesia associated with migraine triggered by anxiety under the effects of the coronavirus (COVID-19) pandemic: A case report

Transient global amnesia (TGA) is a clinical syndrome featured with the sudden onset of primarily short-term loss of anterograde as well as a milder decline of retrograde memory. The etiology is still unclear. Various risk factors relate with TGA and it is thought the vulnerability of CA1 neurons to metabolic stress plays an important role in the pathophysiological cascade. During the quarantine period of the coronavirus (COVID-19) pandemic, a 53-year-old Asian woman with 30 years of migraine history presented the emergency department for the first time to evaluate a sudden onset confusion and forgetfulness with repetitive questioning during migraine attack. Neurologic examination showed preserved orientations for time and person and no abnormalities in motor, speech, sensory, coordination, or cranial nerves. No focal Neurologic finding. Her memory gradually improved and restored to normal baseline over the course of a 24-hour in-patient stay. However, are trograde memory gap still existed a month after the TGA attack. The pathogenesis of TGA is unknown and many risk factors are associated with it, but among them migraine is considered a major risk factor, particularly in female patients aged 40-60 years. The anxiety stressor is a significant trigger for TGA. The pathophysiology argues that the vulnerability of CA1 neurons to metabolic stress plays an important role in TGA.

Checkpoint inhibitor develops histological autoimmune pancreatitis like type 1 diabetes. A case report

Transient global amnesia (TGA) is a clinical syndrome featured with the sudden onset of primarily short-term loss of anterograde as well as a milder decline of retrograde memory. The etiology is still unclear. Various risk factors relate with TGA and it is thought the vulnerability of CA1 neurons to metabolic stress plays an important role in the pathophysiological cascade. During the quarantine period of the coronavirus (COVID-19) pandemic, a 53-year-old Asian woman with 30 years of migraine history presented the emergency department for the first time to evaluate a sudden onset confusion and forgetfulness with repetitive questioning during migraine attack. Neurologic examination showed preserved orientations for time and person and no abnormalities in motor, speech, sensory, coordination, or cranial nerves. No focal Neurologic finding. Her memory gradually improved and restored to normal baseline over the course of a 24-hour in-patient stay. However, are trograde memory gap still existed a month after the TGA attack. The pathogenesis of TGA is unknown and many risk factors are associated with it, but among them migraine is considered a major risk factor, particularly in female patients aged 40-60 years. The anxiety stressor is a significant trigger for TGA. The pathophysiology argues that the vulnerability of CA1 neurons to metabolic stress plays an important role in TGA.

Overexpression of Sirtuin 1 protein in neurons prevents and reverses experimental diabetic neuropathy.

In diabetic neuropathy, there is activation of axonal and sensory neuronal degeneration pathways leading to distal axonopathy. The nicotinamide-adenine dinucleotide (NAD+)-dependent deacetylase enzyme, Sirtuin 1 (SIRT1), can prevent activation of these pathways and promote axonal regeneration. In this study, we tested whether increased expression of SIRT1 protein in sensory neurons prevents and reverses experimental diabetic neuropathy induced by a high fat diet (HFD). We generated a transgenic mouse that is inducible and overexpresses SIRT1 protein in neurons (nSIRT1OE Tg). Higher levels of SIRT1 protein were localized to cortical and hippocampal neuronal nuclei in the brain and in nuclei and cytoplasm of small to medium sized neurons in dorsal root ganglia. Wild-type and nSIRT1OE Tg mice were fed with either control diet (6.2% fat) or a HFD (36% fat) for 2 months. HFD-fed wild-type mice developed neuropathy as determined by abnormal motor and sensory nerve conduction velocity, mechanical allodynia, and loss of intraepidermal nerve fibres. In contrast, nSIRT1OE prevented a HFD-induced neuropathy despite the animals remaining hyperglycaemic. To test if nSIRT1OE would reverse HFD-induced neuropathy, nSIRT1OE was activated after mice developed peripheral neuropathy on a HFD. Two months after nSIRT1OE, we observed reversal of neuropathy and an increase in intraepidermal nerve fibre. Cultured adult dorsal root ganglion neurons from nSIRT1OE mice, maintained at high (30 mM) total glucose, showed higher basal and maximal respiratory capacity when compared to adult dorsal root ganglion neurons from wild-type mice. In dorsal root ganglion protein extracts from nSIRT1OE mice, the NAD+-consuming enzyme PARP1 was deactivated and the major deacetylated protein was identified to be an E3 protein ligase, NEDD4-1, a protein required for axonal growth, regeneration and proteostasis in neurodegenerative diseases. Our results indicate that nSIRT1OE prevents and reverses neuropathy. Increased mitochondrial respiratory capacity and NEDD4 activation was associated with increased axonal growth driven by neuronal overexpression of SIRT1. Therapies that regulate NAD+ and thereby target sirtuins may be beneficial in human diabetic sensory polyneuropathy.