225 - Role of Acute Inpatient Rehabilitation and Neurostimulant Therapy in Lorlatinib-Induced Leukoencephalopathy

Thursday, February 19, 2026

5:00 PM - 6:30 PM AST

Presenting Author(s)

SL

Steven Le, MD

Resident Physician
Schwab Rehabilitation Hospital
Chicago, Illinois, United States

Co-Author(s)

EC

Elizabeth Chang, MD

Resident Physician
Schwab Rehabilitation Hospital
Chicago, Illinois, United States
FK

Fabiolla Kopp, MD

Attending Physician
Schwab Rehabilitation Hospital
Chicago, Illinois, United States

Submitter(s)

SL

Steven Le, MD

Schwab Rehabilitation Hospital
Chicago, Illinois, United States

Case Diagnosis: Lorlatinib-induced leukoencephalopathy

Case Description: A 56-year-old male with ALK fusion gene rearrangement positive non-small cell lung cancer (previously on lorlatinib) with bony metastasis presented for altered mental status and abnormal behaviors with workup suggestive of leukoencephalopathy due to lorlatinib side effect. Despite medication discontinuation, the patient continued to have significant apraxia and anomic aphasia. The patient underwent intensive speech therapies during his acute inpatient rehabilitation stay, with an emphasis on memory, attention, and verbal and written expression strategies. Motor and cognitive improvement was augmented by initiation of methylphenidate. At time of discharge, the patient demonstrated improvement from severe to mild/moderate level of impairment in multiple cognitive domains including memory, comprehension, problem solving, and expression.

Discussions: Lorlatinib, a tyrosine kinase inhibitor commonly used in patients with metastatic NSCLC, can induce central neurotoxicities such as leukoencephalopathy, resulting in profound cognitive and language deficits. In this patient, discontinuation of the offending agent alone was insufficient to reverse symptoms, highlighting the importance of acute inpatient rehabilitation. The AIR setting provided intensive, daily, multidisciplinary therapies targeting language, cognition, and functional independence, while also allowing for physician-led initiation and titration of methylphenidate under close monitoring. The structured environment additionally supported family education, safe discharge planning, and prevention of complications associated with impaired safety awareness and functional decline. These factors collectively contributed to meaningful recovery across multiple domains.

Conclusions: Neurocognitive adverse events associated with lorlatinib use are well described due to its ability to cross the blood brain barrier. Besides discontinuation of the drug, early multidisciplinary neurorehabilitation in the AIR setting — combined with pharmacologic intervention for neurostimulation — may be key to promoting neurorecovery, optimizing safety, and facilitating return of function following leukoencephalopathy.