An update on treatment modalities for ulnar nerve entrapment: A literature review

Context: Ulnar nerve entrapment is a relatively common entrapment syndrome second only in prevalence to carpal tunnel syndrome. The potential anatomic locations for entrapment include the brachial plexus, cubital tunnel, and Guyon�s canal. Ulnar nerve entrapment is more so prevalent in pregnancy, diabetes, rheumatoid arthritis, and patients with occupations involving periods of prolonged elbow flexion and/or wrist dorsiflexion. Cyclists are particularly at risk of Guyon�s canal neuropathy. Patients typically present with sensory deficits of the palmar aspect of the fourth and fifth digits, followed by motor symptoms, including decreased pinch strength and difficulty fastening shirt buttons or opening bottles. Evidence Acquisition: Literature searches were performed using the belowMeSHTerms using Mendeley version 1.19.4. Search fields were varied until further searches revealed no new articles. All articles were screened by title and abstract. Decision was made to include an article based on its relevance and the list of final articles was approved three of the authors. This included reading the entirety of the artice. Anyquestion regarding the inclusion of anarticlewasdiscussed by all authors untilanagreementwasreached. Results: X-rayandCTplay a role in diagnosiswhenabonyinjury is thought to be related to the pathogenesis (i.e., fracture of thehook of the hamate.) MRI plays a role where soft tissue is thought to be related to the pathogenesis (i.e., tumor or swelling.) Electromyography and nerve conduction also play a role in diagnosis. Medicalmanagement, in conjunction with physical therapy, shows limited promise. However, minimally invasive techniques, including peripheral percutaneous electrode placement and ultrasound-guided electrode placement, have all been recently studied and show great promise. When these techniques fail, clinicians should resort to decompression, which can be done endoscopically or through an open incision. Endoscopic ulnar decompression shows great promise as a surgical option with minimal incisions. Conclusions: Clinical diagnosis of ulnar nerve entrapment can often be delayed and requires the suspicion as well as a thorough neurological exam. Early recognition and diagnois are important for early institution of treatment. A wide array of diagnostic imaging can be useful in ruling out bony, soft tissue, or vascular etiologies, respectively. However, clinicians should resort to electrodiagnostic testing when a definitive diagnois is needed. Many new minimally invasive techniques are in the literature and show great promise; however, further large scale trials are needed to validate these techniques. Surgical options remains as a gold standard when adequate symptom relief is not achieved through minimally invasive means. © 2020, Author(s)

Peripheral neuromodulation for the management of headache

Context: Neuromodulation is an expanding field of study for headache treatment to reduce pain by targeting structures within the nervous system that are commonly involved in headache pathophysiology, such as the vagus nerve (VNS), occipital nerves, or sphenopalatine ganglion (SPG) for stimulation. Pharmaceutical medical therapies for abortive and prophylactic treatment, such as triptans, NSAIDs, beta-blockers, TCAs, and antiepileptics, are effective for some individuals, but the role that technology plays in investigating other therapeutic modalities is essential. Peripheral neuromodulation has gained popularity and FDA approval for use in treating certain headaches and migraine headache conditions, particularly in those who are refractory to treatment. Early trials found FDA approved neurostimulatory implant devices, including Cephaly and SpringTMS, improved patient-oriented outcomes with reductions in headaches per month (frequency) and severity. Evidence Acquisition: This was a narrative review. The sources for this review are as follows: Searching on PubMed, Google Scholar, Medline, and ScienceDirect from 1990 - 2019 using keywords: Peripheral Neuromodulation, Headache, vagus nerve, occipital nerves, sphenopalatine ganglion. Results: The first noninvasive neurostimulator device approved for migraine treatment was the Cefaly device, an external trigeminal nerve stimulation device (e-TNS) that transcutaneously excites the supratrochlear and supraorbital branches of the ophthalmic nerve. The second noninvasive neurostimulation device receiving FDA approval was the single-pulse transcranial magnetic stimulator, SpringTMS, positioned at the occiput to treat migraine with aura. GammaCore is a handheld transcutaneous vagal nerve stimulator applied directly to the neck at home by the patient for treatment of cluster headache (CH) and migraine. Several other devices are in development for the treatment of headaches and target headache evolution at different levels and inputs. The Scion device is a caloric vestibular stimulator (CVS) which interfaces with the user through a set of small cones resting in the ear canal on either side and held in place by modified over-ear headphones. The pulsante SPG Microstimulator is a patient-controlled device implanted in the patient�s upper jaw via an hour-long oral procedure to target the sphenopalatine ganglion. The occipital nerve stimulator (ONS) is an invasive neuromodulation device for headache treatment that consists of an implanted pulse generator on the chest wall connected to a subcutaneous lead with 4 - 8 electrodes that is tunneled the occiput. Conclusions: The aim of this review is to provide a comprehensive overview of the efficacy, preliminary outcomes, and limitations of neurostimulatory implants available for use in the US and those pending further development. © 2020, Author(s)

