Considerable Diagnostic Delay Research Articles

Understanding the Diagnostic Odyssey of Women with Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome in Denmark: A Qualitative Interview Study

The diagnosis of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is often a lengthy process that typically occurs during late adolescence. To support optimized and patient-centered care, this study aimed to investigate how women with MRKH syndrome experience the diagnostic process. From January 2021 to March 2021, we conducted in-depth interviews with 18 Danish women (≥25 years) diagnosed with MRKH syndrome. The interviews lasted a median of 92 minutes (range: 67-117). Data were analyzed using thematic analysis. As teenagers or young women at the time, all women had experienced the diagnostic process in the nonspecialized healthcare sector as deeply upsetting due to distressing gynecological examinations, use of inappropriate language, and considerable diagnostic delay. When reaching the specialized health care sector, questions could finally be answered, but this information and support did not significantly alter their feelings of being "deviant" or "flawed". The women continued their diagnostic odyssey beyond the health care system and found online communities that gave them valuable support in living with MRKH syndrome. Women experience the diagnostic odyssey of MRKH syndrome as upsetting and potentially traumatizing beyond the diagnosis. Healthcare professionals can influence young women's understanding and experience of MRKH syndrome by using inclusive language (eg, avoiding "deformity") and addressing all that is normal and functioning (eg, external genitalia and potential for sexual pleasure). In nonurgent conditions, young women should be given the choice to delay a genital examination.

Cerebrotendinous xanthomatosis presenting with schizophrenia-like disorder: A case report

BACKGROUND Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid-storage disorder caused by mutations in CYP27A1 . Psychiatric manifestations in CTX are rare and nonspecific, and they often lead to considerable diagnostic and treatment delay. CASE SUMMARY A 33-year-old female patient admitted to the psychiatric ward for presentation of delusions, hallucinations, and behavioral disturbance is reported. The patient presented with cholestasis, cataract, Achilles tendon xanthoma, and cerebellar signs in adulthood and with intellectual disability and learning difficulties in childhood. After the characteristic CTX findings on imaging were obtained, a pathological examination of the Achilles tendon xanthoma was refined. Re-placement therapy was then initiated after the diagnosis was clarified by genetic analysis. During hospitalization in the psychiatric ward, the nonspecific psychiatric manifestations of the patient posed difficulty in diagnosis. After the patient’s history of CTX was identified, the patient was diagnosed with organic schizophrenia-like disorder, and psychotic symptoms were controlled by replacement therapy combined with antipsychotic medication. CONCLUSION Psychiatrists should be aware of CTX, its psychiatric manifestations, and clinical features and avoid misdiagnosis of CTX for timely intervention.

The diagnostic accuracy of spirometry as screening tool for adult patients with a benign subglottic stenosis

BackgroundThere is a considerable diagnostic delay in the diagnosis ‘benign acquired subglottic stenosis in adults’ (SGS, diagnosed by the reference standard, i.e. laryngo- or bronchoscopy). Patients are frequently misdiagnosed since symptoms of this rare disease may mimic symptoms of ‘asthma.’ The ‘Expiratory Disproportion Index’ (EDI) obtained by spirometry, may be a simple instrument to detect an SGS-patient. The aim of this study was to evaluate the diagnostic accuracy of the EDI in differentiating SGS patients from asthma patients.MethodsWe calculated the EDI from spirometry results of all SGS-patients in the Leiden University Medical Center (LUMC), who had not received treatment 2 years before their spirometry examination. We compared these EDI results with the EDI results of all true asthma patients between 2011 and 2019, who underwent a bronchoscopy (exclusion of SGS by laryngo- or bronchoscopy).ResultsFifty patients with SGS and 32 true asthma patients were included. Median and IQR ranges of the EDI for SGS and asthma patients were 67.10 (54.33–79.18) and 37.94 (32.41–44.63), respectively. Area under the curve (ROC) of the accuracy of the EDI at discriminating SGS and asthma patients was 0.92 (95% CI = 0.86–0.98). The best cut-off point for the EDI was > 48 (i.e. possible upper airway obstruction), with a sensitivity of 88.0%% (95%CI = 77.2-95.0%%) and specificity of 84.4% (95%CI = 69.4-94.1%).ConclusionsThe EDI has a good diagnostic accuracy discriminating subglottic stenosis patients from asthma patients, when compared to the reference standard. This measurement from spirometry may potentially shorten the diagnostic delay of SGS patients. Further studies are needed to evaluate clinical reproducibility.

