Long-term safety and tolerability of bimagrumab (BYM338) in sporadic inclusion body myositis.

OBJECTIVE: To assess the long-term safety and tolerability and to monitor benefits of extended use of bimagrumab in individuals with sporadic inclusion body myositis (sIBM) who completed a single-dose core study. METHODS: In this multicenter, open-label extension study, 10 adults received bimagrumab 10 mg/kg IV every 4 weeks up to 2 years (104 weeks). Safety (primary endpoint) was assessed by recording adverse events (AEs). Clinical benefits were assessed by changes from baseline in thigh muscle volume (TMV), lean body mass (LBM), 6-minute walk distance (6MWD), handgrip, and quadriceps strength. RESULTS: Participants had a mean age of 70.1 (SD 10.4) years. All participants (n = 10) discontinued the treatment due to early termination of the study (n = 7) or AEs (n = 3; myocardial infarction, esophageal carcinoma, and dementia, none of which were treatment related). The most common AEs were muscle spasms and falls (both 9 of 10, 90%), followed by diarrhea (6 of 10, 60%) and acne and skin eruption (both 5 of 10, 50%). At weeks 8 and 16, mean TMV increased from baseline by 4.1% (SD 4.3%) and 4.5% (SD 6.3%). Mean LBM increased from baseline and was sustained at 6.9% (SD 3.9%) at week 76. Means of 6MWD showed a progressive decline from baseline to week 76, during which there was a modest numerical increase in handgrip strength and no significant changes in quadriceps strength. CONCLUSIONS: Long-term treatment up to 2 years with bimagrumab had a good safety profile and was well tolerated in individuals with sIBM. An increase in muscle mass was noted on a group level; however, there was no evidence of clinical improvement. CLINICALTRIALSGOV IDENTIFIER: NCT02250443. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with sIBM, long-term bimagrumab treatment was safe and well tolerated and did not lead to functional improvement.

Ethical Issues in the Neurology of Pregnancy.

Decision making for pregnant women and fetuses who suffer brain injuries is emotionally difficult and conceptually challenging. Occasionally, both the pregnant woman and the fetus have suffered an injury that confers a poor neurological prognosis, and decisions about one of them will have implications for the other-making the process of decision making even more problematic. In this article, decision-making standards and principles are reviewed for both pregnant women and fetuses, using a real case from the author's institution. Practical suggestions are made regarding deliberative processes and consultative models that can help with these difficult cases.

Ethics of Preclinical Dopamine Transporter Imaging.

While dopamine transporter single-photon emission computed tomography (DAT-SPECT) imaging is sensitive and specific when performed in patients with signs or symptoms of parkinsonism, its predictive value is uncertain in healthy subjects, even with patients who have first-degree relatives affected by Parkinson disease. In deciding whether to honor a patient's request for a DAT-SPECT, neurologists must balance a patient's autonomy rights with beneficence and nonmaleficence and also consider the distributive justice implications of ordering the test. Generally speaking, the benefits of a DAT-SPECT will be too small to justify its use in an asymptomatic patient concerned about developing Parkinson disease.

Withdrawing and withholding life-sustaining treatment.

The ethics of decisions to withhold or withdraw life-sustaining therapies are reviewed. Special attention is paid to the ethical and moral distinctions - or lack thereof - between withholding and withdrawing. The ethical principles informing decisions to forgo life-sustaining therapy are covered, along with the difficulty of making such decisions in the face of prognostic uncertainty. Specific advice is provided regarding the decision-making process, and recent literature regarding decision-making in the neurologic intensive care unit is reviewed.

Off-protocol access to study therapies.

The ethics of allowing off-protocol access to a study therapy are explored, using the example of recombinant factor VIIa for intracerebral hemorrhage. rVIIa was later found to be ineffective. While the studies were being performed, researchers struggled with the question of whether a critically ill patient with intracerebral hemorrhage was actually indifferent between the treatment and placebo arms of the trial.

Variability in the Perception of Informed Consent for IV-tPA during Telestroke Consultation.

OBJECTIVE: To study the perception of informed consent among various raters for thrombolysis in acute ischemic stroke patients receiving intravenous tissue plasminogen activator (IV-tPA). METHODS: Twenty randomly selected videotaped telestroke consultations of acute stroke patients administered IV-tPA were retrospectively reviewed. Adequacy of informed consent was reviewed by five raters: a neurologist and emergency physician who routinely treat stroke, a medical risk management paralegal, a bioethicist, and a lay person. Raters assessed the quality of the informed consent presentation by the treating physician and the degree of understanding demonstrated by the patient/family authorizing consent. Factors associated with adequacy of consent were analyzed. RESULTS: Consent was rated as adequately understood by the patient-family in 78.6% cases. Agreement between all five raters with regard to the patient-family understanding of consent was poor and also between the subgroups of non-physician and physician (all k < 0.20). Similarly, the quality of the physician consent process was poor for agreement between all five raters (k = 0.07) or between the subgroup of the three non-physician raters (k = -0.06) and fair between the two physician raters (k = 0.24). The legal reviewer and the bioethicist rated the physician consent process as being of lower quality than did the two physicians and the layperson. CONCLUSION: Despite high variability in the perception of informed consent among raters in this time-sensitive clinical situation, almost 80% of patients were rated by all reviewers as having adequate understanding of risks and benefits of tPA. This suggests the need for a standardized but brief tPA consent process that includes patient/family demonstration of understanding.

Unnecessary time pressure in refusal of life-sustaining therapies: fear of missing the opportunity to die.

During an illness requiring brief use of life-sustaining therapy (LST), patients and surrogates sometimes feel that LST must be withdrawn before it becomes unnecessary to avoid later being stuck living in a debilitated condition that the patient considers worse than death. This fear depends on the belief that the patient can legitimately refuse only artificial LST, so that if such therapies are no longer required, he or she will have missed the 'opportunity to die.' This fear of being stuck with life can lead to premature decisions to terminate LST and is unfounded because adequate ethical and moral justification exists for refusal of not just artificial LST, but also for refusal of natural LST, including oral hydration and nutrition.

Cervical myelopathy caused by retrograde intraneural dissection of anesthetic solution.

Brachial plexus block is a generally safe procedure for postoperative analgesia following shoulder surgery. This report describes brachial plexus block complicated by intraneural dissection of anesthetic solution, resulting in severe damage to the upper spinal cord. Other investigators have hypothesized that this rare complication is caused by accidental needle placement within the substance of the cord. This case demonstrates that the complication can occur despite a peripherally located needle.