Archives of Academic Emergency Medicine. 2023; 11(1): e26 REV I EW ART I C L E Clinical Characteristics, Course, and Outcomes of Verte- bral Artery Dissections in the Postpartum Period; a Pooled Analysis of Published Case Reports Rehab Adel Diab1,6∗, Nour Shaheen2, Abdelrahman Mohamed2, Mahmoud Tarek Hefnawy3,6, Dilawer Chofan Charo4,6, Mostafa Meshref5,6 1. Faculty of Medicine, Al-Azhar University, Cairo, Egypt. 2. Faculty of Medicine, Alexandria University, Alexandria, Egypt. 3. Faculty of Medicine, Zagazig University, Medical Research Group of Egypt, Cairo, Egypt. 4. General Surgery Department, National Hospital in Latakia, Latakia, Syria. 5. Neurology Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt. 6. Medical research Group of Egypt (MRGE), Research Department, Cairo, Egypt. Received: December 2022; Accepted: January 2023; Published online: 4 March 2023 Abstract: Introduction: Vertebral artery dissection (VAD) is a rare, but life-threatening condition. Compared to the general popu- lation, pregnant and postpartum women are more likely to develop VAD. Spontaneous arterial dissections have an am- biguous pathophysiology and may be difficult to manage. This study aimed to pool and analyze the data of published cases in this regard. Methods: We conducted a literature search on February 24, 2022, using MeSH terms of interest in PubMed, Google Scholar, Ovid, Web of Science, and Scopus databases to find studies on VAD following childbirth. Results: A total of 28 studies were included in this review based on a database search. In the studies, 44 postpartum VAD (PPVAD) patients with a mean age of 34.26 ± 3.5 years were included. It took an average of 24.37± 13.7 days from delivery to dissection. 64% of the patients had developed unilateral dissection and 36% had developed bilateral dissec- tion; 70% reported full recovery, and 9% did not achieve full recovery. The most common symptoms were headaches (89%), neck pain (64%), and hypertension (52%). The most common methods of diagnosis were magnetic resonance imaging (MRI) (64%) and computed tomography (CT) angiography (CTA) scan (66%). Only 8 (18%) cases reported the use of electrocardiography (ECG). The recorded outcomes of the patients with unilateral and bilateral postpartum VAD showed no statistical difference. Most of the included studies recommend early suspension and management for a bet- ter prognosis and prevention of complications. Conclusion: PPVAD is a severe medical condition but most cases were fully recovered after an early and proper antithrombotic plan for each case scenario. Keywords: Vertebral artery; vertebrobasilar insufficiency; postpartum period; vertebral artery dissection Cite this article as: Adel Diab R, Shaheen N, Mohamed A, Tarek Hefnawy M, Chofan Charo D, Meshref M. Clinical Characteristics, Course, and Outcomes of Vertebral Artery Dissections in the Postpartum Period; a Pooled Analysis of Published Case Reports. Arch Acad Emerg Med. 2023; 11(1): e26. https://doi.org/10.22037/aaem.v11i1.1814. 1. Introduction Vertebral artery dissection (VAD) can be extracranial or in- tracranial and unilateral or bilateral with different prognoses ranging from complete healing to serious neurological se- quels (1). Dissection of cervical, vertebral, or carotid arter- ∗Corresponding Author: Rehab Adel Diab; Faculty of Medicine, Al-Azhar University, Cairo, Egypt. Postal code: 44718 Email: re- hab_diab97research@outlook.com. Tel: +20 127 245 1274, ORCID: https://orcid.org/0000-0002-6552-4900. ies is rare, but once occurring, it can be fatal. VADs com- monly occur in young poststroke patients but rarely affect patients in the postpartum period (2, 3). The postpartum period is a distressing period associated with headaches and other symptoms that make the diagnosis of postpartum ver- tebral artery dissection (PPVAD) challenging due to common symptoms between both. The incidence of headache report- ing in the postpartum period is ranging from 11% to 80% (4), So the vertebral artery dissection should be considered in differential diagnosis for patients suffering from headaches in the postpartum period for early diagnosis and better out- This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index R. Adel Diab et al. 2 come. The incidence of spontaneous vertebral artery dissec- tion ranges from 1 to 1.5 per 100.00, annually (5). 