Pak J Med Sci. 2024 Dec;40(12PINS Suppl):S99-S102. doi: 10.12669/pjms.40.12(PINS).10978.

ABSTRACT

Paragangliomas are slow-growing, extra-adrenal neuroendocrine tumors with rare intracranial presentation. Although benign, they can be locally aggressive tumors causing bone destruction and compression related symptoms. We report the case of a 19 years old, normotensive female who presented with headache and vertigo for the past six months. Her examination showed right-sided conductive hearing loss and signs of cranial nerve X, vagus nerve palsy. Neuroimaging revealed a lobulated, extra-axial mass measuring 5.4 x 4.2 x 6.8 cm in right cerebellopontine angle (CPA). Subtotal surgical resection was achievable. Histopathology was suggestive of benign, non-secretory paraganglioma. The diagnosis of primary CPA was reached after ruling out other sources of paraganglioma in abdomen, pelvis and thorax. Radiotherapy was advised on follow up visit with no new post-operative deficits seen. Primary CPA paraganglioma should be included in the list of differentials of CPA lesions. Surgical excision in the absence of preoperative embolization of paraganglioma can be successful.

PMID:39703956 | PMC:PMC11654659 | DOI:10.12669/pjms.40.12(PINS).10978

J Otolaryngol Head Neck Surg. 2024 Jan-Dec;53:19160216241301328. doi: 10.1177/19160216241301328.

ABSTRACT

BACKGROUND: Injury to the recurrent laryngeal nerve (RLN) and parathyroid glands (PGs) are the most common and serious complications during the transoral endoscopic thyroidectomy vestibular approach (TOETVA), and their exposure and protection are the most important factors affecting the operation time. Here, we report a novel anatomical landmark and surgical method to shorten the operative time and reduce the chance of injury to the RLN and PGs.

METHODS: According to the different exposure methods of the RLN, patients were divided into the experimental group (from top to bottom, E-group) and the comparison group (from outside to inside, C-group), and 1:1 propensity score-matching (PSM) was performed. The demographics, operative data, postoperative data, and postoperative complications were analyzed by comparing the 2 groups.

RESULTS: After PSM, a total of 206 patients were included. Except for tumor size, there were no significant differences between the 2 groups in terms of sex, age, body mass index, presence of Hashimoto’s thyroiditis, or extent of surgery. Compared with the C-group, the operative time, in minutes, of the E-group was significantly shorter (hemithyroidectomy with central neck dissection (CND), C = 111.81 ± 25.83 vs E = 100.52 ± 16.47, P = .002 and bilateral thyroidectomy with CND, C = 177.87 ± 36.61 vs E = 156.05 ± 25.60, P = .004), the exposure time, in minutes, of the RLN was reduced (hemithyroidectomy with CND, C = 23.31 ± 7.07 vs E = 11.41 ± 2.75, P < .001 and bilateral thyroidectomy with CND, C = 45.64 ± 14.84 vs E = 21.76 ± 5.57, P < .001). The rate of postoperative temporary PGs and RLN injuries were also reduced (transient hypoparathyroidism, C = 13% vs E = 4%, P = .023 and transient RLN palsy, C = 10% vs E = 2%, P = .017). In addition, the remaining parameters such as the amount of bleeding, number of lymph node metastases, postoperative hospital stay, visual analog scale pain score, recurrence rate, and other complication rates were not significantly different between the 2 groups.

CONCLUSION: It is safe and feasible to construct Thyroid-RLN Entry Triangle (Peng’s Triangle) for PGs and RLN protection in TOETVA. It is beneficial to shorten the operation time and reduce postoperative complications, both worthy of clinical promotion.

TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trial Registry (UIN: ChiCTR2300067673, https://www.chictr.org.cn) in accordance with the World Medical Association’s Declaration of Helsinki, 2013.

PMID:39704391 | DOI:10.1177/19160216241301328

Cytokine. 2024 Dec 19;186:156840. doi: 10.1016/j.cyto.2024.156840. Online ahead of print.

ABSTRACT

BACKGROUND: Acute liver injury is a common pathological feature of various clinical diseases, and prolonged liver damage can lead to fibrosis and even liver failure. Studies have reported that the vagus nerve can repair liver injury through the regulation of the cholinergic anti-inflammatory pathway. However, there is limited research on the regulation of interleukin-22 and its role in liver injury. This study aimed to investigate the regulatory effect of vagus nerve receptor α7nAChR on interleukin-22 and whether this regulatory axis can protect against liver injury.

