Lithium is a commonly used to treat bipolar disorder with tremor being the most frequent neuromuscular side effect (1). Lithium intoxication can lead to symptoms such as sluggishness, ataxia, confusion, agitation, and neuromuscular excitability, manifesting as coarse tremors, fasciculations, or myoclonic jerks (2). However, lithium-induced myasthenia is relatively rare, with only six cases reported to date (3–8). These cases primarily involved chronic symptoms, such as exertional weakness, ptosis, diplopia, slurred speech, and dysphagia. In contrast, we report a case of lithium-induced acute myasthenia with recurrent falls as the primary manifestation.

In this case, we hypothesized that the patient’s recurrent falls were caused by the lithium for two primary reasons.

The first and most compelling reason is the temporal relationship between the administration of lithium and the onset of the falls. The patient’s falls began after starting lithium and ceased upon discontinuation of the drug, which occurred twice (Figure 1). At the time of the first fall, the medications administered included lithium, fluoxetine, aripiprazole, lamotrigine, and zopiclone. Among these, only lithium and aripiprazole have been associated with an increased risk of myasthenia, while the others have not (9). Medication changes before the first fall included the discontinuation of aripiprazole and fluoxetine, and an increase in the lithium dose. At the time of the second fall, only lithium was increased, and the falls ceased immediately upon lithium discontinuation, with no other medication changes.

The second reason supporting our hypothesis is that no symptoms or examinations indicated that the falls were caused by another condition. The patient denied experiencing chest tightness, palpitations, or visual disturbances before the falls, and there was no loss of consciousness at the time of the falls. Cardiac evaluations, including Holter dynamic ECG, cardiac ultrasound, and blood pressure measurements (both prone and ambulatory), were all negative, ruling out cardiac syncope due to arrhythmia, valvular heart disease, or orthostatic hypotension. Additionally, the patient was able to recall the details of each fall and did not experience a loss of consciousness during the episodes and two ambulatory EEGs normal, excluding seizures as a potential cause. The patient did not report daytime sleepiness or sleep-related episodes, and the results of multiple sleep latency tests and polysomnography were negative, ruling out narcolepsy. Furthermore, there was no history of thyroid disease, and her current thyroid function tests were normal, making hypothyroidism unlikely. Conversion disorder was also not considered, as the patient showed no psychological triggers or disturbances in the integration of motor, sensory, or cognitive functions prior to the falls.

To date, six cases of lithium-induced myasthenic syndrome have been reported. The first five cases (3–7)were all characterized by chronic symptoms such as exertional weakness, ptosis, diplopia, slurred speech, and dysphagia, which were significantly improved or resolved after lithium was discontinued or its dose was reduced. The sixth case, similar to ours, involved acute myasthenia with sudden falls, but the patient had true myasthenia gravis, with lithium acting only as a precipitating factor (8). While the first five cases of lithium-induced myasthenia primarily presented with chronic symptoms and more localized muscle involvement, particularly affecting the eye and bulbar muscles, our case differed in that the patient experienced multiple episodes of acute weakness involving widespread muscle groups, including the limbs, neck, and bulbar muscles. Each episode was characterized by an abrupt onset of generalized weakness and falls. The heterogeneity in the clinical presentation of lithium-induced myasthenia is evident from these cases.

Lithium-induced myasthenia may involve several mechanisms that affect neuromuscular transmission and postsynaptic stability. First, lithium can reduce the number of acetylcholine receptors (AChRs) in skeletal muscle, potentially by affecting their synthesis, degradation, or transport (10). Lithium can also interfere with AChR metabolism, decreasing receptor stability and impairing synaptic transmission (11). Additionally, lithium inhibits agrin-induced AChR aggregation by disrupting a late step in the agrin signaling pathway, leading to abnormal AChR distribution and impaired synaptic transmission, which may contribute to muscle weakness (12). Lithium may also interfere with acetylcholine synthesis and release from presynaptic terminals, reducing neurotransmitter availability and further impairing signal transmission (13). Furthermore, lithium enhances the effects of neuromuscular blocking agents, such as succinylcholine and pancuronium, which potentiate synaptic inhibition and weaken muscle strength (14, 15). Finally, lithium appears to have a more pronounced effect on neuromuscular junctions (NMJs) in denervated muscles, exacerbating the disruption of synaptic stability and worsening muscle weakness, particularly under pathological conditions (16). These combined effects on AChR metabolism, neurotransmitter release, and NMJ stability likely contribute to the development of lithium-induced myasthenia.

The limitation of this case is that repetitive nerve stimulation or single-fiber electromyography was not performed during the patient’s episodes of muscle weakness to confirm the presence of myasthenia. Additionally, despite thorough differential diagnoses, the possibility of other medications, diseases, or psychological factors contributing to myasthenia gravis cannot be completely excluded.

This case highlights the need for increased awareness among psychiatrists regarding the possibility of lithium-induced myasthenia, a potentially overlooked side effect that requires careful monitoring in patients prescribed lithium. The exact mechanisms by which lithium induces myasthenia are still not fully understood and warrant further investigation in future studies.