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Cognitive impairment in multiple sclerosis (MS) has received considerable interest over the last decades. Heterogeneous patterns of cognitive dysfunction have been reported in literature in relation to the subtype of the disease and the severity of specific cognitive domains affected. Event related potentials (ERPs), especially P300, have been employed to evaluate the cognitive decline in MS and neurophysiological findings agree with data obtained by neuropsychological testing. The objectivity, the reliability and the easy administration are the main features of ERP technique but more specific attention and memory tasks are needed to enhance the clinical value of the methodology. Moreover, ERP recording has the advantage of being feasible even in severe disabled patients. Finally, longitudinal ERP studies are required to investigate the natural course of cognitive dysfunction in MS, to estimate the prognostic value of subclinical defects in different clinical form of the disease and to evaluate clinical benefits of therapeutic and rehabilitative interventions.

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.

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.

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.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.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 (P0.04) and auditory (P0.04) P300 latency and impaired NP tests was found.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.

To evaluate possible cause-effect relationships between hyperostosis frontalis interna and cognitive dysfunction, we performed a neurophysiological (event-related potentials, ERPs) and neuropsychological study in a case of Morgagni-Stewart-Morel (MSM) syndrome associated with frontal lobe compression. Neuropsychological evaluation evidenced selective impairment of executive function. Visual and auditory oddball ERPs revealed delayed P300 latency and reduced auditory P300 amplitude with multi-peaked morphology. ERP abnormalities and cognitive dysfunction could be due to the frontal bone-cortex conflict documented by neuroradiological investigations.

Experimental studies in monkeys have demonstrated that injection of gamma-aminobutyric acid (GABA) agonists into the superior colliculus restricts saccadic eye movements, while injection of GABA antagonists leads to square-wave jerks (SWJ). To investigate the role of GABA in saccadic interruptions of fixation, we treated five patients who had SWJ and square-wave oscillations (SWO) with valproic acid (VPA) (2000 mg/d), which has been shown to increase brain GABA levels. VPA effectively reduced the SWJ/SWO in three patients, abolished them in one patient, but was ineffective in the fifth, who had a localized lesion in the cerebellar vermis. VPA effects may have been due to the restoration of the GABAergic tonic inhibitory action from the substantia nigra pars reticulata to the superior colliculus.

The Sardinians are an ethnically homogeneous population, having a genetic structure quite different from that of all other Italian and European populations. All epidemiological studies carried out in Sardinia since 1975 indicate that this Mediterranean island shows twice the prevalence of multiple sclerosis (MS) compared to continental Italy, but the size of the Sardinian communities so far surveyed has been too small to draw definitive conclusions. To overcome this draw-back, we have studied the frequency of MS in a well-defined area of north-western Sardinia, with a population of about 270,000 in the 1991 census. Based on 276 MS cases, the prevalence on December 31st, 1991, was 102.6 per 100,000. The incidence, averaging 2 per 100,000 in the period of 1962 to 1971, rose to 5 in the period from 1977 to 1991. The present study confirms the higher frequency of MS among Sardinians compared to other Italian populations. Genetic, linguistic and historical data suggest a role of environmental and genetic factors in determining the notable difference in MS risk between Sardinia and the rest of Italy.

Interaction of tonic labyrinth and neck reflexes was studied in 3 healthy volunteers by analyzing changes in Soleus H-Reflex (SHR) area in relation to both lateral tiltings and neck rotations. By using a Kermath chair each subject was tilted laterally from the vertical to the left and to the right up 15 degrees in steps of 5 degrees and at the same time the longitudinal body axis, keeping the head fixed, was rotated to the right and to the left up to 15 degrees in steps of 5 degrees. All combinations of lateral tiltings and neck rotations were tested. Each test position was followed by a return to 0 degree for both rotation and tilting (control position). Twelve H-reflexes of right soleus muscle were recorded in each test and control position and the changes in RSHR area were expressed as percentage variations from the mean value absorbed in the pretest and post-test control position. Our data indicate that in man, as in animals, labyrinth and neck reflexes act in the opposite direction, and that in the static condition their contribution to postural stabilization is equal.

