Clinical patterns and the evolution of relapsing polychondritis based on organ involvement: a Chinese retrospective cohort study

Abstract Background Relapsing polychondritis(RPC) is a rare autoimmune disease and its early diagnosis pose a challenge to medical committee. Defining the clinical patterns and disease course may help early recognition of RPC. Results Sixty-six males and 60 females were included in this study. Their average age at onset were 47.1±13.8 years with a median follow-up of 18 months. Correlation analysis revealed a strong negative correlation between airway involvement and auricular chondritis (r=-0.75，P<0.001). Four distinct clinical patterns were identified: Ear pattern (50.8%), Airway pattern (38.9%), Overlap pattern (4.8%) and Airway-Ear negative pattern (5.6%), and patients with Ear pattern and Airway pattern were further divided into limited and systemic form of RPC (27.8%with limited form of Ear pattern and 24.6% with limited form of Airway pattern initially). During follow-up, a minority of patients with Ear pattern and Airway pattern progressed into Overlap pattern, and some Airway-Ear negative pattern patients progressed into Ear pattern. While a large majority of limited RPC patients remained limited form during follow-up, some patients did become systemic form. Patients with Ear pattern had the highest survival rate and lower inflammatory status. Conclusions RPC patients can be categorized as 4 different clinical patterns and 2 distinct presenting forms (limited and systemic) based on organ involvement, and clinical patterns and presenting forms can evolve during follow-up. Our findings may facilitate early recognition of this rare disease.

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Clinical patterns and the evolution of relapsing polychondritis based on organ involvement: a Chinese retrospective cohort study

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01861-x ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Lei Zhang ◽

Shuang Yun ◽

Tiange Wu ◽

Yujie He ◽

Jinyan Guo ◽

...

Keyword(s):

Early Recognition ◽

Age At Onset ◽

Relapsing Polychondritis ◽

Organ Involvement ◽

Strong Negative Correlation ◽

Negative Pattern ◽

Inflammatory Status ◽

Clinical Patterns ◽

Systemic Form

Abstract Background Relapsing polychondritis (RPC) is a rare autoimmune disease and its early diagnosis remains challenging. Defining the clinical patterns and disease course may help early recognition of RPC. Results Sixty-six males and 60 females were included in this study. The average age at onset were 47.1 ± 13.8 years and the median follow-up period was 18 months. Correlation analysis revealed a strong negative correlation between airway involvement and auricular chondritis (r = − 0.75, P < 0.001). Four distinct clinical patterns were identified: Ear pattern (50.8%), Airway pattern (38.9%), Overlap pattern (4.8%) and Airway-Ear negative pattern (5.6%), and patients with Ear pattern and Airway pattern were further divided into limited and systemic form of RPC (27.8% with limited form of Ear pattern and 24.6% with limited form of Airway pattern initially). During follow-up, a minority of patients with Ear pattern and Airway pattern progressed into Overlap pattern, and some Airway-Ear negative pattern patients progressed into Ear pattern. While a large majority of limited RPC patients remained limited form during follow-up, a minority of limited RPC patients progressed into systemic form. Patients with Ear pattern had the highest survival rate and relatively lower inflammatory status. Conclusions RPC patients can be categorized as 4 different clinical patterns and 2 distinct presenting forms (limited and systemic) based on organ involvement. The clinical patterns and presenting forms may evolve during follow-up. Our findings may facilitate early recognition of this rare disease.

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Clinical patterns and the evolution of relapsing polychondritis based on organ involvement: a Chinese retrospective cohort study

10.21203/rs.3.rs-22652/v1 ◽

2020 ◽

Author(s):

Lei Zhang ◽

Shuang Yun ◽

Tiange Wu ◽

Yujie He ◽

Jinyan Guo ◽

...

Keyword(s):

