Papers by Gretchen Tietjen
Thrombosis Research, 2007
Introduction: Livedo reticularis (LR) refers to the violaceous netlike pattern of skin related to... more Introduction: Livedo reticularis (LR) refers to the violaceous netlike pattern of skin related to arteriopathy at the dermis-subcutis border. Livedo is associated with migraine, and among migraineurs, LR is more common in those with prior stroke. Other evidence of vascular perturbation in migraine comes from studies showing elevated von Willebrand factor (vWF). The purpose of this study is to evaluate global hemostasis in migraineurs, including the subset with LR, using a dynamic flow system simulating physiological conditions, and measuring vWF activity and antigen levels. Materials and methods: Patients with migraine were enrolled from the headache clinic and presence or absence of LR was noted. Age-matched healthy, non-migraine, LR-free individuals were recruited as controls. To evaluate hemostasis, we used the Clot Signature Analyzer (CSA) measuring platelet hemostasis time (PHT), collageninduced thrombus formation (CITF), and clot time (CT). vWF activity and vWF antigen levels were also measured. Results: The mean vWF activity level (142.7 vs. 103.4, p b 0.01) and antigen level (132.1 vs. 104.5, p b 0.05) were higher, and all three hemostasis parameters shorter in the episodic migraineurs than in the controls. The subset of migraineurs with LR had the highest vWF activity (155 F 59, p b 0.05) and vWF antigen (141 F 43, p b 0.05) levels, and the shortest PHT (3.7 F 1.6, p b 0.05). In this subset there was a significant inverse correlation between vWF activity and PHT (r = À 0.51, p = 0.01). Conclusions: For migraineurs, the differences from controls in vWF and PHT are most robust in the LR subset, with the inverse correlation suggesting that endothelial perturbation may be causally related to the response of the platelets.
Headache, Jul 1, 2009
Objective.— To evaluate efficacy and tolerability of a single, fixed‐dose tablet of sumatriptan 8... more Objective.— To evaluate efficacy and tolerability of a single, fixed‐dose tablet of sumatriptan 85 mg/naproxen sodium 500 mg (sumatriptan/naproxen sodium) vs placebo in migraineurs who had discontinued treatment with a short‐acting triptan because of poor response or intolerance.Background.— Triptan monotherapy is ineffective or poorly tolerated in 1 of 3 migraineurs and in 2 of 5 migraine attacks. In April, 2008, the Food and Drug Administration approved the combination therapy sumatriptan/naproxen sodium, developed specifically to target multiple migraine mechanisms. This combination product offers an alternative migraine therapy for patients who have reported poor response or intolerance to short‐acting triptans.Methods.— Two replicate, randomized, multicenter, double‐blind, placebo‐controlled, 2‐attack crossover trials evaluated migraineurs who had discontinued a short‐acting triptan in the past year because of poor response or intolerance. Patients were instructed to treat within 1 hour and while pain was mild.Results.— Patients (n = 144 study 1; n = 139 study 2) had discontinued an average of 3.3 triptans before study entry. Sumatriptan/naproxen sodium was superior (P < .001) to placebo for 2‐ through 24‐hour sustained pain‐free response (primary end point) (study 1, 26% vs 8%; study 2, 31% vs 8%) and pain‐free response 2 hours post dose (key secondary end point) (study 1, 40% vs 17%; study 2, 44% vs 14%). A similar pattern of results was observed for other end points that evaluated acute (2‐ or 4‐hour), intermediate (8‐hour), or 2‐ through 24‐hour sustained response for migraine (ie, pain and associated symptoms), photophobia, phonophobia, or nausea (with the exception of nausea 2 and 4 hours post dose). The percentage of patients with at least 1 adverse event (regardless of causality) was 11% with sumatriptan/naproxen sodium compared with 4% with placebo in study 1 and 9% with sumatriptan/naproxen sodium compared with 5% with placebo in study 2. Only 1 adverse event in 1 study was reported in ≥2% of patients after treatment with sumatriptan/naproxen sodium and reported more frequently with sumatriptan/naproxen than placebo: chest discomfort was reported in 2% of subjects in study 1, and no events met this threshold in study 2. No serious adverse events attributed to study medication were reported in either study.Conclusion.— In migraineurs who reported poor response to a short‐acting triptan, sumatriptan/naproxen sodium was generally well tolerated and significantly more effective than placebo in conferring initial, intermediate, and sustained efficacy for pain and migraine‐associated symptoms of photophobia and phonophobia.
