Neurological Manifestations in Peri-Partum Period: Imaging Overview

Preeclampsia and Cerebrovascular Disease.

We thank Dr Satoru Takeuchi and his colleagues for their comments [1] about our article on the probable causal association between intracranial hypotension (IH) and posterior reversible encephalopathy syndrome (PRES) [2]. They ask us to further debate the possible role of reversible cerebral vasoconstriction syndrome (RCVS) in the clinical history of our patient. RCVS is a group of disorders characterized by the reversible segmental and the multifocal vasoconstriction of cerebral arteries at angiography and severe “thunderclap” headache with or without focal neurological deficits or seizures [3]. In our patient, RCVS was mainly ruled out because of normal MRA findings. As described by Ducros et al. [4], some patients (only 9% of the cases) even with an initial normal MRA could have a repeated MRA showing vessels narrowing, but we did not suspected RCVS because of the headache clinical features and the neurological signs. In fact, our patient presented a bilateral headache, pressure-like, with a postural component, different from the thunderclap headache, typical of RCVS. It is possible that the mild headache onset was consequent to the epidural anesthesia, but the headache did not change in severity until the patient discharge, some days after the end of anesthesia effect. Moreover, the MR findings were typical of PRES, showing multiple symmetric and bilateral hypertintensities on T2-weighted images in the posterior territories, with high signal on DWI, as well as on ADC maps. It has been described that a post-partum RCVS could cause PRES [5, 6], but we supposed that the demonstrated intra-cranial hypotension (IH), subsequent to the inadvertent dural puncture, was the leading cause of PRES. This hypothesis is mainly supported by the prompt resolution of the neurological symptoms and the radiological alterations of both IH and PRES, only after the treatment of IH with a blood patch. This would be difficult to be expected in case of RCVS. Finally, we know that the association between IH and PRES is only a presumption and that there are some limitations of our single experience and of the proofs provided. We look forward to further contributions that could eventually clarify the relationship between IH and PRES.

We read with interest the recent article by Pugliese et al. [1] concerning a case of intracranial hypotension and PRES and the debate that followed [2, 3]. The authors reported a rare patient who presented worsening of headache and seizures at 7 days after spinal anesthesia. Brain MRI showed signs of intracranial hypotension (IH) and posterior reversible encephalopathy syndrome (PRES). Therefore, the authors diagnosed the patient as PRES caused by IH, secondary to spinal anesthesia. We wish to provide further comment. Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by severe acute headache and constriction of cerebral arteries [4, 6]. IH is also a cause of RCVS [5, 7]. RCVS should not be confused with PRES although there is overlap in both the presumed underlying mechanisms and the predisposing factors [5]. Indeed, some patients can actually exhibit RCVS with PRES [4, 5]. The authors ruled out RCVS, mainly because of the subacute and progressive onset of the clinical symptoms and normal MRA findings. However, it is possible that the characteristics of headache may be changed by anesthesia. Further, Ducros et al. [6] described that, in some patients who had an initial normal MRA at a mean of 5.5 days (range 2–9 days) after headache onset, a repeat MRA showed visible narrowings at a mean of 13.6 days (range 9–20 days). In contrast, a repeat MRA was not performed in the cases presented by Pugliese et al., suggesting that the authors cannot rule out the possibility of RCVS.

Microvascular brain injury is well recognized in neuropsychiatric systemic lupus erythematosus (SLE), but cerebral large artery involvement is being debated. Three females with SLE, aged 9 to 14years, had immunosuppressive treatment intensification because of lupus nephritis. Within the following days or weeks, they presented with intense cephalalgia - isolated or associated with neurological symptoms - and no or mild hypertension. Magnetic resonance angiography showed multiple stenoses within the circle of Willis. One patient had subsequent small subcortical cerebral infarction. Two patients were treated for neuropsychiatric SLE; one patient was treated for reversible cerebral vasoconstriction syndrome (RCVS). Angiography normalized within a few weeks in all three patients. Retrospectively, clinical and radiological features suggest that RCVS was the most likely diagnosis in all patients. Multidisciplinary analysis of clinical and angiographic features is recommended, as RCVS is rare in children and its recognition may help to adjust treatment. WHAT THIS PAPER ADDS: Reversible vasoconstriction syndrome was observed in paediatric systemic lupus erythematosus. Thorough imaging analysis was necessary to address this diagnosis in paediatric patients.