Rare Disease ◽

Early Recognition ◽

Relapsing Polychondritis ◽

Organ Involvement ◽

Disease Evolution ◽

Negative Pattern ◽

Inflammatory Status ◽

Clinical Patterns ◽

Systemic Form

Abstract BackgroundRelapsing polychondritis(RPC) is a rare autoimmune disease, of which the diagnosis in early stage is challenging. Defining the clinical patterns and disease evolution may help early recognition of this rare disease.ResultsSixty-six males and 60 females were included with onset age of 47.1±13.8 years and followed up for a median of 18 months. Correlation analysis revealed a strong negative correlation between airway involvement and auricular chondritis (r=-0.75，P<0.001). Four distinct clinical patterns were identified: Ear pattern (50.8%), Airway pattern (38.9%), Overlap pattern (4.8%) and Airway-Ear negative pattern (5.6%) and patients with Ear pattern and Airway pattern were subdivided as limited and systemic form of RPC (27.8% with limited form of Ear pattern and 24.6% with limited form of Airway pattern). During follow-up, a small part of patients with Ear pattern and Airway pattern progressed into Overlap pattern and some Airway-Ear negative pattern patients progressed into Ear pattern. Most of the limited RPC patients remained limited form during follow-up while some patients with limited form progressed into systemic form. Patients with Ear pattern had the highest survival rate and relative lower inflammatory status.ConclusionsRPC patients can be categorized as 4 different clinical patterns and 2 distinct presenting forms (limited and systemic) based on organ involvement, and clinical patterns and presenting forms can evolve during follow-up. Our findings may facilitate early recognition of this rare disease and contribute to an updated classification criteria covering all the clinical spectrum of RPC

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Clinical patterns and the evolution of relapsing polychondritis based on organ involvement: analysis of 126 Chinese patients

10.21203/rs.2.24348/v1 ◽

2020 ◽

Author(s):

Lei Zhang ◽

Shuang Yun ◽

Tiange Wu ◽

Yujie He ◽

Jinyan Guo ◽

...

Keyword(s):

Relapsing Polychondritis ◽

Chinese Patients ◽

Electronic Records ◽

Comprehensive Understanding ◽

Strong Negative Correlation ◽

Inflammatory Status ◽

Auricular Chondritis ◽

Clinical Patterns ◽

Systemic Form

Abstract Objective To explore the clinical patterns of relapsing polychondritis(RPC) to improve clinicians’ comprehensive understanding of the disease. Methods The electronic records of RPC patients that were hospitalized and followed-up by rheumatologists at our hospital between January 1, 2008 and August 31,2019 were retrospectively analyzed. Results Sixty-six males and 60 femaleswere included with onset age of 47.1±13.8 years and followed up for a median of 18 months. Eighty-seven patients (69.1%) did not met with the traditional criteria.Correlation analysis revealed a strong negative correlation between airway involvement and auricular chondritis (r=-0.75，P<0.001). Four distinct clinical patterns were identified: Ear pattern (50.8%), Airway pattern (38.9%), Overlap pattern (4.8%) and Airway-Ear negative pattern (5.6%) and patients with Ear pattern and Airway pattern were subdivided as limited and systemic form of RPC (27.8%with limited form of Ear pattern and 24.6% with limited form of Airway pattern). During follow-up, a small part of patients with Ear pattern and Airway pattern progressed into Overlap pattern andsome Airway-Ear negative patternpatients progressed into Ear pattern. Most of the limited RPC patientsremained limited form during follow-up whilesome patients with limited form progressed into systemic form. Patients with Ear pattern had the highest survival rate and relative lower inflammatory status. Conclusion RPC patients can be categorized as 4 differentclinical patterns and 2 distinct presenting forms (limited and systemic) based on organ involvement.Limited form of RPC is not uncommon in Chinese patients and traditional criteria of RPC are not suitable for early diagnosis.

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CASPR-2 related morvan’s syndrome: Autonomic, polysomnographic & neuropsychological observations

Neurology Clinical Practice ◽

10.1212/cpj.0000000000000978 ◽

2020 ◽

pp. 10.1212/CPJ.0000000000000978

Author(s):

Panda Sudha Swayang ◽

Atchayaram Nalini ◽

Veeramani Preethish-Kumar ◽

Kaviraja Udupa ◽

Ravi Yadav ◽

...

Keyword(s):