METHODS: Rats and the human liver cell line L-02 were treated with carbon tetrachloride to simulate acute liver injury. The experimental groups were divided as follows: control group, model group, model + PNU282987 group, model + MLA group, and MLA group. After the intervention, blood samples, liver tissues, and cells were collected to assess liver function (AST, ALT), inflammation (TNF-α, IL-6,), α7nAChR and interleukin-22 concentrations, apoptosis levels (Bax, BCL-2), and proliferation markers (Ki-67, PCNA) using quantitative real time PCR, Western blot, immunohistochemistry and ELISA.

RESULTS: The results indicated that carbon tetrachloride intervention led to compensatory increases in interleukin-22 while inhibition of α7nAChR decreased interleukin-22 concentrations and exacerbated the injury marked by high levels of AST, ALT and TNF-α,IL-6. Exogenous administration of a vagus nerve agonist alleviated liver injury and was accompanied by an increase in interleukin-22 levels. In rescue experiments, simultaneous inhibition of vagus nerve receptors and administration of exogenous interleukin-22 reduced liver injury and significantly enhanced liver regeneration. Conversely, activation of vagus nerve receptors while inhibiting interleukin-22 aggravated liver injury.

CONCLUSION: This study confirms that vagus nerve receptor α7nAChR can promote liver regeneration and protect against carbon tetrachloride-induced liver injury by regulating interleukin-22.

PMID:39705885 | DOI:10.1016/j.cyto.2024.156840

Int J Surg Case Rep. 2024 Dec 17;126:110751. doi: 10.1016/j.ijscr.2024.110751. Online ahead of print.

ABSTRACT

INTRODUCTION AND IMPORTANCE: Cervical paragangliomas of the vagus nerve are tumors, of wich the nature and location make them extremely rare, representing only 0.012 % of cervical tumors.

CASE PRESENTATION: This article reports the case of a 64 year old patient, consulting for a latero-cervical mass associated with dysphonia, dysphagia, and repeated vagal syncopes, evolving for 10 months. The patient underwent surgical resection of the tumor and the carotid artery, with reconstruction by common carotid to internal carotid Polytetrafluoroethylene (PTFE) graft bypass. The patient recovered with no major postoperative complication.

CLINICAL DISCUSSION: Cervical paragangliomas of the vagus nerve present clinically as a slow-growing latero-cervical mass that damages the cranial pairs, manifesting by dysphonia, dysphagia, vagal syncope and hypertensive peaks. Imaging is a major step in the diagnosis, allowing better planning of the surgical procedure. Magnetic Resonance Imaging (MRI) is considered to be the benchmark imaging for the characterization of the tumor, but Computerised Tomography (CT) Scan, CT angiography and Doppler ultrasonography of Supra-aortic trunks keep an important place in the search of associated vascular lesions. Surgery remains the only curative treatment, but it faces many obstacles, including the difficulty of dissection of the cranial pairs and adjacent vascular structures (especially the carotid artery). The postoperative morbidity is heavy with difficult recovery. The place of radiotherapy is controversial.

CONCLUSION: Paragangliomas of the vagus in the cervical region are rare tumors, of which the localization is even rarer. Surgical excision remains the only curative treatment. Palliative radiotherapy may be considered for some patients.

PMID:39706144 | DOI:10.1016/j.ijscr.2024.110751

Expert Rev Neurother. 2024 Dec 20. doi: 10.1080/14737175.2024.2439512. Online ahead of print.

ABSTRACT

INTRODUCTION: The seizures in Lennox-Gastaut syndrome are typically resistant to treatment. Seven antiseizure medications (ASMs) in the US (six in the UK/EU) are licensed for the treatment of seizures in LGS: lamotrigine, topiramate, rufinamide, clobazam, felbamate (not licensed in the UK/EU), cannabidiol and fenfluramine. Other options include neurostimulation, corpus callosotomy and dietary therapies, principally the ketogenic diet and its variants. New treatments and therapeutic strategies are needed to improve management of both seizures and cognitive/behavioral comorbidities in LGS.

AREAS COVERED: Embase and Medline were searched for articles published between 1 January 2014 and 21 August 2024 reporting efficacy data for pharmacological, neurostimulation, surgical and dietary interventions in individuals with LGS focusing on recent advances. Ongoing and prospective studies were identified from the National Library of Medicine register of clinical trials.

EXPERT OPINION: LGS remains a difficult-to-treat epilepsy. Although no major breakthroughs have been reported, several established and novel ASMs, some surgical strategies and other treatment approaches are of benefit or are showing promise. Progress remains incremental but any improvements in the management of this resistant epilepsy syndrome are worthwhile.

PMID:39706228 | DOI:10.1080/14737175.2024.2439512

Brain Stimul. 2024 Dec 18:S1935-861X(24)01390-1. doi: 10.1016/j.brs.2024.12.1191. Online ahead of print.