To investigate whether internuclear ophthalmoparesis (INO) due to demyelination of the medial longitudinal fasciculus (MLF) provides a model for studying the poorly understood symptom of fatigue in multiple sclerosis (MS). We asked whether repetitive horizontal saccades increased eye movement disconjugacy in patients with MS with INO, but not in healthy subjects.We compared conjugacy of horizontal saccades in 9 patients with INO (4 bilateral, total 13) and 8 controls during minute 1 and minute 10 of a fatigue test; we measured the ratio of abducting/adducting peak velocity (versional disconjugacy index [VDI]).VDI values were greater in patients than controls. During the fatigue test, controls showed no changes of VDI, but patients did (p0.005) for 10/13 INOs, with increased ratios in 5 cases and a decrease in the other 5.Fatigue-induced worsening of conjugacy was observed in milder internuclear ophthalmoparesis (INO), and may reflect deteriorated fidelity of saccadic pulse transmission along demyelinated medial longitudinal fasciculus. Improved conjugacy was observed in the more severe INOs, and may be due to adaptive mechanisms, such as recruitment of vergence to aid gaze shifts. INO may provide an accessible, reductionist model to study how decreased neural transmission influences fatigue in multiple sclerosis, how the brain adapts to it, and whether drugs may prove therapeutic.

Background and Relevance: Intracranial atherosclerosis is responsible for 70,000 ischemic strokes each year in the USA. Noninvasive testingsuch as transcranial Doppler ultrasound (TCD) and magnetic resonance angiography (MRA) to identify intracranial atherosclerosis is in widespread use, but has not been rigorously validated against the gold standard, catheter angiography. The recently NIH-funded Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial will compare warfarin with aspirin for stroke prevention in patients with intracranial atherosclerosis. WASID requires performance of angiography along with TCD and MRA, providing an opportunity to critically evaluate these noninvasive tests. Main Objective: The purpose of the Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) study is to develop the noninvasive diagnosis of intracranial atherosclerosis. The primary aim of SONIA is to define velocity values on TCD and anatomic abnormalities on MRA that identify severe (50–99%) intracranial stenosis of large, proximal arteries seen on catheter angiography. SONIA will define the criteria, or ‘cutpoints’, for an abnormal TCD or MRA and show that they perform with a reliable positive predictive value (PPV). Study Design: SONIA will be conducted in collaboration with WASID. Study-wide cutpoints defining positive TCD and MRA have been developed and reviewed by the site investigators of WASID. Hard copy angiography, TCD and MRA generated in WASID will be centrally read in SONIA. TCD and MRA cutpoints seek to achieve a target PPV of 80% for the identification of severe intracranial stenosis on angiography. Conclusions: Central readings will be used to validate the cutpoints and to develop measures of negative predictive value, and inter- and intra-observer variability. Sensitivity and specificity will be determined after adjustment for verification bias and employed in receiver-operator characteristic analyses. SONIA will use these techniques to develop TCD and MRA cutpoints that minimize the clinical consequences of test errors occurring in the noninvasive evaluation of patients with suspected intracranial atherosclerosis.

Cerebellar pathology commonly shows important motor signs and less evident cognitive dysfunction. The ’cerebellar cognitive affective syndrome’ is characterised by impairment on executive function, spatial cognition, language and behaviour. We report the case of a man with acute onset of transitory motor features and severe mental disorders. Cranial CT and brain MRI revealed extended cerebellar lesions. Neuropsychological assessment disclosed deficits of attention, executive function and memory. Auditory event–related potentials showed abnormal P300. These data suggest a pure “cerebellar cognitive affective syndrome” and strengthen the hypothesis of cerebellar cognitive function modulation.

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.

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.

