Computational analysis of affinity dynamics between the variants of SARS-CoV-2 spike protein (RBD) and human ACE-2 receptor.

The novel coronavirus SARS-CoV-2 resulted in a significant worldwide health emergency known as the COVID-19 pandemic. This crisis has been marked by the widespread of various variants, with certain ones causing notable apprehension. In this study, we harnessed computational techniques to scrutinize these Variants of Concern (VOCs), including various Omicron subvariants. Our approach involved the use of protein structure prediction algorithms and molecular docking techniques, we have investigated the effects of mutations within the Receptor Binding Domain (RBD) of SARS-CoV-2 and how these mutations influence its interactions with the human angiotensin-converting enzyme 2 (hACE-2) receptor. Further we have predicted the structural alterations in the RBD of naturally occurring SARS-CoV-2 variants using the tr-Rosetta algorithm. Subsequent docking and binding analysis employing HADDOCK and PRODIGY illuminated crucial interactions occurring at the Receptor-Binding Motif (RBM). Our findings revealed a hierarchy of increased binding affinity between the human ACE2 receptor and the various RBDs, in the order of wild type (Wuhan-strain) < Beta < Alpha < Gamma < Omicron-B.1.1.529 < Delta < Omicron-BA.2.12.1 < Omicron-BA.5.2.1 < Omicron-BA.1.1. Notably, Omicron-BA.1.1 demonstrated the highest binding affinity of -17.4 kcal mol-1 to the hACE2 receptor when compared to all the mutant complexes. Additionally, our examination indicated that mutations occurring in active residues of the Receptor Binding Domain (RBD) consistently improved the binding affinity and intermolecular interactions in all mutant complexes. Analysis of the differences among variants has laid a foundation for the structure-based drug design targeting the RBD region of SARS-CoV-2.

Randomized Trial of Patient Outreach Approaches to De-implement Outdated Colonoscopy Surveillance Intervals.

BACKGROUND AND AIMS: Guidelines now recommend patients with low-risk adenomas receive colonoscopy surveillance in 7-10 years and those with the previously recommended 5-year interval be re-evaluated. We tested 3 outreach approaches for transitioning patients to the 10-year interval recommendation. METHODS: This was a 3-arm pragmatic randomized trial comparing telephone, secure messaging, and mailed letter outreach. The setting was Kaiser Permanente Northern California, a large integrated healthcare system. Participants were patients 54-70 years of age with 1-2 small (<10 mm) tubular adenomas at baseline colonoscopy, due for 5-year surveillance in 2022, without high-risk conditions, and with access to all 3 outreach modalities. Patients were randomly assigned to the outreach arm (telephone [n = 200], secure message [n = 203], and mailed letter [n = 201]) stratified by age, sex, and race/ethnicity. Outreach in each arm was performed by trained medical assistants (unblinded) communicating in English with 1 reminder attempt at 2-4 weeks. Participants could change their assigned interval to 10 years or continue their planned 5-year interval. RESULTS: Sixty-day response rates were higher for telephone (64.5%) and secure messaging outreach (51.7%) vs mailed letter (31.3%). Also, more patients adopted the 10-year surveillance interval in the telephone (37.0%) and secure messaging arms (32.0%) compared with mailed letter (18.9%) and rate differences were significant for telephone (18.1%; 97.5% confidence interval: 8.3%-27.9%) and secure message outreach (13.1%; 97.5% confidence interval: 3.5%-22.7%) vs mailed letter outreach. CONCLUSIONS: Telephone and secure messaging were more effective than mailed letter outreach for de-implementing outdated colonoscopy surveillance recommendations among individuals with a history of low-risk adenomas in an integrated healthcare setting. (ClinicalTrials.gov, Number: NCT05389397).

Molecular characterization and antifungal activity of lipopeptides produced from Bacillus subtilis against plant fungal pathogen Alternaria alternata.

