Attack-free Intervals Research Articles

Kynurenine pathway of tryptophan metabolism in patients with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an autoinflammatory syndrome characterized by recurrent episodes of fever and aseptic polyserositis. Subclinical inflammation generates a hidden threat to the development of FMF complications such as amyloidosis in attack-free intervals. The kynurenine pathway (KP) has been considered an important player in inflammation and immune response. The study was aimed to measure serum levels of KP metabolites in patients with FMF in the attack-free period. A total of 161 participants were recruited from the rheumatology department in this single-centre, case-control study. Participants meeting the eligibility criteria were divided into healthy controls (n = 80) and FMF (n = 81). The laboratory data were obtained from the electronic registration database. Serum tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxyanthranilic acid, 3-hydroxykynurenine (3HK), and quinolinic acid (QUIN) concentrations were measured with tandem mass spectrometry. Laboratory findings of FMF patients and healthy controls subjects were compared and evaluated. Serum TRP and KYNA levels were significantly decreased in both FMF groups compared to the control group, while the levels of KYN, QUIN, 3HK, the KYN/TRP ratio, and red cell distribution width were higher. TRP degradation by the KP is increased in patients with FMF. KP metabolites can be useful in demonstrating subclinical inflammation.

Craniofacial Autonomic Dysfunction in Migraine: Implications for Treatment and Prognosis.

Craniofacial autonomic signs and symptoms (CASS) are relatively underrecognized in the evaluation of migraine headache. Yet, these features provide insight into diagnostic criterion, therapeutic approaches, and overarching disease burden. This review aims to summarize relevant literature evaluating autonomic dysfunction, with focus on CASS, in migraine through targeted literature searches in PubMed. Full articles of original data published between 1974 and 2019 were identified using MeSH terms with no search limits. Although CASS are typically clinically evaluated by subjective patient report, investigational measures of cranial autonomic function have identified marked distinctions between headache attack and attack-free intervals. The presence of CASS during an attack does not differ based on age, sex, or presence of aura. Unilateral CASS may be predictive of longer, more frequent, and/or severe attacks and often co-occur with sensory dysfunction such as allodynia and photophobia. Although limited research has been performed to evaluate targeted therapeutics for migraine with CASS, triptans and onabotulinumtoxinA may demonstrate greater effects in this group. Migraine remains a debilitating disorder with significant community-wide impacts, necessitating continued evaluation of contributing features. Consideration of CASS provides important insight into potential treatment approaches and the effectiveness of novel therapeutic interventions aimed at improving overall disease burden. However, further investigation is needed to fully understand primary craniofacial features in migraine, and how these might inform individualized treatment decisions.

Familial Mediterranean Fever: an unusual cause of liver disease

BackgroundFamilial Mediterranean Fever is an autoinflammatory disease typically expressed with recurrent attacks of fever, serositis, aphthous stomatitis, rash. Only a few reports describe the association with hepatic involvement.Case presentationWe describe the clinical case of a child affected, since the age of 1 year, by recurrent fever, aphthous stomatitis, rash, arthralgia, associated with abdominal pain, vomiting, lymphadenopathy. The diagnosis of Familial Mediterranean Fever was confirmed by the genetic study of MEFV gene; the homozygous mutation M694 V in exon was documented. A partial control of attacks was obtained with colchicine. The child continued to manifest only recurrent episodes of abdominal pain without fever, however serum amyloid A persisted high, in association with enhanced levels of CRP, AST and ALT (1.5 x n.v.). The dosage of colchicine was increased step by step and the patient achieved a better control of symptoms and biochemical parameters. However, the patient frequently needed an increase in the dose of colchicine, suggesting the possible usefulness of anti-interleukin-1 beta treatment.ConclusionsThe unusual presentation of Familial Mediterranean Fever with liver disease suggests the role of inflammasome in hepatic inflammation. Colchicine controls systemic inflammation in most of the patients; however, subclinical inflammation can persist in some of them and can manifest with increased levels of CRP, ESR, serum amyloid A also in attack-free intervals.

Normal FGF-21-Serum Levels in Patients with Carnitine Palmitoyltransferase II (CPT II) Deficiency.

