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Knowledge about the balance between heritable and nonheritable risk in multiple sclerosis (MS) is based on twin studies in high-prevalence areas. In a study that avoided ascertainment limitations and directly compared continental Italy (medium-prevalence) and Sardinia (high-prevalence), we ascertained 216 pairs from 34,549 patients. This gives a twinning rate of 0.62% among MS patients, significantly less than that of the general population. In continental Italy, probandwise concordance was 14.5% (95% confidence interval, 5.1-23.8) for monozygotic and 4.0% (95% confidence interval, 0.8-7.1) for dizygotic twins. Results in Sardinia resemble those in northern populations but in limited numbers. Monozygotic concordance was 22.2% (95% confidence interval, 0-49.3) probandwise, but no concordant dizygotic pairs were identified. A questionnaire on 80 items possibly related to disease cause was administered to 70 twin pairs, 135 sporadic patients, and 135 healthy volunteers. Variables positively (7) or negatively (2) associated with predisposition and concordance in twins largely overlapped and were mainly linked to infection. If compared with previous studies, our data demonstrate that penetrance in twins appears to correlate with MS prevalence. They highlight the relevance of nonheritable variables in Mediterranean areas. The apparent underrepresentation of MS among Italian twins draws attention to protective factors, shared by twins, that may influence susceptibility.

In order to evaluate whether the results of ultrasound examination may be associated with 30-day outcome, 76 consecutive patients (43 men and 33 women; mean age 68.1 +/- 8.9 years) underwent duplex scanning of the carotid bifurcations and transcranial doppler investigation of the basal skull arteries within the first few hours of the onset of an acute carotid stroke. Forty-three patients (56.6%) had appropriate arterial occlusion at ultrasounds examination. On day 30, 22 patients (28.9%) were self-sufficient, 41 (53.9%) were disabled and 13 (17.1%) were dead. The chi-squared test showed that the ultrasound results were significantly related to 30-day outcome (p = .0003). After logistic regression analysis, the ultrasound results remained independent predictors of 30-days outcome (p = .0129), together with neurological impairment 24 hours after stroke onset and lesion size at control computed tomography. Our study suggests that the results of ultrasound examination may be useful in the management of acute carotid stroke as an early indicator of patients with a worse prognosis.

To assess if Doppler microembolic signals (MES) associated withor = 60% symptomatic extracranial carotid stenosis may predict ischemic recurrences before endarterectomy or angioplasty.All patients withor = 60% carotid stenosis with symptoms in the preceding 2 months were prospectively considered. MES were identified using current criteria. All patients were followed-up until endarterectomy or angioplasty.We studied 50 patients, at a median of 7 days from their last symptom. Twenty patients showed MES (40.0%); median embolus rate was 4/h. During a median follow-up of 19 days 7 patients had recurrences (transient monocular blindness = 2; TIAs=4; stroke=1); 6 of them had shown MES. The association between recurrences and MES was significant (P=0.012).MES may identify patients with symptomatic carotid stenosis who are likely to suffer an ischemic recurrence before endarterectomy. This information may affect medical treatment and referral to the vascular surgeon.

We have investigated recurrence of stroke in a consecutive series of young adults, aged 16 to 45 years, after a first cerebral infarction.From January 1, 1988 to December 31, 1996 we submitted those patients to a diagnostic protocol including angiographic, cardiological, and haematological investigations. The patients were followed at 6 month intervals up to December 31, 1998.We have evaluated and followed-up 135 patients, 71 men and 64 women, who were 3.99% of all the admitted stroke patients. At 12 months after stroke, 83 patients had returned to work, 40 patients were mildly to moderately handicapped, 4 were using a wheel-chair, and 8 had died. Follow-up was 26 to 123 months (mean 68.8). Recurrence of stroke, always of ischaemic nature, was seen in 15 patients (11.1%), 3 to 76 months after the first stroke (mean 27.4), for an annual incidence of 2.26%. Recurrence was significantly associated with Partial Anterior Circulation Syndrome and Haematological subtype of first stroke (respectively, P = 0.0209 and P = 0.0135, chi2 test), but not with age (or = or35 years) or risk factors. Repetition of stroke was never fatal, but it caused heavy disability in 13 patients, 8 of whom had completely or nearly completely recovered after the first event.Our data suggest that recurrence of stroke is a major clinical problem also for the patients aged less than 45 years and that it might be more frequent with specific clinical syndromes and etiologic subtypes of first stroke.

