Objective: To report, to our knowledge, the first case of pseudobulbar affect (PBA) in a patient with progressive supranuclear palsy (PSP) demonstrating improvement with amantadine therapy.

Background: PBA is characterized by sudden, involuntary episodes of laughing or crying disproportionate to emotional state and occurs in multiple neurological diseases, including PSP. It is also described in Amyotrophic Lateral Sclerosis, which may share similar underlying pathophysiology with PSP affecting emotional regulation. The mechanism likely involves dysfunction of cortico-pontine-cerebellar circuits. Current treatments include dextromethorphan/quinidine, SSRIs, and tricyclic antidepressants. Amantadine, an NMDA receptor antagonist that also enhances dopaminergic transmission, has been reported to improve PBA after traumatic brain injury and stroke, but its effect in PSP has not been described.

Method: This is a case study of autopsy-confirmed PSP examining the development and treatment response of PBA.

Results: Female patient developed progressive symptoms of atypical parkinsonism starting at age 66, including vertical gaze palsy, dysarthria, dysphagia, gait impairment, freezing of gait, and falls. MRI brain demonstrated midbrain atrophy. One year after symptom onset, she developed frequent episodes of uncontrolled laughing and crying consistent with PBA. She had modest initial motor benefit with levodopa, but this did not affect her PBA. Three years after symptom onset, amantadine 100 mg twice daily was initiated. At follow-up, her PBA had largely resolved, was no longer bothersome, and was not observed on examination. When amantadine was discontinued due to a medication shortage, her PBA symptoms recurred and were reported to be nearly constant. Re-initiation of amantadine again resulted in prompt resolution. The benefit in controlling PBA persisted for the duration of therapy. The mechanism may relate to NMDA receptor antagonism, similar to the proposed mechanism of dextromethorphan. Enhanced dopaminergic transmission may also contribute, as dopaminergic mechanisms have been implicated in emotional regulation in Parkinson’s disease.

Conclusion: To our knowledge, this is the first report of PBA improvement in PSP with amantadine. Symptom recurrence after discontinuation and resolution upon re-initiation suggest a therapeutic effect, highlighting amantadine as a potential treatment option that warrants further study.

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2. Falconer R, Whitney D, Walters H, Rogers S. Prevalence of pseudobulbar affect (PBA) in Parkinson’s disease: an underrecognized patient burden. Cureus. 2021;13(11):e19960. doi:10.7759/cureus.19960

3. Hakimi M, Maurer CW. Pseudobulbar affect in parkinsonian disorders: a review. J Mov Disord. 2019;12(1):14–21. doi:10.14802/jmd.18051

4. Nabizadeh F, Nikfarjam M, Azami M, Sharifkazemi H, Sodeifian F. Pseudobulbar affect in neurodegenerative diseases: a systematic review and meta analysis. J Clin Neurosci. 2022;100:100–107. doi:10.1016/j.jocn.2022.04.009

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MDS Abstracts - https://www.mdsabstracts.org/abstract/improvement-of-pseudobulbar-affect-in-progressive-supranuclear-palsy-with-amantadine-a-case-report/