3. A 31-year-old man presented with a sudden excruciating headache and seizures. The headache is more severe in the morning a few hours after taking his medication. He had undergone his second kidney transplant and was receiving maintenance treatment with triple immunosuppression (tacrolimus, myfortic and prednisone). His S Cr is 189 µmol/L. MRI Brain (T1 weighted) showed multiple areas of low signal intensity in the pons, medulla oblongata, basal ganglia and also in the cerebral hemispheres. The lumber puncture was entirely normal. Tacrolimus level was 8 ng/ml (within the acceptable range).
- What is the likely diagnosis?
- What is your management plan?
- What are the other conditions that could cause a similar picture?
Dear All
Why the index case is different from the typical clinical presentation of PRES?
Typical PRES findings are occipital headache, seizures, blurring of vision and encephalopathy. This usually occurs due to vasogenic edema of perito-occipital regions of brain secondary to inability of posterior circulation to auto regulate.
But here atypically pons, medulla and basal ganglia are also involved and there are no findings of edema, hence presentation is different
Yes, Dr Saini
Clinically it is not different since the most common presentation is seizures and headache and this happen in the current case
Radiologically it is different since typically PRES (70-90% ) presents by bilateral edema involving the occipital and partial regions (posterior cerebral artery supply region)
Atypical presentation including (1, 2)
And all happen in the current case which is less commonly seen
References
1. Bartynski WS, Boardman JF. Distinct imaging patterns and lesion distribution in posterior reversible encephalopathy syndrome. AJNR Am J Neuroradiol. 2007;28 (7): 1320-7. doi:10.3174/ajnr.A0549 – Pubmed citation
2. Tetsuka S, Ogawa T. Posterior reversible encephalopathy syndrome: A review with emphasis on neuroimaging characteristics. (2019) Journal of the neurological sciences. 404: 72-79.
I agree, Dr Yusuf.
Ajay
the radiological features which involve the Pons, medulla, and basal ganglia, while typical feature is parito-occipital.
I agree, Dr Jamila.
Ajay
not the typical site for the PRES, which is usually an occipitoparietal area and there are MCBs so we need a T2 thick section for further determination as it still could be ischemic MCBs as we can see multiple hypodense lesions in T1 weighted due to cytotoxic edema with ischemia(wide DDX ) while press will be shown in T2 imaging hyperintense symmetrical white matter lesions in the occipitoparietal area
I agree, Dr Saja.
Ajay
Thank you Prof. Halawa.Why the index case is different from the typical clinical presentation of PRES?
The patient in the scenario had early morning sudden excruciating headache, these are red flags associated with brain heamorrhage / malignancy but the imaging attached shows multiple areas of low signal intensity in the pons, medulla oblongata, basal ganglia (are inconsistent with PRESS) and also in the cerebral hemispheres bilaterally (consistent with PRESS),BUT the CSF NORMAL (make PRESS more likely).
I agree, Dr Alshaikh
Ajay
I agree, Dr Ben.
Ajay
Although the typical PRES pattern involves either parieto-occipital pattern, or holohemispheric watershed pattern, or superior frontal sulcus pattern, a central-variant (brainstem pattern) involving the brainstem and basal ganglia has also been seen in PRES, as in the index case .
Reference:
1) Triplett JD, Kutlubaev MA, Kermode AG, Hardy T. Posterior reversible encephalopathy syndrome (PRES): diagnosis and management. Pract Neurol. 2022 Jun;22(3):183-189. doi: 10.1136/practneurol-2021-003194. Epub 2022 Jan 19. PMID: 35046115.
I agree, Dr Amit Sharma.
Ajay
I think its different from the typical clinical presentation of the PRES by its temporal , reversible relation to the time of ingestion of Tacrolimus. Its commonly presented with progressive neurological deficits that evolved over few days with headache visual symptoms, seizures and other subcortical symptoms . This is pointing towards the reversible nature of the syndrome and the direct link to the Tacrolimus.
Radiological findings of vasogenic oedema might be cortical or or entirely subcortical variant involving the brain stem and basal ganglia as its the case here.
PRES is a clinicoradiological syndrome
clinical presentation is variable including headache, confusion, decreased consciousness, visual disturbances, and seizures
along with characteristic neuroimaging findings which is posterior cerebral white matter edema and lesions of the anterior cortex tend to occur in more severe cases
While in this case the lesions were diffuse involving in addition to cerebral hemispheres ,the pons,medulla and basal gangilia
Posterior reversible encephalopathy syndrome is a clinico-radiological diagnosis that present with altered mental state, headache, seizure, and visual loss. It is characterized by white matter vasogenic edema affecting the posterior occipital and parietal lobes of the brain predominantly.
Common causes are fluctuation in blood pressure, pre or eclampsia, renal failure, cytotoxic or autoimmune disease.
On the MRI scan, there is hyperintense T2 weighted and flair sequence
On CT or MR imaging studies, symmetric and often widespread hemispheric watershed vasogenic oedema is noted that predominates in the parietal and occipital lobes followed by the frontal lobes, the inferior temporo-occipital junction, and the cerebellum.
Oedema is usually completely reversible.
PRES syndrome vasogenic edema in the parietal and occipital lobes also an area of the brain stem and basal ganglia is rare.
sit is occipitoparietal symptom .so the patient usuallyypresents withhblurredd vision in addition to otherneurologic symptomsi
Typically, PRES presents as reversible vasogenic edema affecting subcortical white matter as hyperintense signal lesions on T2 in occipitoparietal regions but this case shows low signal lesions in pons, medulla and basal ganglia on T1.
Headache is a manifestation of neurotoxicity common to several immunosuppressive drugs, however the presence of cerebral vasogenic edema is related to the presence of posterior reversible encephalopathy syndrome (PRES).
In theory, PRES can be reversible, and maintaining the drugs that are inducing this state can lead to more serious cases, such as cerebral ischemia or massive infarction.
Exchange Tacrolimus for Ciclosporin is the first alternative, as a decrease in dosage, in this case, may increase the risk of rejection since the treatment is within the desired range. However, Ciclosporin can also evolve with PRES, with switching to Sirolimus a second alternative.
The differential diagnosis includes infections or autoimmune encephalitis, vasculitis, and malignant diseases of the nervous system
REFERENCE:
– Posterior reversible leukoencephalopathy syndrome (PRES) after kidney transplantation: a case report . J. Bras. Nefrol. 40 (1) . Jan-Mar 2018 , https://doi.org/10.1590/1678-4685-JBN-3825
– Wei Zhang , Nobuaki Egashira, Satohiro Masuda. Recent Topics on The Mechanisms of Immunosuppressive Therapy-Related Neurotoxicities. Int. J. Mol. Sci. 2019, 20, 3210; doi:10.3390/ijms20133210
likely diagnosis : PRES.
Management :
1) Exclude CNS infection and stroke. KIV MRA/ MRV of the brain.
2) Close BP and GCS monitoring.
3) BP control with antihypertensive.
4) change tacrolimus for everolimus.
5)antiepileptic.
differential diagnosis
1) Stroke
2) meningitis.
3)
tacrolimus-induced neurotoxicity
Stop tactolimus , CNI free immunosuppression regimen
DD. CNS infections with cryptococcus neoformans, Listeria monocytogenes and Aspergillus funigatus. Viral infections also occur, and are commonly caused by herpes virideae, varicella-zoster virus and papova virus
Basić-Jukić N, Basić-Kes V, Kes P, Furić-Cunko V, Bacić-Baronica K. Neuroloske komplikacije nakon transplantacije bubrega [Neurological complications in renal transplant recipients]. Acta Med Croatica. 2008;62 Suppl 1:76-81. Croatian. PMID: 18578336.
Likely diagnosis in the above case is PRES due to CNI. The reason being the classical picture of clinical headache and seizures with normal lumbar puncture and MRI Brain (T1 weighted) showing low signal intensity in the multiple areas like pons, medulla oblongata, basal ganglia and also in the cerebral hemispheres.The incidence of PRES is 0.5-5% in solid organ transplant and reported with tacrolimus more compared to cyclosporine. Blood levels of tacrolimus have no correlation with PRES.
What is your management plan?
Multidisciplinary team should be involved including a neurophysician ,and transplant physician.It usuay resolves spontaneously within a period of days to week .The main stay of treatment is the supportive management .First thing is to stop the culprit agent ,i.e., Tacrolimus and switch to alternative drug like everolimus .Blood pressure should be controlled and anti-epileptic for seizures should be given . Sepsis if any treated with antibiotics and electrolyte disturbances should be corrected.
What are the other conditions that could cause a similar picture?
CNS infection; multiple abscesses, meningitis and encephalitis.
Posterior cerebral stroke,
Cerebral Venous sinus thrombosis
Encephalopathies related to mitochondrial diseases,
Acute disseminated encephalomyelitis
Hypertensive Encephalopathy
REFERENCE:
Fugate JE, Rabinstein AA. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol. 2015 Sep;14(9):914-925
What is the likely diagnosis?
The diagnosis is PRES : posterior reversible encephalopathy syndrome.
It’s a clinico-radiological syndrome characterized by headache, seizures, altered mentality and loss of vision . It’s occurs due to vasogenic edema affecting mainly the occipital, parietal posterior part of the brain but can occur even in the anterior part.
The risk factors include:
Fluctuating hypertension
Preeclampsia
Sepsis
Shock
Autoimmune disease
HUS
Acute GN
Drug induced .
DDX include:
Intracranial haemmrrhage
Subarachnoid Hg
Subdural Hg
Encephalitis
Autoimmune encephalitis
Herpes simplex encephalitis
Management plan include
Reduction of the offending drug
Decreasing the Bp gradually
Control brain edema
Correction of fluid and electrolyte imbalance.
Why the index case is different from the typical presentation of PRES?
Because the lesion located anteriorly while the classical presentation of PRES is bilateral symmetrical posterior and parietal lesion.
What is the likely diagnosis?
This condition is known as tacrolimus-induced posterior reversible encephalopathy syndrome (PRES). The proposed mechanisms are either hypertension causing auto-regulatory failure or endothelial dysfunction caused by cytotoxic insult, eventually leading to vasogenic odema. (1,2)
Management Plan:
What are the other conditions that could cause a similar picture?
