| Article Access Statistics|
| Viewed||7087 |
| Printed||169 |
| Emailed||6 |
| PDF Downloaded||177 |
| Comments ||[Add] |
| Cited by others ||2 |
Click on image for details.
|Year : 2000 | Volume
| Issue : 4 | Page : 258-61
Antiphospholipid antibody positive young stroke: an analysis of 12 cases.
A Panagariya, A Garg, RK Sureka
Department of Neurology, SMS Medical College & Hospital, Jaipur - 302 004, India. , India
Department of Neurology, SMS Medical College & Hospital, Jaipur - 302 004, India.
Source of Support: None, Conflict of Interest: None
AIMS AND OBJECTIVES: To study clinico-investigative profile of 12 young (<45 years) patients with stroke who tested positive for anti phospholipid antibodies (APLA). SUBJECTS AND METHODS: The diagnostic, clinical, laboratory and radiologic features in 12 APLA positive young patients who presented with stroke were studied. The APLA analysis included estimation of anticardiolipin (aCL) antibodies and lupus anticoagulant (LA). Other relevant tests included anti-nuclear antibody, human immunodeficiency virus, Venereal Diseases Research Laboratory, platelet count, echocardiography and carotid Doppler. APLA positive strokes were those cases where either the immunoglobulin G (IgG) and immunoglobulin M (IgM) were raised or LA was positive, and other known causes were excluded. RESULTS: Levels of IgG (aCL) was raised in 11 cases (mild 7, moderate 1, high 3), IgM was elevated in all the 12 cases (moderate 2, high 10). Of the two LA positive cases both were IgM positive but in one IgG was negative. Five patients showed small multiple bilateral cerebral infarcts on computerised tomography (CT) scan. 5 patients had history of recurrent strokes. Hemiparesis was more frequent than hemiplegia. None presented with dense hemiplegia. All patients recovered to normal functional capacity and did not have recurrence on drugs. CONCLUSION: A preliminary study on APLA positive young strokes showed certain clinical and radiological features, mild to moderate stroke, pre-treatment recurrences, multiple smaller infarcts on CT, which could be clustered in a subgroup of stroke in young. Incidentally these patients showed a good prognosis in terms of long term outcome.
Keywords: Adult, Antibodies, Anticardiolipin, analysis,Antibodies, Antiphospholipid, analysis,Cerebrovascular Accident, immunology,Female, Human, Lupus Coagulation Inhibitor, analysis,Male, Middle Age, Retrospective Studies,
|How to cite this article:|
Panagariya A, Garg A, Sureka R K. Antiphospholipid antibody positive young stroke: an analysis of 12 cases. J Postgrad Med 2000;46:258
|How to cite this URL:|
Panagariya A, Garg A, Sureka R K. Antiphospholipid antibody positive young stroke: an analysis of 12 cases. J Postgrad Med [serial online] 2000 [cited 2015 Aug 2];46:258. Available from: http://www.jpgmonline.com/text.asp?2000/46/4/258/263
Anti phospholipid antibodies (APLA) are a part of heterogeneous group of circulating serum polyclonal immunoglobulins (IgG, IgM, IgA or mixed) that bind negatively charged or neutral phospholipid component of cell membranes and cause increased tendency to venous or arterial thrombosis. There has been a dramatic surge of interest in APLA and associated clinical disorders especially focal ischaemic cerebrovascular diseases. They are probably present in up to 50% of the young persons with stroke and perhaps even in higher prevalence with recurrent ischaemic and diseases like systemic lupus erythematosous (SLE). Due to unexplained aetiology in large number of young stroke patients and absence of conventional predisposing risk factors like hypertension, diabetes, atherosclerosis etc., the importance of APLA estimation may increase many fold.
Twelve young patients of stroke with APLA positivity were assessed in detail to analyse whether they form an independent subgroup having specific pattern of occlusive disease.
Ninety-four young patients (<45 years) with stroke admitted in neurology department, SMS Medical College, Jaipur between March ’96 and June ’98 were studied. Apart from computerised tomography (CT) and Magnetic Resonance Imaging (MRI) (where ever necessary) all the routine and related specific investigations like haemogram, platelet count, activated partial thromboplastin time (aPTT), prothrombin time, chest x-ray, electrocardiogram, liver function and renal function tests, lipid profile, ultrasonography, echocardiography, carotid Doppler studies, anti-nuclear antibody (ANA), VDRL, HIV, were done. Aetiology was established in 64 (68%) cases. These included haemorrhagic stroke due to HT and aneurysm, cerebral venous thrombosis (CVT) related with pregnancy and puerperium, and thrombo-embolic stroke associated with hypertension, diabetes mellitus and valvular heart disease. In the remaining 30 patients where the aetiology could not be established, APLA were tested by anticardiolipin (aCL) antibodies and lupus anticoagulant (LA) estimation on admission (third to tenth day of stroke). aCL was tested by enzyme linked immunosorbent assay (Varelisa cardiolipin kit). Solid phase enzyme immuno essay technology (IEMA) was used to measure titre of antibodies. aCL titres were categorised into negative (<10MPL or GPL units), low positive (10-20MPL or GPL units), moderately positive (21-60MPL or 21-100 GPL units) and highly positive (>60MPL or 100GPL units). LA titre was estimated by dilute Russell viper venom technique (DRVVT). In 11 patients aCL antibodies (both IgG & IgM) were found to be positive in different titres and in one patient LA was positive along with high IgM. This sub group of 12 APLA positive cases was subsequently analysed. Various causes of secondary APLA like SLE, adult/juvenile rheumatoid arthritis, auto-immune thrombocytopaenic purpura, dermatomyositis, polymyositis, syphilis, leprosy, tuberculosis, HIV infections and drugs like chlorpromazine, phenothiazine, phenytoin etc. were excluded by relevant history and investigations. Anti ds-DNA was not done, as facilities were not available.
