Is serum neopterin level a marker of responsiveness to interferon beta-1a therapy in multiple sclerosis?

BACKGROUND: Interferon beta (INFbeta) may induce the expression of several proteins, including neopterin, considered a biological marker of INFbeta activity. OBJECTIVES: The aim of this study was to determine the serum neopterin concentration at the beginning of, and during, IFNbeta-1a therapy in relapsing-remitting multiple sclerosis (r-r MS) patients, and to look for a possible correlation between protein synthesis and the clinical course of the disease. METHODS: Thirteen r-r MS patients were treated with INFbeta-1a (i.m. 6 MIU/week) for 2 years. Blood samples for neopterin determinations were taken daily over a period of 1 week at the end of each 6 months of therapy, and tested for neutralizing antibodies (NABs). RESULTS: Neopterin levels peaked 24-48 h post-injection and returned to baseline after 120 h. After 1 year of therapy, four patients dropped out of the study because of progression of the disease: in these subjects a significant decrement of neopterin was observed. CONCLUSION: Neopterin baseline values were not found to decrease over the 2 years of therapy, and neopterin may be considered to be a useful marker of responsiveness to IFNbeta.

Verbal learning strategies in Parkinson's disease.

Word-list learning was studied in patients with Parkinson's disease (PD) and normal control (NC) participants by means of the selective-reminding procedure of H. Buschke and P. A. Fuld (1974) in 3 learning conditions using semantically unrelated items; semantically related items, whose implicit categorical structure had to be spontaneously guessed; and semantically related items, whose explicit categorical structure was known in advance. The PD patients displayed poor learning in all 3 conditions. To identify the functional locus of the PD patients' deficits, the authors performed a stochastic Markov chain analysis, which allowed individual measurements of encoding, retrieval, and category clustering abilities. PD patients were never significantly impaired in encoding word engrams; their impairment was confined to automatic and intentional retrieval and to the ability to benefit from explicit semantic clues.

Verbal learning strategies in patients with multiple sclerosis.

Word list learning was studied in patients with a definite diagnosis of Multiple Sclerosis and in Normal Control subjects by means of the selective reminding procedure of Buschke and Fuld in two learning conditions: (1) using unrelated items and (2) paired-associate items. The Multiple Sclerosis patients displayed poor learning in both conditions. To identify the functional locus of their deficit, stochastic Markov chain analyses were performed, which allowed individual measurements of encoding, automatic and intentional retrieval abilities. On both tasks, encoding on the first trial and automatic retrieval on the subsequent trials were impaired in Multiple Sclerosis patients, whereas intentional retrieval, both with and without reminding by the examiner, appeared to be preserved. As all of the impaired abilities require a normal speed of information processing, the salient learning deficit of the Multiple Sclerosis patients could be tentatively traced back to the slowing down of their mental activity.

Learning and forgetting processes in Parkinson's disease: a model-based approach to disentangling storage, retention and retrieval contributions.

Learning and forgetting a prose passage was studied in 20 patients with Parkinson's disease and in 20 normal control subjects by means of stochastic models, with the aim of identifying the learning and retaining abilities that are affected by Parkinson's disease. Results suggested that Parkinson's disease patients are impaired in developing automatic processing both during learning and retaining, while functions that require active attention are spared. The automatic/intentional dissociation, which is the hallmark of motor disturbance in Parkinson's disease, extends to memory abilities, and, on the grounds of neuroanatomical, neurochemical and neurophysiological correlates, suggests that the memory deficit in Parkinson's disease may be contingent on a dysfunction of the medial prefrontal-cingulate cortex.

Parkinson's disease affects automatic and spares intentional verbal learning. A stochastic approach to explicit learning processes.