2.4% of symptomatic spontaneous VAD cases presented in the post- partum period and women are 2.5 times more likely than men to get VAD (3, 6). VAD can lead to stroke with an esti- mated incidence of one per 100,000 individuals annually (7), and stroke can lead to VAD (7, 8). The etiology of spontaneous postpartum vertebral artery dis- section is still unknown, but there are potential risk factors that can be considered to predispose it in the postpartum period, like hormonal and hemodynamic changes occurring during pregnancy and Valsalva maneuver (9). Due to the lack of literature about the clinical picture and management of PPVAD, our study aimed to pool and analyze the most frequent symptoms, signs, complications, and the strategies that are widely used in management of these cases. 2. Methods 2.1. Search strategy The literature review was conducted on Feb 24, 2022, using the terms (("Vertebral Artery"[Mesh]) OR ("Verte- bral Artery Dissection"[Mesh] OR "Vertebrobasilar Insuffi- ciency"[Mesh] OR "PICA syndrome" [Supplementary Con- cept]) AND ("Postpartum*"[Mesh]). Using PubMed, Google Scholar, Ovid, Web of Science, and Scopus databases, we searched for case series and case reports on VAD following childbirth. Researchers independently conducted the search to find the studies matching the keywords. All studies re- porting cases of vertebral artery dissection after childbirth were included in the search (Figure 1). The analysis did not include review articles or consensus statements. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used to present inclusions and exclusions (10). 2.2. Study Selection, Data Extraction, and Data Analysis Articles were selected based on predetermined criteria after title and abstract screening by two independent reviewers. The inclusion criteria were clinical case reports or series that reported the clinical characteristics, treatment protocol, and outcomes of PPVAD. Based on the following exclusion crite- ria, several steps were taken to select included studies. 1) Studies that are not tailored for humans (such as in vitro or animal studies), 2) Research not collecting original primary data (review, protocol, editorial, letter, etc.), 3) No full text of the research results was provided (i.e., abstracts of confer- ence posters), and 4) Studies in a language other than En- glish. 2.3. Quality assessment The overall quality of the case series and the case reports was assessed. The Joanna Briggs Institute ( JBI) Critical Appraisal checklist was used in the quality assessment of Case Reports (11), while the NIH Quality Assessment Tool was used for Case Series (12) (Appendix 1 & 2). 2.4. Data Analysis Python 3.0 was used for data management and cleaning as well as statistical analysis. A comparison was made between patients that suffered from unilateral dissection and patients that faced a bilateral dissection. Other variables were inves- tigated as well, like whether having multiple previous preg- nancies affected the final outcome or time to dissection. The Mann-Whitney test was used for numerical data, and Fis- cher’s Exact test was used for categorical data. 3. Results 3.1. Characteristics of included studies In total, 163 studies were found in PubMed, Google Scholar, Ovid, Web of Science, and Scopus using our search criteria. A total of 74 full-text articles were reviewed after excluding duplicate studies, studies lacking clinical data, review arti- cles, and articles unrelated to our study objective. Based on the review, 32 studies met our inclusion criteria; there- fore, 32 studies about vertebral artery dissection after birth were reviewed and analyzed (Figure 1). Characteristics of in- cluded studies are summarized in tables 1 and 2. Studies most commonly reported diagnosis via MRI with 28 (64%) and CT-angiography with 29 (66%) case. Only 8 (18%) cases reported the use of ECG as a diagnostic tool for VAD along- side one or more of the main modalities mentioned. Based on the reported data, most studies used anticoagulant and antiplatelet drugs to treat VAD, including warfarin, aspirin, and enoxaparin as well as antihypertensive drugs. 3.2. Pooled analysis of reported cases Pooled analysis of cases is presented in table 3. The stud- ies included a total of 44 patients who suffered from post- partum vertebral dissection with a mean age of 34.26 ± 3.50 years. The average time between delivery and dissection was 24.37 ± 13.7 days. 28 (64%) of the patients developed unilat- eral dissection, whereas the remaining 16 (36%) developed bilateral dissection. 