ABSTRACT

BACKGROUND: Few treatments are available for individuals with marked treatment-resistant depression (TRD).

OBJECTIVE: Evaluate the safety and effectiveness of FDA-approved adjunctive vagus nerve stimulation (VNS) in patients with marked TRD.

METHODS: This 12-month, multicenter, double-blind, sham-controlled trial included 493 adults with marked treatment-resistant major depression who were randomized to active or no-stimulation sham VNS for 12 months. The primary outcome was percent time in response across months 3-12, with response defined as a ≥50 % change from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS). Several secondary endpoints were evaluated.

RESULTS: Overall, 88.4 % of participants completed the trial. Percent time in MADRS response did not distinguish active from sham VNS. However, ratings from on-site clinicians (Clinical Global Inventory-Impression [CGI-I]), patients (Quick Inventory of Depressive Symptomology-Self Report [QIDS-SR]), and offsite masked raters (Quick Inventory of Depressive Symptomology-Clinician [QIDS-C]) revealed antidepressant benefits significantly favoring active VNS. Active VNS demonstrated significantly more percent time in response on the CGI-I (P = 0.004) and QIDS-SR (P = 0.049), and significantly more percent time in partial response (PR; symptom improvement ≥30 %) on the CGI-I (P < 0.001) and QIDS-C (P = 0.006) versus sham VNS. Active VNS exceeded sham VNS in rate of dyspnea (P = 0.035), a known side effect of VNS. No new adverse events were identified.

CONCLUSIONS: Percent time in MADRS response did not distinguish the treatment groups, but on multiple instruments time in response and PR showed a positive treatment effect. VNS was found safe and effective in participants with marked TRD.

PMID:39706521 | DOI:10.1016/j.brs.2024.12.1191

Front Neurosci. 2024 Dec 4;18:1494272. doi: 10.3389/fnins.2024.1494272. eCollection 2024.

ABSTRACT

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by developmental impairments, inattention, motor hyperactivity, and impulsivity. Currently, there is no effective intervention that can completely cure it. One of the pathogenic mechanisms of ADHD involves abnormalities in the norepinephrine (NE) pathway within the prefrontal cortex (PFC). In recent years, transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive neuromodulation technique, has demonstrated promising potential in the treatment of neurological and psychiatric disorders. However, its application in the management of ADHD remains relatively unexplored. Previous studies have shown that taVNS exerts therapeutic effects on attention, cognition, arousal, perception, and behavioral regulation primarily through activating the vagus nerve conduction pathway, specifically targeting the nucleus tractus solitarius – locus coeruleus – NE pathway. These findings have led to the hypothesis that taVNS may be an effective intervention for ADHD, with NE and its pathway playing a pivotal role in this context. Therefore, this review comprehensively examines the correlation between NE pathway alterations in the PFC and ADHD, the mechanism of action of taVNS, and the potential role of the NE pathway in treating ADHD with taVNS, aiming to provide a theoretical foundation for clinical applications.

PMID:39697776 | PMC:PMC11652481 | DOI:10.3389/fnins.2024.1494272

Alzheimers Dement. 2024 Dec 19. doi: 10.1002/alz.14401. Online ahead of print.

ABSTRACT

INTRODUCTION: While there may be microbial contributions to Alzheimer’s disease (AD), findings have been inconclusive. We recently reported an AD-associated CD83(+) microglia subtype associated with increased immunoglobulin G4 (IgG4) in the transverse colon (TC).

METHODS: We used immunohistochemistry (IHC), IgG4 repertoire profiling, and brain organoid experiments to explore this association.

RESULTS: CD83(+) microglia in the superior frontal gyrus (SFG) are associated with elevated IgG4 and human cytomegalovirus (HCMV) in the TC, anti-HCMV IgG4 in cerebrospinal fluid, and both HCMV and IgG4 in the SFG and vagal nerve. This association was replicated in an independent AD cohort. HCMV-infected cerebral organoids showed accelerated AD pathophysiological features (Aβ42 and pTau-212) and neuronal death.

DISCUSSION: Findings indicate complex, cross-tissue interactions between HCMV and the adaptive immune response associated with CD83(+) microglia in persons with AD. This may indicate an opportunity for antiviral therapy in persons with AD and biomarker evidence of HCMV, IgG4, or CD83(+) microglia.

HIGHLIGHTS: Cross-tissue interaction between HCMV and the adaptive immune response in a subset of persons with AD. Presence of CD83(+) microglial associated with IgG4 and HCMV in the gut. CD83(+) microglia are also associated presence of HCMV and IgG4 in the cortex and vagal nerve. Replication of key association in an independent cohort of AD subjects. HCMV infection of cerebral organoids accelerates the production of AD neuropathological features.

