The prognostic utility of the transcription factor SRF in docetaxel-resistant prostate cancer: in-vitro discovery and in-vivo validation.

BACKGROUND: Docetaxel based therapy is one of the first line chemotherapeutic agents for the treatment of metastatic castrate-resistant prostate cancer. However, one of the major obstacles in the treatment of these patients is docetaxel-resistance. Defining the mechanisms of resistance so as to inform subsequent treatment options and combinations represents a challenge for clinicians and scientists. Previous work by our group has shown complex changes in pro and anti-apoptotic proteins in the development of resistance to docetaxel. Targeting these changes individually does not significantly impact on the resistant phenotype but understanding the central signalling pathways and transcription factors (TFs) which control these could represent a more appropriate therapeutic targeting approach. METHODS: Using a number of docetaxel-resistant sublines of PC-3 cells, we have undertaken a transcriptomic analysis by expression microarray using the Affymetrix Human Gene 1.0 ST Array and in conjunction with bioinformatic analyses undertook to predict dysregulated TFs in docetaxel resistant prostate cancer. The clinical significance of this prediction was ascertained by performing immunohistochemical (IHC) analysis of an identified TF (SRF) in the metastatic sites from men who died of advanced CRPC. Investigation of the functional role of SRF was examined by manipulating SRF using SiRNA in a docetaxel-resistant PC-3 cell line model. RESULTS: The transcription factors identified include serum response factor (SRF), nuclear factor kappa-B (NFκB), heat shock factor protein 1 (HSF1), testicular receptor 2 & 4 (TR2 &4), vitamin-D and retinoid x receptor (VDR-RXR) and oestrogen-receptor 1 (ESR1), which are predicted to be responsible for the differential gene expression observed in docetaxel-resistance. IHC analysis to quantify nuclear expression of the identified TF SRF correlates with both survival from date of bone metastasis (p = 0.003), survival from androgen independence (p = 0.00002), and overall survival from prostate cancer (p = 0.0044). Functional knockdown of SRF by siRNA demonstrated a reversal of apoptotic resistance to docetaxel treatment in the docetaxel-resistant PC-3 cell line model. CONCLUSIONS: Our results suggest that SRF could aid in treatment stratification of prostate cancer, and may also represent a therapeutic target in the treatment of men afflicted with advanced prostate cancer.

Recurrent partial seizures with ictal yawning as atypical presentation of Hashimoto's encephalopathy (steroid-responsive encephalopathy associated with autoimmune thyroiditis).

Hashimoto's encephalopathy (HE), also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), is a rare condition whose pathogenesis is unknown, though autoimmune-mediated mechanisms are thought to be involved. The prevalent neurological manifestations of this disorder are epileptic seizures and psychocognitive disorders associated with EEG alterations. High anti-thyroid antibody titers (particularly in cerebrospinal fluid) and the effectiveness of steroid therapy are usually considered to be crucial elements in the diagnostic process. We describe a 19-year-old female patient who had been referred to the psychiatric unit because of behavioral disorders characterized predominantly by delirium with sexual content. She developed recurrent focal seizures characterized by atypical ictal semiology (repetitive forceful yawning) and a rare EEG pattern (recurrent seizures arising from the left temporal region without evident "encephalopathic" activity). The presence of anti-thyroperoxidase antibodies in her cerebrospinal fluid and a good response to steroids confirmed the diagnosis of HE. The atypical presentation in the case we describe appears to widen the electroclinical spectrum of HE and highlights its importance for differential diagnosis purposes in the neuropsychiatric setting.

Differential diagnosis of endodontic-related inferior alveolar nerve paraesthesia with cone beam computed tomography: a case report.