20 (45%) of the patients reported deliv- ering via vaginal delivery, 16 (36%) reported delivering via C- sections, whereas the remaining 8 (19%) did not report a spe- cific delivery type. The most frequent signs and symptoms were headache 39 (89%) and neck pain 28 (64%). 23 (52%) of the patients had high blood pressure after pregnancy, whereas only 4 (9%) pa- This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index 3 Archives of Academic Emergency Medicine. 2023; 11(1): e26 Table 1: Summary of the included studies; number of patients, mean age (years), obstetric code, delivery type, and vessels affected Study ID No. Mean Age (years) Obstetric Code Delivery type Affected vessels (side) Azad, 2021(19) 12 31.8 NA 9 Vaginal 3 Cesarean 2 Vertebral (R), 4 Vertebral (L),6 Vertebral (Both) Borelli, 2012(31) 1 32 G2P2 Cesarean Vertebral (L) Brantley, 2012(14) 1 32 G3P3 Vaginal Vertebral (L), LAD, IM(L) Cenkowski, 2012(36) 1 35 G2P2 NA Vertebral (R), obtuse marginal coronary artery Drazin, 2012(24) 1 37 PG Vaginal Vertebral (Both) Drăghici, 2021(6) 1 37 G3P3 Cesarean Vertebral (R), Basilar Feldman, 2019(19) 1 41 G5P4 Cesarean Vertebral (R), RSCA Finley, 2015(9) 1 35 G5P5 Cesarean Vertebral (R) Gasecki,1999(42) 4 32.5 G6P4 3 Vaginal 1 Cesarean One vertebral, three internal carotids Gomez-Rojas, 2020(44) 1 37 NA NA Vertebral (Both) Jeannie, 2014(41) 5 33.4 NA 4 Vaginal 1 Cesarean 1 Vertebral (R ), 3 vertebral (Both), 2 Inter- nal carotid (L) Kaplan, 1993(38) 1 41 G4P4 Vaginal Vertebral (L) Keane, 2019(26) 1 30 G2P2 Cesarean vertebral (L), internal carotid (L), PICA Kelft, 1992(27) 1 31 PG Vaginal delivery vertebral (R) Basilar artery Levy, 2011(32) 1 32 G2P3 Vaginal Vertebral, transverse, and sigmoid sinuses (L) Manasewitsch, 2020(25) 1 31 NA Cesarean Vertebral (L) McKinney, 2010(34) 1 41 NA Cesarean Vertebral (Both), Basilar, PCA Mikeal levey 2011(32) 1 32 P3G3 Vaginal Vertebral (R), transverse and sigmoid sinus (L) Mitchell, LA. 2014(39) 1 NA NA NA Vertebral (Both) Monari,2021(45) 1 39 NA Cesarean Vertebral (R) Nehme, 2020(23) 1 36 G2P2 Cesarean Vertebral (both) Nishimura, 2015(29) 1 35 G1P1 NA Vertebral (R) Pires, 2011(33) 1 31 G1P1 Cesarean Vertebral (Both) Previtra, 2012(37) 1 34 NA NA Vertebral (R) Sano, K. 2021(40) 1 38 G2P2 Vaginal Vertebral (L), MCA (Both), PCA (both) Shanmugalingam, 2016(43) 4 31.25 G2P2 Cesarean 1 Vertebral (R), 3 vertebral intramural thrombus Simon, 2015(30) 1 31 G4P4 Vaginal Vertebral (L), Internal carotid (Both) Spence, 2016(35) 1 33 G2P2 NA Vertebral (Both), LAD, LCX, Celiac, SMA, IMA Not applicable (NA), Right (R), Left (L), Gravida 2 /Para 2 (G2P2), PG: Primigravida, LAD: left anterior descending artery; IMA: Internal Mary artery; RSCA: right subclavian artery; PICA: Posterior inferior cerebellar artery; PCA: Posterior cerebral artery; MCA: Posterior cerebral artery; LCX: left circumflex artery ; SMA: Superior mesenteric artery. tients reported hypertension during pregnancy as well. Ad- ditionally, 14 (32%) of the patients had associated syndromes including Opal ski Syndrome, HELP syndrome, Horner Syn- drome, and postpartum angiopathy. Based on the reported data, 2 (5%) patients had at least one failed pregnancy, 5 (11%) patients had trauma injury, 7 (16%) patients had surgical history (3 caesareans, 1 vacuum- assisted vaginal delivery, 1 thyroidectomy, and 2 diagnostic laparoscopies. As for the final outcome, 31 (70%) reported being fully recovered, 4 (9%) did not undergo full recovery and the remaining 9 (21%) did not provide data for follow-up final outcomes. There was no statistical difference between unilateral and bi- lateral cases and also gravid 1 or >1 regarding age distribu- tion, time from delivery to dissection, and final outcomes (Table 4). 4. Discussion VAD is a rare and serious condition in the postpartum period. According to literature, cervical dissection represents 6% of spontaneous dissections in females under 50 years of age (8). Using our results, we found that the mean age of the patients was 34.26 ± 3.50 years. Cervical dissections in the postpar- tum period mainly include vertebral and carotid artery dis- sections; both are reported to occur unilaterally or bilater- ally (9, 13). Our study showed that 64% of the included pa- tients developed unilateral vertebral artery dissection while This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index R. Adel Diab et al. 4 Table 2: Summary of the included