Utilization of intravenous lidocaine infusion for the treatment of refractory chronic pain

Context: Chronic pain accounts for one of the most common reasons patients seek medical care. The financial burden of chronic pain on health care is seen by direct financial cost and resource utilization. Many risk factors may contribute to chronic pain, but there is no definite risk. Managing chronic pain is a balance between maximally alleviating symptoms by utilizing a therapeutic regimen that is safe for long-term use. Currently, non-opioid analgesics, NSAIDs, and opioids are some of the medical treatment options, but these have numerous adverse effects and may not be the best option for long-term use. However, Lidocaine can achieve both central and peripheral analgesic effects with relatively few side effects, whichmaybe an idealcompoundfor managing chronic pain. Evidence Acquisition: This is a Narrative Review. Results: Infusion of lidocaine (2-(diethylamino)-N-(2,6-dimethylphenyl)acetamide), an amino-amide compound, is emerging as a promising option to fill the therapeutic void for treatment of chronic pain. Numerous studies have outlined dosing protocols for lidocaine infusion for the management of perioperative pain, outlined below. While there are slight variations in these different protocols, they all center around a similar dosing regimen to administer a bolus to reach a rapid steady state, followed by infusion for up to 72 hours to maintain the therapeutic analgesic effects. Conclusions: Lidocaine may be a promising pharmacologic solution with a low side effect profile that provides central and peripheral analgesia. Even though the multifaceted mechanism is not entirely understood yet, lidocainemaybe a promising novel remedy in treating chronic pain in various conditions. © 2020, Author(s)

Efficacy of acupuncture in the treatment of chronic abdominal pain

Context: Abdominal pain is a widespread complaint and is one of the common reasons leading patients to seek medical care, either in emergency situations or with their primary providers. While acute abdominal pain is a better defined, usually surgical condition, chronic abdominal pain requires longer, typically lifelong, therapy. Chronic abdominal pain may also present with acute flares and complications. Here we review seminal and novel evidence discussing the use of acupuncture in the treatment of abdominal pain, indications, and conditions that may benefit from this approach. Evidence Acquisition: Chronic abdominal pain is a common complaint causing significant morbidity and disability and has a hefty price tag attached. Recent studies show it may be prevalent in as much as 25 of the adult population. It is defined as three episodes of severe abdominal pain over the course of three months. Chronic abdominal pain could be the result of chronicity of acute pain or of chronic pain syndromes, most commonly IBD syndromes and IBS. While a plethora of treatments exists for both conditions, these treatments usually fall short of complete symptom control, and there is a need for complementary measures to curb disability and increase the quality of life in these patients. Acupuncture is a form of integrative medicine that has long been used in Chinese and traditional medicine, based on the rebalancing of the patient�s Qi, or Ying/Yang balance. It has been shown to be effective in treating several other conditions, and novel evidence may expand its use into other fields as well. Clinical trials studying acupuncture in chronic pain conditions have been promising, and recent evidence supports the use of abdominal pain in chronic abdominal pain conditions as well. Though not curative, acupuncture is a complementary approach that helps reduce symptoms and improved quality of life. Conclusions: Chronic abdominal pain is a widespread condition, mostly affected by the IBS and IBD spectrum. Etiologies are still being studied for these conditions, and while novel treatment approaches are absolute game changers for these patients, many continue to experience some level of symptoms and disability. Acupuncture may provide further alleviation of these symptoms in select patients, thus improving quality of life, reducing disability, and saving healthcare dollars. It is a largely safe and inexpensive method that may significantly contribute to the quality of life of selected patients. © 2021, Author(s)