Over 380 host plant species have been known to develop leaf spots as a result of the fungus Alternaria alternata. It is an aspiring pathogen that affects a variety of hosts and causes rots, blights, and leaf spots on different plant sections. In this investigation, the lipopeptides from the B. subtilis strains T3, T4, T5, and T6 were evaluated for their antifungal activities. In the genomic DNA, iturin, surfactin, and fengycin genes were found recovered from B. subtilis bacterium by PCR amplification. From different B. subtilis strains, antifungal Lipopeptides were extracted, identified by HPLC, and quantified with values for T3 (24 g/ml), T4 (32 g/ml), T5 (28 g/ml), and T6 (18 g/ml). To test the antifungal activity, the isolated lipopeptides from the B. subtilis T3, T4, T5, and T6 strains were applied to Alternaria alternata at a concentration of 10 g/ml. Lipopeptides were found to suppress Alternaria alternata at rates of T3 (75.14%), T4 (75.93%), T5 (80.40%), and T6 (85.88%). The T6 strain outperformed the other three by having the highest antifungal activity against Alternaria alternata (85.88%).

Post-laparotomy Hypoxia: A Case Series.

Postoperative hypoxia is a challenge for surgeons. With the advent of better anesthesia and minimal access surgical techniques, the incidence of postoperative hypoxia in elective cases has decreased. However, the incidence in life-saving emergency procedures still poses a possible threat, and cases seem under-reported. We report a series of five cases of postoperative hypoxia after laparotomy. These cases comprise mesenteric laceration, proximal jejunal perforation, perforated duodenal ulcer, abdominal tuberculosis, and fall from height. Despite different etiologies, they landed up with the complication of postoperative hypoxia, which was attributable to the type of procedure they underwent and not the indication of the procedure itself. Thus, they form an interesting collection of post-laparotomy hypoxia cases. We present them with a compilation of probable causes of postoperative hypoxia in such cases. Postoperative hypoxia presents a diagnostic challenge and requires timely suspicion, prompt intervention to eliminate the cause, and good postoperative care. The major causes include incomplete lung re-expansion, pain-induced restriction in chest-wall/diaphragm mobility, prolonged surgery, a complication of pre-existing lung disease, residual effects of some drugs, and iatrogenic causes. We, therefore, recommend the use of postoperative oxygen support and diligent monitoring of vitals in all cases of laparotomy, allowing prompt and timely patient management. Future studies are warranted to explore the prevalence and possible causes of post-laparotomy hypoxia.

Comparative Evaluation of Microleakage of Zinc Phosphate Cement, Resin-Modified Glass Ionomer, and Two Dual-Cure Resin Cements: In Vitro Study.

Aims: The aim of this study is to evaluate and compare the sealing ability of a new resin cement which was undergoing trial with other three luting cements. Settings and Design: In vitro study. Subjects and Methods: Forty extracted intact human premolars were selected and standardized class 5 preparations for inlays were done at cementoenamel junction of buccal surfaces and direct composite inlay was fabricated. The samples were randomly grouped into 4: Group I luted with Rely X ARC resin cement, Group II with DCRC-10, a new indigenously developed resin cement, Group III with FujiCEM, and Group IV with zinc phosphate. After 24 h storage, samples were thermocycled and immersed in basic fuchsine dye. The longitudinal sections were assessed under a stereomicroscope for microleakage using graded criteria. Statistical Analysis Used: To analyze leakage scores among four groups and between enamel and dentin/cementum margins, Kruskal-Wallis nonparametric test and the Mann-Whitney test at P < 0.05 were used. Results: The dye penetration at cementum/dentin margins showed a statistically significant difference among four groups (P < 0.001). Adhesive luting cements produced lesser leakage scores at both margins than those cemented with zinc phosphate. Conclusions: The indigenously developed resin cement (DCRC-10, Group II) is comparable to that of Group I (RelyX ARC) in terms of its luting efficiency.

Post-COVID Syndrome and Severity of COVID-19: A Cross-Sectional Epidemiological Evaluation From North India.

