Excessive daytime sleepiness in a patient with coexisting myotonic dystrophy type 1, myasthenia gravis and Graves' disease.

A 41-year-old female with history of Graves' disease, bilateral cataract, paroxysmal atrial fibrillation was admitted because of muscle weakness, daytime sleepiness, fatigability, drowsiness, bilateral eyelid ptosis, descending of head and lower jaw. On neurological examination the patient was presented with muscle weakness, muscle atrophy (in face and sternocleidomastoid muscles), features of myotonia and apocamnosis (orbicular muscles). Electromyography revealed myopathic changes, myotonic and pseudomyotonic discharges, positive repetitive nerve stimulation test in proximal muscles. Myotonic dystrophy (MD) diagnosis was confirmed by genetic testing and myasthenia gravis (MG) by a positive titer of cholinergic receptor autoantibodies. In the CSF concentration of hypocretin was significantly decreased.

Relapsing-Remitting Severe Bickerstaff's Brainstem Encephalitis - Case Report and Literature Review.

BACKGROUND: Bickerstaff's brainstem encephalitis (BBE) is a very rare disease of the central nervous system. Aetiology of the disease is auto-immunological. However, it is not entirely understood. Clinically BBE manifests in progressive ophthalmoplegia, ataxia and consciousness disturbances. Clinical symptoms are usually preceded by an unidentified infection of the upper respiratory tract. Usually, the disease has one phase, but individual relapses have also been described. Despite quite severe clinical symptoms, the prognosis is usually good. CASE REPORT: The article presents a case of a patient with relapsing-remitting severe BBE. The case is presented due to the relapsing-remitting clinical course of the disease that resulted in patient's death, rarely described in the literature. We also present the results of subsequent MR scans in the course of the disease, so far described only in individual reports. It is also the first report in the world's literature presenting the results of series of MR spectroscopy (MRS) examinations in the course of BBE. CONCLUSIONS: MR examination is an important component in BBE diagnostics, allowing to differentiate atypical cases and place them under special supervision due to the possibility of the severe clinical course. MR also facilitates differentiation between Miller-Fisher Syndrome (MFS) and BBE in cases of diagnostic doubts. Adding MRS and MRI to the protocol allows us to define the nature of morphological changes more accurately in patients with suspected or diagnosed BBE.

Increased levels of sphingosine-1-phosphate in cerebrospinal fluid of patients diagnosed with tick-borne encephalitis.

BACKGROUND: Tick-borne encephalitis (TBE) is a serious acute central nervous system infection that can result in death or long-term neurological dysfunctions. We hypothesize that changes in sphingosine-1-phosphate (S1P) concentration occur during TBE development. METHODS: S1P and interleukin-6 (IL-6) concentrations in blood plasma and cerebrospinal fluid (CSF) were measured using HPLC and ELISA, respectively. The effects of S1P on cytoskeletal structure and IL-6 production were assessed using rat astrocyte primary cultures with and without addition of plasma gelsolin and the S1P receptor antagonist fingolimod phosphate (FTY720P). RESULTS: We report that acute inflammation due to TBE virus infection is associated with elevated levels of S1P and IL-6 in the CSF of infected patients. This elevated concentration is observed even at the earliest neurologic stage of disease, and may be controlled by glucocorticosteroid anti-inflammatory treatment, administered to patients unresponsive to antipyretic drugs and who suffer from a fever above 39°C. In vitro, treatment of confluent rat astrocyte monolayers with a high concentration of S1P (5 µM) results in cytoskeletal actin remodeling that can be prevented by the addition of recombinant plasma gelsolin, FTY720P, or their combination. Additionally, gelsolin and FTY720P significantly decreased S1P-induced release of IL-6. CONCLUSIONS: TBE is associated with increased concentration of S1P and IL-6 in CSF, and this increase might promote development of inflammation. The consequences of increased extracellular S1P can be modulated by gelsolin and FTY720P. Therefore, blocking the inflammatory response at sites of infection by agents modulating S1P pathways might aid in developing new strategies for TBE treatment.

Does interferon beta therapy affect survival of multiple sclerosis patients?

