Reversible Leukoencephalopathy Research Articles

Pseudotumor Cerebri with Familial Mediterranean Fever in an Adult Patient

Familial Mediterranean fever is an autosomal recessive disease characterized by recurrent episodes of fever, peritonitis, pleuritis and arthritis. Neurological involvement in FMF is rare but serious. Headache, seizures, demyelinating lesions, stroke, posterior reversible leukoencephalopathy syndrome, aseptic meningitis and cranial neuropathy have been reported in the literature. In this paper, we present a combination of FMF and pseudotumor cerebri in an adult patient.

Posterior Reversible Leukoencephalopathy Syndrome (PRES) in a patient with post eclampsia with status epilepticus

Despite the limited number of instances and relatively low knowledge of Posterior Reversible Leukoencephalopathy Syndrome (PRES) among the population of Bangladesh, it is imperative to recognize the gravity of this health issue. The crucial aspect in achieving favorable results is the early detection of the condition, as it allows for the prompt elimination of the precipitating cause and the effective management of blood pressure. The present case study elucidates the significant discoveries pertaining to a patient with posterior reversible encephalopathy syndrome (PRES), as well as the diagnostic and therapeutic strategies used. A female individual who had just undergone a surgical operation known as a cesarean section exhibited symptoms including headache, recurrent convulsions, and loss of consciousness. Subsequent medical evaluation led to the diagnosis of posterior reversible encephalopathy syndrome (PRES). This section presents an examination of the diagnostic process using clinical and radiological characteristics, as well as an overview of the therapy plan. The fast diagnosis and timely beginning of therapy procedures have been identified as crucial factors for achieving early recovery and favorable functional outcomes. J Shaheed Suhrawardy Med Coll 2022; 14(2): 63-65

Neuro-ophthalmic complications of modern anti-cancer drugs

PurposeTargeted cancer therapies have been responsible for a dramatic shift in treatment strategies for cancer, and the number of drugs, classes, and indications are continually growing. Neuro-ophthalmic complications of these medications are an uncommon but important subset of adverse events which profoundly impact vision. This review aims to collate studies and reports of known neuro-ophthalmic complications of targeted therapies and describe their management.MethodsThe anti-cancer drugs included in the review were any drugs targeting specific molecules involved in the cancer disease process. PubMed, EMBASE, and Web of Science were searched using the generic names of each drug and keywords of neuro-ophthalmic conditions. The prescribing information published by the US Food and Drug Administration (FDA) for each drug was also reviewed.ResultsSeveral classes of targeted anti-cancer drugs were found to cause neuro-ophthalmic adverse effects. Immune checkpoint inhibitors are responsible for a raft of immune-related adverse events such as optic neuritis, ischemic optic neuropathy, PRES, and myasthenia gravis. Therapies with anti-VEGF activity can provoke posterior reversible leukoencephalopathy, which commonly presents with visual loss and can be fatal if not treated promptly. Inhibitors of BCR-ABL1, VEGF, ALK, and proteasomes have all been linked to optic nerve disorders which can have debilitating consequences for vision.ConclusionThe neuro-ophthalmic complications of modern anti-cancer drugs can limit or necessitate the withdrawal of these life-prolonging medications. Ophthalmologists should be alert for neuro-ophthalmic complications in these medications to facilitate prompt diagnosis and treatment and reduce the risk of severe and permanent consequences.

Posterior Reversible Leukoencephalopathy With Hemorrhagic Features: A Case Series.

