Resumption of migraine preventive treatment with CGRP(-receptor) antibodies after a 3-month drug holiday: a real-world experience

BackgroundMigraine frequency increases after the cessation of successful preventive treatment with CGRP(-receptor) monoclonal antibodies (mAbs). In this study, we aimed to evaluate the course of migraine after treatment resumption.MethodsPatients with migraine, who started treatment with the same CGRP(-R) mAb after a three-month drug holiday were included in this analysis. We collected headache data at four prospective visits: 1) during the four weeks before the initial mAb treatment (baseline); 2) during the four weeks before the last mAb injection; 3) in weeks 13–16 of the drug holiday; 4) in weeks 9–12 after treatment restart. Outcomes were the changes in monthly migraine days (MMD), monthly headache days (MHD), monthly days with acute medication use (AMD) and Headache Impact Test-6 (HIT-6) scores across the observation period.ResultsThis study included 39 patients (erenumab n = 16; galcanezumab/ fremanezumab n = 23). MMD decreased from 12.3 ± 6.3 at the end of the drug holiday to 7.8 ± 5.5 three months after treatment restart (p = 0.001). The improvement after treatment resumption was similar to the response in the initial treatment period (baseline: 12.3 ± 6.3 MMD vs. 7.5 ± 5.2 MMD before treatment interruption). MHD and AMD showed a significant improvement after treatment restart. HIT-6 scores decreased, indicating a diminished impact of headache on everyday life.ConclusionsReinitiation of treatment with CGRP(-R) mAbs after a drug holiday leads to a significant reduction of migraine frequency and medication use as well as improvement in quality of life.     

A stage-specific sialoglycoprotein in encysting cells of Entamoeba invadens

A novel sialoglycoprotein with an apparent molecular mass of approximately 250 kDa was detected on the surface of cysts of Entamoeba invadens. Sialic acid was identified in this glycoprotein by gas chromatography after methanolysis; N-acetyl- and N-glycolyl neuraminic acid were identified by thin layer chromatography in hydrolysates of partially purified preparations of the 250 kDa glycoprotein as well as in whole cysts. The sialoglycoprotein is stage-specific and could be detected by binding of wheat germ agglutinin and a specific monoclonal antibody (JAM3) only to precysts and mature cysts but not to trophozoites. A 250 kDa protein could be metabolically labeled with [35S]methionine. This, together with the absence of such a glycoprotein in the encystation medium, suggests that the 250 kDa sialoglycoprotein is not an adsorbed serum glycoprotein. Indirect evidence suggests that the parasite may utilize serum components as a source for sialic acid.     

Multiple cerebral infarctions in a patient with Churg-Strauss syndrome

Neurological manifestation of Churg-Strauss syndrome (CSS) is common and usually consists of peripheral neuropathy due to small-vessel vasculitis, while cerebral manifestation is less frequent. We report the case of a 77-year-old woman with multiple cerebral infarctions and hypereosinophilia. The presence of hypereosinophilia, asthma, sinusitis and vasculitis led to the diagnosis of CSS. As cerebral infarctions occurred monophasically and an elevation of heart enzymes was present, we assumed cardiac involvement and multiple cerebral infarctions due to cardiac embolism. Treatment with high-dose IV methylprednisone and cyclophosphamide pulses led to significant improvement. This case illustrates multiple cerebral infarctions in CSS. CSS should always be considered in patients with hypereosinophilia and stroke.     

Aging and brain fitness (Commentary on Voelcker‐Rehage et al.)

The human extrastriate visual cortex contains functionally distinct regions where neuronal populations exhibit signals that are selective for objects. How such regions might play a causal role in underpinning our ability to recognize objects across different viewpoints remains uncertain. Here, we tested whether two extrastriate areas, the lateral occipital (LO) region and occipital face area (OFA), contained neuronal populations that play a causal role in recognizing two‐dimensional shapes across different rotations. We used visual priming to modulate the rotation‐sensitive activity of neuronal populations in these areas. State‐dependent transcranial magnetic stimulation (TMS) was applied after the presentation of a shape and immediately before a subsequent probe shape to which participants had to respond. We found that TMS applied to both the LO region and OFA modulated rotation‐invariant shape priming but, whereas the LO region was modulated by TMS for small rotations, the OFA was modulated for larger rotations. Importantly, our results demonstrate that a node in the face‐sensitive network, the OFA, participates in causally relevant encoding of non‐face stimuli.     

A model of the odontocete middle ear.

The high acoustic sensitivity of the bottlenose dolphin is physically defined and related to the anatomy of the middle ear. The paper presents a conceptual and parametric analysis of the demands imposed by this high sensitivity upon the middle ear mechanisms: the head and the middle ear structures must collect sound energy from a large area and concentrate it onto the oval window. Assuming that the specific input impedance of the mammalian cochlea is relatively constant, and smaller than the characteristic acoustic impedance of water, we find that the impedance matching task of the cetacean middle ear is very different from that of terrestrial mammals: instead of a large pressure amplification, cetaceans need amplification of particle velocity. Our mechanical four-bone model of the odontocete middle ear is based on the anatomy of the tympano-periotic complex and consists of four rigid bone units (tympanic bone, the malleus-incus complex, stapes, periotic bone) connected through elastic junctions. The velocity amplification is brought about by lever mechanisms and elastic couplings. The model produced velocity amplifications ranging from 7- to 23-fold when provided with middle ear parameters from the six odontocete species for which audiograms are available. The model reproduces the complete audiograms of these six species fairly well for frequencies up to about 100-120 kHz.     

Follicle size by ultrasound versus cervical mucus quality: normal and abnormal patterns in spontaneous cycles

Ultrasound (US) has been demonstrated to be the method of choice for diagnosing luteinized unruptured follicle syndrome and to be a valuable adjuvant in the assessment of luteal phase defect. In this prospective study, the use of US with postcoital testing (PCT) is evaluated. Fifty control infertility patients were examined with serial US for follicle dynamics in conjunction with PCT. Standard curves for follicle dynamics versus cervical mucus quality (Insler score) were calculated. Eighteen patients referred for abnormal mucus underwent similar evaluation. Their follicle dynamics versus mucus quality were compared with those of the controls. The findings were: (1) there is a predictable relationship between follicle size and mucus quality, (2) the majority of patients with abnormal mucus have normal follicular dynamics, and (3) a minority of patients with abnormal mucus have either a narrow mucus window or abnormal follicular dynamics. In addition, US was found to be cost-effective in the overall fertility evaluation.     

Mucociliary activity of free transplanted respiratory epithelium]

The function of free grafted respiratory epithelium was investigated in inbred rats. In nine of ten animals it could be shown that the respiratory epithelium not only regenerated as an epithelial surface lining but also regained mucociliary activity. The grafted epithelium was able to secrete mucus, which was equal in protein fragmentation to the secretion of normal nasal mucosa. The grafted respiratory epithelium showed normal ciliary function which could be demonstrated by recording the ciliary beat pattern present and by subsequent histological examination. Morphologically, a regular structure of ciliae (9 + 2) was found on the upper pole of the regenerated ciliated cells.