The effect of recanalization on long-term neurological outcome after cerebral venous thrombosis.

Essentials The role of cerebral venous thrombosis (CVT) recanalization on neurologic outcome is still debated. We studied a large cohort of 508 CVT patients with 419 patient years of radiological follow-up. Recanalization rate is high during the first months after CVT and neurologic outcome is favorable. High recanalization grade of CVT independently predicts good neurological outcome. SUMMARY: Background Studies with limited sample size and with discordant results described the recanalization time-course of cerebral venous thrombosis (CVT). The neurological outcome after a first episode of CVT is good, but the role of recanalization on neurological dependence is still debated. Objectives The aim of the study is to assess the recanalization rate after cerebral venous thrombosis (CVT) and its prognostic role in long-term neurological outcome. Patients/Methods In a retrospective observational multicenter cohort study, patients with an acute first episode of CVT with at least one available imaging test during follow-up were enrolled. Patency status of the vessels was categorized as complete, partial or not recanalized. Neurological outcome was defined using the modified Rankin scale (mRS) as good (mRS = 0-1) or poor (mRS = 2-6). Results Five-hundred and eight patients (median [IQR] age, 39 [28.5-49] years; 26% male) were included. Complete or partial recanalization was not differently represented in patients undergoing scans at different periods of time (from 28-day to 3 month-period up to a 1-3 year-period). mRS at the time of follow-up imaging was available in 483 patients; 92.8% of them had a mRS of 0-1. CVT recanalization (odds ratio [OR], 2.56; 95% confidence interval [CI], 1.59-4.13) was positively associated, whereas cancer (OR, 0.29; 95% CI, 0.09-0.88), and personal history of venous thromboembolism (VTE) (OR, 0.36; 95% CI, 0.14-0.92) were negatively associated as independent predictors of favorable (mRS = 0-1) outcome at follow-up. Conclusions Most patients with a first CVT had complete or partial recanalization at follow-up. Recanalization was independently associated with a favorable neurological outcome.

Long-term outcomes of patients with cerebral vein thrombosis: a multicenter study.

BACKGROUND: Little information is available on the long-term clinical outcome of cerebral vein thrombosis (CVT). OBJECTIVES AND METHODS: In an international, retrospective cohort study, we assessed the long-term rates of mortality, residual disability and recurrent venous thromboembolism (VTE) in a cohort of patients with a first CVT episode. RESULTS: Seven hundred and six patients (73.7% females) with CVT were included. Patients were followed for a total of 3171 patient-years. Median follow-up was 40 months (range 6, 297 months). At the end of follow-up, 20 patients had died (2.8%). The outcome was generally good: 89.1% of patients had a complete recovery (modified Rankin Score [mRS] 0-1) and 3.8% had a partial recovery and were independent (mRS 2). Eighty-four per cent of patients were treated with oral anticoagulants and the mean treatment duration was 12 months. CVT recurred in 31 patients (4.4%), and 46 patients (6.5%) had a VTE in a different site, for an overall incidence of recurrence of 23.6 events per 1000 patient-years (95% confidence Interval [CI] 17.8, 28.7) and of 35.1 events/1000 patient-years (95% CI, 27.7, 44.4) after anticoagulant therapy withdrawal. A previous VTE was the only significant predictor of recurrence at multivariate analysis (hazard ratio [HR] 2.70; 95% CI 1.25, 5.83). CONCLUSIONS: The long-term risk of mortality and recurrent VTE appears to be low in patients who survived the acute phase of CVT. A previous VTE history independently predicts recurrent events.

Neurological and cognitive long-term outcome in patients with cerebral venous sinus thrombosis.