The aim of the study was to evaluate the sensitivity of pSEP in patients affected by probable MS.Bladder dysfunction is the presenting symptom in 2\% of patients affected by multiple sclerosis (MS) and may be present in up to 78\% of them. Abnormalities of somatosensory evoked potentials of the pudendal nerve (pSEP) have been found by many authors in patients affected by clinically defined MS, but little is known of diagnostic reliability of pSEP in early stage of MS.Sixteen patients, eleven females and five males, aged between 18 and 45 years old (mean age 28.9), affected by clinically probable MS, were studied. Six of them reported retention or urge incontinence. pSEP with P1 (P40) scalp wave was analyzed. All patients also underwent visual evoked potentials (VEP), SEP of median and tibial nerves (mSEP, tSEP), brainstem acoustic evoked potentials (BAEPs), MRI of the brain and cerebrospinal fluid (CSF) evaluation. Urodynamic study with simultaneous measurement of intravesical, intraurethral and abdominal pressures with external sphincter electromyography was performed.Abnormalities of the evoked potentials were found in all patients. Abnormalities of the pSEP were observed in all the symptomatic cases and in eight of the remaining ten patients; ten showed no responses from the scalp and four showed P1 increased latency. Urodynamic abnormalities were found in 12 patients and MRI showed demyelinating lesions in 13 patients and oligoclonal bands were found in eight of them.pSEP can be worthwhile as part of the initial diagnostic evaluation in patients affected by MS. It provides information of diagnostic relevance and plays a role in screening patients for urodynamic testing, which, however, is more specific for detecting urethrovesical dysfunctions and preventing urological complications.

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.

Bladder dysfunctions are often observed in patients with multiple sclerosis (MS). In order to evaluate their sensitivity in detecting abnormalities in bladder central control pathways, pudendal nerve somatosensory evoked potentials (pSEPs) were recorded in 16 patients with clinically probable MS: six were affected by retention or urge incontinence, and ten were asymptomatic. Conventional visual, auditory and somatosensory evoked potentials were also recorded, and all of the patients underwent a urodynamic examination. Prolonged latency or the absence of pSEP cortical responses was found in eight of the ten asymptomatic patients, and in all of the symptomatic cases (87.5\%). The urodynamic evaluation revealed abnormalities in 12 patients (75\%). Our findings seem to indicate an early and frequent involvement of bladder control pathways in MS patients, as well as a high rate of subclinical disorders.

A previous epidemiological study on myasthenia gravis (MG) in Sardinia indicated a prevalence rate of 4.5 per 100,000 population and an incidence of 0.25 per 100,000 population in the period 1958-1986. This study, however, investigated the entire Sardinian population (about 1,500,000) and the reported rates are likely to be underestimated. Because the use of a very large population has been found to cause major bias in case finding, the present study was designed to overcome this bias by determining the prevalence and incidence of MG in a well-defined area of Northwestern Sardinia, with a population of about 270,000 (1991 census). Potential MG cases were ascertained using all possible medical sources. The diagnosis of MG was based on the clinical, neurophysiological and conventional pharmacological findings (Tensilon test, response to anticholinesterases). On prevalence day (December 31, 1994) 29 MG patients were living in the study area (17 women and 12 men). Since the total population on prevalence day was 268,926 (137,284 women and 131,642 men), the calculated prevalence was 11.1 per 100,000 population (12.4 women and 9.9 men). The present study shows that the risk of MG in Sardinia is higher than previously suggested. The risk, however, is not significantly different from that found in other comparable Italian and European areas. It contrasts with what has been found for other autoimmune diseases such as multiple sclerosis and insulin-dependent diabetes mellitus in Sardinians, both showing frequencies up to 3-5 times higher than in the rest of Italy.

The sympathetic skin response (SSR) permits recording of the sympathetic amyelinic fibres activity in relation to the function of sudoriparous glands. We recorded the SSR to check the efficacy of "nerve-sparing" technique in surgery of the sympathetic retroperitoneal postganglionic fibres following lymphadenectomy in nonseminomatous testis cancer. The results showed that SSR can be used to verify the integrity of the lumbar sympathetic chains after retroperitoneal lymphadenectomy.