Fibroblast growth factor 21 (FGF-21) is known to be a biomarker for mitochondrial disorders. An upregulation of FGF-21 in serum and muscle of carnitine palmitoyltransferase I (CPT I) and carnitine palmitoyltransferase II (CPT II) knock-out mice has been reported. In human CPT II deficiency, enzyme activity and protein content are normal, but the enzyme is abnormally regulated by malonyl-CoA and is abnormally thermolabile. Citrate synthase (CS) activity is increased in patients with CPT II deficiency. This may indicate a compensatory response to an impaired function of CPT II. In this study, FGF-21 serum levels in patients with CPT II deficiency during attack free intervals and in healthy controls were measured by enzyme linked immunosorbent assay (ELISA). The data showed no significant difference between FGF-21 concentration in the serum of patients with CPT II deficiency and that in the healthy controls. The results of the present work support the hypothesis that in muscle CPT II deficiency, in contrast to the mouse knockout model, mitochondrial fatty acid utilization is not persistently reduced. Thus, FGF-21 does not seem to be a useful biomarker in the diagnosis of CPT II deficiency.

The peculiar features of vestibular function disorders associated with Meniere's disease

The objective of the present study was to reveal the special aspects of vestibular dysfunction in the patients presenting with unilateral Meniere's disease (MD) during the attack-free intervals. The study included 23 patients suffering from unilateral MD; all of them were examined with the use of tonal threshold audiometry, videonystagmography, the caloric test and video head-impulse test (vHIT). The study has demonstrated that the patients with MD are characterized, during the attack-free intervals, by the absence of latent spontaneous nystagmus in conjunction with the positive results of the head shaking test. Moreover, asymmetry of the results of the caloric test together with the normal results of the video head-impulse test is shown to be the characteristic feature of the patients with unilateral MD. The analysis of the degree of sensorineural hearing loss, the caloric test data, and coefficient of labyrinth asymmetry (CLAS) gave evidence of the tendency toward the elevation of the hearing threshold with increasing CLAS.

Interferon Alpha-2a Therapy in Patients with Refractory Behçet Uveitis

ABSTRACTPurpose: To report the results of IFNα2a therapy in patients with Behçet uveitis refractory to azathioprine-cyclosporine combination treatment.Methods: In a retrospective study, 39 patients treated with either azathioprine-cyclosporine combination treatment (group 1, n = 23) or IFNα2a (group 2, n = 16) with a diagnosis of ocular Behçet disease (BD), were included in the study. Group 2 consisted of patients who did not respond to conventional combination therapy, and were therefore treated with IFNα2a. Clinical response and relapse rates were recorded for each group.Results: The mean number of uveitis attacks/year per patient was 0.8 ± 1.6 in Group 1. In Group 2, a significant decrease in the mean number of uveitis attacks/year per patient was observed after initiation of IFNα2a (2.4 ± 1.8 vs 1.3 ± 2.0) (p<0.05). When the two groups were compared after administration of IFNα2a therapy, no statistical difference was found in terms of uveitis attack/year and attack-free intervals, with a partial response to both treatments.Conclusions: IFNα2a therapy is an effective alternative for Behçet uveitis patients where conventional combination therapy fails.

Killer Cell Immunoglobulin-Like Receptor (KIR) Genotype Distribution in Familial Mediterranean Fever (FMF) Patients.

BackgroundFamilial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease predominantly affecting Mediterranean populations. The gene associated with FMF is the MEFV gene, which encodes for a protein called pyrin. Mutations of pyrin lead to uncontrolled attacks of inflammation, and subclinical inflammation continues during attack-free intervals. Killer cell immunoglobulin-like receptor (KIR) genes encode HLA class I receptors expressed by NK cells. The aim this study was to look for immunogenetic determinants in the pathogenesis of FMF and find out if KIR are related to susceptibility to disease or complications like renal amyloidosis.Material/MethodsOne hundred and five patients with FMF and 100 healthy individuals were involved in the study. Isolated DNA from peripheral blood was amplified by sequence specific PCR probes and analyzed by Luminex for KIR genotypes. Fisher Exact test was used to evaluate the variation of KIR gene distribution.ResultsAll patients and healthy controls expressed the framework genes. An activator KIR gene, KIR2DS2, was significantly more frequent in FMF patients (p=0.036). Renal amyloidosis and presence of arthritis were not associated with KIR genes and genotype. KIR3DL1 gene was more common in patients with high serum CRP (p=0.016).ConclusionsAccording to our findings, we suggest that presence of KIR2DS2, which is an activator gene for NK cell functions, might be related to the autoinflammation in FMF. The potential effect of KIR genes on amyloidosis and other clinical features requires studies with larger sample sizes.

