Uremic encephalopathy is a complication of renal failure leading to cerebral dysfunction. It is characterized by nausea, vomiting, lethargy and disorientation in the initial stages progressing to delirium, seizures and later coma, if untreated. Diagnosis is based on clinical signs, cognitive tests, renal function tests, serum biochemistry, and imaging studies of the brain.
Presentation
Uremic encephalopathy (UE) is an acquired metabolic complication of renal failure with accumulation of toxic metabolites which cross the blood brain barrier to cause cerebral dysfunction. It manifests in the form of acute or subacute neurological features which are usually reversible [1] [2] [3] [4]. Initial symptoms of UE are nausea, vomiting, loss of appetite, drowsiness, inability to concentrate emotional lability, irritability, confusion progressing, if untreated, to seizures, delirium, myoclonus, asterixis and coma [5].
Once treatment of renal dysfunction is instituted patients may present with impaired cognition, generalized asthenia, and peripheral neuropathy [6]. Renal dialysis in chronic renal failure or end-stage renal disease is associated with dysequilibrium and dementia. Dialysis-associated disequilibrium is characterized by nausea, muscle cramps, altered sensorium, and seizures while dialysis-associated dementia is a progressive condition with increased incidence of mortality seen in patients on long-term hemodialysis. Dialysis encephalopathy can be either sporadic, epidemic or associated with pediatric renal disease [6].
Entire Body System
- Fatigue
[…] uremic encephalopathy cerebral symptoms seen in patients with uremia, including lethargy, fatigue, inattentiveness, irritability, confusion, sensory disturbances, and sometimes seizures. Medical dictionary. 2011. [medicine.academic.ru]
It develops in patients with acute or chronic renal failure, usually when creatinine clearance (CrCl) levels fall and remain below 15 mL/min. [1, 2, 3, 4] Manifestations of this syndrome vary from mild symptoms (eg, lassitude, fatigue) to severe symptoms [thehealthscience.com]
[…] diseases classified elsewhere G91.8 Other hydrocephalus G91.9 Hydrocephalus, unspecified G92 Toxic encephalopathy G93 Other disorders of brain G93.1 Anoxic brain damage, not elsewhere classified G93.2 Benign intracranial hypertension G93.3 Postviral fatigue [icd10data.com]
Patients with severe cases, however, may be symptomatic and present with listlessness, confusion, fatigue, anorexia, nausea, vomiting, weight gain, or edema. 15 Patients can also present with oliguria (urine output less than 400 mL per day), anuria (urine [aafp.org]
Early symptoms may be subtle, and comprise fatigue, apathy, clumsiness, and impaired concentration. [jnnp.bmj.com]
Neurologic
- Stupor
Drowsiness Diminished ability to concentrate Slowed cognitive functions More severe signs and symptoms of uremic encephalopathy include the following: Vomiting Emotional volatility Decreased cognitive function Disorientation Confusion Bizarre behavior Stupor [emedicine.medscape.com]
These symptoms are followed by shortened attention span and muscular incoordination, asterixis, and lethargy, progressing to stupor and coma. Multiple episodes of PSE are not uncommon. [alzheimer-europe.org]
Clinical Indicators: Showing some of the following signs and symptoms: Altered Mental Status from baseline Coma Confusion Delirium Disorientation Lethargic Psychosis Restlessness Stupor Patient may become more alert when underlying condition is treated [forums.acdis.org]
Further reading [ edit ] The Diagnosis of Stupor and Coma by Plum and Posner, ISBN 0-19-513898-8, remains one of the best detailed observational references to the condition. [en.wikipedia.org]
Diagnosis The diagnosis of encephalopathy depends on the presence of acute or chronic liver disease; altered mental state such as confusion, stupor, or coma; symptoms of central nervous system damage; and abnormal wave patterns on an encephalogram. [encyclopedia.com]
- Altered Mental Status
