Postępowanie terapeutyczne w miastenii

Miastenia jest autoimmunologiczną chorobą złącza nerwowo--mięśniowego, której przebieg kliniczny charakteryzuje dużazmienność objawów. Nasilenie objawów waha się od łagodnychobjawów ocznych, po zagrażający życiu stan, jakim jest przełommiasteniczny. Na miastenię choruje w Polsce około 6000 pacjentów,od wczesnego dzieciństwa do późnej starości. Prawidłowoleczona miastenia jest chorobą o dobrym rokowaniu dla ponad90% pacjentów. Decyzje terapeutyczne powinny uwzględniaćnasilenie objawów klinicznych, obecność patologii grasicy orazwiek i inne problemy zdrowotne pacjenta

Multisystem presentation of Late Onset Pompe Disease: what every consulting neurologist should know

Introduction. Pompe disease is a rare, autosomal recessive, lysosomal disorder caused by deficiency of alpha glucosidase (GAA). It leads to the accumulation of glycogen in body tissues, with severe myopathy and cardiomegaly as a hallmark of the classic infantile form. Non-classical, or late onset, Pompe disease (LOPD) manifests after 12 months of age or in adulthood. Material and methods. The clinical heterogeneity of LOPD causes delay in diagnosis and pharmacological treatment. In the Polish population, it is still underdiagnosed, and the time from onset to diagnosis remains a cause for concern. Clinical implications. Although typically patients present with proximal muscle weakness, high CK or early respiratory insufficiency, they can also suffer from multiple symptoms from other organs. Patients may present with arrhythmias, vascular abnormalities including aneurysms or dilative arteriopathy, gastric or urinary symptoms, or musculoskeletal pathologies. Results. A high index of suspicion among neurologists consulting internal medicine wards would aid early diagnosis of LOPD, while a multidisciplinary approach with the involvement of other specialists can reduce the risk of complications and improve the prognosis for LOPD patients. Patients who manifest with musculoskeletal and respiratory symptoms are prone to be diagnosed sooner than individuals with non-muscular symptoms, and therefore it is important to raise awareness of other manifestations of this disease

Dopa-responsive dystonia or early-onset Parkinson disease – Genotype–phenotype correlation

Objective Dopa-responsive dystonia (DRD) is a rare form of hereditary movement disorder with onset in childhood, characterized by gait difficulties due to postural dystonia with marked improvement after low doses of levodopa. Mutations in the GCH1 gene are the most common cause of DRD, however, in some cases when the disease is associated with parkinsonism mutations in the PARK2 gene may be identified. The aim of this study was to analyze and compare genotype–phenotype correlation. Material/participants Four families with inter- and intrafamilial variability of progressive gait dysfunction due to lower limb dystonia occurring in childhood or adolescence were included in the analysis. Methods General and neurological examination was performed for all affected family members and asymptomatic mutation carriers. The molecular analysis encompassed GCH1 and PARK2 genes. Results All probands were clinically diagnosed with DRD. The molecular analysis revealed, however, that the dopa-responsive dystonia phenotype was caused by a mutation in the GCH1 gene in three families and in the PARK2 gene in one family. Obtained results allowed to establish the final diagnosis for all families as DYT5a or early-onset Parkinson disease (EO-PD). Conclusions Reported cases confirm that the DRD phenotype may have heterogeneous genetic background and may be caused by point mutations or rearrangements in the GCH1 gene as well as in the PARK2 gene. Differential diagnosis and genetic tests covering the analysis of genes causative for DRD and EO-PD should be obligatory in both disorders diagnostics as DRD, mainly adolescent onset dystonia, may be associated with parkinsonism

Andersen-Tawil syndrome: report of 3 novel mutations and high risk of symptomatic cardiac involvement.

IntroductionAndersen-Tawil syndrome (ATS) is a potassium channelopathy affecting cardiac and skeletal muscle. Periodic paralysis is a presenting symptom in some patients, whereas, in others, symptomatic arrhythmias or prolongation of QT in echocardiographic recordings will lead to diagnosis of ATS. Striking intrafamilial variability of expression of KCNJ2 mutations and rarity of the syndrome may lead to misdiagnosis.MethodsWe report 15 patients from 8 Polish families with ATS, including 3 with novel KCNJ2 mutations.ResultsAll patients had dysmorphic features; periodic paralysis affected males more frequently than females (80% vs. 20%), and most attacks were normokalemic. Two patients (with T75M and T309I mutations) had aborted sudden cardiac death. An implantable cardioverter-defibrillator was utilized in 40% of cases.ConclusionsKCNJ2 mutations cause a variable phenotype, with dysmorphic features seen in all patients studied, a high penetrance of periodic paralysis in males and ventricular arrhythmia with a risk of sudden cardiac death

