Successful Reperfusion is Associated with Favorable Functional Outcome despite Vessel Perforation during Thrombectomy: A Case Series and Systematic Review.

BACKGROUND: Arterial perforation is a potentially serious complication during endovascular thrombectomy. PURPOSE: Our aim was to describe interventional approaches after arterial perforation during endovascular thrombectomy and to determine whether reperfusion remains associated with favorable outcome despite this complication. DATA SOURCES: Data from consecutive patients with acute stroke undergoing endovascular thrombectomy were retrospectively collected between 2015 to 2020 from a single-center cohort, and a systematic review was performed using PubMed, EMBASE, and Ovid MEDLINE up to June 2020. STUDY SELECTION: Articles reporting functional outcome after arterial perforation during endovascular thrombectomy were selected. DATA ANALYSIS: Functional outcomes of patients achieving successful reperfusion (TICI 2b/3) were compared with outcomes of those with unsuccessful reperfusion in our single-center cohort. We then summarized the literature review to describe interventional approaches and outcomes after arterial perforation during endovascular thrombectomy. DATA SYNTHESIS: In our single-center cohort, 1419 patients underwent endovascular thrombectomy, among whom 32 (2.3%) had vessel perforation and were included in the analysis. The most common hemostatic strategy was watchful waiting (71% of cases). Patients with successful reperfusion had a higher proportion of favorable 90-day mRS scores (60% versus 12.5%; P = .006) and a lower mortality rate (13.3% versus 56.3%, P = .01) than patients without successful reperfusion. Thirteen articles were included in the systematic review. Successful reperfusion also appeared to be associated with better outcomes. LIMITATIONS: Given the low number of published reports, we performed only a descriptive analysis. CONCLUSIONS: Arterial perforation during endovascular thrombectomy is rare but is associated with high mortality rates and poor outcome. However, successful reperfusion remains correlated with favorable outcome in these patients.

Tandem Carotid Lesions in Acute Ischemic Stroke: Mechanisms, Therapeutic Challenges, and Future Directions.

Approximately 15% of patients undergoing endovascular thrombectomy for anterior circulation acute ischemic stroke have a tandem lesion, defined as a severe stenosis or occlusion of the cervical internal carotid artery ipsilateral to its intracranial occlusion. Patients with tandem lesions have worse outcomes than patients with isolated intracranial occlusions, but the optimal management of their carotid lesions during endovascular thrombectomy remains controversial. The main options commonly used in current practice include acute stent placement in the carotid lesion versus thrombectomy alone without definitive revascularization of the carotid artery. While treatment decisions for these patients are often complex and strategies vary according to clinical, anatomic, and technical considerations, only results from randomized trials comparing these approaches are likely to strengthen current recommendations and optimize patient care.

Exophthalmos following mechanical thrombectomy for anterior circulation stroke: A retrospective study and review of literature.

BACKGROUND: Anecdotal cases of exophthalmos after acute mechanical thrombectomy have been described. We sought to estimate the incidence in a large cohort of patients with acute anterior circulation stroke treated with mechanical thrombectomy. Secondarily, we aimed to evaluate the underlying mechanism and to differentiate it on imaging from other pathology with similar clinical orbital features. METHODS: Between November 2016 and November 2018, we performed a retrospective single-center study of 250 patients who underwent anterior circulation mechanical thrombectomy. Development of exophthalmos was independently evaluated by two readers on preprocedure and 24-h postprocedure non-contrast cerebral CT. RESULTS: In the mechanical thrombectomy cohort, six individuals (2.4%) developed interval ipsilateral exophthalmos at 24 h. Of these, at least two patients developed clinical symptoms. There was almost perfect agreement between assessments of the two readers (Cohen's kappa = 0.907 (95% confidence interval: 0.726, 1.000)). In two patients, there was delayed ophthalmic artery filling on digital subtraction angiography. None of the patients had features of a direct carotid-cavernous fistula. CONCLUSIONS: Exophthalmos is not uncommon after mechanical thrombectomy (2.4%). The underlying mechanism is difficult to confirm, but it is most likely due to orbital ischemia from hypoperfusion or distal emboli.

