Tacrolimus-Induced Neurotoxicity After Transplant: A Literature Review.

Tacrolimus, a calcineurin inhibitor, is an immunosuppressant used globally to prevent rejection after organ transplantation. Although it significantly improves outcomes for solid organ transplant patients, it is associated with various side effects such as nephrotoxicity and neurotoxicity. Tacrolimus-induced neurotoxicity is frequently encountered in clinical practice and can present with a variety of symptoms that may occur even at therapeutic levels. Although tacrolimus-induced neurotoxicity is well documented, there is limited literature available on pharmacologic management. Twenty-eight case reports of tacrolimus-induced neurotoxicity were identified and analyzed in addition to other literature including reviews, retrospective studies, and animal model studies. The severity of cases of tacrolimus-induced neurotoxicity reported ranged from mild symptoms that could be managed with symptomatic treatment to conditions such as posterior reversible encephalopathy syndrome and chronic inflammatory demyelinating polyradiculoneuropathy that may require more immediate intervention. This information was utilized in addition to clinical experience to compile potential management options for prevention and treatment of neurotoxic adverse events. This review is limited by the utilization of primarily retrospective studies and case reports. The available literature on the subject is largely narrative and there are no guidelines on treatment of tacrolimus-induced neurotoxicity at the time of this research. This comprehensive review may guide further studies to investigate the pathophysiology of tacrolimus-induced neurotoxicity and to define patient-specific strategies for mitigation or minimization of neurotoxicity. This is especially important given that management of tacrolimus-induced neurotoxicity can include changes to immunosuppression that can result in an increased risk of rejection.

Delayed-Onset Psychosis Secondary to Tacrolimus Neurotoxicity After Lung Transplant: A Case Report and Systematic Review.

BACKGROUND: Tacrolimus is the most common immunosuppressant used after transplant, yet it can result in moderate-to-severe neurotoxicity in up to 32% of patients. Signs of neurotoxicity can vary from mild (tremor or headache) to severe (posterior reversible encephalopathy syndrome or psychosis. Prompt recognition and management is needed to lead to symptom resolution. OBJECTIVE: The objective of this study is to describe the clinical presentation of tacrolimus-induced psychosis, a type of tacrolimus-inducted neurotoxicity, and distinguish it from other central nervous system disturbances, including delirium. METHODS AND RESULTS: We present a case of delayed onset tacrolimus-induced psychosis with focus on unique clinical features and management strategies. We conducted a systematic review of cases of tacrolimus-induced psychosis using the PubMed database and included 15 manuscripts in our review. CONCLUSIONS: Tacrolimus-induced psychosis is a unique presentation of tacrolimus-related neurotoxicity and can present without the cardinal symptoms of delirium. The data on isolated psychotic symptoms are limited with current literature focusing on more common presentations of tacrolimus-induced neurotoxicity, such as delirium and tremor. Development of psychosis can occur later in the treatment course and at normal tacrolimus serum levels. It can improve with antipsychotic therapies, but primary management should include cross-titration to an alternate immunosuppressant regimen.

Rituximab-associated PRES in antibody-mediated kidney rejection: A case report.

Posterior Reversible Encephalopathy Syndrome (PRES) is a rare neurological disorder with a wide range of neurological symptoms. Different risk factors are known for PRES in patients with a history of kidney transplantation; these patients developing PRES were associated with immunosuppressants and cytotoxic drug therapies, including reports of rituximab therapy. Herein, we report a case of rituximab-associated PRES in the context of antibody-mediated kidney allograft rejection. A 29-year-old male patient with antibody-mediated kidney rejection was treated with rituximab, and then he developed PRES. The patient, who was transplanted with a kidney allograft five years earlier, was continuously treated with standard tacrolimus and mycophenolate mofetil therapy without any symptoms of PRES. Rituximab treatment was started to block an ongoing kidney rejection, and the patient received a second dose of rituximab four days prior to the hospital admission. At admission, the patient demonstrated symptoms of headache, nausea, and photophobia. The brain magnetic resonance imaging (MRI) showed changes consistent with PRES. After 12 days of hospitalization, he was discharged with a complete cessation of the initial symptoms. We postulate that possible endothelial dysfunction caused by rituximab may explain the condition leading to PRES. It is unclear whether rituximab, when used in kidney rejection patients who receive other immunosuppressants, may contribute to PRES.