NEJM Journal Watch, 2004
Triptans and ergot alkaloids are often prescribed for acute treatment of migraine headache, but t... more Triptans and ergot alkaloids are often prescribed for acute treatment of migraine headache, but their associations with vascular events are not well
Neurology, Apr 6, 2015
BACKGROUND: Prolonged rhythm monitoring of patients with cryptogenic stroke increases the chance ... more BACKGROUND: Prolonged rhythm monitoring of patients with cryptogenic stroke increases the chance of detecting paroxysmal atrial fibrillation (PAF), a known cause of stroke. OBJECTIVE: Our objective was to study the rate of PAF detection in cryptogenic stroke patients who were selected by stroke specialists for implantable cardiac monitoring (ICM). METHODS: With institutional review board approval, we retrospectively reviewed medical records of patients who underwent ICM (REVEAL or REVEAL LINQ) between May 2012 to September 2014 at a university hospital. Patients who had ICM for cryptogenic stroke or TIA diagnosed by board certified vascular neurologists were identified. Baseline demographics, risk factors, CHADS2 score, stroke distribution and location were recorded. Duration of arrhythmia and time to diagnosis were also recorded when significant PAF was found. Significant PAF was defined as an episode of irregular heart rhythm, without detectable P waves, lasting more than 15 seconds. RESULTS: Thirty-one patients were included in this analysis including 14 men (45.2[percnt]) and 17 (54.8[percnt]) women, mean age 66.1 (range 38-89). Twelve patients (38.7[percnt]) had previous strokes or TIAs and five (16.1[percnt]) had a patent foramen ovale. Thirty patients had cryptogenic strokes and one patient had a TIA. PAF was detected in 10 of 31 patients (32.3[percnt]). All patients had PAF for at least 2 minutes, mean time to detection was 57.1 days (median 52 days, IQR: 21-57). Bilateral strokes were present in 6 (19.4[percnt]) patients and 9 (29[percnt]) patients had strokes involving multiple vascular territories. Mean CHADS2 score for patients without PAF was 2.33 and with PAF was 2.7. All patients with PAF were asymptomatic and all patients were considered for anticoagulation after diagnosis. CONCLUSION: Long term cardiac monitoring with ICM has a very high yield of detecting PAF in cryptogenic stroke patients when selected by a stroke expert. Disclosure: Dr. Salahuddin has nothing to disclose. Dr. Zaidi has nothing to disclose. Dr. Tietjen holds stock and/or stock options in Johnson & Johnson and Stryker. Dr. Cummings has nothing to disclose. Dr. Jumaa has nothing to disclose.
Annals of Pharmacotherapy, Apr 1, 1994
To assess the risk of bleeding complications in patients treated with combination aspirin and hep... more To assess the risk of bleeding complications in patients treated with combination aspirin and heparin for cerebral ischemia. DESIGN: A retrospective, cohort study. SETTING: A large urban teaching hospital. PATIENTS: One hundred charts of stroke patients who had received anticoagulation with or without aspirin therapy were identified from the Stroke Data Bank. Bleeding rates were compared between the two groups. RESULTS: Forty-two patients who had received heparin and/or warfarin in combination with aspirin were compared with 33 patients who had received anticoagulation alone. The mean duration of anticoagulant therapy was 8.0 and 8.4 days, respectively. Bleeding rates were not different between the two groups: 23.8 percent (10/42) (p=O.78) and 24.2 percent (8/33), respectively. Although the bleeding rate was substantial, there was only one major bleed (severe epistaxis) occurring in a patient receiving anticoagulation only. No patient had an intracerebral hemorrhage. CONCLUSIONS: Our data suggest that combination antithrombotic therapy is safe in a controlled, inpatient setting.
