Thread by @caseyalbin

1/
#ContinuumCase

A 67 yo man with a known, active cancer presents to the ED. His wife reports that he has had worsening headaches, forgetfulness, & confusion. Today, he was increasingly sleepy which triggered the presentation.

An MRI is ordered.
🤔🤔🤔 @ContinuumAAN @LyellJ

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Neurologic complications in cancer patients are tricky. They can be due to
✨Malignant lesions
✨Systemic complications of disease
✨Paraneoplastic disorders
✨Treatment Side effects

3/
You absolutely must have a systemic approach to these patients. I think the best framework for this is in this review by @holroyd_katie, Dan Rubin and Henrikas Vaitkevicius:
pubmed.ncbi.nlm.nih.gov/34619783/

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Reviewing his cancer treatment history which do you find?

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Cancer treatments can cause a wide variety of PNS/CNS complications ranging from Myasthenia Gravis to PML. This review is an excellent overview of some of the CNS complications of various anti-cancer treatments: insightsimaging.springeropen.com/articles/10.11…

Awesome table:

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Briefly, Rituximab may cause PRES and very, very rarely result in reactivation of JC Virus and cause PML.

pubmed.ncbi.nlm.nih.gov/25489887/

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Methotrexate is known to cause a diffuse acute or chronic leukoencephalopathy.

The acute presentation is often hours after treatment and presents with confusion and seizures.

Chronic confusion and worsening aphasia may also occur. See radiopaedia:
radiopaedia.org/articles/metho…

8/
Treatment for this includes rescue leucovorin, dextromethorphan and aminophylline.

9/
CAR T-cells can have a whole host of systemic complications and I am eagerly awaiting @pulmcrit’s chapter on @emcrit / @iBookCC

Generally, the most feared complication of this is diffuse cerebral edema.

A nice “practical” review: pubmed.ncbi.nlm.nih.gov/32503897/

10/
But, the lesion in this case?

Due to nivolumab!

Immune checkpoint inhibitors (ipilimumab, nivolumab ad prembrolizumab) may have a range of PNS/CNS adverse events.

One feature that is unique to ICIs is inducing a subcortical immune-mediated encephalitis👇

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Encephalitis typically falls into two categories for these patients:
📍focal encephalitis, which can include limbic encephalitis
🧠meningoencephalitis (presents with fever, headache, and inflammatory CSF).

Rarely ICIs can cause hypophysitis (particularly ipilimumab).

12/
It is hypothesized that the focal encephalitis may be an unmasking of a previously occult paraneoplastic encephalitis when the patient is exposed to the ICI. These cases are associated with a significantly worse prognosis.

More here:
pubmed.ncbi.nlm.nih.gov/33720308/

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Really not much is known about how to treat these patients. Usually the treatment is withholding the ICI and administering corticosteroids...other induction immunosuppression has also been tried.

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Recap, when approaching neurologic complications in cancer patients, think
♋️cancer itself?
💊 treatment side effect?
🦀paraneoplastic phenomenon?

Neuroradiology can be very helpful in addition to the time course and localization.

15/ To check out more awesome ways in which imaging offers a window into autoimmune, paraneoplastic, and neuro-rheumatologic brain pathology, this is a fantastic review by @Lamaaw27 and TCho @ContinuumAAN
journals.lww.com/continuum/Full…