Immunotherapy with anti-GD2 monoclonal antibody in infants with high-risk neuroblastoma.

Anti-GD2 monoclonal antibodies (mAb) improve the prognosis of high-risk neuroblastoma (HR-NB). Worldwide experience almost exclusively involves toddlers and older patients treated after multimodality or second-line therapies, that is, many months postdiagnosis. In contrast, at our center, infants received anti-GD2 mAbs because this immunotherapy started during or immediately after induction chemotherapy. We now report on the feasibility, safety, and long-term survival in this vulnerable age group. Thirty-three HR-NB patients were <19 months old when started on 3F8 (murine mAb; n = 21) or naxitamab (humanized-3F8; n = 12), with 30″ to 90″ intravenous infusions. Patients received analgesics and antihistamines. Common toxicities (pain, urticaria, cough) were manageable, allowing outpatient treatment. Capillary leak, posterior reversible encephalopathy syndrome, and mAb-related long-term toxicities did not occur. Two 3F8 cycles were aborted due to bradycardia (a preexisting condition) and asthmatic symptoms, respectively. One patient received ½ dose of Day 1 naxitamab because of hypotension; full doses were subsequently administered. Post-mAb treatments included chemotherapy, radiotherapy, and anti-NB vaccine. Among 3F8 patients, 17/21 are in complete remission off all treatment at 5.6+ to 24.1+ (median 13.4+) years from diagnosis. Among naxitamab patients, 10/12 remain relapse-free post-mAb at 1.7+ to 4.3+ (median 3.1+) years from diagnosis. Toxicity was similar with short outpatient infusions and matched that observed with these and other anti-GD2 mAbs in older patients. These findings were reassuring given that naxitamab is dosed >2.5× higher (~270 mg/m2 /cycle) than 3F8, dinutuximab, and dinutuximab beta (70-100 mg/m2 /cycle). HR-NB in infants proved to be highly curable.

Tight vs liberal control of mild postpartum hypertension: a randomized controlled trial.

BACKGROUND: High-quality evidence to inform the management of postpartum hypertension, including the optimal blood pressure threshold to initiate therapy, is lacking. Randomized trials have been conducted in pregnancy, but there are no published trials to guide management in the postpartum period. OBJECTIVE: This study aimed to test the hypothesis that initiating antihypertensive therapy in the postpartum period at a threshold of 140/90 mm Hg would result in less maternal morbidity than initiating therapy at a threshold of 150/95 mm Hg. STUDY DESIGN: We performed a pragmatic multicenter randomized controlled trial of patients aged 18 to 55 years with postpartum hypertension. Patients with chronic hypertension, gestational hypertension, and preeclampsia without severe features were randomized to 1 of 2 blood pressure thresholds to initiate treatment: persistent blood pressure of ≥150/95 mm Hg (institutional standard or "liberal control" group) or ≥140/90 mm Hg (intervention or "tight control" group). Our primary outcome was composite maternal morbidity defined as: severe hypertension (blood pressure ≥160/110 mm Hg) or preeclampsia with severe features, the need for a second antihypertensive agent, postpartum hospitalization >4 days, and maternal adverse outcome secondary to hypertension as evidenced by pulmonary edema, acute kidney injury (creatinine level ≥1.1 mg/dL), cardiac dysfunction (eg, elevated brain natriuretic peptide level) or cardiomyopathy, posterior reversible encephalopathy syndrome, cerebrovascular accident, or admission to an intensive care unit. Secondary outcomes included hospital readmission for hypertension, persistence of hypertension beyond 14 days, medication side effects, and time to blood pressure control. We calculated that 256 women would provide 90% power to detect a relative 50% reduction in the primary outcome from 36% in the standard blood pressure threshold group to 18%, with a 2-sided alpha set at 0.05 for significance. Data were analyzed using R statistical software. RESULTS: A total of 256 patients were randomized, including 128 to the "tight control" group (140/90 mm Hg) and 128 to the "liberal control" group (150/95 mm Hg). Patients in the "tight control" group had a higher body mass index at delivery (37.1±9.4 vs 34.9±8.1; P=.04); other demographic and obstetrical characteristics were similar between groups. The rate of the primary outcome was similar between groups (8.6% vs 11.7%; P=.41; relative risk, 0.73; 95% confidence interval, 0.35-1.53). The rates of all secondary outcomes and the individual components of the primary and secondary outcome measures were also similar between groups. CONCLUSION: In the postpartum period, initiation of antihypertensive therapy at a lower blood pressure threshold of 140/90 mm Hg did not decrease maternal morbidity or improve outcomes compared with a threshold of 150/95 mm Hg.

