- Email: [email protected]
Chapter 14 The mystery of photopsias, visual hallucinations, and distortions
Functional Neuroscience: Evoked Potentials and Related Techniques (Supplements to Clinical Neurophysiology, Vol. 59) Editors: C. Barber, S. Tsuji, S. Tobimatsu, T. Uozumi, N. Akamatsu, A. Eisen © 2006 Elsevier B.V. All rights reserved
97
Chapter 14
The mystery of photopsias, visual hallucinations, and distortions Gastone G. Celesia* Loyola University of Chicago, 3016 Heritage Oak Lane, Oak Brook, IL 60523 (USA)
Can we unravel the mystery of visual hallucinations and other positive spontaneous visual phenomena (PSVP)? Can we find the source of visual percepts arising endogenously from the human brain? Modern neuro-imaging and physiological methods shed light on the pathophysiology of these phenomena and will be reviewed therein. PSVP are visual events occurring in isolation, in the absence of altered consciousness, dementia, or psychosis (Vaphiades et al., 1996; Celesia, 2005). PSVP include phosphenes, photopsias, visual hallucinations, visual distortions, kinetopsias, palinopsia, polyopia, and visual allesthesia. Phosphenes are unstructured lights such as flashes, sparkles, zigzag lines or rainbows, black and white or colored, static or moving. Photopsias are structured images such as geometric figures (triangles, cubes, pyramids, etc.) or other simple pictures often recurring in a repetitive pattern. Kinetopsia from “kineto” motion and “opsis” vision, is an image moving in space. Palinopsia is visual perseveration or the recurrent appearance of a visual image after the stimulus has disappeared. Polyopia is the simultaneous perception of multiple objects or structures. The same object is
*Correspondence to: Gastone G. Celesia M.D., Loyola University of Chicago, 3016 Heritage Oak Lane, Oak Brook, IL 60523, USA. Tel: +1 630 968-2199; Fax: +1 630 968-2179; E-mail: [email protected]
seen multiple times either side by side or in circles. Visual distortions refer to the abnormal perception of figures and objects and can be further subdivided into macropsia, micropsia, pelopsia, teleopsia, and metamorphopsia. Macropsia refers to the appearance of an enlargement in size of all objects seen (Fig. 1, left illustration), whereas micropsia refers to the appearance of a reduction in size of all the objects seen. Pelopsia refers to the perception that objects are closer while teleopsia refers to the perception that the objects are farther away than they are. Metamorphopsia is the distortion of the objects or figures seen (Fig. 1, right illustration). Visual hallucinations consist of complex scenes including people, animals, furniture, landscapes, vehicles that may be stationary or mobile, colored or black and white, and perceived, at least temporarily, as real. Visual hallucinations as part of PSVP are isolated without associated mental disturbances such as dementia, psychosis, or altered state of consciousness. Ophthalmologists refer to these visual hallucinations as the Charles Bonnet syndrome (Bonnet, 1796). PSVP can be due to lesions in any part of the visual system from the retina to the occipital cortex (Table 1). Thus none of the PSVP have localizing value. It is also not unusual that more than one PSVP occur in the same patient; Jacob (1980) reported visual allesthesia and palinopsia in a 24-year-old woman with a right parieto-occipital arteriovenous malformation. We have noted the co-occurrence of visual hallucinations and
98
Fig. 1. Two illustrations from Lewis Carroll’s, Alice’s adventures in Wonderland, illustration by John Tenniel. Left illustration: Alice is very small and meet a puppy “An enormous puppy was looking down at her with large round eyes, and feebly stretching out one paw, trying to touch her.” Lewis Carroll suffered from migraine (Podoll and Robinson, 1999) and his description of Alice may be a manifestation of the macropsia and visual hallucinations seen in his migrainous auras. Right illustration: Alice stretched tall, an example of metamorphopsia.