We studied word list and paired associates learning in patients with idiopathic Parkinson's disease and normal controls by means of a two-stage stochastic model, which allows independent measurements of encoding, storage and retrieval abilities. We preliminarily ascertained that the model components were both sufficient and necessary to account for the overall performance of the subjects, and then compared the learning abilities between the two groups. Parkinson's disease patients were selectively impaired in identifying well-known engrams, for which learning is superfluous, and in automatic retrieval, namely in abilities that do not need attentional effort. By contrast, they were unimpaired in encoding and intentional retrieval, which require a purposeful effort. The automatic-voluntary dissociation of Parkinson's disease patients' motor behaviour is, therefore, paralleled by some features of their memory performance.

How to differentiate retrieval from storage deficit: a stochastic approach to semantic memory modeling.

Some of the methods currently used to differentiate retrieval from storage deficits in brain damaged patients are revisited. Indices based on association or agreement measures among the responses given by the subject on repeated trials, as well as direct estimates of storage and retrieval abilities based on crude percentages, are open to criticism. A simple Markov chain stochastic approach, which is free of the drawbacks of the other methods and which distinguishes storage from retrieval deficits more reliably and powerfully, is proposed.

Newest human herpesvirus (HHV-6) in the Guillain-Barré syndrome and other neurological diseases.

To investigate the presence of human herpesvirus-6 (HHV-6) in patients affected by Guillain-Barré syndrome (GBS) and by other neurological diseases (OND), we examined by indirect immunofluorescence analysis (IFA) the sera and cerebrospinal fluid (CSF) from 28 GBS and 63 OND. Moreover, we tested 150 blood donors (BD) to appreciate the diffusion of HHV-6 infection in the Italian adult healthy population. We found a significantly higher titre of antibody to HHV-6 in the GBS patients compared with OND and BD, although the pathogenicity of the virus is not known.

A model-based study of learning and memory following transient global amnesia attacks.

Verbal learning and forgetting were studied in patients one month after an episode of Transient Global Amnesia and in normal control subjects by means of a two-stage stochastic model, which allows independent measurements of encoding, storage and forgetting. We preliminarily ascertained both the necessity and the sufficiency of the model to account for several performance scores of the two experimental groups, and then compared the learning and forgetting functions between groups. In spite of the analytical power of the statistical method adopted. Transient Global Amnesia was not found to entail persistent impairment of encoding and storage, as well as of retaining memory traces and retrieval algorhythm.

Natural killer cells and lymphocyte subsets in active MS and acute inflammation of the CNS.

Cerebrospinal fluid (CSF) and peripheral blood (PB) lymphocyte subsets were determined by flow cytometry (FCM) in 15 patients with active multiple sclerosis (MS) and 15 patients with acute inflammatory diseases (ID) of the central nervous system (CNS) in order to establish correlations between the two groups of diseases, as well as between the CSF and PB subsets distribution. A panel of monoclonal antibodies was applied to all the samples: Leu3 (CD4), Leu4 (CD3), Leu2 (CD8), Anti-HLA-DR, Leu11 (CD16). Statistical analysis did not show differences in CD3+ nor in CD3+ DR+ T-cells both in the CSF and PB in the two groups of patients. CD4+ cells were significantly higher in the CSF than in the PB, while CD8+, DR+ CD3- and CD16+ cells were constantly lower in the CSF without differences between the two groups of diseases.

Apperceptive and associative forms of prosopagnosia.

Three prosopagnosic patients were given four face tests, two perceptual (an unknown face identification test and an age estimation test) and two also implying memory (a familiarity check test and a famous face recognition test). The patients' performance was assessed with reference to the score distribution of the normal population. A patient was found to fail both perceptual and mnestic tests, without any noticeable difference between them. Also the second patient had poor scores on both kinds of tests, but his impairment was significantly greater on the perceptual ones. The third patient, on the contrary, showed no perceptual deficit and only failed the mnestic tests. His inability to recognize the individuality of an item among members of the same category was strictly confined to faces and never present for other classes of stimuli (cars, coins, personal belongings). This finding is supportive of the thesis that in a few patients the deficit underlying prosopagnosia is face specific.

Space exploration with and without the aid of vision in hemisphere-damaged patients.