AIM: To discuss the use of cone-beam computed tomography (CBCT) in the differential diagnosis of a case of labiomandibular paraesthesia caused by extrusion of endodontic sealer into the mandibular canal. SUMMARY: A 59-year-old woman suffering from a paraesthesia on the left posterior mandible and numbness on the left side of the lower lip was referred to an endodontic specialist 1 month after multiple root canal treatments. A panoramic radiograph revealed the presence of extruded root filling material beyond the apex of the mesial root of the mandibular left second molar and also beyond the apex of the first premolar. A cone beam computed tomography examination was undertaken, which confirmed the presence of radiopaque root canal filling material in the periapical area of the second molar, and revealed that the material was inside the mandibular canal. No extruded filling material was found inside the mental foramen beyond the apex of the first premolar tooth. KEY LEARNING POINTS: Small field of view CBCT (where possible) can be considered an effective radiographic diagnostic device when endodontic-related inferior alveolar nerve or mental foramen paraesthesia are suspected. CBCT is able to provide detailed three-dimensional images of the tooth, the root canal system and the surrounding tissue.

Safe implementation of thrombolysis in stroke-monitoring study in Italy.

BACKGROUND AND PURPOSE: The safe implementation of thrombolysis in stroke-monitoring (SITS-MOST) study was an unique opportunity to test in Italy, where only few centres were expert in thrombolytic treatment before, safety and efficacy of i.v. alteplase within 3 h of ischaemic stroke outside the setting of clinical trials. METHODS: In Italy to participate in the study the clinical centres had to possess organizational and structural characteristics certified by Regional Health Authorities. RESULTS: Seventy-one centres were activated, 56 (79%) treated patients of which 41 (73%) had never used thrombolysis before the study. Globally, 586 patients were included. Baseline median National Institute of Health Stroke Scale of Italian patients was 13 vs. 12 in other European centres (P = 0.0001). Symptomatic intracerebral haemorrhage as per the NINDS/Cochrane definition, mortality and independence (modified Rankin Scale 0-2) rates at 3 months occurred respectively in 6.7% (95% CI: 4.8-9.1), 11.7% (9.2-14.6) and 51.6% (47.4-55.7) of Italian patients compared with 7.3% (6.7-8.0) (P = 0.56), 11.2% (10.4-12.1) (P = 0.75) and 55.1% (53.8-56.4) (P = 0.09) in the European patients and in 8.6% (40/65; 6.3-11.6), 17.3% (14.1-21.1) and 50.1% (44.5-54.7) of the patients treated in the pooled randomized controlled trials. CONCLUSIONS: The SITS-MOST study showed that in Italy i.v. alteplase is safe and effective in routine clinical use also in non-expert centres.

Intravenous Levetiracetam as first-line treatment of status epilepticus in the elderly.

BACKGROUND: Status epilepticus is a condition of prolonged/repetitive seizures that often occurs in the elderly. Treatment in the elderly can be complicated by serious side effects associated with traditional drugs. OBJECTIVE: The aim of this pilot study was to evaluate the short-term efficacy/safety of intravenously administered LEV (IVLEV) as the treatment of choice for SE in the elderly. METHODS: We enrolled nine elderly patients (five female/four male; median age 78 years) with SE. Two patients had a previous diagnosis of epilepsy; in the remaining seven, SE was symptomatic. SE was convulsive in five and non-convulsive in four. All the patients presented concomitant medical conditions (arrhythmias/respiratory distress/hepatic diseases). As the traditional therapy for SE was considered unsafe, IVLEV was used as first-line therapy (loading dose of 1500 mg/100 ml/15 min, mean maintenance daily dose of 2500 mg/24 h) administered during video-EEG monitoring. RESULTS/CONCLUSIONS: In all the patients but one, IVLEV was effective in the treatment of SE and determined either the disappearance of (7/8), or significant reduction in (1/8), epileptic activity; no patient relapsed in the subsequent 24 h. No adverse events or changes in the ECG/laboratory parameters were observed. These data suggest that IVLEV may be an effective/safe treatment for SE in the elderly.

Cellular senescence induced by aberrant MAD2 levels impacts on paclitaxel responsiveness in vitro.