photopsias in several patients with lesions in optic radiations and or occipital lobe. Another controversy in the literature is the statement that PSVP related to central nervous system pathology are predominantly due to right hemispherical lesions (Pailas et al., 1965; Vallar and Perani, 1986; Harvey et al., 1994). Such statement ignores the fact that reports on patients with destructive brain lesions are biased by the exclusion of patients with left-side damage due to the associated language deficits that prevent accurate testing. In our study of hemianopic patients (Vaphiades
et al., 1996) despite this built-in bias, we found no statistically significant differences between right- and left-side lesions. PSVP have a prevalence of around 8–9%. Perhaps the most frequently described PSVP are the phosphenes, photopsias, and metamorphopsias of the migraine aura. Russels et al. (1995) in a study of the Danish population reported an overall lifetime prevalence of migraine of 18%, with migraine aura without headaches occurring in 8% of males and 16% of females. Twenty-six of 2110 subjects in the Framingham
99 TABLE 1 LOCATION OF LESION IN 614 CASES OF PSVP Lesion site
Retina Optic nerve Chiasma/tract Optic radiation Occipital cortex Normal subjects Total number of subjects with PSVP Total number of patients
Total (number)
Total (percent)
84 47 5 3 469 6
1.2 0.7 0.1 0.04 6.5 0.1
614 7211
8.5 100.0
study had migraine aura without headaches, a prevalence of 1.23% (Wijman et al., 1998). Lipton et al. (2002) studied the prevalence of migraine in Philadelphia County and reported a prevalence of 13% in adults. There is a remarkable agreement in all these studies that in the Western world the prevalence is approximately 13% with 3% of patients experiencing visual auras and about 1.2% having visual auras without migraine. Charles Bonnet syndrome (visual hallucinations or other PSVP in the presence of ophthalmologic dysfunction) has been reported in a variety of ocular diseases from cataracts to glaucoma, from retinitis pigmentosa to optic neuritis (Gold and Rabin, 1989; Nesher et al., 2001; Volpe et al., 2001; Burke, 2002). In summary, the most frequent cause of PSVP is migraine followed by ophthalmologic diseases associated with impairment of visual acuity equal or worse than 20/200. There are three possible mechanisms causing PSVP (Fig. 2): (1) excitation; (2) release phenomenon; (3) spreading depression (SD). Excitation can be physiological or pathological. Physiological excitation occurs at the retinal, visual pathways, lateral geniculate nucleus (LGN), and cortical level. Stimulation of the eyeball by deformation, pressure, saccades, electrical and magnetic stimulation produces phosphenes and photopsias by activating
retinal neuronal circuitry and stimulating ganglion cells (Grüsser and Landis, 1991; Lindenblatt and Silny, 2002). Phosphenes were noted in subjects exposed to highdose X-rays. ERGs can be recorded to X-ray stimulation and the amplitude of the b-wave is related to the intensity of the X-ray stimulus (Doly et al., 1980a, b). Astronauts in space have reported seeing flashes of light in the darkness presumably due to high-energy particles (cosmic ray) stimulating the retina photoreceptors (Casolino et al., 2003). Phosphenes and photopsias have been evoked by electrical stimulation of the optic tract, LGN and optic radiations during neurosurgery in humans. Electrical stimulation of the striate cortex and area V2 evokes simple visual forms, while stimulation of surrounding extrastriate areas evokes intermediate visual forms and stimulation of temporal regions elicits visual hallucinations (Penfield and Jasper, 1954; Lesser et al., 1998; Lee et al., 2000). Pathological excitation. Epilepsy is the prototype of a pathological excitatory phenomenon. Phosphenes, photopsias, palynopsia, and polyopia have been described as an aura preceding partial complex seizures and attributed to an epileptic focus localized in the occipital cortex. Visual hallucinations and visual distortions (metamorphopsia, micropsia, macropsia, teleopsia, and pelopsia) are observed at the onset of partial complex seizures originating in the temporal lobe (Penfield and Jasper, 1954). Release phenomenon may produce PSVP. A release phenomenon is essentially a disinhibition of neuronal structures. As a result of disinhibition, there is an increase in the excitability of the disinhibited neurons and an increase in spontaneous activity causing PSVP. fMRI obtained in patients experiencing visual hallucinations correlated with increased cerebral activity in extrastriate cortex (Fftyche et al., 1998). The type of PSVP (from phosphenes to visual hallucinations) will then depend on the specific visual cortical areas activated by the deafferentation. Burke (2002) suggested that visual “hallucinations can be regarded as local paroxysms in the sensory system.” PSVP in macular degeneration, glaucoma, cataracts, macular holes, and other retinopathies (Charles Bonnet syndrome) can be explained as a release phenomenon.