Space exploration carried out under visual control and in its absence (blindfolded condition) was investigated in 20 RBD patients, 10 LBD patients and 20 normal controls with a modified version of Chedru's test (pressing the keys of a keyboard). Conventional tests for visual hemi-inattention permitted to classify RBD patients in a group with visual neglect (RBD VN+) and a group without visual neglect (RBD VN-). On the visual version of the test both RBD groups showed a preference for pressing the keys ipsilateral to the lesion side, but this tendency was more marked in the RBD VN+ group than in any other brain-damaged group. On the tactile version of the test only RBD VN+ patients showed a gradient favouring the pressing of the ipsilateral half of the keyboard. This ipsilateral preference was, however, significantly less marked than that found when the performance was assisted by vision. No relation between neglect in the blindfolded condition and tactile extinction was found. The nature of space exploration in the absence of vision is discussed and the existence of tactile neglect is questioned.

Diagnostic investigations in MS: which is the most sensitive?

In an attempt to establish the efficacy of the different diagnostic tests, 41 multiple sclerosis (MS) patients at different stages of the disease were studied by means of visual evoked potential (VEP) recording, T-lymphocyte subset determination cerebrospinal fluid (CSF) analysis and magnetic resonance (MR) imaging. MR and CSF oligoclonal bands (OB) were the most sensitive techniques for the diagnosis of MS, being positive in 88% of patients, while VEP and helper/suppressor (H/S) T-cell ratio were altered in 54% and 46% of patients respectively. Low significant agreement coefficient were found among the 4 tests and the major value, even though "fairly" significant, was between MR and OB.

Skull asymmetries bear no relation to the occurrence of apraxia. A clinical and CT-scan study in patients with unilateral brain damage.

This study aimed at assessing whether there was a relation between presence or absence of apraxia following a parietal and/or frontal left hemisphere lesion and "typical" skull asymmetries, evidenced by CT scan (prevalence of the left over the right occipital length and width and of the right over the left frontal length and width). Skull asymmetries were measured in a sample of 160 brain-damaged patients and their prevalence was found to agree with those reported by the literature in normal subjects. A subgroup of 72 patients with lesions restricted to the parietal and/or frontal lobe were given a movement imitation test and diagnosed as apraxic, borderline or normal making reference to the performance of 150 control subjects. The incidence in these three groups of typical or atypical occipital and frontal asymmetries was assessed and found not to differ significantly. It is concluded that no consistent relation between hemisphere dominance for praxis and skull asymmetry can be asserted. The study also investigated the relation of idemotor apraxia to the locus of left hemisphere damage and confirmed that both the incidence and the severity of the disorder are much greater following parietal than frontal lesions.

Attentional shift towards the rightmost stimuli in patients with left visual neglect.

In a search task where four letters were displayed to the right of a central fixation point, right brain-damaged patients with visual neglect showed the fastest response when the target was at the rightmost position and progressively slower responses as it moved towards the center of the display. This finding confirms Kinsbourne's claim that in visual neglect an important role is played by the magnetic attraction that the extreme end of the right structured space exerts on the patient's attention.

DNA repair, sensitivity to gamma radiation and to heat shock in lymphocytes from acute, untreated multiple sclerosis patients.

Increases in spontaneous sister chromatid exchange (SCE) and gamma radiation-induced chromosome aberrations have been reported in peripheral blood lymphocytes (PBL) from multiple sclerosis (MS) patients, suggesting the presence of an abnormality in repair in this disease. We tested this hypothesis by measuring the ability to repair DNA and survival, after exposure to low (2-12 Gy) and high (100 Gy) gamma ray doses or to a high temperature (37-45 degrees C), of freshly isolated PBL from 15 patients affected by definite MS and 15 healthy subjects. The MS patients were untreated and in the acute phase of the disease. No significant difference was found between the two groups. We suggest that the previously reported genomic instability may be of viral origin and not due to a genetic defect in repair of DNA in these patients.

