Brain Atrophy and the Risk of Futile Endovascular Reperfusion in Acute Ischemic Stroke.

Background and Purpose- We aimed to evaluate the impact of brain atrophy on long-term clinical outcome in patients with acute ischemic stroke treated with endovascular therapy, and more specifically, to test whether there are interactions between the degree of atrophy and infarct volume, and between atrophy and age, in determining the risk of futile reperfusion. Methods- We studied consecutive patients with acute ischemic stroke with proximal anterior circulation intracranial arterial occlusions treated with endovascular therapy achieving successful arterial recanalization. Brain atrophy was evaluated on baseline computed tomography with the global cortical atrophy scale, and Evans index was calculated to assess subcortical atrophy. Infarct volume was assessed on control computed tomography at 24 hours using the formula for irregular volumes (A×B×C/2). Main outcome variable was futile recanalization, defined by functional dependence (modified Rankin Scale score >2) at 3 months. The predefined interactions of atrophy with age and infarct volume were studied in regression models. Results- From 361 consecutive patients with anterior circulation acute ischemic stroke treated with endovascular therapy, 295 met all inclusion criteria. Futile reperfusion was observed in 144 out of 295 (48.8%) patients. Cortical atrophy affecting parieto-occipital and temporal regions was associated with futile recanalization. Total global cortical atrophy score and Evans index were independently associated with futile recanalization in an adjusted logistic regression. Multivariable adjusted regression models disclosed significant interactions between global cortical atrophy score and infarct volume (odds ratio, 1.003 [95%CI, 1.002-1.004], P<0.001) and between global cortical atrophy score and age (odds ratio, 1.001 [95% CI, 1.001-1.002], P<0.001) in determining the risk of futile reperfusion. Conclusions- A higher degree of cortical and subcortical brain atrophy is associated with futile endovascular reperfusion in anterior circulation acute ischemic stroke. The impact of brain atrophy on insufficient clinical recovery after endovascular reperfusion appears to be independently amplified by age and by infarct volume.

Factors associated with the presence of headache in hospitalized COVID-19 patients and impact on prognosis: a retrospective cohort study.

INTRODUCTION: Headache is one of the most frequent neurologic manifestations in COVID-19. We aimed to analyze which symptoms and laboratory abnormalities were associated with the presence of headache and to evaluate if patients with headache had a higher adjusted in-hospital risk of mortality. METHODS: Retrospective cohort study. We included all consecutive patients admitted to the Hospital with confirmed SARS-CoV-2 infection between March 8th and April 11th, 2020. We collected demographic data, clinical variables and laboratory abnormalities. We used multivariate regression analysis. RESULTS: During the study period, 576 patients were included, aged 67.2 (SD: 14.7), and 250/576 (43.3%) being female. Presence of headache was described by 137 (23.7%) patients. The all-cause in-hospital mortality rate was 127/576 (20.0%). In the multivariate analysis, patients with headache had a lower risk of mortality (OR: 0.39, 95% CI: 0.17-0.88, p = 0.007). After adjusting for multiple comparisons in a multivariate analysis, variables that were independently associated with a higher odds of having headache in COVID-19 patients were anosmia, myalgia, female sex and fever; variables that were associated with a lower odds of having headache were younger age, lower score on modified Rankin scale, and, regarding laboratory variables on admission, increased C-reactive protein, abnormal platelet values, lymphopenia and increased D-dimer. CONCLUSION: Headache is a frequent symptom in COVID-19 patients and its presence is an independent predictor of lower risk of mortality in COVID-19 hospitalized patients.

The role of primary cilia in corpus callosum formation is mediated by production of the Gli3 repressor.

