Monika Nojszewska

The auditory system involvement in Parkinson disease: electrophysiological and neuropsychological correlations.

In the course of Parkinson disease (PD), apart from motor symptoms, presence of mental disturbances such as dementia and depression is common. The aims of this study were to assess the auditory system involvement in patients with PD using electrophysiological and neuropsychological tests and to correlate the cognitive impairment and the auditory evoked potentials tests results. The auditory and cognitive functions were studied in 53 patients with idiopathic PD, mean age 65.8 ± 9.1 years; mean disease duration 7.8 ± 5.0 years; mean motor disability score 2.5 ± 0.8 points in Hoehn-Yahr scale compared with a control group matched for age and sex. In patients and controls, cognitive functions were analyzed electrophysiologically using middle latency auditory evoked potentials (MLAEP) and long latency (event-related potentials, P300) auditory evoked potentials. Neuropsychological testing consisted of Wisconsin Card Sorting Test (WCST). According to WCST results, patients with PD were divided into 2 subgroups: patients with normal and abnormal WCST performance (WCST(−) and WCST(+) subgroups, respectively). Sixteen of 46 patients (34.8%) showed cognitive impairment when evaluated with WCST. Statistically significant differences in middle latency auditory evoked potentials and P300 results between WCST(−) and WCST(+) groups were found consisting of P300 abnormalities in 93.8% patients in WCST(+) and 57.7% in WCST(−) group. Middle latency auditory evoked potentials were abnormal in 71.4% and 63% patients in WCST(+) and WCST(−) group, respectively. P300 was absent significantly more often (P < 0.01) in the subgroup with cognitive impairment. The difference in middle latency auditory evoked potentials results between these subgroups was statistically insignificant. The auditory evoked potentials changes were more common among patients with abnormal WCST performance. According to our results, the auditory evoked potentials of different latencies are helpful in the assessment of cognitive changes accompanying PD.

Clinical and Functional Assessment of Dysautonomia and Its Correlation in Alzheimer’s Disease

The aims were to assess dysautonomia in Alzheimer’s Disease (AD), clinically and electrophysiologically, using sympathetic skin response (SSR) test and R-R interval variation (RRIV) test and to analyze the relationship between symptoms of dysautonomia and SSR/RRIV results. A tota of 54 patients with AD and 37 controls were evaluated using Autonomic Symptoms Questionnaire and SSR/RRIV test. Clinical dysautonomia was observed in 66% of patients (eg, orthostatic hypotension in 34.5%, constipation in 17.2%, urinary incontinence in 13.8%). The SSR test was abnormal in 26%, but the RRIV test was abnormal in 97.7% of cases; there was significant difference in RRIV test results between AD and controls (R mean 8.05% and 14.6%, respectively). In AD, clinical dysautonomia occurs at a various degree, and the abnormal SSR and RRIV test results were not always related to the presence of clinical dysautonomia; this observation points that the tests could be used as a useful tool in the assessment of subclinical dysautonomia.

Sex hormone patterns in women with multiple sclerosis as related to disease activity — a pilot study

BACKGROUND AND PURPOSE The influence of sex hormones on immune system activity in multiple sclerosis (MS) has been suggested by clinical evidence. The aim of the study was to ana-lyse the pattern of sex hormones in MS women and to correlate the hormone pattern abnormalities to the disease course as well as to the magnetic resonance imaging (MRI) results. MATERIAL AND METHODS We studied the serum level of the progesterone, β-oestradiol and prolactin in 46 women with clinical definite MS aged from 19 to 65; mean disease duration was 11.80 ± 9.86 years. The evaluation of the intensity of hormonal changes was done using a scoring system (0-3). On the brain MRI, the presence of brain atrophy, of hypothalamic demyelination as well as demyelination intensity (or degree) were analysed. The evaluation of the degree of demyelination and brain atrophy was done using a scoring system (0-4). RESULTS The main hormonal abnormalities consisted of decreased progesterone level, increased oestradiol level or both. The sex hormone pattern was abnormal in 56% of patients. Hypothalamic lesions were found on MRI in 53% of cases. The abnormal hormonal pattern correlated with intensity of MR changes (p < 0.05, Fishers exact test), but neither with presence of hypothalamic changes nor with disease parameters (Expanded Disability Status Scale, relapse rate, disease duration). CONCLUSIONS It is important to check the hormonal pattern in MS women because according to our results it may be related to the disease activity and probably affects the type of therapeutic intervention. This pilot study will be extended in a larger population.

Value of short exercise and short exercise with cooling tests in the diagnosis of myotonic dystrophies (DM1 AND DM2)

Introduction: Standard electromyography (EMG) is useful in the diagnosis of myotonic dystrophy type 1 (DM1) and type 2 (DM2), but it does not differentiate between them. The aim of this study was to estimate the utility of the short exercise test (SET) and short exercise test with cooling (SETC) in differentiating between DM1 and DM2. Methods: SET and SETC were performed in 32 patients with DM1 (mean age 35.8 ± 12.7 years) and 28 patients with DM2 (mean age 44.5 ± 12.5 years). Results: We observed a significant decline in compound motor action potential (CMAP) amplitude in DM1 with both SET and SETC immediately after effort. In DM2, there was no marked change in CMAP amplitude with either SET or SETC. Conclusions: SET and SETC may serve as useful tools for clinical differentiation between DM1 and DM2, and they may be used as a guide for molecular testing. Muscle Nerve 49: 277–283, 2014

