Distinctive sphingolipid patterns in chronic multiple sclerosis lesions.

Multiple sclerosis (MS) is a CNS disease characterized by immune-mediated demyelination and progressive axonal loss. MS-related CNS damage and its clinical course have two main phases: active and inactive/progressive. Reliable biomarkers are being sought to allow identification of MS pathomechanisms and prediction of its course. The purpose of this study was to identify sphingolipid (SL) species as candidate biomarkers of inflammatory and neurodegenerative processes underlying MS pathology. We performed sphingolipidomic analysis by HPLC-tandem mass spectrometry to determine the lipid profiles in post mortem specimens from the normal-appearing white matter (NAWM) of the normal CNS (nCNS) from subjects with chronic MS (active and inactive lesions) as well as from patients with other neurological diseases. Distinctive SL modification patterns occurred in specimens from MS patients with chronic inactive plaques with respect to NAWM from the nCNS and active MS (Ac-MS) lesions. Chronic inactive MS (In-MS) lesions were characterized by decreased levels of dihydroceramide (dhCer), ceramide (Cer), and SM subspecies, whereas levels of hexosylceramide and Cer 1-phosphate (C1P) subspecies were significantly increased in comparison to NAWM of the nCNS as well as Ac-MS plaques. In contrast, Ac-MS lesions were characterized by a significant increase of major dhCer subspecies in comparison to NAWM of the nCNS. These results suggest the existence of different SL metabolic pathways in the active versus inactive phase within progressive stages of MS. Moreover, they suggest that C1P could be a new biomarker of the In-MS progressive phase, and its detection may help to develop future prognostic and therapeutic strategies for the disease.

Impact of Hyperventilation and Sleep Deprivation Upon Visual Evoked Potentials in Patients with Epilepsy.

OBJECTIVES: The diagnosis of epilepsy can cause many problems, especially when the routine electrophysiological tests are inconclusive. The aim of the present study was to assess the visual evoked potential (VEP) in patients with epilepsy using various kinds of stimulation and activation tests. The VEP parameters were also presented with reference to the type of seizure and abnormalities in electroencephalogram (EEG), including the response to the activation tests. MATERIALS AND METHODS: This study comprised 81 patients with newly diagnosed epilepsy of unknown etiology before initiation of the treatment. The VEP tests were performed at rest, after hyperventilation, and deprivation of sleep. Visual stimulation included an alternating checkerboard pattern and a uniform flash light (FL) with a frequency of 1.88 and 15 Hz. RESULTS: The VEP parameters obtained with the stimulation of a checkerboard pattern did not differ significantly between the patients and controls. Neither the presence of seizure activity in EEG nor the type of seizure significantly affected the VEP parameters. Using the FL stimulation, a significantly prolonged VEP latency was found at the FL frequency of 1.88 Hz and shortened at the frequency of 15 Hz. These changes were augmented after activation tests. In case of the patients with positive intermittent photic stimulation response in EEG, a significant prolongation of P100 latency was shown at rest and after FL stimulation at the frequency of 1.88 Hz. CONCLUSION: Standard activation methods significantly affect the VEP parameters in patients with epilepsy. Changes in the VEP parameters depend on the frequency and the type of the stimulus, as well as the activation method used. These findings suggest a disturbed balance between the glutamatergic and GABAergic systems in the visual excitability of neuronal networks in case of patients with epilepsy.

Cognitive impairment, event-related potentials and immunological status in patients with systemic lupus erythematosus.