Annals of Indian Academy of Neurology, 2012
dependent on artificial heating, ventilation and airconditioning (HVAC) systems. Indoor environme... more dependent on artificial heating, ventilation and airconditioning (HVAC) systems. Indoor environmental quality (IEQ) of artificially ventilated buildings tends to be problematic due to the continuous use of HVAC systems. [1] Additionally, improper operation and maintenance of HVAC systems results in contaminants and gases being circulated from one part of the system to another. IEQ is a measure of various indoor environmental parameters (IEPs) that include illuminance, temperature, sound level, relative humidity (RH), and presence of pollutants [such as volatile organic compound (VOC), particulate matter of less than or equal to 10 μm (PM 10)] and gases (such as carbon monoxide and carbon dioxide). [2] During the last three decades, investigators have reported a high prevalence of symptoms that are associated with poor IEQ among the occupants of artificially ventilated Access this article online Quick Response Code:
Neurology, Apr 10, 2018
Objective: not Applicable Background: Methadone has been widely used in the clinical practice for... more Objective: not Applicable Background: Methadone has been widely used in the clinical practice for pain management, leading to overdosing and abusing. Most of the literature support white matter changes in the cerebellum and brain stem. There has been one other case report that defined MRI periventricular white matter changes secondary to methadone ingestion. Here we will present a unique case of leukoencephalopathy resulting from Methadone overdose. Design/Methods: Case Report Results: 50 year old female who initially was found unresponsive at home after methadone overdose and was taken to the outside hospital where she was intubated and had a prolong hospital course and an MRI showed small foci of restricted diffusion near the vertex in the parasagittal regions. She was later discharged home in a stable condition. Three weeks later she came for a follow up where she was found to have headache, confusion, and blurry vision. She was unable to perform simple calculations and her delayed recall was 0/3. She scored a 20/30 on MOCA. All her blood work was negative. Repeat MRI brain showed diffuse and bilaterally symmetric increased T2 signal in the frontal, parietal, and occipital white matter representing toxic leukoencephalopathy. Conclusions: Methadone-induced toxic leukoencephalopathy has been a rare reported entity. No quantitative measures has been identified causing it. Diagnosis is clinical supported by Imaging that is similar to other causes of Toxic leukoencephalopathy. Treatment is supportive. Literature supports cerebellar swelling with subsequent development of acute hydrocephalus in methadone overdosing. All cases were seen in children less than 3. Our case is unique for which only one other case has been described. Disclosure: Dr Panjwani has nothing to disclose. Dr. Karim has nothing to disclose. Dr. Humayun has nothing to disclose. Dr. Tietjen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly and Company, Dr. Reddy9s Laboratories.
OBJECTIVE: To conduct a literature review evaluating potential risks associated with maternal exp... more OBJECTIVE: To conduct a literature review evaluating potential risks associated with maternal exposure to dihydroergotamine (DHE) during pregnancy. BACKGROUND: Pregnancy risk categories are assigned to US drugs based on evidence from animal and human studies. Current formulations of DHE and ergotamine have the same pregnancy risk category (X), although DHE has fewer vascular and uterine effects. DESIGN/METHODS: A MEDLINE/PubMed search was conducted to identify citations published from January 1945 to October 2011 and describing fetal outcomes associated with DHE or ergotamine use during pregnancy. Included were clinical research, case reports/series, database/retrospective reviews or studies, and articles identified through secondary searches of related articles and references that include primary authors. Study designs, treatment interventions, and outcomes were reviewed. RESULTS: Of 213 potential citations, 11 met criteria for inclusion. Fetal outcome data for >350 infants with DHE exposure in utero did not show a statistically significant increased risk of major congenital malformations. An increased risk of prematurity, however, has been reported. Transient fetal bradycardia was also reported when DHE was used during labor. Increased miscarriage risk was possibly associated with high intravenous doses administered to induce labor. CONCLUSIONS: In this literature analysis, DHE use during pregnancy was not reported to be associated with a statistically significant