studies; time from delivery (days), clinical presentation, comorbidities, investigation, treatment, and final outcome Study ID Time from delivery (days) Clinical presentation Comorbidities Investigation Treatment Outcome Azad, 2021(19) 12 Headache was reported in all cases and some reported neck pain, weakness, and stroke, and a single case reported SAH HTN of pregnancy in all cases, some reported HELLP syndrome, Loeys-Dietz syndrome, Factor V Ledin syndrome, Reversible vasoconstriction syndrome and MTHFR mutation MRI showed the affected arteries in each patient Anticoagulants and endovascular surgery Full recovery Borelli, 2012(31) 10 Headache, hypertension, dizziness, and mild right-side weakness HELLP syndrome and preeclampsia MRI Showed bilateral left predominant thalamic infarction, and CT angiogram showed left Vertebral artery dissection at V3 and V4 segments Antiplatelet (Aspirin) NA Brantley, 2012(14) 7 Hypertension and neck pain ACS ECG with cardiac Biomarkers: suggestive for NSTEMI MRI: not done CT-angiogram: dissection of the left vertebral artery at the level of C6 to C7 and dissection involving the LAD, not the main coronary ECHO 6 days later: no motion, valvular abnormalities with the normal system, IC function Anticoagulant therapy (Heparin), Antiplatelets (Aspirin, clopidogrel) and CABG for coronary dissection Full recovery Cenkowski 2012(36) 210 Nausea, vomiting, chest pain with elevated cardiac enzymes, and one month later presented with numbness in her left arm and face. NA ECG: inferior STEMI CT angiogram: dissection of r.t vertebral v1 segment with aneurysmal dilatation and Obtuse marginal coronary artery. ECHO: EF= 50-55%. Antiplatelet (warfarin) and Antiplatelet (aspirin, clopidogrel), statins, metoprolol, ramipril, nitroglycerin NA Drazin, 2012(24) immediately Headache, neck pain, Hypertension, photophobia and SAH NA MRI: beaded appearance along cervical segments of both vertebral arteries. CT-angiogram: narrowed vertebral arteries. Anticoagulants therapy Full recovery Drăghici, 2021(6) 56 Headache, neck pain dizziness, palsies, stroke, dysphagia, and extracranial stroke Autoimmune thyroiditis MRI: Bilateral infarction of the pons. CT-angiogram: filling defect of the basilar artery with narrowing of the right vertebral artery suggesting dissection Anticoagulant therapy (Heparin with enoxaparin) and Antiplatelets (Aspirin) NA Feldman, 2019(28) 3 Visual symptoms, sensory deficit, intracranial stroke NA MRI: restricted diffusion in r.t cerebellum, right pons, and midbrain CT-angiogram: Areas of narrowing and dilatation artery vertebral artery Aspirin Full recovery Finley, 2015(9) 21 Headache, hypertension, dizziness, vertigo, nausea, vomiting, and visual symptoms NA MRI: diffusion defect within the cerebellar hemispheres bilateral more in the r.t CT-angiogram: R.t VAD with variations in the l.t vertebral artery at the junction with the proximal aorta. Anticoagulant therapy (oral warfarin) Full recovery This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index 5 Archives of Academic Emergency Medicine. 2023; 11(1): e26 Table 2: Summary of the included studies; time from delivery (days), clinical presentation, comorbidities, investigation, treatment, and final outcome Study ID Time from delivery (days) Clinical presentation Comorbidities Investigation Treatment Outcome Gasecki, 1999(42) 14 Headache, vertigo, visual symptoms, cranial nerves palsies, Horner, right side ataxia, sensory deficit, and speech abnormalities NA MRI: some cases show no brain abnormalities, and the others show diffusion defect at areas supplied by the occluded artery CT-angiogram: suggestive of dissection of either vertebral or carotid artery Anticoagulant therapy (Heparin) 3 Full re- coveries and one death Gomez- Rojas. 2020(44) NA Headache, dizziness, vertigo, hypertension, nausea, vomiting, sensory deficit, and neck pain NA MRI: showed a large area of ischemia at PICA territory and smaller areas at the left superior parasagittal cerebellum CT-angiogram: narrowing of the caliber diameter suggesting dissection of both vertebral arteries Anticoagulants (warfarin and solitary case used heparin) Full recovery Jeannie, 2014(41) 23 Headache, hypertension, neck pain, visual symptoms, intracranial SAH NA MRI, MRA and CT-angiogram: suggesting dissection of vertebral and carotid arteries for each corresponding case Anticoagulant therapy (oral or heparin) and dual antiplatelets Full recovery