Conscientious Objection to Aggressive Interventions for Patients in a Vegetative State.

Some physicians refuse to perform life-sustaining interventions, such as tracheostomy, on patients who are very likely to remain permanently unconscious. To explain their refusal, these clinicians often invoke the language of "futility", but this can be inaccurate and can mask problematic forms of clinical power. This paper explores whether such refusals should instead be framed as conscientious objections. We contend that the refusal to provide interventions for patients very likely to remain permanently unconscious meets widely recognized ethical standards for the exercise of conscience. We conclude that conscientious objection to tracheostomy and other life-sustaining interventions on such patients can be ethical because it does not necessarily constitute a form of invidious discrimination. Furthermore, when a physician frames their refusal as conscientious objection, it makes transparent the value-laden nature of their objection and can better facilitate patient access to the requested treatment.

When Respecting Autonomy Is Harmful: A Clinically Useful Approach to the Nocebo Effect.

Nocebo effects occur when an adverse effect on the patient arises from the patient's own negative expectations. In accordance with informed consent, providers often disclose information that results in unintended adverse outcomes for the patient. While this may adhere to the principle of autonomy, it violates the doctrine of "primum non nocere," given that side-effect disclosure may cause those side effects. In this article we build off previous work, particularly by Wells and Kaptchuk ( 2012 ) and by Cohen ( 2013 ), to suggest ethical guidelines that permit nondisclosure in the case when a nocebo effect is likely to occur on of the basis of nonmaleficence. We accept that that autonomy vis-à-vis informed consent must be forestalled, but salvage much of its role by elaborating a practical clinical approach to postencounter follow-up. In doing so, we reconcile a clinically practicable process of determining conditions of disclosure with long-standing ethical commitments to patients.

Pathogenesis underlying hexanucleotide repeat expansions in C9orf72 gene in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder. Mutations in C9orf72 and the resulting hexanucleotide repeat (GGGGCC) expansion (HRE) has been identified as a major cause of familial ALS, accounting for about 40 % of familial and 6 % of sporadic cases of ALS in Western patients. The pathological outcomes of HRE expansion in ALS have been recognized as the results of two mechanisms that include both the toxic gain-of-function and loss-of-function of C9ORF72. The gain of toxicity results from RNA and dipeptide repeats (DPRs). The HRE can be bidirectionally transcribed into RNA foci, which can bind to and disrupt RNA splicing, transport, and translation. The DPRs that include poly-glycine-alanine, poly-glycine-proline, poly-glycine- arginine, poly-proline-alanine, and poly-proline-arginine can induce toxicity by direct binding and sequestrating other proteins to interfere rRNA synthesis, ribosome biogenesis, translation, and nucleocytoplasmic transport. The C9ORF72 functions through binding to its partners-Smith-Magenis chromosome regions 8 (SMCR8) and WD repeat-containing protein (WDR41). Loss of C9ORF72 function results in impairment of autophagy, deregulation of autoimmunity, increased stress, and disruption of nucleocytoplasmic transport. Further insight into the mechanism in C9ORF72 HRE pathogenesis will facilitate identifying novel and effective therapeutic targets for ALS.

Targeting neuroinflammation in distal symmetrical polyneuropathy in diabetes.

Diabetic distal symmetric polyneuropathy is the most common type of peripheral neuropathy complication of diabetes mellitus. Neuroinflammation is emerging as an important contributor to diabetes-induced neuropathy. Long-term hyperglycemia results in increased production of advanced glycation end products (AGEs). AGEs interact with their receptors to activate intracellular signaling, leading to the release of various inflammatory cytokines. Increased release of inflammatory cytokines is associated with diabetes, diabetic neuropathy, and neuropathic pain. Thus, anti-inflammatory intervention is a potential therapy for diabetic distal symmetric polyneuropathy. Further characterization of inflammatory mechanisms might identify novel therapeutic targets to mitigate diabetic neuropathy.

A Simulation to Improve Understanding and Communication of Ethical Dilemmas That Surround Brain Death.

