Different clinical outcomes between cerebral amyloid angiopathy-related inflammation and non-inflammatory form.

OBJECTIVE: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare manifestation related to CAA, thought to be more severe. We aimed to compare the clinical and radiological outcomes of CAA-ri and non-inflammatory CAA. MATERIALS AND METHODS: We retrospectively included all patients with CAA-ri from 13 French centers. We constituted a sex- and age-matched control cohort with non-inflammatory CAA and similar disease duration. Survival, autonomy and cognitive evolution were compared after logistic regression. Cerebral microbleeds (CMB), intracerebral hemorrhage, cortical superficial siderosis and hippocampal atrophy were analyzed as well as CSF biomarker profile and APOE genotype when available. Outcomes were compared using Kaplan-Meier curves and log-rank tests. RESULTS: Data from 48 CAA-ri patients including 28 already reported and 20 new patients were analyzed. Over a mean of 3.1 years, 11 patients died (22.9%) and 18 (37.5%) relapsed. CAA-ri patients were more frequently institutionalized than non-inflammatory CAA patients (30% vs 8.3%, p < 0.001); mortality rates remained similar. MMSE and modified Rankin scale scores showed greater severity in CAA-ri at last follow-up. MRI showed a higher number of CMB at baseline and last follow-up in CAA-ri (p < 0.001 and p = 0.004, respectively). CSF showed lower baseline levels of Aß42 in CAA-ri than non-inflammatory CAA (373.3 pg/ml vs 490.8 pg/ml, p = 0.05). CAA-ri patients more likely carried at least one APOE ε4 allele (76% vs 37.5%, adjusted p = 0.05) particularly as homozygous status (56% vs 6.2%, p < 0.001). INTERPRETATION: CAA-ri appears to be more severe than non-inflammatory CAA with a significant loss of autonomy and global higher amyloid burden, shown by more CMB and a distinct CSF profile. This burden may be partially promoted by ε4 allele.

Vascular cognitive impairment: Advances and trends.

The presence of vascular neurocognitive impairment (whatever the severity) is always associated with a functional impact and increased risk of dependency and institutionalization. However, vascular cognitive impairment remains underdiagnosed, and the mechanisms underlying post-stroke cognitive disorders are still poorly understood. However, the advent of new criteria and a standardized international neuropsychological battery is expected to lead to improved diagnosis and management, and the development of novel techniques (such as brain imaging and amyloid PET) should improve our understanding of the mechanisms underlying vascular cognitive impairment and help to identify potential targets for therapy.

Impaired sexual activity in young ischaemic stroke patients: an observational study.

BACKGROUND AND PURPOSE: The present study sought to determine the impact of stroke on sexual function and well-being in a cohort of young ischaemic stroke patients and identify factors associated with impairment. METHODS: Over a 2-year period, all patients aged 60 or under with ischaemic stroke or transient ischaemic attack (n = 156) were included. Information on sexual function and well-being was obtained by means of a paper questionnaire mailed to participants 1 year after their stroke. Impaired sexual activity (ISA) was defined as a decline in sexual function and/or satisfaction. Psychological well-being was evaluated on the Hospital Anxiety and Depression Scale (HADS). RESULTS: The response rate was 67% (n = 104). Thirty of these responders (29%) reported ISA. Patients with ISA had a higher HADS score (19.7 vs. 11.2 in patients with no impairment; P < 0.001), anxiety score (10.0 vs. 6.3; P < 0.001) and depression score (8.7 vs. 4.8; P < 0.001) and were more likely to have left brain lesions (70% vs. 30%; P < 0.001) and use angiotensin-converting enzyme (ACE) inhibitors (73% vs. 31%; P < 0.001) and diuretics (50% vs. 19%; P = 0.003). In a stepwise logistic regression, depression (odds ratio 9.1, 95% confidence interval 2.45-33.46; P = 0.001) and ACE inhibitor use (odds ratio 6.0, 95% confidence interval 2.11-17.28; P = 0.001) were associated with ISA. CONCLUSIONS: Impaired sexual activity was reported by almost one-third of younger patients 1 year after ischaemic stroke. Factors associated with post-stroke ISA may include specific medications and depression rather than the characteristics of the stroke per se.

Predictors of newly diagnosed atrial fibrillation in cryptogenic stroke: a cohort study.