BACKGROUND: Cognitive impairment (CI) is a frequent problem in lupus patients, regardless of their overt neuropsychiatric (NP) involvement. OBJECTIVES: The aim of our study was to test cognitive abilities in systemic lupus erythematosus (SLE) patients by means of neuropsychological testing and event-related potentials (ERPs), and to search for their cognitive abilities correlations with a wide range of auto-antibodies. MATERIAL AND METHODS: A total of 37 SLE patients were subjected to a battery of neuropsychological tests, recommended by the American College of Rheumatology (ACR), and to ERPs. They were also tested for a wide range of auto-antibodies (anti-cardiolipin (aCL), anti-ß2-glycoprotein I (anti-ß2-GPI), lupus anticoagulant, anti-dsDNA, anti-nucleosome, anti-ribosomal P (anti-Rib-P), anti-ganglioside, anti-Ro/SS-A, and anti-La/SS-B. RESULTS: Cognitive impairment was found in 35% of patients, mostly with NP SLE (NPSLE), and was associated with higher disease activity, measured by the SLE Disease Activity Index (SLEDAI), and with a longer duration of central nervous system (CNS) involvement. There were no differences in the immunological status between CI patients and those without cognitive decline, but some antibodies were correlated with worse results in certain neuropsychological tests (anti-dsDNA and worse results of Rey Complex Figure Test - RCFTc for copying and RCFTr for recall, and of verbal fluency test (VFT); aCL IgG and worse results in Digit Span (DS) and in RCFTc). Event-related potentials showed prolonged N200 and P300 latencies in SLE patients in comparison to controls, but no differences were found between SLE and NPSLE patients. Mean P300 latency was significantly longer in patients without anti-nucleosome antibodies. CONCLUSIONS: Event-related potentials can be used as a complementary tool in assessing CI in SLE patients. The immunological status of patients with CI did not differ from that of patients without cognitive problems.

The relationship between event-related potentials, stress perception and personality type in patients with multiple sclerosis without cognitive impairment: A pilot study.

BACKGROUND: The clinical course of multiple sclerosis (MS) can vary significantly among patients and is affected by exogenous and endogenous factors. Among these, stress and personality type have been gaining more attention. OBJECTIVES: The aim of this study was to investigate the parameters of event-related potentials (ERPs) with regards to stress perception and personality type, as well as cognitive performance in MS patients. MATERIAL AND METHODS: The study group consisted of 30 MS patients and 26 healthy controls. Auditory ERPs were performed in both groups, including an analysis of P300 and N200 response parameters. The Perceived Stress Scale (PSS) was used in the MS group to measure the perception of stress. The D-type Scale (DS14) scale was used to determine the features of Type D personality, characterized by social inhibition and negative affectivity. RESULTS: The score on the PSS corresponded with a moderate or high level of stress perception in 63% of MS patients, while 23% of patients presented with a Type D personality. P300 latencies were significantly longer (p = 0.001), N200 amplitudes were significantly higher (p = 0.004), and N200 latencies were longer in MS patients than in the controls. Strong positive correlations were found between N200 and P300 amplitudes, as well as between the DS14 and PSS results. CONCLUSIONS: Most MS patients experience moderate to severe stress. ERP abnormalities were found in MS patients who did not have overt cognitive impairment and showed correlations with stress levels and negative affectivity. Event-related potentials may be useful in assessing the influence of stress and emotions on the course of MS.

Persistent genital arousal disorder - a case report. / Zespól uporczywego pobudzenia genitaliów ­ opis przypadku.

The persistent genital arousal disorder (PGAD) may coexist with restless legs syndrome and overactive bladder syndrome and share some similarities with these conditions. Thus, the new term: restless genital syndrome (RGS) is proposed. The purpose of this paper is to present a case of PGAD, including the description of the etiology, the diagnostics and the treatment of the disorder. The described patient meets the criteria for PGAD. Organic lesions within nervous and urogenital system were excluded and the psychogenic background of the syndrome was assumed in this case. The patient was diagnosed with personality disorder with a predominance of dependent personality traits and emotional lability. After the failure of pharmacological treatment, systemic psychotherapy with cognitive-behavioral elements was initiated with moderate effect.

PD-1 gene polymorphic variation is linked with first symptom of disease and severity of relapsing-remitting form of MS.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), where inflammation, demyelination together with the axonopathy are the cardinal features on pathologic ground, with a combined genetic and environmental background. The associations of PD-1 single nucleotide polymorphisms (SNPs): PD-1.3 (in intron 4), PD-1.5 and PD-1.9 (both in exon 5) with clinical manifestation of MS in 479 south Polish individuals including 203 MS patients were analyzed. Presence of PD-1.5T allele was linked with the first manifestations of disease: diplopia and pyramidal signs - favored pyramidal signs but protected against of diplopia development. Farther, PD-1.3G/PD-1.5C/PD-1.9C haplotype significantly favored whereas GTC protected against diplopia. Besides, GTT haplotype strongly favored non-severe RRMS outcome and ATC haplotype was specific only for these MS patients. Our population-based case-control study, investigating selected three PD-1 SNPs: PD-1.3, PD-1.5 and PD-1.9, revealed that polymorphic variation may be rather disease-modifying than MS risk factor.

