Brain (1998), 121, 1819–1840 REVIEW ARTICLE Complex visual hallucinations Clinical and neurobiological insights M. Manford1 and F. Andermann2 1Department of Clinical Neurology, Addenbrooke’s Correspondence to: Dr M. Manford, Department of Hospital, Cambridge, UK and 2Montreal Neurological Clinical Neurology, Addenbrooke’s Hospital, Hills Road, Institute, Montreal, Canada Cambridge CB2 2QQ, UK. E-mail: [email protected] Summary Complex visual hallucinations may affect some normal hallucinations are probably due to a direct irritative individuals on going to sleep and are also seen in process acting on cortical centres integrating complex pathological states, often in association with a sleep visual information. (ii) Visual pathway lesions cause disturbance. The content of these hallucinations is defective visual input and may result in hallucinations striking and relatively stereotyped, often involving from defective visual processing or an abnormal cortical animals and human figures in bright colours and release phenomenon. (iii) Brainstem lesions appear to dramatic settings. Conditions causing these affect ascending cholinergic and serotonergic pathways, hallucinations include narcolepsy–cataplexy syndrome, and may also be implicated in Parkinson’s disease. peduncular hallucinosis, treated idiopathic Parkinson’s These brainstem abnormalities are often associated with disease, Lewy body dementia without treatment, disturbances of sleep. We discuss how these lesions, migraine coma, Charles Bonnet syndrome (visual outside the primary visual system, may cause defective hallucinations of the blind), schizophrenia, hallucinogen- modulation of thalamocortical relationships leading to induced states and epilepsy. We describe cases of a release phenomenon. We suggest that perturbation of hallucinosis due to several of these causes and expand a distributed matrix may explain the production of on previous hypotheses to suggest three mechanisms similar, complex mental phenomena by relatively blunt underlying complex visual hallucinations. (i) Epileptic insults at disparate sites. Keywords: visual hallucinations; thalamocortical; arousal; serotonin Abbreviations: 5HT 5 5-hydroxytryptamine; LSD 5 lysergic acid diethylamine tartrate; PGO 5 ponto-geniculo-occipital (waves); REM 5 rapid eye movement Introduction Maury (1848) coined the term hypnagogic hallucinations to (Leaning, 1926). The content of the hallucinations is dramatic; describe his own vivid hallucinations in the state of they are usually in vivid colours and may evolve from simple drowsiness, just before sleep. There have been several further spots of light through geometric patterns to complex images, detailed descriptions of the phenomenon, especially that by or they may be complex from the outset. Sufferers often see Leaning (Baillarger, 1846; Leroy, 1922; Leaning, 1926; human figures or faces (sometimes torsos without heads or Tournay, 1941; Foulkes and Vogel, 1965). Up to one-third vice versa); animals (real or bizarre), sometimes in miniature of normal individuals may experience these hallucinations, (Lilliputian hallucinations) or scenery of outstanding beauty. when going off to sleep, anywhere from once in a lifetime The images may be static or moving and their detail and to most nights, but they are particularly common in the vividness seem to exceed anything experienced in real life. narcolepsy–cataplexy syndrome. The hallucinations may last In contrast to the dreams of deep sleep, the dreamer is on from a few seconds to ù15 min, probably depending on the the outside observing the action which may evolve slightly duration of this stage of drowsiness. Fever may trigger the but there is rarely a ‘plot’ in which the dreamer is actively hallucinations in those predisposed and even in these early involved. Modalities other than vision may be involved, series, it was recognized that sufferers often had poor vision especially faces may talk, but this is relatively uncommon. © Oxford University Press 1998 1820 M. Manford and F. Andermann The emotional reaction to the images may be neutral, pleasant than the other and the symptom resolved after 1 min. Ten fascination or extreme fear. days later he developed a ball of light, with a red and blue Several pathological conditions may be associated with surround in his left visual hemifield, associated with headache very similar, striking hallucinations (often with preserved and mild drowsiness. This lasted 2–3 min but recurred many insight) and altered awareness (Table 1). They include times over several hours. The images then changed to a man peduncular hallucinosis, delirium tremens, drug-induced in a suit and a black butterfly, occurring especially with his hallucinations, migraine coma, treated Parkinson’s disease, eyes shut. The symptoms improved over several days but Lewy body dementia and Charles Bonnet syndrome hallucinations and distressing dreams recurred several weeks (hallucinations of the blind). The patient’s belief in the reality later. Hallucinations always occurred when he was relaxed of the images varies between conditions, and is especially but awake, with his eyes shut and waiting to go to sleep. He affected by cognitive factors and their level of awareness. lay and watched them for prolonged periods until he fell The patients least likely to be distressed by the hallucinations asleep. They were not restricted to one part of the visual are those with Charles Bonnet syndrome, perhaps reflecting field and disappeared on opening his eyes. They never preservation of CNS function and adaptability. In general, occurred at times of poor illumination if his eyes were open. once familiar with the hallucinations, the patients find them He often saw a dwarf whose face was hidden by a lamp. non-threatening and have insight into their nature, in The dwarf was accompanied by a clown in a striped grey distinction to hallucinations associated with psychiatric suit. On one occasion there were three dwarves with egg- illness. shaped heads who were at the bottom of his bed. They were It has been difficult to find a common thread to explain wearing cloaks and playing with his feet, although he did the occurrence of hallucinations in these diverse conditions, not feel anything abnormal in his feet. One dwarf had a but their striking similarity suggests that they may act through ‘comforting golden face with blue eyes’ and told him: ‘It’s related mechanisms, despite apparently disparate lesion sites all over’. He has also seen figures dressed in 17th century and disease processes. The pathology is sometimes Cavalier’s clothes or women in Victorian clothes pushing extracortical, for example in peduncular hallucinosis and wicker perambulators with babies. When asleep he had vivid Charles Bonnet syndrome. In other conditions, for instance dreams including bright, striped fish swimming across his delirium tremens and drug-induced hallucinations, there is view. In retrospect, he understood these hallucinations were no fixed pathological substrate. Although the extracortical not real but, at the time, he was frightened by them. visual system may support some visual function, this is vague Non-insulin-dependent diabetes mellitus and mild hyper- and semiconscious (Cowey and Stoerig, 1991; Matthews and tension were diagnosed at his first presentation, but there Kennard, 1993). It seems likely, therefore, that the visual was no other significant medical history. MRI scan showed detail of these sorts of hallucinations is due to a cortical small specks of increased T signal, consistent with ischaemia phenomenon, although some of the causes may be acting on 2 in the right basal ganglia and right thalamus, including the the cortex indirectly or from a remote site. Previous authors 18 have suggested three basic underlying mechanisms: (i) pulvinar. [ F]Fluorodeoxyglucose-PET showed a larger area irritative processes in the association cortex generating of ischaemia in the right thalamus and ipsilateral occipital discharges falsely interpreted as due to sensory inputs; (ii) cortex (Fig. 1). release phenomena due to defective visual input causing Visual fields and visual evoked potentials were normal. faulty cortical stimulation; and (iii) faulty visual processing in Neuropsychometric assessment was entirely normal with no which inputs are normal but lesions result in an inappropriate visuospatial deficit. Brainstem evoked potentials showed loss pattern of cortical excitation (Cogan, 1973; Asaad and of waves II–IV but a normal I–V interval. No episodes of Shapiro, 1986). These general statements have never been hallucinosis occurred during 48 h of ambulatory EEG. The taken further to try and provide a more detailed neuro- EEG was normal and sleep architecture appeared normal. biological explanation for hallucinations. We describe the similarities and differences in clinical Comment. In his case, the investigations and clinical picture features of the various causes of complex hallucinations in point to an abnormality at thalamic or cortical level although relation to their pathophysiology to try and elucidate possible there is no current clinical or investigation evidence of visual common elements. We shall explore how these conditions pathway malfunction or cortical disease. The reduced blood could influence activity in striate, extrastriate and association flow in occipital cortex may represent primary cortical cortices and in subcortical visual centres. involvement or reduced activity, secondary to under-activity of the afferent thalamic nuclei.