Presentation on theme: "Headache and Subarachnoid Hemorrhage"— Presentation transcript:
1Headache and Subarachnoid Hemorrhage Carly ThompsonFebruary 19, 2009See Rob Halls’ presentation at the end of Carly’s
2Objectives Approach to headache in the ED Migraine Focus on dx, txSubarachnoid HemorrhageOther causes of serious headache
3Headache Epidemiology 4% of ED visitsPrimary HeadachesMigraineTension-TypeClusterSecondaryAll others!1% of headaches are SAH!
4Headache: Historical Features Occult TraumaSigns of abuse/neglectAnticoagulationSAHSudden OnsetMaximal soon after onsetDifferent than previousMeningitisFeverNeck stiffnessImmune compromiseHead/neck infectionTemporal ArteritisJaw claudicationTemporal tendernessVisual symptomsPre-eclampsiaPregnancyPost-partumSpace-occupying lesionProgressiveHx of malignancyNew onset >50yrsWorse in am, head downNeuro signsCerebral Venous ThrombosisBilateral neuro findingsProptosisHypercoaguable stateRecent sinusitisPregnancyCO ToxicityWorse in amOthers affectedEnvironmental exposure
5Question:Name 5 high risk historical features for Subarachnoid Hemorrhage.
6High Risk Features for SAH ThunderclapFirst or worst headache of my lifeAltered mental status / SeizureHeadache with exertion / intercourseHistory of exerciseLocation of pain: occipitonuchalPPV occipitonuchal headache for intracranial pathology is 16%Family history of SAHUp to 4x increased risk in 1st and 2nd degree relatives!
7QuestionWhat is your differential for thunderclap headache? Name 3 (other than SAH).Thunderclap = sudden-onset, severe headache
10QuestionWhat is a subhyaloid hemorrhage and when do you see it?
11Subhyaloid Hemorrhage Gravity-dependent venous hemorrhage between retina and vitreous membrane, convex at bottom, and flat at top when sittingHighly suggestive of SAH: 11-33% of SAH casesTerson’s syndrome – rapid increase in ICP assoc. with hemorrhage – worse outcome
12Low Risk Patient No change in headache pattern No new concerning historical featuresNo focal neurologic symptoms or findingsNo imaging indicated!Meta-analysis:2.4% of those with normal neuro exam have neurologic abnormalities on CT0.4% of those with typical migraine symptoms
13QuestionWhich subsets of patients with headache require neuroimaging in the ED?Name 3 groups.
14Neuroimaging Indications ACEP Clinical Policy (Ann Emerg Med 2008)Level B(1) Headache and new abnormal neuro findingsPPV 39% for intracranial pathologyLR 3.0(2) Sudden-onset severe headache10-15% have serious pathology, often SAH(3) HIV patients with new headacheHeadache – 35% had mass lesionNeurologic complaint – 24% focal lesion1 or more of predicted all focal lesions in a series of patients:New seizureDepressed / altered LOCHeadache different or > 3 days
15Neuroimaging Level C Evidence Age >50 with new headache but normal exam, should be considered for urgent neuroimagingOR 3.3 of pathologic diagnosis
16NeuroimagingOther worrisome features that increase probability of positive findings, but no clear recommendations:Occipital locationWorsening with ValsalvaHeadache waking from sleepAssociated syncopeNausea or sensory distortion
17Neuroimaging Headache in Pregnancy Most headaches are benign CVA – risk increases 3-13xSAH – 20/100,000 deliveriesMigraines: less common60-70%have improvement in migraines during pregnancyConclusion: Insufficient data to drive recommendations for imaging.
18QuestionCan response to therapy be used as a diagnostic tool?
19Response to Therapy Level C No!!! Pain response should not be used. ? Common pathway for pain regardless of etiologyNo RCT to support or refute this.Class III Evidence: Case reports, case series, showing resolution or improvement in pain with analgesics in SAH, meningitis, CO-induced headache, cerebral venous sinus thrombosis, dissection, etc.
20MigraineWhat are the diagnostic criteria for migraine?
