Approach to encephalitis: Clinical sciences

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Introduction0:00–0:33

Encephalitis refers to the inflammation of the brain parenchyma, which can occur due to infections, including herpes simplex virus-, varicella-zoster virus-, West Nile virus-, and Toxoplasma gondii infection; as well as autoimmune conditions, such as acute disseminated encephalomyelitis, anti-NMDA receptor encephalitis and anti-LGI1 encephalitis.

Unstable Patient0:33–1:14

Alright, if your patient presents with a chief concern suggestive of encephalitis, first, perform an ABCDE assessment to determine if they are stable or unstable.
If unstable, stabilize the airway, breathing, and circulation. At this point, you might need to intubate the patient and provide mechanical ventilation.
Next, obtain IV access, consider intravenous fluids, and don’t forget to put your patient on continuous vital signs monitoring, including heart rate, blood pressure, and pulse oximetry.
Finally, if needed, be sure to manage increased intracranial pressure. Now, let’s go back to the ABCDE assessment and take a look at stable individuals.

Stable Patient1:14–2:18

In this case, you should obtain a focused history and physical examination. Your patient or their loved ones will report a new onset of progressive confusion, behavioral or personality changes, or a decreased level of consciousness.
History might also reveal fever, headache, and seizures. Depending on the location of the injury, there might be additional neurologic symptoms like weakness, numbness, changes in vision, language impairment, or incoordination.
On physical exam, you will notice altered mental status, sometimes in combination with focal neurologic deficits. With these findings, consider encephalitis and assess for current signs and symptoms of infection, such as fever, leukocytosis, or a viral exanthem.
If present, consider infectious encephalitis. Next, obtain a brain MRI and perform a lumbar puncture for CSF analysis.

HSV encephalitis2:18–3:35

First, let’s discuss herpes simplex virus, or HSV encephalitis for short. Both HSV type 1 and type 2 can cause encephalitis.
In this case, your patient will likely present with prodromal symptoms consistent with an upper respiratory tract infection.
Sometimes, they might have olfactory hallucinations. If the brain MRI reveals edema and hemorrhage in the temporal lobes and orbitofrontal cortex; and the CSF PCR testing is positive for HSV type 1 or 2, diagnose HSV encephalitis.
Moreover, HSV is the most common cause of encephalitis, and if left untreated, it can be fatal. In other words, if your clinical suspicion is high, always start intravenous acyclovir, even if your PCR results are still pending.
Let’s switch gears and move on to varicella-zoster virus encephalitis. These individuals will report prior or current chickenpox or shingles rash, which are both clinical manifestations of the varicella-zoster virus infection.

VZV encephalitis3:35–5:10

Chickenpox occurs as a result of primary infection, while shingles, also known as herpes zoster, occur due to the reactivation of a virus that has been dormant in the dorsal root ganglia after the initial infection.
Additionally, the varicella-zoster virus can affect the cerebellum, causing cerebellitis and symptoms like loss of coordination, dizziness or vertigo, and gastrointestinal symptoms, such as nausea and vomiting.
Next, the virus can cause vasculopathy, leading to ischemic or hemorrhagic strokes, so be aware that your patient might also present with sudden onset of symptoms suggestive of stroke.
Lastly, the patient is likely immunocompromised or elderly, which puts them at higher risk of virus reactivation. Now, the brain MRI might show ischemic strokes or hemorrhages in the deep brain structures, or edema and hyperintensities in the cerebellum, which is consistent with cerebellitis.
However, regardless of the brain imaging findings, if you identify positive VZV PCR or VZV antibodies in the CSF, diagnose VZV encephalitis.
Next, let’s discuss West Nile virus, which is an arbovirus, meaning a virus causing human disease via mosquito or tick vectors.

West Nile encephalitis5:10–6:21

West Nile is typically transmitted during the summer and fall seasons. These patients will report a recent mosquito bite and non-specific symptoms, including fever and muscle aches.
They might also have a rash. In addition to symptoms of encephalitis, involvement of the basal ganglia and substantia nigra could result in tremors or other abnormal involuntary movements; and the involvement of the cells in the anterior horn could cause weakness in all extremities, which is also known as flaccid paralysis.
Again, these patients are probably immunocompromised, elderly, or have diabetes. Next, the brain MRI will show edema and hyperintensities in the basal ganglia and thalami, while the CSF analysis will reveal positive IgM antibodies for the West Nile virus.
With these findings, diagnose West Nile encephalitis. Next up is Toxoplasma gondii encephalitis.

Toxoplasma gondii encephalitis6:21–7:22

These individuals might be immunocompromised, such as having an HIV infection with a CD4 count of less than 200 cells per microliter, or they might be immunosuppressed, such as after an organ transplantation.
In these situations, encephalitis occurs as a result of reactivation of latent T. gondii infection.
However, if the immune system is not compromised, the likely cause is a primary infection from eating undercooked meat or raw shellfish or ingesting oocytes that were shed in cat feces.
In this case, the brain MRI will show ring-enhancing lesions in the cortex or basal ganglia, while the CSF analysis will be positive for Toxoplasma gondii on PCR.
These findings are suggestive of encephalitis from Toxoplasma gondii. Finally, let’s discuss infectious encephalitis due to a helminth, Taenia solium.

