Silent Cerebral Infarction during Immune TTP Remission - Prevalence, Predictors and Impact on Cognition

Yu, Jia; Brown, Jenna; Salzberg, Eli; Wei, Aria; Gerber, Gloria; Pan, Xiang-Zuo; Moliterno, Alison R.; Streiff, MIchael B.; Kraus, Peggy S.; Logue, Claire; Yui, Jennifer; Naik, Rakhi P.; Latif, Hira; Lanzkron, Sophie; Braunstein, Evan M.; DeBaun, Michael R.; Lin, Doris; Chaturvedi, Shruti

doi:10.1182/blood-2022-167054

Cited by 6 publications

(9 citation statements)

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“…Our radiological findings found white matter hyperintense lesions in most patients, which is consistent with other MRI studies in iTTP. [26][27][28][29] In particular, lesions were predominantly in the frontal lobe, similar to findings by Alwan et al 29 ; using MRI, they demonstrated the prevalence of white matter hyperintense lesions in patients with iTTP associated with an increased risk of cognitive impairment. Specifically, frontal executive functions, memory and general intellectual functioning were commonly affected alongside anxiety and depression.…”

Section: Discussionsupporting

confidence: 72%

Cognitive decline in thrombotic thrombocytopenic purpura survivors: The role of white matter health as assessed by MRI

Hannan,

Hamilton,

Patriquin

et al. 2023

Br J Haematol

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SummaryImmune‐mediated thrombotic thrombocytopenic purpura (iTTP) is a rare condition caused by severe ADAMTS13 deficiency, leading to platelet aggregation and thrombosis. Despite treatment, patients are prone to cognitive impairment and depression. We investigated brain changes in iTTP patients during remission using advanced magnetic resonance imaging (MRI) techniques, correlating these changes with mood and neurocognitive tests. Twenty iTTP patients in remission (30 days post‐haematological remission) were compared with six healthy controls. MRI scans, including standard and specialized sequences, were conducted to assess white matter health. Increased T1 relaxation times were found in the cingulate cortex (p < 0.05), and elevated T2 relaxation times were observed in the cingulate cortex, frontal, parietal and temporal lobes (p < 0.05). Pathological changes in these areas are correlated with impaired cognitive and depressive scores in concentration, short‐term memory and verbal memory. This study highlights persistent white matter damage in iTTP patients, potentially contributing to depression and cognitive impairment. Key regions affected include the frontal lobe and cingulate cortex. These findings have significant implications for the acute and long‐term management of iTTP, suggesting a need for re‐evaluation of treatment approaches during both active phases and remission. Further research is warranted to enhance our understanding of these complexities.

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Section: Discussionsupporting

confidence: 72%

Cognitive decline in thrombotic thrombocytopenic purpura survivors: The role of white matter health as assessed by MRI

Hannan,

Hamilton,

Patriquin

et al. 2023

Br J Haematol

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“…Additionally, neurocognitive function among patients whose most recent TTP episode occurred within 1 year of the study (73%) was significantly more impaired compared to cognitive functioning in survivors whose last episode was more than 1 year prior (31%, p = 0.035) (68). Finally, a recent prospective study of neurocognitive function in iTTP survivors also found that over half had cognitive impairments, most commonly affecting executive function, attention and processing speed (70).…”

Section: Cognitive Impairmentmentioning

confidence: 92%

“…In support of this hypothesis, Cataland et al observed small and large vessel ischemic changes indicative of silent cerebral infarcts on brain MRI in 39% (9 of 23) of TTP survivors who were otherwise clinically stable and without apparently neurological symptoms, thus suggesting a higher prevalence of persistent sub-clinical neurological injury following recovery (68). A recent prospective study found that silent cerebral infarction, defined as magnetic resonance imaging (MRI) evidence of brain ischemic infarction without a corresponding neuro-deficit, was present in 50% of iTTP patients in clinical remission and was strongly associated with the presence of cognitive impairment, particularly major cognitive impairment (70). Given that silent cerebral infarctions are a risk factor for both cognitive impairment (75) and stroke (76) in the general population, it is likely that neurocognitive deficits and stroke in TTP survivors are associated with silent infarctions in the brain.…”

Section: Cognitive Impairmentmentioning

confidence: 99%

Immune thrombotic thrombocytopenic purpura: Spotlight on long-term outcomes and survivorship

Selvakumar

Liu²,

Chaturvedi³

2023

Front. Med.