Agenesis of the corpus callosum (AgCC) is a frequent brain disorder found in over 80 human congenital syndromes including ciliopathies. Here, we report a severe AgCC in Ftm/Rpgrip1l knockout mouse, which provides a valuable model for Meckel-Grüber syndrome. Rpgrip1l encodes a protein of the ciliary transition zone, which is essential for ciliogenesis in several cell types in mouse including neuroepithelial cells in the developing forebrain. We show that AgCC in Rpgrip1l(-/-) mouse is associated with a disturbed location of guidepost cells in the dorsomedial telencephalon. This mislocalization results from early patterning defects and abnormal cortico-septal boundary (CSB) formation in the medial telencephalon. We demonstrate that all these defects primarily result from altered GLI3 processing. Indeed, AgCC, together with patterning defects and mispositioning of guidepost cells, is rescued by overexpressing in Rpgrip1l(-/-) embryos, the short repressor form of the GLI3 transcription factor (GLI3R), provided by the Gli3(Δ699) allele. Furthermore, Gli3(Δ699) also rescues AgCC in Rfx3(-/-) embryos deficient for the ciliogenic RFX3 transcription factor that regulates the expression of several ciliary genes. These data demonstrate that GLI3 processing is a major outcome of primary cilia function in dorsal telencephalon morphogenesis. Rescuing CC formation in two independent ciliary mutants by GLI3(Δ699) highlights the crucial role of primary cilia in maintaining the proper level of GLI3R required for morphogenesis of the CC.

Extracortical origin of some murine subplate cell populations.

The subplate layer, the deepest cortical layer in mammals, has important roles in cerebral cortical development. The subplate contains heterogeneous cell populations that are morphologically diverse, with several projection targets. It is currently assumed that these cells are generated in the germinative zone of the earliest cortical neuroepithelium. Here we identify a pallial but extracortical area located in the rostromedial telencephalic wall (RMTW) that gives rise to several cell populations. Postmitotic neurons migrate tangentially from the RMTW toward the cerebral cortex. Most RMTW-derived cells are incorporated into the subplate layer throughout its rostrocaudal extension, with others contributing to the GABAergic interneuron pool of cortical layers V and VI.

The invertebrate Caenorhabditis elegans biosynthesizes ascorbate.

l-Ascorbate, commonly known as vitamin C, serves as an antioxidant and cofactor essential for many biological processes. Distinct ascorbate biosynthetic pathways have been established for animals and plants, but little is known about the presence or synthesis of this molecule in invertebrate species. We have investigated ascorbate metabolism in the nematode Caenorhabditis elegans, where this molecule would be expected to play roles in oxidative stress resistance and as cofactor in collagen and neurotransmitter synthesis. Using high-performance liquid chromatography and gas-chromatography mass spectrometry, we determined that ascorbate is present at low amounts in the egg stage, L1 larvae, and mixed animal populations, with the egg stage containing the highest concentrations. Incubating C. elegans with precursor molecules necessary for ascorbate synthesis in plants and animals did not significantly alter ascorbate levels. Furthermore, bioinformatic analyses did not support the presence in C. elegans of either the plant or the animal biosynthetic pathway. However, we observed the complete (13)C-labeling of ascorbate when C. elegans was grown with (13)C-labeled Escherichia coli as a food source. These results support the hypothesis that ascorbate biosynthesis in invertebrates may proceed by a novel pathway and lay the foundation for a broader understanding of its biological role.

From wakefulness to sleep: migraine and hypnic headache association in a series of 23 patients.

OBJECTIVES/BACKGROUND: We analyzed characteristics of hypnic headache (HH), migraine and the relationship between both headaches in 23 patients. HH is an uncommon primary headache characterized by exclusively sleep-related attacks. Concurrence of other headaches, mainly migraine, has been reported, but relationship between both syndromes has rarely been considered. METHODS: We prospectively collected data in a headache outpatient office from January 2008 to September 2013. Demographic data and migraine and hypnic headache mean features were assessed. RESULTS: Twenty-three out of 2500 (0.92%) were diagnosed with HH or probable HH, and 16 of them (69.5%) had a history of migraine. Mean age at onset of HH and migraine was 56.2 ± 9.3 and 24.6 ± 12.2 years, respectively. In 12 cases, migraine attacks disappeared at 56.7 ± 9.8 years old. Regarding the relationship between both syndromes, in 10 patients, migraine disappeared and HH began immediately after. In 1 case there was a pain-free period, and in 5 an overlap between both headaches was registered. CONCLUSION: A history of migraine is common in HH patients in our series. Most frequent transition pattern was an immediate change between both syndromes. Hypnic headache and migraine might share a common pathophysiological predisposition.

[Pulmonary complications in pediatric patients with primary immunodeficiency]. / Complicaciones pulmonares en pacientes pediátricos con inmunodeficiencias primarias.