Multiple sclerosis (SM) is a chronic inflammatory and degenerative disease of the central nervous system. Its etiology has not been fully elucidated. For approximately 20 years, drugs have been used, successfully modifying the natural course of relapsing-remitting SM. One of them is interferon beta. Research outcomes of 16- and 21-year-retrospective follow-up of patients who participated in the pivotal interferon beta-1b trial were reported in 2010 and 2012, respectively. After 21 years, mortality rate among patients treated in the first 5 years with interferon beta-1b at a dose of 250µg was significantly lower, irrespective of the cause, as compared to the placebo-controlled group. Interferon beta-1b administered during the first 5 years of the study decreased the risk of death by 46.8% as compared to the placebo patients. Moreover, the studies also confirmed safety of long-term interferon beta-1b therapy. However, not much is known about the effect of interferon beta-1a on patients' survival - the available data are presented in the article.

CSF markers in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS, 'Lou Gehrig disease') is the most common, progressive, neurodegenerative, motor neuron disease, causing damage to upper and lower motor neurons, leading to paralysis and death within 3-5 years. Majority of ALS cases are sporadic ALS (SALS) and only 5-10 % of cases are familial ALS (FALS). Pathogenesis of ALS is complicated and still unclear, including genetic, glutamate excitotoxicity, oxidative stress, mitochondrial dysfunction, neurofilament accumulation, impaired trophic support, altered glial function, viral infection, immune imbalance and impairment of the blood-brain, blood-spinal cord and blood-cerebrospinal fluid barriers (BBB/BSCB/BCSFB). The CSF analysis is still one of the basic laboratory tools and might reflect pathophysiological alterations in the course of the disease and could provide an insight into disease pathomechanisms. The most important aim of its analysis is evaluation of blood-CSF barrier, which is altered in 46 % of ALS patients. The CSF biomarkers may give insight into ALS pathophysiology and may be useful for early, presymptomatic diagnosis, therapeutic monitoring and the development of new therapeutic strategies. This review summarizes the general concepts of biomarkers in CSF of ALS patients and their potential usefulness in further research.

Increased concentration of the CSF Tau protein and its phosphorylated form in the late juvenile metachromatic leukodystrophy form: a case report.

Metachromatic leukodystrophy (MLD) is an autosomal recessive, lysosomal storage disease due to deficiency or absence of arylsulfatase A enzyme (ASA) with sulfatide accumulation in the central and peripheral nervous system, kidneys, and gallbladder, leading to many dysfunctions. One of the clinical forms of the disease is a late juvenile MLD. To our best knowledge, this is the first report describing increased Tau/pTau and normal Aß1-42 concentrations in the CSF of the late juvenile MLD patient.

Depletion of plasma gelsolin in patients with tick-borne encephalitis and Lyme neuroborreliosis.

BACKGROUND/AIMS: Cell damage during the course of inflammation results in cytoplasmic actin release, which if not eliminated by the extracellular actin scavenger system, composed of gelsolin and vitamin D binding protein, can cause dysfunction of hemostasis and toxicity towards surrounding cells. In this study, we test the hypothesis that an inflammatory reaction induced by central nervous system infections such as tick-borne encephalitis (TBE) or Lyme neuroborreliosis (LNB) will result in plasma gelsolin concentration changes in the blood and cerebrospinal fluid (CSF). METHODS: Quantitative Western blot was used to determine gelsolin levels in 58 samples, which include: 29 patients without infection (diagnosed with conditions such as idiopathic cephalalgia, idiopathic Bell's facial nerve palsy and ischialgia due to discopathy in which standard CSF diagnostic tests show no abnormalities), 12 patients diagnosed with TBE, and 17 patients diagnosed with LNB sub forma meningitis. RESULTS AND CONCLUSION: The gelsolin concentration in the blood of patients with TBE (163.2 ± 80.8 µg/ml) and LNB (113.6 ± 56.8 µg/ml) was significantly lower (p < 0.05 and p < 0.001, respectively) compared to the control group (226.3 ± 100.7 µg/ml). Furthermore, there was no statistically significant difference between the CSF gelsolin concentration in patients with TBE (3.9 ± 3.3 µg/ml), LNB (2.9 ± 1.2 µg/ml) and the control group (3.7 ± 3.3 µg/ml). An observed decrease in gelsolin concentration in the blood of TBE and LNB patients supports previous findings indicating the involvement of gelsolin in the pathophysiology of an inflammatory response. Therefore, evaluation of blood gelsolin concentration and administration of recombinant plasma gelsolin might provide a new tool to develop diagnostic and therapeutic strategies for TBE and LNB.