Profile of autonomic dysfunctions in patients with primary brain tumor and possible autoimmunity.

OBJECTIVE: Cerebral lesion due to different neurological conditions could be complicated by autonomic dysfunction, reported in the literature as a sympathetic hyperactivity. The mechanisms of dysautonomia still remains partial. The aim of the study was to assess the profile of autonomic dysfunction in patient with primary brain tumors, with attempt to estimate the additional factors in pathogenesis of dysautonomia. MATERIAL AND METHODS: Neurological examinations, the Low's autonomic disorder questionnaire, electrophysiological autonomic tests (Heart Rate Variability test at rest and during deep breathing, spectral analysis of R-R intervals, sympathetic skin response test), studies of peripheral nerves, blood sampling collection for antibodies were done in 33 patients with recognized primary brain tumors. RESULTS: The averaged Low's Questionnaire score in the patients group was significantly higher than in the controls, systolic blood pressure was increased, heart rate tended to be higher without significance, but heart rate variability was severe low, LF/HF ratio also tended to be higher in the patients group. In SSR test the amplitude of responses from hand and foot was significantly lower without changes in their latencies. We found changes in the electrophysiological tests of peripheral nerves, and positive anti-neural antibodies in 5 patients. CONCLUSIONS: The results of the study indicated to the sympathetic nervous system hyperactivity in patients with primary brain tumors. Local brain lesion with high intracranial pressure, additional peripheral nerve damage probably in the course of autoimmunity, and direct influence of autoimmunity to the central part of autonomic nervous system are possible in the pathogenesis of dysautonomia.

Cognitive performance, fatigue and event-related potentials in patients with clinically isolated syndrome.

OBJECTIVES: Cognitive impairment and fatigue are regarded as important aspects of multiple sclerosis. The aim of this study was to evaluate cognitive performance, the level of fatigue and parameters of event-related potentials (ERP) in patients diagnosed with clinically isolated syndrome (CIS). PATIENTS AND METHODS: The study comprised 44 patients with CIS and 45 healthy controls. Cognitive performance was assessed using the Brief Repeatable Battery of Neuropsychological Tests (BRBNT), fatigue - using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS). Auditory ERP were performed and the parameters of N200 and P300 components were analyzed. Neuropsychological and electrophysiological measures were referred to clinical and radiological features of the disease activity. RESULTS: Forty five% of patients failed in at least one test from BRBNT, mainly within the domains of memory and attention. In 18% of patients FSS corresponded with moderate or severe fatigue. The mean latency of N200 and P300 was significantly longer and amplitude of P300 was lower in those patients with CIS than in the controls. Significant correlations were found between the results of MFIS and tests evaluating verbal memory and attention, as well as between N200 latency and results of tests for verbal memory. CONCLUSIONS: Cognitive performance and fatigue deserve attention from the earliest clinical stage of MS. Abnormalities of event-related potentials in CIS suggest early impact of the disease on functional neural networks.

Event-related potentials and cognitive performance in multiple sclerosis patients with fatigue.

The aim of this study was to evaluate event-related potentials (ERP) and cognition in multiple sclerosis (MS) patients with regard to fatigue and disease-related variables. The study comprised 86 MS patients and 40 controls. Fatigue was assessed using the Fatigue Severity Scale (FSS/FSS-5) and the Modified Fatigue Impact Scale (MFIS/MFISmod). N200 and P300 components of auditory ERP were analyzed. Cognition was evaluated by means of Brief Repeatable Battery of Neuropsychological Tests (BRBNT). The results of ERP and BRBNT were compared between non-fatigued, moderately and severely fatigued MS patients and controls. P300 latency was significantly longer in the whole MS group and in the fatigued patients than in the controls. A positive correlation was found between P300 latency and MFIS/MFISmod results, independent from age and MS-related variables. The fatigued patients scored less than non-fatigued ones in tests evaluating memory, visuomotor abilities and attention. Results of these tests correlated significantly with fatigue measures, independently from MS-related variables. Fatigue in MS patients showed significant relationships with impairment within the memory and attention domains. Parameters of auditory ERP, as electrophysiological biomarkers of cognitive performance, were not independently linked to fatigue.