INTRODUCTION: Primary immunodeficiencies comprise diseases that impair the immune system. Clinical manifestations are characterized by recurrent respiratory infections, which may be complicated by bronchiectasis, peribronchial thickening, abscesses, bullae, and pulmonary fibrosis. The aim of this study was to determine pulmonary complications in pediatric primary immunodeficiency by type. RESULTS. We included 65 patients, 28 patients with humoral immunodeficiency, four with cellular immunodeficiency, 13 with well-defined syndromes, and 20 with phagocytic defects. Patients with cellular immunodeficiency with symptoms began at an early age, and were diagnosed before one year of age (p = 0.01 ). Patients with humoral immunodeficiency had more frequent and early respiratory symptoms (p = 0.01 ). The most common respiratory diseases were acute suppurative otitis media, with sinusitis and pneumonia more common in humoral immunodeficiencies and phagocytic defects. The most common pulmonary complications were bronchiectasis and pulmonary fibrosis interstitial damage, with no statistical difference between primary immunodeficiency type. Pulmonary function tests showed greater impairment in patients with phagocyte defects, but no statistical difference (p = 0.28). The presence of pulmonary complications showed no difference when compared by type of immunodeficiency, agammaglobulinemia only (p = 0.02). CONCLUSIONS: Cell immunodeficiencies are diagnosed as early as the onset of symptoms before the patient is one year old. Humoral immunodeficiencies present maximum upper and lower respiratory infections and increased risk of pulmonary complications, especially agammaglobulinemia.

Nummular headache and epicrania fugax: possible association of epicranias in eight patients.

OBJECTIVES: Epicrania fugax (EF) is a novel syndrome presenting with brief pain paroxysms that always start in a particular area of the head to spread immediately either forward or backward. Paroxysms stem from a focal area, in which a well-shaped continuous pain reminiscent of the symptomatic area described in nummular headache (NH) can be present. We aimed to analyze the association of these two epicranial headaches in eight patients. METHODS: We prospectively assessed all patients with EF attending an outpatient headache office from March 2008, when EF was first described, to June 2012. Among them, we selected those patients with a well-circumscribed continuous pain at the stemming point fulfilling the research diagnostic criteria for NH of the International Classification of Headache Disorders II Edition (ICHD-II) appendix. We considered the demographic and clinical features of the selected patients. RESULTS: Eight patients (five females, three males) were diagnosed with both EF and NH. Mean age of onset was 44.2 ± 12 (range: 23-60). Regarding NH, the diameter of the painful area was 4.4 ± 1 centimeters (range: 3-6) and pain intensity was 4.2 ± 0.7 (range: 3-5) on a 10-point verbal analogical scale (VAS). As for the EF, the radiating paroxysms always started in the NH painful area and lasted 6.6 ± 4.5 seconds (range: 2-15), with a pain intensity of 7.9 ± 1.6 (range 5-10) on the VAS. Five cases had forward radiation, while three cases had backward EF. Four cases had ipsilateral autonomic accompaniments. Six patients required a preventive, and lamotrigine achieved complete response in three of them. CONCLUSION: Although the etiology of NH and EF remains uncertain, both syndromes seem to share a peripheral source. Their association in a number of patients is probably reflecting a pathophysiological connection. Lamotrigine might be a good therapeutic option for those patients presenting with both disorders.

[Clinical and immunological characteristics in pediatric patients with coccidioidomycosis in northeastern Mexico]. / Características clínicas e inmunológicas en pacientes pediátricos con coccidioidomicosis del noreste de México.

BACKGROUND: Coccidioidomycosis is a systemic fungal disease caused by Coccidioides spp. Patients with phagocytic, cellular, or humoral immunodeficiencies exhibit immunodeficiencies that confer increased susceptibility to fungal infections. In Mexico there is an underreporting of this disease and no studies currently describe the immune status of these patients in an endemic area. OBJECTIVE: To describe the clinical and immunological characteristics of pediatric patients with coccidioidomycosis. MATERIALS AND METHODS: Pediatric patients with diagnosis of coccidioidomycosis from two tertiary level hospitals of northeastern Mexico were included, from the period 2008-2012; immune status was assessed by clinical history, immunoglobulins levels, levels of lymphocytes T, B, and NK (natural killer), and the nitroblue tetrazolium test. RESULTS: Thirty patients were included, 18 male (60%). The age at diagnosis was five years (median, range 0.25-13). Twelve were from Coahuila (40%). Residual pulmonary coccidioidomycosis was the clinical type presentation found in 16 patients (53%). A primary humoral immunodeficiency was found in three patients (10%) and a secondary immunodeficiency in another three (10%). Case fatality rate was 16%. CONCLUSIONS: . The disease predominated in male patients. In 33% of patients, levels of IgG were elevated, probably due to stimulation by chronic fungal infection. In 20% of patients, immunodeficiency was documented. There was a high mortality rate.