Why the index case is different from the typical presentation of PRES?
PRES is clinico-radiological diagnosis. Clinical features are characteristic of PRES but MRI in this index case is suggestive of involvement of frontal lobes while in classical PRES there is usually symmetrical and bilateral involvement of posterior and parietal lobes
Reference:
Diagnosis: Posterior reversible encephalopathy syndrome.
Risk factors for PRES:
Blood pressure flactuation
preeclampsia
sepsis and shock
Hemolytic uremic syndrome, acute glomerulonephritis, renal artery stenosis.
Immuno-suppressive drugs : Cyclosporin, Tacrolimus,Sirolimus
Autoimmune disorders as SLE
Hematological disorders as TTP
Management plan
.1.Removal or reduction of the triggering factor as immunosupressive drugs
2.In patients with acute hypertension: gradual reduction of blood pressure not more 25% in the fist hours to avoid ischemia .The goal mean blood pressure is between 105 to 125 mm Hg . IV drugs is preferred.
3.Treatment of convulsion
4.Supportive care with hydration and correction of electrolyte disturbances
Differential diagnosis
Intracranial hemorrhage
Subdural hemorrhage
Subarachnoid hemorrhage
Cerebral sinus venous thrombosis
Herpes simplex encephalitis
Autoimmune encephalitis
Uremic encephalitis
Posterior circulation ischemic or hemorrhagic stroke
Hinduja A. Posterior Reversible Encephalopathy Syndrome: Clinical Features and Outcome. Front Neurol. 2020 Feb 14;11:71.
PRES is a clinico-radio-logical syndrome characterized by a headache,seizures, altered mental status and visual loss and characterized by vasogenic edema affecting the posterior occipital and parietal lobes of the brain.
Reversible posterior leukoencephalopathy syndrome (RPLS)
1- Blood pressure management: Hypertension is a feature in the majority of RPLS patients, regardless of etiology . With gradual blood pressure lowering, patients will often improve dramatically. Except in cases of malignant hypertension, patients with RPLS often present with only moderate levels of hypertension; in the majority of cases, however, this still represents a significant increase above baseline levels.Overaggressive blood pressure lowering can lead to complications; comorbid medical conditions should be considered in management. The use of easily titratable parenteral agents such as clevidipine, nicardipine, and labetalol is effective and safe in reducing the blood pressure to a desirable range . Oral antihypertensive agents have a slower onset of action and are not usually effective in consistently lowering the blood pressure to an appropriate range in hypertensive crises to prevent and treat RPLS.
2- Seizure management: When seizures are documented or strongly suspected, an antiseizure medication that can be given as intravenous bolus or at least does not require titration should be started. Agent selection should take into account renal function (doses of levetiracetam and lacosamide must be adjusted in patients with renal function impairment), sedation potential (a particular concern with phenytoin), and other side effects of the drugs and comorbidities of the patient. The threshold to obtain an EEG should be low in patients with altered consciousness, even in the absence of motor manifestations indicative of seizures. Although some case series report continuation of therapy for one to three months, the antiseizure medication can probably be safely tapered as symptoms and neuroimaging findings resolve, usually after one to two weeks . While long-term follow-up studies are limited, seizure recurrence or epilepsy appear to be rare. In one case series of 127 patients who had recovered from an episode of RPLS, unprovoked seizures occurred in eight patients over a median 3.2 years of follow-up . When recurrent, unprovoked seizures have occurred after recovery from an RPLS episode, it is reasonable to resume or initiate antiseizure medication therapy .
3- Discontinuation of immunosuppressive therapy: Reduction in drug dose or prompt removal of the cytotoxic or immunosuppressive drug is usually recommended in cases of RPLS and is often associated with clinical improvement . However, cases are reported in which symptoms resolve while the medication is maintained. sirolimus appears to be associated with a lower risk of RPLS than tacrolimus. When another immunosuppressive agent is substituted, patients must be followed closely for recurrence of RPLS. Routine surveillance neuroimaging is not recommended, but there should be a low threshold to pursue neuroimaging if symptoms arise suddenly or persist. It is not recommended that agents known to induce RPLS be reintroduced, as recurrence has been reported in this setting, although cases are reported in which the original agent was restarted without re-inciting RPLS.
4- Other: Because comorbid conditions including electrolyte disturbances, fluid overload, uremia, and sepsis are suggested to contribute to the development and prognosis in patients with RPLS, aggressive screening for and treatment of these conditions is recommended. Treatment of thrombotic thrombocytopenic purpura with plasmapheresis or immunoglobulin has resulted in resolution of RPLS . Patients with RPLS have been treated with dexamethasone , but because of its associated risk of hypertension, fluid overload, and electrolyte disturbance as well as the fact that high-dose steroid therapy has been associated with the development of RPLS, this is not a recommended therapy.
5- What are the other conditions that could cause a similar picture?
Some diagnoses that produce similar clinical features and MRI changes include:
a. Cerebrovascular syndromes “top-of-the-basilar” syndrome with bilateral posterior cerebral artery infarctions. Features that help distinguish this syndrome from RPLS include that oculomotor and pupillary abnormalities typically, but not always, accompany the mental status and visual changes in this syndrome, while headache and seizures are relatively uncommon.
b. Central nervous system (CNS) vasculitis or multifocal embolic infarctions such as might occur with infective or nonbacterial thrombotic endocarditis can also produce a clinical syndrome similar to RPLS that includes headache, confusion, and seizures.
c. ischemic stroke
d. Infectious, paraneoplastic, or autoimmune encephalitis – These entities also produce confusion and mental status changes with seizures. Patients with infections typically have fever in addition to neurologic impairments.MRI is often, but not always, abnormal; prominent involvement of the posterior regions is not typical, and usually the cortex is more often affected than the subcortical white matter.Cerebrospinal fluid (CSF) evaluation is essential when these conditions are suspected and usually reveals pleocytosis. Specific testing (culture, antibody testing, polymerase chain reaction) is used to identify the specific cause.
e. Cerebral venous thrombosis – The clinical syndrome of cerebral venous thrombosis (CVT) is highly variable but often includes headache, encephalopathy, and seizures. CVT usually occurs in the setting of genetic or acquired thrombophilia; however, this condition may not be known at the time of presentation. In addition, cancer and certain inflammatory conditions are associated with CVT, as they are with RPLS. In such cases, brain MRI reveals focal or multifocal areas of edema and venous infarction that are usually distinguishable from RPLS. Brain MRI typically reveals thrombus on routine sequences; however, magnetic resonance venography may be required.
f. Acute demyelinating encephalomyelitis – Acute demyelinating encephalomyelitis (ADEM) typically presents with a rapid onset of headache and altered mental status along with multifocal neurologic signs and symptoms; seizures are uncommon but can occur. The clinical setting for ADEM is usually postinfectious or postvaccinial; however, in a significant minority of patients no preceding illness is identified.As with RPLS, MRI findings are prominent and affect the white matter prominently; however, a predilection for posterior regions is not typical.
g. Malignancy, in particular CNS lymphoma, carcinomatous meningitis, or gliomatosis cerebri – Typically such conditions evolve less abruptly than RPLS. MRI findings are heterogenous, but bilateral involvement of posterior white matter is atypical. The diagnosis is typically made by pathologic examination of the CSF or brain tissue. .)
h. Acute toxic leukoencephalopathy – The term “toxic leukoencephalopathy” appears to refer to a category of conditions that include RPLS as well as a slowly progressive white matter disease that occurs with exposures to brain toxins including radiation and heroin .However, there are examples of toxins that appear to produce a distinctive encephalopathic syndrome associated with white matter changes on MRI. These entities should be considered in the differential diagnosis of RPLS, particularly when risk factors are absent. Examples include:
i. Carbon monoxide – Acute severe carbon monoxide poisoning presents with headache, encephalopathy, and seizures. MRI typically shows prominent abnormalities in the globus pallidus in addition to diffuse white matter changes.
j. nhaled hydrocarbons (eg, toluene).
k. Other drugs of abuse – Overdoses of amphetamines, opiates, and/or benzodiazepines have been reported to produce a clinical and radiographic syndrome that overlaps with RPLS. MRI in these settings is reported to more often show restricted diffusion indicating a cytotoxic rather than a vasogenic edema
l. Lead – Acute severe lead poisoning is rare but can produce similar clinical and neuroimaging features.
m. Cranial irradiation – In rare cases an acute encephalopathy with MRI changes occurs when high-dose radiation fractions are administered to a large brain volume
Up to date
Q1- What is the likely diagnosis?
Presentation with headache and seizure in a patient with organ transplantation who was on steroid CNI and with mentioned MRI finding the most probable diagnosis is PRES syndrome. As this patient at high risk for developing PRES syndrome because of the presence of multiple risk factors .
Risk factors in this patient for PRES syndrome.
1- Hypertension.
2- Solid organ transplantation.
3- Renal failure.
4- Corticosteroids.
5- Ciclosporin.
6- Tacrolimus.
7- Mycophenolate mofetil.
Q2- What is your management plan?
Generally the management of PRES is supportive:
1) Removing or treating the suspected cause. (correcting the hypertension or immunosuppressive agent )
2) Patients should be hydrated and electrolyte monitored.
3) cerebral edema causing raised intracranial pressure need neurosurgical consultation.
4) acute hypertension should be controlled . First-line antihypertensive agents include nicardipine , labetalol and nimodipine. second-line agents include sodium nitroprusside, hydralazine and diazoxide. Nitroglycerine is not recommended .
Q3- What are the other conditions that could cause a similar picture?
1- Reversible cerebral vasoconstriction syndrome.
2- Demyelination.
3- CNS vasculitis.
4- Leucoencephalopathy.
5- Central pontine myelinolysis.
6- Acute stroke.
What is the likely diagnosis?
Headache and seizures in a renal Tx recipient on Tac+MMF+steroids.
Normal LP, Tacrolimus level is within target, and Cr 189 umol/L.
MRI brain: Low signal areas in Pons, Medulla, and Basal Ganglion.
All of the above point to Posterior Reversible Encephalopathy Syndrome (PRES).
High creatinine needs further work up and to rule out reversible causes and chronic ones.
