Cause Of Encephalopathy Research Articles

EP1.04-04 Pembrolizumab-Induced Fatal Encephalopathy

Pembrolizumab is a monoclonal antibody against programmed cell death 1 (PD-1) receptor approved for PD-L1 positive metastatic non-small cell lung cancer (NSCLC). Neurologic adverse events associated with anti-PD-1 antibodies are rare but might be fatal. We report a case of fatal encephalopathy in a patient with metastatic NSCLC treated with pembrolizumab. A 65-year-old former smoker woman with advanced lung adenocarcinoma with a KRASmutation and an intermediate expression of PD-L1 (20-30%) previously treated with combination of carboplatin and pemetrexed started pembrolizumab (200 mg, every three weeks) after disease progression. After the second infusion of pembrolizumab, she presented with seizures and decreased level of consciousness. Concerning neurological examination, the patient was vigil, carried out only simple commands with absence of speech. Additionally, her muscular tonus was increased. Blood tests were unremarkable. Electroencephalogram was consistent with diffuse encephalopathy and also showed frequent epileptiform activity. Cerebral computed tomography and magnetic resonance revealed central nervous system (CNS) multifocal demyelination. Cerebrospinal fluid was acellular with glucose and protein within normal range. Also, microbiologic examination and polymerase chain reaction (PCR) assay for cytomegalovirus, herpes simplex 1 and 2 and John Cunningham (JC) virus were negative. Anti-onconeural antibodies were absent. Systemic corticosteroid therapy (dexamethasone 4 mg, every six hours) was initiated, with no improvement. Best supportive care was decided by a multidisciplinary team and patient died one month after admission. After excluding other causes for encephalopathy as paraneoplastic syndrome, CNS infection and metastasis, temporal association with pembrolizumab administration made us suspect of an adverse event of this drug. A case of pembrolizumab-induced encephalopathy was reported in advanced NSCLC, after two doses administration and the patient recovered after high dose corticosteroids. However, another case of nivolumab-induced encephalopathy in advanced renal cell carcinoma was fatal, even with drug discontinuation and high dose corticosteroid therapy. Although anti-PD-1 rarely cause encephalopathy, our case highlights not only its occurrence but also shows that it may be rapidly progressive and irreversible. As this entity probably represents an autoimmune process due to PD-1 block, its course is impossible to predict.

Malnutrition-related hyperammonemic encephalopathy presenting with burst suppression: a case report

BackgroundHyperammonemia is a common cause of metabolic encephalopathy, mainly related to hepatic cirrhosis. Numerous nonhepatic etiologies exist but they are infrequent and not well known, thus, leading to misdiagnosis and inadequate care. Electroencephalography has a proven diagnostic and prognostic role in comatose patients. Burst suppression is a preterminal pattern found in deep coma states and is rarely associated with metabolic causes.Case presentationWe report the case of an 81-year-old Caucasian man presenting with rapidly progressive somnolence and mutism. Soon after his arrival in our hospital, he developed profound coma. A comprehensive diagnostic workup was unremarkable except for admission electroencephalography showing diffuse slowing of cerebral activity with an intermittent pattern of burst suppression. He was admitted to our intensive care unit for supportive care where malnutrition-related hyperammonemia was diagnosed. His clinical course was spontaneously favorable and follow-up electroencephalography demonstrated normal cerebral activity.ConclusionsNonhepatic hyperammonemia is a rare and potentially reversible cause of encephalopathy. Ammonia level measurement should be part of the diagnostic workup in patients with unexplained coma, particularly in the setting of nutritional deficiencies or nutritional supply. Detection of diffuse and nonspecific mild to moderate slowing of cerebral activity (theta-delta ranges) on electroencephalography is common. In contrast, to the best of our knowledge, burst suppression has never been described in association with hyperammonemia.