100
PSVP Pathophysiology
Excitation
Pathological
Physiological
Deformation Phosphenes
Exposure to High dose X-ray
Exposure to Cosmic Ray (astronauts)
Electrical or TMS Stimulation CNS Structures
Epilepsy
Release Phenomenon
Charles Bonnet Syndrome with Ocular pathology
Charles Bonnet Syndrome with CNS Pathology
Spreading Depression
Migraine or Migraine equivalent
Fig. 2. Mechanisms underlying PSVP.
Spreading depression (SD). SD is a depression of cerebral activity that slowly spread to adjacent structures. SD consists of a propagating negative potential with amplitude of 10–30 mV lasting 0.5–1 min (Gorji, 2001). The phenomenon is associated with slow negative potentials, cellular dysfunction, and increase in release of K+ and H+, inducing a refractory period to further stimulation that may last minutes or hours. The wave of depression propagates slowly (3–5 mm/min) in all directions. The visual aura of migraine has been attributed to SD as demonstrated by cerebral blood flow measurements of spreading hypoperfusion (Cao et al., 1999; Gorji, 2001; James et al., 2001). Hadjikhani et al. (2001) recorded fMRI in 3 migraneurs during their visual aura. They reported an increase in blood oxygen level-dependent (BOLD) signals first in the extrastriate
visual areas with spreading at the speed of 3.5 ± 1.1 mm/min over the occipital cortex. These changes were associated with clinical scintillations and were followed by a 15 ± 3 min decrease in MR signal. This decrease was associated with clinical scotoma. Many artists including Pablo Picasso suffered from migraine. Are some of their pictures influenced by their experience as migraneurs? Is SD responsible for artistic expression? Are Pablo Picasso paintings of cubism period a representation of metamorphopsia seen during its migraine’s aura? We will never know for sure but it may be interesting to speculate about the influence of diseases on artistic creativity. In the differential diagnosis of PSVP, we need to consider associated symptoms and signs. Foremost, we need to exclude visual hallucinations and other visual phenomena that arise in patients with delirium
101
PSVP
PSVP with Psychosis
Schizophrenia
Dementia (AD, etc,)
Paranoid States
Affective Psychoses
PSVP with Delirium
Alcohol or Drugs
Systemic or CNS Infections
Agitated Delirium With hemianopia
PSVP with Clear Sensorium
Charles Bonnet Syndrome
Physiologic
Ocular Pathology
Migraine or Migraine equivalent
Epilepsy
Central Visual Pathways Lesions
Fig. 3. Algorithm for PSVP diagnosis.