BACKGROUND: The mitotic arrest deficiency protein 2 (MAD2) is a key component of the mitotic spindle assembly checkpoint, monitoring accurate chromosomal alignment at the metaphase plate before mitosis. MAD2 also has a function in cellular senescence and in a cell's response to microtubule inhibitory (MI) chemotherapy exemplified by paclitaxel. METHODS: Using an siRNA approach, the impact of MAD2 down-regulation on cellular senescence and paclitaxel responsiveness was investigated. The endpoints of senescence, cell viability, migration, cytokine expression, cell cycle analysis and anaphase bridge scoring were carried out using standard approaches. RESULTS: We show that MAD2 down-regulation induces premature senescence in the MCF7 breast epithelial cancer cell line. These MAD2-depleted (MAD2) cells are also significantly replicative incompetent but retain viability. Moreover, they show significantly higher levels of anaphase bridges and polyploidy compared to controls. In addition, these cells secrete higher levels of IL-6 and IL-8 representing key components of the senescence-associated secretory phenotype (SASP) with the ability to impact on neighbouring cells. In support of this, MAD2 cells show enhanced migratory ability. At 72 h after paclitaxel, MAD2 cells show a significant further induction of senescence compared with paclitaxel naive controls. In addition, there are significantly more viable cells in the MAD2 MCF7 cell line after paclitaxel reflecting the observed increase in senescence. CONCLUSION: Considering that paclitaxel targets actively dividing cells, these senescent cells will evade cytotoxic kill. In conclusion, compromised MAD2 levels induce a population of senescent cells resistant to paclitaxel.

[Color-Doppler ultrasound in renal artery stenosis and cardiovascular risk: case report]. / Eco-color-Doppler delle arterie renali nel rischio cardiovascolare: case report.

Renal artery stenosis (RAS) is a common manifestation of generalized atherosclerosis, frequently involving other vascular districts, particularly the coronary tree. Duplex ultrasonography is the diagnostic procedure of choice for screening outpatients for RAS. We report a case of metabolic syndrome in a 63-year-old obese man with atherosclerosis and low-grade RAS that was an important sign of cardiovascular risk. In fact, cardioscintigraphy and coronary arteriography showed severe coronary artery disease. RAS is an independent predictor of adverse cardiovascular events such as myocardial infarction, stroke, and cardiovascular death. In this case, duplex ultrasonography demonstrated the importance of screening for RAS as the expression of coronary artery disease.

Autonomic cardiovascular function and baroreflex sensitivity in patients with cervical dystonia receiving treatment with botulinum toxin type A.

OBJECTIVE: To investigate possible changes in autonomic cardiovascular regulation and cardiopulmonary baroreflex sensitivity in patients with primary cervical dystonia receiving chronic treatment with botulinum toxin type A. METHODS: Short-term power spectral analysis of heart rate and systolic blood pressure variability, high-frequency and low-frequency oscillations of heart rate variability, low frequency/high frequency ratio and baroreflex sensitivity (alpha index) were measured in 12 patients with cervical dystonia before and 2-4 weeks after botulinum toxin type A injection and compared with normative data. RESULTS: Before treatment, at rest, patients had significantly lower high frequency power than healthy subjects (p < 0.01), whereas no differences were found in low frequency power. Botulinum toxin injection in patients induced no changes in either power frequency. In patients before treatment and healthy subjects the low frequency oscillatory components increased similarly from rest to tilt (p < 0.01), but tilt induced lower low frequency values in patients than in healthy subjects (p < 0.01). In patients before treatment, the high frequency variations from rest to tilt remained unchanged, whereas in healthy subjects they decreased significantly (p < 0.01). Botulinum toxin type A injection in patients induced no changes in low frequency or high frequency powers. In patients before treatment the low frequency/high frequency ratio increased slightly from rest to tilt, but in healthy subjects increased significantly (p < 0.01). Botulinum toxin type A left the pretreatment low frequency/high frequency ratio unchanged. The alpha-index measured at rest in patients before treatment was lower than in healthy subjects (p<0.05), whereas during tilt was similar in both groups. The alpha-index measured after botulinum toxin injection in patients remained unchanged at rest and during tilt. CONCLUSIONS: Patients with cervical dystonia receiving treatment with botulinum toxin type A have mild, subclinical abnormalities in autonomic cardiovascular regulation and cardiopulmonary baroreflex sensitivity. These changes do not worsen after acute botulinum toxin type A injection.

