What are the different types of encephalopathy?

Types of Encephalopathy

Encephalopathy is classified into distinct categories based on underlying etiology: hepatic encephalopathy (Types A, B, and C), toxic-metabolic encephalopathy, septic encephalopathy, and chemotherapy-induced encephalopathy, each requiring different diagnostic and management approaches.

Hepatic Encephalopathy Classification

The European Association for the Study of the Liver and American Association for the Study of Liver Diseases provide the most comprehensive classification system for hepatic encephalopathy 1:

By Underlying Disease

• Type A: Results from acute liver failure, with distinct features including risk of increased intracranial pressure and cerebral herniation 1
• Type B: Results predominantly from portosystemic bypass or shunting without intrinsic liver disease, often due to congenital or acquired vascular abnormalities 1, 2
• Type C: Results from cirrhosis and portal hypertension, with clinical manifestations similar to Type B 1

By Severity of Manifestations

Hepatic encephalopathy is graded from minimal (covert) to coma 1:

• Minimal/Covert HE: Cognitive impairment detectable only through psychometric testing, with no clinical evidence of mental change 1
• Grade 1 (Covert): Shortened attention span, altered sleep rhythm, mild cognitive or behavioral changes without disorientation 1
• Grade 2 (Overt): Disorientation in time, inappropriate behavior, lethargy, asterixis present 1
• Grade 3 (Overt): Disorientation in both time and space, confusion, somnolence 1
• Grade 4 (Overt): Coma, no response to painful stimuli 1

By Time Course

• Episodic HE: Discrete episodes of encephalopathy 1
• Recurrent HE: Bouts occurring with intervals of 6 months or less 1
• Persistent HE: Continuous behavioral alterations interspersed with relapses of overt HE 1

By Precipitating Factors

• Precipitated: Triggered by identifiable factors including gastrointestinal bleeding, infection, constipation, electrolyte disturbances, or medications 1
• Non-precipitated: Occurring spontaneously without clear triggers 1

Chemotherapy-Induced Encephalopathy

The ESMO-EONS-EANO guidelines describe several distinct types of cancer treatment-related encephalopathy 1:

Acute Encephalopathy

• Presents with changes in consciousness (impaired attention to delirium with psychotic symptoms), decreased consciousness (drowsiness to coma), and changes in affect (apathy, anxiety, agitation) 1
• May include focal signs like paresis, speech disorders, seizures, and cranial nerve dysfunctions 1
• Associated with classic chemotherapeutics and may be facilitated by concomitant sepsis, pre-existing leukoencephalopathy, and metabolic changes 1

Posterior Reversible Encephalopathy Syndrome (PRES)

• Presents with acute neurological deficits including altered consciousness, visual disturbances, blindness, headaches, and seizures 1
• Results from disruption of blood-brain barrier due to endothelial injury from abrupt blood pressure changes, leading to vasogenic edema 1
• T2-weighted MRI shows hyperintensities involving bilateral parietal-occipital lobes, predominantly in white matter 1
• Risk factors include pre-existing hypertension, renal impairment, autoimmune diseases, high-dose chemotherapy, and immunosuppression 1

Progressive Multifocal Leukoencephalopathy (PML)

• A devastating demyelinating disease of the CNS occurring almost exclusively in immunocompromised patients (mainly CD4 or CD8 immunosuppression) 1
• Prevalence estimated at 0.07% among patients with hematological malignancies 1
• Diagnosed by subacute neurological symptoms, typical MRI findings, and detection of JC virus DNA in CSF 1

Septic Encephalopathy

Septic encephalopathy is the most frequently encountered infection-associated encephalopathy, found in 50-70% of septic patients 1, 3:

• Clinical presentation: Characterized by diffuse brain dysfunction secondary to infection elsewhere in the body without overt CNS infection 3
• Progression pattern: Ranges from slowing of mentation and impaired attention, to delirium, then coma 1, 3
• Diagnosis: Remains a diagnosis of exclusion after ruling out other causes of altered mentation in a febrile, critically ill patient 3
• Neurological examination: Findings are usually symmetrical; asterixis or multifocal myoclonus (typical of metabolic encephalopathies) is rare 1

Toxic-Metabolic Encephalopathy

Toxic-metabolic encephalopathy results from acute cerebral dysfunction due to various metabolic disturbances including medications or illicit drugs 4:

• Can lead to altered consciousness ranging from delirium to coma 4
• May require intensive care and invasive mechanical ventilation 4
• Has excellent prognosis if etiology is rapidly identified and treated adequately 4

Critical Differential Diagnoses

The European Association for the Study of the Liver emphasizes that differential diagnosis must consider 1:

• Metabolic disorders: Diabetic conditions (hypoglycemia, ketoacidosis, hyperosmolar states), electrolyte disorders (hyponatremia, hypercalcemia) 1
• Substance-related: Alcohol (intoxication, withdrawal, Wernicke encephalopathy), drugs (benzodiazepines, neuroleptics, opioids) 1
• Neurological: Neuroinfections, non-convulsive status epilepticus (found in up to 8% of comatose patients), intracranial bleeding, stroke 1
• Other: Psychiatric disorders, severe medical stress, dementia, brain lesions, obstructive sleep apnea 1

Important Clinical Caveats

• Hyponatremia and sepsis can both produce encephalopathy independently and precipitate hepatic encephalopathy through pathophysiological interactions 1
• In end-stage liver disease, uremic encephalopathy and hepatic encephalopathy may overlap 1
• Non-convulsive status epilepticus can mimic or result from acute encephalitis, requiring EEG for diagnosis 1
• Septic encephalopathy may present in early stages of sepsis, even before diagnostic criteria for sepsis are met 3