Distinct regional brain atrophy pattern in multiple sclerosis and neuropsychiatric systemic lupus erythematosus patients.

Differentiation of systemic lupus erythematosus (SLE) from multiple sclerosis (MS) can be challenging, especially when neuropsychiatric (NP) symptoms are accompanied by white matter lesions in the brain. Given the lack of discriminative power of currently applied tools for their differentiation, there is an unmet need for other measures that can aid in distinguishing between the two autoimmune disorders. In this study we aimed at exploring whether brain atrophy measures could serve as markers differentiating MS and SLE. Thirty-seven relapsing-remitting MS and 38 SLE patients with nervous system manifestations, matched according to age and disease duration, underwent 1.5 Tesla magnetic resonance imaging (MRI), including volumetric sequences, and clinical assessment. Voxelwise analysis was performed using ANTS-SyN elastic registration protocol, FSL Randomise and Gamma methods. Cortical and subcortical segmentation was performed with Freesurfer 5.3 pipeline using T1-weighted MPRAGE sequence data. Using MRI volumetric markers of general and subcortical gray matter atrophy and clinical variables, we built a stepwise multivariable logistic diagnostic model to identify MRI parameters that best differentiate MS and SLE patients. We found that the best volumetric predictors to distinguish them were: fourth ventricle volume (sensitivity 0.86, specificity 0.57, area under the curve, AUC 0.77), posterior corpus callosum (sensitivity 0.81, specificity 0.57, AUC 0.68), and third ventricle to thalamus ratio (sensitivity 0.42, specificity 0.84, AUC 0.65). The same classifiers were identified in a subgroup analysis that included patients with a short disease duration. In MS brain atrophy and lesion load correlated with clinical disability, while in SLE age was the main determinant of brain volume. This study proposes new imaging parameters for differential diagnosis of MS and SLE with central nervous system involvement. We show there is a different pattern of atrophy in MS and SLE, and the key structural volumes that are differentially affected include fourth ventricle and posterior section of corpus callosum, followed by third ventricle to thalamus ratio. Different correlation patterns between volumetric and clinical data may suggest that while in MS atrophy is driven mainly by disease activity, in SLE it is mostly associated with age. However, these results need further replication in a larger cohort.

Subcortical gray matter atrophy is associated with cognitive deficit in multiple sclerosis but not in systemic lupus erythematosus patients.

Cognitive impairment is a significant clinical problem both in multiple sclerosis (MS) and systemic lupus erythematosus (SLE) patients. In MS cognitive dysfunction has been associated with brain atrophy and total demyelinating lesion volume. In SLE cognitive impairment is much less understood, and its link to structural brain damage remains to be established. The aim of this study was to identify the relationship between subcortical gray matter volume and cognitive impairment in MS and SLE. We recruited 37 MS and 38 SLE patients matched by age, disease duration and educational level. Patients underwent magnetic resonance imaging (MRI) and a battery of psychometric tests. Severity of cognitive impairment was similar in both cohorts despite larger white matter lesion load in MS patients. Psychometric scores were associated with global and subcortical gray matter atrophy measures and lesion load in MS, but not in SLE. In SLE, the lack of a relationship between cognitive impairment and structural damage, defined either as atrophy or white matter lesions, indicates a different causal mechanism of cognitive deficit.

Humoral Immune Response against Neural Antigens and Its Effects on Cognition in Lung Cancer Patients.

Cognitive impairment develops as a clinical manifestation of immune-mediated indirect effects of malignancy in lung cancer patients. This study aimed to evaluate the effects of humoral immune response on cognition in lung cancer patients. Fifty-one lung cancer patients were subjected to neurological examination: Mini Mental State Examination (MMSE), Trail Making Test (TMT), and Hamilton scale. The Psychology Experiment Building Language software was used for the evaluation of digit span, simple reaction time (SRT), and choice reaction time (CRT) tests. Serum samples were tested for the presence of onconeuronal antibodies and antineural antibodies. The results demonstrate that autoantibodies were found in 31 % patients. MMSE scores were lower (26.7 ± 2.7) in seropositive patients than in seronegative subjects (28.7 ± 1.2; p = 0.013). Executive functions were also influenced by the presence of autoantibodies. The humoral immune response in lung cancer patients affected both SRT and CRT. We conclude that the humoral immune response in lung cancer patients is associated with cognitive impairment. Cognitive impairment is associated with both specific reactions against onconeuronal or antineural antigens and non-organ specific reactions against nucleosome antigens.