Background COVID-19 has now lasted for more than two years as a pandemic and has had enduring effects on the health of people as the post-COVID syndrome. Recent literature has shown the long-term effects of COVID-19 on various organ systems, including but not limited to respiratory, cardiovascular, neurological, musculoskeletal, and gastrointestinal systems. Methods and objectives We aimed to estimate the prevalence of post-acute COVID symptoms in a tertiary care center in northern India; observe the effects of the demographic profile of age, BMI, gender, and presence of comorbidities on the persistence of post-COVID syndrome, and explore any correlation between the severity of COVID-19 disease and the persistence of post-COVID symptoms. We designed a survey containing structured questions evaluating post-COVID symptoms beyond three weeks (post-acute COVID phase), six weeks (post-COVID phase), and 12 weeks of acute illness. It was administered online.  Results Prevalence of post-COVID symptoms both after three and six weeks was reported to be 16.67% and 7.37%, respectively. The most common symptoms to persist were musculoskeletal symptoms (fatigue), followed by upper respiratory symptoms. Disease severity (p<0.05), BMI (p<0.05), and comorbidities were seen to affect post-COVID symptoms significantly, whereas gender and age of the patient had no significant effect. Disease severity significantly affected the persistence of post-COVID symptoms up to 12 weeks; however, this effect does not hold true in long COVID haulers. Also, the risk of developing persistent post-acute COVID symptoms was more in moderate to severe disease than in mild disease. Conclusion The pandemic might be close to over, but it is not out of our lives yet, and the persistence of post-COVID symptoms is exigent.

Neuropsychiatric Manifestations of Autoimmune Encephalitis in a Tertiary Hospital: A Case Series and Current Perspectives.

Importance: Autoimmune encephalitis (AE) refers to a group of neuropsychiatric conditions associated with specific circulating autoantibodies directed against synaptic receptors, neuronal cell surface proteins, and intracellular targets. Increased recognition of these disorders is of value, as affected patients prominently display cognitive impairment, behavioral disturbances, and seizures requiring multidisciplinary teams, with early recognition often impacting prognosis.Observations: This case series is based on a retrospective record review of adult patients diagnosed with AE between January 1, 2010- January 1, 2020. Cases 1 and 2, demonstrating anti- N-methyl-d-aspartate receptor (NMDAR) encephalitis with initial manifestations of neurologic and psychiatric symptoms, correlate with the literature describing a higher prevalence of this condition in young women. Case 3, despite being seronegative, exhibited classic features of anti-NMDAR encephalitis. Case 4 demonstrates a classic presentation of anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis: a middle-aged male with psychosis, altered mentation, and epilepsy. Case 5 had a more indolent neuropsychiatric presentation with mild elevation of N-type voltage-gated potassium channel (VGKC) antibody. Case 6, with glutamic acid decarboxylase 65 (GAD65) antibody, was an elderly female with speech dysfunction and altered mentation, and case 7 was an elderly male with GAD65 antibody who had stiff-person syndrome, ataxia, cognitive decline, and thymoma.Conclusions: This retrospective case series describes the clinical details of 7 individuals with AE and overlapping neuropsychiatric symptoms. This series is limited in scope, with a small number of cases and observational findings, which prevents specific conclusions from being drawn. Despite this limitation, the present article explores the nuances of variable presentations of this disease to inform better interdisciplinary management and emphasize the gap areas that need rigorous research.

Infectious Causes of Stroke.

Stroke is one of the primary causes of mortality and morbidity worldwide. It can be ischemic or hemorrhagic, and the former can be due to an in-situ thrombus or a distant embolus. Despite being a rare cause, stroke can also be caused in the setting of infection. Bacterial agents are the most common cause of stroke, among other infectious agents. Until the antibiotic era, rheumatic heart disease was a predisposing risk factor of infective endocarditis. VZV is the most common cause of strokes in pediatric and adult populations. Cryptococcus and Candida spp are the most common yeasts involved in CNS infections, especially in immunocompromised patients. In COVID-19 patients, ischemic strokes are more common than hemorrhagic strokes. In this review, we will discuss the most common infectious agents, with particular emphasis on COVID-19.

Prevalence of metabolic syndrome and its correlation with sexual dysfunction in adult psychiatric patients treated with psychotropics in a tertiary care hospital.

