Approach to encephalopathy (acute and subacute): Clinical sciences

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Introduction 0:00–0:36

Encephalopathy refers to a change from baseline cognitive status, which can range from mild confusion to a comatose state.
Now, acute or subacute encephalopathy refers to cognitive impairment that has occurred over the last 3 months. Based on the underlying cause, encephalopathy can occur as a result of primary neurologic conditions, but also due to non-neurologic causes, including toxins, metabolic derangements, nutritional deficiencies, and infections.
All right, when a patient presents with chief concerns suggestive of acute or sub-acute encephalopathy, first, perform an ABCDE assessment to determine if they're stable or unstable.

Unstable patient 0:36–1:37

If unstable, stabilize the airway, breathing, and circulation. You might also need to intubate the patient and provide mechanical ventilation.
Next, obtain IV access and consider IV fluids. Finally, put your patient on continuous vital sign monitoring, including heart rate, BP, and pulse oximetry.
Don't forget to manage high intracranial pressure or ICP if needed. Here's a clinical pearl to keep in mind.
Unstable patients with encephalopathy may have medical emergencies like status epilepticus, or conditions associated with high intracranial pressure, such as intracranial hemorrhage.
However, systemic conditions like liver failure and sepsis can also result in encephalopathy. Now, let's go back to the ABCDE assessment and focus on stable patients.

Stable Patient, acute/subacute encephalopathy 1:37–2:12

Your next step here is to obtain a focused history and physical examination. The patient or a loved one will report recent changes in cognition, level of consciousness, or behavior, typically over the last few days to weeks.
Examples of such changes include drowsiness, memory loss, impaired attention, and paranoia. Additionally, the physical exam reveals altered mental status, sometimes in combination with focal neurologic deficits.
These findings are highly suggestive of acute or subacute encephalopathy. So be sure to obtain labs, including a CMP and TSH level.

Metabolic encephalopathy 2:12–2:48

If the sodium, glucose, or TSH levels are extremely high or low, or if you identify elevated levels of liver enzymes, BUN or creatinine, you are probably dealing with metabolic encephalopathy.
Some important conditions associated with abnormal glucose levels include diabetic ketoacidosis and hyper osmolar hyperglycemic state.
On the flip side, if the initial labs are normal, assess for toxin exposure. History might reveal medication or substance overdose, or exposure to toxins like heavy metals or carbon monoxide.

Toxic encephalopathy 2:48–3:07

If this is the case, diagnose toxic encephalopathy. Now, if you rule out toxic encephalopathy, assess the history and physical exam findings for episodes suspicious of seizures.

Seizures 3:07–3:49

If the patient or a loved one report waxing and waning mental status, repeated episodes of altered mental status, or episodes of jerking and shaking movements, Consider seizures as the underlying cause.
To confirm, obtain an electroencephalogram, or EEG for short. If the EEG reveals patterns suggestive of seizures, you have your diagnosis.
Keep in mind that encephalopathy can be present during a seizure, but also after a seizure, during the postictal state. Next, if there are no signs of seizures, you should think of CNS infections.

CNS infection 3:49–5:16

In this case, history will reveal headache, confusion, and fever. Sometimes in combination with neck stiffness, nausea, vomiting, and light sensitivity.
On the exam, you might notice focal neurologic deficits and signs of meningeal irritation, such as nuchal rigidity. Also, you might identify a positive Brudzinski sign, which refers to the flexion of the hip and knees when the neck is passively flexed, and a positive Koenig sign, which is pain on knee extension after holding the hip and knees in a flexed position.
With these findings, consider CNS infection and perform a lumbar puncture to analyze the CSF. But wait, there's a catch.
Before proceeding with a lumbar puncture, be sure to rule out signs of increased intracranial pressure to avoid possible complications such as brain herniation.
Now, if CSF analysis shows an elevated white blood cell count, elevated protein level, and positive culture or PCR, the underlying cause is a CNS infection, such as meningitis or encephalitis.
Keep in mind that infections outside of the CNS can also cause encephalopathy, so always consider obtaining blood and urine cultures as part of your workup.
OK. If there is no CNS infection, you should assess the patient for a stroke or mass lesion by obtaining brain imaging with a CT or MRI.

Stroke 5:16–6:12

In order to cause encephalopathy, a stroke or brain mass must either be large enough to cause mass effect, or they must affect a particular part of the brain, such as the frontal and temporal lobes, bilateral cortices, bilateral thalammi, or the brain stem.
First, let's focus on stroke, which is associated with acute simultaneous onset of symptoms such as difficulty speaking or understanding language, decreased level of consciousness, weakness or numbness, vision changes, and loss of coordination.
If the brain imaging shows ischemic or hemorrhagic lesions, diagnose stroke as the underlying etiology. On the other hand, if the patient reports progressive worsening of symptoms, a headache, possibly with a fever and generalized malaise, and imaging shows an enhancing mass lesion, diagnose a brain mass as the underlying cause.

Brain mass 6:12–6:29

The mass could be an abscess or a tumor. Now, in cases when the brain imaging doesn't reveal a stroke or mass lesion, take a good look at history and physical exam findings to assess the underlying cause.