OBJECTIVES: The main aim of the present study was to assess long-term neurological and cognitive outcome in patients with cerebral venous sinus thrombosis (CVST). METHODS: We re-investigated by means of a face to face interview all patients with a confirmed diagnosis of CVST, collected at our Department over the years 1990-2000. During the interview the presence of headache, epileptic seizures, visual deficits and a new episode following the first occurrence of CVST were checked. Moreover all patients underwent a neurological examination, a functional evaluation, a cognitive assessment to rule out aphasia, apraxia and working memory deficits. Depression of mood was also investigated. RESULTS: On the whole 34 patients entered the study: 10 patients referred episodic headache following the disease. In three cases epileptic seizures were present. A new event occurred in only one patient. Four patients showed pyramidal signs, in two cases visual deficits were present. All patients had no functional disability. We found a mild non-fluent aphasia in three patients, working memory deficits in six patients and depression of mood in six cases. CONCLUSION: The present study demonstrates a good neurological and cognitive long-term outcome in patients with CVST.

Loco-regional thrombolysis in the treatment of cerebral venous and sinus thrombosis: report of two cases.

Although intravenous (i.v.) heparin is widely used as the first line treatment for cerebral venous and sinus thrombosis (CVST), the most appropriate therapy for this disease is still controversial. We report 2 cases of CVST who were successfully treated by means of loco-regional thrombolysis with urokinase. In the first case we chose this treatment instead of i.v. heparin because clinical conditions of the patient appeared critical for life on hospital admission; in the second case loco-regional thrombolysis was performed because a full-dose heparin treatment over 8 days failed to improve the clinical picture of the patient. In the literature, there are no established criteria for the use of loco-regional thrombolysis in CVST. On the basis of our own experience and few previous reports on the matter, we suggest that loco-regional thrombolysis should be considered an appropriate treatment for CVST when patients are at life risk, when an involvement of deep cerebral veins is present or when, after full heparinization, patients are doing poorly clinically.

Low-oestrogen oral contraceptives as a major risk factor for cerebral venous and sinus thrombosis: evidence from a clinical series.

Cerebral venous and sinus thrombosis (CVST) is still considered a severe clinical problem that is difficult to diagnose and manage and is linked to a poor prognosis. Nonetheless, conventional cerebral angiography and magnetic resonance imaging (MRI), or more recently, MR angiography allow a more rapid and precise diagnosis, and prognosis has improved with the use of anticoagulant treatment. We report 23 cases of CVST consecutively admitted to the Institute of Neurology of the University of Parma during the period 1990-1997. In all cases diagnosis was confirmed by means of MRI or conventional angiography of brain vessels. Among the patients, 22 were female and 1 was male. In all patients, plasma levels of protein C, protein S, antithrombin III (ATIII) and antiphospholipid antibodies (APA) were evaluated. In 15 of 23 patients, the presence of factor V Leiden mutation was also determined, and found positive in 3 patients (20%). Of the 22 female patients, 15 (68%) were on low-oestrogen (containing less than 50 microg oestrogen) oral contraceptive (OC) treatment. This percentage of OC use by patients with CVST is much higher than that of the rest of the female Italian population. OC use was associated with the presence of factor V Leiden mutation in two cases, with a deficiency of protein C in 1 case and a deficiency of protein S in another.Whether low-oestrogen Ocs may induce cerebral thromboembolic events is an open matter. According to our data, it may be argued that Ocs, even if at low oestrogen content, represent a major risk factor for CVST. The use of Ocs, as is the case for systemic venous thromboembolic events, may further increase the risk of CVST in women carrying the factor V Leiden mutation or other inherited hyperthrombotic conditions.

Risk of acute cerebrovascular events related to low oestrogen oral contraceptive treatment.