Introduction Posterior reversible leukoencephalopathy syndrome (PRES) is a clinical-radiological condition characterized by reversible subcortical vasogenic cerebral edema of acute or subacute onset in circumstances that disrupt capillary permeability, unfrequently accompanied by cytotoxic and/or hemorrhagic lesions. We describe a case series of PRES with hemorrhagic features. Subjects and methods Electronic medical records of hospitalized patients diagnosed with PRES from January 2009 to December 2021 were collected. Demographic data, medical history, clinical presentation, and outcome were recorded. Variables were compared between patients with and without hemorrhagic features using the Wilcoxon-Mann-Whitney test with a statistical significance level of p<0.05. Results Over a 12-year period, 33 patients were diagnosed with PRES, of whom 10 had hemorrhagic features: seven cortical microbleeds, two intraparenchymal hematomas, and one subarachnoid hemorrhage. Half of the patients were women, with a median age of 45.8 years (interquartile range (IQR) 21.8), and were admitted for non-neurological reasons. The sample included nine transplant recipients (six solid organa, three bone marrowa), with four patients in the immediate post-transplant period. PRES occurred in the context of infections and blood pressure fluctuations under cytotoxic drugs, such as immunosuppressants. Seventy percent showed improvement/resolution on neuroimaging at a median of 70 days (IQR 62.9). The three major hemorrhages occurred in the context of thrombocytopenia. The recorded in-hospital mortality was 10%. When compared to PRES without hemorrhagic features, patients with hemorrhagic features had a lower use of corticosteroids (50% vs. 78.8%; p=0.02) and a higher presence of restrictive lesions on neuroimaging (60% vs. 17%; p=0.04), with no differences in the other analyzed variables. Conclusion Patients with PRES and hemorrhagic features had a lower use of corticosteroids and a higher presence of restrictive lesions on neuroimaging. Further studies are needed to better understand the clinical implications and management of PRES with hemorrhagic manifestations.

Author Response: Teaching NeuroImage: Partially Reversible Widespread Leukoencephalopathy Associated With Atypical Hemolytic Uremic Syndrome.

Author Response: Teaching NeuroImage: Partially Reversible Widespread Leukoencephalopathy Associated With Atypical Hemolytic Uremic Syndrome.

Editors' Note: Teaching NeuroImage: Partially Reversible Widespread Leukoencephalopathy Associated With Atypical Hemolytic Uremic Syndrome.

Editors' Note: Teaching NeuroImage: Partially Reversible Widespread Leukoencephalopathy Associated With Atypical Hemolytic Uremic Syndrome.

Reader Response: Teaching NeuroImage: Partially Reversible Widespread Leukoencephalopathy Associated With Atypical Hemolytic Uremic Syndrome.

Reader Response: Teaching NeuroImage: Partially Reversible Widespread Leukoencephalopathy Associated With Atypical Hemolytic Uremic Syndrome.

Structural and functional implications of SLC13A3 and SLC9A6 mutations: an in silico approach to understanding intellectual disability

BackgroundIntellectual disability (ID) is a condition that varies widely in both its clinical presentation and its genetic underpinnings. It significantly impacts patients’ learning capacities and lowers their IQ below 70. The solute carrier (SLC) family is the most abundant class of transmembrane transporters and is responsible for the translocation of various substances across cell membranes, including nutrients, ions, metabolites, and medicines. The SLC13A3 gene encodes a plasma membrane-localized Na+/dicarboxylate cotransporter 3 (NaDC3) primarily expressed in the kidney, astrocytes, and the choroid plexus. In addition to three Na + ions, it brings four to six carbon dicarboxylates into the cytosol. Recently, it was discovered that patients with acute reversible leukoencephalopathy and a-ketoglutarate accumulation (ARLIAK) carry pathogenic mutations in the SLC13A3 gene, and the X-linked neurodevelopmental condition Christianson Syndrome is caused by mutations in the SLC9A6 gene, which encodes the recycling endosomal alkali cation/proton exchanger NHE6, also called sodium-hydrogen exchanger-6. As a result, there are severe impairments in the patient’s mental capacity, physical skills, and adaptive behavior.Methods and resultsTwo Pakistani families (A and B) with autosomal recessive and X-linked intellectual disorders were clinically evaluated, and two novel disease-causing variants in the SLC13A3 gene (NM 022829.5) and the SLC9A6 gene (NM 001042537.2) were identified using whole exome sequencing. Family-A segregated a novel homozygous missense variant (c.1478 C > T; p. Pro493Leu) in the exon-11 of the SLC13A3 gene. At the same time, family-B segregated a novel missense variant (c.1342G > A; p.Gly448Arg) in the exon-10 of the SLC9A6 gene. By integrating computational approaches, our findings provided insights into the molecular mechanisms underlying the development of ID in individuals with SLC13A3 and SLC9A6 mutations.ConclusionWe have utilized in-silico tools in the current study to examine the deleterious effects of the identified variants, which carry the potential to understand the genotype-phenotype relationships in neurodevelopmental disorders.