mental status (confusion) Cranial nerve signs (nystagmus) Papilledema Hyperreflexia, clonus, asterixis Altered gait Stupor Coma (occurs only if uremia remains untreated and progresses) Author Specialty Editor Board Francisco Talavera, PharmD, PhD Adjunct [emedicine.medscape.com]
Clinical Indicators: Showing some of the following signs and symptoms: Altered Mental Status from baseline Coma Confusion Delirium Disorientation Lethargic Psychosis Restlessness Stupor Patient may become more alert when underlying condition is treated [forums.acdis.org]
It causes altered mental status due to involvement of cerebral cortex termed as uremic encephalopathy. Acute hyperkinetic or hypokinetic extrapyramidal disorder in patients with uremia is a very rare syndrome. [ruralneuropractice.com]
Symptoms and course Fulminant hepatic failure results from severe inflammatory or necrotic liver disease of rapid onset and progressive neurological signs from altered mental status, stupor and coma, often within hours or days. [alzheimer-europe.org]
Hypotension ( low blood pressure ) due to many factors (for example, bleeding, major infection, or blood pressure medications) may result in encephalopathy with symptoms of fainting, weakness, and altered mental status. [emedicinehealth.com]
- Cognitive Impairment
Almost 14% demonstrated mild cognitive impairment, 36.1% demonstrated moderate cognitive impairment, and 37.3% demonstrated severe cognitive impairment 1. [radiopaedia.org]
Most nephrologists consider cognitive impairment to be a major indication for the initiation of renal replacement therapy with dialysis with or without subsequent transplantation. [ncbi.nlm.nih.gov]
[…] by Kurt Jellinger General outline Among metabolic and toxic disorders leading to cognitive impairment, both acute and chronic hepatic and renal failure may have adverse effects on the CNS with serious repercussions for cerebral function causing both neurological [alzheimer-europe.org]
The patient may be generally obtunded, cognitively impaired, and ataxic, with marked day to day fluctuations, or may display focal signs such as hemiparesis. [jnnp.bmj.com]
Workup
Workup in a patient presenting with confusion, nystagmus, hyperreflexia, clonus, asterixis and coma should include a thorough history and neurological examination. An ophthalmic examination may reveal papilledema. UE can be evaluated with many cognitive tests to measure psychomotor speed, short-term recognition and ability to make simple decisions. Laboratory tests are likely to show anemia (due to chronic renal disease), leukocytosis (if there is an underlying infection), with renal function tests [7] showing severely elevated blood urea nitrogen and serum creatinine levels. Serum electrolyte and glucose levels should be ordered to evaluate sodium and blood glucose levels to exclude electrolyte abnormalities, hyperglycemia, and hyperosmolar syndromes. Serum calcium, magnesium, phosphate and parathyroid hormone levels should be checked to exclude other causes of encephalopathy. A toxicology screen should also be performed. An electroencephalogram (EEG) obtained in UE is likely to show a disorganized pattern with absent alpha waves and occasional theta and delta waves.
Imaging studies like magnetic resonance imaging (MRI) or computed tomography (CT) scan of the head are only indicated to exclude intracranial tumors and hematoma or hemorrhage. CT scan findings are not specific for UE but MRI will reveal an increase in signal intensity either in the cerebral cortex or in the basal ganglia. [8] [9]. This is also called the lentiform fork sign. Based on the MRI findings, UE has been classified into two varieties [10]:
- Cortical: involvement of the cortex is more common, develops in any patient with UE, is associated with posterior reversible encephalopathy syndrome (PRES) and not affected by diabetes mellitus [1] [3] [4]. MRI shows mainly vasogenic edema [11].
- Bilateral basal ganglia involvement: this is rare and usually seen in Asian patients with diabetes mellitus [1] [2] [3] [12] [13]. MRI shows vasogenic as well as cytotoxic edema [11].
