Cases That Test Your Skills

A mysterious loss of memory

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Mrs. K develops depressive symptoms and memory loss while being successfully treated for multiple sclerosis and migraines. How would you address her cognitive decline?



Case: Worsening memory

Mrs. K, age 46, is being treated by a neurologist for stable relapsing-remitting multiple sclerosis (MS) and migraine headaches when she complains of worsening memory over the past 5 years. She reports having difficulty recalling details of recent events and conversations. She describes occasional word-finding difficulties and problems maintaining her train of thought. She forgets where she places things and has gotten lost while driving, even on familiar routes. Her husband reports she takes more time to process things in general.

Mrs. K’s cognitive decline has affected her daily life and ability to work. For 4 years, she has been an office assistant at a campground, where she takes phone reservations and keeps a site schedule. Formerly simple tasks—such as taking a phone number—have become increasingly difficult, and she cannot recall a list of 3 things to buy at the supermarket without writing them down.

Her psychiatric history is unremarkable for inpatient or outpatient treatment. She denies a history of head trauma or seizure disorder. Her medical history includes allergic rhinitis, hypothyroidism, mitral valve prolapse, fibrocystic breasts, endometriosis, and temporomandibular joint disorder. Mrs. K had a hysterectomy in 2006. She denies current alcohol or tobacco use.

As a teenager, Mrs. K suffered migraines but did not seek treatment, and her headaches remitted for about 10 years. At age 29, she started to experience tunnel vision. Three years later she reported bilateral foot numbness and was diagnosed with MS. She responded well to interferon beta-1b but her migraines returned, occurring several times a week. Her migraines are successfully treated with topiramate, 75 mg/d, for prophylactic therapy and rizatriptan, 10 mg, as needed for abortive therapy. Her medication regimen also includes:

  • eszopiclone, 2 mg/d, and amitriptyline, 10 mg/d, for insomnia
  • butalbital/aspirin/caffeine, 50/325/40 mg, as needed for tension headaches
  • fexofenadine, 12 mg/d, and budesonide, 32 mcg, 4 sprays/d, for allergy symptoms
  • esomeprazole, 80 mg/d, and famotidine, 20 mg/d, as needed for dyspepsia
  • propranolol, 120 mg/d, for hypertension
  • levothyroxine, 75 mcg/d, for hypothyroidism
  • conjugatedestrogens, 0.45 mg/d, for hypoestrogenemia
  • alprazolam, 0.25 mg/d, aspirin, 81 mg/d, vitamin E, 800 IU/d, and a multivitamin.
Her family history is remarkable for signs of neurocognitive degeneration in her father, age 75. She has 3 siblings with no known neurologic or neuropsychological symptoms.

The neurologist orders neuropsychological testing. Mrs. K demonstrates some depressive symptoms but is within normal limits across all aspects of neurocognition, including basic and complex attention, memory, bilateral motor functioning, expressive and receptive language, visuospatial/constructional function, and self-regulatory/executive functioning. The neurologist refers Mrs. K for psychiatric evaluation of her depressive symptoms.

The author’s observations

Many neuropsychiatric abnormalities may accompany MS (Table).1 These can be classified as cognitive dysfunction or disturbances in mood, affect, and behavior.

Although the cause of cognitive impairment in patients with MS is unclear, its extent and profound impact on functioning has become widely recognized over the past 20 years.2

An estimated 40% to 65% of patients with MS suffer from cognitive dysfunction.1,3 Testing indicates deficiencies most often in:

  • attention
  • information processing speed
  • working memory
  • verbal memory
  • visuospatial function
  • executive functions.4
Although in neuropsychological testing Mrs. K had scored within normal limits on memory, attention, and executive and visuospatial function, at the time of her psychiatric evaluation she is experiencing difficulties in all of these areas. Cognitive decline can occur early in the course of MS, but Mrs. K’s cognitive symptoms began approximately 10 years after she was diagnosed. The extent of the cognitive deficits commonly expands as the disease progresses.1 Cognitive dysfunction is the primary cause of MS patients’ withdrawal from the workplace5 and often leads to:
  • reduced social interactions
  • increased sexual dysfunction
  • greater difficulty with household tasks.6
When she first complained of memory loss, Mrs. K was taking topiramate for migraine prophylaxis. Multiple studies have demonstrated adverse cognitive effects from topiramate;7 however, Mrs. K had noticed substantial memory changes at least 2 years before starting topiramate. She denied experiencing worsening memory after starting topiramate and did not recall any major change after her dosage was increased to 75 mg/d. She chose to continue topiramate because it effectively prevented migraines and, in her mind, was unlikely related to her memory problems.

Long-term interferon beta-1b treatment prevents MS relapses, but a recent study found that interferon beta-1b had a negative impact on patients’ mental health composite score and in most quality-of-life subscales over 2 years.8 Nevertheless, Mrs. K received interferon beta-1b therapy for at least 9 years without noticing cognitive decline.


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