Body of the Abstract: (1) To report a rare case of Reversible Cerebral Vasoconstriction Syndrome (RCVS) and associated intraparenchymal and subarachnoid hemorrhage following induction of spinal anesthesia in an uncomplicated, elective C-section (2) To discuss its potentially life threatening or well-being altering effects (3) To review the pathophysiology, diagnosis and potential treatments of the syndrome. Introduction: Reversible cerebral vasoconstriction syndrome (RCVS) is a rare condition defined clinically by symptoms of a severe recurrent headache described as a thunderclap headache, cerebral vasoconstriction of at least two different arteries on imaging, and resolution of vasoconstriction within three months. Complications include non-aneurysmal subarachnoid hemorrhage, seizure, stroke, and intracerebral hemorrhage. More than half of cases of RCVS occur postpartum or after use of vasoactive substances such as adrenergic or serotonergic drugs. Triggers include illicit drugs, eclampsia, or strenuous physical or sexual activity. As RCVS most commonly occurs during the postpartum period, it is extremely rare to encounter RCVS during the antepartum or peripartum periods. There has been only one other reported case of RCVS while undergoing spinal anesthesia for a C-section. Presented is a patient diagnosed with RCVS after spinal anesthesia during an elective C-section subsequently complicated by seizure, intracerebral and subarachnoid hemorrhage. Case Presentation: A 32-yearold G2 now P2002 patient presented at 39 6/7 weeks gestational age for elective primary C-section for a history of delivery complications with the first pregnancy. Medical history was unremarkable. First pregnancy labor epidural analgesia was uncomplicated. Spinal anesthesia induction was uneventful. Shortly thereafter, dizziness was reported and hypotension and bradycardia (P 42, BP 76/41) developed. Treatment included IV Ephedrine and Glycopyrrolate. Frontal headache developed. The patient then developed a tonic-clonic seizure with gaze deviation and upper limb rigidity lasting 45 seconds. An oral airway was placed for respiratory assistance with 100% oxygen. The patient became alert five minutes later. Vital signs: BP 168/98 P 122.C-section was performed. After incision, the patient had a second tonic-clonic seizure lasting 30 seconds. Midazolam was given. A healthy baby was delivered with Apgars of 7 and 9. The C-section was otherwise uncomplicated. Postoperatively, the patient was alert with stable vital signs. The neurologic exam was intact. The CT showed a 1.9 x 3.8 x 1.2 cm intraparenchymal hemorrhage-right frontal lobe with a subarachnoid hemorrhage in both the right frontal lobe and right sylvian fissure. Exam was normal. Headache continued. Tertiary care facility transfer was arranged. Tertiary care evaluation with 24-hour EEG monitoring, CT angiography (CTA) and CT venogram showed no evidence of venous sinus or cortical vein thrombosis. Magnetic resonance imaging (MRI) and transcranial doppler showed vasospasm diagnostic of RCVS. Subsequent CTA showed vasospasm of three branches of the carotid artery. Hospital discharge occurred on day 6. Six-month neurological follow-up showed resolution of hemorrhage and minimal residual symptoms. Discussion: Literature review discovered only one other case of RCVS with induction of regional anesthesia. To our knowledge the associated seizure activity coupled with intraparenchymal/subarachnoid hemorrhages has not been previously reported. RCVS, an extremely rare phenomenon is estimated to occur in 0.26% of headache patients; is more frequent in middle aged women and may have variable triggering factors. It may be associated with antidepressants, illicit drugs or sympathomimetic meds. Pregnancy and vasoconstrictive meds are risk factors with an occurrence rate of 5%. The pathophysiology is unknown but felt to be due to impaired cerebral vessel autoregulation. It is hypothesized that other factors and substances including endothelial dysfunction, pro and antiangiogenic factors, serotonin, cytokines and vascular endothelial growth factor may play some role. While MRI and doppler imaging may be of assistance, CTA is most useful for diagnosis. Since static imaging alone does not confirm the diagnosis, most cases likely go undiagnosed. Rarely, complications of RCVS include stroke, seizure, cerebral hemorrhage and Posterior Reversible Encephalopathy Syndrome. There is no prophylactic or therapeutic treatment proven effective for RCVS. Recommendations include symptomatic treatment of the headache, blood pressure, and delivery if eclampsia is suspected. Calcium channel blockers are often used for vasodilatory effects, although they have not been proven to improve symptoms or outcome in RCVS. Conclusion: RCVS is a very rarely occurring vascular disorder occasionally seen postpartum. This is the first reported case of associated seizure activity and resultant intraparenchymal and subarachnoid hemorrhage occurring after induction of spinal anesthesia for an uncomplicated C-section. It demonstrates the need for awareness of this disorder as well as knowledgeable hemodynamic anesthesia management specific to its unique features. The RCVS diagnostic and management challenges dictate that case collection and research be continued.