Early Recognition ◽

Age At Onset ◽

Beta Activity ◽

Postural Orthostatic Tachycardia Syndrome ◽

Behavioral Disturbances ◽

Periodic Leg Movements ◽

Double Incontinence ◽

Neuropsychological Profile ◽

Morvan’S Syndrome

Background& Objectives:Morvan’s syndrome is characterized by central, autonomic, and peripheral hyperexcitability due to CASPR-2-antibody. Our objective was to study the clinical spectrum, electrophysiological, autonomic, polysomnographic and neuropsychological profile in patients of CASPR-2 related Morvan’s syndrome.Materials & Methods:Serum and CSF samples that were CASPR2-antibody positive from 2016-2019 were assessed. Among them, patients of Morvan’s syndrome diagnosed based on clinical and electrophysiological basis were included.Results:14(M: F-10:4) patients of Morvan’s syndrome were included with age at onset of 37.1±17.5 years. The clinical features were muscle twitching (12), insomnia (12), pain (11), paraesthesias (9), hyperhidrosis (7), hypersalivation (6), double incontinence (3), spastic speech (2), dysphagia (2), behavioral disturbances (2), seizures (1) cold intolerance (1). Neurological examination revealed myokymia (12), hyperactive tendon reflexes (10), tremor (6). Electromyogram revealed neuromyotonia (12) and increased spontaneous activity (7). Autonomic function tests conducted in eight patients revealed definite autonomic dysfunction (4), orthostatic hypotension (2), early dysfunction (1) and postural orthostatic tachycardia syndrome (1). Polysomnography findings done in six patients revealed insomnia (3), absence of deep sleep (1), high frequency beta activity (1), REM (rapid eye movement) behaviour disorder(1), periodic leg movements(1). Neuropsychological evaluation showed subtle involvement of the left frontal and temporal lobe. Malignancy workup was negative. All patients were treated with steroids. There was complete neurological resolution in follow-up with persistent neuropathic pain in five patients.Conclusions:This study has contributed to the growing knowledge on CASPR2-related Morvan’s syndrome. It is important for an increased awareness and early recognition as it’s potentially treatable by immunotherapy.

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Elucidation of predictors of disease progression in patients with relapsing polychondritis at the onset: potential impact on patient monitoring

BMC Rheumatology ◽

10.1186/s41927-020-00141-8 ◽

2020 ◽

Vol 4 (1) ◽

Author(s):

Jun Shimizu ◽

Yoshihisa Yamano ◽

Kimito Kawahata ◽

Noboru Suzuki

Keyword(s):

Mortality Rate ◽

Disease Progression ◽

Disease Onset ◽

Relapsing Polychondritis ◽

Japanese Patients ◽

Nonparametric Tests ◽

Organ Involvement ◽

Onset Potential ◽

Respiratory Involvement

Abstract Background In patients with relapsing polychondritis (RP), organ involvement developed in those with progressive and/or long disease courses. For their management, elucidation of a subgroup suggesting disease progression is awaited. Methods We previously conducted a physician’s questionnaire-based retrospective study to elucidate major clinical features of Japanese patients with RP. We here evaluated organ involvement at disease onset and at the last follow-up. We then counted cumulative numbers of involved organs at the last follow-up in 229 RP patients and compared them with involved organ numbers at disease onset, as possible indicators of disease progression. We assigned their prognosis at the last follow-up into “patient prognostic stages” from no medication (stage 1) to death (stage 5). We utilized nonparametric tests for group comparisons. Results Involved organ numbers per-patient were 1.13 ± 0.03 at disease onset and 3.25 ± 0.10 at the last follow-up (disease duration was 4.69 ± 0.33 years), and increased along with the patient prognostic stages. At disease onset, 135 and 48 patients had auricular involvement (59% of 229 patients, defined as auricular-onset subgroup; AO) and respiratory involvement (21%, respiratory-onset subgroup; RO), respectively. 46 patients presented with other conditions (20%, miscellaneous-onset subgroup; MO) including CNS, ocular, and inner ear involvement, among others. RO patients showed worse (poorer) prognostic stages than AO patients. MO patients developed respiratory and/or auricular involvement thereafter and then showed significantly higher mortality rate (15%; 7/46) than AO patients (5.9%; 8/135). In RP patients who did not develop respiratory involvement until the last follow-up (throughout the disease course; 117 patients), mortality rate was 19% in 26 MO patients and 3.3% in 91 AO patients. Accordingly, RO patients and MO patients associated with relatively poor prognosis compared with AO patients. Conclusions Allocation of patients to RO and MO subgroups was suggested to associate with poorer prognosis of RP than AO subgroups, especially AO subgroups without respiratory involvement throughout. All RP patients deserve careful monitoring but special attention should be paid to MO patients because of their diverse and accelerated disease progression.

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Electroclinical Features of Epilepsy in Mucopolysaccharidosis III: Outcome Description in a Cohort of 15 Italian Patients

Frontiers in Neurology ◽

10.3389/fneur.2021.705423 ◽

2021 ◽

Vol 12 ◽

Author(s):

Rita Barone ◽

Agata Fiumara ◽

Mariangela Gulisano ◽

Lara Cirnigliaro ◽

Maria Donatella Cocuzza ◽

...