What is your management plan?
PRES management:
1- Reduce dose of tacrolimus by 25% and watch for the effect, Tacrolimus can be switched to Cyclosporin if reduced dose is not effective and m.TOR inhibitors can be used instead.
2- Anti-convulsant medication (avoid Phenytoin because of interaction with CNIs).
3- Neurology consultation.
4- BP control.
5- Measures to reduce brain oedema.
6- Correct abnormal electrolytes especially Magnesium.
Renal Dysfunction Management:
History taking, clinical assessment, look for pre-renal or post renal reversible causes, look for DSA level, and arrange for kidney biopsy of no reversible treatable pre-renal or post-renal cause.
Treatment will depend on the cause.
What are the other conditions that could cause a similar picture?
DD: multi-focal leuco-encephalopathy, CNS infections, malignancy, trauma, infarctions, demyelinating disorders, leukoencephalopathy.
CNI associated Posterior Reversible Encephalopathy Syndrome-PRES
1- MDT should be included
2- BP control
3- lowering the dose of CNI
4- consider changing tacrolimus to Sirolimus or everolimus
5- anti epileptic to control seizure
1- SAH
2- Ischemic or hemorrhagic stroke
3- Hypertensive encephalopathy
4- GCA
5- Mass effect
6- Infection
Typically PRES involves occipital and parietal regions. While atypically some other areas like basal ganglia or brain stem may be involved.
The most likely diagnosis is posterior reversible encephalopathy syndrome (PRES). Risk factors include hypertension, cytotoxic drugs, renal failure, autoimmune disorders & eclampsia.
Management strategy includes proper treatment for hypertension with gradual decreasing of blood pressure leads to improvement in most cases.
; in addition to changing cyclosporine to tacrolimus to control Bp.
Other causes
Atypical forms may be in differential diagnosis for toxic encephalopathy, pontine myelinolysis, meningoencephalitis, hypoxic ischemic encephalopathy cerebral lupus, and malignancy.
Careful treatment for hypertension with gradual decreasing of blood pressure resolve it in most cases. Changing cyclosporine to tacrolimus
Typical PRES have no differential diagnosis, but atypical forms may be in differential diagnosis for toxic encephalopathy, pontine myelinolysis, meningoencephalitis, cerebral lupus, hypoxic ischemic encephalopathy and even malignancy.
kidney transplant recipient presented with sever sudden excruciating headache and seizures. The headache is more severe in the morning, he is on tacrolimus immunosupression ,lumber puncture was entirely normal. Tacrolimus level was 8 ng/ml (within the acceptable range).imaging showed multiple areas of low signal intensity in the pons, medulla oblongata, basal ganglia and also in the cerebral hemispheres most probably Posterior reversible encephalopathy syndrome (PRES) induced by CNI.
Posterior reversible encephalopathy syndrome is an encephalopathy characterized by various neurological symptoms including headache, seizures, impaired consciousness, and visual abnormalities.
incidence of PRES in transplant patients is 0.34% and there are no clear treatment guidelines for PRES associated with CNIs.
criteria for the diagnosis of PRES: neurological symptoms of acute onset, neuroimaging abnormalities of (focal) vasogenic edema, and the reversibility of clinical and/or radiological findings.
Posterior reversible encephalopathy syndrome should be differentiated on imaging from ischemia/infarction (especially in the posterior circulation), demyelinating disease, infectious etiologies (meningitis, encephalitis), progressive multifocal leukoencephalopathy, vasculitis, and reversible cerebral vasoconstriction syndrome.
There are three main treatment options for PRES:
(1) antihypertensive therapy for patients with hypertension.
(2) reduction or discontinuation of the causative drug and replacement with other immunosuppressive agents
so tac to be switched to m TOR .
(3) anticonvulsant measures.
Hypertensive encephalopathy ,eclampsia, vasculitis ,toxic encephalopathy ,encephalitis.
Ishiuchi T, Takagaki M, Nakamura H, Morris S, Sakaki T, Kishima H. Tacrolimus-associated posterior reversible encephalopathy syndrome after kidney transplantation. Int J Case Rep Images 2022;13:101297Z01TI2022.
management correct the electrolytes, treat sepsis if present
blood pressure management
correct any fluid overload
antiseizure medication .continue for 1 to 3 month
discontinue the tacrolimus and start sirolimus.
dexamethasone., most of the patients recover within two weeks..
1-hypertensive encephalopathy and acute blood pressure fluctuation.
2- Acute or chronic renal disease
3-TTP
4-HUS.
5-Eclampsia.
6-immunosuppression, immunomodulatory and chemotherapeutic drugs.
7-cyclosporine.
8-TAC
9- Sepsis.
10-porphyria
11-hypomagnesemia or hypercalcemia
12- transplantation of organs…
references
UpToDate.
.
The clinical feature favor PRESS but the scan does not.
so I could not comments on management.
DEF of PRESS syndrome: its neurological syndrome diagnosed based on clinical and radiological features which are not specific but according to use of cytotoxic immunosuppression which aggravates the symptoms increase the suspicious
· Clinically present with seizures and headache and this happen in the current case with no ocular involvement.
DD based on clinical and MRI findings
· hypertensive encephalopathy and eclampsia
· syndrome of reversible cerebral vasoconstriction
· stroke
· venous thrombosis
· toxic or metabolic encephalopathy
· demyelinating disorders
· vasculitis
· encephalitis among others
· Malignancy, in particular CNS lymphoma, carcinomatous meningitis, or gliomatosis cerebri
· Hypertensive encephalopathy — It is not clear that hypertensive encephalopathy and eclampsia are distinct from RPLS. Hypertensive retinopathy characterized by retinal hemorrhages and/or exudates and papilledema is often identified on funduscopic examination. There is substantial overlap between the clinical syndrome of hypertensive encephalopathy and RPLS, and some may argue whether these are distinct entities. Treatment of hypertension is an essential aspect of treatment in both.
· Reversible cerebral vasoconstriction syndrome — Reversible cerebral vasoconstriction syndrome (RCVS) and RPLS are thought to share a common pathophysiology of dysregulation of cerebral arterial tone. Vasoactive drugs are often implicated as a trigger in RCVS. If there is visual symptoms, seizures, and MRI abnormalities, RCVS should be suspected as these are less commonly a feature than with RPLS. Evidence of arterial constriction is documented by vascular imaging.
· Cerebrovascular syndromes – MRI finding of bilateral posterior cerebral artery infarctions may be confused radiographically with RPLS include the “top-of-the-basilar” syndrome but oculomotor and pupillary abnormalities typically with arterial infarction, but not always, accompany the mental status and visual changes in this syndrome, while headache and seizures are relatively uncommon.
· ischemic stroke can be distinguished by Diffusion-weighted imaging (DWI)
· Infectious, paraneoplastic, or autoimmune encephalitis: Cerebrospinal fluid (CSF) evaluation is essential when these conditions are suspected
· Cerebral venous thrombosis: brain MRI reveals focal or multifocal areas of edema and venous infarction that are usually distinguishable from RPLS. Brain MRI typically reveals thrombus on routine sequences; however, magnetic resonance venography may be required.
· Acute demyelinating encephalomyelitis (ADEM) typically presents with a rapid onset of headache and altered mental status along with multifocal neurologic signs and symptoms; seizures are uncommon but can occur. The clinical setting for ADEM is usually postinfectious or postvaccine.
· Malignancy, in particular CNS lymphoma, carcinomatous meningitis, or gliomatosis cerebri –The diagnosis is typically made by pathologic examination of the CSF or brain tissue. References
Management
Discontinuation of immunosuppressive therapy — Reduction in drug dose or prompt removal of the immunosuppressive drug is usually recommended in cases of RPLS and is often associated with clinical improvement [3-4]. However, cases are reported in which symptoms resolve while the medication is maintained [6]. We have observed that sirolimus appears to be associated with a lower risk of RPLS than tacrolimus.
When another immunosuppressive medication is patients must be followed closely for recurrence of RPLS.
Reintroduced after resolution is not recommended as recurrence has been reported in this setting [5,6], although cases are reported in which the original agent was restarted without reinciting RPLS.
References
1. Bartynski WS, Boardman JF. Distinct imaging patterns and lesion distribution in posterior reversible encephalopathy syndrome. AJNR Am J Neuroradiol. 2007;28 (7): 1320-7. doi:10.3174/ajnr.A0549 – Pubmed citation
2. Tetsuka S, Ogawa T. Posterior reversible encephalopathy syndrome: A review with emphasis on neuroimaging characteristics. (2019) Journal of the neurological sciences. 404:
3. Arnoldus EP, Van Laar T. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996; 334:1745; author reply 1746.
4. Datar S, Singh T, Rabinstein AA, et al. Long-term risk of seizures and epilepsy in patients with posterior reversible encephalopathy syndrome. Epilepsia 2015; 56:564.
5. Baldini M, Bartolini E, Gori S, et al. Epilepsy after neuroimaging normalization in a woman with tacrolimus-related posterior reversible encephalopathy syndrome. Epilepsy Behav 2010; 17:558.
6. Gijtenbeek JM, van den Bent MJ, Vecht CJ. Cyclosporine neurotoxicity: a review. J Neurol 1999; 246:339.
7. Hauben M. Cyclosporine neurotoxicity. Pharmacotherapy 1996; 16:576.
8. Hayes D Jr, Adler B, Turner TL, Mansour HM. Alternative tacrolimus and sirolimus regimen associated with rapid resolution of posterior reversible encephalopathy syndrome after lung transplantation. Pediatr Neurol 2014; 50:272.
9. Hammerstrom AE, Howell J, Gulbis A, et al. Tacrolimus-associated posterior reversible encephalopathy syndrome in hematopoietic allogeneic stem cell transplantation. Am J Hematol 2013; 88:301.
Most likely PRES which is go with his syptoms and also the Normal CSf is excluding the other abnormality.
The mangment plan to carful control of blood pressure.
acording to the q the Fk level within acceptable,so no need interfer.