risk of major congenital malformations. It was however associated with a higher risk of prematurity. Supported by: MAP Pharmaceuticals, Inc. Disclosure: Dr. Silberstein has received personal compensation for activities with Allergan, Amgen, Capnia, Coherex, Iroko Pharmaceuticals, Lilly, MAP, Medtronic, Neuralieve, NINDS, NuPathe, Pfizer, St. Jude Medical as an advisory board member and from Amgen, Nautiluss, Opti-Nose, and Zogenix as a consultant. Dr. Silberstein has received personal compensation in an editorial capacity for Current Pain and Headache Reports and Medlink as an advisory board member. Dr. Silbertsein has received research support from Allergan, BMS, Cumberland, Lilly, MAP, Merck, OptiNose, and St. Jude Medical. Dr. Kori has received personal compensation for activities with MAP Pharmaceuticals, Inc. Dr. Kori holds stock and/or stock options in MAP Pharmaceuticals, Inc. Dr. Kori has received research support from MAP Pharmaceuticals, Inc. Dr. Buse has received personal compensation for activities with Allergan as a scientific advisor. Dr. Buse has received research suprrot or has support pending from Allergan, ENDO, MAP, Nupathe and Merck to the National Headache Foundation. Dr. Marcus has received research support from Pfizer Inc, Merck & Co., Inc., and GlaxoSmithKline, Inc. Dr. Aurora has received personal compensation for activities with GlaxoSmithKline, Inc., Merck & Co., Inc., Ortho-McNeil, Allergan, Inc., MAP Pharmaceuticals, Kyowa, and Neuraleve. Dr. Aurora has received research support from Alexza, Allergan, Inc., GlaxoSmithKline, Inc., Merck, Pfizer, Inc., Ortho-McNeil, MAP pharmaceuticals, Takeda, and Neuraleve. Dr. Tietjen has received personal compensation for activities with MAPP. Dr. Tietjen holds stock and/or stock options in Johnson & Johnson and Stryker. Dr. Tietjen9s institution received research support from Lundbeck Research USA, inc. Dr. Berard has received personal compensation for activities with MAP Pharmaceuticals. Dr. Berard has received research support from MAP Pharmaceuticals, CIHR, FRSQ, and NIH. Dr. Czeizel has nothing to disclose. Dr Lipton has received personal compensation for activities with Allergan, Inc., Boston Scientific, Bristol-Myers Squibb Company, Cognimed, Colucid, Eli Lilly & Company, eNeura Therapeutics, GlaxoSmithKline, Inc., MAP, Merck, Nautilus Neuroscience, Novartis, and NuPathe. Dr. Lipton holds stock and/or stock options in eNeura Therapeutics.
NEJM Journal Watch, 2007
This prospective cohort study addressed the association between lipid levels and risk for subsequ... more This prospective cohort study addressed the association between lipid levels and risk for subsequent stroke in women. More than 27,000 healthy female health professionals (age, 45 or older) in the Women’s Health Study (WHS) provided blood samples for fasting lipid profiles before being randomized to treatment with aspirin (100 mg on alternate days), vitamin E (600 IU on alternate days), both, or neither. Participants were followed up …
Cephalalgia, Nov 17, 2021
Background Headache in patients with moyamoya disease is an under-addressed topic in the medical ... more Background Headache in patients with moyamoya disease is an under-addressed topic in the medical literature. Delay in the diagnosis of moyamoya disease or inappropriate treatment of headache could lead to devastating cerebrovascular outcome. With the evolving understanding of moyamoya disease, migraine pathophysiology, and various migraine-specific medications that have become available, it is crucial to provide an updated overview on this topic. Methods We searched PubMed for keywords including moyamoya disease, moyamoya syndrome, headache in moyamoya, surgical revascularization, surgical bypass, migraine and moyamoya, and calcitonin gene-related peptide (CGRP). We summarized the literature and provide a comprehensive review of the headache presentation, possible mechanisms, the impact of various surgical revascularizations on headache in patients with moyamoya disease, and the medical management of headache incorporating novel migraine-specific treatments. Results and conclusion: The most common headache phenotype is migraine; tension-type headache, hemiplegic migraine, and cluster headache have also been reported. Most patients experience improvement of headache after surgical revascularization, though some patients report worsening, or new-onset headache after surgery. Given the complexity of moyamoya disease, careful consideration of different types of medical therapy for headache is necessary to improve the quality of life while not increasing the risk of adverse cerebrovascular events. More prospective studies are warranted to better understand and manage headache in patients with moyamoya disease.