Introduction: Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) are diagnoses that have a clinical and radiographic overlap. One particular overlap includes the presence of hemorrhage, which we studied in each population to determine its effect on outcomes. Objective: To compare characteristics and outcomes of hemorrhagic PRES and hemorrhagic RCVS populations. Methods: We conducted a review of the electronic health record at a single tertiary center from January 2008 to December 2018. Inclusion criteria were 18 years or older with clinical and radiographic evidence of PRES or RCVS. Patient demographics, presenting symptoms, imaging findings, and outcomes were compared between PRES and RCVS groups. Poor outcome was defined as discharge to skilled nursing facility or death. Analysis was performed using Pearson’s Chi-Square test. Results: Among 281 PRES and 98 RCVS cases, intracranial hemorrhage was seen on imaging in 51 PRES cases (18%) and 34 RCVS cases (35%). Headache was present in all patients with hemorrhagic RCVS but only seen in 40% of hemorrhagic PRES. Use of antidepressants or drugs of abuse was more frequent with hemorrhagic RCVS (53%) as compared to hemorrhagic PRES (7%, p <0.05). Among hemorrhagic PRES, presence of intraparenchymal hemorrhage but not subarachnoid hemorrhage was associated with vasoconstriction on arterial imaging (p<0.05). Length of stay was longer for both hemorrhagic PRES and hemorrhagic RCVS (p<0.001) compared those without hemorrhage. Presence of focal neurological deficits, motor and sensory, was associated with poor outcomes in hemorrhagic RCVS patients (p<0.05). Discharge to a rehabilitation facility was associated with hemorrhagic PRES (p<0.05), no association in those without hemorrhage. There is no evidence that discharge location is significantly different between RCVS hemorrhage and non-hemorrhage groups. Conclusion: Hemorrhage in PRES and RCVS is associated with more clinical deficits at presentation and longer hospital stays. Underlying vasoconstriction is frequent and associated with hemorrhagic PRES.

Response to correspondence concerning “Posterior reversible encephalopathy syndrome (PRES) associated with COVID-19”

