We present the case of a 66-year-old woman referred originally to Dartmouth-Hitchcock Epilepsy Center in 2010 for seizure disorder. In her 20s, she was involved in a motorcycle collision for which she was hospitalized for one week. No known traumatic brain injury (TBI) was diagnosed. Then she developed migraine headaches later, becoming more severe in her 30s. Also in her 30s and 40s, she developed fainting episodes. When she was standing for a long time, she would tumble down and get up. If she stood quickly, she would lose her vision. Those were diagnosed as syncope and were present all her life. It also seemed to run in her family.
Then, in 2007, she developed what she thought were seizures. They occurred when she was lying in bed. She would wake up and shake in the middle of the night. She would not lose consciousness. They were diagnosed as nonepileptic seizures (NES). Of note, the patient denied having any history of trauma, stressful life events, or other current stressors that might have triggered spells.
The patient initiated levetiracetam but nevertheless continued having events where she started whole-body shaking, lasting 5 to 10 minutes. She described having two recent events where she only had shaking of her right hand, arm, and face. After this event, her eyes were closed and she was very tired and slept for several hours. She had two of those right-sided events. All other events previously have included whole body shaking.
In the summer of 2008, she had an event where she was walking to the bathroom at night, she crashed down on the floor, had raccoon eyes and bruises, and was hospitalized elsewhere. There she had tilt table testing, which was positive and she was diagnosed with syncope; however, she was also noted to be hypertensive. She was not started on any medications during that outside hospitalization but was advised to sit at the edge of the bed and stand up slowly.
She also complained of having comprehension difficulties and poor memory, citing difficulties doing the laundry. At times, she was incapable of using a coffee maker that she has used for a long time and her husband confirmed that those events were more frequently occurring. She had not been sleeping very well and had difficulties concentrating. She denied feeling depressed. Physical exam found no cog-wheeling but falling diffusely with positive Romberg's and her eyes closed. She also had difficulties performing tandem gait but was able to walk on her heels and toes. The plan was for her to be admitted for video EEG (VEEG) monitoring and to have neuropsychological testing.
VEEG monitoring six weeks later in April 2010 captured multiple NES but no episodes with ictal correlates. She was discharged with outpatient follow-up outside our institution. A year later, in March of 2011, she re-presented with the chief complaints of headaches and did not have any significant NES spells. At this time, it was noted that while she did not have psychiatric care, she was taking both citalopram and clonazepam as prescribed by her primary care physician (PCP).
Half a year later in September 2011, the patient was seen with the chief complaint of headache as well as worsening depth perception. She was prescribed topiramate for her headaches and considered usage of amitriptyline, although patient was concerned about possibility of weight gain as had happened in the past. The patient was counseled on nonpharmacologic treatments of both anxiety and sleep hygiene. Nine months later in June 2012, the patient first described having more frequent falls as well as worsened headaches. For her symptoms, she was increased on topiramate prescribed hydroxyzine for moderate headaches and zolmatriptan for more severe headaches. The patient did not exhibit significant clinical improvement.
Then, in May 2013, the patient and her family described having hallucinations nearly every night, which consisted of the patient's witnessing other people talking to each other, but never to her directly. These people never talked to her or told her to do things. She denied these as the typical auditory hallucinations worrisome of primary thought disorders consisting of running commentary about the patient's own behavior. The auditory hallucinations were also never present in the absence of visual hallucinations. The visual hallucinations were nonhostile, but the patient's emotions associated with them were of fear due to uncertainty of the intentions of the people she was experiencing. However, she "knew that these people weren't really there" and that when she "turned on the lights, they would disappear." She also described episodes where she was confused and had wandered about. This happened in late February and again early March 2013. Although she had been living in the same house for 37 years, it did not feel like the same house to her.
Visual symptoms included "seeing blue spots under my eyes on the left as well as on my hands." Fundoscopic exam revealed floaters. The patient reported seeing cracks in the wall when looking at a white wall. The patient's husband reported that "she is becoming very forgetful." These hallucinations were thought to be associated with nortriptyline, and dosage was reduced to 10 mg PO at night. It was first thought and documented at the end of May 2013 that the patient may have a neurodegenerative disease especially given significant atrophy of her frontal lobes as evidenced on magnetic resonance imaging (MRI). Four months later, her falls and headaches continued, although now she was "hearing voices that are not threatening." The goal had been to decrease her nightly clonazepam dosage to see if this would allow hallucinations to improve. Of all her concerns, her headaches were causing the most misery.