Keyword(s):

Early Recognition ◽

Age At Onset ◽

Lysosomal Storage ◽

Epileptiform Discharges ◽

Appropriate Care ◽

Behavioral Abnormalities ◽

Eeg Abnormalities ◽

Eeg Changes ◽

Mps Iii

Mucopolysaccharidosis III (Sanfilippo syndromes) types A–D are rare lysosomal storage disorders characterized by heparan sulfate accumulation and neurodegeneration. Patients with MPS III present with developmental stagnation and/or regression, sleep disturbance, and behavioral abnormalities usually in the first years of life. Epilepsy may occur in a proportion of patients during the disease course. However, the progression of epilepsy and EEG changes in MPS III have not been systematically investigated. We report electroclinical features in a cohort of patients with MPS III over a follow-up period ranging from 6.5 to 22 years. Participants include 15 patients (11 females; aged 7–31 years) with MPS III A (n = 7, 47%), MPS III B (n = 5, 34%), MPS III C (n = 2, 13%), and MPS III D (n = 1, 6%). At the time of this study, 8 out of 15 patients (53%) had epilepsy. Epilepsy occurred in patients with advanced disease even in the first decade of life (mean age at onset: 12.1 ± 6.7 years). However, seizure onset may also be associated with abrupt worsening of the neurobehavioral phenotype. The main epilepsy types observed were generalized (four out of eight, 50%), followed by focal (three out of eight, 37%) and combined (two out of eight, 25%) epilepsy and status epilepticus (one out of eight, 12.5%). Seizures were generally controlled by one antiepileptic drug (AED) and most patients (seven out of eight, 87%) were still on therapy after a median follow-up period of 5 years (range: 1–9 years). A total of 66 EEGs were analyzed with a median EEG follow-up duration of 7 years (range: 6 months−14 years). Slowing of the background activity occurred in 7 (46%) patients aged 4–19 years. Epileptiform EEG abnormalities were observed in 10 patients at a mean age of 9.6 ± 2.9 years. EEG epileptiform discharges were not unavoidably linked to epilepsy. Early recognition and careful monitoring of electroclinical features in MPS III is necessary for appropriate care and for the detection of disease progression.

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Early recognition of PIMS-TS: a single centre retrospective review

BMJ Paediatrics Open ◽

10.1136/bmjpo-2020-001011 ◽

2021 ◽

Vol 5 (1) ◽

pp. e001011

Author(s):

Roshni Mistry ◽

Nicola Scanlon ◽

James Hibberd ◽

Fionnghuala Fuller

Keyword(s):

Early Recognition ◽

Febrile Illness ◽

Final Diagnosis ◽

University Hospital ◽

Single Centre ◽

Retrospective Case ◽

Reactive Protein ◽

Review Reports ◽

Specific Symptoms

IntroductionResearch into paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) has focused on tertiary level management. This review reports on symptoms and investigations at presentation.MethodsSingle centre retrospective case note analysis of patients fulfilling PIMS-TS diagnostic criteria from March to May 2020 in a London district level university hospital.ResultsSix patients presented in the week prior to their final diagnosis with fever and non-specific symptoms. Raised C-reactive protein (CRP), lymphopenia and hyponatraemia were noted. Kawasaki-like symptoms were under-represented in all patients.InterpretationThe results suggest that a proportion of children with early PIMS-TS present with a non-specific febrile illness and abnormal blood results. Further research is needed to determine the most appropriate identification and follow-up of these children.

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POS0677 THE ROLE OF MUSCULOSKELETAL ULTRASOUND IN PREDICTING THE RESPONSE TO JAK INHIBITORS: RESULTS FROM A LARGE MONOCENTRIC COHORT

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3850 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 583-583

Author(s):