The natural history of Möbius syndrome in a 32-year-old man.

Möbius syndrome (OMIM#157900) is an extremely rare congenital entity involving bilateral or unilateral palsy of the facial nerve, usually with dysfunction of other cranial nerves (second, third, fifth, sixth, ninth, tenth and twelfth). It was estimated that Möbius syndrome occurs in 1 of 50 000 live births. The aetiology and the pathogenesis of the syndrome remain unknown. The majority of published cases were sporadic. We report on the natural history of a 32-year-old man with de novo Möbius syndrome. The diagnosis was established at the age of 9 months due to partial bilateral facial and abducent nerve palsy. Additionally, the patient demonstrated failure to thrive during infancy and childhood, many dysmorphic features, lower limb anomalies, and hypogonadism in adulthood, but his intelligence was in the normal range. The low quality of life of the patient with Möbius syndrome is emphasized.

[Neurological and emotional profile of carpal tunnel syndrome patients]. / Profil neurologiczny i emocjonalny pacjentów z zespolem ciesni nadgarstka.

UNLABELLED: Our aim was to define the type and frequency of symptoms in patients with neurophysiologically confirmed carpal tunnel syndrome (CTS). We also assessed the incidence of anxiety and depression in CTS and control group. MATERIAL AND METHODS: After carrying out neurophysiologic examination 87 patients were diagnosed with CTS, 50 patients without confirmed CTS diagnosis served as a control group. All patients underwent thorough neurological examination and completed a questionnaire about severity and localization of their symptoms. State-Trait Anxiety Inventory (STAI), Self Rating Anxiety Scale (SAS) and Beck's depression inventory were also filled in by the patients. RESULTS: In CTS patients major symptoms were: paresthesias and nocturnal aggravation of symptoms; pain was predominant sign in control group. There were no statistically significant differences between CTS patients and control group concerning emotional (depression and anxiety) disturbances. In CTS patients depression and anxiety were correlated with: diminished sensation, hand weakness, thenar atrophy and hand pain. CONCLUSIONS: Emotional disturbances appear to be linked with objective CTS symptoms and with pain and they increase with carpal tunnel syndrome intensity.

Plasma gelsolin modulates cellular response to sphingosine 1-phosphate.

Hypogelsolinemia is observed in patients with different states of acute or chronic inflammation such as sepsis, rheumatoid arthritis, and multiple sclerosis. In animal models of sepsis, repletion of plasma gelsolin reduces septic mortality. However, the functions of extracellular gelsolin and the mechanisms leading to its protective nature are poorly understood. Potential mechanisms involve gelsolin's extracellular actin scavenging function or its ability to bind bioactive lipids or proinflammatory mediators, which would limit inflammatory responses and prevent tissue damage. Here we report that human plasma gelsolin binds to sphingosine 1-phosphate (S1P), a pleiotropic cellular agonist involved in various immune responses, and to its synthetic structural analog FTY720P (Gilenya). The fluorescence intensity of a rhodamine B-labeled phosphatidylinositol 4,5-bisphosphate binding peptide derived from gelsolin and the optical density of recombinant human plasma gelsolin (rhpGSN) were found to decrease after the addition of S1P or FTY720P. Gelsolin's ability to depolymerize F-actin also decreased progressively with increasing addition of S1P. Transient increases in phosphorylation of extracellular signal-regulated kinase in bovine aortic endothelial cells (BAECs) after S1P treatment were inhibited by rhpGSN. The ability of S1P to increase F-actin content and the elastic modulus of primary astrocytes and BAECs was also prevented by rhpGSN. Evaluation of S1P and gelsolin levels in cerebrospinal fluid reveals a low concentration of gelsolin and a high concentration of S1P in samples obtained from patients suffering from lymphatic meningitis. These findings suggest that gelsolin-mediated regulation of S1P bioactivity may be important to maintain immunomodulatory balance at inflammatory sites.