To establish if an association exists between use of oral contraceptives (OC) and the occurrence of cerebral arterial thromboembolism, cerebral venous thrombosis and retinal vein/artery thrombosis, we identified all women aged 15-44 years resident in the province of Parma, Italy, who were hospitalized because of a documented cerebral or retinal thromboembolic event during the period 1989-1993. The numbers of users and nonusers of OC were estimated from drug sale data and demographic statistics for the province. There were 21 cases of cerebral arterial thromboembolism during the study period: 10 in OC users and 11 in nonusers, for an estimated incidence rate of 1.70 and 0.35 per 10,000 woman-years OC of use and nonuse, respectively (RR=4.8, 95% CI = 1.8-9.0). Eight cases of cerebral venous thrombosis were observed: 6 in OC users and 2 in nonusers (both in puerperium), for an incidence rate of 1.00 and 0.06 per 10,000 woman-years, respectively (RR=16.7, 95% CI = 3.3-81.4). Finally, 13 cases of retinal vein/artery thrombosis were found: 1 in OC users and 12 in nonusers, for an incidence rate of 0.17 and 0.37 per 10,000 woman-years, respectively (RR=0.46, 95% CI = 0.06-3.7). In our population study the use of low oestrogen OC was associated with an increased risk of cerebral venous thrombosis and ischemic stroke, but not of retinal vein/artery thrombosis.

Risk of venous thromboembolism and stroke associated with oral contraceptives. Role of congenital thrombophilias.

To assess the risk of thromboembolism in women using oral contraceptives (OCs), we identified through computer search in the hospitals of the province of Parma, Italy, all women aged 15-44 who were resident in the province and had a documented thromboembolic event in the years 1989-93. The number of users and nonusers of OCs was estimated by the drug sale data for the province and by the demographic statistics. In cases with venous thromboembolism (VT) the prevalence of concomitant deficiency of antithrombin III, protein C, protein S, and of factor V gene mutation Arg506GIn was evaluated. The incidence rate of VT was 37/59,603 woman-years in users (0.62 per 1000) and 13/303,954 woman-years in nonusers (0.042 per 1000), for a relative risk (RR) of 14.5 (95% confidence interval: 7.8-27.1; P < 0.001); the rate of stroke per 1000 woman-years was 0.17 in users and 0.036 in nonusers (RR = 4.6; 2.9-10.7; P < 0.01). A congenital thrombophilia involving the protein C anticoagulant system was documented in about 25% of young women developing venous thromboembolism while on OCs.

Peroneal muscular atrophy with parkinsonism, ptosis, and congenital strabismus.

Peroneal muscular atrophy (PMA) may be occasionally associated with other neurodegenerative features including parkinsonism. We report the association of PMA of neuronal type with parkinsonism, ptosis and congenital strabismus in a 62-year-old Sicilian woman. The complete syndrome was present only in the proband, but variously combined features were present in ten other family members over four generations, with likely autosomal dominant inheritance. Although a similar syndrome of PMA, ptosis, parkinsonism and dementia was already reported, this family showed a previously undescribed combination of features in view of the presence of congenital strabismus.

Acute esotropia from small thalamic hemorrhage.

A 74 year-old patient developed transient acute esotropia, upward gaze palsy and imbalance of standing and gait. Computed Tomography (CT) demonstrated a small left thalamic hemorrhage in the absence of midbrain lesions. The role of thalamic lesion in the genesis of monocular supranuclear palsy is discussed.

Focal cerebral ischemia in young adults: a collaborative case-control study. The National Research Council Study Group.

Because there is uncertainty about the role of atherogenic and nonatherogenic risk factors for cerebral ischemia in the young, we carried out a multicenter, hospital-based, case-control study. 333 patients (15-44 years) with focal cerebral ischemia (transient ischemic attack or stroke within 8 weeks of admission) were eligible. 25 patients were excluded, according to the protocol. 308 cases were matched by age and gender to one hospital and one population control. Independent risk was shown by logistic conditional regression for migraine with aura [odds ratio (OR) = 14.8], smoking (OR = 3.7), alcohol (OR = 2.8), serum triglycerides (OR = 1.6), arrhythmias (OR = 9.5), mitral stenosis (OR = 56), coronary heart disease (OR = 4.3) and carotid stenosis or occlusion (OR = 41). Serum HDL-cholesterol had a relative protective effect (OR = 0.8). These data confirm the role of atherosclerosis and cardiac diseases as well as migraine with aura and alcohol consumption in the pathophysiology of cerebral ischemia in the young. More thorough prevention programs may contribute to earlier detection and control of all of these risk factors, but further investigations in patients with as yet unidentified risk factors are warranted because the above-mentioned factors do not account for the total risk of ischemic stroke in the young.