Novel SLC13A3 Variants and Cases of Acute Reversible Leukoencephalopathy and α-Ketoglutarate Accumulation and Literature Review.

Acute reversible leukoencephalopathy with increased urinary alpha-ketoglutarate (ARLIAK) is a recently described autosomal recessive leukoencephalopathy caused by pathogenic variants in the SLC13A3 gene. ARLIAK is characterized by acute neurologic involvement, often precipitated by febrile illness, with largely reversible clinical symptoms and imaging findings. Three patients have been reported in the literature to date. Our objective is to report newly identified patients and their genetic variants and phenotypes and review published literature on ARLIAK. This report contributes 4 additional patients to the literature; describes novel variants in SLC13A3; and reviews genetic, biochemical, clinical, and radiologic features of all published patients with ARLIAK. We provide additional genetic, imaging, and laboratory insights into ARLIAK, an atypical leukodystrophy with clinical and radiologic findings that can normalize. Our case series highlights the importance of reanalysis of next-generation sequencing in the diagnostic workup.

Steroid-responsive encephalopathy associated with autoimmune thyroiditis presenting as cortisone sensible psychosis with reversible leukoencephalopathy

IntroductionSteroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) is a frequently discussed neuropsychiatric syndrome with elevated thyroid antibodies in the context of various clinical neuropsychiatric phenotypes. MRI abnormalities are usually nonspecific and treatment can be complex. Case studyWe present a case of a woman in her sixties with SREAT whose psychosis kept worsening under cortisone tapering. After three years with cortisone side effects, therapy was changed to plasmapheresis and rituximab treatment with an excellent initial response, subacute unexplained deterioration with extensive leukoencephalopathy on MRI shortly after, and full recovery with regression of leukoencephalopathy afterwards. DiscussionSREAT varies in clinical and diagnostic presentation. Its precise pathophysiology is unknown, as are the best treatment protocols. The case illustrates that some patients with SREAT syndrome might end up in constellations, in which it proves difficult to wean off steroid treatment and illustrates treatment alternatives such as plasmapheresis and/or rituximab. In addition, it highlights leukoencephalopathy as possible MRI finding in the context of SREAT. Further research is necessary to fully comprehend the (potentially different) pathomechanisms and courses of SREAT.

Stroke-like presentation of acute toxic leukoencephalopathy due to capecitabine treatment with extensive intramyelinic edema.

Stroke-like presentation of acute toxic leukoencephalopathy due to capecitabine treatment with extensive intramyelinic edema.

Випадок мітохондріальної епізодичної міопатії (варіант без атрофії зорового нерва та оборотної лейкоенцефалопатії) у Прикарпатті