Hypogelsolinemia, a disorder of the extracellular actin scavenger system, in patients with multiple sclerosis.

BACKGROUND: Extracellular gelsolin (GSN) and GC-globulin/Vitamin D-binding protein (DBP) appear to play an important role in clearing the actin from extracellular fluids and in modulating cellular responses to anionic bioactive lipids. In this study we hypothesized that cellular actin release and/or increase in bioactive lipids associated with multiple sclerosis (MS) development will translate into alteration of the actin scavenger system protein concentrations in blood and cerebrospinal fluid (CSF) of patients with MS. METHODS: We measured GSN and DBP concentrations in blood and CSF obtained from patients diagnosed with MS (n = 56) in comparison to a control group (n = 20) that includes patients diagnosed with conditions such as idiopathic cephalgia (n = 11), idiopathic (Bell's) facial nerve palsy (n = 7) and ischialgia due to discopathy (n = 2). GSN and DBP levels were measured by Western blot and ELISA, respectively. RESULTS: We found that the GSN concentration in the blood of the MS group (115 ± 78 µg/ml) was significantly lower (p < 0.001) compared to the control group (244 ± 96 µg/ml). In contrast, there was no statistically significant difference between blood DBP concentrations in patients with MS (310 ± 68 µg/ml) and the control group (314 ± 82 µg/ml). GSN and DBP concentrations in CSF also did not significantly differ between those two groups. CONCLUSIONS: The decrease of GSN concentration in blood and CSF of MS subjects suggests that this protein may be involved in chronic inflammation associated with neurodegeneration. Additionally, the results presented here suggest the possible utility of GSN evaluation for diagnostic purposes. Reversing plasma GSN deficiency might represent a new strategy in MS treatment.

Extracellular gelsolin binds lipoteichoic acid and modulates cellular response to proinflammatory bacterial wall components.

The various functions of gelsolin in extracellular compartments are not yet clearly defined but include actin scavenging and antiinflammatory effects. Gelsolin was recently reported to bind endotoxin (LPS) from various Gram-negative bacteria with high affinity. In this study we investigate whether gelsolin also interacts with bacterial wall molecules of Gram-positive bacteria such as lipoteichoic acid (LTA) and whether gelsolin's interaction with bacterial lipids from Gram-negative or Gram-positive bacteria affects their cellular inflammatory responses. A peptide based on the PPI binding site of gelsolin (160-169) binds purified LTA at the same molecular ratio that it binds phosphatidylinositol 4,5-bisphosphate. The OD of recombinant human plasma gelsolin was found to decrease following the addition of purified LTA, and the binding of gelsolin to LTA inhibits F-actin depolymerization by gelsolin. Simultaneously, the ability of LTA to activate translocation of NF-kappaB, E-selectin expression, and adhesion of neutrophils to LTA-treated human aortic endothelial cells was compromised by gelsolin. Gelsolin was able to partially inhibit LPS- or LTA-induced release of IL-8 from human neutrophils but was unable to prevent Gram-positive Bacillus subtilis or Gram-negative Pseudomonas aeruginosa growth and had no effect on the antibacterial activity of the cathelicidin-derived antibacterial peptide LL37. These data suggest that extracellular gelsolin is involved in the host immune recognition of LTA or LPS following release of these molecules from the bacterial outer membrane during cell division or attack by drugs and immune components.

Selected aspects of the epidemiology of multiple sclerosis in Poland - a multicentre pilot study.

