Familial Mediterranean Fever and Central Nervous System Involvement

Abstract

We conducted this study to determine familial Mediterranean fever (FMF)-associated central nervous system involvement including demyelinating lesions, stroke, and posterior reversible leukoencephalopathy syndrome (PRES). Patients with MEFV mutations were systematically reviewed through the Medical Biology Unit database. All samples sent for mutation analysis were screened for 10 common MEFV mutations. Patients with FMF and neurologic disorders according to the clinical records were invited for reevaluation. Lumbar puncture, electroencephalography, and evoked potentials were used to determine the type of neurologic involvement in selected cases. Electrocardiography, transthoracic and/or transesophageal echocardiography, and magnetic resonance imaging and/or angiography were performed to clarify the etiology of cerebrovascular disease. Of 8864 patients in the genetic testing database, 18 with neurologic signs were assessed. The mean age of patients was 31.0 +/- 11.8 years, mean age at first FMF symptom was 12.6 +/- 5.6 years, and mean age at neurologic involvement was 25.8 +/- 12.2 years. Fifty-five percent of patients were women. A homozygote MEFV mutation was detected in 16 of 18 patients (88.8%), and a homozygote M694V mutation was found in 72.2% of patients. We found 7 FMF patients with demyelinating lesions, 7 with cerebrovascular disease, and 4 with PRES. The mean interval between first FMF sign and neurologic involvement was 13.7 +/- 8.9 years in the demyelinating group, and 23.4 +/- 10.3 years in the group with cerebrovascular disease. Mean stroke age was 28.5 +/- 16.4 years. All patients in the PRES group had hypertension. Three different neurologic conditions in FMF patients were noticeable. Demyelinating lesions and cerebrovascular disease were the most common clinical presentations. Approximately 70% of patients had the homozygote M694V mutation. Neurologic involvement is rare but serious in FMF.

Clinical Picture in Adulthood and Unusual and Peculiar Clinical Features of FMF

“…Compared to their spouses, conceivably exposed to the same environmental hazards, FMF patients had similar rate of atherosclerotic CV disease. On the other hand and as mentioned above, ischemic stroke in FMF patients younger than 50 year old was reported by Kalyoncu et al to be more common than expected in age-adjusted general population (0.2 % vs. 0.005-0.01 %) [ 45 ]. Our experience with FMF patients, who suffered ischemic stroke/transient ischemic attack (TIA), was comparable [ 25 ].…”

Pseudotumor Cerebri in a Child With Familial Mediterranean Fever

“…Of these 13 patients, 10 had headaches during acute episodes of the fever, two had convulsions, and another patient had aseptic meningitis. Kalyoncu et al 2 reported 18 patients with neurological signs and detected seven patients with demyelinating lesions, seven patients with cerebrovascular disease, and four patients with reversible posterior leukoencephalopathy syndrome.…”

“…Neurological involvement in FMF is rare and shows a wide spectrum, including optic neuritis, recurrent aseptic meningitis, cranial nerve lesions, IIH, ischemic stroke due to coincidental reasons, and subclinical visual evoked potentials abnormalities with demyelinating lesions. 2,3 Only a few reliable reports are present on the association of FMF and IIH in adults. 4,5 To our knowledge, there is no report involving children.…”

Special Aspects of Familial Mediterranean Fever in Childhood

“…Especially in adulthood cohort studies suggest that multiple sclerosis [ 40 -42 ], cerebrovascular events [ 43 ], and posterior reversible leukoencephalopathy syndrome (PRES) [ 43 ] are associated with FMF. One report describes the occurrence of headache, convulsions, and aseptic meningitis in children with FMF [ 40 ].…”