BACKGROUND: In the past two decades, there has been a profound increase in the incidence of metabolic disorders among the general population, and psychotropics are also said to play a major role in the development of metabolic syndrome. AIM: Determining the prevalence of metabolic syndrome (MetS) and sexual dysfunction (SD) and their correlation in psychiatric patients treated with psychotropics in a tertiary care hospital in Salem region, Tamil Nadu, India. MATERIALS AND METHODS: A cross-sectional study was conducted in the psychiatric department of Vinayaka Mission's Medical College and Hospitals, Salem on patients (n = 108) treated with psychotropics. The sociodemographic information, anthropometric measurements, and laboratory tests for metabolic functions were collected and assessed to determine the presence of metabolic syndrome (as per NCEP ATP III criteria). All the results were statistically analysed and P-value < .05 was considered to be statistically significant. RESULTS: The overall prevalence of MetS in the study population was 25.93%. The study found significant relationships between using olanzapine, risperidone, buspirone, and the presence of MetS. Depression was also found to be associated with the development of MetS. CONCLUSION: From this current study, it may be concluded that the psychiatric population is at risk for developing MetS, and the use of atypical antipsychotics (olanzapine, risperidone), anti-anxiety agent (buspirone) and clinical depression is significantly associated with metabolic syndrome. Hence, the metabolic function of psychiatric patients must be regularly assessed for early detection and management of any metabolic abnormalities. The study did not find a significant correlation between SD and MetS in psychiatric patients.

Hereditary spastic paraplegia.

Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative disorders which involve the corticospinal tracts and present with distinct spasticity and weakness of the lower extremities. The estimated prevalence of HSP is around 1.8/100,000 cases for both autosomal dominant and autosomal recessive types. Classification of HSP is based on inheritance pattern, clinical phenotype, and molecular pathophysiological mechanisms. The most common neuropathological sign is the axonal degeneration involving the lateral corticospinal tracts in both the cervical and thoracic spinal cord. The target of this review article is to provide a comprehensive overview of the HSP classification, neuropathology, and differential diagnosis.

Variants in GNAI1 cause a syndrome associated with variable features including developmental delay, seizures, and hypotonia.

PURPOSE: Neurodevelopmental disorders (NDDs) encompass a spectrum of genetically heterogeneous disorders with features that commonly include developmental delay, intellectual disability, and autism spectrum disorders. We sought to delineate the molecular and phenotypic spectrum of a novel neurodevelopmental disorder caused by variants in the GNAI1 gene. METHODS: Through large cohort trio-based exome sequencing and international data-sharing, we identified 24 unrelated individuals with NDD phenotypes and a variant in GNAI1, which encodes the inhibitory Gαi1 subunit of heterotrimeric G-proteins. We collected detailed genotype and phenotype information for each affected individual. RESULTS: We identified 16 unique variants in GNAI1 in 24 affected individuals; 23 occurred de novo and 1 was inherited from a mosaic parent. Most affected individuals have a severe neurodevelopmental disorder. Core features include global developmental delay, intellectual disability, hypotonia, and epilepsy. CONCLUSION: This collaboration establishes GNAI1 variants as a cause of NDDs. GNAI1-related NDD is most often characterized by severe to profound delays, hypotonia, epilepsy that ranges from self-limiting to intractable, behavior problems, and variable mild dysmorphic features.

Hematoma Risk After Needle Electromyography in Patients Using Newer Oral Anticoagulants.

PURPOSE: To assess the safety of needle electromyography in patients on non-vitamin K oral anticoagulants (NOACs) compared with warfarin. METHODS: A retrospective chart review was done in patients who underwent needle electromyography studies while they were using warfarin and NOACs. After the needle electromyography, all the patients were monitored for 2 hours and ultrasound of high-risk muscle groups was done. The complications were classified based on the International Society on Thrombosis and Hemostasis definitions. RESULTS: Fifty-eight patients were included: 29 were using NOACs and the other 29 were on warfarin. The mean age was 59.33 ± 16 years. Hemorrhagic complications from needle electromyography were noted in 9 patients: 7 (77.7%) NOACs and 2 (22.3%) warfarin. Among them, 6 patients (66.6%) met the diagnostic criteria for Clinically Relevant Non-Major Bleeding criteria proposed by International Society on Thrombosis and Hemostasis and 3 patients (33.4%) had an asymptomatic hematoma on ultrasound evaluation. A total of 267 muscles were tested and only 9 (3.3%) muscles had hemorrhagic complications. One patient (rivaroxaban) had acute bleeding requiring pressure bandage, five patients (two apixaban, two rivaroxaban, and one warfarin) had clinical hematoma that required ice packs, and three patients (two rivaroxaban and one warfarin) had a hematoma on ultrasound of deep muscles. CONCLUSIONS: Patients on NOACs had minimal risk of clinically relevant hemorrhagic complications, and the risk is not significantly different from those on warfarin.

