Lee JY, et al. J Clin Neurol. 2020 Apr;16(2):277-284. https://doi.org/10.3988/jcn.2020.16.2.277

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small-vessel disease caused by mutations in the NOTCH3 gene. Classical pathogenic mechanisms are associated with cysteine gain or loss, but recent studies suggest that cysteine-sparing mutations might have a potential role as a pathogen. In comparison with CADASIL patients in Western countries, there are several differences in Asian patients: (1) prevalent locus of NOTCH3 mutations (exons 2–6 [particularly exon 4] vs. exon 11), (2) age at symptom onset, (3) prevalence of cerebral microbleeds and hemorrhagic stroke, (4) clinical symptoms, and (5) severity of white matter hyperintensities and typical involvement of the anterior temporal pole in magnetic resonance imaging. Both ethnicity and founder effects contribute to these differences in the clinical NOTCH3 spectrum in different cohorts. More functional investigations from diverse races are needed to clarify unknown but novel variants of NOTCH3 mutations. This review may broaden the spectrum of NOTCH3 variants from an Asian perspective and draw attention to the hidden pathogenic roles of NOTCH3 variants.

The diagnostic criteria for primary stabbing headache (PSH) in the 3rd beta edition of International Classification of Headache Disorders (ICDH-3 beta) were recently revised. In the ICDH-3 beta, PSH is defined as short-lasting head pain spontaneous occurring as a single stab or series of stabs without autonomic symptoms and involving all head areas (i.e., not limited to the ophthalmic branch region of the trigeminal nerve). The aim of this study was to investigate the validity of the ICHD-3 beta criteria for PSH in a clinic-based setting. We prospectively collected data from patients with complaint of headache with stabbing pain without apparent cause at an initial visit to a secondary-care hospital from March 2009 to March 2014. Patients were followed up for 2 weeks to assess changes in clinical characteristics and secondary causes of pain. Data from 280 patients with headache with stabbing pain without apparent cause were collected, and 245 patients were followed up for 2 weeks. Secondary causes for stabbing headache were observed in 9 patients (herpes zoster in 7 patients and Bell’s palsy in 2 patients) after 2 weeks. The remaining 236 patients fulfilled the diagnostic criteria for PSH according to ICHD-3 beta. Only 22 patients met the diagnostic criteria for PSH according to ICHD-2. All patients with headache with stabbing pain without cranial autonomic symptoms fulfilled the diagnostic criteria for PSH according to ICHD-3 beta at the initial visit. Secondary causes for headache with stabbing pain were revealed in a small proportion (3.7 %) of patients after 2 weeks of follow-up.

Reversible cerebral vasoconstriction syndromes (RCVS) is a rare disease that is characterized by reversible multifocal stenosis of the cerebral arteries with various clinical manifestations. Though the pathomechanism of RCVS was unclear, we reported RCVS related to the levonorgestrel-releasing intrauterine system (IUS). A previous healthy 36-year-old woman had thunderclap headache after implanting the levonorgestrel-releasing IUS a year ago. In the serial angiography, we initially found left vertebra artery (VA), and then additionally new stenosis of both anterior cerebral arteries and middle cerebral arteries (MCA). Bilateral MCA stenosis improved but developed stenosis of right VA after a week. The mean flow velocities of both MCA increased in the first transcranial doppler (TCD), but normalized in the follow up TCD. Levonorgestrel might act as the vasoconstrictitve factor that increased the level of endothelin-1, diminished the release of NO and raised oxidative low-density lipoprotein (LDL). Although the exact pathological mechanisms for RCVS were not yet elucidated, this case might help clinicians understand the mechanisms of RCVS.

Lee JY, et al. J Clin Neurol. 2020 Oct;16(4):711-713. https://doi.org/10.3988/jcn.2020.16.4.711