Difrentional:
Enecpolopthy,infectious or other inflamtory causes
references:
Barbas AS, Rege AS, Castelberry AW, Gommer J, Ellis J, Brennen TV, Collins BH, Martin AE, Ravindra KV, Vikraman DS, Sudan DL. Posterior reversible encephalopathy syndrome independently associated with tacrolimus and sirolimus after multivisceral transplantation. American Journal of Transplantation. 2013;13:808–810.
What is the likely diagnosis?
In this case the lumbar puncture is clear. This is likely Tacrolimus associated Posterior Reversible Encephalopathy Syndrome-PRES.
What is your management plan?
It is very important to rule out conditions causing sepsis. It is prudent to maintain fluid and electrolyte balance. A multimodality approach is must involving neurologist. Blood pressure should be watched and slowly controlled.
The dose of Tacrolimus must be reduced or stopped and we can switch to Sirolimus as it is associated with less risk of PRES.
Antiepileptics to control siezure
What are the other conditions that could cause a similar picture?
Differential diagnosis of PRES-
Emergent– Ischemia, Thrombosis, Mass effect, Hemorrhage, Hydrocephalus, Seizures, Trauma.
Infectious– Encephalitis, HIV*,PML*,SSPE*, Toxoplasmosis, Neurosyphilis, Septic Cerebral Embolism,Rubella, Lyme Disease
Inflammatory– SLE, Scleroderma, Vasculitis, Multiple sclerosis.
Other– Toxic white matter demyelination, Adrenoleukodystrophy, Uremic encephalopathy.
Typically PRES involves occipital and parietal regions. While atypically some other areas like basal ganglia or brain stem may be involved.
Reference-
Apuri S, Carlin K, Bass E, Nguyen PT, Greene JN. Tacrolimus associated posterior reversible encephalopathy syndrome – a case series and review. Mediterr J Hematol Infect Dis. 2014 Feb 18;6(1):e2014014.
The diagnosis of this case is tacrolimus induced epilepsy and neurological disorder
The management is diagnostic by electroencephalogram and clinical symptoms related to time of drug. Drug level is important to adjusted and correct electrolytes disturbance. Treated with levetiracetam. Patients should be evaluated by neurologist
Other diagnosis is CNS infection like CMV meningitis and encephalitis
CNS malignancy
Cavernous sinus thrombosis
What is the likely diagnosis?
PRES is the most likely diagnosis;
· Symptoms are related to timing of medication(TAC).
· Tacrolimus is associated with PRES.
· CSF analysis is clear, ruling out infective process or vascular process or even PML.
What is your management plan?
· MDT including neurologist.
· May resolve spontaneously1.
· Supportive care is needed.
· Correction of electrolytes abnormality; if any(e.g. hypomagnesemia)
· Medications to control seizure and to relief headache.
· To withdraw the incriminating drug(TAC) or to reduce the dose as possible. Otherwise, to shift TAC to another drug (everolimus, sirolimus) that is less likely to precipitate PRES.
What are the other conditions that could cause a similar picture?
· CNS infection; multiple abscesses, meningitis and encephalitis.
· Malignancy (e.g.; PTLD).
· Veinous sinus thrombosis.
· Ischemic stroke.
· Vasculitis affecting the brain vasculature.
· Hypertension and hypertensive encephalopathy.
· Demyelinating disorders.
· Toxic leukoencephalopathy.
References
1. Fischer M, Schmutzhard E. Posterior reversible encephalopathy syndrome. J Neurol. 2017 Aug;264(8):1608-1616. doi: 10.1007/s00415-016-8377-8. Epub 2017 Jan 4. PMID: 28054130; PMCID: PMC5533845.
One of the more uncommon presentations of tacrolimus side effects is neurotoxicity posterior reversible encephalopathy syndrome (PRES). PRES was initially described by Hinchey et al1 in 1996 as a clinical neuroradiological entity.
There are varying reports of neurotoxicity related to tacrolimus ranging from 7 to 32% in solid organ transplants
The overall incidence of PRES occurs in 0.5%–5% of SOT recipients and is most commonly associated with tacrolimus.
Tacrolimus has been associated with Posterior Reversible Encephalopathy Syndrome (PRES), a disease of sudden onset that can present as a host of different symptoms, depending on the affected area of the brain.
While infectious causes of encephalopathy must always be entertained, the differential diagnosis should also include PRES in the appropriate context.
PRES is an increasingly recognized neurologic disorder with characteristic image findings. Clinically, its presentation can be variable and the differential is wide .
The pathophysiology of PRES still remains unclear. The mechanism of action of Tacrolimus induced PRES may be similar to Cyclosporine. Neurotoxicity associated with Them was thought to be facilitated by hypomagnesemia, hypocholesterolemia, hypertension and the vasoactive agent endothelin.
Cyclosporine is also believed to exacerbate hypertension by inhibiting nitric oxide production.
The mechanism of cellular injury is thought to be secondary to mitochondrial dysfunction as the symptoms of Cyclosporine induced neurotoxicity and mitochondrial encephalopathy appear to be similar.
The syndrome is likely initiated by a breakdown in the blood brain barrier leading to a leakage of fluid into the interstitium of the brain tissue and the development of vasogenic edema.
In addition, immunosuppressant drugs exert cytotoxic effects on the vascular endothelium.
Note that subtherapeutic levels of immunosuppressants have been reported as causing PRES.
Differential Diagnosis of PRES:
Emergent– Ischemia, Thrombosis, Mass effect, Hemorrhage, Hydrocephalus, Seizures, Trauma.
Infectious– Encephalitis, HIV, PML,SSPE,Toxoplasmosis, Neurosyphilis, Septic Cerebral Embolism,Rubella, Lyme Disease.
Inflammatory– SLE,Scleroderma, Vasculitis, Multiple sclerosis.
Other– Toxic white matter demyelination, Adrenoleukodystrophy, Uremic encephalopathy.
Treatment recommendations are based on observational data and vary depending on the associated medical conditions present on each case.
Blood pressure management — Hypertension is a feature in the majority of RPLS patients, regardless of etiology .
With gradual blood pressure lowering, patients will often improve dramatically.
Seizure management — most patients with RPLS and seizures are treated with antiseizure medications .
When seizures are documented or strongly suspected, an antiseizure medication that can be given as intravenous bolus or at least does not require titration should be started. Agent selection should take into account renal function (doses of levetiracetam and lacosamide must be adjusted in patients with renal function impairment), sedation potential (a particular concern with phenytoin), and other side effects of the drugs and comorbidities of the patient .
Discontinuation of immunosuppressive therapy — Reduction in drug dose or prompt removal of the cytotoxic or immunosuppressive drug is usually recommended in cases of RPLS and is often associated with clinical improvement .
However, cases are reported in which symptoms resolve while the medication is maintained .
We have observed that sirolimus appears to be associated with a lower risk of RPLS than tacrolimus.
Other — Because comorbid conditions including electrolyte disturbances, fluid overload, uremia, and sepsis are suggested to contribute to the development and prognosis in patients with RPLS, aggressive screening for and treatment of these conditions is recommended.
PROGNOSIS
Most case series and case reports suggest that RPLS is usually benign. In many cases, RPLS seems to be fully reversible within a period of days to weeks, after removal of the inciting factor and control of the blood pressure .
Radiologic improvement lags behind clinical recovery.
Reference
Tacrolimus Associated Posterior Reversible Encephalopathy Syndrome – A Case Series and Review
Susmitha Apuri, Kristin Carlin, […], and John N. Greene
Update
What is the likely diagnosis?
· This index transplant recipient is on TAC based triple therapy, he suffers from neurological manifestations(headache and seizures) together with MRI radiological features pointing towards a posterior reversible encephalopathy(PRES).However, Other conditions that need to be excluded include infections(LP was negative), metabolic disturbances and structural neurological lesions.
· PRES is one of the uncommon neurotoxic manifestations caused by Tacrolimus. The neurotoxicity related to tacrolimus in solid organ transplant(SOT) ranges between 7-32% while the incidence of PRES in SOT ranges between 0.5-5% (most commonly related to Tacrolimus).However, Studies showed that neurotoxicity does not correlate with the tacrolimus trough levels. It is commonly to occur in the first 3 months post-transplant, when immunosuppression are given in IV bolus form.
· PRES is a clinic-radiological syndrome. The clinical criteria for the diagnosis of TAC-associated PRES are headache, mental status changes, seizures, visual abnormalities and/or focal neurological deficits. patients may experience some or all symptoms. hypertension is a common association with PRES but is not always a component of PRES in patients on immunosuppression.
· The hallmark of PRES is white matter vasogenic edema. The edema which is detected by neuro-imaging (MRI) commonly but not always involves the parito-occipital regions symmetrically due to inability of posterior circulation to auto regulate. In more severe cases anterior cortex is involved. However, a central-variant that involves the brainstem and the basal ganglia has been reported like this index case.
· PRES is usually but not always reversible within days to weeks if identified and treated early and promptly, otherwise it could result in a serious life threatening situation. .
What is your management plan?
· Multidiscipline approach including nephrologist, neurologist, ITU
· There is lack of a definitive strategy reflecting the paucity of studies on that condition.
· conversion from TAC to an alternative regimen like cyclosporine or mTOR inhibitor−based therapy may help. However, Sirolimus itself has been known to cause PRES. Additionally, this is a second transplant and renal functions are impaired. So, a possible strategy is to withdraw the TAC at the time of PRES and then re-introduce it at a lower dose once PRES has resolved or if rejection is proved TAC can continue after consenting the relatives and explaining to them the Pros and Cons of that decision and careful monitor of TAC level
· The role of steroids in the treatment of PRES is debatable, with a possible role in reducing the vasogenic edema
· Optimize blood pressure control being a cardinal risk factor
· Controlling the seizure activity with Lorazepam and introducing an anti-epileptic medication like Keppra to be withdrawn later in liaise with the neurology team.
· Check for electrolyte disturbances especially hypomagnesemia that need to be corrected
What are the other conditions that could cause a similar picture?
