From the Guidelines
The workup for encephalopathy should begin with a thorough history and physical examination, followed by basic laboratory tests and neuroimaging with CT or MRI of the brain, as well as an electroencephalogram (EEG) and lumbar puncture with cerebrospinal fluid analysis if infection or autoimmune causes are suspected. This approach is supported by the most recent and highest quality study, which emphasizes the importance of a detailed workup to confirm the diagnosis and exclude competing possibilities 1. The initial evaluation should rule out central nervous system progression of cancer, seizure activity, infection, and metabolic derangement as causes of neurologic symptoms, and consider paraneoplastic neurologic syndromes and autoimmune encephalopathies 1.
Key Components of the Workup
- Basic laboratory tests: complete blood count, comprehensive metabolic panel, ammonia level, thyroid function tests, and toxicology screening
- Neuroimaging: CT or MRI of the brain to rule out structural causes
- Electroencephalogram (EEG): to assess for seizure activity or specific patterns associated with certain encephalopathies
- Lumbar puncture with cerebrospinal fluid analysis: if infection or autoimmune causes are suspected
- Additional tests: blood cultures, HIV testing, autoimmune panels, heavy metal screening, and vitamin levels (particularly B1, B12)
Considerations for Specific Causes
- Metabolic encephalopathies: arterial blood gases and lactate levels are helpful
- Autoimmune encephalitis: specific antibody panels should be ordered
- Infection: consider CSF analysis, including cytology to rule out leptomeningeal metastasis, and blood cultures
Importance of Prompt Identification and Treatment
Prompt identification and treatment of the underlying cause is crucial for preventing permanent neurological damage, as many forms of encephalopathy are reversible if addressed quickly 1. The workup should be tailored to the clinical presentation, with attention to reversible causes such as infection, metabolic derangements, toxins, and medication effects.
From the Research
Diagnostic Approach to Encephalopathy
The diagnostic approach to encephalopathy involves a thorough history, examination, and investigations to identify the underlying cause. The following steps can be taken:
- Identify the pace of onset and evolution of encephalopathy (sudden, acute, subacute, chronic) 2
- Rule out infectious, toxic, and metabolic etiologies 3
- Consider neurologic disorders, such as stroke and fulminant demyelinating encephalopathies, and use neuroimaging to aid in diagnosis 3
- Suspect autoimmune encephalopathy in patients with unexplained acute or subacute onset encephalopathy or rapidly progressing dementia 3
Laboratory Tests and Investigations
The following laboratory tests and investigations can be useful in diagnosing encephalopathy:
- Combined serum and cerebrospinal fluid (CSF) autoantibody testing to increase the diagnostic yield of autoimmune and paraneoplastic encephalitis 3
- CSF analysis, which is more sensitive than serum for diagnosing NMDA receptor antibodies 3
- Serum analysis, which is more sensitive than CSF for diagnosing voltage-gated potassium channel (VGKC) complex antibodies 3
- Magnetic resonance imaging (MRI), CSF analysis, and electroencephalography (EEG) in select clinical situations 4
- Blood tests, such as blood sugar, blood gases, plasma ammonia, blood lactate, plasma ketones, plasma amino acids, liver function tests, and urinary organic acids, to identify metabolic disorders 5
Treatment and Management
Treatment and management of encephalopathy depend on the underlying cause. The following approaches can be taken:
- Immunotherapy, such as glucocorticoids, intravenous immune globulin, and plasma exchange, for autoimmune encephalitis 3
- Supportive treatment, with attention to cerebral perfusion pressure, for metabolic disorders 5
- Withdrawal of offending medications and treatment of underlying infections or metabolic derangements 4