Cysticercal encephalitis7:22–8:54

The larval stage of T. solium can cause cysticercosis, which consists of cystic deposits that can affect different body organs.
If the helminth affects the brain, we are talking about neurocysticercosis, which is rarely associated with encephalitis.
More commonly, these individuals report isolated headaches or seizures, sometimes in combination with vision loss, eye pain, or an eye mass due to cyst deposits in the eyes.
If the skin is affected, they might even report subcutaneous nodules. Keep in mind that Taenia solium is highly endemic in Central or South America, sub-Saharan Africa, India, and Asia, so your patient will likely come from these regions.
Next, the brain MRI will show multiple intraparenchymal and extra-parenchymal lesions, some of which are calcified. Keep in mind that the same findings could be seen on CT as well.
You might also notice a scolex, which is the head of the tapeworm, with suckers and hooks. While neurocysticercosis is usually diagnosed with neuroimaging, you can also send a CSF sample for Taenia solium antigens or PCR.
If positive, diagnose cysticercal encephalitis. Alright, it’s time to go back and take a look at patients with no signs and symptoms of infection.

Acute disseminated encephalomyelitis8:54–11:11

In this case, you should consider autoimmune encephalitis and assess the time course of symptoms. If symptoms progress over days, consider acute disseminated encephalomyelitis, also known as ADEM.
This is a demyelinating condition that typically affects children. Most commonly, it occurs after a recent viral infection, including measles, chickenpox, rubella, mumps, and influenza.
Rarely, ADEM occurs after vaccination. Patients usually present with a decreased level of consciousness and weakness.
Once you suspect ADEM, the next step is to obtain an MRI of the brain and spine, and obtain CSF samples for analysis, cultures, and PCR testing.
Also, be sure to check the serum for myelin oligodendrocyte glycoprotein antibodies. On the MRI, you will find multifocal, large, poorly demarcated, enhancing lesions in the cortex, white matter, basal ganglia, brainstem, cerebellum, and spinal cord.
Next, the CSF analysis will reveal nonspecific findings, such as elevated white blood cell count with lymphocytic predominance and elevated protein.
The CSF cultures and PCR testing will be negative for infectious agents. Finally, you might identify serum myelin oligodendrocyte glycoprotein antibodies, which are present in about half of the cases of ADEM.
Here's a high-yield fact! Another type of rare delayed post-infectious encephalitis that presents several years after a measles infection is known as subacute sclerosing panencephalitis.
This condition is seen mainly in children and starts with behavioral and personality changes. As the condition progresses, the patient develops cognitive impairment, myoclonus, and seizures.
In later stages, they become unresponsive and paralyzed. Now, let's discuss patients that report symptom progression over the past several weeks.

Anti-NMDA receptor encephalitis11:11–13:06

In this case, assess the underlying cause, which can be either anti-NMDA receptor encephalitis or anti-LGI1 encephalitis.
Individuals with anti-NMDA receptor encephalitis are usually young biological female individuals with prominent behavior changes and psychiatric symptoms, such as hallucinations, delusions, mania, and agitation.
These patients also report changes in sleep patterns and abnormal involuntary movements. Interestingly, they might report a recent HSV encephalitis.
On examination, you will notice pressured or absent speech, also known as mutism. In some cases, you might detect motor abnormalities, such as repetitive mouth, face, or tongue movements, which is known as orofacial or lingual dyskinesias.
Also, there might be involuntary sustained muscle contractions known as dystonia, and rigidity. Finally, you might notice catatonia.
With these findings, consider anti-NMDA receptor encephalitis, so be sure to obtain a CSF sample to look for anti-NMDA receptor antibodies.
If these antibodies are present, diagnose anti-NMDA receptor encephalitis, which is an autoimmune encephalitis that is often paraneoplastic and associated with ovarian teratomas.
If you suspect ovarian teratoma, your next step will be to obtain a transvaginal ultrasound to evaluate further. Okay, when it comes to anti-LGI1 encephalitis, these individuals are usually over 50 years of age with prominent memory loss and emotional lability, which frequently presents as excessive tearfulness.

Anti-LGI1 encephalitis13:06–14:11

The patient will also report having very frequent, brief, one to two-second abnormal movements of the face and arm, sometimes up to a few hundred times a day.
On the physical exam, you will note frequent, sudden facial grimacing and arm posturing, consistent with faciobrachial dystonic seizures.
With these findings, you should consider anti-LGI1 encephalitis, so, your next step is to check for the presence of anti-LGI1 antibodies in the CSF.
If antibodies are present, diagnose anti-LGI1 encephalitis, which is usually not associated with malignancy, but sometimes it might be seen with thymomas and small-cell lung carcinomas.
Alright, as a quick recap… Encephalitis refers to the inflammation of the brain parenchyma, which can occur due to infectious or autoimmune conditions.

Review14:11–15:01

If you are suspecting encephalitis, first assess for signs and symptoms of infection. If present, think of infectious encephalitis and proceed with brain imaging and CSF analysis to find out which pathogen you are dealing with.
Common examples include herpes simplex virus, varicella-zoster virus, West Nile virus, Toxoplasma gondii, and Taenia solium.
On the flip side, if signs are absent, consider autoimmune conditions, such as acute disseminated encephalomyelitis, anti-NMDA receptor encephalitis,