· Hypertensive encephalopathy
· CVAs (ischemia or infarctions)
· Infections (meningitis, encephalitis)
· connective tissue disease/vasculitis
· Malignancies and cancer chemotherapy
· Demyelinating disorders
· Top-of-the-basilar syndrome: bilateral posterior cerebral artery infarctions
References:
1) Kartik Ganesh et al, Posterior Reversible Encephalopathy Syndrome in Kidney Disease. Kidney Int Rep (2018) 3, 502–507
2) Susmitha A. et al, Tacrolimus Associated Posterior Reversible Encephalopathy syndrome-A case series and Review. Mediterranean Journal of Hematology and infectious diseases. 2014; 6
3) Fugate JE, Rabinstein AA. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol. 2015 Sep;14(9):914-925.
– Tacrolimus-associated posterior reversible encephalopathy syndrome (PRES)
– Basic management of PRES includes promptly controlling blood pressure, preventing further or initial seizures, and withdrawing or reducing the offending drug
(Stott VL, Hurrell MA, Anderson TJ. Reversible posterior leukoencephalopathy syndrome: a misnomer reviewed. Int Med J 2005;35:83–90.)
– Here , the patient is considered high immunological risk dure to 2nd transplantation & presence of high creatinine , so can start with decreasing the dose of tacrolimus or shift to cyclosporine , 2nd line to shift to sirolimus with augmentation of steroid dose .
– Renal Biopsy may be considered due to increased creatinine
– inflammatory cerebral amyloid angiopathy
o oedema usually centred on microhaemorrhages
– progressive multifocal leukoencephalopathy (PML)
o periventricular and subcortical involvement, sparing the cortex
o little or no mass effect or enhancement
– severe hypoglycaemia
– posterior circulation infarct
o occipital and cerebellar involvement
o acute infarct demonstrates restricted diffusion; PRES typically does not restrict
– hypertensive brainstem encephalopathy
o absence of parieto-occipital involvement
– gliomatosis cerebri
o more asymmetric
– sagittal sinus thrombosis
– hypoxic-ischaemic encephalopathy
( Dr Daniel J Bell , 01 Oct 2022 at radiopedia )
– Malignancy , viral encephalitis .
Likely diagnosis
Likely diagnosis for this patient can be posterior reversible encephalopathy syndrome or PRES in short.
This condition is a serious complication of using immunosuppressive agents such as cyclosporine or tacrolimus, This patient is on a tacrolimus based IS regimen. Clinical features include headache, mental status changes, focal neurological deficits and/or visual disturbances.
On investigations, CT and MRI show abnormal changes such as changes in subcortical white matter secondary to potentially reversible vasogenic edema. Neurotoxicity associated with tacrolimus can occur even at therapeutic levels.
Management plan
In most cases of PRES, symptoms can be reduced or managed by reducing dosage or withholding tacrolimus for a few days. However, prognosis is not good and PRES is associated with significant risk of morbidity and mortality if it is not recognized and managed promptly. Prompt MRI recognition of this condition is key to patient outcome. MRI represents the most sensitive imaging technique for this condition.
Everolimus or sirolimus based IS regimen can be attempted instead. Steroid dosage can be reduced.
Adequate blood pressure control is important since PRES is linked with hypertension.
Close monitoring of serum magnesium levels will help prevent further or future immunosuppressant neurotoxicity and enhance patient care and outcome.
Differential diagnosis
References
PRES
Treatment is supportive and involves correcting the underlying cause and managing associated complications, such as seizures.
It is essential to recognise the condition promptly and to remove or reverse the precipitating factor, including chemotherapy or an immunosuppressive agent. Patients need to be hydrated and to have any electrolyte disturbances corrected. Patients in whom cerebral oedema is causing raised intracranial pressure may require neurosurgical measures
Viral and autoimmune encephalitis,
Demyelinating disease,
Toxic leucoencephalopathies,
CNS vasculitis,
Central/extrapontine myelinolysis
Acute stroke, especially due to cerebral venous thrombosis
Posterior reversible encephalopathy syndrome (PRES): diagnosis and management.BMJ, practical neurology, volume 22, issue 3.
Reversible posterior leukoencephalopathy syndrome (RPLS) is a clinical radiographic syndrome of heterogeneous etiologies that are grouped together because of similar findings on neuroimaging studies.
Risk factors
1- Hypertension
rapid rise or fluctuations in blood pressure may be more important than the absolute blood pressure
2- Immunosuppressive therapy
RPLS occurs in patients prescribed immunosuppressive and immunomodulatory therapies for malignancy, transplantation, rheumatologic conditions, and other indications.
These drugs are:-
Cyclosporine
Tacrolimus
Ritiximab
Sirolimus
IVIG
The neurotoxic effects of these therapies are well known but still poorly understood. Toxic or even elevated levels of medications are not required for the development of RPLS, and prior exposure to the drug does not appear to be protective
Even after several months of exposure to the drug, patients with therapeutic levels can develop RPLS
Cyclosporine is one of the more common cytotoxic therapies associated with the neurologic deficits of RPLS. After renal toxicity, neurotoxicity is the most serious side effect with cyclosporine, affecting 25 to 59 percent of transplant patients
Hypomagnesemia, hypocholesterolemia, the vasoactive agent endothelin, and hypertension have all been implicated in facilitating cyclosporine neurotoxicity
Elevated serum cyclosporine levels are not related to the onset of neurologic symptoms
Cyclosporine may in turn exacerbate hypertension by inhibiting nitric oxide production
3-Renal disease In the initial case series of RPLS, a variety of renal diseases were prevalent including lupus nephritis and glomerulonephritis
Both acute and chronic kidney disease appear to be associated with RPLS.
4-solid organ, bone marrow, or stem cell transplantation
1-Blood pressure management — Hypertension is a feature in the majority of RPLS patients, regardless of etiology With gradual blood pressure lowering, patients will often improve dramatically.
2-Seizure management by antiseizure medications
3-Discontinuation of immunosuppressive therapy Reduction in drug dose or prompt removal of the cytotoxic or immunosuppressive drug is usually recommended in cases of RPLS and is often associated with clinical improvement However, cases are reported in which symptoms resolve while the medication is maintained
We have observed that sirolimusappears to be associated with a lower risk of RPLS than tacrolimus.
1-Hypertensive encephalopathy
In acute, severe hypertension, acute elevation of blood pressure beyond the upper limits of cerebral autoregulation (typically ≥180/120 mmHg) leads to cerebral edema and neurologic symptoms
2-Eclampsia
Most investigators believe hypertensive encephalopathy and preeclampsia share similar mechanisms .In many patients, the syndrome occurs during the puerperium rather than during pregnancy
3-Reversible cerebral vasoconstriction syndrome
Reversible cerebral vasoconstriction syndrome (RCVS) and RPLS are thought to share a common pathophysiology of dysregulation of cerebral arterial tone.
4-stroke
5-venous thrombosis
6-toxic or metabolic encephalopathy
7-demyelinating disorders
8-vasculitis
9-encephalitis
Reference
Up to date
Diagnosis :Reversible posterior leukoencephalopathy syndrome (RPLS) : it is a neurologic syndrome defined by clinical and radiologic features.
•The typical clinical syndrome includes headache, confusion, visual symptoms, and seizures.
•Typical MRI findings are consistent with vasogenic edema in the subcortical white matter and are predominantly localized to the posterior cerebral hemispheres. The differentiation of vasogenic versus cytotoxic edema with diffusion-weighted imaging (DWI) is helpful in distinguishing RPLS from stroke.
some times there is small IC hemorrhages .
it could be atypical when involves other areas like basal ganglia ,medulla and brain stem which happened in this case ,some times involve grey matter.
It can occur with cyclosporine ,tacrolimus even if in non toxic levels but to lesser extent sirolimus .
Usually DD:
hypertensive encephalopathy
Reversible cerebral vasoconstriction syndrome
Eclampsia
cerebral vein thrombosis
Infectious, paraneoplastic, or autoimmune encephalitis
Malignancy
acute toxic leucoencephalopathy.
in transplant there is high risk of infections and rare cases PTLD
Management:
‘Stop or decrease dose the offending drug
Replace it with sirolimus and F/U to avoid of recurrence of PRES .
seizures control
Brain edema management
-Posterior reversible encephalopathy syndrome (PRES)due to the use of tacrolimus and high-dose steroids
Tacrolimus level is in the therapeutic range although studies revealed that there is no correlation between neurotoxicity and the trough levels of tacrolimus.
The MRI findings and the history are suggestive of PRES.
Also there is association between PRES and HTN
Normal lumbar puncture excludes CNS infection
PRES occurs most commonly within the first 3 months post-transplant, usually following immunosuppression given in the intravenous bolus form.
The common explanatory theory is that severe hypertension overwhelms the autoregulation of the cerebral vasculature, leading to hyperperfusion,
arteriolar dilatation, and vasogenic edema.
Typical magnetic resonance imaging (MRI) features are bilateral symmetrical brain oedema in the cortical and subcortical regions of the parietal and occipital lobes.
-MDT including ICU team and neurologist are mandatory.
Treatment strategy is
· temporary or permanent withdrawal of immunosuppression which is difficult in this case due to rejection risk with elevated serum creatinine also being the second transplant rendering the recipient a high risk case
If the neurological recovery is delayed even after reduction, then temporary stoppage of calcineurin inhibitors may be necessary. Pharmacogenomic studies may help in identifying susceptible patients, as a diagnostic test.
(mTOR)inhibitor based triple immunosupression regimen(everolimus, mycophenolate mofetil, and prednisolone) can be introduced,on the other hand sirolimus itself has been implicated to cause PRES, so the decision to substitute tacrolimus with either cyclosporine or sirolimus should be done taking into consideration the other side effects associated with each drug.
If rejection is confirmed ,immunosuppression can be intensifies with family consent and close drug monitoring as recommended by Alexander S et al 2013 in his care report where complete neurological recovery was reached in his case report without cessation of tacrolimus.
Steroids role is debatable, with a possible role in reducing the vasogenic oedema.
· good control of blood pressure with antihypertensives.
· control of seizures.
-Condition with same picture includes malignancy ,Bone marrow or stem cell transplantation, hypomagnesemia ,hypercalcemia, autoimmune disorders as SLE, toxins as alcohol intoxication or scorpion bite or immunosuppressive medications as Azathioprine and the mentioned above drugs,other drugs as Lithium ,linazolide ,IVIG ,IV contrast.