Cephalalgia heterotopica: a case series of extratrigeminal cluster headache

Introduction Cluster headache is a very disabling neurological disorder that usually presents with unilateral severe headache associated with ipsilateral cranial autonomic symptoms. Even among the typical cases, there is a considerable diagnostic delay and most patients will have seen three general practitioners before being referred to neurology services, some having been to colleagues in dentistry or otorhinolaryngology. The extratrigeminal presentation of this condition poses a great obstacle to a proper diagnostic workup. Objective This consecutive case series study aimed to report clinical features, treatment, and outcome of 3 patients with extratrigeminal Cluster Headache. Materials and Methods Case series of our Headache Clinic. Data disclosure was authorized by the patients through an informed consent form. Results Two males and one female were evaluated. The ages were 53, 64, and 71 years. The mean age of symptoms onset was 50, 60, and 66 years, respectively. Two patients described excruciating shoulder pain and one presents severe pain in the malar area. All patients reported prominent autonomic ipsilateral symptoms such as lacrimation, conjunctival injection, nasal symptoms, and restlessness accompanying pain attacks. Preventive treatment with verapamil and occipital nerve block was useful. Conclusion Extratrigeminal cluster presentation is a diagnostic challenge. Proper recognition of these cases prevents unnecessary examination and treatment trials and directly benefits the patients since effective treatment is already available. A proper case definition of this rare clinical presentation may provide new insight into our understanding of the cluster headache mechanisms. Keywords: Cluster headache, Extratrigeminal headache, Shoulder pain.

Diagnosis and therapy of Mycobacterium marinum: a single-center 21-year retrospective analysis.

In Europe, infections with Mycobacterium (M.) marinum are rare. We conducted a retrospective single-center study to assess the clinical spectrum of M.marinum infection and its diagnosis, treatment and outcome under real-world conditions. Eighteen patients presenting with M.marinum infections between 1998 and 2018 were identified in the data warehouse of the University Hospital Würzburg and considered for detailed analysis. Twelve patients reported aquatic exposure. In 16/18 cases the upper extremities were affected. No invasive infections were detected. Mean time to diagnosis was 15weeks. Histology revealed granulomatous inflammation in 14 patients while mycobacterial cultures were positive for M.marinum in 16 cases. Most patients received antibiotic monotherapy (14/18) while combination therapy was administered in four cases. Treatment (with a median duration of 10weeks) was successful in 13 patients. Five patients were lost to follow-up. Our retrospective analysis of M.marinum infections at a German tertiary referral center revealed a considerable diagnostic delay and the relevance of microbiological culture, PCR and histology for diagnosis. Monotherapy with clarithromycin (rather than doxycycline) appeared as a reasonable treatment option while immunosuppressed or -compromised patients and those with extended disease received combination therapy.

Clinical, endocrine and genetic spectrums of mucopolysaccharidoses type VI in Duhok city, Kurdistan region, Iraq

Mucopolysaccharidoses type VI is a rare disorder and establishing the diagnosis requires assays that are unavailable in a routine care setting. There is an increased risk of considerable diagnostic delay and missing patients due to incorrect diagnosis. The present study was conducted to determine the socio-demographic characteristics, clinical manifestations, and anthropometric parameters of patients with MPS type VI. Patients' enzyme levels and genetic profiles were also examined. The present study included a total of 16 patients who had been diagnosed as MPS type VI and were referred to Hivi Pediatric Hospital in Duhok, Kurdistan Region, Iraq, till the time period of March 2022. Diagnoses were made in all the patients by analyzing the enzyme level. Moreover, a genetic study was performed to confirm the diagnosis. From each of the patients, a blood sample was taken to determine the hematological parameters. Among the study participants, 9 were males and 7 were females. The mean age of the patients was 6.81±4.99 years and the age at diagnosis was 21.13±15.19 months. All of them presented with a course facial features, 75% had short stature, 87.5% had corneal clouding, 12.5% had glaucoma, 68.75% had poor vision, 18.75% of them had optic nerve disease, 56.25% had otitis media, 56.25% had poor hearing, 68.75% had a history of recurrent sinusitis, 50% had an enlarged tongue, and 75% had abnormal teeth. Approximately 56.25% of the patients presented with sleep apnea, 37.5% had obstructive and restrictive airway disease, none of the patients had cardiac arrhythmia, 37.5% had cardiomyopathy, 31.25% had abdominal hepatosplenomegaly, 81.25% had skeletal abnormalities, all of the patients had normal intelligence, 9 (56.25%) had a past medical history of other systemic illness and 7 (43.75%) had a past history of surgery. Out of the total number of patients, 13 patients had c.962T>C (p.(Leu321Pro)) mutation, one patient had c.585T>A (p.(ASP195Glu)) mutation, one patient had c.[585T>A];[753C>G] (Asp195 Glu];[Tyr251 Ter]), and one patient had c.{288C>A];[962T>C] (p.[Ser96Arg];[Leu321Pro]) mutations. Due to the rarity in prevalence, early detection of the said disorder is critical; early treatment may result in improved outcomes, which may have potential significance for newborn screening.