RANDOMIZED CONTROLLED TRIAL ON THE EFFECT OF VRISHA GHRITA IN CHILDHOOD ASTHMA MANAGEMENT

An interventional randomized controlled trial was conducted to evaluate the efficacy of Vrisha Ghrita on Tamaka Swasa (with special reference to bronchial Asthma) with plain Ghrita as control in children aged up to 12 years. Vrisha Ghrita was giv en internally in a divided dos e of 5 - 15ml twice daily along with honey according to the age for a period of 3 months during attack free int ervals. The idea behind trial was to improve the immunological compliance of the child and to conquer recurrent asthma. A total number of 26 children attending OPD (Out patient department) section of the hospital participated in the study. Analysis of the data was done using clinical parameters, routine hematolog y wi th AEC (Absolute Eosinophil Count) , selected immunoglobulin assay, lung function tests, measures of morbidity and asthma and quality of life questionnaire. The assessment reported that effects of Vrisha Ghrita were significant in combating the clinical man ifestations of Tamaka Swasa ( p <0.01), reducing morbidity episodes, school absenteeism, number of unsc heduled visits to doctors (all p <0.01). All these point suggests that the trial drug is highly effective in controlling recurrent episodes of asthma and re spiratory tract infections. However, the results were statistically not significant with respect to h a ematology, immunoglobulin assay and pulmonary function tests. Risks of side effects were minimal in both the groups. The stud y was effective in curtailing the conventionally used bronchodilators and antibiotic therapies in children. Keyw ords: Efficacy Trial, Asthma, Tamaka Swasa , Vrisha Ghrita , Ayurvedic medicine.

Long-term improvement of paroxysmal dystonic choreathetosis with acetazolamide

Sirs: Paroxysmal dyskinesias are a heterogeneous group of movement disorders characterized by recurrent brief episodes of abnormal involuntary movements [1–3] Among them, paroxysmal dystonic choreoathetosis (PDC) is associated with dystonic or choreic attacks unrelated to movement. It may occur spontaneously at rest without any triggering factors but attacks are frequently precipitated by caffeine or alcohol consumption, stress and fatigue. In contrast to paroxysmal kinesigenic choreathetosis (PKC), PDC attacks are more dystonic, usually last longer, and are less frequent with long attack-free intervals [3, 4]. Although most cases are familial, sporadic and secondary forms of PDC have been reported [4, 5]. We report a patient with a sporadic severe PDC which has been dramatically improved by acetazolamide over a period of three years. This 17-year-old boy who had a normal birth and no familial history developed his first symptoms at the age of 12. He presented recurrent episodes of left arm mild dystonia, along with attacks of paroxysmal non-kinesigenic dyskinesia involving the whole body. Short attacks (20 to 120 s) occurred 3 times a week to several times per day. They manifested as dystonia frequently beginning in the lower limbs, either on the left or right side of the body, spreading to the trunk and upper limbs and finally leading to falls. No aura or changes in consciousness were noted and no precipitating factors were reported. Clinical examination was normal. Occasionally, a mild left hand dystonic posture was observed when walking. Blood chemistry was normal. Wilson’s disease was excluded. Antibasal ganglia antibodies were negative on two examinations. Brain MRI, interictal electroencephalograms and iodobenzamide SPECT were normal. A videoencephalogram was performed for three consecutive days during which the patient exhibited several attacks without any epileptic activity on the EEG during attacks. Psychiatric evaluation was unremarkable. Owing to the analogy with paroxysmal ataxia (EA2) [6], screening was performed for CACNA1A gene. Screening by direct DNA sequence analysis of the 47 exons of the CACNA1A gene did not reveal any mutation. Analysis of triplets (involved in SCA6) was also normal. We also sought a mutation in the MR-1 gene encoding for the Myofrillogenesis Receptor 1 [7, 8]. Sequencing of the 10 exons of the transcript specifically expressed in the brain did not detect any mutation in the MR-1 gene. Tiapride chlorydrate, valproate sodium, carbamazepine and clonazepam at usual dosage were ineffective. Owing to similarities between attacks of PDC and periodic ataxia, acetazolamide (10 mg/ kg/day) was used off-label and the attacks resolved within two weeks. During the subsequent three years of follow up, the patient reported only two episodes of attacks during holidays. They clearly occurred when the patient neglected to take his treatment in the morning and they disappeared with acetazolamide, showing the strict correlation between relapse of attacks and drug intake. Treatment with acetazolamide was clinically well tolerated and regular examinationof blood samples was unremarkable. The clinical presentation of our patient points to a diagnosis of PDC because the paroxysmal dystonic attacks were not triggered by any particular movement, unlike in paroxysmal kinesigenic dyskinesia (PKD). Attacks were of short duration but a wide variability of symptoms is frequently noted in PDC, particularly concerning attack duration [2–4]. For example, one patient (P7) in the series of Bressman et al. [4] had attacks lasting only 10 sec to 5min, close to those observed in our patient. The dystonic nature of the attacks, the normal consciousness, and above all the absence of EEG V. Michel, MD AE D. Guehl, MD, PhD B. Bioulac, MD, PhD P. Burbaud, MD, PhD (&) Service de Neurophysiologie clinique Hopital Pellegrin Avenue Amelie-Rabat Leon 33076 Bordeaux, France Tel.: + 33/5 57 57 15 86 Fax: + 33/5 56 89 20 61 E-Mail: Pierre.Burbaud@umr5543. u-bordeaux2.fr