European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage

"BACKGROUND: Intracerebral hemorrhage (ICH) accounted for 9% to 27% of all strokes worldwide in the last decade, with high early case fatality and poor functional outcome. In view of recent randomized controlled trials (RCTs) of the management of ICH, the European Stroke Organisation (ESO) has updated its evidence-based guidelines for the management of ICH. METHOD: A multidisciplinary writing committee of 24 researchers from 11 European countries identified 20 questions relating to ICH management and created recommendations based on the evidence in RCTs using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: We found moderate- to high-quality evidence to support strong recommendations for managing patients with acute ICH on an acute stroke unit, avoiding hemostatic therapy for acute ICH not associated with antithrombotic drug use, avoiding graduated compression stockings, using intermittent pneumatic compression in immobile patients, and using blood pressure lowering for secondary prevention. We found moderate-quality evidence to support weak recommendations for intensive lowering of systolic blood pressure to <140 mmHg within six-hours of ICH onset, early surgery for patients with a Glasgow Coma Scale score 9-12, and avoidance of corticosteroids. CONCLUSION: These guidelines inform the management of ICH based on evidence for the effects of treatments in RCTs. Outcome after ICH remains poor, prioritizing further RCTs of interventions to improve outcome."

Epileptic seizures at initial presentation in patients with brain arteriovenous malformation.

OBJECTIVES: Brain arteriovenous malformations (AVMs) often present with epileptic seizures, but prospective data on the risk of seizures with respect to morphologic AVM characteristics are scarce. METHODS: We studied 155 consecutive patients with AVMs from a prospective, single-center database using demographic and morphologic factors based on prospectively coded MRI and digital subtraction angiography (DSA) data. Univariate analysis and multivariate logistic regression models were used to test the effect of demographic (age and sex) and morphologic characteristics (AVM size, anatomic and arterial location, and venous drainage pattern) on seizures as initial presentation in patients with unruptured brain AVMs. RESULTS: Overall, 45 patients with AVMs initially presented with seizures (29%). By univariate comparison, male sex (p = 0.02), increasing AVM size (p < 0,006), frontal lobe localization (p < 0.0001), arterial borderzone location (p < 0.0006), superficial venous drainage (p = 0.0002), and presence of venous ectasia (p = 0.003) were statistically associated with seizures. The multivariate analysis confirmed an independent effect of male sex, frontal lobe AVMs, and arterial borderzone location on seizure occurrence. All patients with seizures showed the presence of a superficial venous drainage component. CONCLUSIONS: Our study suggests that seizures mainly occur in AVMs with superficial drainage. Other predisposing factors include male sex, increasing AVM size, and frontal lobe and arterial borderzone location. Whether or not interventional treatment has an effect on the long-term risk of epilepsy remains to be determined.

[The second (main) phase of an open, randomised, multicentre study to investigate the effectiveness of an INTEnsive blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT2): protocol and baseline characteristics of patients included in France]. / La seconde phase d'une étude randomisée, multicentrique évaluant en ouvert l'effet de la réduction intensive de la pression artérielle dans l'hémorragie cérébrale (INTERACT2) : protocole et caractéristiques des patients inclus en France.

RATIONALE AND AIM: The INTERACT pilot study demonstrated the feasibility of the protocol, safety of early intensive blood pressure (BP) lowering, and effects on hematoma expansion within 6hours of onset of intracerebral hemorrhage (ICH). This article describes the design of the second, main phase, INTERACT2. INTERACT2 aims to compare the effects of a management strategy of early intensive BP lowering with a more conservative guideline-based BP management policy in patients with acute ICH. This article also compares the baseline characteristics of the patients included in France with the baseline characteristics of the patients included in the pilot study INTERACT1. DESIGN OF THE STUDY: INTERACT2 is an international, prospective, multicentre, open, assessor-blinded outcome (PROBE), randomised, controlled trial. Patients with a systolic BP greater than 150mmHg are centrally randomised to either to an intensive BP lowering treatment (Systolic BP≤140mmHg within 1hour) or to a conservative treatment strategy (target systolic BP of 180mmHg). A projected 2800 subjects are to be enrolled from approximately 140 centres worldwide to provide 90% power (α 0.05) to detect a beneficial effect of early treatment on the primary outcome. STUDY OUTCOMES: The primary outcome is the combined endpoint of death and dependency according to the modified Rankin Scale (mRS) at 90 days. The key secondary outcome is the primary endpoint in those patients treated within 4hours of ICH. Other predefined secondary outcomes are the separate components of the primary endpoint, grades of physical function on the mRS, health-related quality of life on the EuroQoL, recurrent stroke and other vascular events, days of hospitalisation, requirement for permanent residential care, and unexpected serious adverse events. The study is registered under NCT00716079, ISRCTN73916115, and ACTRN12608000362392. POPULATION: As of early July, 152 patients have been included in France. When compared with the patients randomised in the INTERACT1 pilot study, these patients are older, less likely to have had a previous ICH, more often on antiplatelet or warfarin therapy, have a lower diastolic BP, arere more severe clinically (higher NIHSS) and experience their first ICH.

