Sardinia, a high-risk area for multiple sclerosis: a prevalence and incidence study in the district of Alghero

Findings from small descriptive studies carried out in the last few years in Sardinia suggest that this region is now of high rather than medium risk for multiple sclerosis. It is uncertain whether this high prevalence reflects a different approach in case finding over time or a true change in disease occurrence. We report the results of a prevalence and incidence survey conducted in the district of Alghero, a community of 78,000 people in northwest Sardinia. Based on data from 31 patients, the average annual incidence for the period 1971 through 1980 was 4.1 per 100,000. On December 31, 1980, the prevalence rate was 59 per 100,000. The results support the view that Sardinia is now a high-risk area for multiple sclerosis, and further suggest a rise in the occurrence of the disease in recent years

Visual and auditory event related potentials in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is classically described as an upper and lower motor neuron disease without clinical sensory disorders. Various studies have been conducted to explore and understand motor impairment but in the last years also cognitive functions have drawn attention in ALS patients investigating extra-motor involvment. Recent neuropsychological studies have been carried out to evaluate specific cognitive dysfunction also supported by MRI, PET and SPECI findings. All papers report subtle cognitive impairment especially related to the frontal lobe functions. Gil et al (1995) performed an auditory ERPs study and they found 60% of patients had P300 delayed latency. To further investigate the relationship between ALS and cognitive function, visual and auditory oddball ERPs were recorded in 10 patients by using 30 electrodes. Attention was focused on latency and amplitude of P300 and on its topographic distribution. Neuropsychological evaluation allowed to test the cognitive status of patients and psychometric tests were selected to assess intelligence, executive functions, attention, memory, word fluency, visuo-motor and visual-constructive skills. Motor disability was scored by ALS Severity Scale including bulbar and spinal score. Depression state was evaluated by using Hamilton Scale. Results of ERPs were compared to 10 healthy age-matched controls. Preliminary data show abnormalities of P300 in about 50% of patients. Correlations between visual and auditory P300 latency and amplitude, psychometric tests, disease duration, physical disability and depression will be discussed

Are the basal ganglia involved in language comprehension? A neurophysiological attempt

Deficits of language comprehension in non-demented patients with Parkinson's disease (PD) have been observed. These alterations concern verbal fluency, the semantic domain and the cognitive-linguistic flexibility. An involvement of the nucleus candatus in linguistic comprehension has been hypothesized. The event-related potentials (ERPs) represent an electrophysiological tool for studying the global cognitive state (P300) and linguistic functions of semantic and syntactic postlexical integration (N400 and P600, respectively). To evaluate language comprehension in patients with PD by means of ERPs and neuropsychological evaluation and to compare these results with those obtained in a case of restless legs syndrome (RLS) secondary to ischemic stroke in the basal ganglia region

Modulation of masseter exteroceptive suppression by non-nociceptive upper limb afferent activation in humans

The effects induced by non-noxious electrical stimulation of upper limb nerves on exteroceptive suppression (ES) of masseter muscle EMG activity were studied in 15 healthy subjects. EMG activity of masseter muscles was recorded bilaterally and great care was taken to minimise the activation of afferents other than the stimulated ones. Masseter ES was elicited by applying a non-noxious electrical stimulus to the skin above the mental nerve (Mt) of one side, during a voluntary contraction of masseter muscles at a prescribed steady clenching level. Onset and offset latencies and duration of early and late components of masseter ES (ES1 and ES2, respectively) were evaluated in control conditions and compared to those obtained when a non-noxious electrical stimulation was delivered separately to Med or Rad or simultaneously to both nerves (Med-Rad) of one side. Upper limb nerve stimulation could be simultaneous or it could precede or follow Mt stimulation by various time intervals. In control conditions, ES1 latency onset and duration values (mean ± SD) were 11.3±2.9 ms and 16.9±2.1 ms, respectively, and ES2 latency onset and duration values were 44.5±6.0 ms and 28.6±11.1 ms, respectively. No significant differences were observed which were related to the side being recorded. Two types of effects, opposite in nature, were shown on masseter ES, depending on the time intervals between Mt and upper limb nerve stimulation. The first effect, which was facilitatory, consisted of a significant increase in ES1 and ES2 duration. A maximal increase in ES1 duration (134–155% compared to control value) occurred when upper limb nerve stimulation preceded that of Mt by 18–30 ms. Maximal ES2 lengthening (115–145%) was observed when upper limb nerve stimulation followed that of the Mt by 10 ms. The second effect was inhibitory and affected only ES2, which appeared completely eliminated when Med stimulation preceded that of Mt by 40–80 ms. By contrast, ES1 was never suppressed at any interstimulus interval. These data might reflect the different action of the central outflow, following the upper limb-induced effects, on the different neuronal circuits mediating ES1 and ES2