Acute and chronic effects of ethanol on cortical excitability.

OBJECTIVE: We designed this study to find out whether 5Hz repetitive transcranial magnetic stimulation (rTMS) would disclose changes in cortical plasticity after acute intake of ethanol and in patients with chronic alcohol consumption. METHODS: Ten stimuli-5Hz-rTMS trains were applied over the primary motor cortex in 10 healthy subjects before and after acute ethanol intake and in 13 patients with chronic ethanol abuse, but negative blood ethanol levels when studied. The motor evoked potential (MEP) amplitude and the cortical silent period (CSP) duration during the course of rTMS trains were measured. Short-interval intracortical inhibition (3ms) and intracortical facilitation (10ms) were studied by paired-pulse TMS in 4 healthy subjects and 4 patients. RESULTS: In healthy subjects before and after acute ethanol intake, 5Hz-rTMS produced a significant increase in the MEP size and CSP duration during rTMS. The first CSP in the train was significantly longer after than before ethanol intake. In patients 5Hz-rTMS failed to produce the normal MEP facilitation but left the CSP increase unchanged. CONCLUSIONS: Acute and chronic ethanol intake alters cortical excitability and short-term plasticity of the primary motor cortex as tested by the MEP size facilitation and CSP lengthening after 5Hz-rTMS. SIGNIFICANCE: This finding suggests that rTMS is a valid tool for investigating the effects of ethanol on cortical plasticity in humans.

Status epilepticus in epileptic patients. Related syndromes, precipitating factors, treatment and outcome in a video-EEG population-based study.

INTRODUCTION: Status epilepticus (SE) is frequently observed in epileptic patients. We reviewed a series of video-EEG documented SE to define the characteristics of SE in this population. MATERIALS AND METHODS: Retrospective evaluation of 50 epileptic patients with SE, revision of the electro-clinical data and therapies, and definition of the semeiological subtypes, aetiology, outcome and related epileptic syndromes. RESULTS: We identified 28 convulsive (19 focal and 9 generalized) and 22 non-convulsive (8 focal and 14 generalized) SE patients. In 13 patients, SE was situation-related (poor compliance, AED reduction, worsening seizures). In the remaining 37 patients, SE was related to the natural history of epilepsy (progression of underlying pathologies or intrinsic expression of epileptic syndromes); in these last cases, our results show a higher occurrence in cryptogenic frontal epilepsy (p=0.01). We identified two subgroups according to the duration of the event, i.e. SE lasting <12h and SE lasting >12h. Our results showed a worse response to therapy in SE lasting >12h (p=0.01), a better response to therapy in non-convulsive SE than in convulsive SE (p<0.05) and a relationship at statistical significance limit between a poor response to therapy/worse outcome and symptomatic epileptic syndromes (p=0.06). CONCLUSION: SE in epileptic patients has a wide spectrum of electro-clinical features. It may be related to the withdrawal or reduction of AEDs, or may even be the expression of the evolution of epileptic syndromes. Response to therapy is dependent on early diagnosis and therapy.

Expression and heterodimer-binding activity of Ku70 and Ku80 in human non-melanoma skin cancer.

