Routine diagnostics for neural antibodies,clinical correlates,treatment and functional outcome

Objective

To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions.

Methods

Earliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters.

Results

Positive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6–46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-d-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention.

Conclusions

This novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient.

     

Quality of life in Turkish patients with Familial Mediterranean Fever: Association with fatigue,psychological status,disease severity and other clinical parameters

Aim of the work: To evaluate the quality of life (QoL) in Familial Mediterranean Fever (FMF) patients, and determine its association with fatigue, depression, disease severity and other clinical parameters. Patients and methods: Sixty FMF patients were included. QoL was assessed by Short Form-36 (SF-36), depression by Hamilton Depression Scale (HDS), and fatigue by Fatigue severity scale (FSS). Disease severity score and Mutations of the Mediterranean fever (MEFV) gene were assessed. Results: The mean age of patients was 33.73 ± 9.81 years and disease duration 14.6 ± 12.1 years. They were 35 females and 25 males. FMF patients scored significantly higher in FSS (29.9 ± 17.6) and HDS (15.1 ± 8.5) compared to the control (10.6 ± 7.1 and 6.3 ± 9.4; p < 0.0001 respectively) while all SF36 sub-items except mental health were significantly lower (p < 0.05). MEFV gene mutation was present in 49 (81.7%) patients. The visual analogue scale of pain significantly negatively correlated with the FSS (p < 0.0001), HDS (p < 0.0001) and all SF36 sub-items except mental health (p < 0.0001). Disease duration, age of onset, and duration of attacks showed no significant correlation with FSS, HDS and SF36. Delay in diagnosis significantly correlated with FSS (p < 0.0001) and negatively with SF36 sub-items physical role (p = 0.02), general health (p = 0.01) and social functioning (p = 0.03). Age of diagnosis significantly correlated with FSS (p = 0.03) and negatively with SF36-vitality (p = 0.047). There was a significant effect of disease severity on QoL, fatigue and depression (p < 0.05). Conclusion: QoL is associated with fatigue, depression and disease severity in FMF patients. It should be used in routine clinical evaluation as an outcome measure in FMF.