Outcomes of transcutaneous nerve stimulation for migraine headaches: a systematic review and meta-analysis.

BACKGROUND: Implanted and transcutaneous nerve stimulators have shown promise as novel non-pharmacologic treatment for episodic and chronic migraines. The purpose of this study was to summarize the reported efficacy of transcutaneous single nerve stimulators in management of migraine frequency and severity. METHODS: A systematic review of five databases identified studies treating migraines with transcutaneous stimulation of a single nerve. Random effects model meta-analyses were conducted to establish the effect of preventive transcutaneous nerve stimulation on headache days per month and 0-10 numeric rating scale pain severity of headaches for both individuals with episodic and chronic migraines. RESULTS: Fourteen studies, which treated 995 patients, met inclusion criteria, including 7 randomized controlled trials and 7 uncontrolled clinical trials. Transcutaneous nerve stimulators reduced headache frequency in episodic migraines (2.81 fewer headache days per month, 95% CI 2.18-3.43, I2 = 21%) and chronic migraines (2.97 fewer headache days per month, 95% CI 1.66-4.28, I2 = 0%). Transcutaneous nerve stimulators reduced headache severity in episodic headaches (2.23 fewer pain scale points, 95% CI 1.64-2.81, I2 = 88%). CONCLUSIONS: Preventive use of transcutaneous nerve stimulators provided clinically significant reductions in headache frequency in individuals with chronic or episodic migraines. Individuals with episodic migraines also experienced a reduction in headache pain severity following preventive transcutaneous nerve stimulation.

Cryptogenic Intracranial Hemorrhagic Strokes Associated with Hypervitaminosis E and Acutely Elevated α-Tocopherol Levels.

OBJECTIVES: Up to 41% of intracerebral hemorrhages (ICH) are considered cryptogenic despite a thorough investigation to determine etiology. Certain over-the-counter supplements may increase proclivity to bleeding, and we hypothesize that specifically vitamin E may have an association with ICH and acutely elevated serum levels of α-tocopherol. Our aim is to report 3 cases of recently admitted patients with hypervitaminosis E and otherwise cryptogenic ICH. METHODS: At our institution between January and December 2018, 179 patients were admitted with ICH with 73 imputed to be "cryptogenic" (without clear etiology as per Structural vascular lesions, Medication, Amyloid angiopathy, Systemic disease, Hypertension, or Undetermined and Hypertension, Amyloid angiopathy, Tumor, Oral anticoagulants, vascular Malformation, Infrequent causes, and Cryptogenic criteria). Of these, we found 3 (4.1%) clearly admitted to consistent use of vitamin E supplementation for which α-tocopherol levels were checked. We describe the clinical presentation and course of these patients and their etiologic and diagnostic evaluations including neuroimaging and α-tocopherol laboratory data. RESULTS: All patients in this series were consistently consuming higher than recommended doses of vitamin E and developed acute ICH. The first 2 patients both had subcortical (thalamic) intraparenchymal hemorrhages while the third had an intraventricular hemorrhage. Serum α-tocopherol levels in patient A, B, and C were elevated at 30.8, 46.7, and 23.3 mg/L, respectively (normal range 5.7-19.9 mg/L) with a mean of 33.6 mg/L. No clear alternate etiologies to their ICH could be conclusively determined despite thorough workups. CONCLUSIONS: In patients with cryptogenic ICH, clinicians should consider hypervitaminosis E and check serum α-tocopherol level during admission. Reviewing the patient's pharmacologic history, including over-the-counter supplements such as vitamin E, may help identify its association, and its avoidance in the future may mitigate risk. With its known vitamin K antagonism, hypo-prothrombinemic effect, cytochrome p-450 interaction, and antiplatelet activity, vitamin E may not be as benign as presumed. Its consumption in nonrecommended doses may increase ICH risk, which may be underestimated and under-reported.