Kaplan, 1993(38) 17 Headache, hypertension, nausea, neck pain, visual symptoms, extracranial stroke NA MRI: infarction in the left medulla and cerebellar hemisphere. CT-angiogram: dissection of the left vertebral and left PICA Antiplatelet (Aspirin), statins and amlodipine Not Fully recov- ered Keane, 2019(26) 3 Hypertension, headache, neck pain and subarachnoid hemorrhage NA MRI: NA CT-angiogram left vertebral artery dissection with pseudoaneurysm Balloon occlusion of the vertebral artery with Anticoagulant (warfarin) NA Kelft, 1992(27) 1 Headache, confusion, Ataxia, Horner sign, confusion, ipsilateral ataxia, nystagmus, hpa glesia on right side of face and left side of the body. NA MRI: r.t thalamic, post limb of internal capsule and occipital lobe ischemia. CT-angiogram: normal Vertebral artery -angiogram: dissection of the basilar artery with right vertebral affection with proximal thrombosis Antiplatelets (Ticlopidine) Fully re- covered Levy, 2011(32) NA Headache, hypertension, dizziness, nausea, vomiting, sensory deficit, cranial nerve palsies and intracranial stroke Opalski syndrome MRI: infarction in the brainstem and cerebellum. CT-venogram: CVST in the transverse and sigmoid sinus ECHO: mild TR Anticoagulant Therapy (heparin) Full recovery Manasew- itsch, 2020(3) 10 Headache, vertigo, nausea, vomiting, gait abnormalities, ataxia, and stroke chorioamnionitis, IDA MRI: infarction at the left cerebellar hemisphere CT-angiogram: dissection of the left vertebral artery and left PICA Anticoagulant therapy (enoxaparin) NA This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index R. Adel Diab et al. 6 Table 2: Summary of the included studies; time from delivery (days), clinical presentation, comorbidities, investigation, treatment, and final outcome Study ID Time from delivery (days) Clinical presentation Comorbidities Investigation Treatment Outcome McKinney, 2010(34) 6 Hypertension and headache, visual symptoms, and stroke NA MRI: Multiple infarctions at areas supplied by post circulation. CT-angiogram: dissection of both vertebral and basilar arteries with proximal segments dilatation of the posterior circulation. Anticoagulants (Heparin), Antiplatelet (Aspirin), nicardipine infusion and levetiracetam Not Fully recov- ered Mikeal levey, 2011(32) 14 Headache, neck pain, hypertension, vomiting, dizziness, vertigo, visual symptoms, sensory deficit, and intracranial and extracranial stroke Opalski syndrome MRI: infarction of Medulla, cerebellum, and pyramidal dissection CT-angiogram not done ECHO: mild TR Anticoagulants (heparin) Full recovery Mitchell, 2014(39) 10 Headache, dizziness, visual symptoms, sensory deficit, and stroke NA MRI: intramedullary infarction. CT-angiogram: the abnormal appearance of the right vertebral artery Antiplatelet (Aspirin and clopidogrel) Not Fully recov- ered Monari, 2021(5) NA Headache, nausea, vomiting, dizziness, vertigo, visual symptoms, gait abnormalities and stroke NA MRI: infarction of the posterolateral portion of the brain bulb. CT-angiogram: right vertebral artery dissection. Anticoagulant therapy (heparin and enoxaparin) and Antiplatelet (aspirin and clopidogrel) NA Nehme, 2020(23) 10 Headache, neck pain, hypertension, visual symptoms, gait abnormalities, SAH NA MRI: hematomas at dissection sites CT-angiogram: dissection of both vertebral arteries Endovascular surgery with CCB and Antiplatelets (aspirin) NA Nishimura, 2015(29) 5 Headache, neck pain, hypertension, and seizures PRES MRI: infarction in the subcortical white matter CT-angiogram: stenosis of the right vertebral artery Magnesium sulfate and Nicardipine Full recovery Pires, 2011(33) 18 Headache, neck pain, migraine, anosognosia, dysarthria, NA MRI: Contraindicated. Digital subtraction angiogram: dissection of Both ICA and left vertebral artery (string beads) Anticoagulant therapy Not Fully recov- ered Previtra, 2012(37) 14-21 Headache, neck pain, vertigo, nausea, vomiting, Right faciobrachial syndrome, intracranial stroke History of cervical manipulation Brain MRI was normal, SAT MRI did not show dissection in Vertebral (R) Anticoagulants, rehabilitation Full recovery Sano, 2021(40) 18 Headache, neck pain and subarachnoid hemorrhage NA MRI: infarction in both basal ganglia and right occipital cortex CT-angiogram: NA Lowering BP without any thrombolytic therapy Full recovery Shanmugalingam, 2016(43) 5.3 Headache, hypertension, dizziness, and neck pain NA MRI: no evidence of post circulation infarction. CT-angiogram: features suggesting dissection or intramural thrombus of vertebral arteries Anticoagulant therapy or antiplatelets Full recovery This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index 7 Archives of Academic Emergency Medicine. 