Ischemic stroke associated with anticardiolipin antibodies

Anticardiolipin antibodies are a group of antiphospholipid autoantibodies seen primarily in patients with systemic lupus erythematosus and other autoimmune diseases. We report 3 patients, 2 without systemic lupus, who suffered ischemic brain infarction associated with these antibodies in the absence of detectable lupus anticoagulant activity. Anticardiolipin antibodies, possibly associated with a lupus anticoagulant-like thrombotic tendency, may be a newly recognized cause of ischemic stroke.     

Recurrent stroke and vascular events in elderly patients with anticardiolipin antibodies: a prospective study

The presence of anticardiolipin antibodies (aCL) is a recognized risk factor for ischaemic stroke and a predictor of recurrent ischaemic events in young patients, but the significance of positive aCL tests is uncertain in the elderly. We evaluated the frequency of aCL and the risk of recurrence of stroke and other vascular events in a series of 242 consecutive patients aged over 60 years, admitted for brain infarction. All underwent aCL immunoreactivity (ELISA; measured by IgG antiphospholipid, GPL, units) and transoesophageal echocardiography and were later examined or contacted by telephone (mean 2.33±1.25 years, max. 4). Fifty patients (21 %) had at least10 GPL units aCL. There were no differences between these and the other patients in the results of transoesophageal echocardiography, including mitral or aortic valvular thickening, atrial thrombus, atrial spontaneous contrast, strands, and aortic plaques thickness. None had IgG higher than 80 GPL units or was positive for anti-β2 glycoprotein I. Patients with at least 10 GPL units more often had a past history of cerebral infarction than patients lower aCL level. However, the incidence of recurrent stroke was 4.5 per 100 person-year in patients with more than 10 GPL units, and 2.7 per 100 person-year in those with more than 10 GPL units. Kaplan-Meier analysis for any vascular events showed no differences between the two groups. In contrast to young patients, elderly patients with 10 or more GPL units aCL and negative for anti-β2 glycoprotein I do not seem to have a higher risk of vascular events. Received: 5 April 2000 / Received in revised form: 2 August 2000 / Accepted: 11 August 2000     

Cerebral ischemia associated with anticardiolipin antibodies

Eight patients, 3 with systemic lupus erythematosus (SLE) or "SLE-like" disease, 1 with sarcoidosis, and 4 with no connective tissue disease had transient ischemic attacks (TIA) or cerebral infarctions associated with high levels of anticardiolipin antibodies (ACA). Cerebral ischemic events included amaurosis fugax, recurrent hemispheric TIA, cerebral infarction, and multi-infarction dementia. Treatment with acetylsalicylic acid was ineffective in 3 patients. Warfarin, alone or in combination with dipyridamole or steroids, may reduce the risk of further cerebrovascular events.     

Recurrent limbic and extralimbic encephalitis associated with thymoma

A 33-year-old woman, with a 7-year clinical history of invasive thymoma treated at ages 26 and 30 years by thymectomy and radiation, presented with a generalized convulsion and loss of consciousness. Following the seizure there was no neurological deficit and normal tendon reflexes. Magnetic resonance imaging (MRI) of the brain without gadolinium enhancement revealed multiple small lesions of high signal intensity on T2 and diffusion weighted images located in the cortical area beyond the temporal lobes. Brain biopsy demonstrated encephalitis with activated microglias and activated T-cell infiltration. Within 4 months of treatment with nothing other than anticonvulsant therapy, the lesions visible on the original MRI had completely disappeared and the patient was discharged with no neurological symptoms. The patient subsequently had two more episodes with a variety of symptoms such as incontinence, confusion, aphasia, apallial syndrome, and motor paresis. MRI following these episodes again revealed multiple lesions of similar appearance to those of the first episode, although in different locations, and much larger and more numerous. The patient had steroid pulse therapy after both episodes and the lesions noted on brain MRI disappeared within a few months with minimal neurological complications.     

Prospective study of anticardiolipin antibodies in stroke

Over 2 years, 104 patients underwent clinical evaluation and laboratory screening for the presence of abnormal anticardiolipin antibodies to determine the profile of laboratory and clinical findings in patients with stroke and other neurologic disorders. Seven with incomplete or ambiguous data were excluded; of the remaining 97 patients, 31 were greater than or equal to 65 years old. Nine patients suffered systemic lupus erythematosus, 45 suffered brain ischemia, and 43 suffered other nonischemic neurologic disorders. Cardiac arrhythmia, myocardial infarction, and cardiac valvulopathy were grounds for exclusion. The presence of anticardiolipin antibodies was not influenced by age. In the 88 patients without lupus, anticardiolipin antibodies were significantly more common in the group suffering brain ischemia than in the group with nonischemic neurologic disorders (29% versus 5%, p less than 0.01, chi 2 test). These controlled data demonstrate an association between the presence of circulating anticardiolipin antibodies with stroke, but not with other neurologic conditions.     