or psychosis (Fig. 3). Approximately 2% of elderly patients referred to a psychiatric clinic were eventually diagnosed to have Charles Bonnet syndrome related to eye pathology (Berrios and Brooks, 1984; NortinWillison and Munir, 1987). Thus, a careful psychiatric history and mental status examination are required before we conclude that a patient suffers from PVSP. Alcohol, drug withdrawal, or intoxications are the most frequent causative agents of delirium. Delirium can also be seen in systemic infections with high temperature or in infections of the nervous system. However, occasionally visual hallucinations, and delirium are seen in patients with acute insults to the occipital lobe. We have termed this syndrome agitated delirium with hemianopia (Vaphiades et al., 1996). The syndrome is characterized by agitation, confusion, visual hallucinations, and is always associated
with homonymous hemianopia. This syndrome is indicative of specific anatomical lesions involving the mesial aspect of the occipital lobe, the parahippocampal gyrus, and the hippocampus (Medina et al., 1974; Vaphiades et al., 1996). PSVP have been under-reported and underrecognized both by ophthalmologists and neurologists (Siatkowski et al., 1990; Vaphiades et al., 1996). Often individuals with these benign PSVP are treated with neuroleptics and undergo other unnecessary psychiatric treatments. There is some controversy on the definition of Charles Bonnet syndrome and specifically whether it should be limited to ocular pathology or be inclusive of all visual pathways’ lesions. Chaudhuri (2000) defines the syndrome by the triad of “visual hallucinations, visual sensory deprivation, and preserved
102 cognitive status” and includes in the syndrome any visual sensory deprivation whether caused by ocular or central visual pathway deficits. The term Charles Bonnet syndrome applied to both ocular and central vision lesions may be beneficial to physicians and patients in understanding the benign nature of these phenomena and focus on the treatment of the underlying ocular or central pathology. Visual hallucinations in psychosis are associated with auditory hallucinations or with sound, whereas PSVP are always silent. Bonnet (1796) was the first to observe that visual hallucinations in his syndrome were not associated with sound: “because the men and women did not speak, and no sound affected the ear.” Vaphiades et al. (1996) similarly remarked on the absence of sound with PSVP limited to the affected hemifield. Thus the presence of “silent” visual hallucinations or other PSVP should alert the clinician to the possible presence of visual dysfunction. References Berrios, G.E. and Brooks, P. (1984) Visual hallucinations and sensory delusions in the elderly. Br. J. Psychiatr., 144: 662–664. Bonnet, C. (1796) Essai Analytique sur les Faculté de l’Ame. Philibert, Copenhagen, pp. 426–429. (Reprinted by G. Olms Verlag, Hildesheim, 1973, 552 pp.) Burke, W. (2002) The neural basis of Charles Bonnet hallucinations: a hypothesis. J. Neurol. Neurosurg. Psychiatr., 73: 535–541. Cao, Y., Welch, K.M.A., Aurora, S. and Vikingstad, E.M. (1999) Functional MRI-BOLD of visually triggered headache in patients with migraine. Arch. Neurol., 56: 548–554. Casolino, M., Bidoli, V., Morselli, A., Narici, L., DePascale, M.P., Picozza, P., Reali, E., Spacvoli, R., Mazzenga, G., Ricci, M., Spillantini, P., Buezio, M., Bonvicini, V., Vacchi, A., Zampa, N., Castellini, G., Sannita, W.G., Carlson, P., Galper, A., Korotkov, M., Popov, A., Vavilov, N., Avdeev, S. and Fugelsang, C. (2003) Space travel – dual origins of light flashes seen in space. Nature, 422: 680. Celesia, G.G. (Ed.) (2005) Disorders of Visual Processing; Handbook of Clinical Neurophysiology, Vol. 5. Elsevier, Amsterdam. Chaudhuri, A. (2000) Charles Bonnet Syndrome: an example of cortical dissociation syndrome affecting vision. J. Neurol. Neurosurg. Psychiatr., 69: 704–705. Doly, M., Isabelle, D.B., Vincent, P., Gaillard, G. and Meyniel, G. (1980a) Mechanisms of the formation of X-ray induced phosphenes. I. Electrophysiological investigation. Radiat. Res., 82: 93–105. Doly, M., Isabelle, D.B., Vincent, P., Gaillard, G. and Meyniel, G. (1980b) Mechanisms of the formation of X-ray induced phosphenes. II. Photochemical investigation. Radiat. Res., 82: 430–440.