International registry of congenital porto-systemic shunts: a multi-centre, retrospective and prospective registry of neonates, children and adults with congenital porto-systemic shunts

BackgroundCongenital portosystemic shunts (CPSS) are rare vascular malformations associated with the risk of life-threatening systemic conditions, which remain underdiagnosed and often are identified after considerable diagnostic delay. CPSS are characterized by multiple signs and symptoms, often masquerading as other conditions, progressing over time if the shunt remains patent. Which patients will benefit from shunt closure remains to be clarified, as does the timing and method of closure. In addition, the etiology and pathophysiology of CPSS are both unknowns. This rare disorder needs the strength of numbers to answer these questions, which is the purpose of the international registry of CPSS (IRCPSS).MethodA retrospective and prospective registry was designed using secuTrial® by the ISO certified Clinical Research Unit. Given that a significant number of cases entered in the registry are retrospective, participants have the opportunity to use a semi-structured minimal or complete data set to facilitate data entry. In addition, the design allows subjects to be entered into the IRCPSS according to clinically relevant events. Emphasis is on longitudinal follow-up of signs and symptoms, which is paramount to garner clinically relevant information to eventually orient patient management. The IRCPSS includes also three specific forms to capture essential radiological, surgical, and cardiopulmonary data as many times as relevant, which are completed by the specialists themselves. Finally, connecting the clinical data registry with a safe image repository, using state-of-the-art pseudonymization software, was another major focus of development. Data quality and stewardship is ensured by a steering committee. All centers participating in the IRCPSS have signed a memorandum of understanding and obtained their own ethical approval.ConclusionThrough state-of-the-art management of data and imaging, we have developed a practical, user-friendly, international registry to study CPSS in neonates, children, and adults. Via this multicenter and international effort, we will be ready to answer meaningful and urgent questions regarding the management of patients with CPSS, a condition often ridden with significant diagnostic delay contributing to a severe clinical course.

Diagnostic Pathway of Head & Neck Cancer Patients in Ireland: Audit of patterns of first attendance 1983-2019.

##Objectives: This audit explores patterns of HNC patient presentation in primary care in Ireland over four decades and reflects on the possible impact of a 10-year national HNC awareness campaign. ##Materials and Methods: Trends in patient presentation and diagnosis are presented for 920 HNC patients across three time periods: 1983-1990, 2010 and 2018-2019. Descriptive analysis was undertaken using SPSS-v27 on basic demographic details, tumour-related details and primary care referral patterns. ##Results: Patients were generally male (71%), aged 54+ (71%), and 84% were diagnosed with squamous cell carcinoma (SCC). Larynx, tongue and tonsil were the most common sub-sites. General Medical Practitioners (GPs) were the first healthcare contact for 75% cases, with only13% referred by General Dental Practitioners (GDPs). This pattern remained consistent across four decades. GDP role was higher for tongue, floor of mouth and intra-oral tumours (30-47%), with some increase seen in recent years. While symptomology varied by site, symptom burden remained high across the decades with 99.9% exhibiting 1+ NICE ‘red flag signs’ of HNC, suggesting considerable diagnostic delay, despite a 10-year national campaign to raise public and professional awareness. ##Conclusions: This audit highlights the role of GPs in HNC diagnosis, but reveals sub-optimal use of the dental pathway. The high symptom burden reported suggests considerable diagnostic delay. Increased and sustained efforts are required to raise public and professional awareness, encourage regular dental attendance, upskill HCP in opportunistic screening and ensure appropriate responses to symptomatic patients.

