Irreversible Lithium Neurotoxicity: A Review and Case of Toxicity Leading to Bilateral Globus Pallidus Injury

Background/Significance:

Irreversible lithium neurotoxicity often involves the cerebellar region, both in terms of typical symptoms observed as well as imaging findings. In this presentation, we report the first described finding of bilateral globus pallidus injury in the setting of lithium toxicity with subsequent review of pathophysiology and prevention/management strategies for this under-studied yet impairing condition.

Case:

Ms. G is a 52-year-old female with a history of bipolar I disorder on lithium and hypothyroidism who was brought to the emergency department after family found her obtunded at home. She was intubated and admitted to the ICU. Serum results revealed a lithium level of 4.0 mmol/L.

While in the ICU, Ms. G was dialyzed several times with eventual normalization of the lithium level. The EEG revealed moderate diffuse slowing with occasional multifocal epileptiform discharges and generalized periodic discharges up to 2 hertz, consistent with toxic encephalopathy. Levetiracetam was started for seizure prophylaxis. On hospital day 8, Ms. G was extubated but remained stuporous. An MRI of the brain was ordered which revealed T2/FLAIR hyperintensities in the globus pallidus interna bilaterally, previously not visualized on prior brain imaging. By hospital day 10, the patient demonstrated improvement in her mental status but remained confused and only verbalized short, repetitive statements. These symptoms persisted, present even after re-admission later that year.

Discussion:

The body of literature on SILENT (the Syndrome of Irreversible Lithium-Effectuated Neurotoxicity) has focused on patients with long-lasting cerebellar effects including ataxia and apraxia (Adityanjee 2005). Lesions in the globus pallidus, however, are typically the result of respiratory toxins such as carbon monoxide, cyanide, or more recently, COVID-19 (Hegde 2011; Kulick-Soper 2020). In our patient, we propose that demyelination secondary to acute lithium toxicity led to bilateral globus pallidus lesions.

Ms. G had several key risk factors associated with irreversible lithium neurotoxicity including renal impairment, age above 50 years, and hypothyroidism (Baird-Gunning 2017). Furthermore, she developed a fever during the acute phase of toxicity (with fever being a potential harbinger for neurologic injury). The exact mechanism of CNS injury is not well understood. However, fever in settings of severe lithium toxicity is thought to be a pathophysiologic contributor through hemoconcentration and protein coagulation (Adityanjee 2005).

Conclusions/Implications:

Prevention of toxicity remains the best strategy to mitigate potential injury. Monitoring frequency should be adjusted based on concurrent risk factors, in addition to specific education on subtle signs of lithium toxicity due to higher risks associated with chronic toxicity.

References

1. Baird-Gunning J, Lea-Henry T, Hoegberg LCG, Gosselin S, Roberts DM. Lithium Poisoning. J Intensive Care Med. 2017 May;32(4):249–63.

2. Adityanjee, Munshi KR, Thampy A. The syndrome of irreversible lithium-effectuated neurotoxicity. Clin Neuropharmacol. 2005;28(1):38–49.

3. Hegde AN, Mohan S, Lath N, Lim CCT. Differential Diagnosis for Bilateral Abnormalities of the Basal Ganglia and Thalamus. RadioGraphics. 2011 Jan;31(1):5–30.

4. Kulick-Soper CV, McKee JL, Wolf RL, Mohan S, Stein JM, Masur JH, et al. Pearls & Oy-sters: Bilateral globus pallidus lesions in a patient with COVID-19. Neurology. 2020 Sep 8;95(10):454–7.