Fftyche, D.H., Howard, R.J., Brammer, M.J., David, A., Woodruff, P. and Williams, S. (1998) The anatomy of conscious vision: an fMRI study of visual hallucinations. Nature Neurosci., 1: 738–742. Gold, K. and Rabin, P.V. (1989) Isolated visual hallucinations and the Charles Bonnet syndrome: a review of the literature and presentation of six cases. Compr. Psychiatry, 30: 90–98. Gorji, A. (2001) Spreading depression: a review of the clinical relevance. Brain Res. Rev., 38: 33–60. Grüsser, O.J. and Landis, T. (1991) Visual Agnosia and Other Disturbances of Visual Perception and Cognition. CRC Press, Boca Raton, 610. pp. Hadjikhani, N., Sanchez Del Rio, M., Wu, O., Schwartz, D., Bakker, D., Fischl, B., Kwong, K.K., Cutrer, F.M., Rosen, B.R., Tootell, R.B., Sorensen, A.G. and Moskowitz, M.A. (2001) Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc. Natl. Acad. Sci. USA, 98: 4687–4692. Harvey, M., Milner, A.D. and Roberts, R.C. (1994) Spatial bias in visually-guided reaching and bisection following right cerebral strokes. Cortex, 30: 343–350. Jacob, L. (1980) Visual allesthesia. Neurology, 30: 1059–1063. James, M.F., Smith, J.M., Boniface, S.J., Huang, C.L. and Leslie, R.A. (2001) Cortical spreading depression and migraine: new insights from imaging? Trends Neurosci., 24: 266–271. Lee, H.W., Hong, S.B., Seo, W., Tae, D.W. and Hong, S.C. (2000) Mapping of functional organization of human visual cortex. Electrical cortical stimulation. Neurology, 54: 849–854. Lesser, R.P., Arroyo, S., Crone, N. and Gordon, B. (1998) Motor and sensory mapping of the frontal and occipital lobes. Epilepsia, 39: S69–S80. Lindenblatt, G. and Silny, J. (2002) Electrical phosphenes: on the influence of conductivity in homogeneities and small-scale structures of the orbita on the current density threshold of excitation. Med. Biol. Eng. Comput., 40: 354–359. Lipton, R.B., Scher, A.I., Kolodner, K., Liberman, J., Steiner, T.J. and Stewart, W.F. (2002) Migraine in the United States: epidemiology and patterns of health care use. Neurology, 58: 885–894. Medina, J.L., Rubino, F.A. and Ross, E. (1974) Agitated delirium caused by infarction of the hippocampus formation and fusiform and lingual gyri: a case report. Neurology, 24: 1181–1183. Nesher, R., Nesher, G., Epstein, E. and Assia, E. (2001) Charles Bonnet syndrome in glaucoma patients with low vision. J. Glaucoma, 10: 396–400. Norton-Willison, L. and Munir, M. (1987) Visual perceptual disorders resembling the Charles Bonnet syndrome: a study of 434 consecutive patients referred to a psychogeriatric unit. Fam. Pract., 4: 27–31. Paillas, J.E., Cossa, P., Darcourt, G. and Naquet, R. (1965) Etude sur l”épilepsie occipitale (a` propos de 36 observations de lésions occipitales verifiées chirurgicallement). Proceedings of 8th International Congress Neurology III, 193. Penfield, W. and Jasper, H. (1954) Epilepsy and the Functional Anatomy of the Human Brain. Little Brown, Boston, 896 pp. Podoll, K. and Robinson, D. (1999) Lewis Carroll’s migraine experiences. Lancet, 353: 1366. Russell, M.B., Rasmussen, B.K., Thorvaldsen, P. and Olesen, J. (1995) Prevalence and sex-ratio of the subtypes of migraine. Int. J. Epidemiol., 24: 612–618.
103 Siatkowski, R.M., Zimmer, B. and Rosenberg, P.R. (1990) The Charles Bonnet syndrome. Visual perceptive dysfunctionin sensory deprivation. J. Clin. Neuroophthalmol., 10: 215–218. Vallar, G. and Perani, D. (1986) The anatomy of unilateral neglect after right-hemisphere stroke lesions. A clinical CT-scan correlation study in man. Neuropsychologia, 24: 609–622. Vaphiades, M.S., Celesia, G.G. and Brigell, M.G. (1996) Positive spontaneous visual phenomena limited to the hemianopic
field in lesions of central visual pathways. Neurology, 47: 408–417. Volpe, N.J., Rizzo III, J.F. and Lessell, S. (2001) Acute idiopathic blind spot enlargement syndrome: a review of 27 new cases. Arch. Ophthalmol., 119: 59–63. Wijman, C.A., Wolf, P.A., Kase, C.S., Kelly-Hayes, M. and Beiser, A.S. (1998) Migrainous visual accompaniments are not rare in late life. The Framingham study. Stroke, 29: 1539–1543.