Spontaneous Pulmonary Hemorrhage Following Thrombolytic Therapy for Acute Myocardial Infarction

Systemic thrombolysis in the setting of acute myocardial infarction (AMI) remains an effective treatment. However, it exposes to a non-negligible bleeding risk Diffuse pulmonary hemorrhage is a of the rare complication of thrombolysis, it can cause a serious medical emergency potentially leading to fatal acute respiratory failure. We present four cases of diffuse pulmonary hemorrhage following administration of intravenous thrombolytic therapy (Tenecteplase), the Lack of recognition that the lungs too may be a site of spontaneous hemorrhage during thrombolytic therapy may lead to a considerable diagnostic and therapeutic delay. Pulmonary hemorrhage should be considered in the differential diagnosis of patients who receive thrombolytic therapy in whom new roentgenographic pulmonary infiltrates present accompanied by decreases in hematocrit value.

Primary hyperoxaluria in Italy: the past 30\xa0years and the near future of a (not so) rare disease

BackgroundPrimary hyperoxalurias (PHs) are rare autosomal recessive diseases of the glyoxylate metabolism; PH1 is caused by mutations in the AGXT gene, PH2 in GRHPR and PH3 in HOGA1.MethodsHere we report the first large multi-center cohort of Italian PH patients collected over 30 years (1992–2020 median follow-up time 8.5 years). Complete genotype was available for 94/95 PH1 patients and for all PH2 (n = 3) and PH3 (n = 5) patients. Symptoms at onset were mainly nephrolithiasis (46.3%) and nephrocalcinosis (33.7%). Median age at onset of symptoms and diagnosis were 4.0 years and 9.9 years, respectively.ResultsFifty-four patients (56.8%) were diagnosed after chronic kidney disease. Sixty-three patients (66.3%) developed end stage kidney disease (median age 14.0 years). Twenty-one patients had a kidney-only transplant and, among them, seven had a second kidney transplant combined with liver transplant. A combined kidney–liver transplant was carried out in 29 patients and a sequential kidney–liver transplant was performed in two. In five cases a preemptive liver transplant was performed. Those receiving a liver-only transplant tended to have lower kidney function at last follow-up.ConclusionOur study of PHs in Italy underlines a considerable diagnostic delay, which has only slightly decreased in recent years. Therefore, we suggest a more extensive use of both metabolic screening among patients with recurrent kidney stones and genotyping, including unambiguous assignment of minor/major allele status in order to promptly begin appropriate treatment. This will be fundamental in order to have access to the new therapies, which are mainly focused on substrate reduction for the oxalate-producing enzymes using RNA-interference.Graphical abstract

Idiopathic inflammatory myopathies: one year in review 2021

Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare and complex connective tissue diseases, mainly characterised by inflammatory involvement of skeletal muscles. Several other organs may be affected, particularly lungs, heart, skin, gastrointestinal tract and joints, often determining the morbidity and mortality associated with these autoimmune disorders. The course is generally chronic and the onset subacute. This latter aspect, together with the rarity of these conditions, can result in a clinical challenge for the physician with a considerable diagnostic delay. The scientific literature makes continuous advances in the understanding of these diseases, in particular with regards to the pathogenesis, serological findings, diagnostic strategies and therapeutic approaches. The aim of this review is to highlight the most relevant literature contributions published on this topic over the last year.

Unraveling neuronal ceroid lipofuscinosis type 2 (CLN2) disease: A tertiary center experience for determinants of diagnostic delay.

To evaluate the clinical phenotype, disease course, laboratory, and genetic features of patients with CLN2 disease over a 20 year period with a special emphasis on risk factors for diagnostic delay. Thirty patients (23 families) with CLN2 disease, evaluated between 1996 and 2019 in a tertiary referral center in Turkey, were included. Clinical features, diagnostic pathway, disease course, genetic data, electrophysiological, and neuroimaging findings were analyzed, retrospectively. The patients diagnosed between 1996 and 2009, and 2010-2019 were defined as group 1 (G1), and group 2 (G2), respectively. Patients in these two groups were also compared. The median age at symptom-onset was 36 months (20 months-7 years). Most common presenting symptoms were seizures (70%), followed by language delay (43%), and psychomotor regression (27%). Median age at diagnosis was 5.2 years (1.6-11 years) with a median 27 months (1 month-7 years) of diagnostic delay. Age at diagnosis was earlier in G2 (4.6 years vs 7 years, p=0.002), with a shorter time to diagnosis (21 months vs 39 months, p=0.004). Median time between the onset of first symptoms and death was 8.3 years (SE 1.0). Electroencephalograms (EEG) revealed abnormal features predominantly in posterior hemispheral regions and a photoparoxysmal response to intermittent photic stimulation was detected in 53% of the patients. Cerebellar (96%)/cerebral atrophy (83%), and white matter changes (57%) were the most common radiological abnormalities. Most of our patients presented with late-infantile onset seizures. Despite increased availability of enzymatic and molecular testing, there is still a considerable diagnostic delay.