BACKGROUND AND PURPOSE: The aim was to conduct a pilot study of selected epidemiological aspects of multiple sclerosis (MS) in Poland. MATERIAL AND METHODS: Cross-sectional data were collected in 21 centres providing MS treatment. The demographic profile of the patients, medical history of MS, disability status, comorbidity, and diagnostic and treatment modalities were analysed. RESULTS: Data on 3581 patients were obtained, including 2494 women (69.6%) and 1030 men (28.8%) - sex ratio 2.4 : 1. The mean age was 40.7 ± 11.9 years. Monofocal onset was reported in 80.8% of cases - the most frequently reported location of lesions was supratentorial (36.1%), followed by optic nerves (26.5%) and spinal cord (20.1%). The mean disease duration was 10.2 ± 8.8 years (range 0.04-53 years), and the mean time from the first symptoms to MS diagnosis was 2.6 years. Relapsing-remitting MS was reported in 70.5% of patients, secondary progressive in 16.8%, primary progressive in 8.4%, and 'benign MS' in 2.5%. The mean EDSS score was 3.3 ± 2.2 (range 0-9.5). The family history of MS was positive in 6.4% of cases. Comorbidity mainly applied to the musculoskeletal system (6.5%), the urinary system (5.8%) and psychiatric disturbances (5.5%). Brain magnetic resonance studies were available in 96.3% of the patients, evoked potentials in 54%, and cerebrospinal fluid testing in 63.1% - of whom only 41.2% were tested for oligoclonal bands, with 84% of samples being positive. Immunomodulatory drugs were used in 842 patients (24%), predominantly interferon beta (81%) and glatiramer (13%). Mitoxantrone was the most commonly used immunosuppressant. CONCLUSIONS: This project is the first countrywide large-scale MS survey, covering approximately 18% of patients, according to our estimates. The results identify the clinical condition of the patients, as well as diagnostic and treatment modalities.

[Rehabilitation in patients with Parkinson's disease living in the region of Bialystok]. / Postepowanie rehabilitacyjne u pacjentów z choroba Parkinsona zamieszkujacych w rejonie Bialegostoku.

UNLABELLED: Parkinson's disease is one of the most common progressive neurodegenerative diseases of the brain, usually leading to significant disability. Rehabilitation, in addition to symptomatic pharmacotherapy, should be the mainstay of treatment for each patient. The aim of this study was to collect data on the use of different methods of rehabilitation treatment for patients with Parkinson's disease living in the area of Bialystok (before 1998 the province of Bialystok) and evaluation of environmental, social and health factors, which affect the use of this form of treatment. MATERIAL AND METHODS: We evaluated patients with Parkinson's disease treated in neurological departments in Bialystok and Choroszcz near Bialystok over the next 12 months. It was conducted using a specially constructed for this purpose questionnaire. The course of Parkinson's disease was also assessed in the Hoehn and Yahr and the Schwab and England scale. RESULTS: We have studied 88 patients with clinical diagnosis of Parkinson's disease (48 women and 40 men), mean age 68.7 years. It was found that only 73% of those surveyed had ever been rehabilitated. In 27% of patients had never been used any rehabilitation treatment. It was shown that the level of education positively influences the use of rehabilitation, while the coexistence of additional diseases, living in the country and the older age impede the use of physiotherapy. The stage of disease and sex of patients did not affect the use of rehabilitation. Patients were primarily rehabilitated in a hospital. Among the most commonly used treatments were kinesis therapy, massage and hydrotherapy. CONCLUSIONS: The study indicates too low access of patients with Parkinson's disease to rehabilitation and confirms purposefulness of initiating information and education action about the need for physiotherapy treatment in these group of patients.

[Peripheral neuropathies in Lyme borreliosis]. / Neuropatie obwodowe w przebiegu boreliozy z lyme.

UNLABELLED: Lyme borreliosis is a multisystem disease and when involves the nervous system it is termed neuroborreliosis. The symptomatology of peripheral neuroborreliosis is rich and varied. The early symptoms are asymmetric polyradiculopathies and paralysis of the cranial nerves (most commonly facial nerve). Thereafter, there are multifocal mononeuropathies and sensory-motorpolyneuropathies. Difficulties in making a correct diagnosis can result from the long time lag between tick bite and the occurrence of neurological symptoms. In the treatment the most important role play antibiotics. CASE REPORTS: We report the cases of three patients with symptoms of damage to various structures of the peripheral nervous system in the course of Borrelia burgdorferi infection. In all cases, clinical improvement was obtained after treatment with antibiotics, which further confirms the diagnosis of neuroborreliosis. CONCLUSIONS: About neuroborreliosis as a cause of peripheral neuropathy we should always think in the case of vague symptoms of peripheral nervous system lesions in patients with potential exposure to tick bites. Peripheral neuropathies may occur a long interval from the tick bite and are not always preceded by other forms of the disease.