Reversible cerebral vasoconstriction syndrome (RCVS) is an increasingly recognized clinical emergency characterized by acute onset of severe headaches (usually multiple thunderclap headaches) and reversible segmental stenosis of cerebral arteries (1). RCVS is associated with several potentially devastating complications or comorbidities, such as posterior reversible encephalopathy syndrome (PRES) (9%–38%), ischemic stroke (4%–54%), intracerebral hemorrhage (12%–20%), cortical subarachnoid hemorrhage (SAH) (22%–34%), or cervical artery dissection (1%–12%) and even death (2– 7). The prevalence of RCVS is unknown, but it could be higher than that of its most important differential diagnosis—aneurismal SAH when patients complain of thunderclap headaches. Although the clinical features of RCVS are distinct, the diagnosis could sometimes be difficult in the lack of awareness or alertness about the dynamic nature of the disease. This is especially the case in the very early stage of the disease, when cerebral vasoconstrictions might be insignificant on the initial angiographic studies (3,4), and ischemic or hemorrhagic complications might not have occurred. In this issue of Cephalalgia, Kameda et al. report on a case of a 30-year-old woman who developed thunderclap headaches and seizure one week post-partum (8). Magnetic resonance imaging disclosed hyperintense vessel signs and PRES on the initial fluid-attenuated inversion recovery (FLAIR) imaging in the absence of significant vasoconstriction on magnetic resonance angiography (MRA). The hyperintense vessels disappeared one week later, but vasoconstrictions of major cerebral arteries became apparent (8). Although this case is not the first one to report hyperintense vessel sign in patients with RCVS (9,10), the unique finding that hyperintense vessels predated the occurrence of cerebral vasoconstrictions raised several important questions: 1.) Could hyperintense vessel sign help diagnose RCVS in the very early stage of disease? 2.) Does this finding support the centripetal propagation theory? and 3.) How to differentiate hyperintense vessels from cortical SAH, the early complication of RCVS? Hyperintense vessels on FLAIR imaging are hypothesized to be distal branches of the cerebral arteries or their leptomeningeal anastomotic collateral vessels with very low-flow velocities attributed to severe stenosis or occlusion of proximal cerebral arteries (11). In RCVS, FLAIR hyperintense vessels could be noted in up to 22% of patients (10). The presence of hyperintense vessels in RCVS is associated with more severe vasoconstrictions and cerebral hemodynamic derangements, and could herald the occurrence of ischemic stroke or PRES (10). In the case reported by Kameda et al. (8), hyperintense vessels were noted concomitantly with PRES two days after the onset of thunderclap headaches, in the absence of MRA vasoconstrictions. If these FLAIR hyperintense vessels also came from the failure of cerebrospinal fluid (CSF) nulling effect due to stagnant or retrograde flow of distal arterioles or leptomeningeal networks, this rare observation might have serendipitously captured the point when severe vasoconstrictions were still restricted to distal arteries beyond the resolution of routine MRA. In our previous study, MRA vasoconstrictions were not at its worse point until 11–20 days after headache onset (4). In another large series, it was reported that up to 33% of the patients with RCVS had a normal early angiogram (3). In other words, in one-third of the patients,

Introduction: Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome with typical neuroimaging findings of vasogenic cerebral edema in posterior brain regions. Reversible cerebral vasoconstriction syndrome (RCVS) is diagnosed when there is reversible cerebral vessel narrowing and often with thunderclap headache. The two diseases have overlap in clinical and radiographic features. Objective: To compare clinical presentation, vascular abnormalities and imaging findings among PRES and RCVS. Methods: We searched patients in electronic health record at a single tertiary center from January 2008 to December 2018. Inclusion criteria was 18 years or older with clinical and radiographic evidence of PRES or RCVS. PRES was diagnosed by clinical presentation and presence of vasogenic edema on radiographic imaging. RCVS was determined by clinical presentation and transient arterial stenosis. Patient demographics, presenting symptoms, comorbid conditions, and imaging findings were compared between PRES and RCVS populations. Analysis was performed using Fisher’s exact test Results: Seventy-four patients with PRES and 24 patients with RCVS met inclusion criteria. The median age and presenting blood pressure did not differ between PRES and RCVS groups. PRES population consisted of fewer females (70%) compared to RCVS (92%, p=0.05). There was no significant difference in frequency of DWI lesions in PRES (37%) and RCVS (24%, p=0.308). Among patients who had arterial imaging, arterial stenosis was seen in 28% (13/46) of PRES. The occurrence of > 50% FLAIR reversibility was more common in PRES (67%) and seen less frequently in RCVS (27%, p=0.008). Conclusion: There is radiographic overlap between PRES and RCVS. About a quarter of PRES have arterial stenosis, while about a quarter of the RCVS group had FLAIR reversibility.

