Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2-infected older mice with neurological signs.

COVID-19 can cause neurological symptoms such as fever, dizziness, and nausea. However, such neurological symptoms of SARS-CoV-2 infection have been hardly assessed in mouse models. In this study, we infected two commonly used wild-type mouse lines (C57BL/6J and 129/SvEv) and a 129S calcitonin gene-related peptide (αCGRP) null-line with mouse-adapted SARS-CoV-2 and demonstrated neurological signs including fever, dizziness, and nausea. We then evaluated whether a CGRP receptor antagonist, olcegepant, a "gepant" antagonist used in migraine treatment, could mitigate acute neuroinflammatory and neurological signs of SARS-COV-2 infection. First, we determined whether CGRP receptor antagonism provided protection from permanent weight loss in older (>18 m) C57BL/6J and 129/SvEv mice. We also observed acute fever, dizziness, and nausea in all older mice, regardless of treatment. In both wild-type mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels with virtually no IL-6 release in mice lacking αCGRP. These findings suggest that migraine inhibitors such as those blocking CGRP receptor signaling protect against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection, which may have repercussions for related pandemic or endemic coronavirus outbreaks.IMPORTANCECoronavirus disease (COVID-19) can cause neurological symptoms such as fever, headache, dizziness, and nausea. However, such neurological symptoms of severe acute respiratory syndrome CoV-2 (SARS-CoV-2) infection have been hardly assessed in mouse models. In this study, we first infected two commonly used wild-type mouse lines (C57BL/6J and 129S) with mouse-adapted SARS-CoV-2 and demonstrated neurological symptoms including fever and nausea. Furthermore, we showed that the migraine treatment drug olcegepant could reduce long-term weight loss and IL-6 release associated with SARS-CoV-2 infection. These findings suggest that a migraine blocker can be protective for at least some acute SARS-CoV-2 infection signs and raise the possibility that it may also impact long-term outcomes.

Toward a better understanding of persistent headache after mild COVID-19: Three migraine-like yet distinct scenarios.

One year after the outbreak of coronavirus disease 2019 (COVID-19), referrals for persistent headache, often defined as "post-COVID headache," have become increasingly common in outpatient headache clinics. However, it is important to take into consideration that this term may include a spectrum of clinically different headache types. We describe three cases of migraine-like headaches in individuals with a history of mild COVID-19 infection to demonstrate some of the different phenotypes of persistent headaches seen. These cases highlight the importance of a careful evaluation when assessing the complexities of "post-COVID headache" as well as the need to further investigate the different, underlying, pathophysiological mechanisms.

Interference from heterophilic antibodies in D-dimer assessment. A case report.

We describe the case of a 3-year-old girl, admitted to the pediatric ward for three repeated episodes of severe migraine associated with vertigo, with onset 1 week after complete remission from an episode of chicken pox (i.e., varicella-zoster virus infection). All radiological and laboratory examinations were normal, except for a markedly elevated value of D-dimer (i.e. 8998 ng/ml; local reference range: < 243 ng/ml), measured with a commercial latex-enhanced immunoturbidimetric assay. After physical and Doppler ultrasound examination, possible presence of thrombosis was ruled out, and the patient was discharged. In the following year, however, her plasma D-dimer values always remained frankly elevated, so that an analytical interference was suspected. A plasma sample was treated with a specific heterophilic antibodies blocking reagent and then assayed along with the untreated sample, with these showing a marked discrepancy of D-dimer values, that is 232 versus 2877 ng/ml. These results, highly indicative for the presence of heterophilic antibodies, are discussed in the light of the serious challenges that this type of analytical interference may pose on quality and reliability of D-dimer testing.

Asymptomatic shedding of HSV-1 in patients undergoing oral surgical procedures and attending for noninvasive treatment.

Oral surgery and stress can trigger and/or increase asymptomatic shedding of herpes simplex virus type-1 (HSV-1) into human saliva. In this investigation we examined the frequency of HSV-1 shedding in 32 patients undergoing an oral surgery procedure compared with 40 control patients attending for noninvasive treatment. Control patients comprised 18 migraine patients and 22 patients with temporomandibular (TMD) joint problems. Nested-PCR was carried out on oral rinses collected from each patient prior to treatment and 7 days post-treatment. Fifty-two of sixty-one seropositive patients were positive for HSV-1 DNA in one or both oral rinses. The frequencies of HSV-1 shedding for the oral surgery and control patients were 84.6% and 85.7% respectively. Seropositive patients who started shedding after treatment were significantly higher in oral surgery patients (46.2%) compared to control patients (34.3%). Shedding of HSV-1 in the oral cavity is not only increased by direct surgical trauma, but also appears to be common in migraine and TMD patients attending for general dental treatment. Thus pain or pain-induced stress as well as anxiety associated with dental treatment may also be a risk factor for asymptomatic shedding in specific seropositive patients attending for dental treatment.

HIV-related neurological syndromes reduce health-related quality of life.

BACKGROUND: Human immunodeficiency virus (HIV) infection frequently results in neurological complications but the impact of different neurological syndromes on patients' quality of life remains unknown. METHODS: We investigated health-related quality of life (HRQoL) parameters among HIV/Acquired Immune Deficiency Syndrome (AIDS) patients with and without neurological disease, including 11 dimensions of HRQoL within the Medical Outcomes Short-form Health Survey-HIV. RESULTS: Comparisons of sociodemographic and systemic clinical variables did not differ between HIV/AIDS patients with (n=94) and without (n=75) neurological disease. However, patients with neurological diseases exhibited significantly lower HRQoL scores compared to matched controls, which was most evident among HIV/AIDS patients with cognitive impairment and sensory neuropathy. Prospective analysis revealed diminishing HRQoL scores prior to neurological diagnosis followed by a progressive and sustained improvement in HRQoL scores after intervention over a 96-week period. CONCLUSIONS: These studies indicate that while HIV-related neurological diseases are associated with reduced HRQoL scores, enhanced neurological care has a positive impact on HIV/AIDS patients' overall well-being.

Cluster headache associated with parainfluenza virus, preceded and succeeded by migraine.

A serologically proven case of parainfluenza viral infection was associated with the onset and disappearance of cluster headache. The patient had long-standing migraine that ceased during the cluster headache period and recurred when the latter stopped. Possibly, the virus was neurally transmitted to the trigeminal-autonomic system, creating an inflammatory response that transiently precipitated cluster headache and obliterated migraine.