Metabolic encephalopathy secondary to diabetic ketoacidosis: a case report

IntroductionMetabolic encephalopathy is a rare but potentially devastating complication of diabetic ketoacidosis (DKA). This case highlights the dramatic cognitive decline of a young man due to metabolic encephalopathy complicating DKA. The aims of this case report are to highlight metabolic encephalopathy as a complication of DKA and to explore the current research in diabetic related brain injury. The importance of investigation and treatment of reversible causes of encephalopathy is also demonstrated.Case presentationA 35-year-old man with a background of type 1 diabetes mellitus (T1DM) and relapsing remitting multiple sclerosis (RRMS) presented to the emergency department (ED) in a confused and agitated state. Prior to admission he worked as a caretaker in a school, smoked ten cigarettes per day, took excess alcohol and smoked cannabis twice per week.Following initial investigations, he was found to be in DKA. Despite timely and appropriate management his neurological symptoms and behavioural disturbance persisted. Neuroimaging revealed temporal lobe abnormalities consistent with an encephalopathic process. The patient underwent extensive investigation looking for evidence of autoimmune, infective, metabolic, toxic and paraneoplastic encephalopathy, with no obvious cause demonstrated.Due to persistent radiological abnormalities a temporal lobe biopsy was performed which showed marked astrocytic gliosis without evidence of vasculitis, inflammation, infarction or neoplasia. A diagnosis of metabolic encephalopathy secondary to DKA was reached. The patient’s cognitive function remained impaired up to 18 months post presentation and he ultimately required residential care.ConclusionsMetabolic encephalopathy has been associated with acute insults such as DKA, but importantly, the risk of cerebral injury is also related to chronic hyperglycaemia. Mechanisms of cerebral injury in diabetes mellitus continue to be investigated. DKA poses a serious and significant neurological risk to patients with diabetes mellitus. To our knowledge this is the second case report describing this acute complication.

EEG Findings in Posterior Reversible Encephalopathy Syndrome.

Introduction. Posterior reversible encephalopathy syndrome (PRES) is a relatively common cause of encephalopathy in the hospital setting, and the EEG findings have not been well described. The purpose of this study was to review the EEG findings in a series of patients with PRES. Methods. We retrospectively reviewed our electronic medical record database to identify patients who received a diagnosis of PRES at Tampa General Hospital from January 2016 to October 2017. The diagnosis of PRES was suspected on clinical presentation and confirmed by magnetic resonance imaging. We selected patients with PRES who had received at least 1 EEG. EEGs were interpreted by 2 board-certified electroencephalographers. Results. From January 2016 to October 2017, 19 patients were diagnosed with PRES at Tampa General Hospital. Of those, 10 received at least 1 EEG. Four patients were male, 6 were female. The ages ranged from 21 to 87 (mean was 47). The patients had the following clinical presentations: 5 with encephalopathy, 8 with seizures, 2 with vision changes, and 3 with headache (some patients had more than 1 symptom). EEGs findings were as follows: 3 were normal; 3 showed intermittent generalized slowing; 2 showed continuous generalized slowing; 3 showed background slowing; 1 showed background suppression; 1 showed generalized rhythmic delta activity (GRDA); 1 showed GRDA, plus spike/sharp-wave discharges; 1 showed generalized periodic discharges. The etiologies were as follows: 9 from hypertension, 1 secondary to eclampsia, 3 due to posttransplant immunosuppression, and 1 patient was undergoing chemotherapy (some were multifactorial). Conclusion. EEG findings in PRES are diverse, with no specific or even predominant pattern, based on this small sample size.

Hashimoto's Encephalopathy and Seizure Disorders.

Hashimoto's encephalopathy (HE) is a rare, clinically heterogeneous condition associated with positive thyroid autoantibodies. It is increasingly recognized as an important and treatable cause of autoimmune encephalopathy. Thyroid-associated antibodies such as thyroperoxidase (TPO) antibody, thyroglobulin (TG) antibody, and thyrotropin receptor (TR) antibody were found in HE patients with seizure disorders. Although antithyroid antibodies are required for the diagnosis of HE, their role in the pathogenesis of HE remains uncertain. Instead of playing a key role in the pathophysiology processes of HE, it is suggested that thyroid-associated antibodies are hallmarks of HE. Seizure disorders were found in approximately two-thirds of HE patients, and common anticonvulsant therapy alone is usually ineffective. Some patients did not respond to any antiepileptic drugs. The use of immunotherapy can effectively control seizure disorders. Electroencephalography and imaging findings are not specific to HE patients and can also be seen in other causes of encephalopathies. However, the prognosis in the majority of patients with HE was usually good if it is diagnosed and treated correctly.