Olive oil consumption, plasma oleic acid, and stroke incidence: the Three-City Study.

OBJECTIVE: To determine whether high olive oil consumption, and high plasma oleic acid as an indirect biological marker of olive oil intake, are associated with lower incidence of stroke in older subjects. METHODS: Among participants from the Three-City Study with no history of stroke at baseline, we examined the association between olive oil consumption (main sample, n = 7,625) or plasma oleic acid (secondary sample, n = 1,245) and incidence of stroke (median follow-up 5.25 years), ascertained according to a diagnosis validated by an expert committee. RESULTS: In the main sample, 148 incident strokes occurred. After adjustment for sociodemographic and dietary variables, physical activity, body mass index, and risk factors for stroke, a lower incidence for stroke with higher olive oil use was observed (p for trend = 0.02). Compared to those who never used olive oil, those with intensive use had a 41%(95% confidence interval 6%-63%, p = 0.03) lower risk of stroke. In the secondary sample, 27 incident strokes occurred. After full adjustment, higher plasma oleic acid was associated with lower stroke incidence (p for trend = 0.03). Compared to those in the first tertile, participants in the third tertile of plasma oleic acid had a 73% (95% confidence interval 10%-92%, p = 0.03) reduction of stroke risk. CONCLUSIONS: These results suggest a protective role for high olive oil consumption on the risk of stroke in older subjects.

The second (main) phase of an open, randomised, multicentre study to investigate the effectiveness of an intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT2).

RATIONALE: The INTERACT pilot study demonstrated the feasibility of the protocol, safety of early intensive blood pressure lowering and effects on haematoma expansion within 6 h of onset of intracerebral haemorrhage. This article describes the design of the second, main phase, INTERACT2. AIMS: To compare the effects of a management strategy of early intensive blood pressure lowering with a more conservative guideline-based blood pressure management policy in patients with acute intracerebral hemorrhage. DESIGN: INTERACT2 is a prospective, randomized, open label, assessor-blinded end-point (PROBE). Patients with a systolic blood pressure greater than 150 mmHg and no definite indication for or contraindication to blood pressure-lowering treatment are centrally randomised to either of two treatment groups within 6 h onset of intracerebral haemorrhage. Those allocated to intensive blood pressure lowering will receive primarily intravenous, hypotensive agents to achieve a systolic blood pressure target of <140 mmHg within 1 h of randomisation and to maintain this level for up to 7 days in hospital. The control group will receive blood pressure-lowering treatment to a target systolic blood pressure of <180 mmHg. Both groups are to receive similar acute stroke unit care, therapy and active management. Oral antihypertensive therapy is recommended in patients before hospital discharge with a long-term systolic blood pressure goal of 140 mmHg according to secondary stroke prevention guidelines. A projected 2800 subjects are to be enrolled from approximately 140 centres worldwide to provide 90% power (alpha 0.05) to detect a 14% difference in the risk of death and dependency between the groups, which equates to one or more cases of a poor outcome prevented in every 15 patients treated. STUDY OUTCOMES: The primary outcome is the combined end-point of death and dependency according to the modified Rankin Scale at 90 days. The secondary outcomes are the separate components of the primary end-point in patients treated <4 hours of ICH onset, grades of physical function on the modified Rankin Scale, health-related quality of life on the EuroQoL, recurrent stroke and other vascular events, days of hospitalisation, requirement for permanent residential care and unexpected serious adverse events.

Clinical and morphological determinants of focal neurological deficits in patients with unruptured brain arteriovenous malformation.