2023; 11(1): e26 Table 2: Summary of the included studies; time from delivery (days), clinical presentation, comorbidities, investigation, treatment, and final outcome Study ID Time from delivery (days) Clinical presentation Comorbidities Investigation Treatment Outcome Simon, 2015(30) 21 Headache with mildly decreased facial sensation Endometriosis and anemia MRI: Increased intensity of the vertebral and carotid arteries bilaterally with near occlusion of the R.t internal carotid CT-angiogram: dissection of the left vertebral and bilateral internal carotid Anticoagulant therapy (heparin and transferred to another hospital) NA Spence, 2016(35) 21 Hypertension and headache and neck pain Repaired sinus venous ASD, ACS ECG: anterior and inferior STE with reciprocal STD in the lateral leads MRI: NA CT-angiogram: dissection of both vertebral arteries, LAD, LCX, Celiac, SMA, and MA ECHO: no abnormalities detected. Revascularization and Antiplatelet (aspirin, clopidogrel), statins, BB, amlodipine, ramipril, nitroglycerin Full recovery SAH: subarachnoid hemorrhage; HTN: hypertension; HELLP: Hemolysis, Elevated Liver enzymes and Low Platelets; MTHFR: methylenetetrahydrofolate reductase; MRI: magnetic resonance imaging; CT: computed tomography; ECG: electrocardiography; NSTEMI: non-ST-segment elevation myocardial infarction; LAD: left anterior descending artery; ECHO: echocardiography. 36% developed bilateral vertebral artery dissection. Some studies reported the extension of VAD to include the basilar artery and other studies presented multiple vessel dis- sections as reported in a previous study (14) in which there was a rare case of postpartum multi-arterial dissection, in- volving the vertebral artery, coronary artery, and the internal mammary artery (6, 15). The exact incidence rate of cervi- cal dissection is unknown; however, it has an estimated inci- dence of 2.6–3.0 cases per 100,000 population per year, with VAD being 3–5 times less frequent than carotid artery dissec- tion (16, 17). Females are 2.5 times more likely to get VAD than males (17). Moreover, it has been reported that 2.4% of cervical dissections occur in females in the postpartum pe- riod (18). In addition, VAD is a leading cause of ischemic stroke among young people (19). Postpartum cervical dissection can be caused by a variety of underlying factors, but the mechanisms are unclear. There are several hypotheses in literature regarding the effects of pregnancy hormones, especially progesterone, on collagen synthesis in the tunica media of vessels, increasing its sen- sitivity to systemic stressors like hypertension (6, 7, 9, 19). Approximately 31 (70%) of patients presented with neurolog- ical symptoms. The main clinical presentation of VAD is typ- ically acute, severe neck pain in the occipito-cervical region, either with or without headache (20). Our results showed that VAD in females in the postpartum period was mainly pre- sented with headache as the commonest presentation in 39 (89%) of the cases followed by neck pain in 28 (64%), hyper- tension in 23 (52%) and visual defects symptoms in 17 (39%) of the cases. Physical examination in VAD may reveal nys- tagmus, truncal ataxia, loss of taste, impairment in pain and thermal sensation, and ophthalmoplegia; however, that clin- ical picture may be vague, and symptoms overlap with that of the postpartum period making the differential diagnosis even more difficult (20). Investigations used to diagnose VAD are CT, CTA, and MRI. CT scan can show the ischemia in the posterior fossa, subarachnoid hemorrhage, vertebral artery occlusion and mural thrombus. MRI can also prove the di- agnosis but is not always available. CTA can easily show any regularity or thickening in the vascular wall, this makes the CTA the investigation of choice in the case of VAD (20). Our finding showed that two or more of these investigations are usually used to establish the diagnosis or complications and CT was the commonest investigation used with 66% and MRI with 64% of cases. Regarding the management of VAD, antithrombotic therapy should be started as soon as possible. Both antiplatelets and anticoagulants are the main