At this point, referral to embedded psychiatric clinician within the neurology outpatient clinic occurred. The patient met our newly established quality improvement referral criteria by scoring above a certain threshold on depression screening. She was seen initially at the end of November, 2013. In addition to confirming her history above, it was found that family history was significant for early-onset Alzheimer's disease in the patient's brother. Physical exam did not find any cog-wheeling, rigidity, shuffling gait, or gait instability. Mental status exam revealed appearing younger than her stated age, anxious mood and flat affect, and thought content revealing the belief that "there are migrant French-Canadian workers at home threatening to hurt my family members." She had seen them at least twice or thrice.
Her Montreal Cognitive Assessment (MOCA) score was 20/30 (score breakdown: 3/5 on visuospatial/executive: missed trails and did not get hands of clock correct; attention: 5/6: missed serial 7 subtraction; language: 2/3: did not repeat sentences perfectly with regard to pronouns, singular versus plural; delayed recall: 0/5, but recalled all five with category cuing; orientation: 5/6. Her PHQ-9 and GAD-7 scores were 7 and 9, resp.).
It was thought that it would be exceedingly rare, although not impossible, for the patient to have a new-onset psychosis at this age. However, the patient's description of her symptoms was not classically Charles Bonnet syndrome, as she experienced "real people talking and interacting" in addition to just seeing them. We decided to re-do MRI and obtain dementia workup, including B12/folate, and other basic labs, which were all unremarkable.
At our second appointment several months later, we again noticed the constellation of visual hallucinations, cognitive impairment, and history of multiple falls despite not having any clear Parkinsonian features on physical exam. At this appointment, both the patient and her family were more significantly distressed by especially the auditory hallucinations component of her experiences, described as "little people threatening to do things to me or my family." Her PHQ-9 and GAD-7 scores had worsened to 10 and 17, respectively. MRI was unchanged compared to a year ago. It was thought at this time that the patient's distressing symptoms as well as psychotic symptoms could benefit from trial of quetiapine, to which the patient was naive. Concurrently, we aimed to decrease clonazepam dosage from 3 mg to 2 mg per day over several weeks.
At our 3rd appointment, a month later, the patient reported that "everybody is noticing the difference with the Seroquel (quetiapine)." In fact, she described no longer having any AVH. Her quetiapine dosage had been titrated to effect to 200 mg PO QHS. Her PHQ-9 and GAD-7 scores were both zero. Of particular significance was also that the patient had tapered off clonazepam completely. As a result, both her headaches and her memory complaints had also decreased. The patient stated that since she was doing so well, she declined formal MOCA retesting.
However, at our 4th appointment, two months since the previous one, the patient described having horrible headaches and having hallucinations again, described as "I see people in the bathroom dressed in regular clothes, and they just stand there without talking to me." The patient and her family did not seem to think that her headaches and hallucinations were connected. She also stated that sleep was awful despite taking hydroxyzine, melatonin, and quetiapine concurrently. We thus decided to transition her sertraline to venlafaxine using cross-titration.
At our 5th appointment a month and a half later, the patient had in the interim requested increasing quetiapine from 200 to 300 mg PO at night, and she was noticeably improved with both increase of quetiapine and transition from sertraline to venlafaxine. In fact, her headaches were "now gone completely" and her mood symptoms were also improved: "The new medication is a happy pill!" The patient described having minimal auditory and visual hallucinations which were "no longer bothering me."
Approximately 8 months following her initial presentation, the patient described "things as going very well": she was no longer waking up in the morning with any headaches and felt comfortable with seeing "little happy faces at night" when either falling asleep or waking up. At this point, the patient's venlafaxine dosage was 225 mg PO QDay and quetiapine dosage was between 300 and 400 mg PO at night. Given the patient's historical lack of depth perception and known history of floaters, it was thought that Charles Bonnet syndrome could be considered due to response of patient's AH to quetiapine but not her visual hallucinations. The patient was educated about the possibility that she had Charles Bonnet syndrome in addition to meeting criteria for major depressive disorder with Psychotic Features and she was reassured.
Ten to twelve months following her initial presentation, the patient described having a significant improvement in mood symptoms, and clinical exam and family collateral information indicated her Major Depression was in remission. The patient's medication dosages of venlafaxine 225 mg daily and 400 mg quetiapine at night were stable and did not cause any noticeable adverse effects, and discussion about eventually trying to find the minimally effective dose:especially in the case of the latter medication, due to concerns for potential metabolic and extrapyramidal adverse effects:ensued, although the patient and her family wanted to continue the current dosage given lack of any psychiatric symptoms.