Introduction: Providers across multiple specialties may be called upon to perform brain death assessments at hospitals that lack specialty neurology or critical care services. To address this need, we developed a brain death curriculum involving simulation and group discussion to prepare medical trainees for brain death testing and communication with surrogate decision-makers. Methods: A 1-hour session was delivered to trainees rotating through the intensive care unit at William Beaumont University Hospital. One trainee per session participated in a simulation involving a brain-dead patient (SimMan 3G Mannequin) and spouse (confederate) while the remainder of the cohort observed from a separate room. The trainee briefed the spouse about the brain death examination, performed the examination, and communicated their findings. Afterward, the cohort discussed the history, law, and common ethical and communication issues that surround brain death. Results: A total of 35 trainees participated from August 2022 to March 2023. After the session, trainees were more comfortable performing brain death testing (p < .001), responding to ethical issues (p < .001), and communicating with families (p < .001). However, the session did not change their frustration with family members who have a circulatory (p = .72) or high brain (p = .52) view of death. Discussion: The simulation had a positive impact on medical trainees' ability to perform brain death testing and their comfort level in discussing complex ethical issues that surround brain death. Our results support continued simulation training for medical trainees to better prepare them for clinical practice.

Novel strategy: Identifying new markers for demyelination in diabetic distal symmetrical polyneuropathy.

Objective: To develop a novel strategy for identifying acquired demyelination in diabetic distal symmetrical polyneuropathy (DSP). Background: Motor nerve conduction velocity (CV) slowing in diabetic DSP exceeds expectations for pure axonal loss thus implicating superimposed acquired demyelination. Methods: After establishing demyelination confidence intervals by regression analysis of nerve conduction data from chronic inflammatory demyelinating polyneuropathy (CIDP), we prospectively studied CV slowing in 90 diabetic DSP patients with and without at least one motor nerve exhibiting CV slowing (groups A and B) into the demyelination range by American Academy of Neurology (AAN) criteria respectively and 95 amyotrophic lateral sclerosis (ALS) patients. Simultaneously, secretory phospholipase A2 (sPLA2) activity was assessed in both diabetic groups and 46 healthy controls. Results: No ALS patient exhibited CV slowing in more than two motor nerves based on AAN criteria or the confidence intervals. Group A demonstrated a significantly higher percentage of patients as compared to group B fulfilling the above criteria, with an additional criterion of at least one motor nerve exhibiting CV slowing in the demyelinating range and a corresponding F response in the demyelinating range by AAN criteria (70.3 % vs. 1.9 %; p < 0.0001). Urine sPLA2 activity was increased significantly in diabetic groups as compared to healthy controls (942.9 ± 978.0 vs. 591.6 ± 390.2 pmol/min/ml, p < 0.05), and in group A compared to Group B (1328.3 ± 1274.2 vs. 673.8 ± 576.9 pmol/min/ml, p < 0.01). More patients with elevated sPLA2 activity and more than 2 motor nerves with CV slowing in the AAN or the confidence intervals were identified in group A as compared to group B (35.1 % vs. 5.7 %, p < 0.001). Furthermore, 13.5 % of patients in diabetic DSP Group A, and no patients in diabetic DSP Group B, fulfilled an additional criterion of more than one motor nerve with CV slowing into the demyelinating range with its corresponding F response into the demyelinating range by AAN criteria. Conclusion: A combination of regression analysis of electrodiagnostic data and a urine biological marker of systemic inflammation identifies a subgroup of diabetic DSP with superimposed acquired demyelination that may respond favorably to immunomodulatory therapy.

The clinical neurophysiology of COVID-19-direct infection, long-term sequelae and para-immunization responses: A literature review.

The COVID-19 pandemic resulting from the SARS-CoV-2 virus is in its third year. There is continuously evolving information regarding its pathophysiology and its effects on the nervous system. Clinical neurophysiology techniques are commonly employed to assess for neuroanatomical localization and/or defining the spectrum of neurological illness. There is an evolving body of literature delineating the effects of the SARS-CoV-2 virus on the nervous system as well as para-immunization responses to vaccination against this virus. This review focuses on the use of neurophysiological diagnostic modalities in the evaluation of potential acute and long-term neurological complications in patients that experience direct infection with SARS-CoV-2 and analyzes those reports of para-immunization responses to vaccination against the SARS-CoV-2 virus. The neurophysiological modalities to be discussed include electroencephalography (EEG), evoked potentials (EPs), nerve conduction studies and electromyography (EMG/NCV), autonomic function tests, transcranial magnetic stimulation (TMS) and Transcranial Doppler ultrasound (TCD).