Wernicke encephalopathy 6:29–8:37

In this case, you should think of Wernicke encephalopathy, anti-NMDA receptor encephalitis, and Creutzschfeldt-Jakob disease.
Wernicke encephalopathy is associated with confusion, chronic alcohol use, severe malnutrition, and visual disturbances, such as blurry or double vision.
On exam, in addition to altered mental status, you'll notice impaired extraocular movements, nystagmus, and gait ataxia.
With these findings, diagnose Wernicke encephalopathy, which occurs due to deficiency in vitamin B1, which is also known as thiamine.
Keep in mind that vitamin B1 deficiency can also occur due to malabsorption from gastrointestinal surgery, such as bariatric surgery.
Other Vitamin B deficiencies that can result in encephalopathy include vitamin B12 and B3 deficiency. Vitamin B12 deficiency is also associated with polyneuropathy and subacute combined degeneration, which refers to degeneration of the lateral corticospinal tracts and posterior columns.
On the flip side, vitamin B3 deficiency causes a condition known as pellagra, which is characterized by the three D's, dermatitis, diarrhea, and dementia.
Time for a high yield fact. The management of Wernicke encephalopathy includes administration of thiamine.
Be sure to treat this condition on time because the patient might progress and develop Korsakoff syndrome, which is characterized by retrograde and anterograde amnesia and confabulations.
Similarly, if you're treating patients with severe malnutrition or chronic alcoholism who are at risk for Wernicke encephalopathy, always administer thiamine before dextrose or glucose, because thiamine is essential for carbohydrate metabolism.
Next up is anti-NMDA receptor encephalitis, which is an autoimmune encephalitis that is often perineoplastic and associated with ovarian teratomas.

Anti-NMDA receptor encephalitis 8:37–9:56

History typically reveals a young biological female with prominent behavior changes and psychiatric symptoms, including hallucinations, delusions, mania, and agitation.
Additionally, the patient will report changes in sleep patterns and abnormal involuntary movements. In some cases, this type of encephalitis can present after recent encephalitis from herpes simplex virus or HSV.
On exam, you'll notice pressured or absent speech, also known as mutism. The exam might also reveal motor abnormalities, such as repetitive mouth, face, or tongue movements known as orofacial or lingual dyskinesias, involuntary sustained muscle contractions, known as dystonia, and rigidity.
There might also be catatonia. With these findings, consider anti-NMDA receptor encephalitis.
Your next step is to obtain a CSF sample to look for anti-NMDA receptor antibodies. If these antibodies are present, diagnose anti-NMDA receptor encephalitis.
Finally, let's look at Creutzfeldt-Jakob disease, or CJD, which is associated with the abnormal accumulation of prion proteins in brain cells, misfolding of normal prions, and subsequent neurodegeneration.

Creutzfeldt-Jakob disease 9:56–12:07

In this case, the patient will present with rapidly worsening confusion and memory, as well as a decrease in movement and speech.
Additionally, history will reveal vision loss, muscle or limb jerking movements, and loss of coordination. On the exam, you will notice kinetic mutism, which refers to the loss of spontaneous movement and speech despite the patient maintaining an adequate level of consciousness.
Also, you'll identify cortical visual loss, which is the loss of vision due to occipital cortex injury with a normal eye exam.
The exam will also reveal myoclonus, as well as trunk and limb ataxia. At this point, consider Creutzchfeldt-Jakob disease.
So analyze the CSF for 1433 protein, which is a non-specific protein released by damaged cells. Also, you should order a real-time quaking-induced conversion assay to detect misfolded prions.
Finally, don't forget to obtain a brain MRI if it wasn't ordered already, and an EEG. Now, to diagnose Creutzfeldt-Jakob disease, the CSF should show elevated 1433 protein, or the real-time quaking-induced conversion assay should be positive.
In Creutzchfeldt-Jakob disease, the brain MRI will reveal either an abnormal signal in the caudate or putamen, or different cortical regions, which is also known as cortical ribboning.
Additionally, the EEG will show generalized periodic sharp wave complexes. With these findings, you can diagnose CJD, which is usually idiopathic, meaning the underlying cause is unknown.
However, keep in mind that there are also familial cases, iatrogenic cases from surgical contamination and blood transfusions, and transmission of Creutzfeldt-Jakob disease from bovine to humans.
All right. It's a quick recap.

Review 12:07–12:52

Encephalopathy refers to a change from baseline cognitive status, which can range from mild confusion to a comatose state.
Acute or subacute encephalopathy refers to cognitive impairment that has occurred over the last 3 months. Once you diagnose acute or subacute encephalopathy, first, rule out metabolic, toxic, and infectious causes.
Also, consider and evaluate for seizures. Next, obtain a brain CT or MRI to identify possible hemorrhagic and ischemic lesions, as well as brain masses, like tumors.
If the brain imaging does not show a stroke or brain mass, think of Wernicke encephalopathy, anti-NMDA receptor encephalitis, and Creutzfeldt-Jakob disease.