[Posterior reversible encephalopathy syndrome during nilotinib treatment for chronic myeloid leukemia].

Here we present the case of a 50-year-old woman with chronic myeloid leukemia who received nilotinib as initial treatment. After about 2 years of nilotinib therapy, she developed headache, blurred vision, impaired consciousness, and marked hypertension. Posterior reversible encephalopathy syndrome (PRES) was diagnosed, and was strongly suspected to be a vascular adverse event caused by nilotinib. Nilotinib was withheld and the patient was treated with antihypertensive drugs under ventilator management. Her symptoms resolved quickly. The most likely cause of PRES is systemic arterial hypertension and endothelial dysfunction due to direct injury leading to dysfunction at the level of the blood-brain barrier, along with the resultant vasogenic edema. PRES has been reported with some tyrosine kinase inhibitors, but this is the first case of PRES during nilotinib treatment.

Cerebral amyloid angiopathy-related inflammation with posterior reversible encephalopathy syndrome-like presentation: a case report.

BACKGROUND: Cerebral amyloid angiopathy-related inflammation (CAA-RI), which presents with acute or subacute cognitive or functional decline, focal or multifocal neurologic deficits, new onset of seizures, or a combination of seizures and neurologic deficits, shares clinical and radiologic similarities with posterior reversible encephalopathy syndrome (PRES). Differential diagnosis is critical because the treatment principle for these 2 conditions differs greatly. Here, we present a case of PRES-like CAA-RI and the strategy used to discriminate between the 2 conditions. CASE PRESENTATION: A patient with probable CAA-RI was first thought to suffer from PRES. Initial high-dose methylprednisolone therapy caused rapid improvement of the neurologic symptoms but abrupt discontinuation of corticosteroids resulted in clinical relapse and deterioration. Subsequent reinitiation of high-dose methylprednisolone followed by tapering off of oral prednisone led to clinical and radiologic recovery at the 3-month follow-up. CONCLUSIONS: We suggest that in cases where it is difficult to distinguish between CAA-RI and PRES solely based on magnetic resonance imaging, a good response to corticosteroids and an apolipoprotein E (ApoE) ε4/ε4 genotype are critical for establishing a diagnosis of CAA-RI. If there is clinical deterioration, sudden withdrawal of high-dose corticosteroid during the active phase of CAA-RI should be avoided.

Oral agents for acute severe hypertension in children with minimal or no symptoms.

Acute hypertension is common among children admitted to hospital, and large or rapid increases in blood pressure place children at risk of complications such as posterior reversible encephalopathy syndrome. Guidelines in the United States and Europe now include definitions guiding the identification of acute severe hypertension (otherwise known as hypertensive crisis) and its management. This review discusses these recommendations and the appropriate use of oral antihypertensive agents for children with minimal or no symptoms. We focus on the role of oral calcium channel blockers, including isradipine (a second-generation dihydropyridine), given recent changes to regulatory approvals in Australia. The differing pharmacokinetic and pharmacodynamic properties of agents are compared, with the aim of facilitating directed drug selection and dosing.