Reference
-Alexander S, David VG, Varughese S, Tamilarasi V, Jacob CK. Posterior reversible encephalopathy syndrome in a renal allograft recipient: A complication of immunosuppression? Indian J Nephrol. 2013 Mar;23(2):137-9.
– Ganesh A etal. Posterior Reversible Encephalopathy
Syndrome in Kidney Disease. Kidney Int Rep (2018) 3, 502–507
– Triplett JD, Kutlubaev MA, Kermode AG, et alPosterior reversible encephalopathy syndrome (PRES): diagnosis and managementPractical Neurology 2022;22:183-189.
I like your well structured reply. But, there are no references! Please type headings as bold or underline. It would make it easier to read.
PRES is a clinicoradiological syndrome
clinical presentation is variable including headache, confusion, decreased consciousness, visual disturbances, and seizures
along with characteristic neuroimaging findings which is posterior cerebral white matter edema and lesions of the anterior cortex tend to occur in more severe cases
While in this case the lesions were diffuse involving in addition to cerebral hemispheres ,the pons,medulla and basal gangilia
I like your reply, even though it is too short. But, there are no references! Please type headings that would be in bold or underline. It would make it easier to read.
The index patient is a transplant recipient on Tacrolimus, MMF and steroids presenting with complaints of headache and seizures.
Lumbar puncture is normal, ruling out CNS infection. MRI brain reveals multiple areas of low signal intensity in pons, medulla oblongata, basal ganglia and cerebral hemispheres signifying edema.
The clinical and radiological picture points towards PRES (posterior reversible encephalopathy syndrome) in the patient (1). Although the typical PRES pattern involves either parieto-occipital pattern, or holohemispheric watershed pattern, or superior frontal sulcus pattern, a central-variant (brainstem pattern) involving the brainstem and basal ganglia has also been seen in PRES, as in the index case (2).
Tacrolimus level is within acceptable range and the serum creatinine is elevated. This graft dysfunction needs to be evaluated by looking at the probable cause (pre-renal/ renal/ post-renal) by taking a detailed history and other tests including urine routine examination, DSA levels (in view of second transplant) and a kidney biopsy.
Management of PRES includes reduction of dose or withdrawal of the offending drug (tacrolimus in this scenario: reduce dose by 25% and see the response, replacing it with cyclosporin if symptoms persist), treatment of seizure and control of blood pressure (1,3). Antiedema measures need to be used for cerebral edema (1). mTOR inhibitor might be required in place of CNIs if symptoms persist.
Electrolyte imbalances, if any (especially hypomagnesaemia) must be corrected (4). Appropriate antiseizure medications need to be given (avoid phenytoin due to drug interaction with CNIs) and the medications can be tapered and withdrawn, under the guidance of neurophysician, once the acute phase of PRES is resolved (2).
Regarding the graft dysfunction, it needs to be evaluated by looking at the probable cause (pre-renal/ renal/ post-renal) by tests including urine routine examination, DSA levels (in view of second transplant) and a kidney biopsy. The treatment of the underlying cause of graft dysfunction should be done.
Other conditions presenting with similar picture include progressive multifocal leukoencephalopathy, infections (meningitis, encephalitis), malignancy, trauma, vasculitis, cerebrovascular accidents (infarcts/ ischemia), demyelinating disorders, or toxic leukoencephalopathy (5,6).
Refrences:
1) Jeelani H, Sharma A, Halawa AM. Posterior Reversible Encephalopathy Syndrome in Organ Transplantation. Exp Clin Transplant. 2022 Jul;20(7):642-648. doi: 10.6002/ect.2021.0268. PMID: 35924741.
2) Triplett JD, Kutlubaev MA, Kermode AG, Hardy T. Posterior reversible encephalopathy syndrome (PRES): diagnosis and management. Pract Neurol. 2022 Jun;22(3):183-189. doi: 10.1136/practneurol-2021-003194. Epub 2022 Jan 19. PMID: 35046115.
3) Chen S, Hu J, Xu L, Brandon D, Yu J, Zhang J. Posterior Reversible Encephalopathy Syndrome After Transplantation: a Review. Mol Neurobiol. 2016 Dec;53(10):6897-6909. doi: 10.1007/s12035-015-9560-0. Epub 2015 Dec 14. PMID: 26666662.
4) Fischer M, Schmutzhard E. Posterior reversible encephalopathy syndrome. J Neurol. 2017 Aug;264(8):1608-1616. doi: 10.1007/s00415-016-8377-8. Epub 2017 Jan 4. PMID: 28054130; PMCID: PMC5533845.
5) Fugate JE, Rabinstein AA. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol. 2015 Sep;14(9):914-925. doi: 10.1016/S1474-4422(15)00111-8. Epub 2015 Jul 13. Erratum in: Lancet Neurol. 2015 Sep;14(9):874. PMID: 26184985.
6) Shankar J, Banfield J. Posterior Reversible Encephalopathy Syndrome: A Review. Can Assoc Radiol J. 2017 May;68(2):147-153. doi: 10.1016/j.carj.2016.08.005. Epub 2017 Jan 26. PMID: 28131335.
That is a superb summary, Dr Amit Sharma
What is the likely diagnosis?
Sudden excruciating headache and seizures in the morning after taking the immunosuppression ( Tacrolimus )
MRI Brain (T1 weighted) showed multiple areas of low signal intensity in the pons, medulla oblongata, basal ganglia and also in the cerebral hemispheres
Normal Lumbar puncture
Mostly is Tacrolimus-induced posterior reversible encephalopathy
Risk Factors :
Tacrolimus intake
hypertension
Mechanism of PRES :
Disruption in the BBB results in picture similar to that of vasogenic edema vs. cytotoxic edema
This can be understood due to the toxic effects of immunosuppressant drugs on cells, which may cause endothelial damage in arteries and result in fluid leaking into the brain parenchyma ( hypertension and transiently failed autoregulation as the cause of vasogenic edema (rather than cytotoxic edema)
What is your management plan?
Diagnosis mainly clinical and neuroradiologic findings. The mostly clinical symptoms are change in mental status, headache, seizure, and visual disturbances
With Radiological changes
MRI: MRI findings is typically evident in the deep white matter of the occipital and parietal lobes ( Typical picture )
TTT :
Discontinuation of offending drugs : Tacrolimus ( Temporary Stoppage of the drug if the patient low immunological risk of rejection or shifting to other immunosuppressant if high risk of rejection )
Blood levels doesn’t correlate with presence of PRES ( It may occur even if tacrolimus with normal levels )
Control of blood pressure
Magensium Sulphate IV
Control of seizures ( Anticonvulsants )
DD
Other causes of PRES include vasculitis, chemotherapy, transfusions, hemolytic-uremic syndrome, malignancies, and intravenous immunoglobulin or erythropoietin therapy.
The Top of basilar syndrome (i.e. bilateral infarctions of the occipital lobes)
Vascuilitis
Sinus venous thrombosis
Encephalitis
Embolic or hemorrhagic strokes
Ref :
Lee VH, Wijdicks EF, Manno EM, Rabinstein AA. Clinical spectrum of reversible posterior leukoencephalopathy syndrome. Arch Neurol 2008;65:205-10.
Song T, Rao Z, Tan Q, Qiu Y, Liu J, Huang Z, et al. Calcineurin Inhibitors Associated Posterior Reversible Encephalopathy Syndrome in Solid Organ Transplantation: Report of 2 Cases and Literature Review. Medicine (Baltimore) 2016;95:e3173.
That is a good summary, Dr GHanem.
This scenario is due to tacrolimus induced PRES, with typical symptoms.
The management of this patient need admission in ICU under close monitoring and control of convulsion with anticonvulsant.
Tacrolimus shifted to cyclosporin
Differentials:
-Viral encephalitis
-Autoimmune encephalitis
-ADEM
-Progressive multifocal leukoencephalopathy
-Deep cerebral infarct
Hi Dr Ansary.
I expect references.
This is typical scenario of tacrolimus associated PRES syndrome ,with typical symptoms of headache and seizure.
The a typical presentation is the presence of MRI changes in medulla ,pone,and basal ganglia.
The management of this patient need admission in ICU under close monitoring and control of convulsion .
hold TAC and shift to cyclosporin
close bp monitoring
Hi Dr Rihab.
I expect references.
What is the likely diagnosis?
The patient might have tacrolimus-associated leukoencephalopathy.
Several neurological complications have been reported with tacrolimus intake, irrespective of tacrolimus levels. Neurotoxicity is more common early after initiation of the drug, but can happen months or years later.
The drug has high lipophilicity, which facilitates its passage through blood-brain barrier to the brain, leading to cerebral vasodilatation and vasogenic edema,
Radiologically, commonest presentation is described as posterior reversible encephalopathy syndrome, however several MRI studies have shown that imaging characteristics are variable and more heterogenous.
What is your management plan?
1- seizure and GCS monitoring
2- seizure control if needed – Lamotrigine will be good choice
3-screen for cryptococcus, CNS CSF culture for Tuberculosis, HSV screening
4-BP monitor TRO PRES due to hypertension
5-Monitor RP, KIV kidney biopsy if still persistently elevated
6-Electroencephalogram (EEG) need to be done
7- some case scenarios – IV methylprednisolone will help
8- stop tacrolimus and switch to CyA
9-Two-week and 6-week follow-up MRI scans after symptoms resolved
References
That is a good summary, Dr Mariamuthu.
1. The most propable diagnosis is Tacrolimus induced neurotoxicity. The underlying mechanism is not well understood, however TAC induced intense vasoconstriction and endothelial damage, causing severe hypertension and vasogenoc brain edema can be an explanation.This can be described as PRES, typically, it causes intense headache and seizures, while the site of affection in the brain stem and basal ganglia is less common site for PRES. Typical site in subcortical white matter of parieto occipital region at the watershed area.
_ T2 image with areas of high signal intensity is typical for diagnosis of PRES. However, presence of multiple small areas of low signal intensity in the brain stem and basal ganglia suggestive of either atypical PRES (for site ) or CNI induced vasculitis also reported in the literature and needs further confirmation by MRA.
2. The managemnt plan includes:
_ admission to ICU for close monitoring of vital signs, blood pressure and score.
_ decrease dose of tacrolimus or better to shift to sirolimus to eliminate the offending agent. Although, tacrolimus is more neuroticic than cyclosporin, but both can cause it.
