Introduction:MRI of extra-ocular muscles (EOM) in patients with myasthenia gravis (MG) could aid in diagnosis and provide insights in therapy-resistant ophthalmoplegia. We used quantitative MRI to... Show moreIntroduction:MRI of extra-ocular muscles (EOM) in patients with myasthenia gravis (MG) could aid in diagnosis and provide insights in therapy-resistant ophthalmoplegia. We used quantitative MRI to study the EOM in MG, healthy and disease controls, including Graves’ ophthalmopathy (GO), oculopharyngeal muscular dystrophy (OPMD) and chronic progressive external ophthalmoplegia (CPEO).Methods:Twenty recently diagnosed MG (59±19yrs), nineteen chronic MG (51±16yrs), fourteen seronegative MG (57±9yrs) and sixteen healthy controls (54±13yrs) were included. Six CPEO (49±14yrs), OPMD (62±10yrs) and GO patients (44±12yrs) served as disease controls. We quantified muscle fat fraction (FF), T2water and volume. Eye ductions and gaze deviations were assessed by synoptophore and Hess-charting.Results:Chronic, but not recent onset, MG patients showed volume increases (e.g. superior rectus and levator palpebrae [SR+LPS] 985±155 mm3 compared to 884±269 mm3 for healthy controls, p < 0.05). As expected, in CPEO volume was decreased (e.g. SR+LPS 602±193 mm3, p < 0.0001), and in GO volume was increased (e.g. SR+LPS 1419±457 mm3, p < 0.0001). FF was increased in chronic MG (e.g. medial rectus increased 0.017, p < 0.05). In CPEO and OPMD the FF was more severely increased. The severity of ophthalmoplegia did not correlate with EOM volume in MG, but did in CPEO and OPMD. No differences in T2water were found.Interpretation:We observed small increases in EOM volume and FF in chronic MG compared to healthy controls. Surprisingly, we found no atrophy in MG, even in patients with long-term ophthalmoplegia. This implies that even long-term ophthalmoplegia in MG does not lead to secondary structural myopathic changes precluding functional recovery. Show less
Introduction: Diagnosing ocular myasthenia gravis (MG) can be challenging because serum antibodies are often not detected. We aimed to explore whether determining extraocular muscle (EOM) weakness... Show moreIntroduction: Diagnosing ocular myasthenia gravis (MG) can be challenging because serum antibodies are often not detected. We aimed to explore whether determining extraocular muscle (EOM) weakness using orthoptic measures, including an adapted Hess chart examination, can aid in diagnosing MG. Methods: We conducted a prospective study among patients with acetylcholine receptor antibody positive MG (20 recently diagnosed, 19 chronic) and 14 seronegative MG patients. We compared orthoptic measures to 19 healthy and 18 disease controls with Graves orbitopathy, chronic progressive external ophthalmoplegia or oculopharyngeal muscular dystrophy. Maximal eye duction angles were measured using a synoptophore. Gaze deviations between eyes were measured using standard Hess chart examination with addition of 1 min persistent gaze to assess MG-associated fatiguability. Receiver operating characteristics curve analysis was performed. Results: For duction angles, the area under the curve (AUC) was 0.73 comparing MG to healthy, and 0.69 comparing to patient controls. For the outer field of the Hess chart, the AUC was 0.89 comparing to healthy and 0.54 to patient controls. For drift, the AUC was 0.93 comparing to healthy and 0.93 to patient controls. The sensitivity and specificity of the presence of drift was 81% and 100%. Discussion: Orthoptic measurements can be used to diagnose MG by quantifying EOM weakness and fatiguability. Drift during persistent gaze on a Hess chart is specific for MG and could be used for diagnostic purposes. The Hess chart examination is widely available, inexpensive and fast. Moreover, orthoptic measurements may be a clinically relevant outcome measure for clinical trials. Show less
Introduction Diagnosing ocular myasthenia gravis (MG) can be challenging because serum antibodies are often not detected. We aimed to explore whether determining extraocular muscle (EOM) weakness... Show moreIntroduction Diagnosing ocular myasthenia gravis (MG) can be challenging because serum antibodies are often not detected. We aimed to explore whether determining extraocular muscle (EOM) weakness using orthoptic measures, including an adapted Hess chart examination, can aid in diagnosing MG.Methods We conducted a prospective study among patients with acetylcholine receptor antibody positive MG (20 recently diagnosed, 19 chronic) and 14 seronegative MG patients. We compared orthoptic measures to 19 healthy and 18 disease controls with Graves orbitopathy, chronic progressive external ophthalmoplegia or oculopharyngeal muscular dystrophy. Maximal eye duction angles were measured using a synoptophore. Gaze