Is peripheral paraneoplastic neurological syndrome possible in primary brain tumors?

INTRODUCTION: Systemic malignant diseases cause the induction of autoimmunity, for example, paraneoplastic syndromes. There are no proofs of paraneoplastic syndromes in primary brain tumors. The aim of the study was to evaluate the involvement of the peripheral nervous system, together with an assessment of onconeuronal and antineural antibodies as indicators of humoral immune response against nervous system in patients with primary brain tumors. MATERIALS AND METHODS: Clinical examinations, electrophysiological studies of peripheral nerves (motor and sensory conduction velocity studies, conduction velocity distribution tests, thermal and vibratory quantitative sensory tests, and sympathetic skin response tests) and muscles, blood sampling collection (assessment of onconeuronal, and antineural antibodies) were performed on 33 patients with newly recognized primary brain tumors within 2-4 days after their admission to our department. RESULTS: We revealed statistically significant changes of peripheral nerves, more pronounced in the peroneal nerve in standard and conduction velocity distribution tests, as well as in sympathetic skin responses. We revealed significantly higher vibratory thresholds, and pain thresholds for cold and warm in the upper and lower limbs in the study group than in the controls. In five patients, we have identified anti-neuroendothelium, anti-GFAP, anti-MAG, anti-PCNA, and anti-Ro52 antibodies. CONCLUSIONS: In patients with primary brain tumors, electrophysiological changes in peripheral nerves, together with the presence of the antineural antibodies suggest an autoimmune humoral response, and make the diagnosis of paraneoplastic neurological syndrome possible.

The possible meaning of fractional anisotropy measurement of the cervical spinal cord in correct diagnosis of amyotrophic lateral sclerosis.

Diagnosis of amyotrophic lateral sclerosis (ALS) is based on clinical criteria and electrophysiological tests (electromyography, and transcranial magnetic stimulation). In the search for ALS biomarkers, the role of imaging procedures is currently emphasized, especially modern MR techniques. MR procedures were performed on 15 ALS patients and a sex- and age-matched control group. The MR examinations were performed with a 1.5-T MR unit, and the protocol consisted of sagittal T1-weighed images, sagittal and axial T2-weighed images, and sagittal T2-weighed FAT SAT images followed by an axial diffusion tensor imaging (DTI) sequence of the cervical spinal cord. FA values in individual segments of the cervical spinal cord were decreased in the ALS group in comparison with the control group. After comparing FA values for anterior, posterior, and lateral corticospinal columns, the greatest difference was observed between the C2 and C5 segments. Spinal cord assessment with the use of FA measurements allows for confirmation of the motor pathways lesion in ALS patients. The method, together with clinical criteria, could be helpful in ALS diagnosis, assessment of clinical course, or even the effects of new drugs. The results also confirmed the theory of the generalized character of ALS.

Effects of noise and mental task performance upon changes in cerebral blood flow parameters.

The objectives of this paper were to determine whether traffic noise influences the parameters of cerebral blood flow (CBF) measured by functional transcranial Doppler sonography (fTCD) during the performance of mental tasks, and to see whether impact of noise on CBF changes with age. The study comprised 36 healthy volunteers, 22 women and 14 men, aged 25-49 years. The fTCD was performed using a fixed 2-MHz probe, aiming for an evaluation of mean velocity (MFV) and the pulsatility index (PI) in the middle cerebral artery (MCA) on both sides. Subsequently, fTCD was monitored: At rest; during performance of the Paced Auditory Serial Addition Test (PASAT); during exposure to traffic noise; and during concomitant exposure to noise and PASAT performance. MFV and PI were compared for particular conditions and correlated with age. During exposure to noise, flow parameters did not change significantly. PASAT performance in silence increased MFV and decreased PI in MCA on both sides. During PASAT performance, on exposure to noise, MCV and PI changed significantly only in the left MCA. However, values of MFV were significantly lower during noise than in silence. Correlations with age were noted for velocities in the right MCA during PASAT performance in silence and for PI on both sides during PASAT performed in noise conditions. Noise impairs the CBF during mental tasks. A comparison of changes in CBF parameters correlated with age suggests that the involvement of the nondominant hemisphere in managing with noise effects increases with age.

