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many of the patients have remained well for years after a single stroke Skin biopsy aids in diagnosis There are instances in which the radiologic changes caused by recurrent small infarctions are dif cult to distinguish from multiple sclerosis, as discussed in several parts of Chap 36, on demyelinative diseases Associations of the syndrome with transverse myelitis, Guillain-Barre syndrome, hearing loss, and a number of other processes has been suspected but not proven Treatment Warfarin has been used with some bene t in the above conditions Khamashta and colleagues have found that the INR must be maintained close to 3 for effective prevention of stroke According to the study conducted by Crowther and colleagues, an INR of 2 to 3 conferred the same degree of protection from thrombosis as did higher levels, but the number of thrombotic events was low in both groups and there was only one stroke in 114 patients over a period of about 3 years Patients with severe thrombocytopenia and with other intrinsic coagulopathies should be treated with warfarin very cautiously Although the INR is used as a gauge of the level of anticoagulation, it maybe altered by the antibodies; no ideal method for monitoring treatment has been devised Aspirin, on uncertain grounds, is thought not to confer protection for stroke, but in only a few small series has its effect been analyzed In catastrophic cases, intravenous immunoglobulin and plasma exchange have been used with some effect It is most important to eliminate smoking and estrogen-containing compounds, since these greatly raise the risk of stroke Plasma exchange may be useful in fulminant cases Aspirin and heparin are favored in women with recurrent fetal loss related to antiphospholipid antibody (Lockshin and Sammaritano) Thrombotic Thrombocytopenic Purpura (TTP, Moschcowitz Syndrome) This is yet another uncommon but serious disease of the small blood vessels, observed mainly in young adults It is characterized pathologically by widespread occlusions of arterioles and capillaries involving practically all organs of the body, including the brain, as described by Adams and colleagues (1948) The nature of the occluding material has not been completely de ned Fibrin components have been identi ed by immuno uorescent techniques; some investigators have demonstrated disseminated intravascular platelet aggregation rather than brin thrombi TTP is caused by an acquired circulating IgG inhibitor of von Willebrand factor cleaving protease; a rarer familial form is caused by a constitutional de ciency of the protease Clinically, the main features of this disease are fever, anemia, symptoms of renal and hepatic disease, and thrombocytopenia the latter giving rise to the common hemorrhagic manifestations (petechiae and ecchymoses of the skin, retinal hemorrhages, hematuria, gastrointestinal bleeding, etc) Neurologic symptoms are practically always present and are the initial manifestation of the disease in about half the cases Confusion, delirium, seizures, and hemiparesis sometimes remittent or uctuating in nature are the usual manifestations of the nervous system disorder and are readily explained by the widespread microscopic ischemic lesions in the brain Garrett and colleagues have emphasized the presentation of nonconvulsive status epilepticus in TTP, and we have encountered two such cases Gross infarction was not observed In most patients who survive, recovery of the focal neurologic de cits can be expected unless there is an identi able infarction on CT or MRI The CSF is normal except for elevated protein in some cases To our knowledge, a mononeuritis multiplex does not occur The recommended treatment is plasma exchange or plasma infusion.

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Thrombocytosis and Thrombocythemia These terms refer to an increase of platelets above 800,000/mm3 The condition is generally considered to be a form of myeloproliferative disease In some patients there is an enlarged spleen, polycythemia, chronic myelogenous leukemia, or myelosclerosis In several of our patients no explanation of the thrombocytosis was found They presented with recurrent cerebral and systemic thrombotic episodes, often of minor degree and transient Cytopheresis, to reduce the platelets, and antimitotic drugs (hydroxyurea) to suppress megakaryocyte formation, are helpful in ameliorating the neurologic symptoms In one of the cases we have followed, several small lesions, presumably infarctions, were situated in the white matter and simulated multiple sclerosis Polycythemia Vera This is another myeloproliferative disorder of unknown cause, characterized by a marked increase in RBC mass and in blood volume and often by an increase in WBCs and platelets as well This condition must be distinguished from the many secondary or symptomatic forms of polycythemia (erythrocytosis), in which the platelets and white cells remain normal The slightly increased incidence of thrombosis in primary polycythemia is attributed to the high blood viscosity, engorgement of vessels, and reduced rate of blood ow The majority of patients with cerebrovascular manifestations have TIAs and small strokes, but we have seen one case of sagittal sinus thrombosis With very high hematocrit, sludging of red cells may be seen in the retinal vessels The cause of cerebral hemorrhage in this disease is less clear, although a number of abnormalities of platelet function and of coagulation have been described (see Davies-Jones et al) A wide variety of bleeding disorders such as leukemia, aplastic anemia, thrombocytopenic purpura, and hemophilia may also give rise to cerebral hemorrhage Many rare forms of bleeding disease may be complicated by hemorrhagic manifestations; these have been reviewed by Davies-Jones and colleagues Sickle Cell Disease This inherited disease is related to the presence of the abnormal hemoglobin S in the red corpuscles Clinical abnormalities occur only in patients with sickle cell disease ie, with the homozygous state, and not in those with the sickle cell trait, which represents the heterozygous state The disease, which is practically limited to persons of central African and certain Mediterranean origins, begins early in life and is characterized by crises of infection (particularly pneumococcal meningitis), pain in the limbs and abdomen, chronic leg ulcers, and infarctions of bones and visceral organs Ischemic lesions of the brain, both large and small, are the most common neurologic complications, but cerebral, subarachnoid, and subdural hemorrhage may also occur and the vascular occlusions may be either arterial or venous Disseminated Intravascular Coagulation (DIC) This is perhaps the commonest and most serious disorder of coagulation affecting the nervous system The basic process depends on the release of thromboplastic substances from damaged tissue, resulting in the activation of the coagulation process and the formation of brin, in the course of which clotting factors and platelets are consumed Virtually any mechanism that produces tissue damage can result in the release of tissue thromboplastins into the circulation Thus, DIC complicates a wide variety of clinical conditions overwhelming sepsis, massive trauma, cardiothoracic surgery, heat stroke, burns, incompatible blood transfusions and other immune complex disorders, diabetic ketoacidosis, leukemia, obstetric com-.

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