The salient features are shown in [Table - 1]. While IgG was raised in 11 cases (mild 7, moderate 1, high 3), IgM was elevated in all the 12 cases (moderate 2, high 10). Of the two LA positive cases both were IgM positive but in one IgG was negative. Five patients showed small multiple bilateral cerebral infarcts on CT scan. Five patients had history of recurrent strokes. Hemiparesis was a more frequent occurrence than hemiplegia. None presented with dense hemiplegia. Case 4 had suffered more than two episodes of foetal loss. Case 12 had cerebral venous thrombosis with cortical infarcts. All the 12 patients responded well to treatment with anti-platelets, aspirin or ticlopidine (in cases of single stroke) and anticoagulants (in cases of recurrent strokes).
APLA have been reported in 1% to 46% of stroke patients and 1-4% in normal controls, depending on the design and criteria of studies and the age distribution of the patients.,, Nagaraja et al in a study of 60 cases of young stroke found elevated aCL in 23% patients. The anti phospholipid antibodies in stroke study (APASS) indicated an average incidence of 10%. The mean age in the present study was 36.8 years., which is about two decades younger than average age of thromboembolic patients. The predisposing risk factors for stroke like diabetes, hypertension, atherosclerosis and hyperlipidaemia were absent in these patients. Similar low prevalence of recognised risk factors has also been reported in stroke patients with APLA in other studies. The available data so far suggest that APLA should be suspected in young stroke patients with history of previous thrombotic event, deep venous thrombosis, thrombocytopaenia and women with history of recurrent foetal loss.
In the present study, level of aCL both IgG and IgM were raised, while Levine suggested that IgG is the aCL most commonly seen with APLA positive stroke. In the recent study by Tuhrim et al aCL antibodies conferred a four fold increased risk of ischaemic stroke. Young stroke patients tend have higher levels of APLA and multiple infarcts than general stroke population. Whether elevated cardiolipin antibody titre is an independent risk factor is still not conclusive., Patients with migraine headache with or without aura have had APLA and some of these patients had suffered cerebral infarcts. The occurrence of vascular headache in three cases in the present series is consistent with this association, although the mechanism is uncertain. Incidentally, none of the patients in the present study had thrombocytopaenia. Five patients in present series had multiple (two or more) infarcts and in one patient cerebral venous thrombosis was found. Nagraja et al did not observe any case of venous thrombosis while in a study conducted by Mehndiratta et al one out of seven patients had venous stroke. Feldmann and Levine in 1995 also suggested that high titres of APLA are associated with a relatively high risk of recurrent thrombotic events, especially stroke. Five patients in our series had recurrent strokes, but its correlation with high titres of APLA could not be established. The lack of availability of follow up values of aCL is the limitation of the study. On comparing the APLA positive and APLA negative stroke patients in the present study, we found APLA positive stroke group had an average age of 36.8 years which was younger than average age for APLA negative group. More over multiple strokes/TIA episodes were more frequent in APLA positive group than the APLA negative group. These findings are in collaboration with other studies.
APLA leads to a hypercoagulable state by several different mechanisms like endothelial anticoagulant dysfunction, abnormalities of prostacyclin, anti-thrombin III, placental anticoagulant protein, protein C and protein S and complement activation any of which would lead to thrombosis. In addition to these factors, various studies have shown that ?2-glycoprotein I (?2 GPI) may be the key immunogen in the APLAS. LA also requires a co-factor identified as lipid bound prothrombin to interact with negatively charged phospholipids. In this reaction the LA recognizes an epitope that becomes exposed upon calcium mediated binding of prothrombin to phospholipid. The LA by reacting with proteins at these or other sites, may interfere with the normal haemostatic system and contribute to a prothrombotic environment by binding to thrombine activated platelets inhibiting thrombin mediated endothelial cell prostacycline release or inhibitory protein C activation.
Therapeutic options in patients with stroke and APLA include antithrombotics and immune based treatments. Antithrombotics include anticoagulants, subcutaneous heparin or low molecular weight heparin and antiplatelet agents aspirin and ticlopidine. Immune based therapies include corticosteroids and immunosuppressants. In our series, patients with first episode of stroke were put on aspirin or ticlopidine and were followed fortnightly with total blood counts. Patients with recurrent events were put on oral anticoagulant. All patients recovered to normal functional capacity and did not have recurrence. Our findings are in agreement with other study by Munther et al. It is difficult to make any recommendation about preferred therapy as the number of cases with follow up is too small. Besides drug therapy recent studies have indicated that calcium intake in dairy milk has inverse relation with risk for ischaemic stroke. There are no clear recommendations about the duration of the therapy but consensus could favour the life long treatment with antiplatelet drugs or anticoagulants to prevent recurrences.