• Objective. —To study the role of HLA genes in susceptibility and resistance to multiple sclerosis (MS) in Sardinian patients. To verify whether HLA-DQA and HLA-DQB genes differed between unrelated (MSU) and related (MSR) patients, and whether relapsing-remitting and chronic progressive forms of MS are immunogenetically distinct entities. Design. —Case-control study of HLA-DQA and HLA-DQB gene frequency. Setting. —All patients investigated were followed up by our MS referral centers. Patients. —The study involved 116 MSU patients, 67 of whom had a relapsing-remitting form (MSr), 28 of whom had a chronic progressive from-the-onset form (MSc), and 21 of whom had a benign form (MSb), 32 patients with MSR, 19 parents and 27 healthy siblings of patients with MSR, and 86 controls. Selection of patients was random, while control subjects came from families without known immunologic diseases. All patients had definite MS. Main Outcome Measure. —Statistical analysis of gene frequencies was conducted with the ϰ 2 test with correction ( P c ) for the alleles investigated, as was decided before the study began. Results. —The DQA1*0301 allele was found to be increased in patients (MSU vs controls, P c =.008; patients with MSc vs controls, P c =.001; patients with MSR vs controls, P c =.02; and parents vs controls, P c =.04), while the DQA1*0102 allele was found to be diminished in patients with MSr vs controls ( P c =.001 ). Among the DQB genes, the DQB1*0502 allele was diminished in patients with MSr vs controls ( P c =.04), while the sum of DQB1*0201 and *0302 alleles was significantly increased in patients with MSR vs controls ( P c =.003). Conclusion. —Both HLA-DQA and HLA-DQB genes influence genetic susceptibility and resistance to MS. The roles of these genes differ in the various forms of MS. Patients with MSU and MSR both share HLA-DQA susceptibility genes.

Static vestibular influences on extensor tone of the lower limbs in man were studied by analyzing the changes in right soleus H-reflex (RSHR) area in relation to lateral tiltings. Eight normal adult volunteers were tested in an experimental situation designed to minimize all afferent inputs, except the vestibular ones. Each subject was seated on a chair which could be tilted laterally from the vertical to both sides. Lateral tiltings were applied at a random order from the vertical (0 degree, control position) to 4 degrees, 8 degrees, 12 degrees, 16 degrees, and 20 degrees of both sides (test positions). The results showed inhibition in SHR area of the leg ipsilateral to the tilting and facilitation of the contralateral SHR. These data indicate that, in man, as in the decerebrate cat, tonic labyrinth reflexes act asymmetrically and that, in static condition, the vestibular system modulates muscle tone of the lower limbs adequately to counteract lateral perturbation of upright position.

In Wilson's disease neurological manifestations result from the damage in the basal ganglia, even if a widespread degeneration of the brain occurs. The few studies performed using evoked potentials with the aim of identifying subclinical dysfunction in the three major sensory pathways have never shown abnormalities in patients without neurological manifestations. To verify this observation we studied 12 patients suffering from Wilson's disease in a pre-neurological stage by using pattern visual evoked potentials (VEPs), somatosensory evoked potentials (SEPs) to median nerve stimulation and brainstem auditory evoked potentials (BAEPs). Four of these patients had not yet been treated with penicillamine or trientine (triethylenetetramine dihydrochloride), while the remaining 8 patients were on treatment for at least 1 year. In 3 patients of this second group and in 1 patient of the first group we observed a significant (3 SD over the mean) increase in P100 wave latency, while SEPs and BAEPs were found to be abnormal in only 1 patient, respectively.

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.

We treated 3 multiple sclerosis patients who had pendular nystagmus with isoniazid (800 to 1,000 mg/d). Isoniazid abolished the nystagmus and relieved oscillopsia in 2 patients but was ineffective in the 3rd in whom the nystagmus was damped with convergence and vision improved with converging (base-out) prisms.