OBJECTIVE: Some patients with brain arteriovenous malformation (BAVM) present with focal neurological deficits (FNDs) unrelated to clinically discernable seizure activity or hemorrhage. The aim of this study is to determine demographic and morphological AVM characteristics associated with FNDs. METHODS: The 735 patients of the prospective Columbia AVM Databank were analyzed. Univariate and multivariate statistical models were used to test the association of demographic (age, gender), and morphological characteristics (BAVM size, anatomic location, arterial supply, venous drainage pattern, venous ectasia) with the occurrence of FNDs at the time of initial BAVM diagnosis. RESULTS: Fifty-three patients (7%, mean age 40+/-16years, 70% women) presented with FNDs. The multivariate logistic regression model revealed an independent association of FNDs with increasing age (OR 1.03; 95%-CI 1.00-1.05), female gender (OR 2.14; 95%-CI 1.15-3.97), deep brain location (OR 2.46; 95%-CI 1.24-4.88), brainstem location (OR 5.62; 95%-CI 1.65-19.23), and venous ectasia (OR 1.91; 95%-CI 1.01-3.64). No association was found for BAVM size, lobar location, arterial supply and venous drainage pattern. INTERPRETATION: Focal neurologic deficits unrelated to seizures or hemorrhage are a rare initial presentation of BAVMs. The predominance of FNDs among brainstem and deeply located BAVMs and the lack of a significant association of BAVM size with FNDs indicate selective white matter pathway-specific vulnerability, the association with patient age a time dependent effect. The higher frequency of FNDs among women suggests gender-specificity of brain tissue vulnerability.

Vascular risk factors and morphometric data in cervical artery dissection: a case-control study.

BACKGROUND: Limited knowledge exists on vascular risk factors, body height and weight in patients with spontaneous cervical artery dissection (sCAD). PATIENTS AND METHODS: In this case-control study, major vascular risk factors, body weight, body height and body mass index (BMI) of 239 patients obtained from a prospective hospital-based sCAD registry were compared with 516 age- and sex-matched healthy controls undergoing systematic health examinations in the Clinical and Preventive Investigations Center, Paris. Gender-specific analyses were performed. RESULTS: The mean body height was higher in sCAD patients than in controls (171.3 cm (SD 8.6) vs 167.7 cm (8.9); p<0.0001) and sCAD patients had a significantly lower mean body weight (67.5 (12.2) kg vs 69.3 (14.6) kg; p<0.001) and mean BMI (22.9 (3.3) kg/m2 vs 24.5 (4.2) kg/m2; p<0.0001) than controls. The overall frequency of hypertension, diabetes, current smoking, past smoking and hypercholesterolaemia did not differ significantly between sCAD patients and controls. The mean total plasma cholesterol level was identical in both groups (5.5 mmol/l, SD 1.1). Gender specific subgroup analyses showed similar results for men and women. CONCLUSION: Patients with sCAD had a higher body height and a lower body weight and BMI than controls, while major vascular risk factors were similar in sCAD patients and controls.

Triple and quadruple spontaneous cervical artery dissection: presenting characteristics and long-term outcome.

BACKGROUND: Spontaneous cervicocephalic artery dissection (sCAD) of more than two cervical arteries is rare. PATIENTS AND METHODS: Vascular and potential sCAD risk factors, triggering events, clinical and neuroimaging findings, and outcome of patients with multiple sCAD were studied. Patients were drawn from prospective hospital-based sCAD registries. RESULTS: Of 740 consecutive patients with sCAD, 11 (1.5%) had three, and one had four (0.1%) sCAD. Eight of these 12 patients were women. One patient had additional dissections of the celiac trunk and hepatic artery. Vascular risk factors included hypertension (n = 1), hypercholesterolaemia (n = 6), current smoking (n = 5) and migraine (n = 6). No patient had a family history of sCAD, fibromuscular dysplasia (FMD) or connective tissue disease. SCAD was preceded by a minor trauma in five and infection in four patients. Clinical manifestations included ischaemic stroke (n = 8), transient ischaemic attack (n = 3), headache (n = 9), neck pain (n = 4), Horner syndrome (n = 5), pulsatile tinnitus (n = 2) and dysgeusia (n = 1). Brain MRI revealed ischaemic infarcts that affected one vessel territory in seven and two territories in two patients. The 3-month outcome was favourable (modified Rankin scale score 0-1) in 10 patients (83%). No new recurrent stroke or sCAD occurred during a mean follow-up of 50 (SD 29) months. CONCLUSION: Multiple sCAD occurred preferentially in women and caused clinical symptoms and signs mainly in one vascular territory. In none of the patients was FMD or any other underlying arteriopathy apparent. The majority of multiple sCAD was preceded by a minor trauma or infection. Clinical outcome was favourable in most patients, and long-term prognosis benign. The data suggest that transient vasculopathy may be a major mechanism for multiple sCAD.