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Chapter 14
The mystery of photopsias, visual hallucinations, and distortions Gastone G. Celesia* Loyola University of Chicago, 3016 Heritage Oak Lane, Oak Brook, IL 60523 (USA)
Can we unravel the mystery of visual hallucinations and other positive spontaneous visual phenomena (PSVP)? Can we find the source of visual percepts arising endogenously from the human brain? Modern neuro-imaging and physiological methods shed light on the pathophysiology of these phenomena and will be reviewed therein. PSVP are visual events occurring in isolation, in the absence of altered consciousness, dementia, or psychosis (Vaphiades et al., 1996; Celesia, 2005). PSVP include phosphenes, photopsias, visual hallucinations, visual distortions, kinetopsias, palinopsia, polyopia, and visual allesthesia. Phosphenes are unstructured lights such as flashes, sparkles, zigzag lines or rainbows, black and white or colored, static or moving. Photopsias are structured images such as geometric figures (triangles, cubes, pyramids, etc.) or other simple pictures often recurring in a repetitive pattern. Kinetopsia from “kineto” motion and “opsis” vision, is an image moving in space. Palinopsia is visual perseveration or the recurrent appearance of a visual image after the stimulus has disappeared. Polyopia is the simultaneous perception of multiple objects or structures. The same object is
*Correspondence to: Gastone G. Celesia M.D., Loyola University of Chicago, 3016 Heritage Oak Lane, Oak Brook, IL 60523, USA. Tel: +1 630 968-2199; Fax: +1 630 968-2179; E-mail: [email protected]
seen multiple times either side by side or in circles. Visual distortions refer to the abnormal perception of figures and objects and can be further subdivided into macropsia, micropsia, pelopsia, teleopsia, and metamorphopsia. Macropsia refers to the appearance of an enlargement in size of all objects seen (Fig. 1, left illustration), whereas micropsia refers to the appearance of a reduction in size of all the objects seen. Pelopsia refers to the perception that objects are closer while teleopsia refers to the perception that the objects are farther away than they are. Metamorphopsia is the distortion of the objects or figures seen (Fig. 1, right illustration). Visual hallucinations consist of complex scenes including people, animals, furniture, landscapes, vehicles that may be stationary or mobile, colored or black and white, and perceived, at least temporarily, as real. Visual hallucinations as part of PSVP are isolated without associated mental disturbances such as dementia, psychosis, or altered state of consciousness. Ophthalmologists refer to these visual hallucinations as the Charles Bonnet syndrome (Bonnet, 1796). PSVP can be due to lesions in any part of the visual system from the retina to the occipital cortex (Table 1). Thus none of the PSVP have localizing value. It is also not unusual that more than one PSVP occur in the same patient; Jacob (1980) reported visual allesthesia and palinopsia in a 24-year-old woman with a right parieto-occipital arteriovenous malformation. We have noted the co-occurrence of visual hallucinations and
98
Fig. 1. Two illustrations from Lewis Carroll’s, Alice’s adventures in Wonderland, illustration by John Tenniel. Left illustration: Alice is very small and meet a puppy “An enormous puppy was looking down at her with large round eyes, and feebly stretching out one paw, trying to touch her.” Lewis Carroll suffered from migraine (Podoll and Robinson, 1999) and his description of Alice may be a manifestation of the macropsia and visual hallucinations seen in his migrainous auras. Right illustration: Alice stretched tall, an example of metamorphopsia.