BACKGROUND AND PURPOSE: A significant proportion of cryptogenic ischaemic strokes are due to paroxysmal atrial fibrillation (AF). As paroxysmal AF appears to inexorably progress to persistent or permanent AF, this study with long-term follow-up was designed to establish the profile of patients who developed AF after hospital discharge. METHODS: All patients with cryptogenic ischaemic stroke over a 1-year period were included (n = 164). Patients were prospectively followed up at the outpatient clinic. Information on long-term outcome included the presence of newly diagnosed AF (NDAF). A specific NDAF assessment was performed at least 2 years after the index stroke using a structured telephone interview. Baseline clinical, laboratory, and echocardiographic data of these patients were retrospectively recorded. Independent predictive factors were then used to produce a predictive grading score for NDAF, derived by logistic regression analysis. RESULTS: With a median follow-up of 854 days, 22 cases of NDAF (13%) were observed. On multivariate analysis, factors associated with NDAF were age ≥72 years (two points), history of coronary artery disease (one point) or stroke (one point), and left atrial area ≥16 cm(2) (two points) (total score ranging from 0 to 6). Patients with a score ≤1 point did not have NDAF during follow-up. CONCLUSIONS: In cryptogenic ischaemic stroke, the NDAF score can be used to target patients at high risk of developing AF after hospital discharge, as a score of 0-1 was highly predictive of the absence of NDAF during follow-up. These results need to be confirmed in prospective studies.

Differential features of carotid and vertebral artery dissections: the CADISP study.

OBJECTIVE: To examine whether risk factor profile, baseline features, and outcome of cervical artery dissection (CEAD) differ according to the dissection site. METHODS: We analyzed 982 consecutive patients with CEAD included in the Cervical Artery Dissection and Ischemic Stroke Patients observational study (n = 619 with internal carotid artery dissection [ICAD], n = 327 with vertebral artery dissection [VAD], n = 36 with ICAD and VAD). RESULTS: Patients with ICAD were older (p < 0.0001), more often men (p = 0.006), more frequently had a recent infection (odds ratio [OR] = 1.59 [95% confidence interval (CI) 1.09-2.31]), and tended to report less often a minor neck trauma in the previous month (OR = 0.75 [0.56-1.007]) compared to patients with VAD. Clinically, patients with ICAD more often presented with headache at admission (OR = 1.36 [1.01-1.84]) but less frequently complained of cervical pain (OR = 0.36 [0.27-0.48]) or had cerebral ischemia (OR = 0.32 [0.21-0.49]) than patients with VAD. Among patients with CEAD who sustained an ischemic stroke, the NIH Stroke Scale (NIHSS) score at admission was higher in patients with ICAD than patients with VAD (OR = 1.17 [1.12-1.22]). Aneurysmal dilatation was more common (OR = 1.80 [1.13-2.87]) and bilateral dissection less frequent (OR = 0.63 [0.42-0.95]) in patients with ICAD. Multiple concomitant dissections tended to cluster on the same artery type rather than involving both a vertebral and carotid artery. Patients with ICAD had a less favorable 3-month functional outcome (modified Rankin Scale score >2, OR = 3.99 [2.32-6.88]), but this was no longer significant after adjusting for baseline NIHSS score. CONCLUSION: In the largest published series of patients with CEAD, we observed significant differences between VAD and ICAD in terms of risk factors, baseline features, and functional outcome.

[Cerebral venous thrombosis: long-term functional and cognitive outcome in 16 patients]. / Thrombose veineuse cérébrale: étude du devenir fonctionnel et cognitif de 16 cas.

INTRODUCTION: Although the prognosis of cerebral venous thrombosis (CVT) is better than previously reported, long-term behavioral and cognitive sequelae have not been systematically investigated. OBJECTIVE: The aim of this study was to evaluate the long-term functional and cognitive outcome in CVT patients. METHODS: We included all patients admitted to the Neurology department of the Amiens university hospital between January 1997 and December 2002 with the diagnosis of CVT. Outcome between April and June 2003 was evaluated. Patients with cognitive complaints or impaired, MMSE were assessed using a standardized neuropsychological battery and behavioral disorder assessment. RESULTS: Among the 26 patients fulfilling inclusion criteria, 16agreed to participate and formed the study population (13 women; median age: 46.8years). The median follow-up was 34.5months. Functional ability assessed using the modified Rankin Scale (mRk) was relatively spared (mRk=0; n=6; mRk=1; n=6; mRk=2; n=4). Ten patients with cognitive complaints underwent a detailed neuropsychological assessment: it revealed deficits of long-term memory and executive functions. CONCLUSIONS: Despite relatively good functional long-term outcome, our results indicate that CVT patients suffer from long-term memory deficit and moderate executive dysfunction. Such a pattern is close to that observed in arterial stroke although less severe and this warrants a larger study.