Peripheral nerve blocks: a therapeutic alternative for hemicrania continua.

OBJECTIVES: A complete response to indomethacin is required for the diagnosis of hemicrania continua (HC). Nevertheless, patients may develop side effects leading to withdrawal of this drug. Several alternatives have been proposed with no consistent effectiveness. Both anaesthetic blocks of peripheral nerves and trochlear corticosteroid injections have been effective in some case reports. METHODS: Twenty-two patients with HC were assessed in a headache outpatient office. Physical examination included palpation of the supraorbital nerve (SON) and greater occipital nerve (GON) as well as of the trochlear area. RESULTS: In 14 patients, at least one tender point was detected. Due to indomethacin intolerance, at least one anaesthetic block of the GON or SON, or an injection of corticosteroids in the trochlear area, were performed in nine patients. Four of them were treated with a combination procedure. All these patients experienced total or partial improvement lasting from 2 to 10 months. CONCLUSION: Anaesthetic blocks or corticosteroid injections may be effective in HC patients showing tenderness of the SON, GON or trochlear area.

Nummular headache with and without exacerbations: comparative characteristics in a series of 72 patients.

OBJECTIVES: Apart from the characteristic chronic head pain in a coin-shaped circumscribed area, superimposed exacerbations have been described from early reports of nummular headache (NH). In a prospective series, we aim to compare the demographic and clinical characteristics between cases of exacerbations (ENH) and non-exacerbations (NENH) in NH. METHODS AND RESULTS: Seventy-two NH patients (44 female, 28 male) attending a headache outpatient office. As eight patients presented with bifocal NH we analysed 80 painful areas; 47 (58.8%) presented in situ exacerbations. Mean intensity of exacerbations was 7.5 ± 1.6 and they lasted 5.7 ± 11.6 minutes. Exacerbation quality was mostly stabbing. We found no differences between ENH and NEHN groups in age at onset, baseline pain intensity, size of painful area, allodynia or other sensory symptoms, or baseline pain quality. There were no differences between populations with respect to relief with symptomatic therapy, requirement of preventative therapy and its response to preventatives. CONCLUSION: In situ exacerbations superimposed on baseline pain are frequent in NH and might be included in diagnostic criteria. No statistically significant differences were found between ENH and NENH cases in demographic and nosological characteristics, or needing or response to therapy, but these sample sizes are small.

Non-traumatic supraorbital neuralgia: a clinical study of 13 cases.

INTRODUCTION: Supraorbital neuralgia (SON) is an uncommon disorder characterized by pain in the area supplied by the supraorbital nerve, which covers the medial aspect of the forehead, together with tenderness over the supraorbital notch or along the course of the nerve. Few hospital-based series of non-trauma SON have been published. METHODS AND RESULTS: We prospectively analyzed 13 patients (11 females, two males) diagnosed with SON in a headache outpatient clinic over a four-year period. Background pain was mostly dull and of moderate intensity. In addition, nine patients reported sharp, burning or stabbing exacerbations of severe intensity. Eight cases were treated with an anesthetic blockade and achieved complete relief lasting from two to six months. Three patients also received gabapentin, with no or only slight improvement. CONCLUSION: Non-traumatic SON is an uncommon disorder in our headache clinic. Female preponderance and clinical features are comparable to the data collected in previous studies. A spontaneously remitting pattern is not uncommon, and anesthetic blockades are not always required.

Hemicrania continua in a headache clinic: referral source and diagnostic delay in a series of 22 patients.