C. Garufi ◽

F. Ceccarelli ◽

F. R. Spinelli ◽

S. Mancuso ◽

C. Pirone ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Structural Damage ◽

Power Doppler ◽

Response To Treatment ◽

Jak Inhibitors ◽

Inflammatory Score ◽

Inflammatory Status

Background:In the management of chronic arthritis, such as Rheumatoid Arthritis (RA), Ultrasound (US) assessment can provide relevant information about the joint inflammatory status in the diagnostic phase and even more in the monitoring of disease activity and structural damage1,2.Objectives:In this longitudinal study, we aimed to assesse the role of US in predicting the efficacy of JAK-inhibitors (JAKi) in RA patients.Methods:We enrolled RA patients starting baricitinib or tofacitinib. All patients were evaluated at baseline and after 4, 12, 24, 48 weeks. Disease activity was calculated by DAS28CRP. US examination in 22 joints (I–V MCPs and PIPs, wrists) aimed at evaluating inflammatory features (synovial effusion and hypertrophy, power Doppler-PD), through a semi-quantitative scale (0-3). The total US (0-198) and PD (0-66) scores were calculated. We scanned bilateral flexor (I–V fingers of hands) and extensor compartments (1-6) tendons: tenosynovitis was scored as absent/present (0/1), resulting in a total score (0-22).Results:We studied 102 patients (M/F 15/87; median age 59.2 years, IQR 17.75; median disease duration 144 months, IQR 126), 61 treated with baricitinib and 41 with tofacitinib. At baseline, the median total US score was 18 (IQR 19) and the median PD score 2 (4). We observed a significant reduction in both total and PD US scores at all time-points (p<0.0001) (Figure 1). At baseline, 75.4% of patients showed tenosynovitis involving at least one tendon, with a median score of 2 (IQR 3.5) significantly decreasing after 24 weeks (p=0.02). Multivariate analysis, adjusted for baseline DAS28CRP and other concomitant treatments (including glucocorticoids and methotrexate treatment), confirmed the independent association between baseline US (PD and tenosynovitis) scores and the reduction of disease activity at follow-up evaluations.Conclusion:The present study confirmed the early efficacy of JAKi in RA patients by using US evaluation. Furthermore, power doppler and tenosynovitis scores could play a predictive role in response to treatment.References:[1]MUELLER RB, HASLER C, POPP F, et al. Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts. J Clin Med. 2019;8(10):1548.[2]COLEBATCH AN, EDWARDS CJ, ØSTERGAARD M, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. 2013;72(6):804-14.Figure 1.Ultrasound inflammatory score (a) and Ultrasound Power Doppler (PD) score (b) at baseline and follow-up.Table 1.Baseline characteristics of 414 RA patients.WEEKS04122448US inflammatory score18 (19)11 (15.5)9.5 (11.7)7.5 (8)6 (11)US PD score2 (4)0 (2)0 (1)0 (1)0 (0.7)Disclosure of Interests:Cristina Garufi: None declared, Fulvia Ceccarelli: None declared, Francesca Romana Spinelli Speakers bureau: Abbvie, Eli Lilly, Consultant of: Gilead/Galapagos, Eli Lilly, Grant/research support from: Pfizer, Silvia Mancuso: None declared, Carmelo Pirone: None declared, Fabrizio Conti Speakers bureau: Abbvie, Eli Lilly, Sanofi, Pfizer, Consultant of: Gilead/Galapagos

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AB0786 HUGHES–STOVIN SYNDROME: A PECULIAR AUTOIMMUNE ORIGIN OF PULMONARY ANEURYSMS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.4097 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1418.2-1419

Author(s):

P. Triggianese ◽

A. D’antonio ◽

B. Kroegler ◽

A. Ascoli Marchetti ◽

L. Belvivere ◽

...

Keyword(s):