photopsias in several patients with lesions in optic radiations and or occipital lobe. Another controversy in the literature is the statement that PSVP related to central nervous system pathology are predominantly due to right hemispherical lesions (Pailas et al., 1965; Vallar and Perani, 1986; Harvey et al., 1994). Such statement ignores the fact that reports on patients with destructive brain lesions are biased by the exclusion of patients with left-side damage due to the associated language deficits that prevent accurate testing. In our study of hemianopic patients (Vaphiades
et al., 1996) despite this built-in bias, we found no statistically significant differences between right- and left-side lesions. PSVP have a prevalence of around 8–9%. Perhaps the most frequently described PSVP are the phosphenes, photopsias, and metamorphopsias of the migraine aura. Russels et al. (1995) in a study of the Danish population reported an overall lifetime prevalence of migraine of 18%, with migraine aura without headaches occurring in 8% of males and 16% of females. Twenty-six of 2110 subjects in the Framingham
99 TABLE 1 LOCATION OF LESION IN 614 CASES OF PSVP Lesion site
Retina Optic nerve Chiasma/tract Optic radiation Occipital cortex Normal subjects Total number of subjects with PSVP Total number of patients
Total (number)
Total (percent)
84 47 5 3 469 6
1.2 0.7 0.1 0.04 6.5 0.1
614 7211
8.5 100.0
study had migraine aura without headaches, a prevalence of 1.23% (Wijman et al., 1998). Lipton et al. (2002) studied the prevalence of migraine in Philadelphia County and reported a prevalence of 13% in adults. There is a remarkable agreement in all these studies that in the Western world the prevalence is approximately 13% with 3% of patients experiencing visual auras and about 1.2% having visual auras without migraine. Charles Bonnet syndrome (visual hallucinations or other PSVP in the presence of ophthalmologic dysfunction) has been reported in a variety of ocular diseases from cataracts to glaucoma, from retinitis pigmentosa to optic neuritis (Gold and Rabin, 1989; Nesher et al., 2001; Volpe et al., 2001; Burke, 2002). In summary, the most frequent cause of PSVP is migraine followed by ophthalmologic diseases associated with impairment of visual acuity equal or worse than 20/200. There are three possible mechanisms causing PSVP (Fig. 2): (1) excitation; (2) release phenomenon; (3) spreading depression (SD). Excitation can be physiological or pathological. Physiological excitation occurs at the retinal, visual pathways, lateral geniculate nucleus (LGN), and cortical level. Stimulation of the eyeball by deformation, pressure, saccades, electrical and magnetic stimulation produces phosphenes and photopsias by activating
retinal neuronal circuitry and stimulating ganglion cells (Grüsser and Landis, 1991; Lindenblatt and Silny, 2002). Phosphenes were noted in subjects exposed to highdose X-rays. ERGs can be recorded to X-ray stimulation and the amplitude of the b-wave is related to the intensity of the X-ray stimulus (Doly et al., 1980a, b). Astronauts in space have reported seeing flashes of light in the darkness presumably due to high-energy particles (cosmic ray) stimulating the retina photoreceptors (Casolino et al., 2003). Phosphenes and photopsias have been evoked by electrical stimulation of the optic tract, LGN and optic radiations during neurosurgery in humans. Electrical stimulation of the striate cortex and area V2 evokes simple visual forms, while stimulation of surrounding extrastriate areas evokes intermediate visual forms and stimulation of temporal regions elicits visual hallucinations (Penfield and Jasper, 1954; Lesser et al., 1998; Lee et al., 2000). Pathological excitation. Epilepsy is the prototype of a pathological excitatory phenomenon. Phosphenes, photopsias, palynopsia, and polyopia have been described as an aura preceding partial complex seizures and attributed to an epileptic focus localized in the occipital cortex. Visual hallucinations and visual distortions (metamorphopsia, micropsia, macropsia, teleopsia, and pelopsia) are observed at the onset of partial complex seizures originating in the temporal lobe (Penfield and Jasper, 1954). Release phenomenon may produce PSVP. A release phenomenon is essentially a disinhibition of neuronal structures. As a result of disinhibition, there is an increase in the excitability of the disinhibited neurons and an increase in spontaneous activity causing PSVP. fMRI obtained in patients experiencing visual hallucinations correlated with increased cerebral activity in extrastriate cortex (Fftyche et al., 1998). The type of PSVP (from phosphenes to visual hallucinations) will then depend on the specific visual cortical areas activated by the deafferentation. Burke (2002) suggested that visual “hallucinations can be regarded as local paroxysms in the sensory system.” PSVP in macular degeneration, glaucoma, cataracts, macular holes, and other retinopathies (Charles Bonnet syndrome) can be explained as a release phenomenon.
