History: 3 ‘Uncontrollable’ months
Ms. M, age 57, presents to the ER complaining of coordination problems and involuntary limb movements that have gradually worsened over 3 months.
Two months ago, Ms. M’s primary care physician and neurologist diagnosed her with conversion disorder. Brain MRI at the time showed mild chronic ischemic changes; cervical spinal cord MRI was normal. The neurologist referred Ms. M to a psychiatrist, who prescribed duloxetine, dosage unknown. She started having suicidal thoughts and trembling after starting the medication, so she stopped taking it after 1 week.
Physical exam shows upbeat nystagmus, inconsistent sensory findings, limb ataxia that is more pronounced on the right side, and uncontrollable limb movements, particularly of the right arm.
Ms. M is divorced, lives alone, and works as a medical secretary. Four months ago, she marked the fifth anniversary of her daughter’s death from a drug overdose at age 20. Her parents, whom she cared for, died within the last 3 years. Her son recently left home to attend graduate school, and she is estranged from the rest of her family. She endorses depressed mood and grief over her daughter’s death but says she has no one with whom to talk. She also feels persistent guilt, as she was out on a date when her daughter tried to call home shortly before her death.
The limb movements and lack of coordination are increasingly interfering with Ms. M’s life. She often uses her left hand to stop the right from moving and to guide it in simple tasks, such as opening doors. She can no longer hold a cup of coffee in her right hand or stand on stools at work to reach overhead shelves. At presentation, Ms. M’s imbalance and involuntary movements are so severe that she cannot walk. A coworker drove her to the ER.
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The authors’ observations
A neurologist who evaluates Ms. M in the ER is concerned about her vertical nystagmus, which, unlike horizontal nystagmus, is almost always pathologic. The neurology service admits her for further evaluation.
Ms. M’s age, recent normal MRIs, physical presentation, and lack of other findings suggest a paraneoplastic syndrome. Ataxia associated with subacute cerebellar degeneration can indicate an occult malignancy and is closely linked to gynecologic and breast cancers. Cerebellar degeneration often begins with loss of coordination, can be unilateral, and can appear as intention myoclonus.1
Also considered are:
- opsoclonus-myoclonus, which presents with ataxia, myoclonus, and random chaotic eye movements. This paraneoplastic disorder is less common in adults than in children, however.1
- alien hand/limb syndrome, in which the limb unintentionally performs seemingly purposeful movements, often prompting the patient to restrain the limb with the other hand. This syndrome, however, usually localizes to a lesion in the medial frontal lobe or corpus callosum. Ms. M’s brain MRIs show no such lesion.
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Treatment: Searching for answers
We order an extensive neurologic workup for Ms. M, focusing on causes of inherited and acquired ataxias. The evaluation includes:
- brain and cervical spine MRIs to check for focal cerebral and spinal lesions
- EEG to search for seizure activity and slowing characteristic of encephalopathies
- urine heavy metal testing for toxic processes
- thyroid-stimulating hormone testing for hypothyroid-associated ataxia.
Paraneoplastic workup includes chest, pelvic, and abdominal CT; a gynecologic exam; and a mammogram. All results are negative or equivocal.
We also order blood tests for paraneoplastic antibodies, evidence of opsoclonus/myoclonus, and spinocerebellar ataxia genetic testing; and a CSF check for protein 14-3-3 levels suggestive of prion disease. These tests, run at specialized laboratories, take 4 to 6 weeks.
Ms. M remains hospitalized for 7 days for evaluation. Her movement problems persist, though they often abate when she is distracted. Her upbeat nystagmus appears intermittent. Her affect is diverse, often shifting between tearfulness and inappropriate laughter.
Based on interviews with Ms. M, the C/L team sees prominent depressive symptoms including marked difficulty sleeping, appetite loss, and excessive guilt over her daughter’s death. She also seems indifferent towards her disabling motor symptoms.
The C/L team diagnoses Ms. M with chronic and acute adjustment disorder and major depressive disorder. She is initially hesitant to take another antidepressant but agrees to try mirtazapine, 15 mg nightly, to treat her depression, decreased appetite, and sleep problems. After 2 days, mirtazapine is increased to 30 mg nightly as she is tolerating it and is willing to try a higher dosage.