Posterior reversible encephalopathy syndrome ( PRES ), also known as reversible posterior leukoencephalopathy syndrome ( RPLS ), is a rare condition in which parts of the brain are affected by swelling, usually as a result of an underlying cause. Someone with PRES may experience headaches , changes in vision , and seizures , with some developing other neurological symptoms such as confusion or weakness of one or more limbs . The name of the condition includes the word "posterior" because it predominantly, though not exclusively, affects the back of the brain (the parietal and occipital lobes ). Common underlying causes are severely elevated blood pressure , kidney failure , severe infections , certain medications, some autoimmune diseases , and pre-eclampsia . The diagnosis is usually made by a brain scan ( MRI ), in which areas of swelling can be identified.
56-469: PRES can be short for: Pôle de recherche et d'enseignement supérieur Posterior reversible encephalopathy syndrome Pregnenolone sulfate (more commonly called PregS) PRES , Glossing abbreviation for present tense Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title PRES . If an internal link led you here, you may wish to change
112-471: A stroke can also be seen. Other symptoms include, but are not limited to jaundice or paleness of the skin, a fast heart rate or shortness of breath , or dots on the skin known as petechiae . High blood pressure has also been observed as a symptom. As TTP progresses, blood clots form within small blood vessels (microvasculature), and platelets (clotting cells) are consumed. As a result, bruising, and rarely bleeding can occur. The bruising often takes
168-431: A chronic seizure disorder ( epilepsy ). The incidence (number of cases per year) of PRES is not known, but increasing use of MRI scans has led to increased recognition. The incidence of PRES in certain subgroups has been estimated to be approximately 0.8% in those with end stage renal disease, 0.7% in those with SLE, and 0.5% in those with a solid organ transplant. In select single center retrospective cohort studies ,
224-621: A consequence of the blood vessel damage rather than the cause. Some, therefore, include the vasospasm in the "toxic" theory. It is considered likely that these multiple mechanisms all potentially play a role in the development of PRES. There are no formal diagnostic criteria for PRES, but it has been proposed that PRES can be diagnosed if someone has developed acute neurological symptoms (seizure, altered mental state, headache, visual disturbances) together with one or more known risk factors, typical appearance on brain imaging (or normal imaging), and no other alternative diagnosis. Some consider that
280-461: A different diagnosis is more likely. The ISTH guidelines suggested diagnostic and early management strategy. Suggestions included 1) for high pretest probability based on PLASMIC score or French score, start TPE and corticosteroids, and collect plasma samples for ADAMTS13 testing before therapy. Consider caplacizumab if ADAMTS13 test results are expected within 72 hours. If ADAMTS13 <10 IU/dL, continue caplacizumab and rituximab . If ADAMTS13
336-455: A full recovery within hours to days. 8–17% of people with PRES die, although this is not always a direct consequence of the PRES. Of those who have residual symptoms after PRES, this is attributable largely to hemorrhage. Non-resolution of MRI abnormalities has been linked with poorer outcomes. The presence of brain hemorrhage and cytotoxic edema (brain edema with concomittant brain tissue damage)
392-424: A review of 16 new cases and 255 previously reported cases led to the formulation of the classical pentad of symptoms and findings (i.e., thrombocytopenia, microangiopathic hemolytic anemia, neurological symptoms, kidney failure, fever); in this series, mortality rates were found to be very high (90%). While a response to blood transfusion had been noted before, a 1978 report and subsequent studies showed blood plasma
448-529: A wait and watch approach outside of pregnancy. People with refractory or relapsing TTP may receive additional immunosuppressive therapy, e.g. vincristine , cyclophosphamide , cyclosporine A , or splenectomy . Children with Upshaw-Schulman syndrome receive prophylactic plasma every two to three weeks; this maintains adequate levels of functioning ADAMTS13. Some tolerate longer intervals between plasma infusions. Additional plasma infusions may be necessary for triggering events, such as surgery; alternatively,