Pulsatility index in carotid arteries is increased in levothyroxine-treated Hashimoto disease.

The aim of this case-control study was to evaluate carotid hemodynamic variables and traditional cardiovascular risk factors in women with Hashimoto thyroiditis (HT). The study group consisted of 31 females with HT on levothyroxine (L-T4) and 26 euthyroid women with HT without L-T4 matched for age and body mass index (BMI) as controls. Carotid intima-media thickness (CIMT), carotid extra-media thickness (CEMT), and pulsatility indexes in common carotid artery (PI CCA) and in internal carotid artery (PI ICA) were measured. BMI, waist circumference, lipid profile, fasting glucose and insulin levels, and parameters of thyroid function [TSH, free thyroxine (FT4) and antithyroperoxidase antibodies (TPOAbs)] were assessed. The study and the control groups did not differ in age, BMI, waist circumference, lipid profile, fasting glucose, and insulin levels. Results are expressed as median (IQR). Treated HT group had higher FT4 levels than nontreated [17.13 (5.11) pmol/l vs. 14.7 (2.27) pmol/l; p=0.0011] and similar TSH [1.64 (2.08) IU/ml vs. 2.07 (3.14) IU/ml; p=0.5915]. PI CCA and PI ICA were higher in the study group than in controls (p=0.0224 and p=0.0477, respectively). The difference remained statistically significant for PI ICA and PI CCA after adjustment for other variables (coefficient=0.09487; standard error=0.04438; p=0.037 and coefficient=0.1786; standard error=0.0870; p=0.0449, respectively). CIMT and CEMT were similar in both groups (p=0.8746 and p=0.0712, respectively). Women with HT on L-T4 replacement therapy have increased PI in common and internal carotid arteries than nontreated euthyroid HT patients. Therefore, it seems that hypothyroidism, but not autoimmune thyroiditis per se, influences arterial stiffness.

Substantia nigra hyperechogenicity in Polish patients with Parkinson's disease.

BACKGROUND: Hyperechogenicity of the substantia nigra (SN) measured by transcranial sonography (TCS) is a characteristic feature observed in patients with Parkinson's disease (PD). To our knowledge, no SN hyperechogenicity data are available for Polish population. Moreover most of studies come from few centres, which used the one type of ultrasound device. The main aim of the study was to investigate the association between PD and SN hyperechogenicity measured by sonographic machine, not assessed so far. MATERIALS AND METHODS: In this study cross-sectional study SN hyperechogenicity was evaluated in 102 PD patients and 95 control subjects. Midbrain was visualised by Aloka Prosound 7 ultrasound device. SN area measurement, the relation to the clinical features of PD, inter- and intra-observer reliability were evaluated. RESULTS: We confirmed that SN echogenicity is significantly increased in PD patients compared to control subjects (p < 0.001). The area under curve for PD patients vs. controls was 0.93. Receiver operating characteristic analysis indicated a cut-offs for SN echogenicity at 0.19 cm² with accuracy equal to 90%, specificity - 86% and sensitivity - 93.7%. The SN hyperechogenicity was not related to PD clinical findings. Reliability was good if an experienced sonographer performed the SN measurements. CONCLUSIONS: This study shows that the SN abnormality observed by TCS isa specific feature, which can be helpful in the process of PD diagnosing.

Neurological paraneoplastic syndromes in lung cancer patients.