Polyarteritis nodosa presenting with posterior reversible leukoencephalopathy syndrome.

A man in his 20s presented following a generalised tonic-clonic seizure on a background of a recent diagnosis of hepatitis B (HBV). During admission, he was severely hypertensive and imaging findings confirmed a diagnosis of posterior reversible leukoencephalopathy syndrome (PRES). The patient subsequently developed multiorgan involvement with an axonal sensorimotor neuropathy, vascular cutaneous lesions and multiple bilateral renal and splenic infarcts. Based on the 2012 Revised International Chapel Hill Consensus Criteria, a diagnosis of polyarteritis nodosa (PAN) with secondary PRES was made. The patient was given intravenous methylprednisolone, followed by a prolonged course of oral prednisolone, and tenofovir antiviral therapy to target HBV seroconversion. He made a good neurological recovery with resolution of imaging changes. This case highlights the importance of a low threshold for systemic screening for young patients presenting with PRES secondary to uncontrolled hypertension and the importance of viral screening, particularly for HBV.

Interim results from a postmarketing surveillance study of patients with FLT3-mutated relapsed/refractory AML treated with the FLT3 inhibitor gilteritinib in Japan.

OBJECTIVE: Gilteritinib received approval for the treatment of FLT3-mutated relapsed or refractory acute myeloid leukemia in Japan in 2018. In accordance with regulatory requirements, we conducted a multicenter, observational surveillance of gilteritinib use in Japan. METHODS: Patients were followed for 6 months from gilteritinib treatment initiation. The primary endpoint of the surveillance was incidence of adverse drug reactions related to each element of the safety specification defined in the Japanese Risk Management Plan. This interim analysis presents data collected from 3 December 2018 to 20 September 2020. RESULTS: Among 204 patients with case report forms, 107 consented to data publication. Of these 107 patients, 59.8% (n = 64) were male and 58.9% (n = 63) were aged ≥65 years; most received a 120-mg/day initial (80.4%; 86/107) and maximum (74.8%; 80/107) daily dose. The discontinuation rate was 61.7% (66/107); the most common reasons for discontinuation were disease progression (18.7%), transplantation (16.8%) and adverse events (15.0%). The adverse drug reaction rate was 77.6%. The incidences of adverse drug reactions (grade ≥ 3) related to each element of the safety specification were myelosuppression, 44.9% (38.3%); liver function disorder, 24.3% (6.5%); infections, 24.3% (21.5%); prolonged QT interval, 10.3% (2.8%); hemorrhage, 9.3% (6.5%); renal dysfunction, 6.5% (0); hypersensitivity, 5.6% (1.9%); interstitial lung disease, 4.7% (3.7%); cardiac failure/pericarditis/pericardial effusion, 1.9% (0.9%); pancreatitis, 0.9% (0); posterior reversible encephalopathy syndrome, 0.9% (0.9%). The composite complete remission rate was 62.7%; the 6-month overall survival rate was 77.7%. CONCLUSION: Gilteritinib treatment for 6 months in Japan was associated with acceptable efficacy and no new safety concerns were observed.

Anti-neutrophil cytoplasmic antibody-associated vasculitis complicated by thrombotic microangiopathy with posterior reversible encephalopathy syndrome successfully treated with eculizumab: A case report.