[Unruptured brain arteriovenous malformations]. / Malformations artérioveineuses cérébrales non rompues.

Cerebral arteriovenous malformations (AVMs) often become symptomatic in young adults with a variety of neurological symptoms such as epileptic seizures, recurrent headaches, progressive neurological deficits or sudden intracranial hemorrhage. However, recent epidemiological data suggest a large number of AVMs are found without signs of hemorrhage and a relatively low rupture risk of less than 1% per year. Continuous technical progress has led to several specific treatment options for brain AVMs including endovascular embolization, microneurosurgery, and stereotactic radiotherapy, either alone or in any combination. Depending on AVM topography and vascular anatomy, interventional treatment strategies have shown successful occlusion rates ranging between 50 and 100% and a relatively low average procedural morbidity of 10% overall. For unruptured brain AVMs, however, the clinical benefit of invasive treatment remains as yet to be determined. To address this issue, A randomized trial of unruptured brain AVMs (ARUBA) is currently underway evaluating long-term outcome of best possible standard interventional therapy as compared to the natural history risk in a prospective multidisciplinary international study (www.arubastudy.org).

Diagnosis and treatment of dural carotid-cavernous fistulas: a consecutive series of 27 patients.

OBJECTIVES: To report clinical characteristics, angiographical findings and results of endovascular treatment of patients presenting with dural carotid-cavernous fistulas (DCCFs). METHOD: Retrospective analysis of 27 consecutive patients with DCCF referred to a specialised interventional neuroradiology department. RESULTS: Orbital and neuro-ophthalmological symptoms were the most common clinical presentation at diagnosis (n = 25). The venous drainage of the fistula involved the ipsilateral superior ophthalmic vein in 24 patients, the contralateral cavernous sinus in 6 and a leptomeningeal vein in 5 patients. Thrombosis of at least one petrosal sinus was found in 23 patients. 7 patients did not receive endovascular treatment: 3 had spontaneous DCCF obliteration, and 4 had only minor clinical symptoms and no leptomeningeal venous drainage on an angiogram. 20 patients received endovascular treatment via either a transvenous (n = 16) or a transarterial approach (n = 4). Complete occlusion of the fistula was obtained in 14 of 16 (87%) patients treated by the transvenous approach and in 1 of 4 (25%) patients treated by the transarterial approach. 16 patients had early clinical improvement after endovascular treatment. One patient had a cerebral haemorrhage after transvenous embolisation of a DCCF with leptomeningeal drainage. On follow-up, all patients treated by the transarterial route remained symptomatic, whereas 10 of 14 (71%) patients cured by the transvenous route were asymptomatic. CONCLUSIONS: Transvenous embolisation is a safe and efficient endovascular approach to treat patients with DCCF. However, this technique requires a long learning curve.

[The neurology of cerebral arteriovenous malformations]. / Neurologie des malformations artérioveineuses cérébrales.

INTRODUCTION: Brain arteriovenous malformations (AVMs) constitute a neurovascular disorder that comes to clinical attention mainly in young adults in their mid thirties. Associated symptoms often require neurological treatment for symptomatic seizures (focal or generalized), headaches (episodic or chronic), progressive neurological deficits, or spontaneous AVM rupture leading to intracerebral, intraventricular, and/or subarachnoid hemorrhage. STATE OF ART: Little data exist in the medical literature regarding the natural history risk of the disease and no controlled studies are available on the risk of invasive AVM treatment (endovascular, neurosurgery, radiotherapy). PERSPECTIVES: This review focuses on all aspects of neurological brain AVM management and discusses possible predictors of the natural history risk as well as the benefit and risk of invasive treatment. CONCLUSIONS: AVM patient management is ideally based on a trans-disciplinary approach via a neurovascular team of neurologists, neuroradiologists, neurosurgeons, and radiotherapists. A newly diagnosed AVM does not necessarily represent an a priori indication for interventional treatment. The decision in favor or against therapy mainly depends on clinical criteria (ruptured versus unruptured AVM, neurological exam, patient age and co-morbidity, etc.) and the angioarchitecture of the malformation. The ARUBA study is going to be the first randomized clinical trial comparing the risk of invasive treatment versus non-invasive management.