504-510: A worse outcome, and abnormalities in the corpus callosum on MRI have been linked with worse prognosis. Some patterns on electroencephalography (EEG) are also associated with a poorer outcome. After an episode of PRES, even when it was associated with seizure activity, only a small proportion of people remain at risk of ongoing seizures and the majority can eventually discontinue anticonvulsant treatment. Approximately 3% of those with PRES will develop late, recurrent seizures with 1% developing
560-432: Is a metalloproteinase responsible for the breakdown of von Willebrand factor (vWF), a protein that links platelets , blood clots , and the blood vessel wall in the process of blood coagulation . Very large vWF multimers are more prone to lead to coagulation. Hence, without proper cleavage of vWF by ADAMTS13, coagulation occurs at a higher rate, especially in the microvasculature, part of the blood vessel system where vWF
616-400: Is a form of thrombotic microangiopathy (TMA), the formation of blood clots in small blood vessels throughout the body, which can lead to microangiopathic hemolytic anemia and thrombocytopenia . This characteristic is shared by two related syndromes, hemolytic-uremic syndrome (HUS) and atypical hemolytic uremic syndrome (aHUS). Consequently, differential diagnosis of these TMA diseases
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#1732852251853672-406: Is also associated with a poor prognosis. If PRES was caused by pre-eclampsia or eclampsia the prognosis is better than in PRES due to other causes. Factors that predict poorer prognosis are the person's age, the level of C-reactive protein in the blood (a marker of inflammation), altered mental state at the time of diagnosis, and altered markers of coagulation . People with diabetes may have
728-473: Is essential. Both TTP and HUS are characterized by fever , anemia , thrombocytopenia , renal failure , and neurological symptoms. Generally, TTP has higher rates of neurological symptoms (≤80%) and lower rates of renal symptoms (9%) than HUS (10–20% and 90%, respectively). Unlike HUS and aHUS, TTP is known to be caused by a defect in the ADAMTS13 protein, so a lab test showing ≤5% of normal ADAMTS13 levels
784-509: Is identical or closely related with hypertensive encephalopathy , the presence of neurological symptoms in those with a hypertensive emergency . The precise mechanism is PRES is not fully understood, it is considered to be related to a problem with the blood vessels of the brain. There are several theories as to why these blood vessels may become inappropriately permeable and allow the surrounding brain tissue to become swollen . The "vasogenic" theory posits that elevated blood pressure overcomes
840-422: Is indicative of TTP. ADAMTS13 levels above 5%, coupled with a positive test for shiga-toxin / enterohemorrhagic E. coli (EHEC), are more likely indicative of HUS, whereas absence of shiga-toxin/EHEC can confirm a diagnosis of aHUS. Due to the high mortality of untreated TTP, a presumptive diagnosis of TTP is made even when only microangiopathic hemolytic anemia and thrombocytopenia are seen, and therapy
896-676: Is most active due to high shear stress . TTP may also be congenital . Such cases may be caused by mutations in the ADAMTS13 gene. This hereditary form of TTP is called Upshaw–Schulman syndrome (also spelled Upshaw–Schülman). People with this inherited ADAMTS13 deficiency have a surprisingly mild phenotype, but develop TTP in clinical situations with increased von Willebrand factor levels (e.g. infection). Reportedly, less than 5% of all TTP cases are due to Upshaw–Schulman syndrome. People with this syndrome generally have 5–10% of normal ADAMTS-13 activity. A 2024 study suggested that hereditary TTP
952-937: Is not clear if this prognostically relevant. Abnormal apparent diffusion coefficient is seen in about 20% of cases. In 10–25% of cases of PRES there is evidence of hemorrhage on neuroimaging. Various types of hemorrhage may occur: hemorrhage into the brain tissue itself (intraparenchymal hemorrhage), sulcal subarachnoid hemorrhage , and microbleeds. There is no specific treatment for PRES, other than removing or treating any underlying cause. For instance, immunosuppressive medication may need to be withheld. 40% of all people with PRES are unwell enough to require intensive care unit admission for close observation and treatment of complications. Those with PRES with seizures are treated using standard anticonvulsants used in other seizure disorders as there are no specific medications specific to PRES with seizures. However, in those with PRES due to pre-eclampsia or eclampsia , IV magnesium sulfate