Introduction: Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) might represent a pathophysiological spectrum. They are commonly diagnosed separately, based on prominent clinical features. We aimed to compare clinical and radiographic findings of PRES and RCVS. Methods: We performed a retrospective study of adult patients admitted to a tertiary medical center from February 2008 until February 2018 and were diagnosed with PRES or RCVS. Patient demographics, risk factors, clinical features, imaging, and outcomes were compared. Appropriate statistical tests were used to compare the variables and significant findings are reported. Results: There were 281 PRES and 98 RCVS cases meeting diagnostic criteria. Seizures, encephalopathy, and hypertension were more common with PRES, whereas headache was more common with RCVS (p <0.001). Hypertension and transplant recipient or immunocompromised status were associated with PRES (p <0.001), as did diabetes mellitus (p <0.05). Marijuana use, smoking, and obesity were associated with RCVS (p <0.05). ). Intraparenchymal or subarachnoid hemorrhage was found in 51 PRES cases and 34 RCVS cases. Arterial stenosis was present in 19 % of PRES cases. Brain FLAIR MRI hyperintensity that was reversible on follow-up was present in 26% of RCVS cases. Conclusion: PRES and RCVS share common clinical characteristics and might represent a pathophysiological spectrum, though distinct clinical features were noted in our retrospective analysis.

To report 2 cases of reversible cerebral vasoconstriction syndrome (RCVS) with posterior reversible encephalopathy syndrome (PRES) after blood transfusion for severe anemia. RCVS is presented with recurrent thunderclap headache and reversible constriction of cerebral arteries. PRES is a known complication of RCVS. Blood transfusion for severe anemia could be a cause for PRES in few cases; however, it is seldom mentioned as an etiology for RCVS. We report a case series. We report 2 women presented with RCVS with PRES after blood transfusion for anemia, and reviewed another 4 similar cases reported in the literature. Our 2 patients were middle-aged women, with severe chronic anemia (average hemoglobin: 1.45 g/dL), and received multiple blood transfusions (average: 3250 mL) over a period of 5-7 days. They developed thunderclap headache and other symptoms about 1 week after the last blood transfusion. Cerebral vasoconstrictions were demonstrated by magnetic resonance angiography and transcranial color-coded sonography. PRES was found in both of them using magnetic resonance imaging, and one of them also had cytotoxic edema on diffusion weighted image. RCVS with PRES is one complication of blood transfusion in patients under chronic severe anemia (especially when hemoglobin level increased for more than 5 g/dL), particularly in Asian women with menorrhagia. Blood pressure surge and the occurrence of severe headaches or other neurological symptoms should be aggressively monitored within 10 days after the last blood transfusion.

Anaesthesia and neurological disorders in pregnancy

We systematically reviewed case reports of posterior reversible encephalopathy syndrome (PRES), and investigated the characteristics of PRES in pregnant Japanese women and the clinical relevance of reversible cerebral vasoconstriction syndrome (RCVS) in pregnant women with PRES. Articles were collected using the PubMed/Medline and Ichushi-Web databases. This review was ultimately conducted on 121 articles (162 patients). The clinical characteristics of PRES, individual sites of PRES lesions, edema types, and clinical characteristics of RCVS in PRES cases were examined. The most common individual site of PRES lesion was the occipital lobe (83.3%), followed by the basal ganglia, parietal lobe, frontal lobe, brain stem, cerebellum, temporal lobe, thalamus, and splenium corpus callosum (47.5, 42.6, 24.7, 16.1, 9.3, 5.6, 4.3, and 0.0%, respectively). Edema types in 79 cases with PRES were mainly the vasogenic edema type (91.1%), with very few cases of the cytotoxic edema type (3.8%) and mixed type (5.1%). Among 25 PRES cases with RCVS, RCVS was not strongly suspected in 17 (68.0%) before magnetic resonance angiography. RCVS was observed at the same time as PRES in 13 cases (approximately 50%), and between days 1 and 14 after the onset of PRES in the other 12. These results suggest that the basal ganglia is a frequent site of PRES lesions in pregnant women. RCVS may occur at or after the onset of PRES, even if there are no symptoms to suggest RCVS.