Taxonomy and evolution of asymmetric male genitalia in the subgenus Ashima Chen (Diptera: Drosophilidae: Phortica Schiner), with descriptions of seven new species.

The taxonomy of the subgenus Ashima of the genus Phortica is revised. A cladistic analysis of 66 morphological characters is conducted, covering 35 species (28 known and 7 new species: Phortica efragmentata sp. nov., P. andreagigoni sp. nov., P. watabei sp. nov., P. halimunensis sp. nov., P. akutsui sp. nov., P. kerinciensis sp. nov., and P. takehiroi sp. nov.) which correspond to 71.4% of 49 total spp. of Ashima. The resulting cladogram shows that the studied species are separated into several clades/subclades/cluster each highly supported with specific synapomorphies. Those clades/subclades/cluster are newly defined as the following species groups, subgroups or complex: the afoliolata, foliiseta, nigrifoliiseta and angulata species groups; the foliiseta, tanabei, nigrifoliiseta and glabra species subgroups; and the foliiseta species complex. The subgenus Ashima is peculiar in having the asymmetric male genitalia as the ground plan and showing the antisymmetry (i.e. intraspecific mirror-image variation) in some species but the directional asymmetry (i.e. side-fixed asymmetry) in others. The evolution of genital asymmetry in this subgenus is estimated by mapping the states (symmetry, directional asymmetry and antisymmetry) of bilateral structures of male genitalia on the cladogram. This ancestral state reconstruction estimates that the directional asymmetry of male genitalia has evolved at the ancestor of this subgenus and then changed to the antisymmetric state independently in two lineages, the angulata + nigrifoliiseta species groups and the foliiseta species complex. In this study, a standardized terminology recently proposed for the male terminalia of Drosophila melanogaster is extendedly adopted to describe the morphology of male terminalia in the subgenus Ashima, one group of the subfamily Steganinae.

Primary Central Nervous System Lymphoma Presenting as Parkinsonism with Atypical MRI Findings and Elevated 14-3-3 Protein.

Primary central nervous system lymphoma (PCNSL) is a rare neoplasm with an incidence of 2 to 3% of all CNS malignancies. The diagnosis can be challenging, especially with atypical presentations. Movement disorders can be one of the rare presentations of PCNSL. Here, we present an unusual case of gradually progressing Parkinsonism with an elevation of cerebrospinal fluid (CSF) 14-3-3 protein and atypical imaging findings found to have PCNSL. A 76-year-old female patient presented with gait and intermittent speech difficulty. Initial workup revealed a contrast-enhancing lesion in the bilateral putamen and head of caudate without any mass effect. Her symptoms were rapidly progressed over 6 months and presented with mild dysarthria, bradykinesia, mild rigidity, and reduced left arm swinging. These features were consistent with Parkinsonism. The repeat imaging showed the progression of hyperintensities in the bilateral putamen. The patient underwent a stereotypic biopsy of the right caudate nucleus, which revealed PCNSL. She was treated with high-dose methotrexate and is currently in remission. Diagnosis of movement disorders remains clinical and rapid progression of symptoms, and atypical presentation must warrant further imaging and workup.

Painless Legs and Moving Toes Presenting as a Tardive Phenomenon: Case Report and Review of the Literature.

Painless legs and moving toes syndrome is a rare movement disorder. Various conditions like spinal cord trauma, lumbar radiculopathy, peripheral neuropathy, neuroleptic treatment, or traumatic lesions of the soft tissues of the foot can present with this disorder. In our case report, we aim to report a case of a young woman who developed painless legs and moving toes in the setting of chronic neuroleptic usage, which improved after the discontinuation of antipsychotics and treatment with clonazepam. We describe in detail her presentation and clinical examination, along with the review of the literature.

Hyperglycaemic chorea-ballism or unmasking of Huntington's chorea in a patient with diabetes.

Chorea-ballism is a neurological syndrome characterised by violent involuntary movements of one or both extremities. In the last decades, several patients with these involuntary movements were reported in association with hyperglycaemia. Here, we present a unique case of possible Huntington's disease, which could have been unmasked by the hyperglycaemic insult to the basal ganglia in a 64-year-old man who presented with chorea-ballism.

Is Magnetic Resonance Imaging Diffusion Restriction of the Optic Disc Head a New Marker for Idiopathic Intracranial Hypertension?