EEG
- Triphasic Waves
The EEG background in uremic encephalopathy demonstrates bilateral, frontal-predominant slow activity, which may include diphasic and triphasic waves. 3 Photomyoclonic and photoconvulsive responses to photic stimulation may occur. 3 When seizures occur [epilepsy.com]
[…] to diffuse slow activity (theta and delta), triphasic waves with bifrontal predominance may be registered. [neurologyindia.com]
Other Pathologies
- Diffuse Encephalopathy
Key points • Chronic renal failure causes a variety of neurologic disorders affecting the central nervous system and the peripheral nervous system. • These complications include diffuse encephalopathy, seizures, stroke, movement disorders, sleep alterations [medlink.com]
Treatment
We reported a rare case of a patient with UE that had unusual imaging manifestations for whom timely diagnosis and treatment assured recovery. [ncbi.nlm.nih.gov]
The treatment for uremic encephalopathy is dialysis of some sort - peritoneal, etc. - or a kidney transplant, of course. But the latter is not the immediate treatment of choice. [health.stackexchange.com]
This case report a 59 years-old male in regular dialysis treatment with neurologic emergency characterized by neurologic signs as deep sopor the cause of which was uremic encephalopathy. [moh-it.pure.elsevier.com]
Prognosis
Seizures indicated a grave prognosis. Five of six patients with seizures died. In some patients, progressive uremic encephalopathy may develop without hemodialysis. [ncbi.nlm.nih.gov]
Consequently, the prognosis varies from patient to patient and ranges from complete recovery to a poor prognosis that often leads to permanent brain damage or death. [medicinenet.com]
Seizures indicated a grave prognosis. Five of six patients with seizures died. In some patients, progressive wemic encephalopathy may develop without hemodialysis. [neurology.org]
The combination of AKI and neurological disturbances signals a poor prognosis with RRT having little effect on neurological improvement or mortality. [icm-experimental.springeropen.com]
Neurological prognosis after cardiac arrest. N Engl Med 2009;361:605-11. [Figure 1] [Table 1], [Table 2] [neurologyindia.com]
Etiology
[…] of Altered Mental Status such as: Alzheimer’s disease Chemical dependencies CVA or TIA Hx Medications Parkinson’s disease Lewy body dementia Mood disorders Schizophrenia Seizure Hx Tumors Tests to determine etiology may include but are not limited to [forums.acdis.org]
Uremic encephalopathy may occur in a patient with acute kidney injury or chronic kidney failure of any etiology. One contributing factor to uremic encephalopathy may involve imbalances of neurotransmitter amino acids within the brain. [emedicine.medscape.com]
Another theory about the etiology of uremic encephalopathy suggests imbalances of neurotransmitter amino acids within the brain. [thehealthscience.com]
Definition, etiologies and mortalities. JAMA 1996;275:470-3. 49. Garcıa-Martınez R, Simon-Talero M, Cordoba J. Prognostic assessment in patients with hepatic encephalopathy. Dis Markers 2011;31:171-9. 50. Young B. [neurologyindia.com]
Etiology Animal studies have demonstrated impressive activations of biogenic amine expressing cell groups, stress-sensitive areas, and cell groups involved in the regulation of water and electrolyte homeostasis, as well as central autonomic cell groups [radiopaedia.org]
Epidemiology
Written by internationally renowned experts, this clinical reference offers helpful advice with the most recent information on the definition, epidemiology, pathophysiology, and clinical causes of acute kidney failure as a fundamental prerequisite for [books.google.com]
Epidemiology Frequency United StatesMost patients with a CrCl level less than 10% of normal probably develop some degree of encephalopathy; however, they may not be clearly symptomatic. [thehealthscience.com]
There are very few studies dealing with the epidemiology of the encephalopathic aspect of renal dysfunction. [radiopaedia.org]
Methods Statistics Trigonometry Medical & Nursing Anatomy Anesthesiology Audiology Bacteriology Biochemistry Bioethics Biomedical Science Cardiology Cardiovascular Childbirth Chiropractic Dentistry Dermatology Diagnostic Imaging Drugs Endocrinology Epidemiology [brainscape.com]