_control of fits by anticonvulsant like diazepam or midazolam.
_ control of ABP by IV Na nitroprusside or labetalol, with target reduction of 25% of target blood pressure in 1st 6 hours then the remaining over 24_48 h , as rapid decrease of blood pressure can induce cerebral ischemia.
3. Differential diagnosis:
_ encephalitis and CNS infection in such immunocompromised patient (excluded by absence of fever and normal CSF examination).
_ autoimmune encephalitis (excluded by absent change in behaviour and MRI is diagnostic by presence of high signal intensity in frontal region).
_ ADEM also diagnosis by MRI
_ progressive multifocal leukoencephalopathy so viral screening may be required.
_ cerebral stoke better delineated by MRA and MRV.
References:
1.Alexander S, David VG, Varughese S, Tamilarasi V, Jacob CK. Posterior reversible encephalopathy syndrome in a renal allograft recipient: A complication of immunosuppression? Indian J Nephrol. 2013 Mar;23(2):137-9. doi: 10.4103/0971-4065.109439. PMID: 23716922; PMCID: PMC3658293.
2. Shbarou, R.M., Chao, N.J. and Morgenlander, J.C., 2000. Cyclosporin A-related cerebral vasculopathy. Bone marrow transplantation, 26(7), pp.801-804.
That is a very good summary, Dr Shawky.
Posterior reversible encephalopathy syndrome
although her MRI feature is atypical because it involves pons, medulla, and basal ganglia. PRES common involves parito-occipital
Stabilization of the patient
Anticonvulsion, control bpr, correct any electrolyte abnormality (Mg hypomagnesium), change Tacrolimus to CsA, steroid
Diagnosis
It most likely posterior reversible encephalopathy syndrome
The etiology still not well known
Risk factor :
Hypertensive
Eclampsia
Sold organ transplantation
Tacrolimus
Clinical presentation
Altered consciousness ( confusion ,agitation , coma )
Seizures
Headache
Focal deficits
Management :
ICU admission
Control of bp
Anti convulsants
Reduce dose of tac if level is high or change it to cyclosporine
DD:
Autoimmune encephalitis
Infective encephalitis
ICH
Metabolic encephalitis .
Hi Dr Wasef,
That is a very abbreviated reply. I expect references.
Hi Dr Jamila.
That is a very good summary. I expect references.
*Diagnosis is mostly ( PRES ): Posterior Reversible Encephalopathy Syndrome. It occurs 0.5–5% of solid organ transplant patients , commonly associated with tacrolimus . classical presentation of PRES : loss of vision, headache, altered mental function, seizures but ; may include other focal deficits, as weakness or sensory dysfunction that differ from presentation in above case which involves pons , medulla, BG , cerebral hemi-spheres.
*Neurotoxicity is a significant complication of CNI medications and PRES cases has been happened.
*Elevated levels of CNI medications are not always required for PRES development. more-over ,long term drug exposure
*Management: ICU admission , Reduction of tacrolimus dose if trough level was high. change tacrolimus into cyclosporin when Tac level with target level , follow-up with MRI brain ,anti-epleptic drugs , Blood pressure control , analgesics , Steroids to resolve the vasogenic edema, RRT may be required.
*Other conditions do same picture: Infective encephalitis, autoimmune encephalitis, Metabolic encephalopathy , Cerebral venous sinus thrombosis, ICH.
References:
Sodalagunta MB, Kumbhat M, etal.,: Posterior reversible encephalopathy syndrome(PRES). Oxf Med Case Reports. 2017 Apr 3;2017(4).
I would not state radiological differential diagnosis of PRES as ‘Other conditions do same picture’.
What is the likely diagnosis?
Posterior reversible encephalopathy syndrome (PRES)
What is your management plan?
-PRES should be promptly recognized since it is usually reversible with appropriate management.
-Blood pressure management :Hypertension is a feature in the majority of PRES patients, regardless of etiology . With gradual blood pressure lowering, patients will often improve dramatically.
-Discontinuation of immunosuppressive therapy :Reduction in drug dose or prompt removal of the cytotoxic or immunosuppressive drug is usually recommended in cases of PRES and is often associated with clinical improvement .
When another immunosuppressive agent is substituted, patients must be followed closely for recurrence of PRES.
-Other :Because comorbid conditions including electrolyte disturbances, fluid overload, uremia, and sepsis are suggested to contribute to the development and prognosis in patients with PRES, aggressive screening for and treatment of these conditions is recommended.
What are the other conditions that could cause a similar picture?
Differential diagnosis:
1.Hypertensive encephalopathy
2.Eclampsia
3.Reversible cerebral vasoconstriction syndrome
4.Cerebrovascular syndromes .
5.Infective or nonbacterial thrombotic endocarditis.
6.Infectious, paraneoplastic, or autoimmune encephalitis .
7.Cerebral venous thrombosis
8.Acute demyelinating encephalomyelitis
9.Malignancy, in particular CNS lymphoma, carcinomatous meningitis, or gliomatosis cerebri
10.Acute toxic leukoencephalopathy
Likely diagnosis is PRES.
Even with normal tac levels and assuming patient doesn’t have hypertension or is well controlled, I will shift patient to cyclosporine based immunosuppression and withdraw Tacrolimus. This is what we do at our center.
Yes Dr Saini, I appreciate your approach
A 31-year-old with a history of headaches and seizures especially after taking his medication the headache is unbearable. The likely diagnosis based on what was mentioned on the MRI is posterior reversible encephalopathy syndrome. This syndrome PRES is characterized by:
1) Headache
2) Seizures
3) Altered mental status
4) Visual loss
PRES is associated with conditions like:
a) Preeclampsia
b) Eclampsia
c) Infection/sepsis/shock
d) Autoimmune disease
e) Cancer chemotherapy
f) Transplantation including bone and stem cell
g) Hypertension
The possible explanation for the PRES pathology are:
A) cerebral vasoconstriction causing subsequent infarcts in the brain
B) failure of cerebral autoregulation with vasogenic edema
C) endothelial damage with blood-brain barrier disruption further leading to fluid and protein transudation in the brain.
The management of this pathology consists of:
1) Treat the underlying cause
2) Immunosuppressive medications may need to be withheld or reduce the dose.
3) ICU for monitoring
4) Anti-seizure medications
5) Blood pressure control
6) Analgesics
7) Steroids to help with the vasogenic edema
Other conditions that can cause similar syndromes are:
1) Infective encephalitis
2) Autoimmune encephalitis
3) Metabolic or toxic encephalopathy
4) Cerebral venous sinus thrombosis
5) Intracranial bleeding
6) Primary central nervous system vasculitis.
References:
Sudulagunta, R. S., Sodalagunta, B. M., Kumbhat, M., and Nataraju, S. A., Oxford medical case report (2017). Posterior reversible encephalopathy syndrome. 2017 Apr; 2017(4): omx011
Thank you, Marius
Why the index case is different from the typical clinical presentation of PRES?
Posterior reversible encephalopathy syndrome (PRES) is a small vessel microangiopathy of the cerebral vasculature that occurs in 0.5–5% of solid organ transplant recipients, most commonly associated with tacrolimus (Tac).
Clinical manifestations include hypertension and neurologic symptoms.
In hypertension associated or drug-induced PRES, the effective therapy includes withdrawal of offending agent
immediate control of blood pressure
anti-convulsive therapy
and temporary renal replacement therapy (hemodialysis/peritoneal dialysis) if required.
Article informationOxf Med Case Reports. 2017 Apr; 2017(4): omx011.
Published online 2017 Apr 3. doi: 10.1093/omcr/omx011
PMCID: PMC5410886
Thank you
Why the index case is different from the typical clinical presentation of PRES?
**Posterior reversible encephalopathy syndrome (PRES), although it occurs after solid organ transplantation, was reported as related to CNIs. Drug level is not directly related. Many case reports showed reversible scenarios (around 90%). Late diagnosis may lead to unfavourable results. PRES was first described in 1996 by Hinchey et al. but was known previously. It can be related to PreeclampsiaEclampsia, Infection/Sepsis/ShockAutoimmune disease, cancer chemotherapy, Transplantation including BMT, and Hypertension.
**Management is crucial early. Primarily the offending reason should be managed. Stopping the immunosuppressive medication or other drugs is necessary. Control of HT with gradual lowering is essential. Gradual lowering of BP is very important.
———–
Sudulagunta SR, Sodalagunta MB, Kumbhat M, Settikere Nataraju A. Posterior reversible encephalopathy syndrome(PRES). Oxf Med Case Reports. 2017 Apr 3;2017(4):omx011. doi: 10.1093/omcr/omx011. PMID: 28473920; PMCID: PMC5410886.
Triplett JD, Kutlubaev MA, Kermode AG, et alPosterior reversible encephalopathy syndrome (PRES): diagnosis and management practical Neurology 2022;22:183-189. (https://pn.bmj.com/content/practneurol/22/3/183.full.pdf)
Thank you
Why the index case is different from the typical clinical presentation of PRES?
I did not find a clear explanation, but I think the picture here is not classical PRES. It is not limited to the posterior of the brain. That is why we do not have marked visual disturbances etc.
What is the likely diagnosis?
The patient has a history of sudden-onset severe headache with seizure. His MRI T1 showed multiple areas of low signal intensity involving both cerebral hemisphere, basal ganglia, pons and medulla oblongata.
These findings are suggestive of posterior reversible encephalopathy syndrome (PRES)
PRES
– Heterogeneous clinico-radiological diagnosis is based on a combination of neurological features and risk factors supported by distinctive MRI findings.
– The pathogenesis remains unclear, but it appears to be related to disordered cerebral autoregulation and endothelial dysfunction.
-Reversible subcortical vasogenic brain edema caused by the endothelial injury resulting from abrupt changes in blood pressure or direct effects of cytokines on the endothelium.
– PRES can unfold acutely or sub-acutely, with symptoms developing within hours to days
Clinical features:
Its classical presentation is a combination of visual loss, headache, altered mental function, seizures and nausea but may include other focal deficits, including weakness, sensory disturbance or speech disturbance.