DICP, Dec 1, 1991
Dynamic cerebral blood flow (CBF) studies using acetazolamide or hypercapnia as a vasodilatory ch... more Dynamic cerebral blood flow (CBF) studies using acetazolamide or hypercapnia as a vasodilatory challenge have attempted to evaluate intracranial hemodynamics. We report two patients with asymptomatic intemal carotid artery occlusion in whom the vasodilatory stimulus was a single oral dose of antihypertensive medication (prazosin hydrochloride or enalapril maleate). In both patients, changes in regional CBF occurred that were larger than those seen in nine normal controls. One patient experienced an improvement in regional CBF with a reduction in probe pair asymmetry. In the other patient, who had bilateral carotid artery disease, a decrease in regional CBF in all 16 probes (mean decrease 12 percent) and an accentuation of the predose asymmetry were observed. Both patients remained asymptomatic throughout the study. Assessing these effects on cerebral circulation may help identify patients at risk for iatrogenic focal cerebral ischemia and provide information regarding the functional status of the cerebral vasculature.
Current Treatment Options in Neurology, May 18, 2016
This article is part of the Topical Collection on Headache Keywords Childhood maltreatment I Abus... more This article is part of the Topical Collection on Headache Keywords Childhood maltreatment I Abuse I Adverse childhood experiences I Stress I Migraine I Genetics I Epigenetics I Cognitive behavioral therapy Opinion statement Maltreatment during childhood increases vulnerability to a host of health disorders, including migraine. Putative mechanisms linking maltreatment and migraine include stress-induced dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, as well as disruption of other stress-mediating homeostatic systems, including those involving endocannabinoids, monoamine neurotransmitters, oxytocin, and inflammation. Prolonged elevation of glucocorticoids alters the neural architecture of the limbic system, resulting in the structural as well as functional changes described in both maltreatment and in migraine. Although treatment trials for migraine have not stratified participants by abuse history, strategies, such as cognitive behavioral therapy, which alter stress responsivity, may be particularly effective in this subgroup. Some therapies involving the endocannabinoid, serotonergic, oxytonergic, and inflammatory systems are under investigation for migraine. Anti-epileptic drugs such as valproate and topiramate, which are FDA approved for migraine treatment, are also known to interfere with epigenetic changes induced by stress. Discerning the role for this mechanism in treatment of maltreated migraineurs may introduce another therapeutic avenue.
Annals of Neurology, Oct 1, 1990
Four members of a kindred with Creutzfeldt-Jakob disease are reported, i n whom myoclonus did not... more Four members of a kindred with Creutzfeldt-Jakob disease are reported, i n whom myoclonus did not develop and in whom serial electroencephalograms performed late in their illness failed to show periodic sharp wave complexes. Otherwise, the patients' disease duration, clinical features, and neuropathological findings were similar to those described in sporadic cases of Creutzfeldt-Jakob disease. Our findings and those reported by others suggest that periodic electroencephalographic activity may be rqre i n familial forms of Creutzfeldt-Jakob disease, as it is i n other slow transmissible encephalopathies. Tietjen GE, Drury I. Familial Creuufeldt-Jakob disease without periodic EEG activity.
Journal of Clinical and Experimental Neuropsychology, Apr 1, 1999
Neurologic events associated with antiphospholipid antibodies (aPAs) include transient ischemic a... more Neurologic events associated with antiphospholipid antibodies (aPAs) include transient ischemic attack, stroke, and vascular dementia in individuals much younger than is typically observed with these disorders. The present study evaluated 27 non-elderly adults with aPAs but without concurrent disease processes or history of neurologic event and 27 age- and education-matched controls. MANOVA (p <.01) indicated group differences in executive functioning, verbal learning and memory, and visuospatial ability. In contrast, gross attentional processes and fine motor skills appeared unaffected by the syndrome. Moreover, the frequency of impaired neuropsychologic performance was greater among individuals with aPAs than among controls (p <.01). The presence of cognitive deficits in otherwise asymptomatic patients with aPAs indicates a preclinical phase of neurologic involvement and may prove to be the most sensitive markers of the syndrome.
