Latent Cerebral Venous and Sinus Thrombosis

The incidence of cerebral venous and sinus thrombosis (CVST) is still unknown. Several assumptions of the incidence have been made. In the one and only series of consecutive brain autopsies series by Towbin in1973 CVST was found in 10,9 % of patients aged 60 years or more. These findings suggest that the true incidence of CVST is higher than generally thought, but there are no other reports supporting these findings. Therefore in order to determine the incidence of latent CVST we conducted a new prospective post mortem study. All brain autopsies performed in our hospital between 1996 and 1998 on patients 60 years of age or older were examined for the presence of CVST in a prospective way. We examined the sagittal sinus, the torcula, the straight sinus, both transverse sinuses, and both sigmoideal sinuses for the presence of thrombosis. The clinical condition, medication, brain-imaging results, clinical cause of death, general findings from the body autopsy and definite cause of death were recorded. Additionally we requested the annual mortality figures of CVST at the department of the National Agency for Statistics of the Netherlands (CBS). A consecutive and prospective series of 102 brain autopsies was performed in our general hospital during a period of two years. We found one case of latent CVST in our series of 102 patients. Comparison with the findings of Towbin using a chi-square test yielded a significant difference in the incidence of latent CVST (χ₂ = 7.65, p < 0.01) between the two studies. The present autopsy study demonstrates that latent CVST is rare. Received: 7 June 2002, Received in revised form: 14 October 2002, Accepted: 21 October 2002 Correspondence to H. P. Bienfait, MD     

Migraine aggravation caused by cephalic venous congestion

BACKGROUND: Cerebral venous distension is thought by some to serve as a source of migraine pain. Previous investigators have tried to modify pain intensity by induction of additional venous congestion via compression of both internal jugular veins (Queckenstedt's maneuver). The magnitude of blood flow within the internal jugular veins depends markedly on body position, and inconsistencies in positioning may have influenced their results. OBJECTIVE: To investigate the effect of Queckenstedt's maneuver, performed both in the upright and in the supine body position, in migraineurs during an acute attack. METHODS: Twenty-five patients (18 women, 7 men; mean age +/- SD, 35.4 +/- 13.3 years) with International Headache Society-defined migraine without aura were evaluated. Queckenstedt's maneuver was performed in both body positions during an acute migraine attack, involving constant application of manual pressure to both internal jugular veins for 30 seconds. Headache intensity was rated before, during, and after Queckenstedt's maneuver on a scale extending from 1 (mild) to 10 (intolerable). RESULTS: Seventeen patients (68%) reported an increase of headache intensity in the supine position during Queckenstedt's maneuver. In the sitting position, pain increase was observed only in 6 patients (24%). The magnitude of pain increase was significantly greater in the supine position compared to the upright position (P=.02). CONCLUSIONS: Our results support a role for cerebral venous congestion in the generation of migraine pain and suggest body position may influence the clinical expression of that process.     

Venous thromboembolism and occult malignancy

Trousseau is considered to be the first to have recognised a relation between venous thromboembolism (VTE) and malignancy. Illtyd James and Matheson in 1935 were the first in the Anglo-Saxon literature, at least to our knowledge, to report the observation of a patient with occult cancer at time of his venous thrombosis. Meanwhile, cancer has become an established risk factor for VTE. The prevalence of concomitant cancer in patients presenting with VTE varies considerably between the studies due to differences in, for instance, threshold of suspicion, screening methods, and characteristics of the patients like age. A consistent observation is the low prevalence of concomitant cancer in patients with secondary thrombosis, comparable to the prevalence in the general population. A 3–19-fold increase in prevalence of concomitant cancer has been reported in patients presenting with an idiopathic VTE. The same applies for occult cancer in patients with secondary and idiopathic VTE. The prevalence of occult cancer in patients with secondary VTE is comparable with the prevalence of cancer in the general population, while the prevalence of occult cancer in patients with idiopathic VTE is 4–10%. It seems possible to detect a substantial number of additional cancer patients, at time of diagnosis of idiopathic VTE, by means of extensive screening. However, results of randomised trials, evaluating the effect on survival rate, are lacking.     

Treatment of venous thromboembolism in cancer patients

The management of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with cancer can be a clinical dilemma. Comorbid conditions, warfarin failure, difficult venous access, and a high bleeding risk are some of the factors that often complicate anticoagulant therapy in these patients. In addition, the use of central venous access devices is increasing but the optimal treatment of catheter-related thrombosis remains controversial. Unfractionated heparin (UFH) is the traditional standard for the initial treatment of venous thromboembolism (VTE) but low molecular weight heparins (LMWHs) have been shown to be equally safe and effective in hemodynamically stable patients. For long-term treatment or secondary prophylaxis, vitamin K antagonists remain the mainstay treatment. However, the inconvenience and narrow therapeutic window of oral anticoagulants make extended therapy unattractive and problematic. As a result, LMWHs are being evaluated as an alternative for long-term therapy. New antithrombotic agents are being tested in clinical trials and may have the potential to replace conventional treatment. The role of inferior vena cava filters in cancer patients remains ill defined but these devices remain the treatment of choice in patients with contraindications for anticoagulant therapy.     

