Hyperglycemia and diabetes have different impacts on outcome of ischemic and hemorrhagic stroke.

INTRODUCTION: Stroke is the second leading cause of long-term disability and death worldwide. Diabetes and hyperglycemia may impact the outcome of stroke. We examined the impact of hyperglycemia and diabetes on in-hospital death among ischemic and hemorrhagic stroke patients. MATERIAL AND METHODS: Data from 766 consecutive patients with ischemic (83.15%) and hemorrhagic stroke were analyzed. Patients were classified into four groups: ischemic and diabetic; ischemic and non-diabetic; hemorrhagic and diabetic; and hemorrhagic and non-diabetic. Serum glucose was measured on admission at the emergency department together with biochemical and clinical parameters. RESULTS: Mean admission glucose in ischemic stroke patients with diabetes was higher than in non-diabetic ones (p < 0.001) and in hemorrhagic stroke patients with diabetes than in those without diabetes (p < 0.05). Mean admission glucose in all patients who died was significantly higher than in patients who survived. In multivariate analysis, the risk factors for outcome in patients with ischemic stroke and without diabetes were age, admission glucose level and estimated glomerular filtration rate (eGFR), while in diabetics they were female gender, admission glucose level, and eGFR; in patients with hemorrhagic stroke and without diabetes they were age and admission glucose levels. The cut-off value in predicting death in patients with ischemic stroke and without diabetes was above 113.5 mg/dl, while in diabetics it was above 210.5 mg/dl. CONCLUSIONS: Hyperglycemia on admission is associated with worsened clinical outcome and increased risk of in-hospital death in ischemic and hemorrhagic stroke patients. Diabetes increased the risk of in-hospital death in hemorrhagic stroke patients, but not in ischemic ones.

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.

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.

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.

Quality of life in Polish patients with multiple sclerosis.

PURPOSE: This study is a pilot evaluation of the quality of life (QoL) in Polish patients with multiple sclerosis (MS). MATERIAL/METHODS: Data from 21 centers in Poland were collected from May 2008 to January 2009. QoL was assessed using the questionnaire Euro Quality of Life (EQ-5D), with Polish population norms. Demographic profile of patients, duration/form/relapsing activity of the disease, disability and comorbidity were also analyzed. RESULTS: Data from 3521 patients (F/M ratio 2.4:1) were collected. The average EQ-5D index was 0.8 ± 0.27 and the mean score in a visual analog scale (EQ-VAS) was 65.6 ± 21.5. There was a highly significant positive correlation between both indices (r=0.7334, p<0.0001). The mean patient age was 40.7 years (11.2-92.3 years) and disease duration was 10.3 ± 8.8 years (0.04-53 years). 74.2% of subjects had relapsing-remitting form of MS, while 17.2% were classified as secondary progressive and 8.6% as primary progressive. In the group of relapsing-remitting MS subjects there were 2.5% patients with "benign MS". The average degree of disability on EDSS scale was 3.6 ± 2.2, while disability ≥6 was observed in 20.3% of patients. Most patients did not have other diseases besides MS. CONCLUSIONS: This is the first large study of QoL in patients with MS in Poland (approximately 18% of all patients). Our results confirm a reduction in QoL compared with the general population. Further studies are indicated to identify the modifiable risk factors (e.g. type of treatment) that may affect QoL.

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.

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.

[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.

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.

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.

Cerebrospinal fluid leakage--reliable diagnostic methods.

Prompt diagnosis and early treatment of cerebrospinal fluid (CSF) leakage minimizes the risk of severe complications. In patients presenting with clear fluid nasal discharge it is important to identify the nature of the rhinorrhea. The CSF leakage may occur as post-traumatic, iatrogenic, spontaneous or idiopathic rhinorrhea. The differential diagnosis of CSF rhinorrhea often presents a challenging problem. The confirmation of CSF rhinorrhea and localization of the leakage may be diagnosed by CT, MRI cisternography and MRI cisternography in combination with single photon emission tomography or radioisotopic imaging. Although these methods allow estimation of the CSF leakage with high accuracy, they are expensive and invasive procedures. Therefore, biochemical methods are still used in the differentiation. Although the most common diagnostic method for screening CSF leakage is glucose oxidase, its diagnostic sensitivity and specificity is generally unsatisfactory. False negative results may occur with bacterial contamination and false positive results are common in diabetic patients. Glucose detection is not recommended as a confirmatory test. As such, other biomarkers of the CSF leakage, such as beta-2-transferrin (beta-2 trf) and beta-trace protein (betaTP) are necessary to identify and confirm of this condition.

Moyamoya disease: Diagnostic imaging.

Moyamoya disease is a progressive vasculopathy leading to stenosis of the main intracranial arteries. The incidence of moyamoya disease is high in Asian countries; in Europe and North America, the prevalence of the disease is considerably lower. Clinically, the disease may be of ischaemic, haemorrhagic and epileptic type. Cognitive dysfunction and behavioral disturbance are atypical symptoms of moyamoya disease.Characteristic angiographic features of the disease include stenosis or occlusion of the arteries of the circle of Willis, as well as the development of collateral vasculature. Currently, magnetic resonance angiography and CT angiography with multi-row systems are the main imaging methods of diagnostics of the entire range of vascular changes in moyamoya disease.The most common surgical treatment combines the direct arterial anastomosis between the superficial temporal artery and middle cerebral, and the indirect synangiosis involving placement of vascularised tissue in the brain cortex, in order to promote neoangiogenesis. Due to progressive changes, correct and early diagnosis is of basic significance in selecting patients for surgery, which is the only effective treatment of the disease. An appropriate qualification to surgery should be based on a comprehensive angiographic and imaging evaluation of brain structures.Despite the rare occurrence of moyamoya disease in European population, it should be considered as one of causes of ischaemic or haemorrhagic strokes, especially in young patients.

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.

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.

[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.

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.

Intrathecal increase of sphingosine 1-phosphate at early stage multiple sclerosis.

Sphingosine 1-phosphate (S1P) is a pleiotropic mediator that is critically involved in the development of an inflammatory response in various pathological conditions. We hypothesize that during the course of multiple sclerosis (MS) development, chronic inflammation will result in the alteration of S1P levels in blood and cerebrospinal fluid (CSF). We evaluated S1P concentrations in blood and CSF obtained from 66 subjects, including 40 patients diagnosed with MS and 26 subjects of a control group that included patients diagnosed with idiopathic cephalgia and idiopathic (Bell's) facial nerve palsy. HPLC techniques were used to determine S1P levels. We found that S1P concentrations in blood of the MS subject group (361.7+/-150.7 nM) did not differ from those of the control group (371.9+/-142.5 nM). However, S1P concentrations in CSF of the MS group were significantly higher (p<0.01) compared to the control group (2.2+/-2.7 versus 0.69+/-1.1 nM). The increase of S1P concentration in CSF of MS subjects suggests that this bioactive lipid is involved in chronic inflammation associated with MS and it may be useful to study S1P in a number of neurodegenerative diseases to provide better understanding of the mechanisms governing their development.