Metagenomic Analysis of Cerebrospinal Fluid from Patients with Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of central nervous system of unknown etiology. However, some infectious agents have been suggested to play a significant role in its pathogenesis. Next-generation sequencing (NGS) and metagenomics can be employed to characterize microbiome of MS patients and to identify potential causative pathogens. In this study, 12 patients with idiopathic inflammatory demyelinating disorders (IIDD) of the central nervous system were studied: one patient had clinically isolated syndrome, one patient had recurrent optic neuritis, and ten patients had multiple sclerosis (MS). In addition, there was one patient with other non-inflammatory neurological disease. Cerebrospinal fluid (CSF) was sampled from all patients. RNA was extracted from CSF and subjected to a single-primer isothermal amplification followed by NGS and comprehensive data analysis. Altogether 441,608,474 reads were obtained and mapped using blastn. In a CSF sample from the patient with clinically isolated syndrome, 11 varicella-zoster virus reads were found. Other than that similar bacterial, fungal, parasitic, and protozoan reads were identified in all samples, indicating a common presence of contamination in metagenomics. In conclusion, we identified varicella zoster virus sequences in one out of the 12 patients with IIDD, which suggests that this virus could be occasionally related to the MS pathogenesis. A widespread bacterial contamination seems inherent to NGS and complicates the interpretation of results.

Peripheral nerve involvement in myotonic dystrophy type 2 – similar or different than in myotonic dystrophy type 1?

INTRODUCTION Multisystem manifestations of myotonic dystrophies type 1 (DM1) and 2 (DM2) are well known. Peripheral nerve involvement has been reported in DM1 but not in genetically confirmed DM2. The aim of our study was to assess peripheral nerve involvement in DM2 using nerve conduction studies and to compare these results with findings in DM1. METHODS We prospectively studied patients with genetically confirmed DM2 (n=30) and DM1 (n=32). All patients underwent detailed neurological examination and nerve conduction studies. RESULTS Abnormalities in electrophysiological studies were found in 26.67% of patients with DM2 and in 28.13% of patients with DM1 but the criteria of polyneuropathy were fulfilled in only 13.33% of patients with DM2 and 12.5% of patients with DM1. The polyneuropathy was subclinical, and no correlation was found between its presence and patient age or disease duration. CONCLUSIONS Peripheral nerves are quite frequently involved in DM2, but abnormalities meeting the criteria of polyneuropathy are rarely found. The incidence of peripheral nerve involvement is similar in both types of myotonic dystrophy.

Yeast model analysis of novel polymerase gamma variants found in patients with autosomal recessive mitochondrial disease

Replication of the mitochondrial genome depends on the single DNA polymerase (pol gamma). Mutations in the POLG gene, encoding the catalytic subunit of the human polymerase gamma, have been linked to a wide variety of mitochondrial disorders that show remarkable heterogeneity, with more than 200 sequence variants, often very rare, found in patients. The pathogenicity and dominance status of many such mutations remain, however, unclear. Remarkable structural and functional conservation of human POLG and its S. cerevisiae ortholog (Mip1p) led to the development of many successful yeast models, enabling to study the phenotype of putative pathogenic mutations. In a group of patients with suspicion of mitochondrial pathology, we identified five novel POLG sequence variants, four of which (p.Arg869Ter, p.Gln968Glu, p.Thr1053Argfs*6, and p.Val1106Ala), together with one previously known but uncharacterised variant (p.Arg309Cys), were amenable to modelling in yeast. Familial analysis indicated causal relationship of these variants with disease, consistent with autosomal recessive inheritance. To investigate the effect of these sequence changes on mtDNA replication, we obtained the corresponding yeast mip1 alleles (Arg265Cys, Arg672Ter, Arg770Glu, Thr809Ter, and Val863Ala, respectively) and tested their effect on mitochondrial genome stability and replication fidelity. For three of them (Arg265Cys, Arg672Ter, and Thr809Ter), we observed a strong, partially dominant phenotype of a complete loss of functional mtDNA, whereas the remaining two led to partial mtDNA depletion and significant increase in point mutation frequencies. These results show good correlation with the severity of symptoms observed in patients and allow to establish these variants as pathogenic mutations.

Does quantitative EMG differ myotonic dystrophy type 2 and type 1

Genetic testing is considered the only reliable diagnostic approach in myotonic dystrophy. However it has recently been reported that a considerable number of patients with genetically proven types of the disease have unusual phenotypic presentation. The aim of our study was to evaluate motor unit reorganization reflected by various electrophysiological abnormalities in myotonic dystrophies and to compare findings between type 1 (DM 1) and type 2 myotonic dystrophy (DM2). Quantitative electromyography (EMG) recordings in 63 patients (33 with DM1 and 30 with DM2) from the biceps brachii (BB), rectus femoris (RF), first dorsal interosseus (FDI), and tibialis anterior (TA) muscles were analyzed. Mean amplitude and size index (SI) of motor unit potentials recorded in TA and RF muscles, mean potential duration in TA, and mean SI and the number of outliers with amplitude above the normal range in BB were significantly increased in DM2 as compared to DM1. Myotonic discharges were recorded more frequently in DM1 than in DM2. EMG findings significantly differ between DM1 and DM2. The presence of high amplitude potentials in lower limb muscles in DM2 patients, atypical for myogenic muscle lesions, could be explained by muscle fiber hypertrophy observed in muscle biopsies.

“Cure” for multiple sclerosis (MS)—Evolving views of therapy goals in patients on different stages of the disease: A pilot study in a cohort of Polish MS patients

New aggressive treatments promise improvement of results in the treatment of multiple sclerosis (MS), however, with high risk of serious complications. In this study, we analyzed patients’ acceptance for risks connected with the MS treatment.

WITHDRAWN: 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).