Mitochondrial episodic myopathy with/or without optic nerve atrophy and reversible leukoencephalopathy (MEOAL, OMIM 251900) belongs to rare primary mitochondrial myopathies, caused by nuclear genome DNA mutations with autosomal recessive inheritance. Purpose - to inform about the case of this current rare mitochondrial miopathy and encrease the knowledge of practical doctors in scope of diagnostics and treatment of the current orphan pathology Clinical case. In the clinical case being presented herein, the sick child had a severe course of the disease in the form of episodes of severe myopathy (during one of them there was a need for long-term mechanical lungventilation with the placement of a tracheostomy) in combination with severe metabolic crises. During crises, persistent keto- and lactic acidosis, a sharp increase in transaminases (alanine aminotransferase and aspartate aminotransferase) and creatine kinase in blood serum were observed. The patient did not have optic nerve atrophy or leukoencephalopathy. A similar course of the disease is described in the literature by different authors in only 3 cases. Molecular genetic analysis (Invitae laboratory, San Francisco) revealed 2 mutations of the FDX2 gene (the disease is associated with this gene) with uncertain pathogenic significance. Considering the presence of cardinal symptoms of MEOAL, this diagnosis was set to the patient, and therefore the detected mutations of the FDX2 gene should be considered as pathogenic. Conclusions. A thorough syndromic analysis of the phenotype together with a set of paraclinical examinations, including modern molecular genetic methods, made it possible to establish a clinical diagnosis of an extremely rare primary mitochondrial myopathy, which will contribute to further elucidation of relationships in the «genotype-phenotype» system and, possibly, reclassification of pathogenic genotypes in modern databases, as well as finding optimal approaches in treatment and rehabilitation of patients. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Transient Cortical Blindness Following Cerebral Angiography: A Case Report (P2-5.015)

<h3>Objective:</h3> We would like to report a case of Transient cortical blindness following cerebral angiography <h3>Background:</h3> Transient cortical blindness (TCB) is a rare complication following cerebral angiography. Its pathophysiology remains uncertain. We would like to report a case of TCB in a patient during follow up cerebral angiogram for post coil embolization of left internal carotid aneurysm. <h3>Design/Methods:</h3> 50-year-old woman with history of hypertension presents with bilateral vision loss during follow up cerebral angiography for ruptured left internal carotid artery aneurysm status post coiling. This was associated with headache, nausea, and emesis. No associated neurologic deficits. Review of symptoms was otherwise negative. CT Head and CTA showed no acute abnormalities. MRI done on admission showed no evidence of abnormalities. Ophthalmology saw the patient and exam was unrevealing. After 24 hours her vision gradually improved and was back to baseline after 48 hours with no intervention. <h3>Results:</h3> Transient Cortical Blindness is a rare but dramatic complication of cerebral angiogram. It is characterized by loss of perceived vision, normal fundi, normal papillary reflexes, and intact extraocular movements. Symptoms can occur at the start of the cerebral angiography procedure or until serval hours after. The recovery of normal vision may start within the first few hours, but may take as long as 5 days. Two hypothesis exist: could be due to a neurotoxic effect of contrast agent causing osmotic disruption of blood-brain barrier or could be the result of posterior reversible leukoencephalopathy syndrome leading to perivascular edema. There is no known treatment known to improve the condition. <h3>Conclusions:</h3> In summary, we reported a case of TCB following vertebral angiography, a rare but dramatic complication of cerebral angiography. Radiologists and clinicians should be aware of this complication. When it occurs, one should reassure the patient about the excellent prognosis of this condition. <b>Disclosure:</b> Dr. Gomez has nothing to disclose. Dr. Harris has nothing to disclose.

Neuro-Ophthalmic Visual Impairment in the Setting of COVID-19.

We set out to describe in detail the afferent neuro-ophthalmological complications that have been reported in association with coronavirus disease 2019 (COVID-19) infection. We describe and elaborate on mechanisms of disease, including para-infectious inflammation, hypercoagulability, endothelial damage, and direct neurotropic viral invasion. Despite global vaccination programs, new variants of COVID-19 continue to pose an international threat, and patients with rare neuro-ophthalmic complications are likely to continue to present for care.Afferent complications from COVID-19 include homonymous visual field loss, with or without higher cortical visual syndromes, resulting from stroke, intracerebral hemorrhage, or posterior reversible leukoencephalopathy. Optic neuritis has frequently been reported, sometimes along with acute disseminated encephalomyelopathy, often in association with either myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) or less commonly aquaporin-4 seropositivity or in newly diagnosed multiple sclerosis. Ischemic optic neuropathy has rarely been reported. Papilledema, resulting either from venous sinus thrombosis or idiopathic intracranial hypertension in the setting of COVID-19, has also been described.Observed afferent neuro-ophthalmic associations need to be confirmed though larger comparative studies. Meanwhile, the range of possible complications should be recognized by neurologists and ophthalmologists alike, to facilitate faster diagnosis and treatment of both COVID-19 and its neuro-ophthalmic manifestations.