Lung cancer is recognized among the most frequent causes of paraneoplastic neurological syndromes (PNS). Neurological syndromes in subjects with systemic malignancy remain a clinical and diagnostic challenge. The aim of the study was to evaluate the frequency of NPS, their clinical manifestation and association with onconeural antibodies in patients with lung cancer. Fifty patients hospitalized with the diagnosis of PNS participated in the study. Neurological evaluation consisted of the Rankin scale (mRS), the Barthel index (BI), and testing for the presence of onconeural antibodies by means of indirect immunofluorescence, as screening, and Western blotting as confirmation. The majority of lung cancer patients (64%) aged 62 ± 10 had NPS symptoms. Their neurological condition and daily living activities were reasonable: mRS (1.0; 0.0-4.0) and BI (100; 7.4-100) scores. Classical PNS were found in 30% of cases and included sensory neuropathy (16%), paraneoplastic cerebellar degeneration (12%) as the most frequent symptoms. Autoimmune reaction was observed in 42% of lung cancer patients and in 20% was represented by well-characterized onconeural antibodies. Anti-Hu antibody was identified as the most frequent. In conclusion, PNS signs in lung cancer patients have both classical and non-classical features. In the course of SCLC only well-characterized onconeural antibodies were identified. The presence of well-characterized onconeural antibodies is strongly associated with classical features of PNS.

Patient-reported quality of life in multiple sclerosis differs between cultures and countries: a cross-sectional Austrian-German-Polish study.

BACKGROUND: Patient-reported quality of life (QOL) is an outcome measure in clinical trials in multiple sclerosis (MS), but translated QOL instruments may affect the actual comparability of data. OBJECTIVES: We aimed to investigate possible differences in QOL in MS between cultures and countries. We employed the Functional Assessment of Multiple Sclerosis (FAMS) Version 4 questionnaire, which is a state-of-the-art QOL instrument. METHODS: Some 484 MS patients from Austria (145), Germany (144), and Poland (195) aged 20-60 years, and stratified for sex and disease severity as measured by the Expanded Disability Status Scale (EDSS) score completed the respective FAMS translation and a socio-demographic questionnaire. RESULTS: Analysis of variance and post-hoc Scheffé-test showed that 64% of the FAMS items were answered significantly differently (p < 0.001) between the three countries. A multivariate regression analysis including all the available disease-related and socio-demographic variables revealed the factors age, EDSS score, employment, social contacts, MS course, and country to be significant predictors of both the total FAMS score and the score for items answered differently between the three countries. CONCLUSIONS: Differences exist in the QOL of MS patients from Austria, Germany, and Poland which seem to lie beyond the impact of disease severity. They appear to be related to culture or other country-specific factors, as country was an independent predictor of differently answered items of the FAMS and thus also of the whole FAMS. QOL instruments should consider this aspect to faithfully reflect subjective information such as patient-reported benefit of treatment in multinational clinical trials.

Onconeuronal and antineuronal antibodies in patients with neoplastic and non-neoplastic pulmonary pathologies and suspected for paraneoplastic neurological syndrome.

OBJECTIVE: Onconeuronal antibodies are important diagnostic tool in patients with suspicion of paraneoplastic neurological syndromes (PNS). However, their role in PNS pathophysiology and specificity for particular neurological manifestation remains unclear. The aim of this study was to evaluate onconeuronal and antineuronal antibodies in patients with pulmonary pathologies and suspected for PNS. MATERIAL AND METHODS: Twenty one patients with pulmonary pathologies were selected from the database of 525 consecutive patients with suspicion of PNS. Patients' sera were screened for the presence of onconeuronal and antineuronal antibodies by means of indirect immunofluorescence; the presence was confirmed by Western blotting. Clinical data were obtained from medical records, hospital data base, and questionnaire-based direct telephone contact with patients. RESULTS: Among 21 patients, aged 54 +/-11, with pulmonary pathologies, the most frequent neurological manifestations were neuropathies. Typical PNS included paraneoplastic cerebellar degeneration (PCD) and limbic encephalitis (LE). We found cases with multiple onconeuronal antibodies (anti-Ri and anti-Yo) and coexisting PNS (PCD/LE). Well-defined onconeuronal antibodies were identified in 23.8% of patients. Among antineuronal antibodies, the most frequent were anti-MAG (23.8%). ROC curves analysis revealed high sensitivity of onconeuronal and antineuronal antibodies for typical PNS and lower for pulmonary malignancies. CONCLUSIONS: Tests for antibodies are highly sensitive for the diagnosis of typical paraneoplastic neurological syndromes. Anti-myelin and anti-MAG antibodies are associated with non-neoplastic pulmonary diseases. Patients with well-defined onconeuronal antibodies require careful screening and follow-up, because the PNS diagnosis indicates a high probability of an underlying malignancy.

