A 61-year-old man presents for evaluation of new-onset cognitive impairment, which has developed over the past 6 to 8 months. He has bipolar disorder, for which he has been taking lithium carbonate (Eskalith) for the past 15 years. This therapy kept his mood stable until a relapse of depression and mania 1 year ago required hospitalization and an increase in the lithium dose, which was then lowered somewhat after he improved (see below). His cognitive symptoms appeared gradually within 2 months after his release from the hospital.
He now has difficulty concentrating, a tendency to substitute words incorrectly during conversation, and difficulty recalling names and “retrieving memories.” He also reports a worsening tremor in his dominant hand that compromises his ability to eat with a spoon or a fork. He complains of increasing daytime somnolence, which began when his lithium dose was increased and improved when the dose was decreased.
The patient is a mathematician and recently finished revising the curriculum for an undergraduate course in advanced mathematics that he teaches. He does not smoke cigarettes, and he drinks alcohol only socially. He has no other medical conditions and no known cardiovascular risk factors.
Current and recent medications
- Lithium carbonate 600 mg twice daily (before his hospitalization he had been taking 600 mg twice daily; this was increased to 1,500 mg/day during the hospitalization and then decreased to the current dose as maintenance therapy)
- Divalproex (Depakote) 250 mg every night
- Gabapentin (Neurontin) 400 mg every night (the dosages of divalproex and gabapentin have remained unchanged since before his hospitalization)
- A multivitamin daily
- Naproxen (Naprosyn, Aleve) 250 mg up to two times a week for arthritic knee pain
- Aripiprazole (Abilify). This antipsychotic drug was recently discontinued because of parkinsonian symptoms, which then gradually improved.
- Memantine (Namenda), which is indicated for the treatment of moderate to severe Alzheimer disease. The patient reports that he stopped taking it after 3 weeks because he did not perceive it to be helping.
THE INITIAL EVALUATION
Temperature 98.3°F (36.8°C), pulse 60 beats per minute, respirations 16 per minute, blood pressure 126/64 mm Hg sitting and 118/71 mm Hg standing.
The patient is well groomed, alert, and cooperative. His head, eyes, ears, nose, and throat are normal. His teeth are in good condition. His skin is normal. We note no thyromegaly, carotid bruits, or palpable lymphadenopathy. His lungs are clear to auscultation. Results of cardiac, abdominal, and musculoskeletal examinations are all normal.
His deep tendon reflexes, sensory and motor testing, and gait are normal. The cerebellar examination is normal, aside from a mild tremor in his right hand when it is outstretched, with no resting tremor or cogwheel rigidity.
On the Mini-Mental State Examination (MMSE) he scores a perfect 30/30 (normal 24–30). He can draw a clock normally. His score on the short-form Geriatric Depression Scale is 4/15 (a score of 6 or higher indicates depression).
- Serum lithium level 0.8 mmol/L (therapeutic range 0.5–1.5 mmol/L) (his previous values are not available)
- Thyroid-stimulating hormone level 1.61 μU/mL (normal 0.40–5.50)
- Complete blood cell count and comprehensive metabolic panel values are within normal limits.
Magnetic resonance imaging
Noncontrast magnetic resonance imaging of the head reveals two nonspecific punctate foci of high signal intensity on T2-weighted images in the left frontal white matter, but the results are otherwise normal.