[Moyamoya disease as a rare cause of ischaemic stroke--case report]. / Choroba moyamoya jako rzadka przyczyna udaru niedokrwiennego mózgu--opis przypadku.

UNLABELLED: Moyamoya disease is a rare, progressive disease of the vessels diagnosed according to characteristic abnormalities of brain arteries in the angiography. The incidence of moyamoya disease in Europe is lower than in Asia and its clinical course in European population is probably different from Asiatic (older age of onset and rare incidence of hemorrhagic strokes). CASE REPORTS: Two young patients were diagnosed as moyamoya disease on the basis of clinical symptoms (ischaemic stroke) and results of brain vessels' angiography, which documented an occlusion of both internal carotid arteries above branching-off the ocular arteries in the first patient and stenosis of distal internal carotid arteries and proximal medial and anterior cerebral arteries in the second one. Both patients are under control of the Neurological Outpatient Department and their neurological state is stable. CONCLUSIONS: Despite that moyamoya disease is a rare cause of ischaemic stroke, it should be always considered as one of etiologic factors, especially in young patients.

[A case of Pompe disease treated with acid alpha-glucosidase]. / Przypadek choroby Pompego efektywnie leczony kwasna alfa-glukozydaza.

Pompe disease (type II glycogenosis--GSD II) is a progressive metabolic myopathy caused by lysosomal storage of glycogen due to deficiency of acid alpha-glucosidase. We present the case of a 32-year-old patient with Pompe disease diagnosed 14 years ago in whom enzyme replacement therapy with recombinant human acid alpha-glucosidase (rhGAA) (20 mg/kg i.v. every 2 weeks) has been administered for about 18 months. Despite the fact that therapy was started in the advanced phase of Pompe disease we observed clinical improvement (increased muscle bulk and muscle strength as well as increased range of movements in the distal parts of limbs). In addition, we noticed less effort dyspnoea and use of a respirator during the day shortened to 2-3 hours (previously 5 hours). According to the observation of our patient, we suggest that enzyme replacement therapy causes clinical improvement.

[Transverse myelitis]. / Poprzeczne zapalenie rdzenia kregowego.

Transverse myelitis is a disease with various pathogenesis. It leads to a partial or total transverse lesion of the spinal cord structures resulting in an acute or subacute: motor (paralysis or paresis), sensory (most often with sensory level) and autonomic symptoms and signs. Its etiology is complex and sometimes difficult to establish explicitly. The most frequent reason of transverse myelitis is infection, but there are other factors like: postinfectious, neoplastic, paraneoplastic, demyelinating, immunological (connective tissue diseases), vascular and others. Idiopathic transverse myelitis accounts for about 10-40% of cases, and despite thorough diagnostics its aetiology cannot be established. Transeverse myelitis has been known for years, but it still poses a big problem both diagnostically and therapeuthically. Its course is frequently serious leading to persistent neurological damage and permanent disability. Diagnostic methods of choice are spinal cord MRI and CSF examination with assessment of oligoclonal bands, biomarkers of inflammatory process, 14-3-3 protein and neuronal specific enolase. Its treatment is determined by established aetiology. Many inconsistencies, no clear cut definition of the disease and lack of diagnostic criteria are being discussed by the group of experts working in Transverse Myelitis Consortium Group.

[Estimation of brain atrophic processes among patients with past history of TBE (with EEG evaluation)]. / Ocena zaników mózgowych u chorych po przebytym kzm w polczeniu z ocena zapisu EEG --doniesienie wstepne.

The aim of the study was estimation of brain atrophic processes among patients with past history long lasting, or encephalitic course (8-10 years after) TBE with using planimetric measurements of CT scans in connection with EEG evaluation. 34 patients were enrolled to the study. First results suggest the presence of sequel past TBE as increased percentage pathology in EEG evaluation as well increasing of anterior horns lateral ventricules, dilatation the III ventricule as a result of fastened brain atrophy in relation to the age of the patients.