Dorsal root ganglion (Drg) and chronic pain

Context: Chronic neuropathic pain is a common condition, and up to 11.9 of the population have been reported to suffer from uncontrolled neuropathic pain. Chronic pain leads to significant morbidity, lowered quality of life, and loss of workdays, and thus carries a significant price tag in healthcare costs and lost productivity. dorsal root ganglia (DRG) stimulation has been recently increasingly reported and shows promising results in the alleviation of chronic pain. This paper reviews the background of DRG stimulation, anatomical, and clinical consideration and reviews the clinical evidence to support its use. Evidence Acquisition: The DRG span the length of the spinal cord and house the neurons responsible for sensation from the pe-riphery. They may become irritated by direct compression or local inflammation. Glial cells in the DRG respond to nerve injury, pro-ducing inflammatory markers and contribute to the development of chronic pain, even after the resolution of the original insult. While the underlying mechanism is still being explored, recent studies explored the efficacy of DRG stimulation and neuromodu-lation for chronic pain treatment. Results: Several reported cases and a small number of randomized trials were published in recent years, describing different meth-ods of DRG stimulation and neuromodulation with promising results. Though evidence quality is mostly low, these results provide evidence to support the utilization of this technique. Conclusions: Chronic neuropathic pain is a common condition and carries significant morbidity and impact on the quality of life. Recent evidence supports the use of DRG neuromodulation as an effective technique to control chronic pain. Though studies are still emerging, the evidence appears to support this technique. Further studies, including large randomized trials evaluating DRG modulation versus other interventional and non-interventional techniques, are needed to further elucidate the efficacy of this method. These studies are also likely to inform the patient selection and the course of treatment. © 2021, Author(s)

Carpal tunnel release surgery- a systematic review of open and endoscopic approaches

Context: Carpal tunnel syndrome (CTS) is the most frequent peripheral compression-induced neuropathy observed in patients worldwide. Surgery is necessary when conservative treatments fail and severe symptoms persist. Traditional Open carpal tunnel release (OCTR) with visualization of carpal tunnel is considered the gold standard for decompression. However, Endoscopic carpal tunnel release (ECTR), a less invasive technique than OCTR is emerging as a standard of care in recent years. Evidence Acquisition: Criteria for this systematic review were derived from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two review authors searched PubMed, MEDLINE, and the Cochrane Database in May 2018 using the following MeSH terms from 1993-2016: �carpal tunnel syndrome,' �median nerve neuropathy,' �endoscopic carpal tunnel release,' �endoscopic surgery,' �open carpal tunnel release,' �open surgery,' and �carpal tunnel surgery.' Additional sources, including Google Scholar, were added. Also, based on bibliographies and consultation with experts, appropriate publications were identified. The primary outcome measure was pain relief. Results: For this analysis, 27 studies met inclusion criteria. Results indicate that ECTR produced superior post-operative pain outcomes during short-term follow-up. Of the studies meeting inclusion criteria for this analysis, 17 studies evaluated pain as a primary or secondary outcome, and 15 studies evaluated pain, pillar tenderness, or incision tenderness at short-term follow-up. Most studies employed a VAS for assessment, and the majority reported superior short-term pain outcomes following ECTR at intervals ranging from one hour up to 12 weeks. Several additional studies reported equivalent pain outcomes at short-term follow-up as early as one week. No study reported inferior short-term pain outcomes following ECTR. Conclusions: ECTR and OCTR produce satisfactory results in pain relief, symptom resolution, patient satisfaction, time to return to work, and adverse events. There is a growing body of evidence favoring the endoscopic technique for pain relief, functional outcomes, and satisfaction, at least in the early post-operative period, even if this difference disappears over time. Several studies have demonstrated a quicker return to work and activities of daily living with the endoscopic technique. © 2020, Author(s)