[Intracranial hemorrhages associated with oral anticoagulant therapy. Analysis of 38 cases]. / Hémorragies intracrâniennes associées à un traitement anticoagulant oral. Analyse de 38 observations.

The major risk of oral anticoagulant therapy is haemorrhage potentially affecting all organs. Bleeding in the central nervous system is a rare but severe complication of anticoagulant therapy. This study aimed to analyse a series of intracranial haemorrhages. This series from the Regional Pharmacovigilance Center of Amiens included spontaneously reported and retrospectively collected cases from January 1999 to December 2000. During this period, 38 cases of intracranial bleeding possibly related to oral anticoagulant administration were reported; 19 women and 19 men, median age 69.5 (29 to 87) years. In 34% of the cases, patients died and in 18% neurologic sequelae were still present at the time of the evaluation. In 21 cases (62%), the INR (International Normalized Ratio) was higher than the therapeutic range recommended for the indication. Among the most frequent risk factors, hypertension and recent minor trauma are highlighted in this series. In 17 cases, oral anticoagulants were associated with potentially potentiating drugs. Mental status changes or headache were prominent early symptoms which had often been present for days. Our data confirm that anticoagulant-associated intracranial haemorrhages are not rare, can be severe, potentially fatal and are probably underestimated by physicians. The fact that more than 50% of patients in this series were overanticoagulated at the time of bleeding suggests that many cases of intracranial haemorrhage could be prevented by improved anticoagulation control. Epidemiological studies are needed in order to prospectively evaluate the incidence of this type of complication and its avoidance. The value of anticoagulation clinics can be discussed.

Medullary gnathostomiasis in a white patient: use of immunodiagnosis and magnetic resonance imaging.

A 48-year-old French diplomat presented with a sensory-motor paraparesis of rapid onset, leading to paraplegia. Successive magnetic resonance image scans showed lesions of the thoracic spinal cord that were at different levels from one examination to the next. Specific anti-gnathostome antibodies were detected by means of enzyme-linked immunosorbent assay and Western blot test in both plasma and cerebrospinal fluid. Albendazole treatment prevented disease progression, but only partial regression of the neurologic symptoms was obtained.

[MELAS syndrome (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes]. / Syndrome MELAS (Encéphalopathie Mitochondriale avec Acidose Lactique et pseudo-accidents vasculaires cérébraux).

BACKGROUND: The MELAS syndrome (Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes) belongs to the category of mitochondrial disorders. The most common molecular etiology of the syndrome is a mutation A to G transition at base pair 3243 in the mitochondrial genome. The phenotype is varied and depends on the proportion of DNA muted and which organ on aerobic metabolism suffers most. CASE-REPORT: An 17 year-old woman had successively neurosensory hearing loss, renal disease, cardiomyopathy, diabetes mellitus, lactic acidosis and stroke-like episodes that evoked a MELAS syndrome. DISCUSSION: The skin manifestations of patients with MELAS syndrome are scaly, pruritic, diffuse erythema, reticular pigmentation, moderate hypertrichosis, seborrheic eczema, atopy and vitiligo. Our patient presented severe hirsutism and reticular pigmentation of the limbs. No abnormal histologic and electron microscopic findings were noted in the skin or the follicles involved.

The association between the Val34Leu polymorphism in the factor XIII gene and brain infarction.

Factor XIII catalyzes the formation of covalent bounds between fibrin monomers, thus stabilizing the fibrin clot and increasing its resistance to fibrinolysis. The frequency of a frequent Val34Leu polymorphism in the FXIII A-subunit gene has been shown to be lower in patients with myocardial infarction or venous thrombosis than in controls, whereas it was higher in patients with hemorrhagic stroke than in controls. Our aim was to study the relation between brain infarction (BI) and the FXIII Val34Leu polymorphism in 456 patients consecutively recruited with a BI confirmed by MRI, and 456 matched controls. The distribution of genotypes was different in cases (63. 2% Val/Val; 30.9% Val/Leu; 5.9% Leu/Leu) compared with controls (49. 8% Val/Val; 42.8% Val/Leu; 7.4% Leu/Leu; P <.001). Carrying the Leu allele was associated with an OR of 0.58 (95% CI = 0.44-0.75). A similar association was observed in cases and controls free of previous cardiovascular or cerebrovascular history (OR = 0.51; 95% CI = 0.36-0.73). No heterogeneity of this association was observed after stratification on the main BI subtypes. Adjustment for traditional vascular risk factors did not modify these findings. In addition, the effect of smoking was modified by the polymorphism (P =.05); the effect of smoking was weaker among Leu carriers than among noncarriers. In conclusion, there was a negative association of the FXIII Val34Leu polymorphism with BI, thus suggesting a protective effect of the Leu allele against thrombotic cerebral artery occlusion. In addition, our results suggest that among Leu carriers, the protective effect of the polymorphism outweighed the effect of smoking. (Blood. 2000;95:586-591)