A 47-year-old man developed a persistent form of alexia without agraphia as the result of a haemorrhagic intracerebral lesion in the left inferior temporo-occipital region, due to the rupture of an arteriovenous malformation. Surgical evacuation of the haematoma and excision of the malformation did not produce any modification of the reading deficit, which remained unchanged during a 4-year follow-up. The reading deficit was restricted to words and the patient was able to read only letter-by-letter, so that the whole words were reconstructed from the auditory names of the letters. So far, the disconnection explanation is the standard explanation of alexia without agraphia and the present case of verbal alexia may be regarded as being within this overall category. However, this explanation meets with unanswered questions that suggest more flexible interpretations. Neurolinguistic studies have questioned the unique character of alexia without agraphia as a clinical entity and, in contrast to the disconnection hypothesis, support the notion that the different varieties of alexia that are traditionally described represent distinctive syndromes, each with its own clinical features and pathophysiological basis. In this context, the reading properties in this case seem fully compatible with a deficit of the visual word-form system postulated by Warrington and Shallice, that is, the relatively early stage of the reading process through which a word-form or equivalent unit is attained. This system might be lateralized to the left hemisphere, as suggested by the fact that this case, like other cases of verbal alexia, had sustained damage to the left hemisphere and did not show any differential preservation of the reading of concrete words.

Quantitative eye movement recordings in a patient with suspected multiple sclerosis who had alternating esotropia, horizontal nystagmus and downbeat nystagmus showed occasional monocular macro square wave jerk intrusions and oscillations in the fixating eye during spontaneous monocular fixation, and binocular macro square wave jerk oscillations during the effort to fuse. Base-out (converging) prisms suppressed nystagmus, oscillopsia, and macro square wave jerks, and restored normal binocular function.

Three patients with postural and intention cerebellar tremor caused by a cerebellar infarction in the superior cerebellar artery distribution were studied; treatment with carbamazepine resulted in marked improvement.

Electrophysiological examination was performed on 50 type II diabetic patients to verify whether insulin secretory reserve is a factor influencing the susceptibility to develop polyneuropathy. The results showed that less significant metabolic derangement related to high insulin secretory reserve, and not the high insulin secretory reserve by itself, may prevent the development of neuropathic disorders. These data are consistent with the current opinion that diabetic polyneuropathy is the consequence of the metabolic derangement caused by chronic hyperglycemia.

Static vestibular influences on upper limb flexor tone were studied in man by analyzing the changes in flexor carpi radialis H reflex area with lateral tilting of the longitudinal body axis. Ten healthy volunteers and 2 labyrinthine defective patients were tested in an experimental situation designed to minimize all afferent inputs except vestibular ones. Each subject was seated on a chair which could be tilted laterally to the left or the right from the vertical. Head and trunk were fixed upright, upper and lower limbs in half-flexed position and forearm in an intermediate position between supination and pronation. Lateral tilting was applied at random from the vertical (0 degrees control position) to left and right (4 degrees, 8 degrees, 12 degrees, 16 degrees, 20 degrees test positions). Each test position was followed by a return to 0 degrees and in each control and test position 20 consecutive H reflexes were recorded. The data observed in the normal subjects showed flexor tone inhibition in the arm which was tilted downwards and facilitation in the contralateral arm. These findings suggest that in man, like in animals, labyrinth reflexes act asymmetrically and in the opposite direction to neck reflexes.

Quantitative eye movement recordings in a patient with suspected multiple sclerosis who had alternating esotropia, horizontal nystagmus, downbeat nystagmus, and saccadic dysmetria, showed occasional macro square wave jerk intrusions and oscillations in the fixating eye during spontaneous monocular fixation, and binocular macro square wave jerk oscillations during the effort to fuse.

An electrophysiological investigation on 29 dialysis patients was performed with the aim of verifying whether serum parathyroid hormone (PTH) and aluminum (Al) levels may play a role in the pathogenesis of uremic neuropathy. All patients except 1 showed electrophysiological abnormalities. Both PTH and Al levels were found to be significantly correlated with the time on dialysis. On the contrary, the values of each single electroneurographic parameter did not show any correlation with the duration of dialysis, PTH levels and Al levels. The authors conclude that PTH and Al does not seem to play a role in the etiology of uremic neuropathy.