Epidemiology and healthcare utilization of neurogenic bladder patients in a US claims database. Neurourol Urodyn. 2011;30:395–401. View Article PubMed Google Scholar Copyright [bmcneurol.biomedcentral.com]
Pathophysiology
The pathophysiology of uremic encephalopathy is not well understood and multiple potential 'uremic toxins' have been evaluated. Of these, parathyroid hormone is the only substance to be clearly linked to clinical findings. [indiana.pure.elsevier.com]
The pathophysiology of uremic encephalopathy is not well understood and multiple potential "uremic toxins" have been evaluated. Of these, parathyroid hormone is the only substance to be clearly linked to clinical findings. [ncbi.nlm.nih.gov]
Prompt identification of uremia as the cause of encephalopathy is essential because symptoms are readily reversible following initiation of dialysis. [5, 6] Pathophysiology Uremic encephalopathy has a complex pathophysiology, and many toxins that accumulate [thehealthscience.com]
Although the detailed pathophysiology of UE is still unknown, the MRI and clinical changes observed in this patient suggest that diffuse edematous brain damage is one of the characteristic features of UE. [jstage.jst.go.jp]
Written by internationally renowned experts, this clinical reference offers helpful advice with the most recent information on the definition, epidemiology, pathophysiology, and clinical causes of acute kidney failure as a fundamental prerequisite for [books.google.com]
Prevention
Can encephalopathy be prevented? Many cases of encephalopathy can be prevented. The key to prevention is to stop or limit the chance of developing any of the multitudes of causes of encephalopathy. [medicinenet.com]
Collaborative Meta-Analysis of Randomised Trials of Antiplatelet Therapy for Prevention of Death, Myocardial Infarction, and Stroke in High Risk Patients. [books.google.es]
The treatments and prevention of each are discussed. © Thieme Medical Publishers. [ncbi.nlm.nih.gov]
Meta-analysis: low-dose dopamine increases urine output but does not prevent renal dysfunction or death. Ann Intern Med. 2005;142(7):510–524. 22. Ho KM, Sheridan DJ. Meta-analysis of frusemide to prevent or treat acute renal failure. [aafp.org]
Written by internationally renowned experts, this clinical reference offers helpful advice with the most recent information on the definition, epidemiology, pathophysiology, and clinical causes of acute kidney failure as a fundamental prerequisite for prevention [books.google.com]
References
- Wang HC, Cheng SJ. The syndrome of acute bilateral basal ganglia lesions in diabetic uremic patients. J Neurol. 2003;250:948–955.
- Kim TK, Seo SI, Kim JH, Lee NJ, Seol HY. Diffusion-weighted magnetic resonance imaging in the syndrome of acute bilateral basal ganglia lesions in diabetic uremia. Mov Disord. 2006;21:1267–1270.
- Wang HC, Brown P, Lees AJ. Acute movement disorders with bilateral basal ganglia lesions in uremia. Mov Disord. 1998;13:952–957.
- Prüss H, Siebert E, Masuhr F. Reversible cytotoxic brain edema and facial weakness in uremic encephalopathy. J Neurol. 2009;256:1372–1373.
- Chertow GM, Marsden PA et.al. Brenner and Rector's The Kidney. Saunders. ISBN:1416061932.
- Mahoney CA, Arieff AI. Uremic encephalopathies: clinical, biochemical and experimental features. Am J. Kidney Dis. 1982 Nov; 2(3):324 -36
- Yamamoto T, Satomura K, Okada S, et al. Risk factors for neurological complications in complete hemolytic uremic syndrome caused by Escherichia coli O157. Pediatr Int. 2009 Apr; 51(2):216-9.
- Schmidt M, Sitter T, Lederer SR, Held E, Schiffl H. Reversible MRI changes in a patient with uremic encephalopathy. J Nephrol. 2001 Sep-Oct;14(5):424-7.
- Kim DM, Lee IH, Song CJ. Uremic Encephalopathy: MR Imaging Findings and Clinical Correlation. AJNR Am J Neuroradiol. 2016 Sep; 37 (9):1604-9.
- Kang E, Jeon SJ, Choi S-S. Uremic encephalopathy with atypical magnetic resonance features on diffusion weighted images. Korean j Radiol. 2012 Nov-Dec; 13(6): 808-811
- Yoon CH, Seok JI, Lee DK, An GS. Bilateral basal ganglia and unilateral cortical involvement in a diabetic uremic patient. Clin Neurol Neurosurg. 2009;111:477–479.
- Raskin NH. Neurological complications of renal failure. In: Aminoff MJ, editor. Neurology and general medicine. New York: Churchill Livingstone; 1995. pp. 303–319.
- Raskin NH, Fishman RA. Neurologic disorders in renal failure (first of two parts) N Engl J Med. 1976;294:143–148.