Encefalopatía por cefepima en paciente renal: una reacción adversa a medicamento

La reacción adversa a medicamentos es un problema importante para la salud de pacientes en manejo hospitalario, encontrado de manera regular durante la práctica médica y cuya asociación no identificamos de forma oportuna, pero que aumentan la morbimortalidad y la estancia hospitalaria; en este artículo presentamos el caso clínico de un paciente con encefalopatía severa asociada al uso de cefepima, el deterioro clínico evidenciado durante su proceso de hospitalización y el razonamiento a través del cual se identificó una reacción adversa tipo A como causa de encefalopatía.

EEG in WNV Neuroinvasive Disease.

Neuroinvasive West Nile virus (WNV) is rare, occurring in less than 1% of those infected, and may manifest as meningitis, encephalitis, and/or acute flaccid paralysis. Patients may present initially with nonspecific symptoms including fevers. Although rare, neuroinvasive WNV is associated with significant morbidity and mortality. The mainstay of treatment is supportive care. Electroencephalography (EEG) allows for identification of nonconvulsive status epilepticus and other epileptiform and nonepileptiform patterns suggestive of underlying cognitive dysfunction. Our aim was to describe specific EEG patterns observed in WNV neuroinvasive disease. A retrospective chart review was conducted. West Nile virus was confirmed with serum and/or cerebrospinal fluid markers. Patients with a history of abnormal EEG were excluded. Electroencephalography reports were classified into categories based on the presence of epileptiform activity, focal slowing, generalized periodic discharges with triphasic morphology, and frontally predominant generalized rhythmic delta activity. In our cohort of 34 patients, 60% of focal EEG abnormalities were anterior-predominant, seen as epileptiform discharges, focal slowing, or frontally predominant generalized rhythmic delta activity. Nonepileptiform EEG patterns included nonspecific slowing and generalized periodic discharges with triphasic morphology. Two patients had electrographic seizures, one arising from the frontocentral head region. EEGs are important in the evaluation of WNV infection to rule out seizures or alternative causes of encephalopathy, and because of the risk of nonconvulsive seizures or status epilepticus in encephalitis. Although an anterior predominance of EEG abnormalities was seen in our cohort, this most likely is more correlative to encephalopathy than WNV itself. Although a specific correlative EEG pattern may not accompany all cases of WNV neuroinvasive disease, WNV should be considered as a possible etiology in patients presenting with an encephalitic or meningitic syndrome in the presence of abnormal EEG findings including encephalopathic patterns, particularly those with anterior predominant EEG changes.

To what extent can clinical characteristics be used to distinguish encephalitis from encephalopathy of other causes? Results from a prospective observational study

BackgroundRecognizing patients with encephalitis may be challenging. The cardinal symptom, encephalopathy, has a wide array of differential diagnoses. In this prospective study we aimed to explore the etiology of encephalitis and to assess the diagnostic accuracy of symptoms and clinical findings in patients with encephalitis in an encephalopathic population.MethodsPatients with acute onset of encephalopathy (n = 136) were prospectively enrolled from January 2014–December 2015 at Oslo University Hospital, Ullevaal. Clinical and biochemical characteristics of patients who met the case definition of encephalitis were compared to patients with encephalopathy of other causes.ResultsAmong 136 patients with encephalopathy, 19 (14%) met the case-definition of encephalitis. For 117 patients other causes of encephalopathy were found, infection outside the CNS was the most common differential diagnosis. Etiology of encephalitis was confirmed in 53% (4 bacterial, 4 viral, 1 parasitic, and 1 autoimmune). Personality change, nausea, fever, focal neurology, recent travel history, and low inflammation markers were significantly more abundant in patients with encephalitis, but the diagnostic accuracy for individual parameters were low (area under the curve (AUC) < 0.7). The combination of fever (OR = 6.6, 95% CI, 1.6–28), nausea (OR = 8.9, 95% CI, 1.7–46) and a normal level of ESR (erythrocyte sedimentation rate < 17 mm/hr, OR = 6.9, 95% CI, 1.5–33) was significant in multivariate analysis with an AUC (area under the curve) of 0.85 (95% CI, 0.76–0.94). Moderately increased pleocytosis in CSF (5-100 × 106/L) further increased the diagnostic accuracy of this combination, AUC 0.90 (95% CI, 0.81–0.98).ConclusionsThere is a wide diversity in differential diagnoses in patients with encephalopathy, and no single symptom or finding can be used to predict encephalitis with high accuracy in this group. The combination of fever, nausea and a low ESR in an encephalopathic population, increased the diagnostic accuracy of encephalitis compared to solitary parameters. The triad could be a useful clinical tool for early diagnosis of encephalitis, and these patients should be considered for further diagnostics such as lumbar puncture (LP).

