Clinical Manifestations of Encephalopathy
Encephalopathy presents as global cerebral dysfunction characterized by altered consciousness, cognitive changes, and behavioral disturbances, ranging from subtle attention deficits to deep coma, with or without focal neurological signs. 1
Core Clinical Features
Consciousness and Cognitive Changes
- Altered level of consciousness progresses through a spectrum from impaired attention and confusion to delirium with psychotic symptoms, drowsiness, and ultimately coma 1
- Cognitive dysfunction manifests as attention deficits, impaired working memory, slowed psychomotor speed, and visuospatial dysfunction—often detectable only through formal neuropsychological testing in early stages 2
- Disorientation (76% of cases) represents a cardinal feature, particularly in infectious encephalitis 1
- Fluctuating mental status with waxing and waning confusion is typical, especially in metabolic and septic encephalopathy 3, 4
Behavioral and Personality Changes
- Personality alterations including apathy, anxiety, agitation, irritability, and disinhibition may be reported by family members before the patient recognizes problems 1, 2
- Behavioral changes (41% of cases) and speech disturbances (59% of cases) are common presenting features 1
- Sleep-wake cycle disturbances with excessive daytime sleepiness are frequent, though complete sleep-wake reversal is less common 2
Motor and Neurological Manifestations
Movement Abnormalities
- Asterixis (flapping tremor) is a hallmark finding in early to middle stages, elicited by hyperextending the wrists with fingers separated or having patients rhythmically squeeze the examiner's fingers; it can also be checked in feet, legs, arms, tongue, and eyelids 5, 2
- Parkinsonian features including hypomimia, muscular rigidity, bradykinesia, hypokinesia, and monotonous/slow speech are common 2
- Decreased motor activity or rarely increased motor activity accompanies the altered mental status 3
Focal Neurological Signs
- Focal deficits may include paresis, speech disorders, and cranial nerve dysfunctions despite the global nature of encephalopathy 1
- Seizures occur in approximately one-third of patients, presenting as generalized tonic-clonic seizures, myoclonus, or status myoclonus 1, 2
Associated Systemic Features
Fever and Systemic Illness
- Fever is present in 91% of infectious encephalitis cases on admission, with most others having a history of recent febrile illness 1
- Headache, nausea, and vomiting are classical accompanying features in infectious etiologies 1
Important Clinical Distinctions
Features Suggesting Non-Encephalitic Encephalopathy
The differential diagnosis should consider metabolic, toxic, autoimmune causes, or sepsis outside the CNS, especially when these features are present 1:
- Past history of similar episodes
- Symmetrical neurological findings
- Myoclonus
- Clinical signs of liver failure
- Lack of fever
- Acidosis or alkalosis
Temporal Patterns
- Acute presentation (hours to days) with fever, altered behavior, personality changes, consciousness alterations, new-onset seizures, or focal neurological signs should raise suspicion for encephalitis or CNS infection 1
- Subacute presentation (weeks to months) should trigger investigation for autoimmune, paraneoplastic, or metabolic etiologies 1
Severity Grading
Encephalopathy severity ranges from Grade I (behavioral changes with minimal consciousness alteration) to Grade IV (complete unresponsiveness to pain), with asterixis typically appearing at Grade I-II and disappearing as patients progress to stupor and coma (Grade III-IV). 5, 2
Critical Pitfalls
- Asterixis is not pathognomonic for hepatic encephalopathy and occurs in other metabolic encephalopathies including uremia, hypercapnia, and medication toxicity (specificity 45%) 5
- A normal Glasgow Coma Score at presentation can occur, as it is a crude tool for detecting subtle behavioral changes 1
- Symptoms may precede clinical signs of sepsis in sepsis-associated encephalopathy, making early recognition challenging 4, 6
- Lethargy, cognitive impairment, altered memory and mental processing, and disturbed sleep-wake cycles are typically present but may be subtle initially 3