Multiple cerebral infarctions and dementia associated with anticardiolipin antibodies

Antibodies to negatively charged phospholipids including cardiolipin have been recognized in the sera of patients with systemic lupus erythematosus and other disorders. We report 4 patients who experienced cerebral infarctions and dementia in association with anticardiolipin antibodies. These patients did not have the characteristic lupus anticoagulant or systemic lupus erythematosus. The occurrence of anticardiolipin antibodies in patients with multiple cerebral infarctions who do not have evidence of a systemic vasculitis or inflammatory condition suggests that this association may be more common than previously recognized. It may be useful to test for the presence of anticardiolipin antibodies in patients who have unexplained cerebral infarctions.     

Recurrent stroke associated with cannabis use

Drug misuse represents a risk factor for cerebrovascular disease, especially among young people. Despite the fact that cannabis is the most widely used illicit drug, there are only a few reports associating its use with cerebrovascular disease. We describe a patient who suffered three ischaemic strokes immediately after cannabis consumption. Other stroke aetiologies were ruled out, and neuroimaging revealed infarcts in different arterial areas as well as evidence of non-atherosclerotic arterial disease, which suggests an underlying vasculopathy of uncertain (toxic or inflammatory) origin. Cannabis use may be associated with ischaemic stroke in young patients, but its mechanism is unclear.     

A case of optic neuritis associated with anticardiolipin antibodies]

We reported a case of optic neuritis with the persistence of severe visual loss and central scotoma in a 26-year-old woman who was proven to have biologic false positive test for syphilis, and the elevated serum titres of IgG and IgM anticardiolipin antibodies. C.S.F. findings showed the absence of oligoclonal bands and the presence of IgM anticardiolipin antibody. She was treated twice at intervals of two weeks with methylprednisolone 1000 mg intravenously daily for three days (pulse therapy), and was started on oral prednisolone 60 mg daily which tapered gradually. After the second treatment of the pulse therapy, her visual acuity was improved remarkably and the titre of anticardiolipin antibodies became normal. Her clinical course seemed to be different from that of the optic neuritis of multiple sclerosis, in which many of patients recover near normal visual acuity after a first attack. We suggested that antiphospholipid antibodies might play a role in the etiology of her optic neuritis.     

Recurrent acute cerebellar ataxia associated with anti-cardiolipin antibodies

Various autoantibodies are detected in patients with acute cerebellar ataxia (ACA). Although an autoimmune process may contribute to the mechanism of ACA, its pathophysiology is not completely understood. We report a girl with recurrent ACA and anti-cardiolipin antibodies. Her cerebral blood flow imaging showed hypoperfusion in the cerebellum, which improved when the anti-cardiolipin antibodies disappeared. Our case suggests that vasculopathy or non-vascular neurotoxicity in the cerebellum caused by antiphospholipid antibodies leads to acute cerebellar ataxia.     

High titer of anticardiolipin antibody is associated with first-ever ischemic stroke in Taiwan

BACKGROUND AND PURPOSE: The association between anticardiolipin antibody (aCL) and ischemic stroke is controversial, and there are few case-control studies of Asian populations. The aim of this study, therefore, was to determine whether aCL is an independent risk factor for ischemic stroke in Taiwanese patients over the age of 40 years. METHODS: Both the IgG and IgM isotypes of aCL were measured in 273 patients (> 40 years of age) hospitalized for first-ever ischemic stroke and in 181 non-stroke controls. Results were defined as: negative (< 10 IgG phospholipid units [GPL] or < 7.5 IgM phospholipid units [MPL]); low positive (10-20 GPL or 7.5-15 MPL); or, high positive (> 20 GPL or > 15 MPL). Odds ratios (OR) were estimated by logistic regression with adjustment for potential confounders. RESULTS: A high positive IgG aCL was present in 4.4% of the stroke patients and 1.2% of the controls. Age- and sex-adjusted analysis showed a borderline association between a high positive level for aCL IgG titer and stroke, with an OR of 4.01 (95% CI 0.87-18.37; p = 0.0739). Final analysis, with adjustments for age, sex, hypertension, diabetes, tobacco smoking, atrial fibrillation, left ventricular hypertrophy and hyperlipidemia, revealed an OR of 5.25 (95% CI 1.06-25.89; p = 0.0419). CONCLUSIONS: The results of this study suggest that elevated titer of aCL IgG (> 20 GPL) is associated with first-ever ischemic stroke in Taiwanese patients aged over 40 years. High positive aCL titer is related to ischemic stroke after adjustment for conventional cerebrovascular risk factors, indicating that it is probably an independent risk factor for ischemic stroke.     