Transcranial Ultrasound in Comparison to MRI in Evaluation of Hypoxic Ischemic Injury in Neonates

Background: Hypoxic-ischemic injury is the most common cause of encephalopathy in newborns. Objectives: The goal of our study was to demonstrate the role of transcranial ultrasound (TCUS) compared to MRI in assessment of neonatal encephalopathy. Patients and methods: Consecutive thirty sex neonates with hypoxic-ischemic encephalopathy (HIE) were included. All cases had undergone MR imaging as well as transcranial ultrasound study of the brain. The study was conducted between May 2015 and September 2017. They were collected from the Neonatology Intensive Care Unit at Elsayed Galal and El-Demerdash University Hospitals. Results: Our study found that stages I and II showed mild to moderate HIE presented with peripheral pattern and white matter injuries while stage III revealed severe HIE presented with central pattern of injury (BGT). In addition, our study reported that all patients with stage III of HIE showed severe central pattern on MRI. Conclusion: MRI imaging is considered a sensitive technique in detecting different MR patterns of encephalopathy in newborns. MRI placed other imaging modalities in diagnostic assessment and early predictor of future development of neurological abnormalities in neonates with encephalopathy.

Current knowledge on Hashimoto's encephalopathy: a literature review.

Hashimoto's encephalopathy is a rare disease, with a reported prevalence of 2.1 per 100 000. Clinical manifestations include confusion, decreased state of consciousness, cognitive deficit, seizures, myoclonus, ataxia, and focal neurological deficits. Due to the wide variety of signs and symptoms, clinical diagnostic suspicion is essential. Diagnosis is based on three pillars: the presence of neurological clinical manifestations after ruling out other causes of encephalopathy. 2) Presence of increased antithyroid antibodies. 3) Significant clinical improvement after the administration of immunomodulation. The treatment of Hashimoto's encephalopathy pursues two objectives: to control the autoimmune process and to control the complications of the disease. Although in most cases recovery is complete with treatment, the risk of relapse can range from 12.5 to 40% in follow-ups to 2 years.

Hyperammonemic Encephalopathy: A Rare Presentation of Valproic Acid Toxicity in the Absence of Liver Impairment

Hyperammonemia can occur due to a broad range of etiologies and is commonly found in the setting of liver impairment. However, the absence of liver pathology presents a diagnostic challenge. Valproic acid (Valproate) toxicity has been associated with hyperammonemic encephalopathy, but it is a rare occurrence and can be overlooked. Case 1) A 28-year-old woman presented with 3-days of altered mentation, elevated ammonia level and normal liver function. The patient's mentation improved with Lactulose therapy and was subsequently discharged. She had a readmission shortly thereafter with the same presentation. Patient was on Valproate for epilepsy treatment. Valproate levels were elevated, but discontinuing Valproate removed the inciting cause of encephalopathy. She improved with no further hospitalizations. Case 2) A 57-year-old woman presented with 2-hours of altered mentation after intentional overdose. Patient had elevated ammonia and Valproate levels without hepatic impairment. Discontinuation of Valproate and L-carnitine therapy improved patient's encephalopathy. These cases represent a rare complication of Valproate use. Its effect on urea cycle is thought to be one possible explanation for hyperammonemia. Management includes discontinuation of the drug and symptomatic treatment with Lactulose. We also highlight L-carnitine as proposed treatment for such toxicity. It is important for clinicians to be mindful of both hepatic and non-hepatic causes of hyperammonemia. These patients remind us to act with benevolence, utilizing a stepwise approach to diagnosis and treatment in order to improve patient outcomes. In retrospect, in our first case such consideration would have prompted earlier discontinuation of Valproate, potentially avoiding hospital readmission.

Posttransplant autoimmune encephalitis.