Mild thrombocytosis secondary to iron-deficiency anemia and stroke.

A 45-year-old woman with mild thrombocytosis secondary to iron-deficiency anemia suffered from hemispheric infarction in absence of vascular, cardiac or coagulation pathologies. The modest raise of the platelets count seemed as the sole possible cause for the cerebral infarction. We wish to emphasize the inconstant benignity of mild non essential thrombocytosis at levels less than 1 million/cu.mm.

Spontaneous hemiballism and disappearance of parksinsonism following contralateral lenticular lacunar infarct.

Hemiballism was observed in a 77-year-old woman with Parksinson disease after a contralateral lenticular infarct without apparent involvement of the subthalamic nucleus. Parkinsonian signs ipsilateral to the hemiballism remained abolished despite subsequent nearly complete recovery from the hyperkinesias. It is argued that clinical events were due to a single ischemic lesion of the putamen-pallidum complex.

Involuntary grasping and groping responses to space-related visual stimuli.

Involuntary groping-grasping responses to visual stimuli were studied in relation to the location of the stimuli in the space surrounding the patient. The following space-related patterns of stimulus-response were observed in four patients: (a) responses were evoked only by visual stimuli in the hemispace ipsilateral to the arm involved; (b) responses were evoked only by visual stimuli within the reach of maximal arm extension; (c) responses were evoked only by visual stimuli in the space around the hand; (d) all such patterns were variously combined. These findings are discussed in relation to the general problem of specific correlations between sensorimotor subsystems and peripersonal behavioral space.

Abnormal muscle mitochondria in ischemic claudication.

The gastrocnemius and quadriceps muscles findings in 18 patients with chronic arterial insufficiency were reviewed with regard to mitochondrial changes. Prominent mitochondrial alterations were present in eight out of 18 patients. The comparison of clinical data between patients with and without mitochondrial changes revealed that in this latter group all patients were at stage IV, whereas the degree of ischemic disease was milder in the other group: the difference in distribution of patients at stage IV between the two groups was statistically significant. This supports the view that mitochondrial changes are expression of adaptive modification rather than damage.

[Retrospective study of 50 cases of spinal meningioma]. / Studio retrospettivo di 50 casi di meningioma spinale.

The clinical history prior to surgery of 50 consecutive cases of spinal meningioma was reviewed. The following features turned out to be particularly interesting: a 7:1 female to male ratio; the symptoms began after the sixth decade in no less than 66% of patients; only 36% were correctly diagnosed as having spinal tumor at the first clinical examination; the average duration of symptoms was 16 months prior to surgery. Such findings are discussed and compared with those of the previous reports.

[Epidemiological study on tremor in the aged]. / Studio epidemiologico sul tremore della terza età.

203 hospitalized old-aged patients were examined for the presence of tremor. This physical sign was found in 58.6% of cases. By far the largest diagnostic category resulted that of essential tremor: 46.7% of all patients investigated and 77.8% of all cases of tremor. The frequency of this type of tremor was found to increase proportionally to age. The conclusion is drawn that also tremor, as well as other neurological signs frequently demonstrable in "normal" old people (for example, the so-called primitive reflexes), should be inscribed in the group of the phenomena due to the ageing process itself.

[Disturbances of equilibrium in the aged]. / I disturbi dell'equilibrio nella terza età.

The occurrence during the last year of vestibular disorders, faints and drop attacks was investigated in 150 patients consecutively admitted to a geriatric hospital. The clinical features of these episodes were recorded by means of a proper questionnaire. True vertigo and/or feeling of unstable equilibrium were referred by 54,6% of the patients inquired into, whereas episodes interpretable as faints and drop attacks showed by far lower prevalences, respectively 13,3% and 6%. The Authors call attention to the difficulties in differential diagnosis among these three kinds of phenomena in the current practice.