Evaluation of the Degradation of the Selected Projectile, Commissural and Association White Matter Tracts Within Normal Appearing White Matter in Patients with Multiple Sclerosis Using Diffusion Tensor MR Imaging - a Preliminary Study.

BACKROUND: The aim of the study was to assess the impairment of the selected white matter tracts within normal appearing white matter (NAWM) in multiple sclerosis (MS) patients using diffusion tensor imaging (DTI). MATERIAL/METHODS: Thirty-six patients (mean age 33.4 yrs) with clinically definite, relapsing-remitting MS and mild disability (EDSS - Expanded Disability Status Scale 1-3.5) and 16 control subjects (mean age 34.4 yrs) were enrolled in the study. DTI examinations were performed on a 1.5T MR scanner. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained with a small ROI method in several white matter tracts within NAWM including: the middle cerebellar peduncles (MCP), the inferior longitudinal fasciculi (ILF), inferior frontooccipital fasciculi (IFOF), genu (GCC) and splenium of the corpus callosum (SCC), posterior limbs of the internal capsules (PLIC), superior longitudinal fasciculi (SLF) and posterior cingula (CG). There were no demyelinative lesions within the ROIs in any of the patients. RESULTS: A significant decrease in FA was found in MS patients in both the ILFs and IFOFs (p<0.001) and in the left MCP and right SLF (p<0.05), compared to the normal subjects. There were no significant differences in FA values in the remaining evaluated ROIs, between MS patients and the control group. A significant increase in ADC (p<0.05) was found only in the right PLIC and the right SLF in MS subjects, compared to the control group. CONCLUSIONS: The FA values could be a noninvasive neuroimaging biomarker for assessing the microstructural changes within NAWM tracts in MS patients.

Emotional prosody expression in acoustic analysis in patients with right hemisphere ischemic stroke.

OBJECTIVES: The role of the right cerebral hemisphere in nonverbal speech activities remains controversial. Most research supports the dominant role of the right hemisphere in the control of emotional prosody. There has been significant discussion of the participation of cortical and subcortical structures of the right hemisphere in the processing of various acoustic speech parameters. The aim of this study was an acoustic analysis of the speech parameters during emotional expression in right hemisphere ischemic strokes with an attempt to reference the results to lesion location. MATERIALS AND METHODS: Acoustic speech analysis was conducted on forty-six right-handed patients with right-middle cerebral artery stroke, together with 34 age-matched people in the control group. We compared the results of acoustic studies between patients with varying infarct locations and the control group. RESULTS: Variations in fundamental frequency during verbal expression of joy, anger and sadness were significantly smaller in the patient group than in the control group. Cortical lesion caused more restrictions in fundamental frequency variation in the expression of joy and a lower voice intensity in expressions of anger and joy compared to those patients with subcortical lesions. CONCLUSIONS: Cortical lesion was associated with a more impaired expression of emotional prosody than subcortical lesion. The results indicate the leading role of the cortical structures of the right hemisphere in the expression of emotional prosody.

Progressive subacute Miller-Fisher syndrome successfully treated with plasmapheresis.

BACKGROUND: Miller-Fisher Syndrome (MFS) is a rare acute polyneuropathy composed of the clinical triad of ataxia, areflexia and ophthalmoplegia, with a monophasic, self-limited course and spontaneous improvement. CASE REPORT: The authors present a 65-year-old man with Miller-Fisher syndrome consisting of bilateral ophthalmoplegia, trigeminal and facial nerve palsy, mild ataxia and peripheral neuropathy. The disease had a progressive, subacute course within 3 months. A high titer of anti-GQ1b antibodies was detected. As a result of plasmapheresis, complete recovery was achieved. CONCLUSIONS: The presented case was atypical in its clinical course and treatment. It could support the theory of the continuity between MFS, Bickerstaff brainstem encephalitis (BBE), and Guillain-Barré syndrome (GBS).