Risk factors include;
Hypertensive encephalopathy and acute blood pressure fluctuations
Acute or chronic renal diseases
Thrombotic thrombocytopenic purpura
Hemolytic and uremic syndrome
Eclampsia
Vasculitis; SLE, PAN
Transplantation (solid organs, bone marrow, stem cells)
Immunosuppressive, immunomodulatory, and chemotherapeutic drugs
Sepsis.
MRI finding:
–Typical findings are bilateral areas of white matter edema in the posterior cerebral hemispheres, particularly the parieto-occipital regions, but variations do occur.
– It can be asymmetrical
– Although abnormalities primarily affect the subcortical white matter, the cortex and basal ganglia are often involved
– The distribution of abnormalities is usually not confined to a single vascular territory
– Extensive vasogenic edema has been associated with worse clinical outcomes in some series but not with the severity of clinical presentation.
Misnomer:
– The clinical syndrome usually resolves within a week if promptly recognized and treated; however, the syndrome is not always reversible.
-If PRES is not recognized and treated early, it can lead to severe and life-threatening situations
-It is often not confined to either the white matter or the posterior regions of the brain.
PRES in SOT:
-The overall incidence of PRES was 0.49% – 6% in SOT recipients.
– Severe neurotoxicity in renal patients is usually multifactorial, with patients systemically unwell, uremic and receiving combinations of potentially neurotoxic drugs
-Most common causes reported in the literature are secondary to hypertensive crisis or immunosuppression.
– Commonly occurs within the first 3 months post-transplant, usually following IS given in the IV form.
CNI and PRES:
-Neurotoxicity is a significant complication of CNI use, and PRES has been reported.
-Toxic or even elevated levels of medications are not required for the development of PRES and prior exposure to the drug does not appear to be protective.
-Even after several months of exposure to the drug, patients with therapeutic levels can develop RRES
-In the article by Wong et al., most patients with PRES had serum tacrolimus levels in the therapeutic range
– polymorphisms in CYP3A5, ABCB1 and MDR1 genes were linked to calcineurin-associated neurotoxicity.
What are the other conditions that could cause a similar picture?
Because the symptoms linked to PRES commonly occur in other conditions, its diagnosis is challenging and requires clear communication among clinicians and radiologists.
DDx:
Vascular
– Cerebral venous sinus thrombosis
– Intracranial hemorrhage
– Posterior circulation stroke
– Primary central nervous system vasculitis
Non-vascular
– Infective encephalitis
– Autoimmune encephalitis
– Metabolic/toxic encephalopathy
What is your management plan?
-Aggressive BP management.
-Antiepileptic drugs should be used to treat seizures, and anesthesia and ventilation should be instituted in generalized status epilepticus to protect the airway in obtunded patients.
– Corticosteroids to improve vasogenic edema, but there is no evidence for their use in PRES.
-Rapid withdrawal of the trigger appears to hasten recovery and avoid complications.
-In a setting of PRES with no suspected rejection and low-risk transplant, reduction or even temporary interruption of tacrolimus may be beneficial in neurological recovery.
– However, immunosuppression withdrawal can be detrimental, and in fact, it may need to be intensified due to concomitant acute rejection of the allograft.
-As CsA and tacrolimus exhibit similar pharmaceutical effects. In such cases, replacing CNIs with non-CNIs is the appropriate approach.
What is the difference between T1-weighed and T2-weighed MRI?
blob:https://fship.worldkidneyacademy.org/d64850de-5570-40e4-b3d3-eb6c8f42b280The timing of radiofrequency pulse sequences used to make T1 images results in images which highlight fat tissue within the body.
The timing of radiofrequency pulse sequences used to make T2 images results in images which highlight fat AND water within the body.
So, this makes things easy to remember.
T1 images – 1 tissue type is bright – FAT
T2 images – 2 tissue types are bright – FAT and WATER
Fatty tissue is distinguished from water-based tissue by comparing it with the T1 images – anything that is bright on the T2 images but dark on the T1 images is fluid-based tissue
For example, the CSF is white in this T2 image and dark in the T1 image above because it is a free fluid and contains no fat.
References:
-Alexander S, David VG, Varughese S, Tamilarasi V, Jacob CK. Posterior reversible encephalopathy syndrome in a renal allograft recipient: A complication of immunosuppression? Indian J Nephrol. 2013 Mar;23(2):137-9. doi: 10.4103/0971-4065.109439. PMID: 23716922; PMCID: PMC3658293.
– Triplett JD, Kutlubaev MA, Kermode AG, Hardy T. Posterior reversible encephalopathy syndrome (PRES): diagnosis and management. Pract Neurol. 2022 Jun;22(3):183-189. doi: 10.1136/practneurol-2021-003194. Epub 2022 Jan 19. PMID: 35046115.
-Song T, Rao Z, Tan Q, et al. Calcineurin Inhibitors Associated Posterior Reversible Encephalopathy Syndrome in Solid Organ Transplantation: Report of 2 Cases and Literature Review. Medicine (Baltimore). 2016;95(14):e3173. doi:10.1097/MD.0000000000003173
– Hobson EV, Craven I, Blank SC. Posterior reversible encephalopathy syndrome: a truly treatable neurologic illness. Perit Dial Int. 2012;32(6):590-594. doi:10.3747/pdi.2012.00152
Thank you
Why the index case is different from the typical clinical presentation of PRES?
Diagnosis:
CNI induce neurotoxicity
It suspected when patient develop new onset seizure while on CNI( no obvious other cause of seizure) & within 1 year of transplantation. Typical MRI abnormalities include parity-occipital &/or posterior frontal cortex &/or subcortical white matter lesions.
Atypical MRI abnormalities occur in brain stem, basal ganglia, cortical or subcortical frontal region without posterior predominance.
Mechanisms of CNI induce neurotoxicity:
Management:
Differential diagnosis:
References:
Thank you
Why the index case is different from the typical clinical presentation of PRES?
Because it involve atypical region as brainstem ,basal ganglia and cortical and subcortical frontal areas.
What is the likely diagnosis?
Posterior reversible encephalopathy syndrome (PRES)
Both transplantation and tacrolimus are risk factors for PRES
Also, both acute and chronic kidney disease may be associated with PRES
What is your management plan?
1. IV antiseizure medication
2. Reduce dose of tacrolimus
3. Aggressive BP control
What are the other conditions that could cause a similar picture?
1. Reversible cerebral vasoconstriction syndrome
2. Hypertensive encephalopathy
3. Chronic subcortical white matter ischemic changes
4. “Top-of-the-basilar” syndrome with bilateral posterior cerebral artery infarctions
5. Infectious, paraneoplastic, or autoimmune encephalitis
6. Cerebral venous thrombosis
7. Acute demyelinating encephalomyelitis (ADEM)
https://www.uptodate.com/contents/reversible-posterior-leukoencephalopathy-syndrome/contributors
Thank you
Why the index case is different from the typical clinical presentation of PRES?
Posterior Reversible Encephalopathy Syndrome
The mechanism of action of Tacrolimus-induced PRES may be like Cyclosporine. Neurotoxicity associated with Cyclosporine was thought to be facilitated by hypomagnesemia, hypocholesterolemia, hypertension, and the vasoactive agent endothelin.
Admission of the patient
1) exclude other DD
2) correct any electrolyte abnormalities
3) monitoring of BP
4) discontinuation of tacrolimus and replace it with mTOR; sirolimus because neurological complications associated with tacrolimus can occur even if tacrolimus is within the therapeutic range
Differential Diagnosis of PRES:
Emergent- Ischemia, Thrombosis, Mass Effect, Hemorrhage, Hydrocephalus, Seizures, Trauma.
Infectious- Encephalitis, HIV*, PML*, SSPE*, Toxoplasmosis, Neurosyphilis, Septic Cerebral Embolism, Rubella, Lyme Disease.
Inflammatory- SLE*, Scleroderma, Vasculitis, Multiple sclerosis.
Other- Toxic white matter demyelination, Adrenoleukodystrophy, Uremic encephalopathy.
Reference
=======
Apuri, S., Carlin, K., Bass, E., Nguyen, P. T., & Greene, J. N. (2014). Tacrolimus Associated Posterior Reversible Encephalopathy Syndrome – A Case Series and Review. Mediterranean Journal of Hematology and Infectious Diseases, 6(1). https://doi.org/10.4084/MJHID.2014.014
Thank you
Why the index case is different from the typical clinical presentation of PRES?
What is the likely diagnosis?
This is Posterior reversible encephalopathy syndrome (PRES) due to tacrolimus
What is your management plan?
What are the other conditions that could cause a similar picture?
Jeelani H, Sharma A, Halawa AM. Posterior Reversible Encephalopathy Syndrome in Organ Transplantation. Experimental and Clinical Transplantation: Official Journal of the Middle East Society for Organ Transplantation. 2022 Jul 1;20(7):642-8.
Thank you
Why the index case is different from the typical clinical presentation of PRES?
– T1 MRI show multiple hypo intense lesions in brain stem and posterior fossa indicating demyelinating lesions.
– Tacrolimus-induced neurotoxicity presenting as demyelinating lesions include:
1- Acute leukoencephalopathy ( during first year of treatment).
2- Chronic and delayed leukoencephalopathy .
3- PRES : with similar radiological and clinical characteristics as leukoencephalopathy.
DD
1- viral infection : JC virus , HSV , EBV ,HIV varicella and CMV virus.
2- bacterial infection: tuberculosis, borrelia.
3- Autoimmune leukoencephalopathy.
Management plan
1- stabilization of general conditions , control seizure with anticonvulsant drugs.
2- Decrease the tacrolimus dose or switch to evirolimus
3- Pulse IV methylprednisolone for 3-5 days.
Ref:
Barragán-Martínez D, Simarro-Díaz A, Calleja-Castaño P, Hernández-Laín A, Ramos-González A, Villarejo-Galende A. Delayed tacrolimus leukoencephalopathy, a rare and reversible cause of dementia. Neurol Neuroimmunol Neuroinflamm. 2017 Jan 10;4(2):e319. doi: 10.1212/NXI.0000000000000319. PMID: 28101519; PMCID: PMC5226274.
Thank you
Why the index case is different from the typical clinical presentation of PRES?