Reversible leukoencephalopathy and venous thrombosis in classical homocystinuria

Reversible leukoencephalopathy and venous thrombosis in classical homocystinuria

PSAT051 Posterior Reversible Leukoencephalopathy Syndrome Associated With Cushing's Syndrome

Abstract Background Corticosteroids can induce hypertension through a variety of mechanisms such as vasoconstriction, increased hepatic production of angiotensinogen, sympathetic activity, and possible direct cardiotoxic effect. Posterior reversible leukoencephalopathy syndrome (PRES), a syndrome with unclear pathogenesis, can be the consequence of blood pressure elevation in these patients, which can present with headaches, altered consciousness, visual disturbances, or seizures. CASE REPORTA 57-year-old African American woman with a history of hypertension on Lisinopril 40mg as an outpatient, who was brought to the emergency department (ED) by family members due to altered mental status (AMS). Daughter reports that a day prior to the admission the patient has complained of feeling unwell, with mild shortness of breath and anxiety. On admission, she was found to be on sinus tachycardia with heart rate between 100-140bpm and severely hypertensive at 203/107mmHg. Toxicology screen was positive for cannabinoids, which the patient admitted to vapping the night prior. At the ED, Stroke alert was called due to altered mentation and weakness, however CT brain showed no large infarct or hemorrhage. MRI was obtained and showed patchy t2/flair hyperintense signal abnormality predominantly of the subcortical white matter in the bilateral frontoparietal lobes, most conspicuous at the vertex. Findings could reflect acute hypertensive encephalopathy (PRES). The patient had a Cushingoid appearance, with truncal obesity, moon face and reported easy bruising. Given the clinical findings and severe hypertension, serum cortisol was obtained at night and was found to be elevated at 34. 08UG/DL (3.44 - 16.76 ug/dl). ACTH was mildly low at 5 pg/mL (6-50pg/mL). 24-hour urine cortisol was then ordered and also found to be elevated at 818mcg/24h (4-50mcg/24h). Blood pressure was controlled with antihypertensive medications (nifedipine 60mg and carvedilol 12.5mg), AMS resolved and patient was discharged home with follow up with endocrinology for further Cushing's workup. Conclusion Cushing Syndrome is a known cause of secondary hypertension that should not be neglected. Patients that present with severe or resistant hypertension regardless of age should be worked up for possible secondary cases. Patients with Cushing syndrome are at elevated cardiovascular risk and the sooner the diagnosis is made, the better, so they can receive appropriate treatment. Hypertensive crisis can present as PRES syndrome and patients with clinical suspicion for Cushing should be worked up for the condition. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Departments Of Nephrology, Emergency And Pneumology, Fundació Salut Empordà

We present the clinical case of a 33-year-old woman on haemodialysis who suffered a severe hypertensive crisis during the sessions. In one of them, she developed Posterior Reversible Leukoencephalopathy Syndrome (PRES)

Teaching NeuroImage: Partially Reversible Widespread Leukoencephalopathy Associated With Atypical Hemolytic Uremic Syndrome.

A 43-year-old woman presented with altered mental status and hypertension. She had a 3-day history of oliguria. The blood test detected microangiopathic hemolytic anemia, thrombocytopenia, and severe kidney injury. The absence of shiga-like toxin, ADAMTS13 autoantibodies, and normal ADAMTS13 activity were consistent with a diagnosis of atypical hemolytic uremic syndrome (aHUS) and then confirmed by a renal biopsy. Genetic tests ( CFH, CFHR1-5, MCP/CD46, CFI, C3, CFB, THBD , and DGKE ) were unremarkable. Nevertheless, a history of anemia and kidney failure in her younger brother suggested a genetic etiology.

