WITHDRAWN: Evidence for a relatively high proportion of DM2 mutations in a large group of Polish patients.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, 10.1016/j.pjnns.2018.02.008. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

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).

The N-terminal pro-brain natriuretic peptide as a marker of mitoxantrone-induced cardiotoxicity in multiple sclerosis patients.

BACKGROUND AND PURPOSE: Mitoxantrone (MTX) has been shown to reduce progression of disability and number of clinical exacerbations in patients with progressive multiple sclerosis (MS). Prolonged administration of MTX, however, is limited by the risk of cardiotoxicity. Cardiac monitoring in MTX-treated patients includes usually measurement of left ventricular ejection fraction (LVEF) by means of echocardiography. The N-terminal pro-brain natriuretic peptide (NT-proBNP) represents a novel diagnostic tool in the assessment of heart failure. This study was aimed to evaluate the usefulness of NT-proBNP for early detection of MTX-induced cardiotoxicity in MS patients. MATERIALS AND METHODS: We measured the NT-proBNP plasma levels in 45 MS patients who completed 24-month MTX therapy and in 37 MS patients of control group. RESULTS: The median NT-proBNP plasma value was 15.12pg/mL. In 12 MTX-treated patients (27%), NT-proBNP plasma values were elevated, though this subgroup of patients neither clinical showed evidence of myocardial damage nor had the LVEF value <50%. In five patients with normal NT-proBNP, we observed LVEF decline >10%. We did not observe correlations between the NT-proBNP levels and patient age, MS duration, relapses index, Extended Disability Status Scale (EDSS), MTX single dose and the total cumulative dose of MTX. In 8 patients (22%) from control group, NT-proBNP plasma levels were also elevated. CONCLUSIONS: The results of our study confirm that MTX therapy is safe for carefully selected and closely monitored MS patients. We believe that serial evaluation of NT-proBNP levels (before, during and after MTX therapy) can identify MS patients at high risk for MTX-induced cardiotoxicity.

Mitochondrial encephalomyopathy: towards diagnosis. A case report.

Mitochondrial diseases may cause a wide range of central and peripheral nervous system disorders, as well as muscle disorders. The diagnostic workup routinely includes electrophysiological, morphological, neuroimaging and genetic studies. In some cases, the diagnosis may be ascertained only when mitochondrial DNA (mtDNA) examination in the muscle is performed. We report on a case of a 24-year-old woman, with a 7-year history of slowly progressive cerebellar syndrome and bilateral ptosis. Mitochondrial encephalomyopathy was suspected, based on the clinical picture and results of examinations, but the typical red ragged fibers were not found in the muscle biopsy. The results of molecular analysis of mtDNA showed a mtDNA deletion in the muscle and, on a level detectable only with polymerase chain reaction method, in blood leukocytes. This case emphasizes the important role of mtDNA studies in muscle in nonspecific multisystem mitochondrial disorders, even without clinical muscle involvement.

Recurrent K3E mutation in Cu/Zn superoxide dismutase gene associated with amyotrophic lateral sclerosis.

Cu/Zn superoxide dismutase (SOD1) gene mutations are the most frequently reported genetic causes of amyotrophic lateral sclerosis (ALS). The objective of the study was to describe a clinical phenotype and haplotype background of Polish and Japanese ALS patients harbouring the K3E SOD1 mutation. The K3E mutation was identified by direct sequencing, high resolution melting analysis or high-throughput microarray-based resequencing system. Microsatellite polymorphic markers flanking SOD1 were genotyped in members of six kindreds and two SALS patients. Results demonstrated that the K3E mutation was responsible for classic ALS. The median age of onset was 54 years. The clinical phenotype did not substantially differ between SALS and FALS cases of either ethnic origin, with some intrafamiliar variabilities. There was a limb onset in 92% of patients. In patients with bulbar syndrome, dysphagia predominated over dysarthria. Respiratory insufficiency was found in 61.1% of patients (19-84 months after the first symptoms onset). Median survival was 101 months with age of death ranging from 45 to 77 years. K3E was the most frequent SOD1 mutation among Polish FALS patients. It originated independently, on different haplotype background in the Polish and Japanese populations. In conclusion, recurrent K3E mutation results in a relatively slowly progressing limb onset ALS with classic phenotype.