1008-456: Is often established with an initial emergent presentation of one or more classic symptoms and a complete blood count revealing severe thrombocytopenia. The PLASMIC score, Bentley score, and French TMA score have been used to assess clinical probability of TTP. A definitive diagnosis of TTP may be established when a laboratory assay of ADAMTS13 identifies under 10% of normal enzyme function. Borderline or normal ADAMTS13 activity suggests
1064-412: Is often present. Similarly, the majority of people with PRES have an impaired kidney function, and 21% are receiving regular hemodialysis . In PRES related to medications, there may be an interval of weeks to months between the initiation of the treatment and the development of PRES. After a hematopoietic stem cell transplantation (bone marrow transplant) the risk of PRES is approximately 8%, whereas
1120-577: Is poorly understood, as ADAMTS13 activity is generally not as depressed as in idiopathic TTP, and inhibitors cannot be detected. Probable etiology may involve, at least in some cases, endothelial damage, although the formation of thrombi resulting in vessel occlusion may not be essential in the pathogenesis of secondary TTP. These factors may also be considered a form of secondary aHUS; people presenting with these features are, therefore, potential candidates for anticomplement therapy. The underlying mechanism typically involves autoantibody-mediated inhibition of
1176-410: Is started. Transfusion is contraindicated in thrombotic TTP, as it fuels the coagulopathy. Since the early 1990s, plasmapheresis has become the treatment of choice for TTP. This is an exchange transfusion involving removal of the person's blood plasma through apheresis and replacement with donor plasma ( fresh frozen plasma or cryosupernatant ); the procedure must be repeated daily to eliminate
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#17328522518531232-500: Is supportive: removal of the cause or causes and treatment of any of the complications, such as anticonvulsants for seizures. PRES may be complicated by intracranial hemorrhage , but this is relatively rare. The majority of people recover fully, although some may experience some residual symptoms. PRES was first described in 1996. PRES usually has an acute onset. Most people with PRES experience headaches and seizures; many also experience visual changes, confusion, drowsiness, weakness of
1288-499: Is the preferred medication for both seizures and hypertension. There are no universally accepted blood pressure lowering goals in those with PRES and hypertension, however, if there is a hypertensive emergency, the blood pressure may lowered quickly, but not less than 25% within the first hour with the goal of blood pressure normalization within 24 to 48 hours. There are no blood pressure lowering agents that are specifically used in PRES with hypertension, but commonly used agents include
1344-400: Is thought to kill the B cells and thereby reduce the production of the inhibitor. A stronger recommendation for rituximab exists where TTP does not respond to corticosteroids and plasmapheresis. Caplacizumab is an adjunct option in treating TTP as it has been shown that it induces a faster disease resolution compared with those people who were on placebo . However, the use of caplacizumab
1400-487: Is underdiagnosed and should be considered in cases of unexplained stroke, neonatal jaundice, and severe pre-eclampsia. The study estimated the global prevalence of hereditary TTP at 40 per million, in contrast to previously reported estimates of 0.5 to 2.0 per million. Secondary TTP is diagnosed when the person's history mentions one of the known features associated with TTP. It comprises about 40% of all cases of TTP. Predisposing factors are: The mechanism of secondary TTP
1456-549: Is ≥20 IU/dL, consider to stop caplacizumab and seek other diagnoses. If ADAMTS13 activity is borderline, use clinical judgment; 2) for low or intermediate pretest probability, still consider TPE and corticosteroids, but withhold caplacizumab until plasma ADAMTS13 test results are available; if ADAMTS13 activity is <10 IU/dL, consider adding caplacizumab and rituximab; if ADAMTS13 activity is ≥20 IU/dL, no caplacizumab should be used and other diagnoses should be sought; if ADAMTS13 activity falls borderline, consider other diagnoses. TTP
1512-630: The post partum period accounted for a notable portion (12–31%) of the cases in some studies; TTP affects about one in 25,000 pregnancies. TTP was initially described by Eli Moschcowitz at the Beth Israel Hospital in New York City in 1924. Moschcowitz ascribed the disease (incorrectly, as now known) to a toxic cause. Moschcowitz noted his patient, a 16-year-old girl, had anemia, small and large bruises, microscopic hematuria , and, at autopsy, disseminated microvascular thrombi. In 1966,