lines in treatment, in a previous randomized trial (CADISS Trial) there was no difference in the efficacy of anticoagulants and antiplatelets in prevent- ing stroke in patients suffering from vertical artery dissec- tions including carotid and vertebral arteries (21). Addition- ally, this conclusion was supported by a case series study of twelve patients who suffered cervical dissections, in which there was no difference in prognosis or complications (19). Anticoagulation is to be started with low-molecular-weight or unfractionated heparin followed by oral anticoagulation, while antiplatelets are applied for mono or dual therapy (10). This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index R. Adel Diab et al. 8 Figure 1: PRISMA flow diagram of study screening and inclusion. Antiplatelets are widely preferred because of their availabil- ity and low cost. According to existing guidelines, antithrom- botics should be continued for about three to six months, with no clear clinical evidence of the exact duration yet (1, 9). In the absence of exact duration and choice of antithrom- botic strategy, it is recommended to be individually adapted according to each case scenario (22). Clearly, this was evident from the management strategies in our included reports, in which antithrombotic choice was re- spected. 31 patients (70%) showed a full recovery after proper management while 4 cases (9%) showed incomplete recov- ery and the rest were not reported. Although postpartum VAD can carry a good prognosis it can cause permanent dam- ages if complicated with stroke and infarction. VAD can de- velop complications such as cerebellar and brain stem infarc- tions, subarachnoid hemorrhage, pseudoaneurysm and cra- nial nerves affection (20). And all of these complications are reported in postpartum VAD in the included cases, either as a sign or a complication, along with stroke that developed in 10 patients (23%) and the subarachnoid hemorrhage that devel- oped in 6 patients (14%); thus, early diagnosis and manage- ment of VAD are required, the sooner the better. 5. Limitations and recommendations This study should be considered in light of several limita- tions. The first limitation is that there is a small number This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index 9 Archives of Academic Emergency Medicine. 2023; 11(1): e26 Table 3: Pooled analysis of data of patients with post-partum verte- bral artery dissection (n = 44) Variables Number (%) Age (year) Mean ± SD 34.26 ± 3.50 Previous deliveries No 30 (68.1) Signs and Symptoms Headache 39 (88.3) Neck pain 28 (63.6) Hypertension 23 (52.2) Visual symptoms 17 (38.6) Stroke 10 (22.7) Dizziness 10(22.7) Nausea 10 (22.7) Vomiting 9 (20.4) Vertigo 8 (18.2) Sensory deficits 7 (15.9) Subarachnoid hemorrhage 6 (13.6) Dysphagia 5 (11.3) Ataxia 4 (9.0) Cranial nerve 3 (6.8) Gait problems 3 (6.8) Palsies 3 (6.8) Hearing changes 2 (4.5) Weakness 1 (2.2) Delivery Type Vaginal 20 (45.4) Cesarean 16 (36.4) Arteries dissected Unilateral dissection 28 (63.6) Bilateral dissection 16 (36.4) Pseudo-aneurysm 4 (9.0) Recovery status Full recovery 31 (70.4) Not fully recovered 4 (9.0) Data are presented as frequency (%). SD: standard deviation. of cases, there is also lack of follow-up data. The specific dose of antithrombotic is different in each case scenario and cannot be generalized. Secondly, some clinical pictures are not completely reported when the cases are transported from one center to another or in case of long duration of hospital admission, in which not all the complications or side effects are fairly mentioned. The lack of literature about postpar- tum dissections is a remarkable limitation so further reports and high-quality evidence-based studies are strongly recom- mended. 6. Conclusions PPVAD is a severe medical condition; most cases were fully recovered after an early and proper antithrombotic plan for each case scenario. Headache and neck pain were the com- monest PPVAD presentations. Age, type of delivery, and Gravida were not statistically associated with PPVAD. Unilat- eral and bilateral postpartum VAD showed no statistical dif- ference in the recorded outcomes of the patients. Most of the included studies recommend early suspicion and manage- ment for a better prognosis and prevention of complications. 