The causes of encephalopathy in the posttransplant setting are diverse and include medication toxicity (e.g., posterior reversible encephalopathy syndrome), infections (e.g., human herpes virus type 6 [HHV-6]), and neoplastic disease (posttransplant lymphoproliferative disorder). Autoimmune etiologies are not well recognized in this setting, although a few cases are described.1–5 Herein, we report 3 patients with posttransplant autoimmune encephalitis (AE).

Predictors of neural-specific autoantibodies and immunotherapy response in patients with cognitive dysfunction

Recognition of autoimmunity as a cause of encephalopathy has increased. Recent studies have validated the use of Antibody-Prevalence-in-Epilepsy (APE) and Responsive-to-immunotherapy-in-Epilepsy (RITE) scores in the evaluation and management of autoimmune-epilepsy. We aim to assess the utility of these models for patients with cognitive dysfunction. Among the evaluated patients, 17% had antibodies universally associated with autoimmune-encephalopathy. NMDA-R-IgG and LGI1-IgG were the most common antibody specificities. Antibody-Prevalence-in-Epilepsy-and-Encephalopathy (APE2) score ≥ 4 was 99% sensitive and 93% specific for neural-specific-antibodies. Responsive-to-immunotherapy-in-Epilepsy-and-Encephalopathy (RITE2) score ≥ 7 had 96% sensitivity and 86% specificity for favorable initial immunotherapy response. Application of these models may optimize autoantibody evaluations and immunotherapeutic trials.

S91. EEG findings in Posterior Reversible Encephalopathy Syndrome (PRES)

Posterior Reversible Encephalopathy Syndrome (PRES) is a relatively common cause of encephalopathy in the hospital setting, and the EEG findings have not been well described. The purpose of this study was to review the EEG findings in a series of patients with PRES. We retrospectively reviewed the EEGs of patients who received a diagnosis of PRES at Tampa General Hospital from January 2016 to October 2017. We reviewed the clinical presentation, MRI findings and EEG. From January 2016 to October 2017, 19 patients were diagnosed with PRES at Tampa General Hospital. Of those, 10 received at least one EEG. Four patients were male, 6 were female. The ages ranged from 21 to 87 (mean was 47). The patients had the following clinical presentations: 4 with encephalopathy (“mental status changes”), 8 with seizures, 1 with status epilepticus, 2 with vision changes, and 1 with headache (some patients had more than one symptoms). EEGs findings were as follows: 2 were normal; 2 showed intermittent generalized slowing; 3 showed continuous generalized slowing; 2 showed background slowing; 1 showed background suppression; 1 showed generalized rhythmic delta activity (GRDA); 1 showed GRDA, plus spike/sharp-wave discharges; 1 showed excessive beta activity; 1 showed lateralized periodic discharges; 1 showed generalized periodic discharges. The etiologies were as follows: 9 from hypertension, 1 secondary to eclampsia, and 3 due to tacrolimus (some were multifactorial). MRI supported the diagnosis of PRES and showed the following: 4 had bilateral parietal and occipital lobe T2 hyperintensities, 2 had bilateral occipital T2 hyperintensities, 1 had right occipital T2 hyperintensity, 1 had bilateral cerebellum and occipital lobe T2 hyperintensities, 1 had bilateral parietal, temporal, and left frontal T2 hyperintensities, and 1 had bilateral parietal, frontal, and occipital T2 hyperintensities. EEG findings in PRES are diverse, with no specific or even predominant pattern, based on this small sample size.

A novel assessment and treatment approach to patients with Hashimoto's encephalopathy.

SummaryHashimoto’s encephalopathy (HE) is rarely reported with only a few hundred cases published. Diagnosis is made in patients with an appropriate clinical picture and high antithyroperoxidase (anti-TPO) antibodies after infectious, toxic and metabolic causes of encephalopathy have been excluded. There is little objective data on the neurocognitive impairment in patients with HE and their improvement with treatment. We present the case of a 28-year-old woman with HE. Approach to management was novel as objective neuropsychological assessment was used to assess her clinical condition and response to treatment. Intravenous immunoglobulin (IVIg) as the first-line treatment instead of steroids. She responded well. The case illustrates that a different approach is required for the diagnosis and treatment of HE. A new diagnostic criteria is proposed that includes neurocognitive assessment, serum and CSF antibodies, an abnormal EEG and exclusion of other causes of encephalopathy. Furthermore, treatment should be tailored to the patient.Learning points:Neurocognitive assessment should be carried out to assess the extent of brain involvement in suspected Hashimoto’s encephalopathy pre- and post- treatment.Treatment of Hashimoto’s encephalopathy should be tailored to the patient.Unifying diagnostic criteria for Hashimoto’s encephalopathy must be established.