Incomplete Anterior Spinal Artery Syndrome Responsive to Intrathecal Baclofen.

Anterior cord syndrome (ACS) occurs as a result of ischemia in the territory of the anterior spinal artery (ASA). Although spinal cord strokes are rare, the ASA is the most commonly affected vessel in the spinal cord. The typical presentation of an ASA stroke is paraparesis or paraplegia, bilateral loss of pain and temperature sensation, and fecal or urinary incontinence; the underlying neural structures responsible for these symptoms include the corticospinal tracts and anterior horns, anterolateral spinothalamic tracts, and lateral horns, respectively. ACS is a feared complication of aortic procedures and has been well-documented to occur during or after endovascular abdominal aortic aneurysm revascularization (EVAR). We report a case of incomplete or partial ACS presenting with delayed-onset spasticity and instability several months following EVAR, who was subsequently treated with intrathecal baclofen. We hypothesize that this patient's ischemia selectively damaged descending white matter tracts responsible for modulating the stretch receptor reflex, including damage to the corticospinal tract, which likely also impaired positional stability.

Neonatal Fc Receptor Inhibitor Therapeutics in Neuromuscular Disease.

ABSTRACT: The Neonatal Fc Receptor (FcRn) is integral to a wide variety of processes including IgG recycling, serum albumin turnover, and bacterial opsonization. Thus, targeting FcRn will increase antibody degradation including pathogenic IgGs. FcRn inhibition provides a novel therapeutic mechanism by which autoantibody titers are reduced resulting in clinical improvement and disease abatement. The FcRn targeting mechanism is similar to that of intravenous immunoglobulin (IVIg) in which saturated FcRn facilitates accelerated pathogenic IgG degradation. Recently, the FcRn inhibitor efgartigimod was approved for the treatment of myasthenia gravis. Subsequently, clinical trials of this agent have been conducted for numerous inflammatory conditions involving pathogenic autoantibodies. These disorders include the Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, and inflammatory myositis. Other disorders traditionally treated with IVIg may also benefit from FcRn inhibition in certain contexts. This manuscript discusses the mechanism of FcRn inhibition, preclinical data, and the results of clinical trials of this agent for a wide range of neuromuscular diseases.

Guillain-Barré syndrome after H1N1 vaccination in the United States: a report using the CDC/FDA Vaccine Adverse Event Reporting System (2009).

BACKGROUND: Although the Guillain-Barré syndrome (GBS) can be associated with the seasonal influenza vaccine, there is no definite evidence that GBS is associated with H1N1 influenza vaccination. The objective of this report is to study the occurrence and characteristics of GBS after H1N1 vaccine administration in the United States in 2009. METHODS: Data were acquired from the Vaccine Adverse Event Reporting System and supplemented by additional information obtained from the Center for Biologics Evaluation and Research, under the Federal Freedom of Information Act. RESULTS: A total of 62 individuals (mean age 46.51 ± 22.41 years), 33 of whom were men, developed GBS associated with the H1N1 influenza vaccination in 2009. Sixty GBS cases were reported within 6 weeks after vaccination, with 31 cases (50.0%) reported in the first 2 weeks. The estimated rate of occurrence of GBS was 6.2 cases per 10 million vaccinations, which is comparable to the rate of GBS in the general population. CONCLUSION: The higher rate of GBS reports in the first 6 weeks after H1N1 vaccination suggests that some GBS cases may be triggered by H1N1 vaccination. This warrants early recognition, treatment, and active surveillance in the postvaccination setting.

Atypical presentation of Creutzfeldt-Jakob disease: a rare but important cause of rapidly progressive dementia.

We report an atypical presentation of sporadic Creutzfeldt-Jakob disease (CJD) in a 74-year-old woman that illustrates the difficulty in diagnosing this rare, but important, cause of rapidly progressive dementia. Despite well-established criteria, this diagnosis is often missed or substantially delayed (Table 1). In this case, a precipitous cognitive decline associated with a urinary tract infection initiallysuggested delirium. Although atypical CJD was considered as a cause when symptoms persisted, a definitive diagnosis was established postmortem when the cerebrospinal fluid (CSF) prion protein 14-3-3 tested positive. Creutzfeldt-Jakob disease must be considered in the differential diagnosis of rapidly progressive dementia as Connecticut accounts for approximately three of the more than 200 cases diagnosed nationally.

