Hyun Ah Choi

Blood–brain barrier breakdown in reversible cerebral vasoconstriction syndrome: Implications for pathophysiology and diagnosis

Diagnosis of reversible cerebral vasoconstriction syndrome (RCVS) is currently based on luminographic findings of vasoconstriction. In addition to vasoconstriction, the blood–brain barrier (BBB) breakdown has been postulated as a central mechanism of RCVS. Our aim was to document BBB breakdown in patients with RCVS and its role for the pathophysiology‐based diagnosis of RCVS.

Characteristics and demographics of reversible cerebral vasoconstriction syndrome: A large prospective series of Korean patients

Objectives To report demographics and characteristics of reversible cerebral vasoconstriction syndrome (RCVS) in the Korean cohort. Methods We prospectively recruited patients with definite (imaging-proven) RCVS and probable (imaging-negative) RCVS who visited Samsung Medical Center between June 2012 and September 2016. Clinical manifestations, neuroimaging, treatment, and clinical outcomes were evaluated in all patients. Characteristics of RCVS without typical causes (“idiopathic RCVS”) were compared with those of RCVS with identifiable causes (“secondary RCVS”). International Classification of Headache Disorders (ICHD)-3 beta criteria for 6.7.3 RCVS and 6.7.3.1 probable RCVS were tested. Results A total of 138 patients (104 definite and 34 probable RCVS) were included in this study. Patients with definite RCVS were predominantly female (85.6%) and middle-aged (mean, 50.7 [range, 23–82] years). Probable RCVS was associated with less female predominance (70.6%, p = 0.049), more typical manifestations (p < 0.001), and none of neurological complications. One-hundred and one (97.1%) patients with definite RCVS had headache, but the typical “recurrent and/or triggered” thunderclap headache was reported in only 83 (82.2%). In most patients with definite RCVS (84.6%), RCVS was idiopathic, while only 16 (15.4%) had secondary causes. Compared to those with secondary RCVS, patients with idiopathic RCVS were older (52.8 ± 11.42 vs. 39.1 ± 9.55 years, p < 0.001). Patients with secondary RCVS had more complications than those with idiopathic RCVS (40.5% vs. 12.5%, p = 0.018). Among idiopathic RCVS patients, 33 (37.5%) reported a preceding event or a change in lifestyle, environment, health, or medication within one month before onset. Conclusion In our cohort, RCVS was benign and idiopathic in most patients, and occurred frequently in middle-aged women. Manifestations of RCVS were more diverse than previously recognized, and forms without any headache existed. Different genetic, social, and environmental factors should be taken into account to unveil the spectrum and pathophysiology of RCVS.

Intracranial structural alteration predicts treatment outcome in patients with spontaneous intracranial hypotension.

Background Intracranial structural dislocation in spontaneous intracranial hypotension (SIH) can be measured by various intracranial angles and distances. We aimed to identify the clinical significance of structural dislocation in relation to treatment outcome in patients with SIH. Methods In this retrospective analysis, we identified patients with SIH who received an epidural blood patch (EBP) at Samsung Medical Center from January 2005 to March 2015. Structural dislocation in pretreatment MRIs of SIH patients was assessed by measuring tonsillar herniation, mamillopontine distance, the angle between the vein of Galen and straight sinus (vG/SS angle), the pontomesencephalic angle, and the lateral ventricular angle. After the first EBP, poor response was defined as the persistence of symptoms that prompted a repeat EBP. Results Out of the 95 patients included, 31 (32.6%) showed poor response. Among the radiological markers of structural dislocation, the vG/SS angle was associated with poor response (49.82 ± 16.40° vs 66.58 ± 26.08°, p = 0.002). Among clinical variables, premorbid migraine (p = 0.036) was related to poor response. In multivariate analysis, reduced vG/SS angle was independently associated with poor response (OR 1.04 [95% CI 1.01 – 1.07] per 1° decrease, p = 0.006). In 23 patients who underwent MRI after successful treatment, the vG/SS angle significantly increased after the EBP (p < 0.001, by paired t-test), while two patients with aggravation or recurrence showed a further reduction of their vG/SS angles. Conclusions Intracranial structural dislocation, measured by the vG/SS angle, is associated with poor response to the first EBP in patients with SIH. Successful treatment can reverse the structural dislocation.

