A mysterious loss of memory

Table

Neuropsychiatric conditions associated with MS

EVALUATION: Dysthymia

Mrs. K reports memory problems as her chief complaint. She also complains of a depressed mood, irritability, distractibility, and insomnia since her memory problems began, and admits being readily tearful. Mrs. K has difficulty “turning off her thinking” at night, which leads to delayed sleep onset, but denies sleeplessness, racing thoughts, or feelings of euphoria.

Her thought process is coherent and goal-directed, and she denies having auditory or visual hallucinations or active or passive suicidal or homicidal ideation. She scores 29/30 on the Mini-Mental State Exam, but by interview she appears to have impaired remote memory. Mrs. K demonstrates unimpaired judgment and good insight.

The author’s observations

Mrs. K meets DSM-IV-TR criteria for dysthymic disorder and agrees to start mirtazapine, 15 mg at bedtime. I chose this antidepressant because Mrs. K continues to complain of difficulty falling asleep, and mirtazapine is known to significantly decrease sleep latency and increase total sleep time. Approximately one-half of patients with MS will experience depression.^1,9 In a recent study of 245 MS patients followed in a neurology clinic, two-thirds of those who met criteria for major depressive disorder did not receive antidepressants.¹⁰

TREATMENT: A new strategy

After 2 more months Mrs. K’s mood is euthymic and she demonstrates a bright affect, but she experiences continued decline in short- and long-term memory and reports increasing frustration with simple tasks. The rest of her mental status exam is unremarkable. I instruct her to reduce the mirtazapine dosage to 15 mg/d.

At the next visit 10 weeks later, she again presents with a euthymic mood and a bright affect. She says she attempted to decrease mirtazapine but experienced increased irritability so she remained on the 30-mg dose, with a positive effect on her mood and reduced irritability. Unfortunately, her memory problems persist.

Approximately 2 years after Mrs. K’s first visit, I devise a new pharmacologic strategy. Mrs. K believes that she no longer is depressed and that her only problem is her inability to recall events. To address this, I decide to try memantine, which has been shown to cause modest improvement in clinical symptoms in severe stages of Alzheimer’s disease¹¹ and also has been reported to be useful in the treatment of cognitive impairment in some bipolar disorder patients.¹² I start memantine at 10 mg/d and titrate up to 20 mg/d in 3 months.

The author’s observations

Mrs. K’s substantial memory improvement while receiving memantine warrants considering the drug for patients with cognitive dysfunction attributable to MS. Memantine is an uncompetitive NMDA receptor antagonist that the FDA approved in 2003 to treat moderate-to-severe Alzheimer’s disease (Box).^11,13 It is generally well tolerated and safe, with a low potential for drug-drug interactions. In clinical trials of patients receiving memantine for Alzheimer’s disease and vascular dementia, the most commonly reported side effects were dizziness, headache, constipation, and confusion.¹⁴

A recent trial of memantine therapy for MS at the University of Navarra was suspended for reversible mild-to-moderate neurologic side effects.¹⁵ A phase II/phase III double-blind placebo-controlled trial at the University of Oregon designed to determine whether memantine is an effective treatment for memory and cognitive problems associated with MS is recruiting participants.¹⁶