Needle EMG muscle identification: A systematic approach to needle EMG examination.

The proper performance of needle electromyography (EMG) requires that the examiner obtain a brief but comprehensive history, perform a directed examination and generate a short differential diagnosis as part of the initial patient encounter. Equally as important is to set reasonable expectations for this study's performance as electronic media do not necessarily portray all of the nuances of an electrodiagnostic study. In addition to these preliminary steps, this minimonograph discusses equipment used in EMG evaluations, EMG examination techniques, muscles commonly sampled, pain reduction techniques, and special considerations that may require study modification such as anticoagulation, lymphedema, obesity and supervening infection. Clinicians performing these studies will maximize useful data collection while minimizing patient discomfort if all of these recommendations are followed.

Neurologic and neuroscience education: Mitigating neurophobia to mentor health care providers.

Neurologic disorders are among the most frequent causes of morbidity and mortality in the United States. Moreover, the current shortfall of neurologists is expected to worsen over the coming decade. As a consequence, many patients with neurologic disorders will be treated by physicians and primary care providers without formal neurologic training. Furthermore, a pervasive and well-described fear of neurology, termed neurophobia, has been identified in medical student cohorts, residents, and among general practitioners. In this article, members of the American Academy of Neurology A.B. Baker Section on Neurological Education review current guidelines regarding neurologic and neuroscience education, contextualize the genesis and the negative consequences of neurophobia, and provide strategies to mitigate it for purposes of mentoring future generations of health care providers.

Nerve conduction studies and EMG in carpal tunnel syndrome: Do they add value?

This paper summarises the views of four experts on the place of neurophysiological testing (EDX) in patients presenting with possible carpal tunnel syndrome, in guiding their treatment, and in reevaluations. This is not meant to be a position paper or a literature review, and heterogeneous viewpoints are presented. Nerve conduction studies should be performed in patients presenting with possible carpal tunnel syndrome to assist diagnosis, and may need to be repeated at intervals in those managed conservatively. There is evidence that local corticosteroid injection is safe and effective for many patients, thereby avoiding or deferring surgical decompression. All patients should undergo EDX studies before any invasive procedure for CTS (injection or surgery). Needle EMG studies are not obligatory, but may be needed in those with severe disease and those in whom an alternate or concomitant diagnosis is suspected.

Murine central and peripheral nervous system transcriptomes: comparative gene expression.

The central and peripheral nervous systems exhibit significant embryological, morphological, and functional differences. Moreover, the pathology of most acquired and hereditary neurological diseases preferentially targets specific components of the nervous system. In order to test the hypothesis that central and peripheral neural transcriptomes show fundamental quantitative differences, Affymetrix GeneChip expression arrays were used to compare murine lumbar spinal cord (SC) and dorsal root ganglion (DRG) gene expression. As the crucial component of a novel technique to preserve RNA integrity, mice were perfusion-fixed with RNAlater before the SC and DRG were harvested. As per Affymetrix terminology, a total of 111 transcripts were present (P) on all DRG arrays, absent (A) on all SC arrays, and demonstrated at least 10-fold greater expression in DRG than in SC. Conversely, a total of 112 transcripts were present on all SC arrays, absent on all DRG arrays, and showed at least 10-fold greater expression in SC than in DRG. For a subset of transcripts, quantitative real-time RT-PCR was used to corroborate and validate microarray results. Among those genes enriched in DRG, many belonged to a few distinct functional classes: G-protein coupled receptor-protein signaling pathways, potassium transport, sodium transport, sensory perception, and cell-surface receptor-linked signal transduction. In contrast, genes associated with synaptic transmission, organic acid transport, neurotransmitter transport, and circulation were enriched in SC. Notably, the majority of genes causally associated with hereditary neuropathies were highly enriched in DRG. These differential neural gene expression profiles provide a robust framework for future molecular and genetic studies of neuropathy and SC diseases.

Undiagnosed patent foramen ovale presenting as a cryptogenic brain abscess: case report and review of the literature.