1568-527: The Upshaw–Schulman syndrome ). In 1998, the majority of cases were shown to be caused by the inhibition of the enzyme ADAMTS13 by antibodies . Knowledge of this relationship between reduced ADAMTS13 and the pathogenesis of TTP is credited to two independent groups of researchers (Furlan and Tsai) who published their research in the same issue of the New England Journal of Medicine . ADAMTS13
1624-424: The enzyme ADAMTS13 . This results in decreased break down of large multimers of von Willebrand factor (vWF) into smaller units. Less commonly TTP is inherited , known as Upshaw–Schulman syndrome , such that ADAMTS13 dysfunction is present from birth. Diagnosis is typically based on symptoms and blood tests. It may be supported by measuring activity of or antibodies against ADAMTS13. With plasma exchange
1680-421: The intravenous medications nicardipine , clevidipine or labetalol which are fast acting, quickly adjustable, and can be given using continuous infusion with close monitoring. Of the blood pressure lowering agents available, nitrates may need to be avoided as there is a concern that this may aggravate the PRES even while lowering the blood pressure. With adequate treatment, 70-90% of people with PRES make
1736-516: The normal capability of blood vessels in the brain to maintain a normal cerebral blood flow . The excessive pressure damages the endothelial layer and the blood–brain barrier , leading to swelling (edema). The predilection toward the posterior brain may be explained by the reduced density of sympathetic innervation in the posterior circulation compared to the anterior circulation (thus a reduced adaptive capacity to fluctuations or elevations in blood pressure). The "vasogenic" theory seems to explain
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1792-521: The parietal and occipital lobes ; this pattern is present in more than half of all cases. FLAIR sequences can be better at showing these abnormalities. Some specific other rare patterns have been described: the superior frontal sulcus (SFS) watershed pattern, a watershed pattern involving the entire hemisphere (holohemispheric), and a central pattern with vasogenic oedema in the deep white matter, basal ganglia , thalami , brainstem and pons . These distinct patterns do not generally correlate with
1848-402: The "neuropeptide/cerebral vasoconstriction" theory, some specific substances ( endothelin 1 , thromboxane A2 ) trigger spasm of the blood vessels with resultant vessel wall damage and edema. The latter hypothesis is supported by the frequent finding of diffuse blood vessel spasms (vasoconstriction) in many people with PRES, and the evidence for decreased perfusion, although the spasm may also be
1904-489: The abnormalities need to be shown to be reversible. If lumbar puncture is performed this may show increased protein levels but no white blood cells . Computed tomography scanning may be performed in the first instance; this may show low density white matter areas in the posterior lobes. The diagnosis is typically made with magnetic resonance imaging of the brain. The findings most characteristic for PRES are symmetrical hyperintensities on T 2 -weighed imaging in
1960-414: The almost 50% of cases of PRES where there had been severely elevated blood pressure. It is also called the "breakthrough" theory, or the "hyperperfusion theory". This theory does not explain the edema in many other cases where the blood pressure has been normal or even low; in fact, the edema tends to be more severe in those without abnormally elevated blood pressure. In PRES secondary to other causes,
2016-459: The arm and/or leg on one side of the body (hemiplegia), difficulty speaking, or, more rarely, other neurological symptoms. Some people with PRES may experience coma . The visual changes in PRES may include hemianopsia (inability to see the left or right part of the visual field), blurred vision, lack of visual awareness on one side , visual hallucinations , and cortical blindness . Seizures occur in about two thirds of cases with seizures being
2072-424: The blood smear), and various clinical signs such as petechiae , purpura , neurologic symptoms, myocardial ischemia, mesenteric ischemia , and renal abnormalities. Notably, the complete classic pentad of TTP symptoms—microangiopathic hemolytic anemia, thrombocytopenia, renal abnormalities, fever, and neurologic abnormalities—is only seen in about 10% of acute cases at initial presentation. Clinical suspicion of TTP
2128-475: The blood vessel damage has been attributed to other mechanisms. The "cytotoxic" theory suggests that it is direct cell damage by toxins (usually medications) that precipitates the edema. The "immunogenic" theory suggests a role for the immune system (specifically T cells ). Some consider the cytotoxic and immunogenic theories together as a single "toxic" theory. There appears to be a role of cytokines in causing endothelial dysfunction. Finally, according to