A Descriptive Investigation of the Prevalence of Neurological Disorders in People Treated Hemodialysis for End-Stage Renal Disease

Objectives: Patients with end-stage renal disease (ESRD) who were receiving hemodialysis were the subjects of a study to determine the neurological effects of the treatment. Methodology: ESRD patients at the Institute of kidney diseases hayatabad peshawar were the subjects of this descriptive research, which ran from jan to Dec 2021. Before participating in the trial, all Chronic Kidney Disease (CKD) patients had been on Hemodialysis (HD) for at least six months. HD patients were monitored for a total of six months in this study. Neurological events were observed and recorded at this period. All patients on HD, regardless of gender or age, were included in this research, which was conducted between the ages of 17 and 77. In this research, patients under the age of 15 years, those with acute renal failure, congestive cardiac failure, cirrhosis of the liver, malignancy, disseminated intravascular coagulation, sepsis, meningitis, or encephalitis, were all ruled out as candidates for inclusion. The data was analysed using SPSS version 2.2. Results: Intradialytic hypotension, Cerebrovascular accident, Encephalopathy, Dialysis dementia, Neuropathy, Dialysis disequilibrium, Reversible leukoencephalopathy, Central pontine myelinosis, Autonomic dysfunction, and Myopathy were the most common neurological consequences. Conclusions: Our patients on hemodialysis suffer from the most prevalent neurological complication: Intradialytic hypotension. While the long-term result and prognosis of this group may be affected by cerebrovascular illnesses and Dialysis dementias, it is important to examine them as soon as possible. Keywords: neurological problems, (ESRD),frequency, hemodialysis , end-stage renal disease.

Bevacizumab combined with platinum-based chemotherapy in patients with primary or relapsed ovarian cancer: Meta-analysis and literature review.

5582 Background: Epithelial ovarian cancer has the highest mortality rates among all gynecological malignancies and is the fifth leading cause of cancer-related deaths in females. Previously, the treatment of ovarian cancers included cytoreductive surgery in combination with platinum-based chemotherapy. While this treatment regimen initially resulted in a good response, most of the patients subsequently relapsed. Given the role of Vascular Endothelial Growth factor (VEGF) and angiogenesis in the progression of ovarian cancer, VEGF inhibitors such as Bevacizumab were considered in the treatment of advanced or relapsed ovarian cancer patients. We conducted a meta-analysis to compare the efficacy of Bevacizumab with platinum-based chemotherapy to platinum-based chemotherapy. Methods: A thorough systematic literature review identified five eligible studies reporting the efficacy of bevacizumab with platinum-based chemotherapy in the treatment of advanced or recurrent Ovarian cancer as compared to control group receiving platinum-based chemotherapy alone. These studies were randomized Phase III clinical trials, one of which was recently published in 2021. Summary estimates of the clinical endpoints were calculated with risk ratio (RR) and 95% confidence intervals using the random-effects model. Heterogeneity between studies was examined with COCHRAN’S Q based 12 statistics. The primary endpoint was progression free survival at 12 months while secondary endpoints were overall survival and certain adverse effects. Results: Our pooled analysis from the five studies included 4,648 patients. 2,641 were in the Bevacizumab and platinum-based treatment group while 2007 patients in sole-platinum based chemotherapy group. There was a statistically significant difference in primary outcome of progression free survival at 12 months was noted (RR = 1.56 (95% CI: 1.09 to 2.24; p = 0.020). 33,4% of patients in the treatment group as compared to 22.9% observed in the control group attained PFS at 12 months. The secondary outcome of overall survival at 12 months was seen in 76.7% patients in treatment group as compared to 73.02% observed in control group. This was no statistically significant difference in this case (RR = 1.04 (95% CI: 0.96 to 1.12; p = 0.34). Adverse effects including hypertension, proteinuria, arterial and venous thromboembolism, posterior reversible leukoencephalopathy syndrome occurred more frequently in the treatment group. Conclusions: Results from our meta-analysis support the superiority of Bevacizumab with platinum-based chemotherapy over platinum-based chemotherapy with regards to PFS. However, the OS benefit remains questionable.