Background Idiopathic intracranial hypertension (IIH) is a headache syndrome due to raised intracranial pressure of unknown etiology. Before making the diagnosis of IIH, secondary causes of raised intracranial pressure must be ruled out. The radiological features associated with this condition have variable sensitivity and specificity. In this case series, we aim to describe a potential new radiological marker of IIH, that is, diffusion restriction, in the optic disc head and propose that this can be a specific finding in the appropriate clinical picture. Importance IIH causes vision loss and disabling daily headaches. The diagnosis of this condition is based on history and physical examination findings. Magnetic resonance imaging (MRI) is used to exclude other causes, but specific radiological markers for the diagnosis of IIH are lacking. Observations Five patients presented with the main complaint of headache, which was associated with blurry vision. All of our patients had a formal neuro-ophthalmological evaluation that confirmed the presence of optic disc edema in both eyes. They also underwent an MRI of the brain that showed diffusion restriction in the optic nerve head in either eye or both eyes. Patients underwent lumbar puncture in the lateral decubitus position, which revealed cerebrospinal fluid opening pressures > 25 cm H 2 O. They all responded well to standard treatments, with the resolution of symptoms in their follow-up appointments. Conclusion and Relevance The MRI diffusion restriction in the optic nerve head may be a reliable noninvasive marker for the diagnosis of IIH in the appropriate clinical picture.

A clinical scoring system for congenital contractural arachnodactyly.

PURPOSE: Congenital contractural arachnodactyly (CCA) is an autosomal dominant connective tissue disorder manifesting joint contractures, arachnodactyly, crumpled ears, and kyphoscoliosis as main features. Due to its rarity, rather aspecific clinical presentation, and overlap with other conditions including Marfan syndrome, the diagnosis is challenging, but important for prognosis and clinical management. CCA is caused by pathogenic variants in FBN2, encoding fibrillin-2, but locus heterogeneity has been suggested. We designed a clinical scoring system and diagnostic criteria to support the diagnostic process and guide molecular genetic testing. METHODS: In this retrospective study, we assessed 167 probands referred for FBN2 analysis and classified them into a FBN2-positive (n = 44) and FBN2-negative group (n = 123) following molecular analysis. We developed a 20-point weighted clinical scoring system based on the prevalence of ten main clinical characteristics of CCA in both groups. RESULTS: The total score was significantly different between the groups (P < 0.001) and was indicative for classifying patients into unlikely CCA (total score <7) and likely CCA (total score ≥7) groups. CONCLUSIONS: Our clinical score is helpful for clinical guidance for patients suspected to have CCA, and provides a quantitative tool for phenotyping in research settings.

White Matter Hyperintensities in Patients with Sporadic Hemiplegic Migraine.

BACKGROUND AND PURPOSE: To identify the differences in overall occurrence, location, and disease burden of white matter hyperintensities (WMH) in patients with sporadic hemiplegic migraine (SHM) and patients with migraine headaches. METHODS: We included patients who met diagnostic criteria proposed by the third International Classification of Headache Disorders (ICHD-3) for SHM and migraine headache. WMHs were identified using T2 fluid-attenuated inversion recovery axial sequence and classified based upon the location. The disease burden was assessed using Scheltens visual rating scale. RESULTS: Fifty patients met the diagnostic criteria for SHM and 100 patients for migraine headache. Patients in the study group were similar to the control group in terms of age (47.7 ± 12.2 years vs. 48.17 ± 9.7 years; P = .814) and gender (M: F; 14:36 vs. M: F 25:75; P = .693). WMH were found in 28 (56%) patients with SHM and 44 (44%) in patients with migraine headache. The proportion of patients with WMH was not different between the two groups (P = .166). On univariate analysis, the proportion of patients with WMH in parietal, occipital, and infratentorial regions was higher in patients with SHM. White matter burden determined by visual rating scale and proportion of patients with lesions ≥5 mm in diameter was also significantly higher in patients with SHM. On multivariate analysis, the WMH occurrence in the parietal lobe (P = .043) was found to be significantly higher in SHM. CONCLUSIONS: The WMH occurrence in patients with SHM is significantly more in the parietal lobe when compared to those with migraine headaches. WMH burden was also higher in patients with SHM, and larger white matter lesions occurred more frequently in these patients with SHM (compared to ordinary migraineurs).