Theranostic Approach in Breast Cancer: A Treasured Tailor for Future Oncology.

Breast cancer is the most frequent invasive malignancy and the second major cause of cancer death in female subjects mostly due to the considerable diagnostic delay and failure of therapeutic strategies. Thus, early diagnosis and possibility to monitor response to the treatment are of utmost importance. Identification of valid biomarkers, in particular new molecular therapeutic targets, that would allow screening, early patient identification, prediction of disease aggressiveness, and monitoring response to the therapeutic regimen has been in the focus of breast cancer research during recent decades. One of the intensively developing fields is nuclear medicine combining molecular diagnostic imaging and subsequent (radio)therapy in the light of theranostics. This review aimed to survey the current status of preclinical and clinical research using theranostic approach in breast cancer patients with potential to translate into conventional treatment strategies alone or in combination with other common treatments, especially in aggressive and resistant types of breast cancer. In addition, we present 5 patients with breast cancer who were refractory or relapsed after conventional therapy while presumably responded to the molecular radiotherapy with 177Lu-trastuzumab (Herceptin), 177Lu-DOTATATE, and 177Lu-FAPI-46.

Gender differences in patient journey to diagnosis and disease outcomes: results from the European Map of Axial Spondyloarthritis (EMAS)

Introduction/objectivesTo evaluate the journey to diagnosis, disease characteristics and burden of disease in male and female patients with axial spondyloarthritis (axSpA) across Europe.MethodData from 2846 unselected patients participating in the European Map of Axial Spondyloarthritis (EMAS) study through an online survey (2017–2018) across 13 countries were analysed. Sociodemographic characteristics, lifestyle, diagnosis, disease characteristics and patient-reported outcomes (PROs) [disease activity –BASDAI (0–10), spinal stiffness (3–12), functional limitations (0–54) and psychological distress (GHQ-12)] were compared between males and females using chi-square (for categorical variables) and student t (for continuous variables) tests.ResultsIn total, 1100 (38.7%) males and 1746 (61.3%) females participated in the EMAS. Compared with males, females reported considerable longer diagnostic delay (6.1 ± 7.4 vs 8.2 ± 8.9 years; p < 0.001), higher number of visits to physiotherapists (34.5% vs 49.5%; p < 0.001) and to osteopaths (13.3% vs 24.4%; p < 0.001) before being diagnosed and lower frequency of HLA-B27 carriership (80.2% vs 66.7%; p < 0.001). In addition, females reported higher degree of disease activity in all BASDAI aspects and greater psychological distress through GHQ-12 (4.4 ± 4.2 vs 5.3 ± 4.1; p < 0.001), as well as a greater use of alternative therapies.ConclusionThe patient journey to diagnosis of axSpA is much longer and arduous in females, which may be related to physician bias and lower frequency of HLA-B27 carriership. Regarding PROs, females experience higher disease activity and poorer psychological health compared with males. These results reflect specific unmet needs in females with axSpA needing particular attention.Key Points• Healthcare professionals’ perception of axSpA as a predominantly male disease may introduce some bias during the diagnosis and management of the disease. However, evidence about male-female differences in axSpA is scarce.• EMAS results highlight how female axSpA patients report longer diagnostic delay and higher burden of the disease in a large sample of 2846 participants of 13 European countries.• Results reflect unmet needs of European female patients. Healthcare professionals should pay close attention in order to accurately diagnose and efficiently manage axSpA cases while further research should be developed on the cause of reported gender differences.