[Duality of angiotensin II receptors and risk for stroke and cancer: what is the connection?]. / Dualité des récepteurs de l'angiotensine II et risque d'accidents vasculaires cérébraux et de cancer: quels liens entre eux?

Angiotensin II (AII) acts by 2 types of receptors: the ATI receptor which mediates its actions on vasoconstriction, renin (inhibition) and aldosterone (stimulation) secretions, cellular proliferation and angiogenesis and the non-AT1 (often called AT2) receptors. Mainly expressed in the embryon these latter may favor cellular differentiation and recruitment of collateral circulation. Angiotensin converting enzyme inhibitors (ACEI) decrease the synthesis of All and therefore the stimulation of both receptor types whereas AT1-receptor antagonists (AT1RA) block only the stimulation of these latter and increase the stimulation of AT2 receptor since they increase the production of All secondarily to the inhibition of the feedback of renin secretion by All. Experimentally ACEI and AT1RA decrease angiogenesis and cellular proliferation and favor cellular differentiation which could explain the protective effect of ACEI against cancer suggested recently in a Scotish study. Despite of their common suppressive effect on angiogenesis AT1RA may better than ACEI protect against ischemic events specially the cerebral ones because they favor the rapid recruitment of collateral circulation. This has been demonstrated for losartan in case of abrupt ligation of the carotid in the gerbil since its previous administration protects against fatal cerebral ischemia whereas its previous administration with enalapril abolishes this protection. These data may explain why, in the CAPP trial, captopril which has prevented more effectively diabetes occurrence could not be proved superior to diuretics and/or betablocker in the prevention of myocardial infarction and specially of strokes for which exist on the contrary a suspicion of a lower protection. Therefore a comparative trial between AT1RA and ACEI in the prevention of stroke recurrence should appear as a priority for Public Health and Pharmaceutical Industry Authorities.

Multiple large and small cerebellar infarcts.

To assess the clinical, topographical, and aetiological features of multiple cerebellar infarcts,18 patients (16.5% of patients with cerebellar infarction) were collected from a prospective acute stroke registry, using a standard investigation protocol including MRI and magnetic resonance angiography. Infarcts in the posterior inferior cerebellar artery (PICA)+superior cerebellar artery (SCA) territory were most common (9/18; 50%), followed by PICA+anterior inferior cerebellar artery (AICA)+SCA territory infarcts (6/18; 33%). One patient had bilateral AICA infarcts. No infarct involved the PICA+AICA combined territory. Other infarcts in the posterior circulation were present in half of the patients and the clinical presentation largely depended on them. Large artery disease was the main aetiology. Our findings emphasised the common occurrence of very small multiple cerebellar infarcts (<2 cm diameter). These very small multiple cerebellar infarcts may occur with (13 patients/18; 72%) or without (3/18; 22%) territorial cerebellar infarcts. Unlike previous series, they could not all be considered junctional infarcts (between two main cerebellar artery territories: 51/91), but also small territorial infarcts (40/91). It is suggested that these very small territorial infarcts may be endzone infarcts, due to the involvement of small distal arterial branches. It is possible that some very small territorial infarcts may be due to a microembolic process, but this hypothesis needs pathological confirmation.

[Primary and secondary prevention of ischemic cerebrovascular accidents of arteriosclerosis by platelet inhibitors]. / Prévention primaire et secondaire des accidents ischémiques cérébraux liés à l'anthérosclérose par les antiplaquettaires.