Multiple mononeuropathy due to vasculitis associated with anticardiolipin antibodies: a case report

This report illustrates a case of peripheral nerve vasculitis associated with elevated anticardiolipin antibodies. A 49-year-old female with a history of seven spontaneous abortions initially complained of pain and numbness in her right calf that later spread to the left foot and ankle. Over the next few months, she developed a Raynaud phenomenon and livedo reticularis. Clinical examination revealed signs of multiple mononeuropathy. Right sural nerve biopsy performed two months after the beginning of the disease revealed active necrotizing arteritis of the epineural arteries with transmural inflammatory infiltrate and thrombosis. Vasculitis is a rare finding in sural nerve biopsies, usually in patients with systemic vasculitis or autoimmune connective tissue diseases. However, vasculitis restricted to the peripheral nerves has also been described. Our patient had no clinical or laboratory features of any autoimmune disorder and also no signs of systemic vasculitis. We discuss the potential role of anticardiolipin antibodies in the pathogenesis of vasculitis.     

Psychosis associated with thymoma

The case history of a 19-year-old black woman who died the day after she was treated for psychosis is described. The remarkable finding in her mental status was hyper-religiosity and in postmortem was a thymoma. The report discusses the relationship between thymoma and psychosis as well as the need to look for an organic etiology in patients manifesting a sudden psychotic regression with hyper-religiosity.     

Voltage-gated potassium channel antibodies associated limbic encephalitis in a patient with invasive thymoma

Recently, limbic encephalitis (LE) associated with Voltage-gated potassium channel antibody (VGKC-Ab) has been postulated as a new autoimmune disorder. Most previously reported cases of VGKC-Ab-associated LE were non-paraneoplastic, and reports of a paraneoplastic type are rare. Here we describe a 59-year-old woman with paraneoplastic VGKC-Ab-associated LE preceding the recurrence of invasive thymoma. There was a close temporal relationship between the clinical course and the changes of the VGKC-Ab titer. Unlike many of the non-paraneoplastic VGKC-Ab-associated LE cases, our cases showed the more extensive high intensity lesions on MRI and the absence of seizure and hyponatremia.     

Idiopathic intracranial hypertension and anticardiolipin antibodies

The association of idiopathic intracranial hypertension (IIH) or pseudotumour cerebri (PTC) with anticardiolipin antibodies (aCL-Abs) has been only acknowledged recently. However, its true incidence is as yet unknown. In this retrospective study, the co-occurrence of IIH and aCL-Abs was looked for among a relatively large group of patients diagnosed with IIH or PTC in the neuro-ophthalmology clinic during the years of 1992-8. All patients underwent routine blood tests and the presence of activated protein C resistance and protein S and protein C deficiency were recorded. ACL-Abs were determined in all patients. The co-occurrence of IIH and aCL-Abs was found in three out of 37 patients (8.1%), which is higher than the incidence of aCL-Abs in the general population but considerably lower than that reported in two previously published studies. The aCL-Ab positive patients in our series were significantly older and thinner than those in whom antibodies were undetected. In conclusion, it seems that patients with this association should be considered as a unique subgroup of IIH.     

Paraneoplastic diseases associated with thymoma

Abstract Background Thymoma is frequently associated with paraneoplastic diseases (PDs), most commonly with myasthenia gravis (MG). This association is thought to depend on thymoma's capacity to produce and export T lymphocytes. Objective (1) To determine the frequency and characteristics of thymoma-associated PDs other than MG; (2) to evaluate T cell maturation in thymomas with and without PDs. Methods We studied 260 patients with thymoma (associated with MG in 228). The occurrence of PDs was monitored together with the tumor outcome. Phenotypic characterization of thymocyte subsets in 14 thymoma samples (7 with and 7 without MG) was performed by FACS. Results A total of 47 PDs was diagnosed in 41/260 patients (15.8 %). Neurological PDs included neuromyotonia, limbic encephalitis, polymyositis, subacute hearing loss, psychosis and sleep disorders. A broad spectrum of nonneurological PDs were observed, among these, hematological and cutaneous diseases prevailed. Like MG, these disorders occurred either in the presence of the thymoma or at different times after thymomectomy; their onset often heralded a tumor recurrence. In thymomas from MG subjects, we found an increased proportion of fully mature CD4 single positive (SP) thymocytes and a reduced frequency of CD4SPCD25⁺ cells; the latter finding may reflect a deficient generation of T regulatory cells, a reduced intratumorous activation of T cells, or both. Conclusions We confirm the strong association of thymoma with PDs. These disorders often occurred in MG patients and their course in relation to thymoma was similar to that of MG. In accordance with previous observations, we found some alterations in the intratumorous production of mature CD4⁺ T cells that could be involved in the pathogenesis of paraneoplastic autoimmunity.