deviations between eyes were measured using standard Hess chart examination with addition of 1 min persistent gaze to assess MG-associated fatiguability. Receiver operating characteristics curve analysis was performed.Results For duction angles, the area under the curve (AUC) was 0.73 comparing MG to healthy, and 0.69 comparing to patient controls. For the outer field of the Hess chart, the AUC was 0.89 comparing to healthy and 0.54 to patient controls. For drift, the AUC was 0.93 comparing to healthy and 0.93 to patient controls. The sensitivity and specificity of the presence of drift was 81% and 100%.Discussion Orthoptic measurements can be used to diagnose MG by quantifying EOM weakness and fatiguability. Drift during persistent gaze on a Hess chart is specific for MG and could be used for diagnostic purposes. The Hess chart examination is widely available, inexpensive and fast. Moreover, orthoptic measurements may be a clinically relevant outcome measure for clinical trials. Show less
Al-Nofal, M.; Boer, I. de; Agirman, S.; Wilms, A.E.; Najafabadi, A.Z.H.; Terwindt, G.M.; Notting, I.C. 2022
Background: The brain and retina share many neuronal and vasculature characteristics. We investigated the retinal microvasculature in patients with a monogenic vasculopathy using optical coherence... Show moreBackground: The brain and retina share many neuronal and vasculature characteristics. We investigated the retinal microvasculature in patients with a monogenic vasculopathy using optical coherence tomography angiography (OCTA). OCT-A is a novel precise non-invasive imaging method that may provide biomarkers suitable for diagnosis and follow-up of small vessel diseases. Methods: In this exploratory cross-sectional study, eleven RVCL-S patients and eleven age-matched healthy control participants were included. The size of the foveal avascular zone (FAZ) and the vascular density of the superficial capillary networks in the retina were measured by OCT-A. Results: The symptomatic and presymptomatic patients showed significantly lower vascular density values than controls in the foveal region [median (IQR) 18.2% (15.8-18.6) vs. 24.4% (21.5-26.8) (p < 0.001), 29.8% (29.6-30.8) vs. 33.2% (32.0-33.6) (p = 0.002), respectively]. The FAZ was significantly larger in the symptomatic RVCL-S patients than in the control group [13,416 square pixels [7,529-22,860] vs. 1,405 square pixels [1,344-2,470] (p < 0.001)]. No significant difference was identified in measurements of FAZ comparing presymptomatic and controls. Conclusion: Our findings with OCT-A demonstrated that RVCL-S causes an increase in the size of the FAZ in symptomatic RVCL-S patients compared to healthy participants. Moreover, there is a decrease in vessel density in the superficial capillary networks in both symptomatic and presymptomatic patients. In the future, newly developed precise objective instruments such as OCT (-A) may provide important tools in determining disease activity for follow up of common small vessel diseases. Show less
Vuijk, F.A.; Bruin, C. de; Peeters-Scholte, C.M.P.C.D.; Notting, I.C. 2022
Introduction: Idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure without an evident cause. Obesity and the female sex have been recognized as risk... Show moreIntroduction: Idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure without an evident cause. Obesity and the female sex have been recognized as risk factors for the development of this syndrome. Until now, Graves' disease has only been described in the literature as the probable cause of IIH in 7 patients. This report describes the case of a young girl with Graves' disease presenting with symptoms of intracranial hypertension (IH). Case Presentation: A 21-month-old girl presented with progressive symptoms of poor weight gain and bilateral exophthalmos. She also experienced difficulty sleeping, diarrhea multiple times per day, irritability, and heat intolerance. Laboratory investigation showed elevated free T4, fully suppressed TSH, and elevated anti-TSH antibodies, consistent with a diagnosis of new-onset Graves' disease. She was successfully treated with monotherapy thiamazole, titrated to the lowest possible dose of 1.25 mg once daily with normalization of thyroid function tests within 3 months of treatment initiation. After 18 months of treatment, her condition unexpectedly deteriorated as papilledema and slight esotropia were found at a routine checkup. An MRI and lumbar puncture showed increased intracranial pressure, but no underlying anatomical cause for the IH was found. Acetazolamide therapy was started, and papilledema in both eyes resolved within weeks. Unfortunately, papilledema has recurred several times over the following 2 years when attempts were made to decrease the acetazolamide dose. Discussion/Conclusion: This case report is the first to describe a very young patient who developed significant IIH in the chronic stage of Graves' disease. IIH development seemed to be related to the progression of the Graves' ophthalmopathy, rather than initiation of thiamazole therapy or fluctuations in serum fT4 levels. Show less