[Risk factors and short-term prognosis in ischemic and hemorrhagic attacks: review of 503 patients admitted to the Neurologic Clinic of Modena]. / Fattori di rischio e prognosi a breve termine nell'ictus ischemico ed emorragico: revisione di 503 pazienti ricoverati presso la Clinica Neurologica di Modena.

Cerebrovascular risk factors, characteristics of the lesion (ischaemia or haemorrhage in the carotid or vertebro-basilar area) and mortality in the acute phase were studied in 503 patients admitted for first stroke. Seventy-five per cent of the patients had an ischaemic lesion and 25% a hemorrhagic one. Most of the ischaemic lesions occurred in patients aged 71-80 years, while haemorrhagic strokes hit subjects aged 61-70 years. Hypertension favors haemorrhage and heart disease and the older age favors ischaemia. Coma at onset negatively influences prognosis; mortality is more frequent among older patients, subjects in coma or with haemorrhagic lesions. Twelve per cent of the patients died in the first three weeks post-onset.

Right posterior brain-damaged patients are poor at assessing the age of a face.

The ability to order unknown faces by age was investigated in right and left brain-damaged patients, divided into posterior and non-posterior groups on the basis of CT scan findings. A face recognition test and a figure ground discrimination test were also given. All three tests were affected by brain damage, but their sensitivity to the locus and side of lesion varied. While no hemispheric difference was found on the figure ground discrimination test, the face age test significantly discriminated patients with right posterior injury from any other brain-damaged group. The face recognition test occupied an intermediate position, with right posterior patients significantly impaired in comparison with right non-posterior patients and marginally impaired with respect to left posterior patients. Aphasia did not affect the performance of left brain-damaged patients on any of the tests. The findings are interpreted as evidence that damage of the right posterior hemisphere areas disrupts the structural encoding of visual information. Four prosopagnosic patients were also tested. Only those showing signs of apperceptive agnosia failed on the face age test.

Frequency and recognition judgement by young and elderly adults.

The aim of this study was to compare the performance of young and elderly subjects at two different memory tasks (frequency judgement and word recognition) under two retrieval conditions (forced and unforced choice) in order to determine the source of any incidental age-related memory deficit. Fifty young subjects (aged from 15 to 35 yr) and 50 elderly subjects (aged from 60 to 85) participated in this study. The results showed a significant difference between age groups at word recognition independent of retrieval condition, while frequency judgement was found significantly impaired in elderly as compared with young subjects only when an unforced choice procedure was required. It is suggested that age related memory impairment is not dependent on the nature of the task, but rather to the amount of retrieval information which is given to the subjects.

Neurophysiological and CSF immunological study of 19 patients affected by acute idiopatic optic neuritis.

We studied 19 patients affected by acute idiopatic optic neuritis (ON), with neurophysiological tests: visual (VEP), somatosensory (SSEP), acoustic (ABR) evoked potentials and study of the blink reflex (BR), and with cerebrospinal fluid (CSF) examination, in order to detect "silent" lesions in the central nervous system (CNS) and/or immunological alterations, suggestive of multiple sclerosis (MS). The percentage of cases with at least one altered CSF IgG parameter (IgG index, IgG synthesis/day and IgG oligoclonal bands) has been higher than that of cases with one or more altered neurophysiological tests, regardless of the apparently intact eye VEP. If we also included this last test, the 2 percentages become identical. The validity of these tests in predicting the evolution of ON in MS is discussed.

Myelin basic protein in the CSF of patients with multiple sclerosis, optic neuritis and various neurological diseases.

We tested 104 patients for myelin basic protein (MBP) content in the CSF. Of these subjects 14 were selected as control group, 36 were affected by multiple sclerosis (MS), 14 by optic neuritis (ON) and 42 presented other not primarily demyelinating neurological diseases (ND ND). CSF MBP level was significantly higher in the MS group than in the other groups of patients, while no statistical difference was found between the MS patients with acute exacerbation and those in remission.