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Advances in diagnosis and treatment have dramatically improved survival of acute immune thrombotic thrombocytopenic purpura (iTTP) and iTTP has evolved from an acute fatal condition to a chronic relapsing disorder. In addition to the risk of iTTP relapse, iTTP survivors are at risk of multiple adverse health outcomes including higher than expected rates of all-cause mortality, increased rates of stroke and other cardiovascular disease, and higher rates of morbidities such as obesity, hypertension, and autoimmune disorders. iTTP survivors also report neurocognitive impairment, depression, and reduced quality of life. Women with iTTP are at risk for recurrent iTTP, preeclampsia, and other maternal and fetal complications in subsequent pregnancies. ADAMTS13 activity during clinical remission has emerged as an important targetable risk factor for iTTP relapse and other outcomes including stroke and all-cause mortality. This review summarizes current literature regarding the epidemiology and potential mechanisms for adverse long-term sequelae of iTTP, outlines current best practices in iTTP survivorship care, and highlights a research agenda to improve long-term iTTP outcomes.

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“…5 In this new therapeutic era, the prevalence of neurological complications and pattern of brain damage observed during these rare conditions remain poorly described both at the acute phase and during long-term follow-up. Recent data suggest that a significant proportion of survivors could present with symptomatic but also silent cerebral injuries 6 . In the present study, we aimed to report the brain lesions appearing in the acute phase of iTTP and HUS and whether predictors of these acute lesions could be identified.…”

Section: Introductionmentioning

confidence: 99%

Predictors of acute ischemic cerebral lesions in immune-mediated thrombotic thrombocytopenic purpura and hemolytic uremic syndrome

Neuman

Joseph

Bouzid³

et al. 2023

Preprint

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Background: The immune form of thrombotic thrombocytopenic purpura (iTTP) and the hemolytic and uremic syndrome (HUS) are two major forms of thrombotic microangiopathy (TMA). Their treatment has been recently greatly improved. In this new era, both the prevalence and predictors of cerebral lesions occurring during the acute phase of these severe conditions remain poorly known. <break><break>Aim: The prevalence and predictors of cerebral lesions appearing during the acute phase of iTTP and shigatoxin-producing Escherichia coli-HUS or atypical HUS were evaluated in a prospective multicenter study. <break><break>Methods: Univariate analysis was performed to report the main differences between patients with iTTP and those with HUS or between patients with acute cerebral lesions and the others. Multivariable logistic regression analysis was used to identify the potential predictors of these lesions. <break><break>Results: Among 73 TMA cases (mean age 46.89 15.99 years (range: 21-87 years) with iTTP (n = 57) or HUS (n= 16), one third presented with acute ischemic cerebral lesions on magnetic resonance imagery (MRI); two individuals also had hemorrhagic lesions. One in ten patients had acute ischemic lesions without any neurological symptom. The neurological manifestations did not differ between iTTP and HUS. In multivariable analysis, 3 factors predicted the occurrence of acute ischemic lesions on cerebral MRI: 1) the presence of old infarcts on cerebral MRI, 2) the level of blood pulse pressure, 3) the diagnosis of iTTP. <break><break>Conclusion: Cerebral MRI is crucial to detect both symptomatic and covert ischemic lesions at the acute phase of iTTP and HUS and helps identify patients with old infarcts, at the highest risk of neurological worsening. The diagnosis of iTTP further increases the risk of ischemic lesions but also an increased level of blood pressure that may represent a potential target to further improve the therapeutic management of these conditions.

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Silent Cerebral Infarction during Immune TTP Remission - Prevalence, Predictors and Impact on Cognition

Cited by 6 publications

References 0 publications

Cognitive decline in thrombotic thrombocytopenic purpura survivors: The role of white matter health as assessed by MRI

Cognitive decline in thrombotic thrombocytopenic purpura survivors: The role of white matter health as assessed by MRI

Immune thrombotic thrombocytopenic purpura: Spotlight on long-term outcomes and survivorship

Predictors of acute ischemic cerebral lesions in immune-mediated thrombotic thrombocytopenic purpura and hemolytic uremic syndrome

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