21Migraine: Diagnosis Recurrent headache disorder – IHS Criteria Headache lasts 2-72 hoursAt least 2 of:UnilateralPulsatingModerate to SevereAggravation by routine activityAt least 1 of:Photophobia or PhonophobiaNausea and/or vomitingAt least 5 attacksHx, physical and neurologic exam do not suggest other organic disease
22Migraine: Diagnosis Migraine without Aura Migraine with Aura: Aura reversible focal neurologic symptoms that usually develop over 5-20 min and last <60 min, headache begins during aura or within 60 minutesVisual positive / negative featuresSensory positive / negative featuresDysphasic speech
23Question TRUE! True or False? Migraines can be associated with autonomic and sinus symptomsi.e. nasal congestion, rhinorrhea, tearing, colour and temperature change, changes in pupil sizeTRUE!
24Question Which of the following are associated with migraine? Family history of migraineMotion sicknessObesity
25Associated FactorsFamily history and motion sickness are risk factors for developing migraineObesity is associated with increased frequency and severity of migraines
26Migraine: Treatment US Headache Group: Educate pts about condition and tx; encourage active participation in managementUse migraine specific agents in pts with severe migraine, and those who respond poorly to NSAIDs or combination analgesicsUse non-oral route for pts with sig N/VConsider self-administered rescue meds for pts with severe migraineGuard against medication overuse headaches by using prophylactic medication in pts with frequent headaches
27QuestionList 5 treatment options for migraine in the emergency department.
29Mild Analgesics in Migraine Some pts can get optimal response with mild analgesics (NSAIDs, acetaminophen)Not advisable >10x /monthRCTs: Acetaminophen, ibuprofen, naproxen, diclofenac, ASA, acetaminophen + ASA + caffeineIndomethacin: limited data, some specific migraine types are responsive to indomethacin for abortive therapy, benefit: suppository form
30Triptans Specific tx: 5-HT 1b/d agonist ->inhibit dural nociception Advantage: multiple preparationsSC, IN, PORCT and systematic reviews: all triptans have been shown effective in acute migrainePts who don’t respond to one may respond to another
31QuestionSo, why don’t we commonly use triptans in the ED?
32Limitations of Triptans More effective if used early!Development of central sensitizationContraindications:Patients with pregnancy, uncontrolled htn, ischemic heart disease, peripheral vascular disease, Prinzmetal’s angina, ischemic CVA, familial hemiplegic migraine, basilar migraine24 hours of other 5-HT agonist (ergots), MAOIs with some triptansSevere liver impairmentInteractions: P450 cytochromeAdvisory July 2006 – concomitant use with SSRIs or SNRIs increases risk of serotonin syndrome; advise discussion of benefit vs risk
33Ergots: Ergotamine Mechanism: Efficacy: Side effects: 5HT 1b/d receptor agonistEfficacy:Alone failed to show efficacySide effects:Nausea, vomitingVascular occlusion and rebound headachesLong-term: Associated with CADAvoid in pts with CAD, PVD, htn, hepatic and renal disease and those with prolonged auraEuropean Consensus Panel:Treatment of choice in few pts due to issues of efficacy and side effects
34Ergots: Dihydroergotamine Fewer side effects: no dependence or rebound headachesAdvantage: IV, IM, SC, IN useContraindications:Htn, CAD, PVD, Prinzmetal’s, MAOIs, sepsis, severe hepatic or renal dysfunction, high dose ASA tx, pregnancyHemiplegic or basilar migraineWithin 24 hours of triptan or other serotonin agonistsCYP3A4 inhibitors: some macrolides, antifungals, protease inhibitors
35Question How does DHE compare to the triptans for efficacy? More effective?Same?Less effective?
36DHE: Efficacy vs Placebo: vs Triptan: vs Dopamine Antagonist: Proven by systematic review / RCTs, especially when given with anti-emeticvs Triptan:Less effective on most measures compared head-to-head with sumatriptanvs Dopamine Antagonist:Less effective than chlorpromazine on some measures
37Dopamine Antagonists Benefits: Antiemetic IV metoclopramide IV or IM chlorpromazine and prochlorperazine
38Chlorpromazine: Largactil / Thorazine Chlorpromazine 5-15mg IV or 0.1mg/kg IVRCT vs Placebo (Bigal 2002 J Emerg Med):Significant improvement in scores of pain, nausea, vomiting, photo/phonophobia at 60 minNNT 2Side effects:Hypotension / Postural hypotension (18%)May be exacerbated by opioids, pre-tx with fluid bolusAlpha-antagonistDrowsinessPregnancy: Class C
39Prochlorperazine: Stemetil, Compazine Prochlorperazine 10mg IVSide effects:HypotensionDrowsinessDystonic ReactionsCardiac arrhythmiasPregnancy Class C: Isolated reports of congenital anomalies, jaundice, EPS, hyper/hyporeflexia – if occasional low-dose suggested to be safeFDA Alert (June 2008): Association with increased mortality when used for treating dementia-related psychosis
40QuestionHow does prochlorperazine compare to metoclopramide?
