Neurological Manifestations in Familial Mediterranean Fever: Results of 22 Children from a Reference Center in Kayseri, an Urban Area in Central Anatolia, Turkey

Canpolat, Mehmet; Gümüş, Hakan; Gündüz, Zübeyde; Düşünsel, Ruhan; Kumandaş, Sefer; Bayram, Ayşe Kaçar; Yel, Sibel; Poyrazoğlu, Hatice Gamze; Yılmaz, Kenan; Doğanay, Selim; Yıkılmaz, Ali; Dündar, Munis; Per, Hüseyin

doi:10.1055/s-0036-1593374

Cited by 14 publications

(19 citation statements)

References 23 publications

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“…Looking in more detail on neurological manifestations in patients w/o MS, headache was the most prevalent symptom among low-penetrance variant carriers irrespective of the underlying genotype. This finding demonstrates a similar result compared to AID patients carrying disease-causing variants, of whom headache syndromes were also reported at a high frequency such as 84% of CAPS and 72% of FMF patients [12,39]. A greater proportion of patients with NLRP3 variants showed CN affection, which supports findings of our previous study and underscores the vulnerability of cranial nerves to inflammation caused by NLRP3-associated inflammasome activation [24].…”

Section: Discussionsupporting

confidence: 88%

“…This was underscored by a high number of abnormal MRI and CSF findings in those patients. CNS inflammation is often observed in patients with pathogenic NLRP3 mutations but has also been reported in patients with MEFV mutations [5,12,14,15,39,40]. Regarding NLRP3, neurological involvement was so far reported for 40-95% of CAPS patients and has mainly been linked to the pathogenic R260W mutation of the NLRP3 gene, while the V198M variant was negatively associated with neurological involvement [12,13,35].…”

Section: Discussionmentioning

confidence: 99%

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Neurological phenotypes in patients with NLRP3-, MEFV-, and TNFRSF1A low-penetrance variants

Mulazzani

Wagner

Havla

et al. 2020

J Neuroinflammation

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Background: Neurological manifestations and the co-occurrence of multiple sclerosis (MS) have been reported in patients with autoinflammatory diseases (AID) and variants of the NLRP3-, MEFV-, or TNFRSF1A gene. However, type and frequency of neurological involvement are widely undetermined. Methods: We assessed clinical characteristics of 151 (108 with MS) patients carrying NLRP3-, MEFV-and TNFRSF1A low-penetrance variants from the Institute of Clinical Neuroimmunology. We evaluated demographic, genetic, and clinical features with a focus on central nervous system (CNS) involvement including magnetic resonance imaging (MRI) results and cerebrospinal fluid (CSF) data. The disease course of AID patients with MS was compared to a matched MS control group without mutations. Results: The genetic distribution comprised 36 patients (23%) with NLRP3-and 66 patients (43%) with TNFRSF1A low-penetrance variants as well as 53 (34%) patients carrying pathogenic mutations or low-penetrance variants in the MEFV gene. MS patients displayed most frequently the R92Q TNFRSF1A variant (n = 51; 46%) followed by the Q703K NLRP3 variant (n = 15; 14%) and the E148Q substitution (n = 9; 8%) in the MEFV gene. The disease course of MS was not influenced by the genetic variants and did not differ from MS patients (n = 51) without mutations. AID patients without MS most frequently harbored MEFV mutations (n = 19, 43%) followed by NLRP3-(n = 17, 39%) and TNFRSF1A (n = 8, 18%) low-penetrance variants. Sixteen (36%) of them suffered from severe CNS involvement predominantly recurrent aseptic meningoencephalitis and optic neuritis accompanied by abnormal MRI and CSF results. Severe CNS inflammation was associated with the Q703K allele. Headache was a highly prevalent neurological symptom (up to 74%), irrespective of the underlying genetic variation. The NLRP3 cohort without MS more frequently exhibited affections of the cranial nerves (CN) (p = 0.0228) and motor symptoms (p = 0.0455). Elevated acute-phase reactants were detected in all patients, and fever episodes were present in up to 50%. Arthralgias were the most frequently identified constitutional symptom among all subgroups.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Neurological phenotypes in patients with NLRP3-, MEFV-, and TNFRSF1A low-penetrance variants

Mulazzani

Wagner

Havla

et al. 2020

J Neuroinflammation

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“…A recent study by Canpolat et al 21 of 22 children with FMF showed neurological findings included headache in 16 patients (72.7%), epilepsy in six patients (27.3%), pseudotumor cerebri in two patients (9.1%), multiple sclerosis in one patient (4.5%), and tremor in one patient (4.5%). The most common MEFV gene mutation in these patients was M694V (40.9%).…”

Section: Discussionmentioning

confidence: 93%

<p>Neurological Manifestations in Familial Mediterranean Fever: a Genotype-Phenotype Correlation Study</p>