Acute hyperkinetic syndrome due to ephedrone abuse.

OBJECTIVES: A new form of manganese poisoning is related to the intravenous use of self-prepared methcathinone hydrochloride (ephedrone). Manganese encephalopathy typically manifests as a levodopa-resistant parkinsonism. MAIN POINTS: A 32-year-old drug-addicted man with acute gait disturbances after the ephedrone injections was presented. Choreic movements, severe postural instability, and "cock-walk" gait were observed. Magnetic resonance imaging T1 images showed high signal intensity of white matter in the basal ganglia and pituitary gland, and T2 images showed decreased signal mostly of globus pallidus with decreased N-acetylaspartate and choline levels in MR spectroscopy. CONCLUSIONS: The unusual pattern of MR imaging may explain the unusual clinical symptoms with dominant hyperkinetic syndrome.

Assessment of visual and auditory evoked potentials in multiple sclerosis patients with and without fatigue.

The aim of the study was to evaluate visual and brainstem auditory evoked potentials (VEP, BAEP) in multiple sclerosis (MS) patients with regards to fatigue and disease-related variables. The study comprised 86 MS patients and 40 controls. Fatigue was assessed using the Fatigue Severity Scale (FSS/FSS-5) and the Modified Fatigue Impact Scale (MFIS). Latencies and amplitudes of the P100 component of VEP and the I-V components of BAEP were analyzed. The results of EP were compared between non-fatigued, moderately and severely fatigued MS patients and controls. P100 latency was increased and amplitude decreased in moderately and severely fatigued MS subjects. The latency of the V component of BAEP and interlatencies I-III-V were increased in severely fatigued patients. The amplitude of the V component was lowered in fatigued patients. VEP and BAEP abnormalities were usually one-sided. Interocular P100 latency difference tended to correlate with FSS/FSS-5. The parameters of VEP and BAEP correlated with functional system scores but not with MS duration, overall degree of disability or its progression over time. Significant, usually asymmetrical VEP and BAEP abnormalities were found in fatigued MS patients, with no relationships to disease-related variables. EP may be considered an electrophysiological marker of fatigue in MS patients.

[Rare clinical form of glioblastoma multiforme]. / Rzadkie kliniczne odmiany glejaka wielopostaciowego.

Glioblastoma multiforme (glioblastoma multiforme - GBM) is the most malignant tumor classified by WHO. It is also the most common primary CNS tumor with a very aggressive course and unfavourable prognosis, usually develops in adults, and is typically located supratentorially in the fronto-temporal region. However, the literature describes an unusual position of GBM (e.g. spinal cord, pons, pineal region), familial gliomas unconnected with the family of gliomas predisposed to the occurrence of syndromes, unusual glioma and metastatic sites, gliomas transplanted with organs. In this paper, based on the available literature, the authors discuss an unusual and rare form of glioblastoma multiforme.

Magnetic resonance spectroscopy findings as related to fatigue and cognitive performance in multiple sclerosis patients with mild disability.

BACKGROUND: The origin of fatigue in multiple sclerosis (MS) remains unclear. Magnetic resonance spectroscopy (MRS) provides an insight into metabolic properties of the brain. OBJECTIVES: The aim of the study was to evaluate brain MRS measurements in MS patients, with regard to fatigue and cognition. METHODS: The study comprised 32 MS patients and 43 controls. Fatigue was assessed using the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS) and cognition - using the Brief Repeatable Battery of Neuropsychological Tests (parts of BRBNT). MRS voxels were placed in the parietal white matter (PWM) and the posterior cingulate gyrus (PCG); N-acetyl-aspartate (NAA), choline (Cho) and myoinositol (mI) to creatine (Cr) ratios were determined. Relationships were searched between MRS measurements and fatigue as well as BRBNT results. RESULTS: MS patients in comparison with controls showed decreased NAA/Cr and increased mI/Cr ratios in PCG and PWM, respectively. No significant relationships between MRS parameters and fatigue measures, BRBNT results or MS-related variables were found. CONCLUSIONS: The decrease of NAA and increase of mI within white and gray matters in MS patients do not show a significant relationship with cognitive performance or fatigue.