41Proclorperazine vs Metoclopramide RCT: Coppola (1995) Annals of Emerg Med> 50% reliefStematil 82% Maxeran 48% Placebo 29%RCT: Jones (1996) Am J of Emerg MedPartial or complete reliefStematil 67% Maxeran 34% Placebo 16%
42Metoclopramide: Maxeran, Reglan Maxeran 10mg IVEfficacy:Meta-analysis Colman (2004) BMJGenerally poor studiesOR 2.84 for reduction of pain in headacheLess effective than chlorpromazine and prochlorperazine in relieving pain, but not always statistically significant1 Trial: No difference between aggressive metoclopramide (20mg IV q30 min up to 4x with diphenhydramine 25mg IV q1 hour up to 2x) vs sumatriptan 6mg SCBenefits:Pregnancy Class BCan be combined with DHE, other analgesicsSide Effects:DrowsinessDystonic reactions: <1-25%, increased risk in young males
43Other Options? Some pts will not respond to routine treatment. Consider wait-times, location (ED vs clinic)Treat aggressively.Do not use following meds on a chronic basis due to habit-forming nature and rebound headaches.BenzosOpioidsBarbiturates
44QuestionHow can you prevent migraine recurrence?
45Parenteral Dexamethasone Colman I et al. (2008) BMJMeta-analysis of 7 RCTs.Dexamethasone 10-25mg IV or IM vs placeboSimilar acute pain reductionRecurrence rates at 72 hours RR 0.74 ( )NNT 9Similar side effect profile
46QuestionCan you name the complications of a migraine?
47Migraine: Complications Status migrainosusChronic migrainePersistent aura without infarctionMigrainous infarctionMigraine-triggered seizure
48Summary: Migraine Tx in the ED Fluid bolus: NS 1L bolus IVNSAID: If used <10x/monthNausea / vomiting: consider PR indomethacinPO: acetaminophen vs ibuprofenDopamine antagonist:Stemetil 10mg IVMaxeran 10mg IV (Pregnancy)Opioid:Morphine 2-5mg IV prnDHE / Triptan:If early presentation, contraindications to othersRizatriptan, eletriptan, almotriptanSumatriptan: IN, SC or Zolmitriptan: IN, PO
49Subarachnoid Hemorrhage EpidemiologySAH 1% of all headaches in ED10% of hemorrhagic strokes10% of “worst headache ever”Prevalence: 3-25 / 100,000Mean age: 55 (Range 20-60)Reported in pediatricsMiss Rate?Variable 5-50% (30% average)Acceptable miss rate: 0%!
55Aneurysms in the Public Prevalence of saccular aneurysms5% at autopsy20-30% have multiple aneurysms
56QuestionCan you name 3 risk factors for rupture?
57Risk Factors for Rupture of Aneurysms SmokingDose-dependent, esp. women, disappears soon after quitting, RR 2.2HypertensionRR 2.5, OR 2.6EtOHModerate to heavy consumption RR 2.1, OR 1.5Family HistoryOR 4.0GeneticsAutosomal dominant / recessive / multifactorial / anticipationElastin gene, Platelet adhesive glycoproteinPhenylpropanolamineAppetite suppressants, cold remedies, case-control study – risk factor in womenEstrogen deficiencyPremenopausal women and reduced risk compared to age-matched postmenopausal women (OR 0.24), HRT (OR 0.47)Physical ExertionOrgasm, moderate exertion OR 2.7?Anticoagulants
58QuestionWhat proportion of patients with SAH from aneurysm have a sentinel bleed?