Stroke, Nov 1, 1998
Background and Purpose-The aim of our study was to characterize the patient profile and prognosti... more Background and Purpose-The aim of our study was to characterize the patient profile and prognostic value associated with high positive IgG (Ͼ100 GPL) anticardiolipin antibodies (aCL). Methods-We studied the clinical, laboratory, radiological, and prospective historical features of ischemic cerebrovascular disease in patients with Ͼ100 GPL titers. From our neurology department, 27 consecutive patients were prospectively identified and followed up (mean follow-up time, 34 months). Results-The mean age of our cohort was 41 years. Lupuslike illness occurred in 3; 23 had primary antiphospholipid syndrome, including 3 who met criteria for Sneddon's syndrome; 1 patient had progressive systemic sclerosis. Cerebral infarcts occurred in 74% and were recurrent in 37%. Systemic ischemic events, most commonly deep vein thrombosis, occurred in 37%. Tobacco use was documented in 85%, hyperlipidemia in 74%, hypertension in 44%, and diabetes mellitus in 7% of patients. A prominent headache history was present in 67%. Lupus anticoagulant (LA) was present in 72%, approximately one half had positive antinuclear antibodies and thrombocytopenia, and one quarter had a false-positive VDRL. We compared mean GPL levels in patients testing positive for specific laboratory features of antiphospholipid syndrome with those testing negative for these parameters. Only the LA(ϩ) group had a significantly higher mean GPL than the LA(-) group (Pϭ0.006). Brain imaging showed nonlacunar infarcts in 73% and lacunes in 12%. Of 19 cerebral angiograms, 5 (26%) showed large-vessel occlusive disease and 6 (32%) branch obstruction. Echocardiograms were abnormal in 75%: thickened left-sided valves in 33% and vegetations in 12%. Recurrent cerebrovascular ischemic events were observed in 96%, with transient events (mean rate, 25%/y) occurring 5 times more frequently than strokes (mean rate, 5%/y). Using a standardized disability scale blinded to aCL titer, neurological impairment was severe in 7%, moderate in 30%, and mild or nonexistent in 63%, and unrelated to mean GPL value (Pϭ0.567). Titers fluctuated greatly for individual patients, and most did not consistently test as highly positive. An analysis of fluctuation in symptom severity with concurrent GPL values did not show a statistically significant correlation. Compared with historical controls having a wide range of positive titers, the presence of high IgG aCL titers did not confer a worse prognosis for disability and recurrent ischemic events. Conclusions-Our data suggest that cerebrovascular events associated with high positive GPL are frequently multiple and minor (with no disability-titer correlation), present in relatively young patients, and often associated with tobacco abuse, hyperlipidemia, LA, systemic ischemic events, and occult cardiac disease.
Stroke, Feb 1, 2017
Background: Early stroke identification and treatment with mechanical thrombectomy (MT) increases... more Background: Early stroke identification and treatment with mechanical thrombectomy (MT) increases likelihood of favorable outcome. We compared our MT time efficiencies before and after Rapid Arterial oCclusion Evaluation Alert (RACE) bypass protocol (RA) implementation in Lucas County (LC) Ohio. Methods: Our RA protocol mandates emergent comprehensive stroke center transfer for patients with RACE score ≥ 5. We compared MT cases for RA patients (N=37) from Jul 2015-Jun 2016 with procedures performed on Stroke Alerts [(SA) N=56] from preceding 2 years. Transfers from outside LC, private transport and inhospital cases were excluded and only patients brought via LC-EMS were included in the analysis. Basic demographics, risk factors, 911 call to treatment, and outcomes were compared. Results: Treatment times including 911 call to IV tPA treatment, groin puncture, and recanalization were all significantly faster in the RA cohort (see graphic). Overall RA patients achieved recanalization and favorable outcomes at higher rate, although the latter was not statistically significant. Conclusion: Our experience indicates that RA protocol is highly effective in enhancing overall time efficiency for MT and may contribute to improved clinical outcomes. Further prospective studies are warranted.
Journal of Vascular Access, Feb 19, 2018
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Papers by Gretchen Tietjen