100
PSVP Pathophysiology
Excitation
Pathological
Physiological
Deformation Phosphenes
Exposure to High dose X-ray
Exposure to Cosmic Ray (astronauts)
Electrical or TMS Stimulation CNS Structures
Epilepsy
Release Phenomenon
Charles Bonnet Syndrome with Ocular pathology
Charles Bonnet Syndrome with CNS Pathology
Spreading Depression
Migraine or Migraine equivalent
Fig. 2. Mechanisms underlying PSVP.
Spreading depression (SD). SD is a depression of cerebral activity that slowly spread to adjacent structures. SD consists of a propagating negative potential with amplitude of 10–30 mV lasting 0.5–1 min (Gorji, 2001). The phenomenon is associated with slow negative potentials, cellular dysfunction, and increase in release of K+ and H+, inducing a refractory period to further stimulation that may last minutes or hours. The wave of depression propagates slowly (3–5 mm/min) in all directions. The visual aura of migraine has been attributed to SD as demonstrated by cerebral blood flow measurements of spreading hypoperfusion (Cao et al., 1999; Gorji, 2001; James et al., 2001). Hadjikhani et al. (2001) recorded fMRI in 3 migraneurs during their visual aura. They reported an increase in blood oxygen level-dependent (BOLD) signals first in the extrastriate
visual areas with spreading at the speed of 3.5 ± 1.1 mm/min over the occipital cortex. These changes were associated with clinical scintillations and were followed by a 15 ± 3 min decrease in MR signal. This decrease was associated with clinical scotoma. Many artists including Pablo Picasso suffered from migraine. Are some of their pictures influenced by their experience as migraneurs? Is SD responsible for artistic expression? Are Pablo Picasso paintings of cubism period a representation of metamorphopsia seen during its migraine’s aura? We will never know for sure but it may be interesting to speculate about the influence of diseases on artistic creativity. In the differential diagnosis of PSVP, we need to consider associated symptoms and signs. Foremost, we need to exclude visual hallucinations and other visual phenomena that arise in patients with delirium
101
PSVP
PSVP with Psychosis
Schizophrenia
Dementia (AD, etc,)
Paranoid States
Affective Psychoses
PSVP with Delirium
Alcohol or Drugs
Systemic or CNS Infections
Agitated Delirium With hemianopia
PSVP with Clear Sensorium
Charles Bonnet Syndrome
Physiologic
Ocular Pathology
Migraine or Migraine equivalent
Epilepsy
Central Visual Pathways Lesions
Fig. 3. Algorithm for PSVP diagnosis.
or psychosis (Fig. 3). Approximately 2% of elderly patients referred to a psychiatric clinic were eventually diagnosed to have Charles Bonnet syndrome related to eye pathology (Berrios and Brooks, 1984; NortinWillison and Munir, 1987). Thus, a careful psychiatric history and mental status examination are required before we conclude that a patient suffers from PVSP. Alcohol, drug withdrawal, or intoxications are the most frequent causative agents of delirium. Delirium can also be seen in systemic infections with high temperature or in infections of the nervous system. However, occasionally visual hallucinations, and delirium are seen in patients with acute insults to the occipital lobe. We have termed this syndrome agitated delirium with hemianopia (Vaphiades et al., 1996). The syndrome is characterized by agitation, confusion, visual hallucinations, and is always associated
with homonymous hemianopia. This syndrome is indicative of specific anatomical lesions involving the mesial aspect of the occipital lobe, the parahippocampal gyrus, and the hippocampus (Medina et al., 1974; Vaphiades et al., 1996). PSVP have been under-reported and underrecognized both by ophthalmologists and neurologists (Siatkowski et al., 1990; Vaphiades et al., 1996). Often individuals with these benign PSVP are treated with neuroleptics and undergo other unnecessary psychiatric treatments. There is some controversy on the definition of Charles Bonnet syndrome and specifically whether it should be limited to ocular pathology or be inclusive of all visual pathways’ lesions. Chaudhuri (2000) defines the syndrome by the triad of “visual hallucinations, visual sensory deprivation, and preserved
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