Pain as the only symptom of cervical artery dissection.

BACKGROUND: Headache or neck pain is a frequent symptom of spontaneous cervical artery dissection (sCAD). PATIENTS AND METHODS: Patients were drawn from an ongoing hospital-based registry of consecutive cases diagnosed with sCAD. Only patients with isolated pain were included in this series. Pain topography, dynamics, severity and quality, imaging findings and outcome were analysed. RESULTS: 20 of 245 (8%) patients with sCAD presented with pain as the only symptom (mean (SD) age 39 (8) years; 14 (70%) women). Of them, 12 had vertebral artery dissection, 3 had internal carotid dissection and 5 had multiple dissections. The median delay from symptom onset to diagnosis was 7 days (range 4 h to 29 days). 6 patients presented with headache, 2 with neck pain and 12 with both. Onset of headache was progressive in 6, acute in 8 and thunderclap-type in 4 patients; neck pain was progressive in 7 and acute in 7. Headache was throbbing in 13 and constrictive in 5 patients; neck pain was throbbing in 4 and constrictive in 10. Pain was unilateral in 11 and bilateral in 9. Pain was different from earlier episodes in all but one case. All patients were pain free at 3 months. CONCLUSION: Pain may be the only symptom in sCAD, even when multiple arteries are dissected. Pain topography, dynamics, quality and intensity were heterogeneous. Data from this study lend support to recommendations favouring imaging studies of the cervical arteries in patients with new-onset unexplained headache or neck pain.

Predictors of hemorrhage in patients with untreated brain arteriovenous malformation.

BACKGROUND: Intracranial hemorrhage is a serious possible complication in patients with brain arteriovenous malformation (AVM). Several morphologic factors associated with hemorrhagic AVM presentation have been established, but their relevance for the risk of subsequent AVM hemorrhage remains unclear. METHODS: The authors analyzed follow-up data on 622 consecutive patients from the prospective Columbia AVM database, limited to the period between initial AVM diagnosis and the start of treatment (i.e., any endovascular, surgical, or radiation therapy). Univariate and multivariate logistic regression and Cox proportional hazard models were applied to analyze the effect of patient age, gender, AVM size, anatomic location, venous drainage pattern, and associated arterial aneurysms on the risk of intracranial hemorrhage at initial presentation and during follow-up. RESULTS: The mean pretreatment follow-up was 829 days (median: 102 days), during which 39 (6%) patients experienced AVM hemorrhage. Increasing age (hazard ratio [HR] 1.05, 95% CI 1.03 to 1.08), initial hemorrhagic AVM presentation (HR 5.38, 95% CI 2.64 to 10.96), deep brain location (HR 3.25, 95% CI 1.30 to 8.16), and exclusive deep venous drainage (HR 3.25, 95% CI 1.01 to 5.67) were independent predictors of subsequent hemorrhage. Annual hemorrhage rates on follow-up ranged from 0.9% for patients without hemorrhagic AVM presentation, deep AVM location, or deep venous drainage to as high as 34.4% for those harboring all three risk factors. CONCLUSIONS: Hemorrhagic arteriovenous malformation (AVM) presentation, increasing age, deep brain location, and exclusive deep venous drainage appear to be independent predictors for AVM hemorrhage during natural history follow-up. The risk of spontaneous hemorrhage may be low in AVMs without these risk factors.

Orgasmic headache and middle cerebral artery dissection.

A patient with a 20 year history of primary orgasmic headache is described who, after suffering an unusually severe episode of orgasmic headache was found to have a middle cerebral artery dissection. This unusual association of primary and secondary orgasmic headache emphasises the need for a thorough diagnostic examination when the orgasmic headache differs from that of previous episodes or is associated with neurological symptoms.