Introduction: Nontraumatic convexity subarachnoid hemorrhage (cSAH) is a non-aneurysmal variant associated with various etiologies. Methods: We performed retrospective review of consecutive cSAH admitted to a large comprehensive stroke center, from 8/1/06-1/1/16. We abstracted data on demographics, neuroimaging, and clinical presentation; trauma was excluded. Cases were categorized: cryptogenic (negative work-up), susceptibility-weighted imaging-confirmed amyloid angiopathy (AA), posterior reversible encephalopathy syndrome (PRES), imaging-confirmed reversible cerebral vasoconstriction syndrome (RCVS), cerebral venous thrombosis (CVT), large artery occlusion (LA), or other known cause (sepsis, endocarditis, cerebral infarcts, or malignancy). Results: We identified 84 cases of cSAH occurring in 83 patients. Etiology subgroups were: 25% cryptogenic (N=21), 16% AA (N=13), 13% PRES (N=11), 13% RCVS (N=11), 11% CVT (N=9), 8% LA (N=7), and 14% other (N=12). Among cryptogenic patients, 8 had suspected clinical RCVS and 1 had suspected AA. There were significant differences in age, gender, and clinical presentation among etiology subgroups. AA patients were the oldest (mean 75.6 years), while RCVS patients were the youngest (45.6 years, p<0.0001). The majority of AA cohort was male (61%), whereas PRES and RCVS cohorts were exclusively female (100%, p=0.0002). Transient neurologic symptoms were common in AA (69%) but rare in RCVS (0%, p=0.01); headache was common in RCVS (80%) but unusual in AA (15%, p=0.001). Among 11 patients with confirmed RCVS, initial vascular imaging was negative in 6 (55%); repeat vascular imaging was necessary to diagnosis vasoconstriction (mean delay 5 days, range 3 -16 days). Conclusions: To our knowledge, this is the largest case series of cSAH patients. Convexity SAH has a broad range of etiologies, with the most common being cryptogenic, RCVS, PRES, and AA. In our cohort, cSAH due to AA most typically presented as older males with transient neurological symptoms; cSAH due to RCVS presented as younger females with headache. Over half of patients with cSAH due to RCVS required repeat vascular imaging to confirm vasoconstriction. Further research is warranted to clinically characterize this complex variant of SAH.

Reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES) are both rare disorders. The pathophysiology of both diseases is not yet fully understood. We report the unique case of a 19-year-old comatose woman who was brought to the ER after a series of generalized tonic-clonic seizures 6days post peridural anesthesia for cesarean section. Vital signs and initial laboratory testing including urine analysis and drug screening were unremarkable. Initial cranial CT scan showed an acute small subdural hematoma (17mm length×6mm width×30mm height), cerebral edema with slit ventricles, and slight cerebellar tonsillar herniation as signs of intracranial hypotension. CT angiography depicted narrowing of the proximal intracranial vessels consistent with RCVS. MR imaging was also suggestive of both intracranial hypotension and RCVS and showed, in addition, vasogenic edema consistent with PRES. An extensive CSF leakage involving T1 to L2/L3 was confirmed by spinal MRI. The patient underwent conservative therapy for intracranial hypotension (e.g., head-down position) as well as epidural blood patch, which led to regression of the clinical symptoms within a few days. Follow-up MRI showed complete resolution of all radiological changes. In summary, our patient developed clinical and neuroradiological signs of intracranial hypotension and a combination of PRES and RCVS associated with a CSF leakage caused by peridural anesthesia; by treating the intracranial hypotension, the other syndromes resolved. From a clinical point of view, it is important to look for CSF leakage as a treatable possible cause of PRES and/or RCVS triggered by intracranial hypotension as in our patient postpartum. Moreover, it is vital to obtain a good history as, in cases of suspected CSF leakage with classic postural headache, a recent spinal/cranial procedure is typically present.