Cohort studies currently available suggest that the most effective platelet inhibitors for the secondary prevention of ischaemic cerebrovascular accidents are acetylsalicylic acid and ticlopidine. Aspirin reduces the risk by 20%. It seems that moderate doses (100-300 mg/day) are sufficient and better tolerated. Ticlopidine would seem to be more effective than aspirin as it reduces the risk by more than 20% with respect to aspirin therapy. Only aspirin has been evaluated in the setting of primary prevention and it seems to be ineffective in preventing cerebral infarction. Nowadays, other anti-platelet molecules are under evaluation, one of which is Clopidogrel.

[Neurologic complications in a case of Werner syndrome]. / Complications neurologiques dans un cas de syndrome de Werner.

A 39 year old caucasian man was admitted in 1994 to the neurological department with a left pure motor hemiplegia that appeared suddenly. This patient showed typical features of Werner's syndrome. He had a hoarse voice, a diffuse muscle weakness and atrophy in the upper and lower limbs with chronic ulcers on the legs. His scalp and public hair were sparse. Cranial MRI revealed several lesions in the white matter, low signal intensity on T1 weighted images and high signal on T2 weighted images. Cerebrospinal fluid (CSF was inflammatory with hypercytosis and proteinorachia was 0.50 g/l with synthesis of IgG. Sural nerve biopsy revealed muscle atrophy and the loss of myelinated fibers. Thus, central and peripheral nervous systems were affected in this case.

[Clinico-radiological data of 48 cases of immunocompetent primary cerebral lymphoma]. / Données clinico-radiologiques de 48 cas de lymphomes cérébraux primitifs immunocompétents.

In this article clinical and neuroradiological features from a cohort of 48 immunocompetent patients who have a histologically proved primary cerebral lymphoma are considered. Our series consisted of 27 men and 21 women with an average age of 59. The clinical results gave 73% patients with a focal deficit, 46% with deterioration of vigilance, 35% intracranial hypertension, and only 8% with epilepsy, which was never revealing. We observed 4 uveitis of which 3 revealed, and preceded by several months, the neuroradiological manifestations. Histological classification using the criterias of the Working Formulation showed that 92% of our patients had a large cell lymphoma (class G or H). Precise analysis of computed tomography features of 40 patients revealed 46 lesions (most of them were isodense) before contrast medium administration. In all the cases, the lesion enhancement was intense and homogeneous. In 50% of the cases, there were multiple lesions. Sixty lesions were of the supra tentorial compartment, lobar in 32 cases, deep in 28 cases. Fifteen were infratentorial. From our experience, we can put forward the following suggestions: 1) Neuroradiological aspects suggesting primary cerebral lymphomas exist but none of them are specific. 2) Research of an uveitis is important, as this makes the histological diagnosis more simple. 3)The prescription of corticosteroids should be delayed until the histological diagnosis is certain because the primary cerebral lymphoma, which is very corticosensitive, is likely to disappear with this treatment and then change the biopsy results.

[Meningopapillitis disclosing Lyme disease]. / Méningo-papillite révélatrice d'une maladie de Lyme.

A 65 old year woman was admitted to the hospital for a low back pain, a fever and an elevated sedimentation rate. Four months later she noted a progressive visual loss first affected the right eye (visual acuity: 6/10) and then the left (visual acuity : 6/10). Fundus examination showed a bilateral papilledema. CT Scan and MRI were normal. A lumbar puncture disclosed a lymphocytic pleocytosis (68 leukocytes/mm3), an increase in protein level (1,9 g/l) and oligoclonal bands. A serologic test for B. Burgdorferi was positive both in blood (1/64 degrees) and in cerebrospinal fluid (> or = 1/128). The patient was treated with intravenous ceftriaxone 2 g daily for 2 weeks. Fifteen days later the low back pain had disappeared and the CSF cellular count had decreased to 20 leukocytes/mm3. Seven months later, CSF was normal (2 leukocytes/mm3, protein level: 0.65 g/l.); Titer against B. Burgdorferi had improved to 1/160 in serum and 1/16 in CSF; visual acuity had improved to 8/10 on left, and was the same on right.

[Rare lesions of the internal carotid arteries]. / Lésions rares des artères carotides internes.

The rare lesions of internal carotid arteries are varied in both their appearance and their cause. Schematically, in addition to congenital anomalies, of which fibromuscular dysplasia is no doubt the most frequent, should be noted lesions of inflammatory, infectious, traumatic and iatrogenic origin. The fact that the relationship between some of these lesions and cerebral vascular accidents is not clearly established, leads to diagnostic and therapeutic problems which are difficult to resolve.