Subclinical Left Ventricular Dysfunction in Migraine Attacks

The aim of the present study was to evaluate cardiac performance of patients with migraine attacks during the overload produced by phenylephrine infusion. Background.-It is known that circulatory changes occur during migraine. However, the relationship between this finding and transient cardiac dysfunction is still unknown. By means of two-dimensional direct M-mode echocardiography, we measured fractional shortening, ejection fraction, and mean velocity of circumferential fibers shortening in 18 patients with migraine and in 10 normal subjects as a control group. These measures were performed in two different periods: during attack-free intervals and during attacks. Pain intensity of typical migraine attack was evaluated on a 0 to 10 scale. Cardiac size and function were normal at rest in both groups. However, during migraine attacks, phenylephrine infusion provoked significant decrease in fractional shortening, EF, and mean velocity of circumferential fibers shortening, followed by concomitant increase of headache severity. On the other hand, during the attack-free interval and in the control group phenylephrine infusion did not show significant changes in cardiac function parameters. Our data suggest that left ventricular dysfunction during the phenylephrine test could participate in the complex pathophysiological mechanism of migraine attacks.

Abnormal Platelet Mitochondrial Function in Patients Affected by Migraine With and Without Aura

To investigate energy metabolism in migraine, we determined platelet mitochondrial enzyme activities in 40 patients with migraine with aura and in 40 patients with migraine without aura during attack-free intervals and in 24 healthy control subjects. NADH-dehydrogenase, citrate synthase and cytochrome-c-oxidase activities in both patient groups were significantly lower than in controls (p < 0.01), while NADH-cytochrome-c-reductase activity was reduced only in migraine with aura (p < 0.01). No alteration in succinate-dehydrogenase was observed. Monoamine-oxidase activity differed between sexes (p < 0.05) but within each sex group no difference was observed between patients and controls. We hypothesize that the defect in mitochondrial enzymes observed indicates a systemic impairment of mitochondrial function in migraine patients.

Imbalance of heart rate regulation in cluster headache as based on continuous 24-h recordings

An altered autonomic balance is considered to be a pathogenetic factor in cluster headache syndrome, although there is varying data on sympathetic and/or parasympathetic activation during attacks and/or attack-free intervals. The aim of the present study was to evaluate the day/night pattern of heart rate during the active and remission phases of cluster headache. In addition, the relationship between heart rate changes and the site of pain was investigated to determine if an autonomic imbalance was related to the lateralization of pain. Thirty-nine patients (34 with primary episodic cluster headache and five with primary chronic cluster headache and 30 healthy controls underwent 24-h Holter ECG recording. Nine cluster headache patients were monitored during both phases of the disease. The data obtained confirmed the existence of a disordered chrono-organization in cluster headache (phase-shift of approximately 1 h of heart rate rhythm during the cluster period) together with a low heart rate variability and a higher occurrence of arrhythmias in cluster headache patients with right-sided pain. Differences were also observed in the cluster headache patients when headache free, excluding the pain itself as a reason for the abnormality. The chronobiological data point out a transient rhythmic dysfunction, while heart rate variability changes, mostly related either to the phase of the disease or to the site of pain, probably reflects a central, site-related, dysfunction of the autonomic nervous system in cluster headache.