7. Declarations 7.1. Acknowledgments We would to express our sincere thanks to all authors of the included studies and to Medical research group of Egypt un- der supervision of Dr. Ahmed Negida for their support and encouragement in carrying out this project. 7.2. Conflict of interest The authors have no conflict of interest to declare. 7.3. Fundings and supports None. 7.4. Authors’ contribution Rehab Adel Diab: Conceptualization, Writing-Original draft, review, and editing. Nour Shaheen: Methodology, Writing- Original draft, review, and editing. Abdelrahman Mohamed: Formal Analysis Mahmoud Tarek Hefnawy: Writing-Original draft, review, and editing Dilawer chofan charo: Writing- Original draft, review, and editing Mostafa Meshref: Writing- Original draft, review, and editing. All Authors read and ap- proved final version of the manuscript. 7.5. 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Case Reports in Medicine. 2020;2020:1-16. 45. Monari F, Busani S, Imbrogno MG, Neri I, Girardis M, Ghirardini A, et al. Vertebral artery dissection in term pregnancy after cervical spine manipulation: a case re- port and review the literature. Journal of Medical Case Reports. 2021;15(1). This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index R. Adel Diab et al. 12 Appendix 1: The Joanna Briggs Institute ( JBI) Critical Appraisal checklist for Case Reports (11) Study ID Were patient’s de- mographic characteris- tics clearly described? Was the patient’s history clearly described and presented as a timeline? Was the current clinical condition of the patient on presen- tation clearly described? Were diagnostic tests or assessment methods and the results clearly described? Was the interven- tion(s) or treatment proce- dure(s) clearly described? Was the post- intervention clinical condition clearly described? Were adverse events (harms) or unantici- pated events identified and described? Does the case report provide takeaway lessons? Total yes, (Maxi- mum = 8) Nehme, 2020(23) Yes Yes Yes Yes Yes Yes Yes Yes 8 Drazin, 2012(24) Yes Yes Yes Yes Yes Unclear No Yes 6 Manasewitsch, 2020(25) Yes Yes Yes Yes Yes Unclear Unclear Yes 6 Monari, 2021(5) Yes Yes Yes Yes Yes Yes Yes Yes 8 Drăghici, 2021(6) Yes Yes Yes Yes Yes Yes No Yes 7 Keane, 2019(26) Yes Yes Yes Yes Unclear Yes Yes Yes 7 Van de Kelft, 1992(27) Yes Yes Yes Yes Unclear Yes Yes No 6 Feldman, 2019(28) Yes Yes Yes No Yes Yes Yes Yes 7 Finley, 2015(9) Yes Yes Yes Yes No Yes Yes Yes 7 Nishimura, 2015(29) Yes Yes Yes Yes Yes Yes Yes Yes 8 Simon, 2014(30) Yes Yes Yes Yes No Yes No No 5 Borelli, 2012(31) Yes No Yes Yes Unclear Yes No Yes 5 Levey, 2011(32) Yes Yes Yes Yes Yes Yes Yes Yes 8 Hutton P, 2010(14) Unclear Yes Yes Yes Unclear Yes No Yes 5 Pires, 2011(33) Unclear No Yes Yes Unclear Unclear Yes Yes 4 McKinney, 2010(34) Yes Unclear Yes Yes Yes Yes Yes Yes 7 Levy, 2011(32) Yes Yes Yes Yes Yes Yes Yes Yes 8 Spence, 2016(35) Yes Yes Yes Yes Yes Yes Yes Yes 8 Keane, 2019(26) Yes Yes Yes Yes Yes Yes Yes Yes 8 Cenkowski, 2012(36) Yes No Yes Yes Yes Yes Yes Yes 7 Previtra, 2012(37) Yes Unclear Yes Yes Yes Yes Yes Yes 7 Kaplan, 2016(38) Yes Yes Yes Yes Yes Unclear Yes Yes 7 Mitchell, 2014(39) No Yes Yes Yes Yes Yes Yes Yes 7 Sano, 2021(40) Yes Yes Yes Yes No Yes Yes Yes 7 This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index 13 Archives of Academic Emergency Medicine. 2023; 11(1): e26 Appendix 2: The NIH Quality Assessment Tool for Case Series, Good: Met 7-9 criteria, Fair: Met 4-6 criteria, Poor: Met 0-3 criteria (12) Study ID Was the study ques- tion or objec- tive clearly stated? Was the study population clearly and fully described, including a case definition? Were the cases consec- utive? Were the subjects compa- rable? Was the inter- vention clearly de- scribed? Were the outcome measures clearly defined, valid, reliable, and implemented consistently across all study participants? Was the length of follow-up ade- quate? Were the statistical methods well- described? Were the results well- described? Total Quality Score Quality Jeannie, 2014(41) Yes Yes Yes NA Yes Yes Yes NR Yes 7 Good Gasecki, 1999(42) Yes Yes NR NA No Yes Yes NR Yes 5 Fair Shanmu- galingam, 2016(43) Yes Yes No NA Yes Yes Yes NR Yes 6 Fair Azad, 2021(19) Yes Yes Yes Yes Yes No Yes Yes Yes 8 Good NA: not applicable, NIH: National Institutes of Health, NR: not reported. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: https://journals.sbmu.ac.ir/aaem/index.php/AAEM/index Introduction Methods Results Discussion Limitations and recommendations Conclusions Declarations References