Peduncular Hallucinosis in the Context of Juvenile Pilocytic Astrocytoma

Neurologist Jacques Lhermitte first described peduncular hallucinosis (PH) in 1922 as a rare, heterogeneous syndrome characterized by visual hallucinations secondary to lesions of the brainstem and thalamus (1–3). Prevalence of the condition is unknown; a meta-analysis conducted by Galetta and Prasad (4) identified 85 proposed cases of PH in the available literature. The etiology of these lesions includes stroke, neoplasm, and infection (3, 4). The unique presentation of hallucinations associated with PH is thought to be associated with damage to the reticular and visual systems of the brainstem (5, 6). Visual hallucinations associated with PH may involve auditory or tactile sensations and be accompanied by behavioral abnormalities. Such hallucinations frequently contain elements from nature and real or fictional characters (3). PH generally resolves without treatment, but antipsychotic agents, such as olanzapine and quetiapine, have demonstrated efficacy in management of persistent hallucinations (7). Our case adds insight to the unclear pathophysiology of the phenomenon and contributes to the limited literature on PH in younger patient populations.

Case Presentation

A 25-year-old female with a complex medical history, including juvenile pilocytic astrocytoma (JPA) treated with chemotherapy and radiation, epilepsy, adrenal insufficiency, and hypothyroidism, presented to the emergency department (ED) with a 2-week history of worsening auditory and visual hallucinations. From a psychiatric standpoint, the patient had no primary psychiatric diagnoses before the onset of the hallucinations. The patient had gross motor and speech delays and was blind and deaf at baseline. Outpatient medications included hydrocortisone, oxcarbazepine, and tramatenib, a targeted chemotherapy drug. A week prior to her ED presentation, she was started on oral olanzapine 5 mg by an outpatient psychiatrist for her hallucinations, but she experienced no improvement in symptoms.

The patient’s hallucinations included “singing hairs,” waterfalls on the walls and ceilings, and “green goo” enveloping her body. She also reported having conversations with fictional television characters. The patient’s family reported a 7-month history of similar hallucinations, including “evil black clouds” and a stuffed animal giving commands, along with several hospitalizations for altered mental status during this period. The patient’s laboratory workup was notable for mild hyponatremia at 132 mEq/L (reference range, 135–145). Head computed tomography without contrast obtained on admission revealed an unchanged position of the suprasellar mass. The stability of the tumor was confirmed with magnetic resonance imaging with contrast (Figure 1).

Because of the patient’s complex medical history, the differential diagnosis was broad, but her history and constellation of symptoms supported the diagnosis of PH. Olanzapine was gradually increased to 5 mg twice daily, and her hallucinations became less frequent and distressing in nature. At the time of discharge, the patient was medically stable with improvements in orientation and verbal communication.

Discussion

We outlined the development of visual and auditory hallucinations in a 25-year-old female with a history of JPA. The differential diagnosis for the hallucinations included PH, Charles Bonnet syndrome (CBS), chemotherapy-induced psychosis, and other primary psychiatric or general medical pathologies.

PH is a syndrome of auditory, visual, or tactile hallucinations as a manifestation of midbrain, pontine, or thalamic insult (5). The patient’s tumor was located in the sellar and hypothalamic regions, with mass effect on the optic chiasm, right frontal lobe, and pons, consistent with the anatomy that is typically affected in PH (6). The content of the patient’s hallucinations, involving vivid, complex imagery of people and themes from nature, is very similar to that in previously reported cases of PH (5, 6). The presence of auditory hallucinations in conjunction with visual hallucinations also helps differentiate PH from other neuropsychiatric diagnoses involving sensory hallucinations. Furthermore, the duration and chronicity of the patient’s hallucinations were consistent with this diagnosis. Some reports have described sleep-wake disturbances as a sequela of PH, which our patient also experienced (5).

Another consideration was CBS, which presents as visual hallucinations thought to be a result of disinhibited neurons in the visual cortex that have lost afferent input (8). These hallucinations range from abstract images to complex formed images of objects or other people. For patients with this syndrome, onset of hallucinations typically arises within the first year of ocular insult (9). In this case, however, the patient developed the hallucinations many years following the onset of visual impairment. Additionally, CBS does not involve hallucinations in auditory or other sensory modalities, which our patient experienced.

The details of this patient’s case raise the possibility of musical ear syndrome (MES). MES has been described as the auditory counterpart of CBS, because it is characterized by auditory hallucinations in individuals with hearing loss and preserved cognitive function (10, 11). Although the etiology is not entirely clear, it is theorized that MES may result from loss of sensory afferent input, similar to CBS (10). In both MES and CBS, patients are typically aware that their hallucinations are unreal, which is consistent with our patient’s presentation (10–12).

Because of the delicate location of the patient’s tumor, nonsurgical treatment options for disease recurrence were investigated via tumor genomic studies. Guided by her oncology team, she was treated with trametinib, a selective MEK 1/2 pathway inhibitor targeting the Ras-Raf mitogen-activated protein kinase pathway. Use of these targeted molecular inhibitors in cancer therapy is relatively novel, and the neurologic and psychiatric effects of these drugs remain poorly understood. Previous reports have cited altered mental status and hallucinations as side effects of targeted tyrosine kinase inhibitors (13, 14). In this case, it should be noted that despite discontinuation of the medication, the hallucinations continued to worsen.

The social implications of intensive therapies and prolonged hospitalizations at a young age could be a contributing factor to the development of a primary psychiatric disorder. Based on DSM-5 criteria, schizophrenia or a mood disorder with psychosis could present with hallucinations similar to those of the patient (15). Because of the patient’s impaired communication and developmental delays, collection of a full psychiatric history was limited. However, the patient had no previously established psychiatric diagnoses. The presence of hallucinations without overlapping features of schizophrenia or a mood disorder with psychosis, including flat affect, mania, apathy, or delusions, further points away from a primary psychiatric etiology.

Medical and iatrogenic causes for the hallucinations were explored during the patient’s admission. Outpatient medications that could have contributed to alterations in mental status included hydrocortisone and oxcarbazepine. However, the medication doses had not been changed recently. The hyponatremia at admission could present with encephalopathic symptoms, such as altered mental status or confusion (16). This diagnosis was lower on the differential because of the persistence of symptoms despite electrolyte repletion. Cognitive dysfunction and psychosis as a late effect of childhood central nervous system irradiation have also been reported (17). The lack of any new neurologic deficits during the onset of the hallucinations makes this a less likely cause, particularly given the stable imaging findings.

This report proposes a case of PH in a patient with JPA. Although rare, the patient’s psychiatric abnormalities coupled with her medical history were consistent with the pathophysiology of the disorder. Taken together, PH should be considered when a patient with neurologic pathology presents with the unique constellation of symptoms characterized by the syndrome. Future research could explore long-term outcomes of patients with PH to better grasp the prognosis of the syndrome.

Key Points/Clinical Pearls