Genetic susceptibility to multiple sclerosis in Sardinians: an immunological study

Objectives - We studied the in vitro production of variably MS-related cytokines from Sardinian MS and healthy donors bearing the two “Sardinian” MS-associated HLA-DR alleles: DR3 and DR4, with the purpose to evidentiate possible differences in their immune response. Materials and methods - ELISA were used for detection of cellular products by mitogen-activated peripheral blood mononuclear cells. Results - PHA-activated HLA-DR4+/DR3- mononuclear cells produce significantly higher amounts of TNF-α compared with the DR3 +/DR4-, In addition, homozygous HLA-DR3+ mononuclear cells from MS patients produce significantly lower amounts of IL-10 than those from homozygous HLA-DR3+ healthy donors. Conclusion - The abnormal production of detrimental or regulatory cytokines may account for the genetic susceptibility to MS in different HLA-subgroups of Sardinian MS patients

Visual and auditory event-related potentials in sporadic amyotrophic lateral sclerosis

Objectives: To investigate the relationship between amyotrophic lateral sclerosis (ALS) and cognitive function by means of oddball event-related potentials (ERPs) and to determine the usefulness of this methodology in the cognitive status assessment of physically disabled patients. Methods: Visual and auditory oddball ERPs were recorded in 16 consecutive sporadic ALS patients. A comprehensive battery of neuropsychological (NP) tests assessed intelligence, executive functions, attention, memory, word fluency, visuo-motor and visual-constructive skills. Results: All patients performed visual and auditory ERPs and 75% of cases showed abnormal N200 and/or P300 waves. Ten patients (62.5%) carried out the entire psychometric evaluation with significant impairment on tests of executive function and attention. A significant correlation between delayed visual (P&lt;0.04) and auditory (P&lt;0.04) P300 latency and impaired NP tests was found. Conclusions: In agreement with literature data, our findings confirm the hypothesis of cognitive impairment in ALS patients especially on attention and executive functions suggesting a more extensive degeneration beyond the motor areas. ALS causes severe physical disabilities and such a condition may interfere with NP testing. Thus, the P300 seems to be a useful tool for the assessment of cognition and attention when severe physical deficits are present.</br

Non-nociceptive upper limb afferents modulate masseter muscle EMG activity in man

Recent electrophysiological data obtained in anaesthetized rats evidenced jaw muscle excitatory responses to the electrical stimulation of type II limb somatosensory afferents. In the present work, we describe an inhibitory reflex evoked in human masseter muscles by stimulation of non-nociceptive fibres travelling in the median and radial nerves (MED and RAD, respectively). Eighteen healthy volunteers participated in the study. Subjects were seated on a comfortable chair, with the complex head-mandible-neck-trunk and the limbs securely fixed to the chair. Attempts were made to minimize possible interferences due to the activation of afferents other than the stimulated ones. The subjects were instructed to contract masseter muscles at a submaximal level and to maintain a stable level of muscle contraction during all trials. EMG voluntary activity was recorded from both masseter muscles by means of coaxial needle electrodes before and after the electrical stimulation of MED and/or RAD at intensities below pain threshold. In all subjects, MED stimulation induced bilaterally a marked depression of masseter EMG activity, which occurred at a latency of 23.6±2.1 ms and lasted 27.8±6.6 ms. RAD stimulation also induced a marked reduction in masseter EMG activity, but this effect was clearly observed in 9 out of 18 subjects, and it showed latency (30.2±7.5 ms) and duration (44.9±5.4 ms) significantly longer in comparison with the MED-induced effect. All subjects exhibited the inhibitory period in masseter EMG following the simultaneous stimulation of both nerves; this one appeared at a latency not significantly different (25.3±5.9 ms) and lasted much more (37.4±8.2 ms) than EMG depression evoked by MED stimulation. The duration of masseter muscle inhibition, induced by MED and/or RAD stimulation, was inversely related to the level of EMG activity, while latency was not related to it. Significant increases in the inhibitory period duration were also observed by increasing stimulus intensity, within a subthreshold range for the activation of nociceptive fibres. In all cases, the inhibitory period was followed by a later excitatory rebound activity, whose latency and duration depended on the duration of the preceding EMG inhibition and on the background level of masseter activation. In conclusion, results evidenced that the activation of arm somatosensory fibres modulates masseter muscle activity in normal man. This might lead to a coordination between limb and masticatory muscle activity, which is required in several complex motor acts