Expression of fibrinogen receptors in platelets of migraine patients--correlation with platelet GPIIb content and plasma cholesterol.

Binding of fibrinogen to platelets washed from blood of migraine patients (n = 30) and control donors (n = 24) was compared. In addition, contents of platelet glycoprotein IIb and platelet fibrinogen were determined in both groups by radioimmunoassay. The receptor capacity for fibrinogen in platelets activated by ADP was significantly higher (p less than 0.01) in migraine patients (52,505 +/- 4,925) than in controls (33,881 +/- 3,965). The mean contents of GPIIb (3.51 +/- 0.34 micrograms/10(8) platelets) and fibrinogen (37.26 +/- 4.05 micrograms/10(8) platelets) in migraine platelets were also markedly increased (p less than 0.01 and p less than 0.001, respectively) when compared to controls (2.21 +/- 0.18 micrograms of GPIIb and 18.75 +/- 2.29 micrograms of fibrinogen per 10(8) platelets, respectively). There was a high correlation between the number of fibrinogen receptors exposed by ADP and the total amount of platelet GPIIb both in migraine patients (R = 0.69, p less than 0.01) and controls (R = 0.62 p less than 0.01), as well as plasma cholesterol in the case of migraine patients (R = 0.82, p less than 0.001).

Immunofluorescent analysis of antibodies against neurons in the case of paraneoplastic syndrome.

The authors report clinical and neuropathological findings especially immunofluorescent detection of antineuronal antibodies in the case of paraneoplastic syndrome in course of the small-cell lung carcinoma. The clinical symptoms, observed in 48-year-old woman, covered bilateral pyramidal syndrome, cerebellar syndrome, myasthenic syndrome and impairment of the cranial nerves. Neuropathological investigation revealed paraneoplastic encephalopathy in the form of encephalitis. Immunofluorescent analysis showed brightly fluorescent neurons standing out against a dull background.

Atypical case of sporadic Creutzfeldt-Jakob disease (CJD) in a young adult.

The great concern exists that new variant of CJD (nvCJD) developed as a result of exposure to bovine spongiform encephalopathy (BSE)-infected meat products. Therefore, all cases of CJD in the young, as the one of ours are the matter of interest. The 21-year-old female developed a rapid progression of pyramidal, extrapyramidal and cerebellar signs, visual loss and psychiatric symptoms, leading to death in 16 weeks. The microscopic features were: a neuronal loss accentuated in cerebral cortex with extensive astroglia proliferation and spongiform changes. Immunohistochemical staining, revealed the presence of "synaptic" deposits of PrP in the cerebral cortex and in the cerebellum. No florid amyloid plaques were present. The case was diagnosed as a sporadic CJD, with some features of Heidenhein variant (visual symptoms) and corticostriatocerebellar category. The pathological findings excluded a nv CJD which is linked with BSE.

[Pathomechanisms of pain attacks in Horton's headache (cluster headache)]. / W sprawie patomechanizmu napadów w bólu gllowy Hortona (klasterowym).