Analysis of PITX3 gene in patients with multisystem atrophy, progressive supranuclear palsy and corticobasal degeneration.

Interactions of transcriptions factors Nurr1, Pitx3, and EN1 are involved in the maturation and survival of adult midbrain dopaminergic neurons during a lifetime. The aim of the study was to evaluate the presence of mutations and single nucleotide polymorphisms in PITX3 gene in clinically diagnosed multisystem atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). In the group of 77 patients with MSA, 44 with PSP, and 6 with CBD, no pathogenic mutations were identified.

A case report of 'variant' biochemical phenotype of Niemann-Pick C disease and a discussion of therapeutic options.

Niemann-Pick disease type C is a rare hereditary disorder caused by mutation-disrupted metabolism of cholesterol and low-density lipoprotein (LDL). In most patients, symptoms begin in childhood with severe clinical progression. We present a patient with heterozygote mutations 3001A>G and 3019C>G with late onset of the disease and positive response to treatment with miglustat. Behaviour and educational problems in childhood were probably related to the disease diagnosed later.

A single-fibre electromyography study of neuromuscular transmission in patients with cluster headache.

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.

[Psychotic symptoms and cognitive impairment in neurosarcoidosis. Case report and review of literature]. / Objawy psychotyczne i zaburzenia poznawcze w przebiegu neurosarkoidozy--opis przypadku i przeglad pismiennictwa.

Clinical involvement of the nervous system occurs in about 5% of patients with sarcoidosis. We describe a fatal case of a young patient with neurosarcoidosis with a relatively rare psychotic syndrome in the course of neurosarcoidosis, presenting itself as a depressive syndrome with delusions. The neurological manifestations consisted of cerebellar symptoms, peripheral neuropathy and general epileptic seizures. Cerebrospinal fluid examination, serum angiotensin-converting enzyme level, magnetic resonance imaging, chest radiography, gallium isotope scanning and other tests were used as diagnostic tools. He was treated with steroids, methotrexate and neuroleptics ineffectively. The patient died because of complications related to neurosarcoidosis. The diagnosis of neurosarcoidosis was confirmed by autopsy.

Recurrent G41S mutation in Cu/Zn superoxide dismutase gene (SOD1) causing familial amyotrophic lateral sclerosis in a large Polish family.

Mutations in the superoxide dismutase-1 (SOD1) gene have been found in 12-23% of patients with a diagnosis of ALS. Here we describe a large ALS Polish family with a branch in France, carrying a G41S mutation in the SOD1, and characterized by an early onset of the disease and extremely short survival time. The mutation has been initially detected in Italian ALS families with common founder effect. However, in the Polish population the G41S mutation most probably originated from an independent mutation event, as indicated by haplotype analysis. Collected data support the hypothesis that a SOD1 mutation is not the sole factor determining the clinical ALS phenotype.

New therapeutic targets for amyotrophic lateral sclerosis.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is one of the most devastating neurological disorders, affecting approximately half a million people worldwide. Currently there is no cure or prevention for ALS. Although ALS is a rare condition, it places a tremendous socioeconomic burden on patients, family members, caregivers and health systems. AREAS COVERED: The review examines the mechanisms that may contribute to motor neuron degeneration in ALS, among which oxidative damage, glutatamate excitoxicity, mitochondrial dysfunction, impaired axonal transport, apoptotic cell death, growth factor deficiency, glial cell pathology and abnormal RNA metabolism are potential targets for ALS treatment. The article provides an overview of clinical trials performed to date in attempts to treat ALS with regard to molecular mechanisms and pathways they act on. It also discusses new trials based on recently developed molecular biology techniques. EXPERT OPINION: Despite significant effectiveness of several potential therapeutics observed in preclinical trials, the results were not translatable to patients with ALS. The development of effective treatments of ALS strictly depends on understanding the primary cause of the disease. This goal will only be achieved when we identify the trigger point for motor neuron death in ALS.