Neuropsychophysiological findings in a case of long-standing overt ventriculomegaly (LOVA)

Long-standing overt ventriculomegaly in adults (LOVA) is a clinical entity characterized by chronic hydrocephalus with infant onset, slow evolution and clinical disturbances during adulthood. Few cases are reported in literature describing the evident contrast between the severity of hydrocephalus and the relatively spared neurological functioning and cognitive aspects. The authors describe a 59-year-old man with congenital hydrocephalus complaining of persistent gait impairment. Neurological examination showed a mild paraparesis, severe higher cortical function impairment but relatively sparing of daily living activity. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a very remarkable ventriculomegaly compressing the brain cortex but sparing the cerebellum and the brainstem. Brain Single Photon Emission Computer Tomography (SPECT) showed a prevalent cerebellar perfusion as well. Neuropsychological testing was consistent with severe cognitive deterioration and attention disorders. Language and praxis functions seemed to be preserved. Auditory oddball ERPs (P300) showed morphological abnormalities especially of late components. This case report demonstrates in vivo the level of adaptation to which human brain can reach under chronic mechanic stress conditions. The striking poor cerebral parenchyma representation and the relatively spared language and praxic abilities account for a functional reorganization of residual structures due to the neural plasticity

Longitudinal study of cognitive dysfunction in multiple sclerosis: neuropsychological, neuroradiological, and neurophysiological findings

Objective: (1) To assess cognitive function and cerebral magnetic resonance imaging (MRI) involvement in relapsing-remitting multiple sclerosis; (2) to monitor disease evolution, cognitive dysfunction, and cerebral lesion burden over time (mean 8.5 year follow up period); (3) to study the relation between clinical, neuropsychological, and MRI data. On follow up assessment, visual and auditory oddball event related potentials (ERPs) were recorded as psychophysiological evaluation of cognitive status. Correlations between neuropsychological, MRI, and ERP data were also analysed. Methods: Neuropsychological study assessed verbal and non-verbal IQ, deterioration index (DI) from WAIS subtests, conceptual reasoning, attention, verbal and visuospatial short-term and long term memory. MRI assessment detected presence of demyelinating lesions by using a semiquantitative method as well as cortical and subcortical atrophy over time. Results: Attention, short-term and long term visuospatial memory were mildly impaired at baseline and remained unaltered longitudinally. At retesting a significant worsening of verbal long term memory (p=0.023), DI presence (p=0.041) and the increase of supratentorial and subtentorial MRI lesions load (p=0.001) emerged. Expanded disability status scale score correlated significantly with total lesion burden at both evaluations (p=0.043 and p=0.024 respectively). Temporal, occipital, and frontal horn lesions as well as cortical atrophy correlated significantly with attention and memory tests at baseline. Follow up assessment revealed significant correlation between cortical atrophy and attention as well as visuospatial short-term memory; spatial long term memory correlated significantly with lesions in body of lateral ventricle and frontal lobe. ERP study showed P300 latency abnormalities in 75% of patients, involving specifically more visual P300 (58.4 % of cases) than auditory wave (41.6 %). Visual P300 latency and amplitude correlated significantly with DI and auditory P300 latency with frontal horn and brain stem lesions. Conclusions: These findings revealed mild cognitive impairment in MS patients particularly consistent with slowing information processing over time. Increased MRI lesions do not correlate with the clinical course of the disease and cognitive deficit evolution. Thus, cognitive dysfunction could be related to disease peculiarity and not to the time course. Correlations between P300, neuropsychological, and MRI findings provide further information about ERP application to examine cognitive impairment in MS and probably to investigate their neural origin.</br

Prevalence of primary blepharospasm in Sardinia, Italy: a service-based survey

We performed a service-based epidemiological study of primary blepharospasm in the island of Sardinia (Italy). Due to its favorable geographical location, we are confident we will provide reliable data from patients seeking botulinum toxin treatment. A total of 53 patients were assessed. Prevalence was estimated to be 32.2 per 1 million (95% confidence interval, 23.0-40.8). These results are in line with those obtained in other similar surveys, that is, record-based, and performed in various European regions such as Northern England, the Munich area, as well as the Epidemiologic Study of Dystonia in Europe