To evaluate the presence of microembolic signals (MES) in the middle cerebral artery distal to a stented carotid artery late after stent deployment. MES may be a signal of thrombus formation at the stent level.Two patient groups were studied with transcranial Doppler at different intervals after deployment of Palmaz stents or Wallstents for stenosis of the internal or common carotid artery. Group 1: from 6 to 12 months after stent deployment; Group 2:12 months after stenting.One out of 19 patients in Group 1 showed MES (5.0%); however, this patient also had two mechanical heart valves. None out of 17 patients in Group 2 had MES.Carotid stents seem to have a very low emboligenic potential after the early post-deployment period. This is a reassuring message for present and future patients harboring such stents.

Objective: To determine the direct costs of hospital care of acute ischemic stroke in a large Italian hospital, and to identify the main components of such costs. Background: Cost containment in stroke care requires an up-to-date assessment of expenditures in the different areas of stroke management. However, costs may vary among countries because of different health system organizations. Methods: All patients with ischemic stroke admitted during 1996 were considered. Total cost was the sum of a daily component, reflecting personnel wages and general care, and an ancillary component, reflecting mostly investigations and treatments. The real costs were used, not fixed charges. Results: We included 245 patients, with a mean length of stay (LOS) of 13.1 ± 7.0 days, and an in-hospital case fatality rate of 8.2%. The mean total cost per patient was 5,087,000 ± 2,536,000 Italian Lira (LIT; $3,289 ± $1,640), with a mean cost per day of 388,000 LIT ($251). Approximately 80% of total costs were due to the daily component and 20% to the ancillary component. A multiple linear regression model of length of stay, which determines the daily cost, showed that the Rankin score at entry, the clinical syndrome type, and the destination at discharge independently contributed to LOS. A second linear regression model showed that younger age and longer LOS significantly increased ancillary costs. Conclusions: The containment of hospital costs of ischemic stroke may be achieved mostly through measures that reduce LOS, such as effective treatments and a quicker deployment.

We report a series of nine patients younger than 45 years with angiographically-documented cerebral venous thrombosis, consecutively referred to our Stroke Unit from 1988 to 1994. Two of them were men and seven were women. Eight patients initially complained of headache, often associated with other symptoms of increased intracranial pressure. Seven patients had focal motor deficits and four suffered from epileptic seizures. None of the patients died. Only one patient remained severely disabled, whereas the others recovered self-sufficiency within two months. The use of oral contraceptives was closely associated with the occurrence of venous thrombosis in the women. Cerebral venous thrombosis is to be kept in mind in the differential diagnosis of stroke in the young.

Introduction - We have undertaken a prospective study to measure anticardiolipin antibodies of IgG isotype within the first few hours of an acute non-hemorrhagic stroke. Material and methods - We have collected blood samples at entry from one hundred patients (53 men and 47 women), mean age 67.4 years, referred within 6 h of a first-ever non-hemorrhagic stroke, and from an equal number of age- and gender-matched control patients. Results - IgG anticardiolipin antibodies were ≥10 GPL in 26 patients and in 5 controls (p

Essential thrombocytemia (ET) is a clonal myeloproliferative disorder of unknown cause, characterized by an increased number of apparently normal platelets. It has been related to a large number of mild ischemic complications, but rarely to acute stroke associated with documented large vessel thrombosis. We report the cases of 6 patients with acute ischemic stroke associated with ET (4 men and 2 women; mean age 61.7: range 49-78 years). The diagnosis of ET followed the onset of the stroke. The number of platelets was never greatly increased at the time of the stroke, and two patients presented no major risk factors for stroke. The involvement of the posterior circulation was observed in three patients, that of the anterior circulation in two patient and that of the border territory in one. The obstruction of large intracranial or extracranial vessels was detected in all of the patients, and all of them were treated with antiplatelet agents (aspirin or ticlopidine). The outcome was good in 3 patients, fair in one and bad in two. We retain that ET might be a cause of acute ischemic stroke as a result of large vessel obstruction.

