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Year : 2004  |  Volume : 50  |  Issue : 3  |  Page : 197-199

Thrombotic thrombocytopenic purpura -induced posterior leukoencephalopathy in a patient without significant renal or hypertensive complications

Department of Neurology, Walter Reed Army Medical Center, 6900 Georgia Ave, NW, Bldg # 2, DC - 20307, USA

Date of Submission06-Feb-2004
Date of Decision15-Mar-2004
Date of Acceptance15-Apr-2004

Correspondence Address:
John P Ney
Department of Neurology, Walter Reed Army Medical Center, 6900 Georgia Ave, NW, Bldg # 2, DC - 20307,
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Source of Support: None, Conflict of Interest: None

PMID: 15377805

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 :: Abstract 

A 40-year-old male with recent-onset idiopathic thrombotic thrombocytopenic purpura (TTP) developed focal transient neurological findings lasting for several hours, remitting, then recurring in a different pattern. Brain magnetic resonance imaging (MRI) was consistent with a posterior leukoencephalopathy and electroencephalography demonstrated lateralized slowing during an episode. No acute ischemic changes were found on diffusion-weighted imaging. Close monitoring in an intensive care setting revealed no significant hypertensive episodes. The patient’s condition resolved with plasmapheresis and immunoglobulin therapy. The relation of TTP to reversible posterior leukoencephalopathy syndromes is discussed. Clinical features of this case suggest a mechanism for TTP-induced leukoencephalopathy independent of hypertension and renal failure.

Keywords: Purpura, thrombotic thrombocytopenic; encephalopathy, hypertensive; brain oedema

How to cite this article:
Hawley J S, Ney JP, Swanberg M. Thrombotic thrombocytopenic purpura -induced posterior leukoencephalopathy in a patient without significant renal or hypertensive complications . J Postgrad Med 2004;50:197-9

How to cite this URL:
Hawley J S, Ney JP, Swanberg M. Thrombotic thrombocytopenic purpura -induced posterior leukoencephalopathy in a patient without significant renal or hypertensive complications . J Postgrad Med [serial online] 2004 [cited 2023 Jun 8];50:197-9. Available from:

Thrombotic thrombocytopenic purpura (TTP) is a form of haemolytic anaemia with neurological abnormality as a salient feature.[1] Serial neuroimaging studies of patients with neurological dysfunction and TTP suggest an association with reversible posterior leukoencephalopathy syndrome (RPLS). Acute hypertensive events and renal failure have been postulated as the likely underlying aetiology to this radiographic finding.[2] In contrast to this hypothesis, we report a patient with TTP having neurological dysfunction and neuroimaging consistent with posterior leukoencephalopathy syndrome despite the absence of significant hypertension or clinical nephropathy.

 :: Case History Top

A previously healthy 40-year-old man was seen in the Emergency Department for the rapid onset of right upper and lower extremity weakness of an hour's duration. During evaluation by the consulting neurologist, the patient developed difficulty in speaking. Language examination was characterized by non-fluent speech with severely impaired naming but intact comprehension and repetition. Visual fields were full to confrontation. He had a right hemiparesis without brisk reflexes. Tactile sensation and coordination were intact. A CT scan of the head was normal. Investigations showed a hematocrit of 19% with a platelet count of 31,000/mm3, LDH of 2059 IU/L, and haptoglobin of <10.0 mg/dl. His white blood cell count was within normal limits. Schistocytes (fragmented red blood cells) were evident on a peripheral blood smear prompting a tentative diagnosis of TTP. A complete blood count drawn two weeks prior for evaluation of an upper respiratory tract infection showed a hematocrit of 41% and platelets of 178,000/mm3. He was normotensive but had a mild fever of 100.4°F. The patient was admitted to intensive care for further monitoring. Three hours after the initial examination, his speech had returned to baseline and he had normal strength.

The day after admission, he developed left upper extremity weakness and confusion with impaired attention but largely normal language. He did not appear to have a hemineglect. An electroencephalogram obtained during this episode depicted marked slowing in the posterior right hemisphere without evidence of epileptiform activity. A brain MRI showed no acute changes on diffusion weighted imaging, but T2 signal attenuation was seen in the posterior periventricular white matter, greater on the right, consistent with vasogenic oedema [Figure - 1]. Brain MR Angiography was normal. A lumbar puncture had unremarkable results. A human immunovirus (HIV) test was negative and blood cultures had no bacterial or fungal growth.

His confusion and attentional difficulties persisted with slow improvement over two weeks with the initiation of daily plasma exchange and intravenous gammaglobulin beginning on hospital Day two. He remained in intensive care for one week and was transferred to the medicine ward after his platelet count and hematocrit had normalized. Brain MRI obtained eight months later showed nearly complete resolution of the T2 signal changes seen on the first MRI [Figure - 2].

He was on a cardiac monitor with frequent blood pressure monitoring throughout his ICU stay, with recorded mean arterial pressures between 90mm and 110mm Hg. Daily serum creatinine did not exceed 1.0 mg/dl. He had no other stigmata of hypertension or renal dysfunction.