2184-588: The body. This results in a low platelet count , low red blood cells due to their breakdown , and often kidney , heart , and brain dysfunction. Symptoms may include large bruises , fever , weakness , shortness of breath , confusion , and headache . Repeated episodes may occur. In about half of cases a trigger is identified, while in the remainder the cause remains unknown. Known triggers include bacterial infections , certain medications, autoimmune diseases such as lupus , and pregnancy . The underlying mechanism typically involves antibodies inhibiting
2240-409: The enzyme ADAMTS13 , a metalloprotease responsible for cleaving large multimers of von Willebrand factor (vWF) into smaller units. The increase in circulating multimers of vWF increases platelet adhesion to areas of endothelial injury, particularly where arterioles and capillaries meet, which in turn results in the formation of small platelet clots called thrombi . As platelets are used up in
2296-418: The form of purpura, while the most common site of bleeding, if it occurs, is from the nose or gums. Larger bruises ( ecchymoses ) may also develop. The classic presentation of TTP, which occurs in less than 10% of people, includes five medical signs. These are: TTP, as with other microangiopathic hemolytic anemias (MAHAs), is caused by spontaneous aggregation of platelets and activation of coagulation in
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2352-426: The formation of thrombi, this then leads to a decrease in the number of overall circulating platelets, which may then cause life-threatening bleeds. Red blood cells passing the microscopic clots are subjected to shear stress , which damages their membranes, leading to rupture of red blood cells within blood vessels, which in turn leads to microangiopathic hemolytic anemia and schistocyte formation. The presence of
2408-442: The incidence of PRES on neuroimaging in those with eclampsia was between 75 and 98%, with a much smaller incidence of PRES seen in those with pre-eclampsia. Younger age at pregnancy (median age 23 in one study), presence of eclampsia, and primigravida (having a first pregnancy) are all associated with a greater risk of PRES in pregnant people. PRES was first described in 1996 in a group of 15 patients identified retrospectively in
2464-491: The inhibitor and abate the symptoms. If apheresis is not available, fresh frozen plasma can be infused, but the volume that can be given safely is limited due to the danger of fluid overload. Plasma infusion alone is not as beneficial as plasma exchange. Corticosteroids ( prednisone or prednisolone ) are usually given. Rituximab , a monoclonal antibody aimed at the CD20 molecule on B lymphocytes , may be used on diagnosis; this
2520-554: The initial symptom in about 50% of cases. In children seizures may be seein in up to 90% of cases of PRES. If seizures occur they may be focal or generalized . About 18% of people who have seizures develop status epilepticus , where seizures are not controllable with simple measures. Causes that may contribute to the development of PRES are: immunosuppression (especially for organ transplantation , e.g. with tacrolimus ), severe infection and/or sepsis , chemotherapy , autoimmune disease, and pre-eclampsia. High blood pressure
2576-413: The link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=PRES&oldid=1214064794 " Category : Disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages Posterior reversible encephalopathy syndrome The treatment for PRES
2632-559: The nature of the symptoms or their severity, although severe edema may suggest a poorer prognosis. If the appearances are not typical, other causes for the symptoms and the imaging abnormalities need to considered before PRES can be diagnosed conclusively. In many cases there is evidence of constriction of the blood vessels (if angiography is performed), suggesting a possible overlap with reversible cerebral vasoconstriction syndrome (RCVS). Diffusion MRI may be used to identify areas of cytotoxic edema caused by poor blood flow (ischemia) but it
2688-437: The platelet count may be monitored closely around these events with plasma being administered if the count drops. Measurements of blood levels of lactate dehydrogenase , platelets , and schistocytes are used to monitor disease progression or remission. ADAMTS13 activity and inhibitor levels may be measured during follow-up, but in those without symptoms the use of rituximab is not recommended. Apadamtase alfa (Adzynma)