BACKGROUND: Experimental data suggest that exposure to ultraviolet radiation may indirectly induce DNA double-strand breaks. AIM: To investigate the contribution of the non-homologous end-joining repair pathway in basal and squamous cell carcinomas. METHODS: Levels of Ku70 and Ku80 proteins were determined by immunohistochemical analysis and Ku70-Ku80 heterodimer-binding activity by electrophoretic mobility shift assay. Matched pathological normal margins and skin from healthy people were used as controls. RESULTS: A significant increase in Ku70 and Ku80 protein levels was found for both tumour types as compared with normal skin (p<0.001). Squamous cell carcinoma showed increased immunostaining as compared with basal cell tumours (p<0.02). A direct correlation was found between Ku70 and Ku80 protein levels and expression of the proliferation markers Ki-67/MIB-1 (p<0.02 and p<0.002, respectively) in basal cell carcinoma. DNA binding activity was increased in basal cell carcinoma samples as compared with matched skin histopathologically negative for cancer (p<0.006). In squamous cell carcinomas, however, the difference was significant only with normal skin (p<0.02) and not with matched pathologically normal margins. CONCLUSIONS: Overall, an up regulation of the Ku70 and Ku80 protein levels seems to correlate only with tumour proliferation rate. As non-homologous end joining is an error-prone mechanism, its up regulation may ultimately increase genomic instability, contributing to tumour progression.

Altered response to rTMS in patients with Alzheimer's disease.

OBJECTIVE: In this study, we tested the excitability of cortical motor areas in patients with Alzheimer's disease. Because repetitive transcranial magnetic stimulation (rTMS) modulates cortical excitability, possibly by inducing a short-term increase in synaptic efficacy, we used rTMS to investigate motor cortex excitability in patients with Alzheimer's disease. METHODS: We tested the changes in the size and threshold of motor evoked potential (MEP) and cortical silent period (CSP) duration evoked by focal rTMS delivered in 10 trains of 10 stimuli at 5Hz frequency and 120% rMth intensity in a group of patients with Alzheimer's disease, and age-matched controls. In a further session, rTMS was also delivered at 1Hz frequency (trains of 10 stimuli, 120% rMth). RESULTS: Whereas in control subjects, 5Hz-rTMS elicited normal MEPs that progressively increased in size during the train, in patients, it elicited MEPs that decreased in size. The increase in the duration of the CSP was similar in patients and healthy controls. One hertz rTMS left the MEP amplitude unchanged in patients and healthy controls. CONCLUSIONS: The lack of MEP facilitation reflects an altered response to 5Hz-rTMS in patients with Alzheimer's disease. SIGNIFICANCE: Our rTMS findings strongly suggest an altered cortical plasticity in excitatory circuits within motor cortex in patients with Alzheimer's disease.

[A contrast with good intentions]. / Un contrasto a fin di bene.

A seventy-five-year-old woman with moderate chronic renal failure was admitted to evaluate a complex renal cyst in the frame of acquired cystic kidney disease. Computed tomography (CT) was performed without contrast media due to the risk of radiocontrast-induced nephrotoxicity. Sonographic investigation at our ultrasound unit revealed a hypoechoic lesion measuring 20x20 mm in size by conventional B-mode sonography, confirmed by NTHI. The Hypoechoic lesion was consistent with complex renal cyst or renal tumour. This finding triggered investigation with CEUS.A sulphur hexafluoride-filled microbubble contrast medium was injected intravenously. The focal lesion CES pattern was characterized by intralesional enhancement in the arterial phase. Further diagnostic imaging including CT with contrast media confirmed a lesion consistent with renal tumour. The patient underwent right-sided nephrectomy; histopathological work-up revealed a renal cell carcinoma. Contrast-enhanced sonography could be clinically useful for the differential diagnosis of kidney lesions in patients with chronic renal failure.

Venlafaxine and bladder function.