59Sentinel Headache30-50% of patients have a sentinel headache that precedes SAH by 6-20 days
60Clinical Features Abrupt onset, severe headache “thunderclap” Lateralized 30%At night 30% (During day / activity 60%)Onset associated with brief LOC, seizure, nausea, vomitingMeningismus / Aseptic meningitisNormal neurologic findings at presentation 50%
65Pitfalls in Diagnosis Wasn’t the worst headache of their life! Neurologic exam was normal!50% have normal neurologic exam!Pain improved with treatmentRemember: SAH CAN improve with treatment!CT head was negativeRBCs decreased from tubes 1-3 / Misinterpretation of LPNo LP done
66CT Head: LimitationsTechnical ability of CT scanners to identify small hemorrhage / artifact / boneProtocol and age of scanner – thin slicesExpertise of readerAnemia Hb<100 – blood appears isodenseTime: decay in sensitivityInability to diagnose other causes of headache: meningitis, etc.
67Question How sensitive is CT scan at day 1 for SAH?
68CT Scan: SensitivityAs blood is diluted and degraded flowing through SA space -> decreased sensitivityBMJ (2006)<12 Hrs 98%24 hrs 93%>7 days <50%Memory aide:Day 1 90%Day 2 80%Day 3 70%Day 4 60%
69QuestionWhy do you do a CT then if ruling out SAH?
70CT Scan for SAH: Advantages Traumatic LP:13% may be traumatic (>400 RBCs)LP Limitations:Cerebral venous thrombosisUnruptured aneurysmArterial dissectionPituitary apoplexy
71QuestionDoes an LP need to be routinely performed on ED patients to rule out SAH if normal noncontrast CT head?Why?
72Lumbar Puncture ACEP (2008) Level B Evidence. Lumbar puncture should be performed to rule out SAH.Rates of SAH confirmed by LP after normal CT %
73QuestionWhat 3 features do you see on LP in SAH?
75Opening Pressure Normal? 6-20cmH20 is normal in adults and children 25cmH20 may be normal in obese ptsUtility:Helpful to distinguish SAH from traumatic tap2/3 of SAH may have elevated opening pressureOther diagnoses: spontaneous intracranial hypotension, benign intracranial hypertension, cerebral venous sinus thrombosis
76QuestionDoes clearing of blood (i.e. declining RBC count from tubes 1->4) rule out SAH?
77Elevated Red Blood Cell Count Clearing of blood is unreliable.There is no cutoff which has been shown to reliably exclude SAH.However, if tap done late >12 hours, and absence of xanthochromia, but presence of RBC = negative tap.No way to tell traumatic tap vs SAH if early <12 hours tap.
78Question What is xanthochromia? When does it appear? How long does it last?
79XanthochromiaYellow colour caused by bilirubin and oxyhemoglobin due to lysis of RBCsOxyHb -> Heme oxidase enzyme -> BilirubinProcess may take 6-12 hoursOnset: Blood in CSF for at least 2 hoursPeak: 48 hoursDuration: Up to 2-4 weeks
80QuestionName 2 methods for analyzing your sample tubes for xanthochromia.Which is more sensitive?
81Xanthochromia: Analysis SpectrophotometrySpin CSF, run through spectrophotometer, look for oxyHb or bilirubin peak at 410nm and 460nmMost sensitiveLow-moderate specificityNot always availableVisual AnalysisSpin CSF, compare to identical test tube with equal volume tap water against white backgroundCalgary Health Region’s methodLess sensitive, but may be >95% if >12 hours after SAH
82Question Name 3 false positives for xanthochromia. (Xanthochromia but no SAH!)
84QuestionWhich patients can safely undergo LP without neuroimaging?
85LP Before CT? ACEP (2008). Level C Evidence. Adults patients with headache and signs of elevated ICP should have neuroimaging before LP.Papilledema, absent venous pulsations of fundoscopy, altered LOC, focal neuro deficits, signs of meningeal irritationIn the absence of clinical findings suggestive of increased ICP, LP can be performed without obtaining neuroimaging.
86QuestionIn a patient with sudden-onset, severe headache who has negative findings (both CT head and LP) is there a need for further emergent imaging?
87Further Investigation ACEP (2008). Level B Evidence.Patients with sudden-onset, severe headache with negative CT head, normal opening pressure, negative findings on CSF analysis, do NOT need emergent angiography, and can be discharged with follow-up recommended.Note: Consider other causes of sudden-onset, severe headache like pituitary apoplexy, cerebral venous sinus thrombosis, arterial dissections, cerebellar stroke Further imaging may be indicated to rule out these causes.