Fat and carbohydrate metabolism during and following hemorrhagic shock in puppies: A comparison of different resuscitation protocols

Shock states continue to carry a high mortality rate in the pediatric age group. Using a puppy model, we measured the initial metabolic response to hemorrhagic shock and to 3 resuscitation regimens: whole blood 1∶1 (replacement∶shed), lactated Ringer's 3∶1, and 5% albumin in lactated Ringer's 1∶1. Despite the immature nature of the puppy's enzyme, cardiovascular, and nervous systems, responses very similar to those in adult animals were seen. Serum glucose and free fatty acids rose during shock and declined with resuscitation as cardiac output returned toward normal. Serum lactate levels rose similarly but continued to rise for a short period after resuscitation and were associated with a further fall in pH consistent with “hidden acidosis.” Only small changes were noted in triglyceride and cholesterol levels. The metabolic responses noted following each of the 3 resuscitation protocols were similar. This study suggests that the immature animal responds to hemorrhagic shock in ways similar to the adult. The better initial hemodynamic response to resuscitation with high-volume lactated Ringer's or lactated Ringer's with 5% albumin was offset by the better buffering capacity of blood resuscitation. All 3 regimens were equally efficacious in providing initial metabolic recovery in this experimental hemorrhagic shock model. Les états de choc s'accompagnent d'une mortalité élevée chez les enfants. En ayant recours à l'expérimentation chez le chiot, les auteurs ont mesuré les modifications métaboliques initiales en réponse au choc hémoragique et à sa correction par 3 agents différents: sang complet (1∶1), solution de Ringer (3∶1) et solution de Ringer enrichie de 5% d'albumine. Malgré la nature immature des enzymes du chiot, du système cardio-vasculaire et du système nerveux, les réponses furent identiques à celles observées chez le chien adulte. Le glucose et les acides gras libres s'élevèrent au cours du choc et s'abaissèrent lors de la réanimation dès que le débit cardiaque revint à la normale. Les niveaux du lactate sanguin s'élevèrent de la même manière mais l'élévation continua pendant une courte période après la réanimation, cependant que le pH s'abaissait, démasquant une “acidose cachée”. Les taux des triglycérides et du cholestérol furent seulement discrètement altérés. Les réponses métaboliques étudiées en fonction des 3 méthodes de réanimation furent identiques. Cette étude suggère que le chiot répond de la même façon que le chien adulte au choc hémorragique et que les 3 méthodes de réanimation employant chacune des agents différents ont une efficacité identique. Los estados shock mantienen una elevada mortalidad en los grupos de edad pediátrica. Utilizando un modelo de shock en cachorros, se determinó la respuesta metabólica inicial al shock hemorrágico y a tres diferentes regimenes de resucitación: sangre total 1∶1 (reemplazo: pérdida), lactato de Ringer 3∶1, y albúmina al 5% en lactato de Ringer 1∶1. A pesar de la naturaleza inmadura de los sistemas enzimático, cardiovascular y nervioso del cachorro, las respuestas fueron muy similares a las observadas en animales adultos. La glucosa sérica y los ácidos grasos libres ascendieron durante el shock y declinarion en la medida que el débito cardiaco retornaba a lo normal. Los niveles de lactato sérico ascendieron en forma similar, pero continuaron su ascenso por un corto periodo de tiempo después de la resucitación, encontrándose asociados con una caida adicional del pH consistente con “acidosis oculta”. Sólo se presentaron cambios leves en los niveles de triglicéridos y colesterol. Las respuestas metabólicas observadas en cada uno de los tres protocolos de resucitación fueron similares. Este estudio sugiere que el animal inmaduro responde al shock hemorrágico de manera similar al adulto. La mejor respuesta hemodinámica inicial a la resucitación con altos volúmenes de lactato de Ringer o con lactato de Ringer con albúmina al 5%, fue compensada con una mejor capacidad de amortiguación observada en la resucitación con sangre. Los tres regimenes fueron igualmente eficaces en lograr la recuperación metabólica inicial en este modelo experimental de shock hemorrágico.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41311/1/268_2005_Article_BF01655348.pd

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes