Historical Trends in the Diagnosis of Peduncular Hallucinosis

Peduncular hallucinosis (PH) describes the clinical syndrome of vivid, dream-like visual hallucinations that intrude on normal wakefulness. Additional clinical deficits, especially ophthalmoparesis, have historically been an important part of the diagnosis and localization of this syndrome. We examined how modern neuroimaging has impacted the diagnosis of PH. We reviewed all available cases of PH, including 3 of ours and all previously reported in the literature. We determined whether other eye movement abnormalities were part of the clinical presentation and whether a neuroimaging study was performed to make the diagnosis. A total of 85 cases were identified and evaluated. Eye movement abnormalities were present in 12/15 (80%) without a neuroimaging study but in only 24/70 (34%) of cases in which a neuroimaging study was performed (P = 0.001). Although eye movement abnormalities historically have been considered a key localizing clinical feature supporting the diagnosis of PH, we found that in the era of modern neuroimaging, co-occurring eye movement abnormalities are far less frequent and are not a requisite feature of the diagnosis.

Original Contribution Historical Trends in the Diagnosis of Peduncular Hallucinosis Kristin M. Galetta, MD, Sashank Prasad, MD Background: Peduncular hallucinosis (PH) describes the clinical syndrome of vivid, dream-like visual hallucinations that intrude on normal wakefulness. Additional clinical deficits, especially ophthalmoparesis, have historically been an important part of the diagnosis and localization of this syndrome. We examined how modern neuroimaging has impacted the diagnosis of PH. Methods: We reviewed all available cases of PH, including 3 of ours and all previously reported in the literature. We determined whether other eye movement abnormalities were part of the clinical presentation and whether a neuroimaging study was performed to make the diagnosis. Results: A total of 85 cases were identified and evaluated. Eye movement abnormalities were present in 12/15 (80%) without a neuroimaging study but in only 24/70 (34%) of cases in which a neuroimaging study was performed (P = 0.001). Conclusions: Although eye movement abnormalities historically have been considered a key localizing clinical feature supporting the diagnosis of PH, we found that in the era of modern neuroimaging, co-occurring eye movement abnormalities are far less frequent and are not a requisite feature of the diagnosis. Journal of Neuro-Ophthalmology 2018;38:438-441 doi: 10.1097/WNO.0000000000000599 © 2017 by North American Neuro-Ophthalmology Society also had nausea, vomiting, complete left third and sixth nerve palsies, right-sided weakness, and bilateral tremors. On the basis of these findings, Lhermitte clinically localized the lesion to the midbrain and pons, but he did not have anatomical proof at the time (2,3). In 1927, Van Bogaert (4) described a similar case, with fascicular third nerve palsy and crossed hemiparesis, in which a midbrain lesion was confirmed at autopsy. In 1936, De Morsier (5) suggested that the lesions producing this hallucinatory syndrome may be anatomically diverse. Most previously published cases of PH also have included other prominent neurological signs, in particular eye movement abnormalities, that aided localization to the brainstem (6). With the development of modern imaging techniques, however, it has become possible to identify cases of PH attributed to a small brainstem or diencephalic lesion, while other neurologic abnormalities are not evident. In this study, we review all available cases of PH to examine the impact of modern neuroimaging on the diagnosis of this condition without reliance on other accompanying clinical deficits. METHODS I n his original report of peduncular hallucinosis (PH) in 1922, Lhermitte (1) described a 72-year-old woman with vivid, formed visual hallucinations especially at dusk. She Department of Neurology (KMG, SP), Brigham and Women's Hospital, Boston Massachusetts; and Department of Neurology (KMG), Massachusetts General Hospital, Harvard Medical School, Boston Massachusetts. The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the full text and PDF versions of this article on the journal's Web site (www. jneuro-ophthalmology.com). Address correspondence to Sashank Prasad, MD, Department of Neurology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02215; E-mail: [e-mail] 438 We reviewed all published cases of PH, beginning with Lhermitte's original description. Cases were found by searching PubMed, ScienceDirect, Google Scholar, and MEDLINE using the following specific key search terms: "Peduncular Hallucinosis," "Lhermitte hallucinations," "brainstem hallucinations," and "Lhermitte syndrome." Articles in foreign languages were translated into English. Articles that presented unique case reports were considered for inclusion. Additional studies were identified by checking the reference lists of the retrieved studies. Peduncular hallucinosis was defined by the authors of each individual case report. Patients with afferent visual loss, visual field deficits, toxic exposure, and preexisting psychiatric conditions were excluded, but our ability to identify the presence of these features was limited by the details provided in each published report. Galetta and Prasad: J Neuro-Ophthalmol 2018; 38: 438-441 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Patients were grouped based on whether a diagnostic neuroimaging study had been performed. We determined the frequency of reported eye movement abnormalities among patients in each group using chi-square modeling. Stata 13.1 (StataCorp, College Station, TX) software was used to perform all statistical analyses and calculations. Three cases of PH which we evaluated, all without associated eye movement abnormalities, also were included in the analysis. Case 1 A 34-year-old woman with a history of cerebral palsy, migraines, and multiple sclerosis was referred for neurologic evaluation with new visual illusions for several weeks. At night, she often would see a bright green light and other unformed patterns. She also observed vivid formed hallucinations, including frogs, lizards, or mice on the floor. These visual illusions did not occur during the daytime. They were not associated with her headaches. On examination, she was alert and oriented, with a visual acuity of 20/25 in each eye. Color vision and confrontation visual fields were normal, as were ocular ductions and alignment. The fundus examination was unremarkable, and the remainder of the neurologic examination showed no new deficits, with stable, mildly reduced sensation on the right face and body, mild proximal weakness in the left arm and right leg, dysmetria of the left arm on finger-to-nose testing, increased reflexes on the right, and ataxic gait. Brain MRI showed a new lesion in the dorsal pons (Fig. 1A). There also were stable periventricular, subcortical, and callosal white matter lesions. Case 2 A 71-year-old man with a history of hypertension and coronary artery disease came to the hospital after sudden onset occipital and neck pain. He was found to have extensive subarachnoid hemorrhage at the foramen magnum extending into the fourth ventricle. Five days after the onset of symptoms, he noticed visual hallucinations, which he described as scenes reminiscent of "British movies," such as people in top hats walking along the Thames River. He also recalled seeing other hallucinations of door numbers melting in front of him and a duck sitting on his shoulder. He noticed that the visual hallucinations were more frequent when he was drowsy. Examination demonstrated normal attention, memory, and language. Visual acuity was 20/40, right eye and 20/25, left eye. Color vision and confrontation visual fields were normal. The ocular ductions were full except for slight limitation of upgaze. There was no nystagmus. Slit-lamp examination revealed mild cataracts while the fundus examination in each eye was unremarkable. Strength and sensation were normal. There was mild bradykinesia and a slight postural tremor in both hands. The reflexes were 3+ at the biceps, patella, and ankles bilaterally. His gait was slightly slow. Brain computed tomography (CT) showed subarachnoid blood around the foramen magnum tracking into the fourth ventricle and around the midbrain, occipital, and posterior parietal lobes (Fig. 1B). Subsequent CT scans over the next 3 days showed near resolution of the hemorrhage and the patient's symptoms resolved. Case 3 An abbreviated description of this case was previously published (7). A 66-year-old man with a history of hypertension, hyperlipidemia, and atrial fibrillation was hospitalized for gastric bypass surgery and on awakening reported "weird visions." He described seeing a flooded boat and synchronized swimmers in red, white, and blue uniforms FIG. 1. Neuroimaging in patients with peduncular hallucinosis. A. Case 1. Axial FLAIR MRI shows an area of increased signal (arrow) in the dorsal pons. B. Case 2. Axial computed tomography reveals hemorrhage around the brainstem. C. Case 3. Diffusion-weighted MRI demonstrates a punctate infarction in the inferior dorsal midbrain on the left side. Galetta and Prasad: J Neuro-Ophthalmol 2018; 38: 438-441 439 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution (see Supplemental Digital Content, Video, http://links. lww.com/WNO/A282). He saw warped clocks, snakes that seemed to wrap around his legs, and smoke rising from the nursing station. He was lucid during these hallucinations with normal level of arousal, attention, and memory. Visual acuity was 20/25, right eye, and 20/20, left eye. Visual fields were normal to confrontation testing, and eye movements and ocular alignment were normal. Strength, sensation, coordination, reflexes, and plantar responses were normal. Brain MRI revealed a small area of diffusion restriction in the left dorsal midbrain, in the region of the superior colliculus (Fig. 1C). The hallucinations abated significantly after 1 week. In follow-up evaluation 2 months later, his wife reported that he had begun to kick and shout during dreams, consistent with rapid eye movements behavior disorder. The neurologic examination remained normal. RESULTS A total of 101 cases of PH were collected; 85 met the inclusion and exclusion criteria. Many cases documented the neurologic examination as "otherwise unremarkable" or "normal" (see Supplemental Digital Content, Table E1, http://links.lww.com/WNO/A281). Only 10 cases clearly documented that visual fields were normal, although it was not clear by what method they were tested. The ages of patients ranged from 8 to 87 years, with a mean age of 56.3 ± 18.2 years. There were 25 cases that clearly defined the number of days from beginning of hallucinations to resolution. Among these reports, the average duration of symptoms was 44.8 ± 88.8 days. There were 68 case reports with clearly defined etiologies of PH. These included a variety of lesions involving disparate sites in the rostral brainstem or thalamus, including ischemic infarction (43 cases), mass lesion (10 cases), subarachnoid hemorrhage of the basal cisterns (4 cases), demyelination (3 cases), intraparenchymal hemor- rhage (4 cases), vasospasm (1 case), encephalitis (2 cases), and venous congestion (1 case). Among patients with PH, associated eye movement abnormalities were reported much more frequently in patients before the era of modern neuroimaging compared with those reported more recently (Fig. 2). Among patients without CT or MRI imaging, 12/15 (80%) had associated eye movement abnormalities. By contrast, among those with CT or MRI, 24/70 (34%) had associated eye movement abnormalities. The difference between these groups was statistically significant (P = 0.001). DISCUSSION Visual hallucinations are a relatively common neurological complaint, often associated with migraine, visual loss, seizures, neurodegenerative conditions, or triggered by a variety of pharmacological agents. Peduncular hallucinosis is an uncommon but important cause of visual hallucinations, caused by a structural lesion of the rostral brainstem or diencephalon. An accurate diagnosis is critical to establish the underlying etiology and institute appropriate management. Eye movement abnormalities historically have been considered a key clinical feature supporting the diagnosis of PH. As such, the conventional view of PH is that it is common to have "other associated signs from damage to adjacent structures in the midbrain including unilateral or bilateral oculmotor nerve palsy, hemiparkinsonism, hemiparesis, and gait ataxia" (6). Since the first clinicoradiographic case of PH was reported in 1987 (8), however, several reports have documented a range of lesions producing this dramatic syndrome in the absence of eye movement abnormalities, and sometimes without any objective neurologic deficits. Our analysis of all reported cases before and after the advent of modern neuroimaging demonstrates that concomitant eye movement abnormalities are only present FIG. 2. Clinical presentation of peduncular hallucinosis (PH) over time. The proportion of cases of PH with eye movement abnormalities (in light gray) and those without (in dark gray) is shown by decade. Above each bar is the total number of cases reported in these subgroups. 440 Galetta and Prasad: J Neuro-Ophthalmol 2018; 38: 438-441 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution in a minority of cases and are not a requisite feature of the diagnosis. It is important for clinicians to be aware that PH can present without other objective deficits, and that neuroimaging studies can help confirm a suspected diagnosis. Peduncular hallucinosis is often a challenging diagnosis, especially in the absence of objective neurologic findings referable to the brainstem. We have shown that posterior circulation infarction is the most common cause, implying that PH is an important consideration in patients with vascular risk factors who acutely develop vivid hallucinations. Patients with PH often describe complex hallucinations, particularly of animals and people. Among cases where the duration was clearly described, the hallucinations typically improved substantially over the course of several months. Our review revealed a variety of lesion locations causing PH. Boes et al (7) also showed that PH may result from anatomically disparate lesions. Their analysis used resting state functional imaging data in normal individuals to demonstrate that the responsible lesion causing PH is associated, in virtually all cases, with a distributed functional network that includes association visual areas. The implication of this finding, as Lhermitte had originally proposed, is that an acute lesion within the thalamus or rostral brainstem can give rise to hallucinations by causing disinhibition of neural activity in remote, functionally connected visual areas. A limitation of our study is that many of the reported cases of PH lacked documentation of visual acuity and visual fields. This raises the possibility that some of these patients may have had release hallucinations. Documentation of afferent visual function in future reports may help define PH more accurately. Our analysis of cases of PH without other neurologic signs highlights that isolated hallucinations can be the sole Galetta and Prasad: J Neuro-Ophthalmol 2018; 38: 438-441 presenting feature of this condition. Modern imaging has redefined the anatomic correlates of this dramatic clinical disorder (7). STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: S. Prasad and K. M. Galetta; b. Acquisition of data: K. M. Galetta; c. Analysis and interpretation of data: S. Prasad and K. M. Galetta. Category 2: a. Drafting the manuscript and revising it for intellectual content: S. Prasad and K. M. Galetta. Category 3: a. Final approval of the completed manuscript: S. Prasad and K. M. Galetta. REFERENCES 1. Lhermitte M. Syndrome de la calotte du pedoncule cérébral. Les troubles psycho-sensoriels dans les lesions du mésocéphale. Revue Neurologique. 1922;2:1359-1365. 2. Rozanski J. Peduncular hallucinosis following vertebral angiography. Neurology. 1952;2:341-349. 3. 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Ann Neurol. 1987;21:602-604. 441 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.