88Further Investigation Perry et al. (2008) Annals of Emerg Med.2 Canadian EDs, 592 patientsCT and LP to rule out SAH (10.3% had SAH)CT negNo xanthochromia by visual inspectionRBCs in final tube <5 x 106RBC/LOthers followed 6-36 monthsRate of subsequent SAH: 0%Rate of subsequent aneurysm: 1 / 592 required surgery, but “did not contribute to initial presentation”
90QuestionCan you name 3 causes of headache that might be associated with exertion?
91Exertional Headache SAH Carotid or Vertebral Artery Dissection Pts with SAH more likely to have participated in exertion that day, compared to previous OR 2.7Carotid or Vertebral Artery DissectionPrimary Exertional HeadacheBilateral pulsatile pain during or after exercise, lasts 5min – 48 hours, not usually assoc. with N/VRule out: SAH, angina, vascular abnormalities, pheoTx: indomethacin, propranolol, naproxenPrimary Headache Associated with Sexual ActivityPreorgasmic: usually secondary to muscle tensionOrgasmic: associated with CVA / dissection and SAHUnpredictablePrevention: indomethacin, B-blockers, propranololAcute tx: triptans
92QuestionCan you describe the most common headache symptoms in brain tumour?
93Brain Tumour 50% have headaches Typical headache: Tension-type (77%)Migraine (9%)Typical headache:Bilateral, worse ipsilaterally, bending over (32%), nausea and vomiting (40%), worse with ValsalvaClassic “early morning headache” – uncommon!Reliable findings:Nausea, vomiting, worsening with change in position, abnormal neurologic exam, significant change in headache pattern
94Triptans: Comparison Few trials comparing triptans head to head Rizatriptan (Maxalt), eletriptan (Relpax), almotriptan (Axert) had highest likelihood of successSumatriptan was recently released with fast dissolving tabsSumatriptan (Imitrex): SC, IN, POZolmitriptan (Zomig): IN, PO
95Headache: Emergent Diagnoses Core Rounds Feb19,2009Rob Hall MD, FRCPC
96Case 41yo female PMHx DM1 on insulin Mild headache and Numbness right arm/mouth and weakness left grip, subacute, 1 weekNo fever or illicit drug useOCP started 2 weeks agoNo hx seizures, no traumaWaiting in ED bed, GTC 1 min sz, chemstrip normal, ativan 2mg iv, post ictal and combative after, no focal findings after szInvestigations?Thoughts on dx?
98Cerebral Vein Thrombosis “DVT of the BRAIN”Venous clot then infarct and/or bleed at grey-white junctionTransverse sinus most common location, often multiple sinuses
99Clinical Presentations STROKE SYNDROMEOften not typical arterial distributionSEIZUREHEADACHECan be basically any description of headache (thunderclap uncommon)
100Risk Factors for CVT (present in 85%) Head and neck infectionsHypercoagulable statesEstrogensPregnancyCancerHypercoag syndrome: lupus AC, protein C def, etcHematologic disorders: leukemias, polycythemia, thrombocytosis, sickle cellVasculitis: SLE, GCA, wegener’s, Bechet’s, etc
101Exam findings Highly variable Three clues Head infection + Neuro symptomsPapilledema (? Sensitivitiy)Stroke findings in non-arterial distributionLP will show elevated opening pressure without other cause
102CT head (plain) findings Sensitivity 60-70% (30-40% normal)Delta sign = dense triangle from hyperacute thrombosed superior saggital sinusCord sign = thrombosed cortical veinVenous infarcts with secondary hemorrhage in non-arterial distributionHTN bleeds: thalamus, IC, CB, ponsVenous infarct bleeds: bilateral at grey-white junction
106CVT and Carotid/vert dissections. Which is better CT or MR? “I think that most radiologists reading these studies would say that both CTV and CTA have a higher sensitivity due to CT's inherent spatial resolution advantage which is very good on our latest multidetector scanners. CT is our favoured study where there is concern for venous sinus thrombosis and carotid/vertebral dissection. The research will catch up.”