Behçet's disease: diagnostic and prognostic aspects of neurological involvement

This study was conducted to describe clinical and prognostic aspects of neurological involvement in Behçet's disease (BD). Patients referred for neurological evaluation fulfilled the criteria of the International Study Group for Behçet's Disease. We analyzed disability and survival by the Kaplan-Meier method, using Kurtzke's Extended Disability Status Scale (modified for BD) and the prognostic effect of demographic and clinical factors by Cox regression analysis. We studied 164 patients; of the 107 diagnostic neuroimaging studies: 72.1% showed parenchymal involvement, 11.7% venous sinus thrombosis (VST) and the others were normal. CSF studies were performed in 47 patients; all with inflammatory CSF findings (n=18) had parenchymal involvement. An isolated increase in pressure was compatible with either VST or normal imaging. The final diagnoses were VST (12.2%), neuro-Behçet's syndrome (NBS) (75.6%), isolated optic neuritis (0.6%), psycho-Behçet's syndrome (0.6%), and indefinite (11%). VST and NBS were never diagnosed together. Ten years from onset of BD 45.1% (all NBS) reached a disability level of EDSS 6 or higher, and 95.7±2.1% of the patients were still alive. Having accompanying cerebellar symptoms at onset or a progressive course is unfavorable. Onset with headache or a diagnosis of VST is favorable. Two major neurological diagnoses in BD are NBS and VST. These are distinct in clinical, radiological, and prognostic aspects, hence suggesting a difference in pathogenesis.     

Blepharoclonus and Arnold-Chiari malformation

OBJECTIVE: Blepharoclonus (BLC) denotes a large amplitude, involuntary tremors of the orbicularis oculi muscles, observed during gentle closure of the eyelids. BLC may follow major head trauma. Four patients with Arnold-Chiari malformation (ACM) and BLC are described. MATERIALS AND METHODS: The first patient had facial numbness for 5 months; the remaining patients had headaches following minor head or cervical spinal injuries. Brain magnetic resonance imaging (MRI), electroencephalogram (EEG) blink reflexes, mental and facial nerve responses and facial electromyogram (EMG) were performed. RESULTS: All patients exhibited ACM on brain MRI. The first patient had coincidental dural venous malformation, empty-sella turcica and familial digital dysplasia. She exhibited oculopterygoid synkinesis. The last 3 patients had posttraumatic headache; the second and third patients had limited features of Ehlers-Danlos syndrome (EDS). The second patient had cervical spinal fusion and the fourth a cervical syrinx. All the patients had BLC on gentle eyelid closure. CONCLUSION: BLC is an underdiagnosed neuro-ophthalmological sign of ACM.     

Treatment of deep cerebral venous thrombosis by local infusion of tissue plasminogen activator

BACKGROUND

Treatment of extensive intracranial venous sinus thrombosis with thrombolytic drugs is described, although the indications for and most efficacious technique for achieving thrombolysis remain uncertain. We report the successful lysis of superficial and deep venous system thrombosis by infusion of recombinant human tissue-type plasminogen activator (rt-PA) into the anterior superior sagittal sinus.

CASE DESCRIPTION

A 34-year-old man presented with headaches followed by decreased level of consciousness and left hemiplegia. Angiography showed thrombosis of the superior sagittal and both transverse and straight sinuses with extension into the internal cerebral veins. The superior sagittal sinus was catheterized via a transfemoral route and rt-PA, 25 mg, was infused. There was no significant change in the thrombosis. The catheter was left in place and rt-PA was infused at 1 mg/minute for 19 hours. Repeat angiography showed resolution of the thrombosis. The patient was placed on heparin and then coumadin. He recovered completely.

CONCLUSIONS

This report suggests that superselective infusion of thrombolytics into thrombosed intracranial venous sinuses can lyse intracranial venous sinus thrombosis. The thrombolytic agent must be infused for hours. The apparent successful lysis of clot in the deep venous system when infusion was into the superior sagittal sinus might be related to diffusion of rt-PA throughout the intracranial venous system or to improved venous outflow caused by lysis of clot in superficial dural sinuses.     

Hormone replacement therapy (HRT) and anaesthesia

Br J Anaesth 2001; 86: 709–16     

Increased levels of tissue plasminogen activator antigen and factor VIII activity in nonvalvular atrial fibrillation: relation to predictors of thromboembolism

INTRODUCTION: Given that nonvalvular atrial fibrillation (AF)-associated stroke can be either cardioembolic or atherothrombotic, we investigated the relationships between nonvalvular AF and hemostatic factors reflecting intrinsic thrombogenic and atherogenic potentials (tissue plasminogen activator [t-PA] antigen, plasminogen activator inhibitor-1, and factor VIII activity). We also evaluated the clinical applicability of these hemostatic factors by examining whether AF subjects with established clinical or echocardiographic predictors of thromboembolism had higher levels of these factors. METHODS AND RESULTS: Of the 3,212 participants of a Chinese population-based study, 53 subjects (1.7%) with AF were identified. Among the hemostatic factors measured, t-PA antigen (median 12.8 vs 8.1 ng/mL; P < 0.01) and factor VIII activity (median 155% vs 133%; P < 0.05) were significantly higher in AF subjects after adjustment for age and sex. In multivariate analysis, features independently associated with t-PA antigen levels were AF, sex, body mass index, systolic blood pressure, total cholesterol, triglycerides, and left ventricular systolic dysfunction. Features independently associated with factor VIII activity levels included AF, age, and total cholesterol. Levels of both t-PA antigen and factor VIII activity were primarily elevated in AF subjects with predictors of thromboembolism (age > 75 years, hypertension, diabetes, and left ventricular systolic dysfunction), whereas in AF subjects with no thromboembolic predictors, plasma levels of hemostatic factors examined were similar to those without AF. CONCLUSION: We demonstrated that nonvalvular AF was independently associated with increased peripheral levels of t-PA antigen and factor VIII activity. Levels of both hemostatic factors were primarily elevated in AF subjects with predictors of thromboembolism. Whether these hemostatic factors are independently predictive of future thromboembolic events in AF patients requires further investigation.