Natural course of untreated cluster headache: A retrospective cohort study:

Objective To determine the natural course of cluster headache. Methods We screened patients with cluster headache who were diagnosed at Samsung Medical Center and lost to follow-up for ≥5 years. Eligible patients were interviewed by phone about the longitudinal changes in headache characteristics and disease course. Remission was defined as symptom-free 1) for longer than twice the longest between-bout period and 2) for ≥5 years. Results Forty-two patients lost to follow-up for mean 7.5 (range, 5.0–15.7) years were included. The length of the last bout did not differ from the first one, while the last between-bout period was longer than the first one (p = 0.012). Characteristics of cluster headache decreased over time: Side-locked unilaterality (from 92.9% to 78.9%), seasonal and circadian rhythmicity (from 63.9% to 60.9% and from 62.2 to 40.5%, respectively), and autonomic symptoms (from 95.2% to 75.0%). Remission occurred in 14 (33.3%) patients at a mean age of 42.3 (range, 27–65) years, which was not different from the age of last bouts in active patients (p = 0.623). There was a trend for more seasonal and circadian predilection at baseline in the active group (p = 0.056 and 0.063, respectively) and fewer lifetime bouts and shorter disease duration in patients in remission (p = 0.063 and 0.090). Conclusions This study first shows the natural courses of cluster headache. Features of cluster headache become less prominent over time. Remission occurred regardless of age. Although no single predictor of remission was found, our data suggest that remission of cluster headache might not be a consequence of more advanced age, longer duration of disease, or accumulation of lifetime bouts.

Serial testing of the ICHD-3 beta diagnostic criteria for probable reversible cerebral vasoconstriction syndrome: A prospective validation study

Objectives To serially test the International Classification of Headache Disorders (ICHD) 3rd edition beta version criteria for 6.7.3.1 probable reversible cerebral vasoconstriction syndrome (probable RCVS) in patients with thunderclap headache. Methods We prospectively screened consecutive patients with thunderclap headache who visited the Samsung Medical Center between October 2015 and March 2017. Patients were included in the analysis if they a) visited our hospital within 1 month after onset, b) completed a diagnostic work-up, and c) had no secondary causes other than RCVS. The ICHD-3 beta 6.7.3.1 criteria were evaluated serially during the first visit (visit 1), 2 weeks after the first visit (visit 2), and 1–3 months after onset (visit 3). Results A total of 99 patients completed this study. Based on the first clinical and radiological evaluation, 63 (63.6%) were diagnosed with angiogram-proven RCVS, whilst 36 (36.4%) showed normal neuroimaging. The ICHD-3 beta 6.7.3.1 criteria were fulfilled in 76.2% of patients with angiogram-proven RCVS. In patients with normal angiograms, the ICHD diagnosis of probable RCVS changed over time: 25.0%, 47.2%, and 38.9% at visits 1, 2, and 3, respectively. The sensitivity and specificity of the criteria at visit 1 were 72.4% and 95.5%, respectively, for the prediction of a final diagnosis of overall (angiogram-proven + probable) RCVS. Conclusions The ICHD-3 beta criteria for probable RCVS are applicable for patients with thunderclap headaches at the acute stage, with the exception of criterion C3. Criteria C1 and C2 are less reliable when applied at the first visit. Repeated evaluation is necessary to enhance diagnostic sensitivity.

Chronic paroxysmal headache secondary to an orbital metastatic leiomyosarcoma: A case report.

Background Intraorbital lesions associated with symptomatic trigeminal autonomic cephalalgias (TACs) are rarely reported. We present a case of orbital metastatic leiomyosarcoma, presenting with chronic paroxysmal hemicrania-like headache. Case report A 43-year-old man presented with a severe paroxysmal headache in his left periocular and frontal area for a year. The attacks occurred 10–12 times per day, lasting 10–15 minutes with ipsilateral lacrimation and conjunctival injection. Neurological examination and brain MRI without contrast were unremarkable. Different medications were tried, without beneficial effects. A follow-up contrast-enhanced brain MRI performed one year after the baseline MRI revealed an enhancing mass in the left superior oblique muscle. Orbital metastatic leiomyosarcoma arising from the thigh was revealed. He received gamma knife surgery, which completely resolved the headache. Discussion Intraorbital lesion should be considered a possibility in patients with headache mimicking TACs. Baseline contrast-enhanced MRI is essential, and repeated MRI scans might be needed if clinically indicated.

Longitudinal changes in cerebral blood flow velocities in different clinical courses of migraine

Objective To assess longitudinal changes in cerebral blood flow velocities (ΔCBFVs) according to the clinical course of migraine. Methods We retrospectively included migraine patients with two or more attacks per month at baseline who were followed up within 2 years with transcranial Doppler in a tertiary headache clinic. ΔCBFVs were analyzed in relation to clinical courses, defined as remission (0–1 headache days/month), persistence (2–14/month), or progression (≥15/month) in episodic migraine (EM), and conversion to EM (<15/month) and persistence (≥15/month) in chronic migraine (CM). Results A total of 166 patients (90 EM and 76 CM) were included. In EM, the remission group (n = 30) showed a decrease in CBFV in the middle cerebral artery (MCA) and the basilar artery (BA). The progression group (n = 10) showed increasing CBFVs in the bilateral MCAs. Patients with the persistence course (n = 50) showed generally unchanged CBFVs. In CM, ΔCBFVs decreased in the BA and increased in the posterior cerebral artery (PCA) after conversion to EM (n = 61), whereas they remained unchanged in the persistence group (n = 15). In all patients, % change in headache days was positively correlated with the %ΔCBFVs of the bilateral MCAs and the BA. Conclusions CBFV changes are associated with the different clinical courses of migraine. The association is more prominent in EM than CM.