V. Rakocevic Stojanovic

Influence of multisystemic affection on health-related quality of life in patients with myotonic dystrophy type 1.

AIM To assess health-related quality of life (HRQoL) in patients with DM1, to identify muscular, multisystemic, central and social factors that may affect QoL and to define a DM1 patient in risk of poor QoL. PATIENTS AND METHOD This cross-sectional study comprised 120 DM1 consecutive patients. The following scales were used: Multidimensional Scale of Perceived Social Support (MSPSS), Muscular Impairment Rating Scale (MIRS), battery of neuropsychological tests, acceptance of illness scale (AIS), Hamilton rating scale for depression (Ham-D), Krupps Fatigue Severity Scale (FSS), Daytime Sleepiness Scale (DSS) and SF-36 questionnaire. RESULTS HRQoL was impaired in DM1 patients in both physical and mental domains (PCS was 41.8±23.5, MCS 47.0±24.3 and total SF-36 score 45.6±24.0). The most significant factors correlating with better SF-36 total score were younger age (β=-0.45, p<0.001), shorter duration of disease (β=-0.27, p=0.001), higher education (β=0.20, p=0.009), less severe muscular weakness (β=-0.52, p<0.001), normal swallowing (β=0.22, p=0.005), absence of fainting (β=0.31, p=0.002), absence of snoring (β=0.21, p=0.036), better acceptance of disease (β=-0.17, p=0.036), lower depressiveness (β=-0.46, p=0.001), lower fatigue (β=-0.32, p=0.001), absence of cataract (β=-0.21, p=0.034), absence of kyphosis (β=0.31, p=0.004) and absence of constipation (β=0.24, p=0.016). Second linear regression analysis revealed that depressed (β=-0.38, p<0.001) and elder patients (β=-0.27, p=0.007) and as well as those with poor acceptance of illness (β=-0.21, p=0.006) were in especially higher risk of having poor HRQoL (R(2)=0.68). CONCLUSION We identified different central, social, muscular, cardiorespiratory and other factors correlating with HRQoL. It is of great importance that most of these factors are amenable to treatment.

The predictive value of the presence of different antibodies and thymus pathology to the clinical outcome in patients with generalized myasthenia gravis

OBJECTIVES To analyze the predictive value of anti-acetylcholine receptor antibodies (anti-AChR Ab) and anti-muscle specific kinase antibodies (anti-MuSK Ab), as well as the thymus pathology to the clinical outcome in patients with generalized myasthenia gravis (MG). METHODS We analyzed 138 patients with generalized MG, who were thymectomized and assayed for anti-AChR Ab and anti-MuSK Ab. RESULTS Anti-AChR Ab were detected in 84% of patients, while anti-MuSK Ab were present in 36% of the AChR Ab negative patients. Severe forms of the disease were more frequent in MuSK Ab positive, compared to the AChR Ab positive and complete seronegative patients. Thymic lymphoid follicular hyperplasia (LFH) was present in 60%, thymoma in 23%, atrophic thymus in 9% and the normal thymus in 8% of patients. LFH was more frequent among women, while thymoma and atrophic thymus were more frequent in men. The younger patients mainly had LFH and normal thymus, while thymoma and atrophic thymus were more frequent in older patients. The mildest clinical presentation was present in patients with normal thymus, while severe forms of the disease were registered in the patients with thymoma. The AChR Ab positive patients had more often LFH and thymoma, while within MuSK Ab positive patients atrophic thymus was most common. CONCLUSION The best disease outcome was observed in patients with normal thymus or LFH with anti-AChR Ab or without both types of antibodies.

Leptin and the metabolic syndrome in patients with myotonic dystrophy type 1

Rakocevic Stojanovic V, Peric S, Lavrnic D, Popovic S, Ille T, Stevic Z, Basta I, Apostolski S. Leptin and the metabolic syndrome in patients with myotonic dystrophy type 1.
Acta Neurol Scand: 2010: 121: 94–98.
© 2009 The Authors Journal compilation

Dependent and paranoid personality patterns in myotonic dystrophy type 1

To analyze frequency and type of personality pattern in patients with myotonic dystrophy type 1 (DM1), to correlate these findings with clinical data, and to assess its possible influence on quality of life (QoL).

High frequency of DQB1*05 and absolute absence of DRB1*13 in muscle-specific tyrosine kinase positive myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disease but certain genetic factors predispose its development. Since susceptibility to different forms of MG is linked to a number of allelic variants, the aim of this study was to explore the human leukocyte antigen (HLA) profile of our patients with muscle‐specific tyrosine kinase (MuSK) MG.

Electrophysiological findings in patients with low density lipoprotein receptor related protein 4 positive myasthenia gravis.

The aim was to determine the electrophysiological profile of our cohort of low density lipoprotein receptor related protein 4 (LRP4) positive myasthenia gravis (MG) patients.

Rupture of the middle cerebral artery aneurysm as a presenting symptom of late-onset Pompe disease in an adult with a novel GAA gene mutation

Report of a patient with late onset Pompe disease caused by a novel GAA gene mutation who presented with subarachnoid hemorrhage due to rupture of the middle cerebral artery aneurysm.

Prospective measurement of quality of life in myotonic dystrophy type 1

Generic patient reported outcome measures have had varied success in tracking QoL in myotonic dystrophy type 1 (DM1).

5. Molecular genetics of myotonic disorders in Serbian patients

Purpose: To present genetic findings in myotonic dystrophy type 1 (DM1) and autosomal recessive axonal neuropathy with neuromyotonia (ARAN-NM) in Serbia. Methods: Various DNA analyses were used to characterize DMPK CTG repeats, which expansions cause DM1. Linkage analyses and next generation sequencing were used to identify gene associated with ARAN-NM. Results: In a cohort of 35 unrelated DM1 patients we found association between expansion-biased somatic instability of mutant alleles over time and progression of neuromuscular symptoms, negative linear correlation of age at onset and average expansion size in patients with progenitor allele less than 245 repeats, and lack of correlation between expansion size and cardiac involvement and polyneuropathy. The large sized normal alleles (>18 repeats), from which expanded alleles originate, had frequency of 8.72% in 235 healthy controls, indicating similar DM1 incidence in Serbia as in Europe (∼1/8000), which was subsequently confirmed by molecular epidemiological study. Loss-of-function mutations in the HINT1 gene were identified as a major cause of ARAN-NM and all Serbian patients were p.R37P homozygote with confirmed founder effect. Conclusion: The main cause of myotonic disorders is the DMPK CTG and a new gene associated with ARAN-NM is the HINT1 , indicating different genetic basis from other genetically characterized non-dystrofic myotonic syndromes.