Boer, I. de; Steenmeijer, S.R.; Pelzer, N.; Al-Nofal, M.; Dijkman, G.; Notting, I.C.; Terwindt, G.M. 2022
Background: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a monogenic small vessel disease caused by mutations in TREX1. Several organs, including... Show moreBackground: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a monogenic small vessel disease caused by mutations in TREX1. Several organs, including retina and brain, are affected. Analyzing retinal anatomy is increasingly used as a biomarker for ophthalmological and neurological disorders (due to the shared embryological origin of retina and brain). Optical coherence tomography (OCT) provides a noninvasive cross-sectional visualization of optic disc and macula. We aimed to use OCT to investigate retinal layer thickness in RVCL-S. Methods: Cross-sectional, 17 TREX1 mutation carriers (34 eyes) and 9 controls (18 eyes) underwent comprehensive ophthalmologic assessment followed by spectral domain OCT for measuring peripapillary retinal nerve fiber layer (pRNFL) thickness and total macular volume (TMV). Secondary outcomes included measuring thickness of individual macular retinal layers and peripapillary sectors. Findings were analyzed using generalized estimating equations to account for intereye correlation. Results: TREX1 mutation carriers had decreased pRNFL thickness (median [interquartile range] 76 [60-99] vs 99 [87-108] mu m, P < 0.001) and TMV (8.1 [7.4-8.5] vs 8.7 [8.4-8.8] mm(3), P = 0.006) compared with controls. With the exception of the temporal sector, the thickness of all peripapillary sectors was decreased in TREX1 mutation carriers. Ganglion cell layer (30 [22-37] vs 39 [36-41] mu m, P < 0.001) and inner plexiform layer (27 [24-34] vs 34 [31-35], P = 0.001) were thinner in TREX1 mutation carriers. Notably, in 9 of 12 eyes with normal funduscopic examination, retinal thinning was already detected. Conclusions: RVCL-S, which may serve as a vascular retinopathy model, is associated with retinal thinning in the peripapillary and macular area. OCT findings can potentially serve as early biomarkers for RVCL-S and other vascular retinopathies. Show less
Purpose The condition of pituitary apoplexia contains the clinical spectre from life-threatening emergency to asymptomatic self-limiting course, which partly determines diagnostic delay and... Show morePurpose The condition of pituitary apoplexia contains the clinical spectre from life-threatening emergency to asymptomatic self-limiting course, which partly determines diagnostic delay and management. Outcome evaluation of course and management of pituitary apoplexia is hampered by the diverse presentation of this condition and requires appraisal. This study aimed to describe the patient journey, clinical presentation, and management of various types of pituitary apoplexy in a new classification to facilitate future outcome evaluation and identify unmet needs in the care process. Methods A single-center retrospective patient chart study was conducted between 2005-2021 (N = 98). Outcome measures were clinical symptoms at first presentation in hospital, being headache, consciousness, visual acuity, visual field defects (VFD), ophthalmoplegia, nausea, vomiting, fever, and hypopituitarism and care process characteristics. Results Mean age was 47.6 +/- 16.6 years (51.0% male). We describe their patient journey and identified three different types, differing in clinical presentation, in-hospital route, and final treatment, e.g., Acute (type A, 52%), Subacute (type B, 22.5%), and Non-acute (type C, 25.5%). Type A generally presents with acute onset headaches, VFD, or ophthalmoplegia emergency setting, with lowest mean visual acuity of both eyes and frequent hypocortisolism. Conclusions Pituitary apoplexy can be approached as a spectrum of disease with 3 main subtypes, with a different initial presentation, different in-hospital route resulting in different management. Acknowledging subtypes with particular needs for (emergency) referrals to Pituitary Tumors Center of Excellence (PTCOE) will serve patient care improvements, outcome evaluations and address areas for improvement. Show less