A 43-year-old man with no significant medical history but poor oral hygiene presented with fever and new-onset tonic-clonic seizures secondary to a left parieto-occipital brain abscess defined by computed tomography, magnetic resonance imaging, and surgical evacuation. A comprehensive workup looking for a source of infection was unremarkable including computed tomography of the chest, abdomen, and pelvis; blood cultures; and a tagged white blood cell scan. A transesophageal echocardiogram bubble study revealed the presence of a patent foramen ovale (PFO) but no other abnormalities. Culture of the material obtained at surgery revealed flora commonly found in the oropharynx that responded to antibiotic therapy. A review of the literature revealed three other cases in which a brain abscess from flora commonly found in the oropharynx was associated with a PFO. We hypothesize that the underlying mechanism is a significant bacterial load from poor dentition that enters the arterial circulation through a PFO and forms the nidus for a brain abscess. Surgical evacuation is the preferred method for diagnosis and initial treatment. If a brain abscess is identified without any adjacent source of infection, a recent head trauma, or a neurosurgical procedure, then a transesophageal echocardiogram is indicated to exclude a PFO. If a PFO is found, then hematogenous spread of flora normally found in the oropharynx through a right to left shunt should be suspected. Surgical evacuation followed by intravenous antibiotics specific to the identified organisms is warranted. Once the infection is eliminated, anatomic closure of the PFO with good oral hygiene practices may be the best course of action for preventing recurrences.

Subjective and objective outcomes of botulinum toxin type A treatment in vestibulodynia: pilot data.

OBJECTIVE: To collect pilot data on the efficacy of intramuscular botulinum toxin type A (BTX/A) injection into the levator ani muscles to relieve coital pain, reduce pelvic floor tension and instability, and reduce vestibular hyperalgesia in vestibulodynia. STUDY DESIGN: Two subjects meeting diagnostic criteria for vestibulodynia were treated with 20 units and 40 units of BTX/A at 12-week intervals. Outcomes included a visual analogue scale (VAS), weekly coital pain diaries, surface electromyography (sEMG) and a vulvar algesiometer. RESULTS: BTX/A modestly reduced coital pain in 1 patient and was ineffective in the other. Pelvic floor hypertonicity and variability were markedly reduced in both patients, but negligible changes occurred in vestibular hyperalgesia. The patient with greater pelvic floor tension had more of a reduction in diary-rated coital pain 2 weeks after the injection (29% vs. 9%) and on the VAS at 12 weeks (15% vs. 3%). CONCLUSION: BTX/A injections may be effective in reducing coital pain in vestibulodynia with levator ani tenderness but have little effect on vestibular allodynia. The relationship between pelvic floor hypertonicity and decreased coital pain suggests that vestibulodynia may be a variant of chronic regional pain syndrome. The dose and volume of BTX/A injected may be related to the degree of relief.

Pregnancy-related increases in sensory perception thresholds are not correlated with serum progesterone levels.

BACKGROUND: Why pregnant women require smaller doses of anesthetic agents still remains speculative. One hypothesis proposes that pregnancy raises sensory perception thresholds, perhaps through a progesterone-mediated effect. This study was undertaken in order to quantify any changes in sensory perception thresholds after parturition and to correlate these changes with the expected decrease in postpartum serum progesterone levels. METHODS: Nineteen gravid women scheduled to undergo an elective Cesarean section consented to participate. Sensory current perception threshold (CPT) testing was performed before and 7 days after an elective Cesarean section. CPT was defined as the minimum amount of constant current stimulation that can be reproducibly detected at a particular frequency. CPT values were determined on the distal phalanx of the nondominant index finger at 2000 Hz, 250 Hz, and 5 Hz monofrequency stimulation. Seven women permitted serum progesterone level determinations at the prepartum and the postpartum CPT testing sessions. RESULTS: Parturition resulted in a statistically significant decrease in the sensory CPT at all 3 frequencies tested, (p < 0.05). However, there was no significant correlation between the postpartum reduction in serum progesterone levels and the observed postpartum decrease in CPT for any frequency, (r < 0.5). CONCLUSIONS: CPTs are significantly reduced after parturition. However, this reduction does not appear to be significantly correlated with the reduction in serum progesterone levels.