Thrombotic microangiopathy is characterised by endothelial cell injury, intravascular platelet-fibrin thrombi, and vascular damage, leading to acute kidney injury, thrombocytopenia, and microangiopathic haemolytic anaemia. Among the autoimmune diseases related to thrombotic microangiopathy, anti-neutrophil cytoplasmic antibody-associated vasculitis-related thrombotic microangiopathy cases have been rarely reported; therefore, the optimal treatment for associated vasculitis-related thrombotic microangiopathy remains unknown. An 84-year-old woman without significant medical history presented with a 1-month history of general fatigue, fever, and deteriorating bilateral leg numbness and was admitted to our hospital. She had elevated myeloperoxidase anti-neutrophil cytoplasmic antibody levels, polyneuropathy, and rapid progressive glomerulonephritis because of pauci-immune crescentic glomerulonephritis, as revealed by a kidney biopsy. Accordingly, we diagnosed her with microscopic polyangiitis. After administering methylprednisolone pulse therapy, rituximab, and intravenous immunoglobulin, the patient's mental state deteriorated, presenting signs of thrombotic microangiopathy with posterior reversible encephalopathy syndrome. Intermittent haemodialysis and plasma exchange were initiated; however, her condition did not improve, and eculizumab administration was initiated thereafter. The patient's symptoms showed a remarkable response to eculizumab; thrombotic microangiopathy findings, kidney function, and neurological symptoms improved after only two doses of eculizumab, and she achieved sustained remission. The extremely effective course of eculizumab treatment indicated that overt complement activation affected the development of thrombotic microangiopathy. Anti-neutrophil cytoplasmic antibody-associated vasculitis-related thrombotic microangiopathy may be mediated by complement activation, and prompt induction of eculizumab therapy may be a superior strategy to prevent organ damage. Further studies should elucidate the role of complement activation in associated vasculitis-related thrombotic microangiopathy and the efficacy of eculizumab treatment.

Posterior Reversible Encephalopathy Syndrome in the Setting of Asparaginase-associated Pancreatitis in 2 Pediatric Patients With Acute Leukemia.

Asparaginase, a critical component of current pediatric acute leukemia treatment protocols, is associated with a number of serious side effects, one of which is pancreatitis. Pancreatitis can result in significant morbidity and mortality from necrosis, pseudocyst formation, hemorrhage, systemic inflammation, intestinal perforation, and sepsis. Another rare complication of pancreatitis is posterior reversible encephalopathy syndrome, likely mediated by systemic inflammation secondary to pancreatic autodigestion and proinflammatory cytokine-mediated vascular endothelial damage. Here, we review this association in the literature and report 2 pediatric patients with leukemia who developed posterior reversible encephalopathy syndrome in the setting of asparaginase-associated pancreatitis.

Linezolid-Associated Posterior Reversible Leuco-encephalopathy Syndrome in a Patient with Disseminated Tuberculosis.

Neurological side-effects of linezolid manifesting as a posterior reversible leuco-encephalopathy syndrome (PRES) is rare. Early identification of this offending drug might reverse this catastrophic event. We report a 45-year-old female, who was diagnosed as a case of disseminated tuberculosis and was treated with antitubercular drugs (ATT), but later developed ATT-induced hepatitis. She was then put on modified ATT (moxifloxacin, terizidone, and linezolid). In the next two days she developed an altered sensorium. Brain imaging was suggestive of PRES. Linezolid was withdrawn, following which she showed an excellent clinical and radiological recovery.

Efficacy of renin-angiotensin-aldosterone system blockades for acute phase hypertensive emergencies in patient complicating severe acute kidney injury.

Renin-angiotensin-aldosterone system (RAAS) is primarily involved with pathological mechanism of developing hypertensive emergencies. However, none of clinical practice guidelines mention RAAS blockers for the treatment of hypertensive emergencies. A 44 year-old woman presented with severe hypertension, brain stem posterior reversible encephalopathy syndrome and severe acute kidney injury (AKI). We started anti-hypertensive therapy with continuous intravenous nitroglycerin and oral calcium channel blocker (CCB) and spironolactone. Since severe AKI persisted despite this therapy, we administered losartan potassium, which resulted in improvement in her blood pressure and creatinine. Clinical course of our patient suggests that timely initiation of ARB and spironolactone for hypertensive emergencies could be beneficial in terms of blood pressure control and for protection of target organs from this condition.