107ED Management Dilantin if seized Manage elevated ICP Heparin Majority of evidence shows improvement trends (no major large RCT showing statistically conclusive results)Shown to be safe even with hemorrhages!Cochrane review 2001RR death 0.33 (95%CI )RR death or disability 0.46 ( )
108Further Management Optic nerve fenestrations Acetazolamide Case reports of lyticsLP/VP shuntsHemicraniectomy for severe ICP problems
110Is Idiopathic Intracranial HTN and CVT a spectrum of disease? IIHTN > CVT
111Idiopathic Intracranial HTN (IIHTN) Old terms = Pseudotumor cerebri, Benign IHTN, meningitis CerosaDiagnostic criteria for IIHTN requires imaging to rule out CVT
112Idiopathic Intracranial HTN (IIHTN) Opening pressure > 20 cm H20 (usu 25-45)Headache MUCH better after LP!Signs/symptoms of increased ICPNo focal signs (except 6th palsy)No mass lesionNo hydrocephalusNormal CSF valuesCTV/MRV to exclude CVT
113Idiopathic Intracranial HTN (IIHTN) Main ED PEARL is to consider the diagnosis and do an LP“Consider”Obese, female, OCPHypercoag statesSubacute, unexplained headaches, return visits, normal imagingVisual symptoms: blurry vision, diplopia
114Carotid and Vertebral Dissections 2% of ischemic strokes overall but 20% of ischemic CVA < 45yoThink of in young patientPathology the same with major vs minor traumaMay be VERY minor (yoga, cough, stretching, etc)Unknown if “spontaneous” really occur
116Giant Cell (Temporal) Arteritis: the basics Older personSubacute headacheSystemic symptomsJaw claudicationAssociation with PMRRisk of vision lossElevated ESRDiagnose by temporal artery biopsyTreat with steriods
117Giant Cell Arteritis: some pearls Extremely rare < 50 years oldPooled analysis 1435 pt, only 2 < 50yoTemporal artery findings (large, absent pulse, tenderness) fairly specific but not sensitiveNormal ESR (< 20 mm/hr) excludes dx, moderate ESRs don’t (20-50 mm/hr)<20 mm/hr 96% sensitive<40 mm/hr 95% sensitive< 50 mm/hr 89% sensitive
118Giant Cell Arteritis: some pearls Temporal artery biopsyInitial bilateral biopsies 88% sensitiveRepeat if initial biopsies negativeBiopsy will be abnormal for weeks after initiation of steriod; try to have it done soon but not emergentlyTreatmentPrednisone 60 mg po odASASTART before biopsy
119APPROACH to ED HEADACHE Headache is a high risk complaint.Consider serious causes in every case.Majority of badness excluded with good history and physical.More complex than just ordering CT head!
120Headache and normal CT head; ddx of “bad” causes? Ischemic strokeHTN encephalopathyPre-eclampsiaCO toxicityVasculitis/GCAAACGCNS infectionCVTIIHTNSAHCarotid/vertebral dissectionWhich can be excludedBy hx/pe?
121Headache and normal CT head; ddx of “bad” causes? Ischemic stroke - hx and physicalHTN encephalopathy - physicalPre-eclampsia - hx and physicalCO toxicity - hxVasculitis/GCA - hxAACG - physicalCNS infectionCVTIIHTNSAHCarotid/vertebral dissection - CTA/MRAWhich can be excludedBy a normal LP?
122Headache and normal CT head; ddx of “bad” causes? Ischemic stroke - hx and physicalHTN encephalopathy - physicalCO toxicity - hxVasculitis/GCA - hxAACG - physicalCNS infection > LPCVT > LP (+/- CTV)IIHTN > LPSAH > LPCarotid/vertebral dissection - CTA/MRA/Angio
123Lumbar puncture is a useful test to exclude some nasty causes of headache Opening pressure is worthwhile.
125Headache motherhood statements Chronic migrainers with toradol allergies get badness to. Be diligent.Approach headache like chest pain - good hx/pe and directed investigations to exclude badness.Have a ddx of badness and “run the list” with every headache.Headache is more than migraine and SAH.Anyone can thing to order a CT head. A good clinician will pick up the less common but serious diagnoses.Older patient with no hx migraine: be cautious.
126Miscellaneous pearls What INR before LP? What platelet level is c/I to LP?35yo healthy male, collapsed, Vfib arrest, bystander cpr and defib at 5min, persistent coma, diagnosis?How to decrease post LP headache?Needle size, pokes, non-cutting, styletBedrest and IVF not helpful