UNLABELLED We have investigated the reliability of transcranial doppler compared with cerebral angiography in acute ischemic stroke in the middle cerebral artery territories. We studied 48 patients, 28 men and 21 women, mean age 68.1 (range 54-75), observed within 5 h of the onset of ischemic stroke in the middle cerebral artery territory. Ultrasound evaluation (duplex scanner and transcranial doppler) and cerebral angiography were carried out in close sequence immediately after CT scan. CT was repeated by Day 7 to estimate the infarct size: 27/48 patients had intracranial arterial obstructions. An acoustic temporal "window" was not found in 6.25%. Transcranial doppler showed a sensitivity of 80.0% and a specificity of 90.0% compared with cerebral Angiography for patients with patent acoustic temporal "windows". Accuracy was 79.2%, when patients with no "windows" were included. With respect to intracranial internal carotid artery and middle cerebral artery mainstem, transcranial doppler showed a sensitivity of 95.0%, and a specificity of 92.0%. Including patients with no windows, accuracy was 87.5%. CONCLUSIONS Our data suggest that Transcranial Doppler can be reliably used to demonstrate intracranial internal carotid artery or middle cerebral artery mainstem obstructions in the acute phase of a brain infarction.

We have tested the feasibility of local intraarterial thrombolytic therapy in ischemic stroke in the carotid artery territories observed within 5 h of the onset of symptoms. Only 5 of 615 consecutive patients were enrolled. They were 1 man and 4 women aged 50 to 75 years. Angiography disclosed occlusion of the M2 tract in one, of the M3 tract in one, of the carotid siphon in one of M4 tract in two. Intraarterial urokinase was infused at a mean dosage of 560,000 units close to the site of occlusion. Four of them had partial or complete recanalisation at early angiographic control and were independent at 6th month control. The one who did not demonstrate recanalisation was confined to a wheelchair. One patient, who had recanalisation, sustained a hemorrhagic transformation of the brain ischemia not interfering with outcome. Our experience, at the light of the low rate of enrollment, despite the results, suggest that intraarterial thrombolysis may be a therapeutic tool for selected patients with stroke in the carotid artery territories and not a routinary treatment for them.

To elicit possible variations in the CSF concentrations of copper, iron and manganese due to Parkinson disease (PD) or to the stage reached, we tested 11 patients with idiopathic PD, 6 untreated and 5 on long term L-dopa, versus 22 age and sex matched patients with other neurological disorders (control group-CG). The CSF levels of the three metals, measured by electrothermal atomization, did not differ significantly between the PD group and CG or between either of the PD subgroups and CG. Our findings therefore do not support the hypothesis that CSF Cu is a marker of PD.

We have observed 9 patients (8 men and 1 woman), 58 to 77 years of age with neuropathy with only sensory symptoms and insidious onset. Five of them (4 men and 1 woman) aged 65 to 77 years, had normal serum electrophoretic profiles, while the others (all men), 58 to 74 years, had IgM monoclonal gammopathy of undetermined significance (MGUS). Clinical data were consistent with a sensory neuropathy affecting predominantly the kinesthetic sense (position and vibration sensation). The electrophysiological data indicated predominant sensory axonal neuropathy. Morphological data confirmed the primary axonal damage. Western immunoblot showed that the IgG from a patient without MGUS reacted with a 55 kD protein of dorsal root ganglion homogenate. Three of four patients with IgM MGUS were serum reactive against chondroitin sulfate C (ChS-C) in double immunodiffusion. After absorption with ChS-C the monoclonal peak completely disappeared from two patients and was decreased in the third patient. Our data indicate that immunological abnormalities are part of the pathogenesis for a subgroup of chronic neuropathy with only sensory symptoms.