In view of the still unexplained pathomechanism of Horton's cluster headaches 9 patients were given a challenge test with nitroglycerin while at the same time the attacks were blocked with indomethacin. The attacks were provoked with one dose (1 mg) of nitroglycerin. Then during 3 days the patients took 75-100 mg indomethacin which dose was quite sufficient for inhibition of the activity of arachidonic acid cyclooxygenase. On the fourth day another nitroglycerine provocation was done. No inhibitory effect of indomethacin on the attack was observed. It seems doubtful that products of arachidonic acid cyclooxygenation play any role in the pathomechanism of this headache.

[Platelet aggregation in patients with migraine during the pain attack and in the pain-free period]. / Agregacja pllytek krwi u chorych na migrene w czasie napadu bólu i w okresie bezbólowym.

In 31 women with a history of migraine platelet aggregation was studied between migrainous attacks, and in 14 of them during an attack of migraine. The method of Born and Cross was used. The rates of the first and second phases of aggregation were calculated and the quantitative index of aggregation curve according to Cavallero was calculated. Adrenaline in concentrations of 2 and 4 micron M was used as the aggregating factor. No differences were found in the mean rates of the first phase of aggregation between the patients and the controls. The rate of the second phase in the time between migraine attacks was significantly higher in patients with migraine (p less than 0.001) than in healthy subjects. During migraine attack the mean rate of the second phase decreased significantly (p less than 0.02 and p less than 0.001). These changes of the rate of the second phase may be explained as due to disturbances in the release of the aggregating substances from platelets and accumulation of platelet-activating substances.

[Effect of total cholesterol level on platelet aggregation in patients with migraine]. / Wplyw stezenia cholesterolu calkowitego na agregacje plytek krwi u chorych na migrene.

In 34 women with simple migraine the total cholesterol concentration in the serum and the platelet aggregation index according to Wu and Hoak were determined. The blood cholesterol levels differed in them. Two groups of patients were isolated: group I with cholesterol level above the upper normal range and group II with cholesterol within this range. The mean concentration of this lipid differed significantly between these groups (p less than 0.001). The platelet aggregation index in group I was significantly lower than in the group with normal cholesterol level (p less than 0.05). During migraine attack a further fall was observed in the platelet aggregation index in the group with high cholesterol level (p less than 0.01). The authors suppose that cholesterol concentration may be one of the factors determining differences in platelet behaviour in migraine patients.

[Controlled study of iprazochrome effectiveness (Divascan) in prophylactic treatment of migraine]. / Kontrolowane badania skutecznosci iprazochromu (Divascan) w profilaktycznym leczeniu migreny.

The study was designed as double blind, placebo controlled. The patients were treated with 15 mg of iprazochrome daily in three equal doses for eight weeks, or--with equal amount of placebo tablets. The effectiveness was calculated with the use of Migraine Score (MS) by Couch et. al. 44 patients completed the study. In 21 the therapy was positive: 16 out of them were treated with iprazochrome, 5--with placebo. In 23 patients the treatment was negative: 19 out of them took placebo, 4--iprazochrome. Statistical analysis showed significant influence (chi 2 test: p < 0.001; Youle coeff. = 0.88). In iprazochrome group mean decrease of MS was significant after treatment (p < 0.01), but not significantly changed in the placebo group. According to our results iprazochrome was found effective in the prophylaxis of migraine.

[Sodium valproate versus propranolol in the prophylactic treatment of migraine]. / Porównanie dzialania soli sodowej kwasu walproinowego i propranololu w leczeniu profilaktycznym migreny. Doniesienie wstepne.

In the recent years sodium valproate (SV) has been proposed as a prophylactic drug in migraine. Several reports documented a positive effect of SV in migrainous patients. The authors present the results of the open study in 35 women with migraine without aura treated with the daily dose of 1000-1500 mg of SV, during 10 weeks. The results were compared with the effect of propranolol administered to the same patients, in daily dose of 120-160 mg during 10 weeks. The effects were similar: in both methods more than 50% reduction of frequency and severity of attacks was obtained. The side effects were generally mild; in no case the treatment was stopped. The authors conclude that in the future SV might be administered in migraine prophylaxis as the first choice drug.