Though the study comprises of a small sample certain inferences can be drawn. The APLA positive young stroke cases may constitute an independent subgroup with certain clinical, investigatory and prognostic predictors. Thus, they have mild to moderate strokes, more often multiple smaller infarcts on CT/MRI, history of pretreatment recurrences and relatively better, immediate and long term outcome.
| :: References|| |
Levine SR, Brey RL, Joseph CL, Havstad S. Risk of recurrent thromboembolic events in patients with focal cerebral ischaemia and antiphospholipid antibodies. Stroke 1992; (2 Suppl):I29-32. |
|2.||Feldmann E, Levine SR. Cerebrovascular disease with antiphospholipid antibodies. immune mechanism, significance and therapeutic options. Ann Neurol 1995; 37(Suppl 1):S114-130. |
|3.||Coull BM, Levine SR, Brey RL. The role of antiphospholipid antibodies in stroke. Neurol Clin 1992;10:125-143. |
|4.||Harris EN. Serological detection of antiphospholipid antibodies. Stroke 1992;23(2 Suppl):I3-6. |
|5.||Anticardiolipin antibodies are an independent risk factor for first ischemic stroke. The Antiphospholipid Antibodies in Stroke Study (APASS) Group. Neurology 1993;43:2069-73. |
|6.||Brey RL, Hart RG, Sherman DG, Tegeler CH. Antiphospholipid antibodies and cerebral ischemia in young people. Neurology 1990;40: 1190-1196. |
|7.||Montalban J, Rio J, Khamashta MA, Davalos A, Codina M, Swana GT, et al. Value of immunological testing in stroke patients. A prospective multicenter study. Stroke 1994;25:2412-2415. |
|8.||Asherson RA, Khamashta MA, Ordi Ros J, Derksen RHW, Machin SJ, Barguinero J, et al. The primary antiphospholipid syndrome. Major clinical & serological features. Medicine 1990;68:366-374. |
|9.||Nagaraja D, Christopher R, Manjari T. Anticardiolipin antibodies in ischaemic stroke in young. Indian experience. J Neurol Sci 1997;150: 137-142. |
|10.||Levine SR, Brey RL, Sawaya KL, Salowich-Palm L, Kokkinos J, Kostrzema B, et al. Recurrent stroke and thrombo-occlusive events in antiphospholipid syndrome. Ann Neurol 1995;38:119-24. |
|11.||Panagariya A, Makkar RK. APLA and Stroke. South Asian Journal of Preventive Cardiology 1999;3:6-7. |
|12.||Levine SR. Most commonly asked questions about antiphospholipid antibodies. The Neurologist 1996;2:79-84. |
|13.||Tuhrim S, Rand JH, Wu XX, Weinberger J, Horowitz DR, Goldman ME, et al. Elevated anticardiolipin antibody titre is a stroke risk factor in a multiethnic population independent of Iso type of degree of positivity. Stroke 1999; 30:1561-1565. |
|14.||Ahmed E, Stegmayr B, Trifunovic J, Weinehall L, Hallmans G, Lefvert AK. Anticardiolipin antibodies are not an independent risk factor for stroke: an incident case-referent study nested within the MONICA and Vasterbotten cohort project. Stroke 2000;31:1289-1293. |
|15.||Levine SR, Deegan MJ, Futrell N, Welch KM. Cerebrovascular and neurologic disease associated with antiphospholipid antibodies: 48 cases. Neurology 1990;40:1181-1189. |
|16.||Mehndiratta MM, Bhattacharya A, Gupta M, Khawaja GK, Puri V. Antiphospholipid antibodies syndrome in ‘stroke in young’. Neurol India 1999; 47:122-126. |
|17.||Fleck RA, Rapaport SI, Rao LV. Antiprothrombin antibodies and the lupus anticoagulant. Blood 1988;72:512-519. |
|18.||Khamashta MA, Cuadrado MJ, Mujic F, Taub NA, Hunt BJ, Hughes GR. The management of thrombosis in the antiphospholipid antibody syndrome. N Engl J Med 1995;332:993-997. |
|19.||Iso H, Stampfer MJ, Manson JE, Rexrode K, Hennekens CH, Colditz GA, et al. Prospective study of calcium, potassium, and magnesium intake and risk of stroke in women. Stroke 1999;30:1772-1779.
[Table - 1]
|This article has been cited by|
||Pregnancy, patent foramen ovale and stroke: a case of pseudoperipheral facial palsy
| ||Giberti L, Bino G, Tanganelli P |
| ||NEUROLOGICAL SCIENCES. 2005; 26 (1): 43-45 |
||Anticardiolipin antibodies as markers of physiologic stress: a case study of idiopathic stroke in a young adult
| ||Segler CP |
| ||MEDICAL HYPOTHESES. 2004; 63 (3): 461-463 |