 :: Discussion Top

TTP is a thrombotic microangiopathy with Coombs' negative haemolytic anaemia and thrombocytopenia. The clinical presentation is characterized by the pentad of signs and symptoms of renal failure, fever, microangiopathic haemolytic anaemia (MAHA), thrombocytopenia, and neurological dysfunction. The diagnosis is strongly suggested by the presence of elevated lactate dehydrogenase and schistocytes.[3] Neurological abnormality is present in 50 to 60% of patients during the acute phase of illness.[4]

TTP-related end-organ dysfunction is related primarily to microangiopathic disturbances. Damage to endothelial cells within the blood vessel wall accelerates the formation of platelet-rich microthrombi which can cause microinfarctions of affected tissue. This coagulopathy can lead to serious neurological compromise from stroke or haemorrhage, but case series with MRI and CT implicate altered cerebrovascular autoregulation as a mechanism.[5] A posterior leukoencephalopathy is posited on the basis of these studies. Normalization of follow-up imaging with clinical resolution of neurological abnormality makes infarction unlikely.

Reversible posterior leukoencephalopathy syndrome (RPLS), is seen in several conditions which share acute hypertension as a significant feature. Chronic hypertension, renal insufficiency and eclampsia are associated with acute elevations in systemic blood pressure that can alter the permeability of cerebral vessels, resulting in petechial haemorrhage and fluid transudation through a disrupted blood-brain barrier.[6] RPLS in the setting of TTP is thought to share this mechanism of hypertensive encephalopathy. In a neuroimaging analysis of 12 patients with TTP, six presented with cerebral oedema associated with hypertension and renal failure. Only one of the twelve had cerebral oedema with normal creatinine and a maximum blood pressure of 140/85.[7]

Patients with RPLS present with confusion and lethargy. Visual disturbances can occur with occipital lobe involvement. Seizures have also been reported.[8] Asymmetric hemiparesis can occur despite relatively symmetric lesions. The symptoms are highly variable[9] and may largely be dependent on the extent of cerebral vasogenic oedema.

We present a patient with TTP, normal to slightly elevated blood pressure with normal renal function who had posterior predominant vasogenic oedema on brain MRI consistent with posterior leukoencephalopathy. We attribute his confusion and inattention to this lesion. The absence of seizures and visual obscurations may be secondary to lack of cortical involvement. Furthermore, this patient demonstrated that renal dysfunction and subsequent hypertension, while present in many TTP patients, are not necessary prerequisites to RPLS. We postulate that TTP alters endothelial function whereby increased permeability of the blood-brain barrier creates a lower threshold for formation of brain oedema.

This case shows the importance of the prompt recognition and treatment of patients with TTP. The classic pentad of findings is not present in all cases, and failure to diagnose can lead to a lethal outcome. However, neurological impairment with TTP occurs in the majority of patients, making the role of the neurologist potentially invaluable. With proper treatment 90% of patients survive an episode of TTP, generally without permanent organ damage.[10] This case illustrates that cerebral oedema can occur in TTP with only minor perturbations in blood pressure and normal renal function. Careful observation of the patient's neurological condition may be a clue toward the diagnosis and management of this hazardous illness.

 :: References Top

1.Meloni G, Proia A, Antonini G, De Lena C, Guerrisi V, Capria S, et al. Thrombotic thrombocytopenic purpura: Prospective neurologic, neuroimaging and neurophysiologic evaluation. Haematologica 2001;86:1194-9.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Ruggenenti P, Remuzzi G. The pathophysiology and management of thrombotic thrombocytopenic purpura. Eur J Haematol 1996;56:191-207.  Back to cited text no. 2  [PUBMED]  
3.Moake JL. Thrombotic microangiopathies. N Engl J Med 2002;347:589-600.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.George JN, Vesely SK, Terrell DR. The Oklahoma Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP-HUS) Registry: A community perspective of patients with clinically diagnosed TTP-HUS. Semin Hematol 2004;41:60-7.  Back to cited text no. 4  [PUBMED]  
5.Mukherjee P, McKinstry RC. Reversible posterior leukoencephalopathy syndrome: Evaluation with diffusion-tensor MR imaging. Radiology 2001;219:756-65.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996;334:494-500.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Bakshi R, Shaikh ZA, Bates VE, Kinkel PR. Thrombotic thrombocytopenic purpura: brain CT and MRI findings in 12 patients. Neurology 1999;52:1285-8.  Back to cited text no. 7  [PUBMED]  
8.Arora A, Chowdhury D, Daga MK, Arora N, Gaiha M. Reversible posterior leukoencephalopathy syndrome: A report of 2 cases. Neurol India 2001;49:311-3.   Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Vesely SK, George JN, Lammle B, Studt JD, Alberio L, El-Harake MA, et al. ADAMTS13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: Relation to presenting features and clinical outcomes in a prospective cohort of 142 patients. Blood 2003;102:60-8.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Bell WR, Braine HG, Ness PM, Kickler TS. Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: Clinical experience in 108 patients. N Engl J Med 1991;325:398-403.  Back to cited text no. 10  [PUBMED]  


[Figure - 1], [Figure - 2]

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