BACKGROUND: Occasional case reports describe urinary incontinence in patients taking the selective serotonin and norepinephrine reuptake inhibitor antidepressant venlafaxine. OBJECTIVE: In this study the authors investigated the possible effect of venlafaxine on urinary function in a series of 9 patients with urinary retention resulting from spinal cord lesions. They primarily sought to understand whether the reported venlafaxine-induced urinary incontinence was a specific drug-induced effect and, if so, whether venlafaxine might be an effective treatment of urinary retention. METHODS: During a 1-week baseline period, patients measured postvoiding residual volume through a catheter and recorded the number of micturitions within 24 hours. At the end of the baseline period, venlafaxine 75 mg extended-release on a once-daily evening administration schedule was added to their therapy for 1 week. RESULTS: None of the patients reported severe/uncontrollable side effects while taking venlafaxine. Extended-release venlafaxine (75 mg/day) significantly reduced the postvoiding residual volume and increased the micturition rate; the volume diminished on the first day of treatment and remained stable over the ensuing days. CONCLUSION: These findings suggest that venlafaxine could be useful to improve voiding in patients with spinal cord disease.

Nonrandom chromosome changes in multiple sclerosis.

In order to study the role of genetic factors in multiple sclerosis, cytogenetic analysis was performed on 48 patients with the clinically defined disease. We found a high incidence of subjects (50%) with abnormal chromosomes, showing premature centromere division of the X chromosome and structural aberrations, translocations, or deletions that could suggest preferential breakpoints. Correlation between clinical and cytogenetic data showed that cytogenetic abnormalities were more common in patients with high frequency of relapse or with a progressive form of the disease.

Randomized placebo-controlled trial of mitoxantrone in relapsing-remitting multiple sclerosis: 24-month clinical and MRI outcome.

We designed a randomized, placebo-controlled, multicentre trial involving 51 relapsing-remitting multiple sclerosis patients to determine the clinical efficacy of mitoxantrone treatment over 2 years. Patients were allocated either to the mitoxantrone group (27 patients receiving I.V. infusion of mitoxantrone every month for 1 year at the dosage of 8 mg/m2) or to the placebo group (24 patients, receiving I.V. infusion of saline every month for 1 year) using a centralized randomization system. Disability at entry and at 12-24 months was evaluated by four blinded neurologists trained in the application of the Kurtzke Expanded Disability Scale (EDSS). In addition, the number and clinical characteristics of the exacerbations over the 24 months were recorded by the local investigators. MRI, at 0, 12 and 24 months, was performed with a 0.2 T permanent unit. MRI data were analysed by two blinded neuroradiologists. All patients underwent a clinical evaluation. A statistically significant difference in the mean number of exacerbations was observed between the mitoxantrone group and placebo group both during the 1st and the 2nd year. Although there was no statistically significant benefit in terms of mean EDSS progression over 2 years, the proportion of patients with confirmed progression of the disease, as measured by a one point increase on the EDSS scale, was significantly reduced at the 2nd year evaluation in the mitoxantrone group. Forty-two (23 mitoxantrone, 19 placebo) patients underwent all MRI examinations during the 24-month period. We observed a trend towards a reduction in the number of new lesions on T2-weighted images in the mitoxantrone group. Our study suggests that mitoxantrone might be effective in reducing disease activity, both by decreasing the mean number of exacerbations and by slowing the clinical progression sustained by most patients after 1 year from the end of treatment.

Prevalence, awareness, treatment and control of hypertension in the elderly: results from a population survey.

Prevalence, awareness, treatment and control of hypertension were assessed in 1032 (90%) of 1147 elderly (> or = 65 years) inhabitants of three Italian villages. Blood pressure (BP) was measured at home on two separate occasions following a standardised protocol. Persons taking antihypertensive drugs or with BP values > or = 140/90 mm Hg were considered as affected by hypertension. Prevalence of hypertension was 64.8%, with higher rates in women than men, and in those aged 75-84 than in those aged 65-74. Diabetes, strokes and hypercholesterolaemia were more frequent in hypertensive than normotensive people, whereas cardiac diseases, overweight and smoking did not differ significantly between hypertensive and normotensive people. Of the 669 hypertensive patients, 439 (65.6%) were aware of their hypertension, 398 (59.5%) were being treated, and 70 (10.5%) had their hypertension controlled. Of the 230 unaware patients, 201 (87.4%) had had their BP measured in the previous year. Of these, 174 (86.6%) had stage 1 hypertension, while 27 had stage 2 hypertension with SBP values <170 mm Hg. Overall, the patients with stage 1 hypertension accounted for 68.3% of the untreated and 50.5% of the treated patients. The use of a single drug was more frequent in patients with controlled (97.1%) or stage 1 (97.0%) than with stages 2-3 (18.9%) hypertension. The drugs prescribed most were angiotensin-converting enzyme (ACE) inhibitors (45%), followed by diuretics (43%). As our findings suggest that BP values can be effectively reduced by treating or increasing drug treatment in stage 1 hypertensive patients, data on safety and effectiveness of this policy are urgently needed. Journal of Human Hypertension (2000) 14, 825-830