Context: Transsphenoidal surgery is standard care in the treatment of hormone-secreting pituitary adenomas. Current clinician-reported surgical outcome measures are one-dimensional, typically... Show moreContext: Transsphenoidal surgery is standard care in the treatment of hormone-secreting pituitary adenomas. Current clinician-reported surgical outcome measures are one-dimensional, typically focusing primarily on complete or partial resection, and secondarily on complication rates. However, outcomes are best reflected by the delicate balance of efficacy and complications at patient level.Objective: This study proposes a novel way to classify and report outcomes, integrating efficacy and safety at the patient level.Methods: Retrospective chart review of all pure endoscopic transsphenoidal surgical procedures for acromegaly, Cushing's disease, and prolactinoma between 2010 and 2018 in a single tertiary referral center. We present our results in a classic (remission and complications separate) and in a novel outcome square integrating both outcomes, focusing on intended and adverse effects (long-term complications). This resulted in 4 outcome groups, ranging from good to poor. We use this approach to present these outcomes for several subgroups.Results: A total of 198 surgical procedures were included (44 reoperations). Remission was achieved in 127 operations (64%). Good outcome was observed after 121 (61%), and poor outcome after 6 (3%) operations. When intended effect of surgery was applied (instead of remission), good outcome as intended was achieved after 148 of 198 surgeries (75%) and poor outcome after 4 (2%).Conclusion: Quality of a surgical intervention can be presented in 4 simple categories, integrating both efficacy and safety with flexibility to adapt to the individualized situation at patient, disease, and surgical strategy and to the outcome of interest. Show less
Gagaouzova, B.S.; Datema, M.; Thijs, R.D.; Tannemaat, M.R.; Steenmeijer, S.R.; Notting, I.C.; Dijk, J.G. van 2021
Background: Pure autonomic failure (PAF) and multiple system atrophy (MSA) are rare disorders causing severe autonomic failure. Their initially similar clinical presentation may lead to years of... Show moreBackground: Pure autonomic failure (PAF) and multiple system atrophy (MSA) are rare disorders causing severe autonomic failure. Their initially similar clinical presentation may lead to years of diagnostic difficulties. Improving the differentiation would have an important impact on patients and families in view of better prediction of disease progression. Objective: To investigate whether several new non-invasive autonomic tests are beneficial in discriminating between PAF and MSA. Methods: Patients and controls underwent two tests examining the autonomic innervation of the skin (Sudoscan and water-induced skin wrinkling) and one test measuring retinal nerve fiber layer thickness in the eye. Results: The skin vasomotor tests yielded differences between the disease and control groups, but did not discriminate between PAF and MSA. No differences in retinal nerve fiber layer thickness were found between the groups. Conclusion: The tests applied in this study may help to confirm autonomic failure but did not support the differential diagnosis between PAF and MSA. Show less
Purpose To evaluate whether the occurrence of chiasmal herniation coincides with visual field (VF) deterioration and to compare the course of VF defects in patients with and without radiological... Show morePurpose To evaluate whether the occurrence of chiasmal herniation coincides with visual field (VF) deterioration and to compare the course of VF defects in patients with and without radiological chiasmal herniation following treatment of pituitary adenoma. Methods This retrospective cohort study included 48 pituitary macroadenoma patients with chiasm compression, divided into three groups: Group 1 (N = 12), downward displaced optic chiasm and deteriorated VFs; Group 2 (N = 16), downward displaced optic chiasm; Group 3 (N = 20), control-group matched for tumour size and follow-up VFs, in mean deviation (dB). VFs were compared over time and a severity index, Chiasm Herniation Scale (CHS), for herniation based on radiological parameters was designed. Results After treatment, all groups showed improvement of VFs (Gr1: 2.97 dB p = 0.097, Gr2: 4.52 dB p = 0.001 and Gr3: 5.16 dB p = 0.000), followed by long-term gradual deterioration. The course of VFs between patients with and without herniation was not significantly different (p = 0.143), neither was there a difference in the course before and after herniation (p = 0.297). The median time till onset of herniation was 40 months (IQR 6 month-10 years) and did not significantly differ (p = 0.172) between the groups. There was no relation between VFs and the degree of herniation (p = 0.729). Conclusion Herniation does not appear to have clinical relevance with respect to VF outcome. The newly designed CHS is the first scoring system to quantify the severity of herniation and, in the absence of alternatives, may be useful to describe MRI findings to serve future added value in larger sized outcome studies. Show less
