Department of Psychiatry and Behavioral Sciences Eastern Virginia Medical School Norfolk, Virginia
Disclosures The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products. Dr. Spiegel is on the Speaker’s Bureau for Allergan Pharmaceuticals.
CASE 2 Akinetic mutism secondary to subarachnoid hemorrhage
Ms. G, age 47, is brought to an outside hospital with syncope and a severe headache radiating to her neck. Upon arrival, she is unconscious and requires intubation. A non-contrast head CT scan shows diffuse subarachnoid hemorrhage, 6 mm right midline shift, and a small left frontal subdural hematoma. A CT angiography of her head and neck reveals a 0.7 cm anterior paraclinoid left internal carotid artery aneurysm with ophthalmic involvement. Evidence of underlying left and right carotid fibromuscular dysplasia is also seen. Ms. G is transferred to our facility for neurosurgical intervention.
Neurosurgery proceeds with aneurysm coiling, followed by left craniotomy with subdural evacuation and ventriculostomy placement. Her postoperative course is complicated by prolonged nasogastric hyperalimentation, mild hypernatremia and hyperglycemia, tracheostomy, and recurrent central fever. She also develops persistent vasospasm, which requires balloon angioplasty of the left middle cerebral artery.
The psychiatry team is consulted on postoperative day 29 to assess for delirium. The CAM-ICU is positive for delirium, with nocturnal accentuation of agitation. Ms. G demonstrates paucity of speech and minimal verbal comprehension. She starts oral ziprasidone, 5 mg/d at bedtime. In addition to her original CNS insult, scopolamine patch, 1.5 mg, to decrease respiratory secretions, and IV metronidazole, 500 mg every 8 hours, for skin-site infection, may have been contributing to her delirium.
Ms. G’s delirium quickly resolves; however, on day 32 she continues to demonstrate behavioral and cognitive slowing; The NPI A/I frequency score is 28, with a severity score of 3, for a total score of 84, indicating severe behavioral disturbance on the NPI A/I subsection. Methylphenidate, 2.5 mg/d, is started and the next day is increased to 5 mg twice a day to treat severe akinetic mutism. Ms. G also is switched from ziprasidone to olanzapine, 2.5 mg/d at night.
By day 37, the tracheostomy is decannulated, and Ms. G demonstrates a full level of alertness, awareness, and attention. Her affect is full range and appropriate; however, she demonstrates residual language deficits, including dysnomia. On day 38, Ms. G is discharged with an NPI A/I subscale score of 5, indicating a mild behavioral problem.
What these cases demonstrate about DDM
These 2 cases are part of a larger, emerging conversation about the role of dopamine in DDM. Although not fully elucidated, the pathophysiology of abulia, apathy, and akinetic mutism is thought to be related to multiple neurotransmitters—especially dopamine—involved in the cortico-striatal-pallidal-thalamic network.1,8 This position has been supported by reports of clinical improvement in patients with DDM who are given dopaminergic agonists (Table 1).3,9-32
The clinical improvement seen in both of our patients after initiating methylphenidate is consistent with previous reports.10-13 Methylphenidate was selected because of its favorable adverse effect profile and potentially rapid onset of action in DDM.10-13 In cases where oral medication cannot be administered, such as in patients with akinetic mutism, short-term adjunctive IM olanzapine may be helpful, although it is not a first-line treatment.3,15
Interestingly, both of our patients showed improvement with low doses of methylphenidate. Ms. E showed rapid improvement at 2.5 mg/d, but eventually was increased to 10 mg/d. For Ms. G, who demonstrated severe akinetic mutism, rapid improvement was noted after the initial 2.5 mg/d dose; however, because of reports of efficacy of olanzapine in treating akinetic mutism, it is possible that these medications worked synergistically. The proposed mechanism of action of olanzapine in akinetic mutism is through increased dopamine transmission in the medial prefrontal cortex.3,15 Ms. G’s methylphenidate dose was increased to 5 mg/d, which was still “subtherapeutic,” because most reports have used dosages ranging from 10 to 40 mg/d.10-13 Although there were favorable acute results in both patients, their long-term requirements are unknown because of a lack of follow-up. Our findings are also limited by the fact that both patients were recovering from neurosurgical procedures, which could lead to natural improvement in symptoms over time.
