Q. X. is a 63-year-old woman with a long history of BD with mixed episodes. She is unmarried, retired, and lives alone. Q. X. shared a positive anamnesis for mood disorders with her mother, who suffered from a depressive-anxious disorder and her niece who was recently diagnosticated with BD type I; none of them have been treated with lithium. Since adolescence, she showed cyclothymic-irritable temperament with an inclination to impulsivity, affective instability, and sudden anger's outbursts that caused impairment of interpersonal relationships. The onset of the psychopathological picture goes back to the age of 19 when, following her sister's sudden death, she experienced depressive mood with dysphoric cues, apathy, abulia, and elevation of anxiety, Hyperarousal, intrusive thoughts, and reexperiencing. The symptomatology resolved spontaneously without needing a pharmacological treatment. After 11 years, consequently to the ending of a sentimental relationship, she underwent a resurgence of the previously described picture; this time, addressing a psychiatrist who prescribed a therapy based on lithium salts, at unspecified dosage. In the years, she was followed by many specialists who discontinued treatment with lithium salts and carried out several unspecified therapeutic modifications, with little psychoaffective compensation, only to reintroduce lithium in 2008 (lithium carbonate up to 750 mg/day), over time variously associated with antipsychotics, antidepressants, and benzodiazepines, with a good psychoaffective and sociooccupational compensation. Over the following years, the average values of lithemia always remained around 0.60-0.70 mEq/L. In 2019, at 61, the patient begun to manifest distal tremors in the extremities of the upper limbs and in the mandibular district. For this reason, in January 2020, she underwent a cerebral SPECT with DaTscan whose results were not compatible with a nigrostriatal degeneration.
In September 2021, following her retirement, she faced a resurgence of the symptomatology with depressed mood, reduced energy level, irritability, social withdrawal, increased anxiety levels, and feelings of emptiness and loneliness with a tendency to clinophilia, referring also an aggravation of the tremors for which she received a diagnosis of "Essential Tremor" and a prescription for propanolol without however perceiving a clinical benefit and therefore, subsequently and independently suspended. In December 2021, for the worsening of the tremors that now also involved the lower limbs and three episodes of sudden fall accompanied by psychomotor slowdown, generalized tremors, reduced alertness, spatiotemporal disorientation, and aphasia, Q.X. made numerous accesses to the local E.R. without however referring any clinical improvement. She was therefore admitted to the local hospital psychiatric department where she underwent a dosage of lithemia (0.83 mEq/L at the time of hospitalization) and the complete interruption of the psychopharmacological therapy. Five days later, Q.X. was transferred to the neurologic department where she underwent a rachicentesis, resulting negative for autoimmune encephalopathy autoantibodies, TAU/B-amyloid protein and protein 14.3.3, a brainstem MRI that did not show any significant alteration, and CT scan that excluded the presence of blood collections and focal densitometric alterations. The neurological evaluation deposed for a case of extrapyramidal disease a treatment with levodopa/carbidopa up to 100/25 mg/day was suggested, still without benefits. During the hospitalization, Q.X. showed a progressive improvement in vigilance, spatiotemporal orientation, and motor skills.
One month later, Q.X. was discharged with a final diagnosis of "Acute behavioral decompensation in subjects with BD with negative neurological investigations" and a therapy based on valproic acid (750 mg/day), quetiapine (100 mg/day), and diazepam (8 mg/day). During the following days, Q.X. re-presented a depressive mood, elevated anxiety and internal tension, emotional lability with crying crisis, social withdrawal, and tendency to clinophilia. For this reason, she was then hospitalized in the psychiatric ward of Pisa Hospital. At the beginning of hospitalization, Q.X. showed distal tremors in the upper limbs bilaterally and at the mandibular region. She underwent a routine ECG and blood test resulting normal except for a slight anemia and minor alteration in the metabolic profile. Electrolytes, coagulation profile, renal, and thyroid function were found normal. An EEG was performed (Figures 1 and 2), reporting a symmetrical trace, consisting of a background rhythm at 8-9 Hz, not very regular, distributed on the posterior regions, reacting to the opening of the eyes, interspersed at rapid bianterior rhythms, and isolated potential theta sometimes of pointed appearance mainly anterior and resulting in "isolated pointed anomalies with anterior prevalence" and a neurological consultation suggested a possible compatibility with lithium encephalopathy. During the hospital stay, Q.X. was treated with valproic acid (900 mg/day), quetiapine (100 mg/day), paroxetine (20 mg/day), trimipramine (35 mg/day), diazepam (7 mg/day), and pramipexole (0.36 mg/day) showing a progressive improvement with the reduction of the tremor until complete disappearance, mood improvement, reduction of the internal tension and anxious quota, disappearance of emotional lability, and adequate thinking in form and content. The improvement was such as to allow her discharge from the hospital.