Why, Whom, and How to Screen for Chronic Thromboembolic Pulmonary Hypertension after Acute Pulmonary Embolism

Chronic thromboembolic pulmonary hypertension (CTEPH) is considered a long-term complication of acute pulmonary embolism (PE). Diagnosing CTEPH is challenging, as demonstrated by a considerable diagnostic delay exceeding 1 year, which has a negative impact on the patient's prognosis. Dedicated screening CTEPH strategies in PE survivors could potentially help diagnosing CTEPH earlier, although the optimal strategy is unknown. Recently published updated principles for screening in medicine outline the conditions that must be considered before implementation of a population-based screening program. Following these extensive principles, we discuss the pros and cons of CTEPH screening, touching on the epidemiology of CTEPH, the prognosis of CTEPH in the perspective of emerging treatment possibilities, and potentially useful tests and test combinations for screening. This review provides a modern perspective on CTEPH screening including a novel approach using a simple noninvasive algorithm of sequential diagnostic tests applied to all PE survivors.

Delay in the diagnosis of pulmonary tuberculosis in The Gambia, West Africa: A cross-sectional study

ObjectivesTo investigate the pattern of tuberculosis (TB) care initiation and risk factors for TB diagnostic delay in The Gambia. MethodsIn this cross-sectional study, adult patients diagnosed with pulmonary TB (pTB) in public facilities in the Greater Banjul Area of The Gambia were consecutively recruited from October 2016 to March 2017. Diagnostic delay was defined as >21 days from the onset of at least one symptom suggestive of pTB to diagnosis. Logistic regression analyses were used to investigate risk factors for diagnostic delay. ResultsOverall, 216 pTB patients were included in the study; the median (Interquartile Range (IQR)) age was 30 (23–39) years and 167 (77%) were male patients. Of the 216 patients, 110 (50.9%) of them initiated care-seeking in the formal and informal private sector and 181/216 (83.8%) had TB diagnostic delay. The median (IQR) duration from the onset of symptoms to TB diagnosis was 34 (28–56) days. Age groups 18–29 years (aOR 3.2; 95% CI 1.2–8.8 [p = 0.02]) and 30–49 years (aOR 5.1; 95% CI 1.6–16.2 [p = 0.006]) and being employed (aOR 4.2; 95% CI 1.7–10.5 [p = 0.002]) were independent risk factors for TB diagnostic delay. ConclusionThere is considerable TB diagnostic delay in The Gambia, and this is likely to be worsened by the COVID-19 pandemic.

Desquamative gingivitis: a challenging diagnosis for clinicians.

Introduction Diagnosis of underlying causes for desquamative gingivitis (DG) is often delayed in clinical settings, but little is known about factors influencing its delayed diagnosis. We investigated the diagnostic patterns and associated factors in a cohort of patients presenting primarily with DG.Materials and methods A total of 41 patients presenting primarily with DG were interviewed to evaluate professional and patient diagnostic delays. Severity of DG was evaluated using the desquamative gingivitis clinical score (DGCS) proposed by Arduino <i>et al.</i> (2017).Results The study sample was composed of 29 females and 12 males. On average, patients waited 10.8 ± 10 months (range 4-20 months) before seeking their first professional consultation (that is, patient delay). Less severe disease and female gender were significantly associated with longer patient delay. Patients consulted an average of 4.1 ± 2 healthcare professionals (range two to six) before a definitive diagnosis was reached, with an average professional delay of 7.3 ± 5 months (range 2-11 months). Professional delay was positively correlated with the number of professional consultations (r = 0.69) and absence of other oral mucosal lesions or extraoral involvement.Conclusions Considerable diagnostic delay is a feature of the natural history of DG. Increased patient knowledge and professional awareness regarding DG symptoms and diagnostic measures is needed to reduce diagnostic delay and improve patients' experience with this disease.