Hemicrania continua (HC) is a unilateral and continuous primary headache with superimposed exacerbations frequently associated with autonomic features. Diagnostic criteria of HC, according to II Edition of International Classification of Headache Disorders require complete response to indomethacin. HC is probably misdiagnosed more often than other primary headaches. We aim to analyze characteristics of a series of 22 consecutive cases of HC. We recruited patients from a headache outpatient clinic in a tertiary hospital over a 3-year period (January 2008 to January 2011). We prospectively gathered demographic and nosological characteristics and considered referral source and delay between onset of headache and diagnosis of HC. Twenty-two patients (14 females, 8 males) out of 1,150, who attended the mentioned clinic during the inclusion period (1.9 %) were diagnosed with HC. All cases responded to indomethacin. No patient received a diagnosis of HC before attending our headache office. Mean latency of diagnosis was 86.1 ± 106.5 months (range 3-360). 11 patients (50 %) were referred from primary care, with 9 (40.9 %) from other neurology clinics and 2 (9.1 %) from other specialities offices. According to our series, HC is not an infrequent diagnosis in a headache outpatient clinic. Diagnostic delay is comparable to data collected in previous studies. As HC is frequently misdiagnosed, we thing there is a need for increasing the understanding of this entity, potentially responsive to indomethacin.

Gout. What's up doc? / Gota. ¿Qué hay de nuevo, doctor?

A considerable improvement in the knowledge of gout has taken place in the 2decades of the XXIth century. Definitions of disease, estate, and clinical situations, along with a new nomenclature, have been agreed. More importantly, the concept of gout as a "curable" or "controllable" disease has been settled. We know for the first time its prevalence in Spain. Factors associated to disease, the genetics that condition the predisposition to develop hyperuricemia and the structure and functions of the transportome complex that control the renal and intestinal handling of urate have been examined. Imaging techniques have come to support diagnosis. Different primary therapeutic targets have been defined depending on the burden of disease, and targets for secondary prevention considered. We know how to best prescribe available medications and prevent the risk of adverse events. Finally, we have understood the importance of adherence, education, and empower patients during treatment instead of blaming them.

A randomized clinical trial of a writing workshop intervention to improve autobiographical memory and well-being in older adults.

BACKGROUND: Despite much research on methods to improve new learning and memory in old age, there is virtually no literature on the improvement of autobiographical memory (AM). The present study assessed the effectiveness of a structured autobiographical writing workshop for improving AM, mood and self-concept in older adults. METHODS: Fifty-one nondemented older adults (67-96 years) participated. AM was assessed with the Autobiographical Memory Interview (AMI) and the Remote Memory Word Association Task (RMWAT). After completing baseline (BL) testing, participants were randomized to a structured autobiographical writing workshop, a reminiscence group (active control condition) or a no-treatment control group. Follow-up testing was completed at 8 and 34 weeks after BL. RESULTS: Repeated measures ANOVAs failed to reveal a group-by-time interaction for any of the autobiographical memory (AM) measures. Across groups, there was a decrease in number of mid- and late-life events reported (on the AMI), and memories tended to be less detailed (on the RMWAT) although more pleasant memories were reported with repeated testing. Mood remained unchanged; ratings of self-concept improved across all groups. CONCLUSIONS: This is the first study of its kind to use a randomized group design to test an intervention for AM in older adults. In general, our specific intervention was ineffective for increasing recall from one's life story, mood or self-concept. Methodological limitations and suggestions for future investigation are discussed.

Epicrania fugax with backward radiation: clinical characteristics of nine new cases.

Epicrania fugax (EF) is a novel syndrome, described as a paroxysmal and brief head pain, starting in posterior cranial regions and rapidly spreading forward ipsilateral eye, nose or forehead. Two patients with comparable clinical features stemming from frontal scalp to ipsilateral posterior regions have been recently described and proposed as backward radiation epicrania fugax (BREF). We report a new series of nine BREF and compare their clinical characteristics with 18 forward radiation EF (FREF). Since first description of BREF in February 2010 we have assessed nine patients (four males, five females) with this clinical picture at an outpatient headache office in a Tertiary Hospital. Comparison is established with 18 FREF patients (6 males, 12 females), attended since the publication of first series of EF in March 2008. We found no differences between BREF and FREF, respectively, in age at onset (43.4 ± 13.1 vs. 42.5 ± 17.7 years), female/male ratio (5/4 vs. 12/6), pain intensity (6.9 ± 2.1 vs. 6.8 ± 2.1 in a 0-10 visual analogical scale), duration (7.1 ± 4.9 vs. 5.7 ± 4.3 s) and frequency of episodes per day (7 ± 8.4 vs. 9.9 ± 15.4). Patients in BREF group presented less frequently interictal pain in stemming point (22.2 vs. 55.5%) and accompanying autonomic signs (33.3 vs. 55.5%), but without statistical significance in both the cases. This series reinforces the proposal of EF as a new headache variant or a new headache syndrome. Clinical picture of brief pain paroxysms starting in the anterior scalp and radiating backwards does not fit known headaches or neuralgias and might correspond to a reverse variant of EF, clinical characteristics of which are comparable to FREF.