Pulmonary Embolism ◽

Ct Angiography ◽

Early Recognition ◽

Endovascular Embolization ◽

Ocular Involvement ◽

Arterial Aneurysm ◽

Filter Placement ◽

Invasive Approach ◽

Oral Ulcers

Background:Hughes-Stovin Syndrome (HSS) is a rare potentially fatal vasculitis supposedly belonging to the spectrum of Behçet disease without ocular involvement. HSS tends to play by a temporal pattern, starting with thrombosis and followed by formation of pulmonary aneurysms. Since its mortality can reach 25% of cases, the early recognition and the appropriate therapy represent the major challenges.Objectives:In this report, we aimed at describing a rare case of HSS successfully treated in accordance with a prompt combined management with endovascular approach and immunosuppressive treatments.Methods:We described a Caucasian 33-year-old man presented to the Emergency Room of our Hospital with hemoptysis associated with dyspnea and chest pain, without fever and hypotension, with a 2-year history of painful genital and oral ulcers. Blood test revealed anemia, elevated white cell count with increased C-reactive protein (77 mg/L) and D-dimer (2740 ng/mL). Doppler ultrasonography of legs showed thrombosis of the left femoral vein, while CT-angiography reported multiple aneurysms of the pulmonary arteries. An early and extensive work-up for infections and autoimmunity did not document relevant abnormalities. An appropriate genetic assessment revealed the HLA-B51 positivity. The patient immediately underwent endovascular embolization with coils and plugs of the largest pulmonary aneurysm, and inferior vena cava filter placement. Then, he started methylprednisolone (1 mg/kg/day) IV for three days in association with LMWH (6000 IU/day). Prednisone (1 mg/kg/day) in combination with cyclophosphamide (100 mg daily) were started orally, with tapering of steroids within a month. At the tight follow up (1 month and 3 months later), no genital and oral ulcers nor vascular thrombosis occurred, and acute phase reactants were in normal range. The 3-month-CT angiography showed a complete resolution of the aneurysms and no new changes.Results:The peculiar diagnosis of HLAB51 positive HSS with multiple pulmonary aneurysms was made. The appropriate imaging followed by a prompt endovascular embolization of aneurysms with LMWH treatment were successfully performed. Interestingly, the oral combination therapy with corticosteroid and cyclophosphamide showed a rapid efficacy with a relevant safety profile. At the tight follow up, the young man improved significantly with clinical signs and pulmonary changes (Figure 1 next page).Conclusion:This case is of interest because of the early recognition of such a rare disease that allowed an adequate combined radiological, vascular, and rheumatologic approach. In our case, LMWH resulted useful in preventing the pulmonary embolism, despite the use of anticoagulants is still debated in HSS. Moreover, the endovascular embolization let a less invasive approach to surgery without the need for multiple surgical procedures. For the first time, we documented that oral cyclophosphamide showed an early efficacy as a first line therapy of a HLA-B51 HSS.References:[1]Keskin M, Polat G, Ayranci A, et al. Insidious Hughes Stovin Syndrome: Journey From Pulmonary Embolism to Pulmonary Arterial Aneurysm. Turk Thorac J. 2020;21:350-353.[2]Valdés-Corona LF, Kimura-Hayama E, Méndez-Cano VH, et al. Hughes-Stovin syndrome: an uncommon cause of pulmonary aneurysms. Rheumatology (Oxford). 2020;59:2183-2184.Figure 1.Disclosure of Interests:None declared

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Disease course of Neurofibromatosis Type 2; a 30-year follow-up study of 353 patients seen at a single institution

Neuro-Oncology ◽

10.1093/neuonc/noaa284 ◽

2020 ◽

Author(s):

Claire Forde ◽

Andrew T King ◽

Scott A Rutherford ◽

Charlotte Hammerbeck-Ward ◽

Simon K Lloyd ◽

...

Keyword(s):

De Novo ◽

Radiation Treatment ◽

Univariate Analysis ◽

Age At Onset ◽

Neurofibromatosis Type ◽

Neurofibromatosis Type 2 ◽

Disease Course ◽

Number Of Patients

Abstract Background Limited data exists on the disease course of Neurofibromatosis Type 2 (NF2) to guide clinical trial design. Methods A prospective database of patients meeting NF2 diagnostic criteria, reviewed between 1990–2020, was evaluated. Follow-up to first vestibular schwannoma (VS) intervention and death was assessed by univariate analysis and stratified by age at onset, era referred and inheritance type. Interventions for NF2-related tumours were assessed. Cox regression was performed to determine the relationship between individual factors from time of diagnosis to NF2-related death. Results Three-hundred-and-fifty-three patients were evaluated. During 4643.1 follow-up years from diagnosis to censoring 60 patients (17.0%) died. The annual mean number of patients undergoing VS surgery or radiotherapy declined, from 4.66 and 1.65 respectively per 100 NF2 patients in 1990-1999 to 2.11 and 1.01 in 2010-2020, as the number receiving bevacizumab increased (2.51 per 100 NF2 patients in 2010-2020). Five patients stopped bevacizumab to remove growing meningioma or spinal schwannoma. 153/353 (43.3%) had at least one neurosurgical intervention/radiation treatment within 5 years of diagnosis. Patients asymptomatic at diagnosis had longer time to intervention and better survival compared to those presenting with symptoms. Those symptomatically presenting <16 and >40 years had poorer overall survival than those presenting at 26-39 years (P=0.03 and P=0.02 respectively) but those presenting between 16-39 had shorter time to VS intervention. Individuals with de novo constitutional variants had worse survival than those with de novo mosaic or inherited disease (P=0.004). Conclusion Understanding disease course improves prognostication, allowing for better informed decisions about care.

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