Twelve parkinsonian patients (6 men and 6 women), mean age 60.5 years, range 47-72, were examined with autonomic test when de novo and after 2 years of continuous levodopa treatment. They were all free from any disease interfering with autonomic examination. When de novo they had a significant decrease of heart rate response to deep breathing and to laying to standing tests if compared with an age- and sex-matched control group (15.6 +/- 8.8 vs. 28.6 +/- 12.1, P less than 0.01 and 7.0 +/- 7 vs. 14.2 +/- 5, P less than 0.01). After 2 years of levodopa treatment they had a non-significant decrease of heart rate response to deep breathing test (21.8 +/- 10.6, P N.S.) and a still significant decrease of heart rate response to laying to standing test, but at a lesser level (7.7 +/- 7.0, P less than 0.05). Furthermore, they showed a significant decrease of the systolic and MAP orthostatic pressure to tilting table (-9.2 +/- 12.0 vs. +4.9 +/- 8.9 and -4.5 +/- 8.4 vs. +4.7 +/- 5.1, both P less than 0.01) probably due to medication. The other tests were never significant. We hazard as possible explanation an action of levodopa on dopaminergic neurons in the nucleus dorsalis of vagus.

Somatosensory evoked potentials (SEPs) following median nerve stimulation were used to monitor cerebral function during 26 carotid endarterectomies. The patients with minor SEP variations had no neurological deficits on regaining consciousness while the one with more serious SEP variations had a transient deficit. The method thus seems useful in the early detection of ischemic brain impairment.

Nerve conduction velocity and visual evoked potential studies were conducted in 31 patients with chronic renal failure undergoing periodic hemodialysis. The results indicate damage to the central nervous system, such as delayed P100 wave, even in the absence of clinical signs, and to the peripheral nervous system, such as distal sensorimotor neuropathy. The degree of peripheral involvement correlates with the duration of dialysis and with some blood chemistry values but not with the evoked potential parameters. There is no correlation between central and peripheral nervous damage, which presumably points to a difference in pathogenesis.

There is little evidence of autonomic dysfunction in PD, although autonomic disturbance was included in the original description by J. Parkinson. In addition, there are no data for de novo PD patients. We selected 14 de novo parkinsonians (seven men and seven women), aged 62.7 +/- 8.2 years, with mild disease (stage 1 through 2 on the Hoehn and Yahr's scale), without history of diabetes, heart disease, or alcoholism, and without neuropathy or orthostatic hypotension. Fourteen age- and sex-matched normal persons were controls. We found a highly significant difference in the respiratory sinus arrhythmias during deep breathing (p less than 0.01); the basal heart rate, the respiratory sinus arrhythmias during quiet breathing, and the Valsalva ratios did not differ statistically, however. In the absence of neuropathy and orthostatic hypotension and in the presence of normal Valsalva ratios, we believe that the abnormality found by us may apply only to parasympathetic dysfunction, perhaps at a central level. In addition, the abnormality seems to be independent of stage and therapy.

3 patients with Myotonic Dystrophy (MD) and associated leg motor neuropathy, confirmed in two of them by biopsy of one branch of lateral popliteal nerve, were studied with Multimodality Evoked Potentials. Abnormalities of VEPs and BAEPs, in agreement with literature, were found in all patients. Median SEP peripheral conduction velocity, N9-N13 and N13-N20 conduction time were normal. On the contrary, all patients showed reduced lower limb SEP peripheral conduction velocity niloutstanding normal nerve biopsy. These results suggest in MD neurological abnormalities occur outside muscular system, too.

The motor and sensory conduction velocities were measured, and the somatosensory evoked potentials were recorded on median nerve stimulation in 20 epileptics on long-term carbamazepine therapy. The plasma drug levels were monitored and found to be consistently within therapeutic range. The electrophysiological study showed that the motor and sensory conduction velocities in the lower limbs were significantly lower than in age-and sex-matched controls, while no significant variation was found in the somato-sensory evoked potentials. There was no correlation between the neurophysiological data and any of the pharmacological data, such as duration of treatment, plasma levels and dose of drug per Kg of bodyweight per day.