Etten, E.S. van; Boer, I. de; Steenmeijer, S.R.; Al-Nofal, M.; Wermer, M.J.H.; Notting, I.C.; Terwindt, G.M. 2020
Background and purpose Investigating mutation carriers with Dutch-type hereditary (D-) cerebral amyloid angiopathy (CAA), offers the possibility to identify markers in pre- and symptomatic stages... Show moreBackground and purpose Investigating mutation carriers with Dutch-type hereditary (D-) cerebral amyloid angiopathy (CAA), offers the possibility to identify markers in pre- and symptomatic stages of CAA. Optical coherence tomography (OCT) has shown potential to detect retinal changes in several neurodegenerative diseases. The aim of the present exploratory study was to investigate thinning of retinal layers as a possible (early) biomarker in D-CAA mutation carriers. Methods Twenty-one D-CAA mutation carriers (n = 8 presymptomatic,n = 13 symptomatic, median age 50 years) and nine controls (median age 53 years) were scanned using spectral-domain OCT. Symptomatic mutation carriers were defined as having a history of >= 1 symptomatic intracerebral hemorrhage. D-CAA mutation carriers and controls were recruited from our D-CAA cohort and a healthy control cohort. Total peripapillary retinal nerve fiber layer (pRNFL) thickness, six regions of pRNFL, total macular volume (TMV), and individual macular region thickness were measured and analysed, adjusted for age. Results The overall median (interquartile range) thickness of pRNFL was lower in symptomatic, but not presymptomatic D-CAA mutation carriers compared with controls [91 (86-95) mu m vs. 99 (87-108) mu m;P = 0.006]. Both presymptomatic [111 (93-122) mu m vs. 131 (123-143) mu m;P < 0.001] and symptomatic carriers [119 (95-128) mu m vs. 131 (123-143) mu m;P = 0.034] had a thinner temporal-superior quadrant of the pRNFL versus controls. TMV or individual macular layer thickness did not differ between carriers and controls. Conclusions Thinning of the retinal nerve fiber layer may be a candidate marker of disease in hereditary CAA. Further studies are needed to determine whether retinal thinning is present in sporadic CAA and estimate its value as a marker for disease progression. Show less
Keene, K.R.; Vught, L. van; Velde, N.M. van de; Ciggaar, I.A.; Notting, I.C.; Genders, S.W.; ... ; Beenakker, J.W.M. 2020
Although quantitative MRI can be instrumental in the diagnosis and assessment of disease progression in orbital diseases involving the extra-ocular muscles (EOM), acquisition can be challenging as... Show moreAlthough quantitative MRI can be instrumental in the diagnosis and assessment of disease progression in orbital diseases involving the extra-ocular muscles (EOM), acquisition can be challenging as EOM are small and prone to eye-motion artefacts. We explored the feasibility of assessing fat fractions (FF), muscle volumes and water T2 (T2(water)) of EOM in healthy controls (HC), myasthenia gravis (MG) and Graves' orbitopathy (GO) patients. FF, EOM volumes and T2(water)values were determined in 12 HC (aged 22-65 years), 11 MG (aged 28-71 years) and six GO (aged 28-64 years) patients at 7 T using Dixon and multi-echo spin-echo sequences. The EOM were semi-automatically 3D-segmented by two independent observers. MANOVA and t-tests were used to assess differences in FF, T2(water)and volume of EOM between groups (P< .05). Bland-Altman limits of agreement (LoA) were used to assess the reproducibility of segmentations and Dixon scans. The scans were well tolerated by all subjects. The bias in FF between the repeated Dixon scans was -0.7% (LoA: +/- 2.1%) for the different observers; the bias in FF was -0.3% (LoA: +/- 2.8%) and 0.03 cm(3)(LoA: +/- 0.36 cm(3)) for volume. Mean FF of EOM in MG (14.1% +/- 1.6%) was higher than in HC (10.4% +/- 2.5%). Mean muscle volume was higher in both GO (1.2 +/- 0.4 cm(3)) and MG (0.8 +/- 0.2 cm(3)) compared with HC (0.6 +/- 0.2 cm(3)). The average T2(water)for all EOM was 24.6 +/- 4.0 ms for HC, 24.0 +/- 4.7 ms for MG patients and 27.4 +/- 4.2 ms for the GO patient. Quantitative MRI at 7 T is feasible for measuring FF and muscle volumes of EOM in HC, MG and GO patients. The measured T2(water)was on average comparable with skeletal muscle, although with higher variation between subjects. The increased FF in the EOM in MG patients suggests that EOM involvement in MG is accompanied by fat replacement. The unexpected EOM volume increase in MG may provide novel insights into underlying pathophysiological processes. Show less
The original version of the article unfortunately contained an error in Figure 2. The term 'Refer within 3 days' should read 'Refer as soon as possible'. Corrected version of Figure 2 is given below.