Why and when to measure ammonemia in cirrhosis?

Hyperammonemia plays a key role in the pathophysiology of hepatic encephalopathy (HE) and most HE treatments are ammonia-lowering drugs. However, the usefulness of measuring ammonemia in routine practice remains controversial and not recommended systematically even when neurological symptoms are present. First, ammonemia measurement should be carefully performed in order to avoid a falsely elevated result. When performed, a normal ammonemia in a cirrhotic patient with neurological symptoms should lead to reconsider the diagnosis of HE. Indeed, literature data show that most cirrhotic patients with HE have an elevated ammonemia, which is however individually poorly correlated with the severity of symptoms. Nevertheless, elevated ammonemia seems to be a factor of bad prognosis in cirrhosis. A decrease in ammonemia after treatments is well proven but it is not determined whether it is associated with clinical efficacy. Repeated measurements could be useful in this context, especially in non-responders, to help differentiating other causes of encephalopathy, such as drug induced. In acute liver failure, the prognostic value of hyperammonemia is well described and could help an early recognition the most severe forms of this disease. We will also discuss how integrating ammonemia into the diagnostic work-up of liver failure and/or encephalopathy. Ammonemia is also essential to diagnose urea cycle disorders or drug toxicity that both need specific interventions.

Paraneoplastic Encephalopathy in a Patient With Metastatic Lung Cancer: A Case Study

Paraneoplastic Encephalopathy in a Patient With Metastatic Lung Cancer: A Case Study

The ketogenic diet is effective for refractory epilepsy associated with acquired structural epileptic encephalopathy.

Ketogenic diet therapies have proven efficacy for refractory epilepsy. There are many reports of their use in the genetic developmental and epileptic encephalopathies; however, little attention has been paid as to whether the diet is also effective in individuals with an acquired structural aetiology. We observed remarkable efficacy of the diet in two patients with hypoxic-ischaemic encephalopathy. We then analysed our cases with refractory structural epilepsies of acquired origin to characterize their response to the ketogenic diet. The classical ketogenic diet was implemented with dietary ratios of 3:1 to 4.4:1. Seizure frequency at 1month, 3months, 6months, 1year, and 2years was ascertained. A responder was defined as greater than 50% seizure reduction compared to baseline. Seven of the nine patients were responders at 3months. Somewhat surprisingly we found that the ketogenic diet was effective in patients with a developmental and epileptic encephalopathy due to an acquired structural aetiology. This cohort may not be routinely considered for the ketogenic diet because of their structural and acquired, rather than genetic, basis. The ketogenic diet should be considered early in the management of patients with acquired structural encephalopathies as it can improve seizure control with the potential to improve developmental outcome. The ketogenic diet was effective in children with epilepsy associated with an acquired structural aetiology.

Funduscopy in Cerebral Malaria Diagnosis: An International Survey of Practice Patterns.

Cerebral malaria (CM) is a significant cause of mortality and morbidity in sub-Saharan Africa, particularly among young children. Malarial retinopathy is the most specific clinical finding in CM, and fundus examination could help clinicians distinguish CM from other causes of encephalopathy in resource-poor areas. To assess clinician knowledge, practice patterns, and barriers to the use of funduscopy in the diagnosis of CM, we designed a descriptive multinational survey of clinicians in malaria endemic areas. Results of this survey showed that 19% of respondents were not aware of the utility of eye examinations for malarial retinopathy, and almost half (49%) never or almost never examine the eyes in cases of suspected CM. Educating clinicians about malarial retinopathy could be important in improving diagnostic specificity for CM.

Unusual cause of encephalopathy after brain surgery

For patients who have had a recent neurosurgical procedure, a visit to the emergency department for encephalopathy may automatically prompt a neurosurgical consult. We present a case of a patient...