By using dopplersonographic techniques we compared the blood flow of glaucomatous eyes to that of normal eyes. 65 glaucomatous eyes belonging to 33 patients (14 men and 19 women) of an average age of 67.1 years were compared to 38 normal eyes belonging to 19 subjects of an average age of 66.5. We investigated the ophthalmic arteries both in the supertrochlear area and in the lateral superorbital area. We discovered a high statistical difference in the examination of the blood flow velocity in the lateral superorbital area and versus the controls. It is possible that information from posterior ciliary artery flow could be obtained by the Doppler examination at that point of the orbit.

A 40 year-old woman with a rapidly progressive proximal muscle deficit of all four limbs had an acute myopathy secondary to hyperthyroidism. Biopsy of the quadriceps femoris revealed signs of non specific muscle impairment with type II fiber atrophy. Treatment with methimazole and correction of the thyroid condition led to rapid disappearance of the disorders. Eighteen months later the clinical status was normal and a second quadriceps femoris biopsy showed that the muscle had normalized.

Parasympathetic function in 7 Huntington's chorea patients with a duration of the disease ranging from 1 to 20 years, was evaluated by studying R-R intervals during quiet and deep breathing and Valsalva manoeuvre. All 7 patients were free of neuropathy, orthostatic hypotension, heart or lung disease and had had no medication for at least 15 days prior to hospitalization. Seven normal subjects served as controls. On the whole, the responses of the Huntington's chorea patients were not significantly different from those of the controls. Abnormal responses to all the tests were received in only one patient and a low R-R variability during deep breathing in the youngest patients. Unlike other Central Nervous System degenerative disorders, in Huntington's disease parasympathetic autonomy seems to be sufficiently preserved.

Summary: Somatosensory evoked potentials from median nerve stimulation were recorded in 12 patients with newly diagnosed epilepsy, before and after 1 year of treatment with carbamazepine. The plasma concentrations of the drug were consistently within therapeutic range. We assessed the latencies of the early components at the level of the cervical spine (N9 and N13) and on the parietal scalp (P14, N20, P25) and the interpeak latencies (N9-NI3, N13-N20, P14-N20). None of the patients presented anomalies in any of the parameters, and there was no significant difference between the patient and control means or between the patient means before and after 1 year of treatment. RESUME Les potentiels evoques somesthesiques obtenus par stimulation du nerf median ont ete enregistres chez 12 patients presentant une epilepsie fraichement diagnostiquee avant et apres une annee de traitement par carbamazepine (CBZ). Les taux san-guins du medicament ont ete maintenus dans les zones therapeutiques. Nous avons mesure la latence des composants precoces au niveau de la moelle cervicale (N9 et N13) et au niveau du scalp parietal (P14, N20, P25), ainsi que les latences entre les pics (N9-N13, N13-N20, P14-N20). Aucun des patients n'a presenteľanomalie ľaucun de ces parametres; nous n'avons pas constate de difference significative entre les valeurs moyennes obtenues chez les patients et chez les controles, ou chez les patients apres une annee de traitement par CBZ. RESUMEN En 12 pacientes con diagnostico de epilepsia reciente se han registrado los potenciales evocados somatosensoriales, me-diante estimulacion del nervio mediano, antes y despues de un ano de tratamiento con carbamezepina. Las concentraciones plasmaticas de la droga estuvieron siempre dentro del rango terapeutico. Hemos determinado las latencias de los componentes precoces a nivel de la columna cervical (N9 y N13) y en el cuero cabelludo parietal (P14, N20 y P25) y las latencias “interpicos” (N9-N13, NI3-N20, P14-N20). Ninguno de los pacientes pre-sento anomalias en los citados parametros y no se observaron diferencias significativas entre los promedios de los pacientes y de los controles o entre los promedios de los pacientes antes y despues del tratamiento.