[The comparison of sodium valproate and ergotamine titrate plus caffeine in the abortive treatment of migraine attacks]. / Porównanie dzialania soli sodowej kwasu walproinowego i winianu ergotaminy z kofeina w doraznym leczeniu napadów migreny. Doniesienie wstepne.

The contemporary measures against migraine attacks are not fully satisfying, thus the migraine episode is still a challenge in treatment. In 1993 Hering and Steiner proposed valproic acid for the interruption of migraine attacks. The authors present the results of their own study comparing the effects of sodium valproate (SV) and ergotamine plus caffeine (Coffecorn) in this respect. 82 attacks in 20 patients were treated altogether. The effectiveness of SV was statistically not different from that of ergotamine--the drug recognized formerly as the first choice one in the abortion of migraine attacks.

[Intima-media complex thickness of common carotid artery as a risk factor for stroke]. / Grubosc kompleksu intima-media tetnic szyjnych wspólnych oceniona metoda ultrasonografii jako czynnik ryzyka udaru niedokrwiennego mózgu.

Intima-Media Thickness (IMT) of Common Carotid Artery (CCA) could be seen as the atherosclerotic risk factors' final morphological effect. We investigated the hypothesis that IMT of CCA is significantly different in sex- and age-matched groups of persons with stroke and healthy subjects. 47 patients with first-ever atherothrombotic stroke proven by CT were investigated. Patients with atrial fibrillation, valvular heart disease and left ventricular hyperthrophy were excluded. The IMT of CCA were estimated by High-Resolution B-Mode Ultrasonography. All the patients had bilateral IMT measurement within 20 mm proximal to the carotid bulb on the far wall in the anterioposterior and laterolateral plane. The results were compared with those obtained in 50 healthy sex- and age-matched subjects. We found a strong association between IMT and stroke (p < 0.0001). Mean IMT was 0.96 mm (SD 0.18) in patients and 0.70 mm (SD 0.09) in controls. The presence of atherosclerotic plaques was 0.34 and 0.08 for patients and controls respectively (p = 0.0025). IMT of CCA is strongly positively associated with the risk for stroke. The frequency of atherosclerotic plaques in CCAs is statistically significantly higher in stroke patients than in control group.

[Morphology of demyelination plaques vs cognitive and emotional disorders in multiple sclerosis patients]. / Morfologia ognisk demielinizacyjnych a zaburzenia funkcji poznawczych i emocjonalnych u chorych na stwardnienie rozsiane.

The interrelationship between psychological examination and MRI findings was studied in 70 patients with MS. The cognitive and emotional functions were examined by a battery of tests: Wechsler Adult Intelligence Scale, Visual Retention Test, Hamilton Depression Scale. In MRI examination the localization, area, and the morphology of the plaques were examined. According to plaque's morphology the patients were divided into two groups: with confluent plaques and those with patchy-shaped ones. The signs of dementia were found significantly more frequently in the group with confluent plaques (p. < 0.04). In this group of patients also single-function disorders like disturbances of verbal memory, attention, visual memory, cause- and effect thinking, abstract thinking, and visual-motor coordination were significantly more frequent (p. < 0.01). In the same group the signs of fatigue syndrome were more frequently encountered (p. < 0.02). The authors conclude that the disturbances found in cognitive function may reflect the symptoms of subcortical dementia in MS patients.

[The effect of large dose prednisone therapy on immunological markers in multiple sclerosis]. / Wplyw leczenia stwardnienia rozsianego duzymi dawkami Encortonu na humoralne markery immunologiczne.

The effect of large-dose prednisone therapy (3960 mg over 56 days) on humoral immunological markers and MRI pattern was studied in 25 patients with clinically definite multiple sclerosis. There was a decrease in levels of some studied markers (TNF in CSF, MBP level, IgG index, kappa chains in urine and kappa/creatinine ratio) after the treatment, but the differences reached statistical significance in some groups only. The decrease of total lesion area in MRI was not statistically significant. The obtained results proved clearly, that the above mentioned immunological markers might be helpful for monitoring of therapy in MS patients.