Diagnostic delay for superficial and deep endometriosis in the United Kingdom

A Cross-sectional study was undertaken at a specialist centre in the United Kingdom investigating duration and causes of delay in the diagnosis of endometriosis. One hundred and one women completed a self-reported questionnaire containing 20 items about their psychosocial, symptoms and experiences. The statistical analysis included a Mann-Whitney U test. A p value of .05 was considered statistically significant. The Spearman’s rank correlation was also calculated. Overall, there was a median delay of 8 years (Q1–Q3: 3–14) from the onset of symptoms to a diagnosis of endometriosis. Factors such as menstrual cramps in adolescence, presence of rectovaginal endometriosis, normalisation of pain and the attitudes of health professionals contributed to a delayed diagnosis (p values<.05). There was a negative correlation indicating the earlier the onset of symptoms, the greater the delay to diagnosis (Spearman’s Rank Correlation Coefficient –0.63, p<.01). The results of this study highlight a considerable diagnostic delay associated with endometriosis and the need for clinician education and public awareness.Impact statementWhat is already known on this subject? The diagnostic delay of 7–9 years with endometriosis has been reported globally. In an effort to standardise surgical treatment, improve outcomes, and shorten delays specialist endometriosis centres were introduced in 2011. There has been no recent quality improvement assessment since the establishment of such centres.What do the results of this study add? This is the most recent evaluation in the United Kingdom since the introduction of specialist endometriosis centres. There is a considerable diagnostic delay associated endometriosis in the United Kingdom with a median of 8 years. The delays seem not to have improved over the last two decades. We have identified medical and psychosocial factors that may contribute to such delays. These include factors such as menstrual cramps in adolescence, presence of rectovaginal endometriosis, normalisation of pain and attitudes of health professionals contribute to a delayed diagnosis.What are the implications of these findings for clinical practice and/or further research? The results of this study, highlight the need for clinician education and public awareness to decrease the long term-morbidity and complications that result from untreated endometriosis.

The clinical and radiological profile of primary lateral sclerosis: a population-based study.

Primary lateral sclerosis is a progressive upper-motor-neuron disorder associated with markedly longer survival than ALS. In contrast to ALS, the genetic susceptibility, histopathological profile and imaging signature of PLS are poorly characterised. Suspected PLS patients often face considerable diagnostic delay and prognostic uncertainty. To characterise the distinguishing clinical, genetic and imaging features of PLS in contrast to ALS and healthy controls. A prospective population-based study was conducted with 49 PLS patients, 100 ALS patients and 100 healthy controls using genetic profiling, standardised clinical assessments and neuroimaging. Whole-brain and region-of-interest analyses were undertaken to evaluate patterns of grey and white matter degeneration. In PLS, disease burden in the motor cortex is more medial than in ALS consistent with its lower limb symptom-predominance. PLS is associated with considerable cerebellar white and grey matter degeneration and the extra-motor profile of PLS includes marked insular, inferior frontal and left pars opercularis pathology. Contrary to ALS, PLS spares the postcentral gyrus. The body and splenium of the corpus callosum are preferentially affected in PLS, in contrast to the genu involvement observed in ALS. Clinical measures show anatomically meaningful correlations with imaging metrics in a somatotopic distribution. PLS patients tested negative for C9orf72 repeat expansions, known ALS and HSP-associated genes. Multiparametric imaging in PLS highlights disease-specific motor and extra-motor involvement distinct from ALS. In a condition where limited post-mortem data are available, imaging offers invaluable pathological insights. Anatomical correlations with clinical metrics confirm the biomarker potential of quantitative neuroimaging in PLS.

Quand penser à une maladie de surcharge lysosomale (Morquio inclus) ?

Lysosomal storage diseases (LSDs) are a group of over 70 diseases that are characterized by lysosomal dysfunction, caused by progressive accumulation of metabolites due to defects in lysosomal enzymes and degradation pathways, most of which are inherited as autosomal recessive traits. These disorders are individually rare but collectively affect more than 1 in 4000 live births. LSDs typically present in infancy and childhood, although adult- onset forms also occur. Lysosomal storage diseases (LSDs) are rare systemic and progressive genetic metabolic diseases, which present a wide heterogeneity (from severe to attenuated form) and a wide phenotypic spectrum of nonspecific manifestations, which may lead to considerable diagnostic delay. The precise diagnosis can be difficult or impossible, taking into account clinical variability and overlapping symptoms among LSD. The most of these disorders manifest with neurological, musculoskeletal and visceral signs. If severe subtypes are often readily diagnosed, the more attenuated subtypes are frequently missed or diagnosis is significantly delayed. Early diagnosis has become essential since effective disease-specific treatments, including enzyme replacement therapy and stem cell transplantation, have become available for certain LSDs, necessary to prevent the development of disabling and irreversible manifestations. Diagnosis of LSD is driven by clinical suspicion and several clinical approaches are possible: what presentations should prompt consideration of a LSD? Is it a neurological or a visceral phenotype? How thinking about a mucopolysaccharidoses, an oligosaccharidoses, a sphingolipidoses? How to discuss for each clinical sign or symptom the differential diagnosis of all LSD?