2744-624: The records of the New England Medical Center in Boston and Hôpital Sainte Anne in Paris. The name was revised in 2000 from "leukencephalopathy" to "encephalopathy" as the former suggested that it only affects the white matter of the brain, which is not the case. Thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura ( TTP ) is a blood disorder that results in blood clots forming in small blood vessels throughout
2800-804: The risk is lower (0.4-6%) after a solid organ transplant. The following autoimmune conditions have been found to be associated with PRES: thrombotic thrombocytopenic purpura (TTP), primary sclerosing cholangitis (PSC), rheumatoid arthritis (RA), Sjögren syndrome , polyarteritis nodosa (PAN), systemic sclerosis , systemic lupus erythematosus (SLE), granulomatosis with polyangiitis (GPA), Crohn's disease and neuromyelitis optica (NMO), as well as hemolytic-uremic syndrome (HUS). A number of other associations have also been reported, including some other groups of medications, blood transfusion , elevated calcium levels , decreased magnesium levels , postpartum cerebral angiopathy , and drugs of abuse ( cocaine and amphetamine ). It has been suggested that PRES
2856-451: The risk of death has decreased from more than 90% to less than 20%. Immunosuppressants , such as glucocorticoids , and rituximab may also be used. Platelet transfusions are generally not recommended. About 1 per 100,000 people are affected. Onset is typically in adulthood and women are more often affected. About 10% of cases begin in childhood. The condition was first described by Eli Moschcowitz in 1924. The underlying mechanism
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#17328522518532912-478: The small blood vessels. Platelets are consumed in the aggregation process and bind vWF . These platelet-vWF complexes form small blood clots which circulate in the blood vessels and cause shearing of red blood cells, resulting in their rupture and formation of schistocytes . The two best understood causes of TTP are due to autoimmunity ( acquired TTP), caused by autoantibodies targeting ADAMTS13 , or congenital TTP : an inherited deficiency of ADAMTS13 (known as
2968-482: The thrombi reduces blood flow to organs resulting in cellular injury and end organ damage . Depression is common in those recovering from TTP; 59% of recovered TTP patients screened positive for depression within 11 years after recovery. Thrombotic thrombocytopenic purpura (TTP) initially presents with a range of symptoms that may include severe thrombocytopenia (platelet count usually < 30,000/mm³), microangiopathic hemolytic anemia (evidenced by schistocytes in
3024-1047: Was approved for medical use in the United States in November 2023. The use of ADAMTS13 is well established for the treatment of congenital TTP. The mortality rate is around 95% for untreated cases, but the prognosis is reasonably favorable (80–90% survival) for people with idiopathic TTP diagnosed and treated early with plasmapheresis . The incidence of TTP is about 4–5 cases per million people per year. Idiopathic TTP occurs more often in women as well as people of African descent, and TTP secondary to autoimmune disorders such as systemic lupus erythematosus occurs more frequently in people of African descent, although other secondary forms do not show this distribution. Although Black people are at an increased risk for TTP, its presentation in Black people does not have any distinguishable features compared to those of other races. Pregnant women and women in
3080-758: Was associated with increase bleeding tendencies in some studied subjects. Its cost-effectiveness has also been questioned. Use of caplacizumab without plasmapheresis has been reported in select patients. The MAYARI study was designed to evaluate the effectiveness of this option. The ISTH guidelines recommended for first acute episode and relapses of immune-mediated TTP (iTTP), add corticosteroids to therapeutic plasma exchange (TPE) and consider adding rituximab and caplacizumab . For asymptomatic iTTP with low plasma ADAMTS13 activity, consider rituximab outside of pregnancy, but prophylactic TPE during pregnancy. For asymptomatic congenital TTP, offer prophylactic plasma infusion during pregnancy, and consider plasma infusion or
3136-401: Was determined in the 1980s and 1990s. The signs and symptoms of TTP may at first be subtle and nonspecific. Many people experience an influenza-like or diarrheal illness before developing TTP. Neurological symptoms are very common and vary greatly in severity. Frequently reported symptoms include feeling very tired , confusion , and headaches . Seizures and symptoms similar to those of
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