Acute posterior reversible encephalopathy syndrome (PRES) in setting of interferon-beta use: case presentation with reduction of edema in 72 h after cessation of interferon-beta therapy with sub-clinical inflammation.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) represents a transient change in mental status with associated vasogenic edema of cortical and subcortical brain structures. It is often attributed to multifactorial etiology including hypertension and altered hemodynamics and disruption of vessel integrity. Patients with autoimmune disease and certain immune modulator therapies are at greater risk. CASE PRESENTATION: A 54-year-old female with past medical history of well-controlled multiple sclerosis on interferon-beta since 2013, presented with witnessed tonic colonic seizure. She also was noted to demonstrate left gaze deviation and left-sided hemiparesis. MRI fluid-attenuated inversion recovery sequence showed hyperintensity of the subcortical U fibers, concentrated in the occipital, parietal lobes and frontal lobes. Systolic blood pressure was 160 mmHg on arrival. The patient was started on seizure prophylxis and Interferon beta was discontinued. The patient's mentation, seizures and hemiapresis significantly improved in next 72 h with tight blood pressure control, and had notble improvement on MRI imaging and inflammatory markers. Lumbar puncture CSF results were devoid of infectious and autoimmune pathology. CONCLUSIONS: A middle-aged female with multiple sclerosis who was on chronic IFN-beta presented to the emergency room with a witnessed tonic-clonic seizure, with MRI T2 FLAIR imaging consistent with PRES. She had notable clinical improvement with decreased edema on imaging and improved inflammatory markers 72 h after cessation of IFN-beta therapy.

Systemic lupus erythematosus complicated with reversible posterior encephalopathy syndrome: a case report.

A 28-year-old female patient was hospitalized primarily because of "intermittent fever for 28 days aggravated by systemic rashes, oral ulcer, and edema in both eyelids for 5 days." During treatment, convulsions and loss of consciousness occurred. Magnetic resonance imaging (MRI) of the head revealed an abnormal signal with shadows in the bilateral frontal, parietal, temporal, and occipital lobes; cerebellar hemispheres; and basal nodes, with high signal intensity on T2 weighted imaging (T2WI), on fluid-attenuated inversion-recovery, and of the apparent diffusion coefficient and low signal intensity on T1WI and diffusion weighted imaging. Therefore, the patient was diagnosed with systemic lupus erythematosus (SLE) with reversible posterior encephalopathy syndrome (RPES). Intravenous high-dose methylprednisolone and cyclophosphamide were administered for blood pressure control, which effectively controlled the disease. Therefore, when patients with SLE and hypertension or renal insufficiency or those receiving high-dose methylprednisolone or immunosuppressants suddenly present with neurologic abnormalities, a diagnosis of RPES must be considered, and head MRI is the first choice for diagnosis of this disease. In terms of treatment, the blood pressure should be quickly controlled, and the primary disease should be aggressively treated.

Miller Fischer and posterior reversible encephalopathy syndromes post COVID-19 infection.

COVID-19 infection displays heterogeneity of clinical manifestations in symptomatic and asymptomatic patients. We report on a child with Miller Fischer syndrome (MFS) and posterior reversible encephalopathy syndrome (PRES) post-COVID-19 infection. An 11-year-old boy presented with vomiting, headache, blurred vision, dysarthria, dysphagia, respiratory failure, muscle weakness, and unsteadiness. He had been exposed to COVID-19 through an asymptomatic elder brother two months prior to his illness. The MRI brain showed findings consistent with PRES and the diagnosis with Miller Fischer variant of the Guillain-Barré syndrome was made. A cerebrospinal fluid analysis revealed cytoalbuminous dissociation, and a nerve conduction velocity study conclusively showed polyneuropathy. A fluoroscopy of the diaphragms found that there was limited movement in both. Although children seem to be less affected by COVID-19 infection, this report highlights on an important neurological complications that can develop in children and its presence should be taken into consideration when diagnosing different forms of Guillain-Barré.