PMID:39698934 | DOI:10.1002/alz.14401

Epilepsia Open. 2024 Dec 19. doi: 10.1002/epi4.13075. Online ahead of print.

ABSTRACT

Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy (DEE) characterized by multiple types of drug-resistant seizures (which must include tonic seizures) with classical onset before 8 years (although some cases with later onset have also been described), abnormal electroencephalographic features, and cognitive and behavioral impairments. Management and treatment of LGS are challenging, due to associated comorbidities and the treatment resistance of seizures. A panel of five epileptologists reconvened to provide updated guidance and treatment algorithms for LGS, incorporating recent advancements in antiseizure medications (ASMs) and understanding of DEEs. The resulting consensus document is based on current evidence from clinical trials and clinical practice and the panel’s expert opinion, focusing on new ASMs with novel mechanisms of action, such as highly purified cannabidiol and fenfluramine. For a patient presenting with newly diagnosed LGS or suspected LGS, the recommended first-line treatment continues to be valproate. If this is ineffective as monotherapy, adjunctive therapy with, firstly, lamotrigine and secondly, rufinamide, is recommended. If seizure control remains suboptimal, subsequent adjunctive ASM treatment options include (alphabetically) cannabidiol, clobazam, felbamate, fenfluramine, and topiramate, although evidence for these is more limited. Whenever possible, no more than two ASMs should be used together. Nonpharmacological treatment approaches should be used in conjunction with ASM therapy and include ketogenic diet therapies, vagus nerve stimulation, and corpus callosotomy. Patients with LGS that has evolved from another type of epilepsy who are not already being treated with valproate should be transitioned to valproate and then managed using the same algorithm as for newly diagnosed LGS. Older patients with established LGS should be reviewed at least annually by a suitably experienced neurologist. The revised guidance aims to improve seizure control and quality of life for patients with LGS through personalized, evidence-based treatment strategies while addressing the challenges of accurate diagnosis and management in a rapidly evolving therapeutic landscape. PLAIN LANGUAGE SUMMARY: Lennox-Gastaut syndrome (LGS) is a severe type of epilepsy that usually starts in childhood but continues into adulthood. It is characterized by a variety of different types of seizures (abnormal electrical activity in the brain), which are difficult to treat and often cause people with the condition to fall and injure themselves. Most people with LGS have learning difficulties and need a lot of support, often in residential care. The authors are experts in treating people with LGS and this article provides up-to-date guidance and advice on how best to care for those with the condition.

PMID:39700524 | DOI:10.1002/epi4.13075

Brain Stimul. 2024 Dec 18:S1935-861X(24)01382-2. doi: 10.1016/j.brs.2024.12.1187. Online ahead of print.

ABSTRACT

BACKGROUND: Depression treatments aim to minimize symptom burden and optimize quality of life (QoL) and psychosocial function.

OBJECTIVE: Compare the effects of adjunctive versus sham vagus nerve stimulation (VNS) on QoL and function in markedly treatment-resistant depression (TRD).

METHODS: In this multicenter, double-blind, sham-controlled trial, 493 adults with TRD and ≥4 adequate but unsuccessful antidepressant treatment trials (current episode) were randomized to active (n = 249) or sham (n = 244) VNS (plus treatment as usual) over a 12-month observation period. Quarterly outcomes included QoL with the Q-LES-Q, Mini-Q-LES-Q, and EQ-5D-5L, and function with the WHODAS 2.0 and Work Productivity and Activity Impairment Questionnaire (WPAI) item 6. Differences between treatment groups in change in scores from baseline and percentage of time with a meaningful response in Q-LES-Q, Mini-Q-LES-Q, and WPAI item 6 scores were analyzed.

RESULTS: Active VNS was superior to sham in mean change in scores from baseline in the Mini-Q-LES-Q (P = 0.050) and WPAI item 6 (health condition’s effect on regular activities [P = 0.050]) used as continuous variables, with a similar trend for Q-LES-Q (P = 0.061). Active VNS was superior to sham in time spent in clinically meaningful benefit (categorical analyses) using the Q-LES-Q (P = 0.029), Mini-Q-LES-Q (P = 0.011), and WPAI item 6 (P = 0.039). The WHODAS 2.0 (P = 0.304) and EQ-5D visual analog scale (P = 0.125) failed to reveal between-group differences.

CONCLUSION: Active VNS was superior to sham VNS in improving QoL and psychosocial function in patients with TRD. VNS has a broader therapeutic impact than symptom improvement alone in patients with marked psychosocial impairment.

PMID:39701918 | DOI:10.1016/j.brs.2024.12.1187