Reproducibility of transcranial Dopplersonography: a validation study.

Transcranial Doppler-sonography (TCD) is a useful noninvasive technique for the measurement of intracranial arterial blood flow velocity. The present study evaluated the reproducibility of this method for repeated measurements of flow velocity in the anterior, middle and posterior cerebral, and basilar arteries. Thirty-six patients (23 males and 13 females) were studied. Three measurements were made by the same examiner on each patient with a time interval of 1 h between the first and the second examination, and about 24 h between the first and the third examination. The statistical evaluation for the reproducibility was performed by calculating the correlation coefficient (r). The results showed good reproducibility of TCD for all arteries both between the first and second and between the first and third measurements (r = 0.78-0.97; p less than 0.001), but when the middle cerebral artery mean velocity is low the posterior cerebral artery reproducibility is poorest (r = 0.42-0.54).

A prevalence study of multiple sclerosis in L'Aquila, central Italy.

We report the results of an epidemiologic study in the Municipality of L'Aquila, Abruzzo, Central Italy, undertaken to estimate the prevalence rate of Multiple Sclerosis (MS). On December 31, 1984, the prevalence was 33.2 per 100,000 (34.2 when age and sex is standardized to the Italian population). In agreement with recent intensive surveys from different regions in the North and South of Italy, our data indicate that the prevalence of MS in Italy is higher than 30 per 100,000, and emphasize the importance of small population studies in the epidemiology of MS. Our findings suggest that in Italy the risk for MS is higher than recorded before.

Prevalence and outcome of symptomatic carotid lesions in young adults. National Research Council Study Group.

OBJECTIVE: To estimate the prevalence and outcome of symptomatic internal carotid artery lesions in young adults. DESIGN: Multicentre hospital based observational study with five year follow up. SETTING: Seven neurological departments in northern and central Italy. SUBJECTS: 240 patients (115 men) aged 15-44 with a recent transient ischaemic attack or stroke in the carotid territory. MAIN OUTCOME MEASURES: (a) Prevalence of symptomatic internal carotid artery stenosis or occlusion detected by continuous wave Doppler ultrasonography at entry; (b) incidence rates of cerebral, cardiac, and non-vascular death; non-fatal stroke; and non-fatal myocardial infarction. RESULTS: Carotid stenoses of 50-99% and occlusions were found in 38 patients (15.8%). Both conditions were significantly more frequent in patients aged over 35 and in those with hypertension, diabetes mellitus, and stroke at entry. The standardised mortality ratio at five years was 10.5 (95% confidence interval 5.0 to 19.3). Survival of patients with stenoses of 0-49% and occlusions was significantly better than that of patients with stenoses of 50-99%. Carotid stenosis of 50-99% was an independent predictor of death (hazard ratio 7.9; 95% confidence interval 2.2 to 29) and non-fatal stroke (hazard ratio 7.4; 1.5 to 37.4). CONCLUSIONS: The prevalence of carotid stenosis or occlusion in young adults after a cerebrovascular event is low. Though patients with high grade symptomatic carotid stenosis are at risk of non-fetal and fetal events, patients with internal artery occlusion apparently have a benign prognosis.