Neuropsychiatric lupus with posterior reversible encephalopathy syndrome: a rare presentation.

Systemic lupus erythematosus presenting with neuropsychiatric symptoms (NPSLE) along with posterior reversible encephalopathy syndrome (PRES) is rare. A young woman of 29 years presented with various neuropsychiatric symptoms along with low-grade fever, occasional headache, skin rash, arthralgias and gradually became non-ambulatory over last 6 months. After admission, she had an episode of generalised tonic-clonic seizure, followed by drowsiness. She was normotensive. Investigations revealed no evidence of any underlying infection, normal renal functions and electrolytes; but other parameters were supportive to a diagnosis of NPSLE. MRI brain showed vasogenic oedema characterised by symmetrical hyperintensities over posterior brain regions in T2 and fluid attenuated inversion recovery images with no restricted diffusion in diffusion weighted image suggestive of PRES. A diagnosis of NPSLE presenting with PRES, particularly in the absence of hypertension and abnormal renal functions was made, which is a rare presentation. She responded well to immunomodulatory therapy with methylprednisolone and monthly cyclophosphamide.

Erythropoietin-Associated Posterior Reversible Encephalopathy Syndrome.

INTRODUCTION: This case demonstrates an underrecognized cause of posterior reversible encephalopathy syndrome (PRES). CASE REPORT: We report a 51-year-old male with a history of essential hypertension without preexisting renal impairment who presented with 3 days of occipital headache and convulsive status epilepticus in the setting of refractory hypertension. He had been receiving outpatient human recombinant erythropoietin injections for virally mediated bone marrow suppression, which worsened his baseline hypertension. Magnetic resosnance imaging (MRI) of the brain on admission showed diffuse bilateral, symmetric signal hyperintensities and patchy enhancement involving the cortex and white matter in both cerebral hemispheres. His blood pressure and seizures were successfully treated during hospital admission, with complete resolution of his neurological deficits. MRI brain performed 6 weeks from initial scan showed normalization of his prior findings. CONCLUSION: Recombinant human erythropoietin (RhEPO) may be an underrecognized cause of PRES and should be considered in patients receiving this treatment regardless of the absence or presence of renal impairment. RhEPO-mediated precipitation/exacerbation of hypertension, alterations in cerebral blood flow, and changes in endothelial integrity may underlie this association. MRI signal changes are reversible and typical for that of PRES, and significant improvement of symptoms can be expected.

Posterior reversible encephalopathy syndrome as the first manifestation of mixed connective tissue disorder: a case report.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a neurological syndrome characterised by a range of neurological symptoms and signs, and distinctive neuroimaging findings reflecting vasogenic oedema. Posterior reversible encephalopathy syndrome has been described in association with many autoimmune diseases, but its association with mixed connective tissue disorder (MCTD) is very rare. After an extensive review of the literature, we found only three cases of posterior reversible encephalopathy syndrome in association with mixed connective tissue disorder. But unlike other cases, in our patient, PRES is the presenting manifestation of mixed connective tissue disorder which is first of its kind. CASE PRESENTATION: We present a 30-year-old female from Southern India who had initially reported with complaints of fever, multiple episodes of vomiting and cough with expectoration. She had accelerated hypertension and moderate thrombocytopenia. Two days later, she developed sudden onset of visual disturbances and had a drop in sensorium. Neuroimaging done was suggestive of atypical posterior reversible encephalopathy syndrome, and autoimmune workup was positive for mixed connective tissue disorder. With prompt blood pressure control and anti-seizure medications, she recovered completely. CONCLUSION: Early diagnosis and prompt control of blood pressure, along with anti-seizure measures, play a crucial role in management. Awareness about this rare association is essential for early diagnosis and treatment, and therefore reducing the risk of permanent neurologic deficits. This case is being reported because of its rarity.