Salehzadeh

Ahad

Motezarre

et al. 2020

OARRR

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Background and Aims: Familial Mediterranean Fever (FMF) is a periodic autoinflammatory disease with an autosomal recessive hereditary pattern. The aim of this study is to explain the spectrum of possible neurological manifestations and its genotypephenotype correlation in patients with familial Mediterranean fever. Methods: In this case series study, data of 311 FMF patients at the FMF Registration Center in Iran (http://www.fmfiran.ir/) was studied. Patient's information was entered into a researcher designed questionnaire. Data were analyzed by SPSS software. Results: The mean age of the 181 male and 130 female patients was 23.01 years, ranging from 3-78 years old. Twelve common MEFV gene analyses were performed in 311 patients, with mutated results in 187 (60.1%) patients. The most common neurological manifestations were headache in 47.26%; 64.1% of those were persistent and 35.9% had a recurrent nature. Other neurological manifestations were vertigo (83 patients, 26.7%), paresthesia (72 patients, 23.2%), tremor (53 patients, 17%), disorientation (40 patients, 12.9%), breath-holding (23 patients, 7.4%), migraine (19 patients, 6.1%), syncope (8 patients, 2.6%), epilepsy (7 patients, 2.3%), febrile seizure (4 patients, 1%), and ataxia (5 patients, 1.6%). There were no cases of stroke or metabolic disorders among these patients. Conclusion: The prevalence of epilepsy among FMF patients was significantly higher than the general population. FMF patients with negative results for MEFV gene mutations had significant frequency of headache, paresthesia, breath-holding, and ataxia.

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“…Few cases were detected in the literature about FMF and MS coexistence. Most of these reports do not provide any information about immunomodulating/immunosuppressive therapies for MS. [5][6][14][15][16] In some cases, therapies for MS were reported while their effects on FMF attacks were not. 17,18 Ceylan et al 19 reported two cases of FMF with MS. MS diagnosis was established by cervical MRI findings and oligoclonal band results in one case and by cranial MRI findings in the other case.…”

Section: Discussionmentioning

confidence: 99%

Familial Mediterranean Fever and Multiple Sclerosis Successfully Treated With Interferon Beta-1a: A Case Report

Öztürk

2019

Arch Rheumatol

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Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder. It is characterized by recurrent attacks of fever, peritonitis, pleuritis, and synovitis and common in Mediterranean people including Turks, Arabs, Armenians, and non-Ashkenazi Jews. 1 The responsible gene for FMF is MEFV located on chromosome 16p. Multiple sclerosis (MS) is the most common demyelinating disease of central nervous system. MS is characterized by inflammation and demyelination and caused by several environmental and genetic factors. Patients with FMF have a susceptibility to develop MS. Mutations of genes like MEFV encoding pyrin protein may promote development of MS disease. 2 Akman-Demir et al. 3 suggested a four-fold increased rate of FMF among MS patients. Currently, there is no curative treatment for both diseases. Immunomodulatory drugs display beneficial effects by decreasing severity and frequency of MS attacks. CASE REPORT A 37-year-old male patient was admitted to our department with numbness of lower extremities and difficulty in walking in September 2017. He had been suffering from numbness for more than three months and from gait disturbance for the last month. A few years before, he had numbness on lower extremities but he did not admit to any hospital and his complaints were completely resolved within two weeks. In his neurological examination, hypoesthesia in right ABSTRACT Multiple sclerosis (MS) is the most common demyelinating disease in Turkey while familial Mediterranean fever (FMF) is the most common periodic fever syndrome worldwide. In this article, we report a 37-year-old male patient admitted with complaint of difficulty in walking. He had been taking colchicine at admission for 27 years. Despite this therapy, he had been experiencing twice monthly severe FMF attacks. After systemic and neurological examinations, laboratory tests and cranial and spinal magnetic resonance imaging, he was diagnosed as MS. Interferon (IFN) beta-1a was initiated three times/weekly subcutaneously for MS treatment. He stopped colchicine treatment after five months of IFN treatment because he did not suffer from any FMF attacks. He is still attack free for both diseases for a follow-up duration of 12 months. IFN beta is one of the most preferred agents for MS treatment but not one of the agents used for the treatment of FMF. Interferon beta can be a treatment of choice in patients with coincident FMF and MS and can be used in colchicine-resistant patients after being studied in systematic clinical studies.

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Neurological Manifestations in Familial Mediterranean Fever: Results of 22 Children from a Reference Center in Kayseri, an Urban Area in Central Anatolia, Turkey

Cited by 14 publications

References 23 publications

Neurological phenotypes in patients with NLRP3-, MEFV-, and TNFRSF1A low-penetrance variants

Neurological phenotypes in patients with NLRP3-, MEFV-, and TNFRSF1A low-penetrance variants

<p>Neurological Manifestations in Familial Mediterranean Fever: a Genotype-Phenotype Correlation Study</p>

Familial Mediterranean Fever and Multiple Sclerosis Successfully Treated With Interferon Beta-1a: A Case Report

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