Familial partial lipodystrophy associated with the heterozygous LMNA mutation 1445G>A (Arg482Gln) in a Polish family.

Familial partial lipodystrophy (FPLD) belongs to the family of laminopathies - disorders associated with mutation in the lamin A/C gene (LMNA). FPLD is characterized by loss of subcutaneous adipose tissue from the limbs, trunk and buttocks, with its concomitant accumulation on the face, neck and intra-abdominal region, and by metabolic disorders. We present the first Polish family with FPLD confirmed genetically. A 34-year-old woman admitted with myalgia and cushingoid appearance was found to have a round face with double chin, neck bump, and loss of fat on extremities. Diagnostic tests revealed impaired glucose tolerance and increased levels of liver enzymes, and ultrasonography revealed hepatic steatosis. Her 9-year-old daughter presented a similar phenotype, but no fat loss. A genetic test revealed the presence of a heterozygous LMNA gene mutation: c.1445G>A, consistent with the "hot spot" for FPLD. Treatment with metformin to improve insulin resistance and address the diabetes proved successful.

The analysis of selected neurotransmitter concentrations in serum of patients with Tourette syndrome.

BACKGROUND AND PURPOSE: Metabolic disturbances of excitatory and inhibitory neurotransmitters are implicated in pathogenesis of Tourette syndrome (TS). The aim of the study was to measure serum concentrations of glutamic acid, g-aminobutyric acid (GABA) and glycine in TS patients and evaluate any correlation between neurotransmitter levels and age at onset, actual age, gender, tic severity, duration of the disease and concomitant psychiatric disorders. MATERIAL AND METHODS: Sixty-seven TS patients, aged 16-59, and 57 healthy controls, aged 19-37, were enrolled in the study. Information regarding medical history and physical investigation was collected using a short questionnaire. Sixty-seven percent of patients were medication-free at the time of examination and the rest had withheld treatment for 24 hours before. Blood samples were taken after a 12-hour fasting period. HPLC technique was used. RESULTS: The TS group had higher glutamic acid and lower GABA levels. Glycine concentrations were comparable. No differences regarding neurotransmitter concentrations between treated and non-treated patients were found. Patients with concomitant obsessive-compulsive disorder and severe tics had higher glutamate levels. Glutamate concentrations correlated positively with the number of comorbid psychiatric disorders and GABA concentrations correlated negatively with the number of behavioural problems in patients with comorbidities. There was no correlation between analysed neurochemicals and age, gender, age at onset or disease duration. CONCLUSIONS: Imbalance between excitatory and inhibitory systems in the brains of TS patients may be reflected by glutamate and GABA serum level changes. Glutamate and GABA may be biomarkers of the disease and high concentration of glutamate may indicate more severe course of TS.

Polymorphisms in the factor VII gene and ischemic stroke in young adults.

Polymorphic configurations of the coagulation factor VII gene (F7) are associated with plasma levels of FVII antigen (FVII:Ag) and FVII coagulant activity (FVII:C). Our aim was to determine whether F7 polymorphisms influence risk of ischemic stroke in young adults. One hundred and fifty survivors of ischemic stroke before the age of 45 and an equal number of age and sex-matched controls were genotyped for five F7 polymorphisms: the -A670C transversion, -323 decanucleotide insertion (P + 10), the number (which varies between five and eight) of a 37 base pair repeat polymorphisms in intron 7 (IVS7), amino acid substitution R353Q, and +154AA insertion. 353Q, P + 10 and +154AA were demonstrated to associate with significantly decreased plasma FVII:Ag, whereas -670C and IVS7 seven or higher were associated with a tendency towards increased plasma FVII:Ag. The former three polymorphisms were significantly more common in control individuals than in patients, whereas the latter two were significantly more common in patients than in control individuals. The multiple logistic regression analysis revealed that two F7 polymorphisms, -670C and IVS7 seven or higher, are independent risk factors for ischemic stroke in young adult patients.