Carbohydrate metabolism and insulin secretion were investigated in 26 patients with Parkinson's disease before and during L-dopa treatment. Oral glucose tolerance tests were performed on 13 patients treated with L-dopa alone and on 7 patients treated with L-dopa combined with Carbidopa. Intravenous glucose tolerance tests were performed on additional 6 patients treated with L-dopa alone. Results indicate that chronic L-dopa administration does not modify glucose metabolism. It was observed only a significant decrease of insulin secretion after oral glucose in the early phase (15th day) of treatment with L-dopa alone. This temporary effect may be related to the peripheral conversion of L-dopa to dopamine since insulin secretion during combined therapy was normal. The mechanism by which L-dopa transiently inhibits insulin release is not clear. Perhaps the oral administration of L-dopa alone causes an alteration in some gastrointestinal functions which are involved in the handling of oral glucose.

A boy with a left-hemispheric cerebellar astrocytoma had upbeat nystagmus exhibiting increasing-velocity slow phases. The nystagmus improved after excision of the tumour.

To the Editor.— The etiopathogenesis of motor neuron disease (MND) is at present unknown. It is likely that various factors play a role in its pathogenesis, 1.2 and certainly anterior horn cell degeneration can occur in a number of other diseases. 3-6 In the patient described here (a more detailed description will be published elsewhere), MND developed during the course of severe thyrotoxicosis, and was diagnosed on the basis of clinical, electrophysiological, and morphological findings. Report of a Case.— In a woman who was known to have Graves' disease, a bulbar form of amyotrophic lateral sclerosis (ALS) developed over a six-year follow-up period. The earliest neuromuscular manifestations appeared in 1973 (age 59 years) when, during an episode of severe hypermetabolism, she first noted hoarseness of the voice and difficulty in swallowing. At this time, a neurological examination showed slight weakness of the lower facial muscles, slight dysphagia for liquids, and

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.

Intensive search of all cases of MS occurring in the Sardinian commune of Macomer since 1912 indicated that MS was absent up to the early 1950s. All 13 ascertained cases had clinical onset in the years 1952-1981. During this period, the average annual incidence was 4.8 per 100,000; the highest incidence was found in the period 1957-1961, slowly decreasing up to 1981. MS was probably introduced after 1945, when the centuries-old isolation of Macomer ended and the native population came into contact with individuals from high- and medium-risk areas.

Prevalence studies carried out in Sardinia from 1975 suggest an increasing occurrence of MS. However, it is questionable whether this increase represents a real change in MS incidence or simply reflects longer survival. Data from 79 patients indicated the average annual incidence for the period 1965 through 1985 was 3. 4 per 100, 000. On December 31, 1985, the prevalence rate was 69 per 100, 000. Evaluation of MS temporal trends showed a significant increase in MS incidence during the study period: values ranged around two per 100, 000 in the triennial periods 1965–1967, 1968–1970, and 1971–1973, and around five in each triennium from 197-7 onward.

On the basis of previous epidemiologic studies, Parkinson disease was thought to be evenly distributed throughout the world. These studies, however, were conducted only on North European populations. The position with regard to the Mediterranean peoples was still unknown, and we therefore studied the frequency of Parkinson disease on the island of Sardinia, where some ethnic groups of the Mediterranean stock are represented. Based on 967 accepted cases, the prevalence 100,000 population on January 1, 1972, was 65.6; the average annual incidence for the period 1961 through 1971 was 4.9. These figures are one-half of the figures established for North Europeans. Our findings suggest racial differences in predisposition to Parkinson disease. Some Negroid features are present in Sardinians. If, as seems likely, Africans prove to be relatively unsusceptible to the disease, the risk for Sardinians and other Mediterranean ethnic groups might be intermediate between North Europeans and Africans.