Purpose Surgery in patients with non-functioning pituitary macroadenomas (NFMA) is effective in ameliorating visual function. The urgency for decompression, and preferred timing of surgery related... Show morePurpose Surgery in patients with non-functioning pituitary macroadenomas (NFMA) is effective in ameliorating visual function. The urgency for decompression, and preferred timing of surgery related to the preoperative severity of dysfunction is unknown. Methods Systematic review for evidence to provide clinical guidance for timing of surgical decompression of the optic chiasm, and a cohort study of 30 NFMA patients, in whom mean deviation (MD), and severity of visual dysfunction was assessed. Results Systematic review 44 studies were included with a total of 4789 patients. Postoperatively, visual field defects improved in 87.0% of patients, stabilized in 12.8% and worsened in 1.0%. Specific protocols regarding timing of surgery were not reported. Only seven studies (16.7%) reported on either the duration of visual symptoms, or diagnostic, or treatment delay. Cohort study 30 NFMA patients (50% female, 60 eyes, mean age 58.5 +/- 14.8 years), had a median MD of - 5.3 decibel (IQR - 3.1 to - 10.1). MD was strongly correlated with clinical severity (r = - 0.94, P < 0.0001), and were used for severity of defects cut-off values: (1) normal > - 2 dB, (2) mild - 2 dB to - 4 dB, (3) moderate - 4 to - 8 dB, (4) severe - 8 to - 17 dB, (5) very severe < - 17 dB. Conclusion Surgical decompression is highly effective in improving visual function. Uniform, quantitative grading of visual dysfunction was lacking. MD is a promising quantitative outcome measure. We provide recommendations for the evaluation of timing of surgery, considering severity of visual impairment, which will need further validation based on expert clinical practice. Show less
Purpose:Craniofacial fibrous dysplasia (CFD) is a subtype of fibrous dysplasia/McCune-Albright syndrome (FD/MAS) characterized by FD lesions in one or more of the skull bones. The orbit is often... Show morePurpose:Craniofacial fibrous dysplasia (CFD) is a subtype of fibrous dysplasia/McCune-Albright syndrome (FD/MAS) characterized by FD lesions in one or more of the skull bones. The orbit is often involved, with facial pain, facial deformity, and increased risk of compressive optic neuropathy as associated clinical manifestations possibly leading to altered illness perceptions and impairments in quality of life(QoL). The aim of this study was to evaluate illness perceptions and QoL in patients with CFD among our FD/MAS cohort.Methods:One hundred ninety-one patients were included. Illness perceptions and QoL were assessed by using validated questionnaires, that is, the Illness Perceptions Questionnaire-Revised and the Short-Form 36. Patients were first grouped as CFD versus non-CFD, a second selection was based on the presence of "Isolated CFD" versus "CFD+PFD/MAS." Non-CFD patients were grouped as monostotic fibrous dysplasia "MFD" versus polyostotic "PFD/MAS."Results:Patients with isolated CFD attributed less symptoms to their disease compared with patients with CFD+PFD/MAS (p < 0.05). Furthermore, patients with isolated CFD reported better QoL on all domains (except role emotional and mental health) compared with patients with CFD+PFD/MAS (p < 0.05). Patients with isolated CFD also reported better QoL compared with non-CFD groups (on 3 out of 8 subscales) (p < 0.05).Conclusions:Patients with isolated CFD attribute less symptoms to their disease and report better QoL compared with patients with CFD with extracranial involvement or FD without cranial involvement. These findings indicate that craniofacial involvement alone is not sufficient to cause negative illness perceptions and impairments in QoL. Therefore, it can be postulated that isolated CFD should be considered a unique patient subtype within the spectrum of FD/MAS patients. Show less