Elektromiografia pojedynczego włókna u chorych na klasterowy ból głowy

Background and purpose Mutations of CACNA1A, which encodes a neuronal P/Q Ca2+ channel, are present in patients with familial hemiplegic migraine, and possibly in other types of migraine as well. This calcium channel is also involved in neuromuscular transmission. In our previous study we confirmed that the single-fibre electromyography (SFEMG) method can demonstrate a neuromuscular transmission deficit in migraine with aura. The aim of our present study was to estimate the neurotransmitter dysfunction in cluster headache and to compare the results between patients with cluster headache and those with migraine with aura. Material and methods We selected 6 patients with cluster headache and 6 patients with migraine with typical aura. SFEMG of the voluntarily activated extensor digitorum communis muscle was performed. Results The SFEMG results were in the normal range in the cluster headache group and in the healthy controls. Slight neuromuscular transmission disturbances were present in patients with migraine with aura. Conclusions The abnormal neuromuscular transmission detectable by SFEMG may reflect a genetically determined dysfunction of the P/Q Ca2+ channels in a group of migraineurs with aura. Conversely, absence of neuromuscular abnormalities in cluster headache patients could be explained by different aetiology not resulting in channelopathy. Single-fibre electromyography could be a helpful tool in clinically questionable cases in differentiating between cluster headache and migraine with aura.Wstęp i cel pracy U chorych na migrenę rodzinną połowiczoporaźną, a także z innymi postaciami migreny z aurą stwierdzono mutację w genie CACNA1A dla kanału wapniowego P/Q. Z uszkodzeniem tego kanału wapniowego związane są zaburzenia przewodzenia nerwowo-mięśniowego. We wcześniejszej pracy autorzy opisali badanie za pomocą elektromiografii pojedynczego włókna (SFEMG) zaburzeń przewodzenia nerwowo-mięśniowego u osób z migreną, stwierdzając ich obecność u części pacjentów z migreną z aurą. Celem niniejszego badania jest odpowiedź na pytanie, czy u pacjentów z klasterowym bólem głowy występują podobne zaburzenia, i porównanie wyników otrzymanych u osób z klasterowym bólem głowy z wynikami pacjentów z migreną z aurą. Materiał i metody Elektromiografię pojedynczego włókna wykonaną z mięśnia zginacza długiego palców przeprowadzono u 6 pacjentów z klasterowym bólem głowy i zestawiono ją z wynikami 6 chorych na migrenę z aurą. Wyniki Wyniki SFEMG w grupie chorych na klasterowy ból głowy mieściły się w prawidłowych granicach, podobnie jak w grupie kontrolnej zdrowych osób. W grupie pacjentów z migreną z aurą stwierdzono łagodne zaburzenia transmisji nerwowo-mięśniowej. Wnioski Nieprawidłowe wyniki SFEMG mogą wskazywać na genetycznie uwarunkowaną dysfunkcję kanału wapniowego w grupie chorych na migrenę z aurą w przeciwieństwie do chorych na klasterowy ból głowy, u których najprawdopodobniej etiologia choroby ma inne podłoże. Badanie SFEMG może być badaniem pomocniczym w różnicowaniu niepewnych przypadków klasterowego bólu głowy imitujących migrenowy ból głowy

MLPA based detection of mutations in the dystrophin gene of 180 Polish families with Duchenne/Becker muscular dystrophy

Duchenne/Becker muscular dystrophy (DMD/BMD) is a recessive, X-linked disorder caused by a mutation in the dystrophin gene. Deletions account for approximately 60–65% of mutations, duplications for 5–10%. The remaining cases are mainly point mutations. According to Monaco theory clinical form of the disease depends on maintaining or disrupting the reading frame. The purpose of the study was to determine frequency and location of deletions and duplications in the dystrophin gene, to determine the compliance between maintaining/disrupting the reading frame and clinical form of the disease and to check the effectiveness of MLPA (multiplex ligation-dependent probe amplification) in the detection of these mutations in hemizygous patients and heterozygous female carriers. The material is composed of combined results of molecular diagnosis carried out in years 2009–2012 in 180 unrelated patients referred with the diagnosis of DMD/BMD tested by use of MLPA. We identified 110 deletions, 22 duplication (in one patient two different duplications were detected) and 2 point mutations. Deletions involved mainly exons 45–54 and 3–21, whereas most duplications involved exons 3–18. The compliance with Monaco theory was 95% for deletions and 76% for duplications. Most of mutations in the dystrophin gene were localized in the hot spots – different for deletions and duplications. MLPA enabled their quick identification, exact localization and determination whether or not they maintained or disrupted the reading frame. MLPA was also effective in detection of deletions and duplications in female carriers

Serum interleukin 15 levels in patients with seropositive myasthenia gravis do not correlate with disease severity

Aim To assess interleukin 15 (IL-15) serum levels in patients with seropositive myasthenia gravis (MG); searching for potential relationship between IL-15 levels and clinical features such as gender, age at onset, clinical presentation or treatment received. Background IL-15 plays pivotal role in T-cell dependent autoimmunity. Increased IL-15 serum levels have been reported in several autoimmune diseases including MG patients from Japan. Patients and methods Sera of 42 seropositive MG patients (66.7% women), mean age 50.6±23.7 years) have been tested by ELISA for IL-15 levels. Results There were no statistically significant differences between IL-15 serum levels in MG patients in comparison with controls as well as between subgroups of MG patients (early vs. late onset and thymoma MG). Mean/median IL-15 serum levels were similar in MG patients treated with corticosteroids (CS) and CS naïve. Outliers (very high values) were seen only in untreated generalized MG patients. Conclusions Serum interleukin 15 levels in patients with seropositive myasthenia gravis do not correlate with disease severity

Evidence for a relatively high proportion of DM2 mutations in a large group of Polish patients

Introduction: Myotonic dystrophies (DMs) type 1 (DM1) and type 2 (DM2) are autosomal dominant, multisystem disorders, considered the most common dystrophies in adults. DM1 and DM2 are caused by dynamic mutations in the DMPK and CNBP genes, respectively. Methods: Molecular analyses were performed by PCR and the modified RP-PCR in patients, in their at-risk relatives and prenatal cases. Results: The analysis of Polish controls revealed the range of 5-31 CTG repeats for DM1 and 110-228 bp alleles for DM2. Among 318 confirmed probands - 196 (62%) were DM1 and 122 (38%) – DM2. Within DM1families, 10 subjects carried a low expanded CTG tract (< 100 repeats), which resulted in a full mutation in subsequent generations. Two related individuals had unstable alleles–188 bp and 196 bp without common interruptions. Conclusion: The relative frequencies of DM1/DM2 among Polish patients were 68% and 32%, respectively, with a relatively high proportion of DM2 mutations (1.6:1)