アンケート調査からみたメニェール病の経過

We investigated the course of Meniere's disease by questionnaires sent to 94 patients in June 1992. Sixty-seven of them sent back information as to whether they still had attacks of vertigo and whether they had been treated since they visited our clinic between 1981 and 1986.On the basis of their responses, they were divided into 2 groups: those who had not been treated or had been treated only when they had attacks of vertigo (natural course group) and those who had been treated for a certain period (treated group).We judged that they were cured of vertigo if the period without attacks was over 2 years and longer than their maximum attack-free intervals. The percentage of cures was similar in the 2 groups, but the time between the first and the last attack of vertigo was longer in the natural course group than in the treated group.

Interferon Production in Patients with Recurrent Hereditary Polyserositis

Peripheral blood cells, obtained from patients with recurrent hereditary polyserositis (RHP) during attack-free intervals, were found to produce less interferon-γ than cells from healthy controls when stimulated with phytohaemagglutinin. A similar, although less pronounced hyporesponsiveness was observed for interferon-α, produced after stimulation with Sendai virus. Treatment of the patients with colchicine appeared to restore, or partly restore, the interferon-α and interferon-γ responsiveness, although neither interferon could be demonstrated in sera from the patients. However, the RHP patients displayed significantly raised serum levels of β2-microglobulin, a substance whose synthesis is stimulated by interferon. The interferon abnormality in RHP may be a secondary phenomenon, but it cannot be excluded that it has a pathogenetic role in the development of the disease.

Attack-free Interval of Meniere's Disease and Vestibular Meniere's Disease

Meniere's disease and vestibular Meniere's disease have episodic vertigo followed by remission in which the patients feel perfectly well. Recurrences may come at intervals varying from a few days to several years. The duration of attacks showed an irregular pattern producing both a longest period without a vertigo attack and a shortest period without a vertigo attack. In this presentation, clinical characteristics between Meniere's disease and vestibular Meniere's disease were studied by using the maximum and minimum intervals. The following results were obtained.1. Most patients with a 1-2 year history of Meniere's disease were found to have a maximum attack-free interval of within 6 months. Patients with a history of 2-5 years and 5-10 years were found to have maximum attack-free intervals of 2-5 years.2. The minimum attack-free interval of Meniere's disease was not influenced by the duration of the disease.3. The minimum attack-free interval of Meniere's disease was observed most often within 7 days. The minimum attack-free interval of vestibular Meniere's disease was observed most often over 7 days.4. Regarding bilaterality, sex and age of onset, there was no significant difference in patient with a history of over 2 years in maximum and minimum attack-free intervals of Meniere's disease.5. Patients with Meniere's disease can be divided into 3 groups; those with cochlear and vestibular symptoms starting at the same time, and those with the vestibular symptoms starting before or after cochlear symptoms: All 3 groups had the same tendency in terms of maximum and minimum attack-free intervals.6. For the prognosis of Meniere's disease, it is convinient to use the accumulated frequency of maximum intervals.

The effect of percutaneous nitroglycerin upon the concentration of serotonin, epinephrine and norepinephrine in venous blood from migrainous subjects during attack-free intervals.

THE EFFECT OF PERCUTANEOUS NITROGLYCERIN UPON THE CONCENTRATION OF SEROTONIN, EPINEPHRINE AND NOREPINEPHRINE IN VENOUS BLOOD FROM MIGRAINOUS SUBJECTS DURING ATTACK-FREE INTERVALS T. Dalsgaard-Nielsen, T. Dalsgaard-NielsenSearch for more papers by this authorB. Bryndum, B. BryndumSearch for more papers by this authorF. Fog-Møeller, F. Fog-MøellerSearch for more papers by this authorI. Kemp Genefke, I. Kemp GenefkeSearch for more papers by this author T. Dalsgaard-Nielsen, T. Dalsgaard-NielsenSearch for more papers by this authorB. Bryndum, B. BryndumSearch for more papers by this authorF. Fog-Møeller, F. Fog-MøellerSearch for more papers by this authorI. Kemp Genefke, I. Kemp GenefkeSearch for more papers by this author First published: January 1975 https://doi.org/10.1111/j.1526-4610.1975.hed1404231.xCitations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume14, Issue4January 1975Pages 231-234 RelatedInformation