Neurological symptoms in Covid-19 patients in the emergency department.

BACKGROUND: Coronavirus disease 2019 (Covid-19) might present neurological symptoms. We aimed to evaluate the frequency of them at the moment of emergency department (ED) visit and their impact in the prognosis. METHODS: Retrospective cohort study including all consecutive hospitalized cases between March 8th and April 11th, 2020. Covid-19 diagnosis was confirmed by polymerase chain reaction test and/or serology. We compared, in patients with and without neurological symptoms on admission, demographic, clinical presentation, and frequency and type of abnormal laboratory values. We analyzed the variables that were associated with in-hospital all-cause mortality by Cox-regression log-rank test. RESULTS: We included 576 hospitalized patients, 250 (43.3%) female, aged 67.2 years. At the moment of ED visit, 320 (55.6%) described neurological symptoms, including anosmia (146, 25.3%), myalgia (139, 24.1%), headache (137, 23.8%), and altered mental status (98, 17.0%). Neurological symptoms started the first symptomatic day in 198 (54.2%) cases. Patients with neurological symptoms presented later to the ED (7.9 versus. 6.6 days, p = .019). Only four (0.6%) cases had no typical Covid-19 general symptoms, and only six (1.9%) had a normal laboratory results, for a sensitivity of 98.7% (95% confidence interval (CI): 96.6%-99.6%) and 98.1% (95% CI: 95.7%-99.2%), respectively. In the multivariate Cox-regression of mortality predictors, anosmia (HR: 0.358, 95%CI: 0.140-0.916) and altered mental status (HR: 1.867, 95%CI: 1.162-3.001) were significant. CONCLUSION: Neurological symptoms were the most frequent extrapulmonary symptoms. They were present in half of the Covid-19 patients at the time of the ED visit. Anosmia on admission was an independent predictor of lower in-hospital mortality and altered mental status on admission predicted in-hospital mortality.

Anosmia is associated with lower in-hospital mortality in COVID-19.

BACKGROUND: Anosmia is common in Coronavirus disease 2019, but its impact on prognosis is unknown. We analysed whether anosmia predicts in-hospital mortality; and if patients with anosmia have a different clinical presentation, inflammatory response, or disease severity. METHODS: Retrospective cohort study including all consecutive hospitalized patients with confirmed Covid-19 from March 8th to April 11th, 2020. We determined all-cause mortality and need of intensive care unit (ICU) admission. We registered the first and worst laboratory parameters. Statistical analysis was done by multivariate logistic and linear regression. RESULTS: We included 576 patients, 43.3% female, and aged 67.2 years in mean. Anosmia was present in 146 (25.3%) patients. Patients with anosmia were more frequently females, younger and less disabled and had less frequently hypertension, diabetes, smoking habit, cardiac and neurological comorbidities. Anosmia was independently associated with lower mortality (OR: 0.180, 95% CI: 0.069-0.472) and ICU admission (OR: 0.438, 95% CI: 0.229-0.838, p = 0.013). In the multivariate analysis, patients with anosmia had a higher frequency of cough (OR: 1.96, 95%CI: 1.18-3.28), headache (OR: 2.58, 95% CI: 1.66-4.03), and myalgia (OR: 1.74, 95% CI: 1.12-2.71). They had higher adjusted values of hemoglobin (+0.87, 95% CI: 0.40-1.34), lymphocytes (+849.24, 95% CI: 157.45-1541.04), glomerular filtration rate (+6.42, 95% CI: 2.14-10.71), and lower D-dimer (-4886.52, 95% CI: -8655.29-(-1117.75)), and C-reactive protein (-24.92, 95% CI: -47.35-(-2.48)). CONCLUSIONS: Hospitalized Covid-19 patients with anosmia had a lower adjusted mortality rate and less severe course of the disease. This could be related to a distinct clinical presentation and a different inflammatory response.