- Email: [email protected]
CS10.2 Multifocal ERG in assessment of retinal disorders
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Clinical Symposia / Clinical Neurophysiology 117 (2006) S5–S17
group. Two forms have been recognised in hyperekplexia; a major and a minor form. The major form of hyperekplexia is characterised by excessive startle reflexes, startle-induced stiff falls and continuous stiffness in the neonatal period. The cause of the major form is mainly genetic with mutations in the a1 subunit of the glycine receptor or related genes. Patients with the minor form suffer from excessive startle reflexes without signs of stiffness. The cause of the minor form is not genetic and largely unknown. Additional brainstem abnormalities point toward a symptomatic minor form, but in patients with a nonsymptomatic minor form the cause is difficult to establish. A startle-EMG study should be performed to determine whether the excessive response can be classified as a startle reflex. Neuropsychiatric startle disorders form the second group. In this group of patients excessive startling as well as behavioural features occur. Examples include culture-specific disorders such as the ’Jumping Frenchmen of Maine’ and anxiety disorders. Startle motor patterns have not been investigated in detail and therefore, neuropsychiatric startle syndromes can currently not be identified on specific features. The third group is formed by disorders in which startling stimuli can induce responses other than startle reflexes, for example startle-induced epilepsy and reticular reflex myoclonus. The phenomenology and pathophysiology of stimulus-induced disorders is diverse. Further electrophysiological studies of startle disorders are required and will lead to improved discrimination between the groups. doi:10.1016/j.clinph.2006.07.033
CS10.1 Visual electrophysiology in retinal and optic nerve and cortical disorders G. Harding Aston University, Neurosciences Research Institute, UK Visual electrophysiology, particularly the electroretinogram (ERG) and visual evoked potentials (VEP) can be used to highlight the location of lesions in the visual system. Monocular ERGs can indicate the integrity of rod, cone and ganglion systems in the retina utilising scotopic photopic and 30 Hz stimulation. Pattern ERG allow the separation of reception and ganglion function using the P50 and N95 responses. More recently, multifocal ERGs allow detailed analysis of separate retinal locations combining the detail of static perimetry with objective responses from the retina. Visual evoked potentials to flash and pattern stimulation have been used for 40 years to locate post-retinal lesions. By combining monocular stimulation with multichannel recordings it is possible to locate lesions as prechiasmal or optic nerve, chiasmal and post-chiasmal. The combination of these two techniques, the ERG and VEP allow lesions to be located at all levels of the visual system and allow objective evidence of functional visual loss. Combined ERGs and VEPs provide good indications of
outcome when traumatic injuries to the visual system occur. The ERG is indicative of a variety of retinal conditions including retinitis pigmentosa, cone-dystrophy, retinal detachment, occlusive retinal vascular disease and other conditions affecting the layers of the retina. Combined with VEP they are helpful in diagnosing macular degeneration and central serous retinopathy although in the latter case multifocal ERGs are better. The VEP has been used for many years for diagnosing acute optic neuritis or demyelinating disease although its pre-dominant value has been overtaken by improvements in MRI scanning. It must be remembered however that MRI reflects anatomy whereas evoked potentials represent function. More central conditions such as localised trauma to the occipital regions are represented in asymmetric responses, correlating with field defects. Other diffuse but discrete cortical changes, such as those in Alzheimer’s disease also affect the VEP delaying the flash response but preserving the latency of the pattern reversal response. Recently a novel antiepileptic drug, vigabatrin, has been shown to be associated with peripheral visual field losses which appear permanent and irreversible. Using ERGs, it has proved possible to separate the effects of receiving the drug from those correlated with the field defect. Cone-ganglion function has been shown to be affected and reflected in the amplitude of the 30 Hz response. In spite of findings of microvaculation in the myelin sheath of animals VEPS were unaffected and there is no evidence in anatomical studies that humans are affected. Other antiepileptic drugs also affect the ERG. The lack of affect of vigabatrin on the VEP became fortuitous in assessment of visual function in patients too young to be examined by perimetry. By utilising a divided pattern stimulus with separate reversal rates for central and peripheral fields it is possible to test children as young as three years for preservation of peripheral field function. Compliance with this test is extremely high, and the test has high sensitivity and specificity. The development of detailed visual stimuli such as the multifocal stimulus will increase the utility of both the ERG and the VEP. In addition the temporal resolutions of these techniques give them a massive advantage over the slow functional MRI. doi:10.1016/j.clinph.2006.07.034
CS10.2 Multifocal ERG in assessment of retinal disorders D. Keating, S. Parks Gartnavel General Hospital, ElectroDiagnostic Imaging Unit, UK Background: In recent years, multifocal electroretinography (mfERG) has added a new dimension to objective investigation of retinal disorders. The technique uses simultaneous stimulation of multiple retinal sites to obtain spatial information on retinal function. The stimulation sequence also contains multiple frequency components
Clinical Symposia / Clinical Neurophysiology 117 (2006) S5–S17
with the composite multifocal ERG waveform containing information on temporal processing or retinal adaptation. Aims/Objectives: There are many variables which influence the multifocal ERG response. These variables include, stimulus luminance, method of stimulus delivery, length of stimulation sequence, field of view and recording bandwidth. These parameters were systematically investigated to produce a robust method for performing multifocal ERG in a routine clinical setting. Methods: The parameters listed above were investigated to optimise the signal to noise ratio of the multifocal ERG records. A protocol for clinical testing was formulated based on the results. Since 1994, 5221 patients have been tested using the clinical protocol. Results: The chosen recording protocol included an 8 min recording period with 61 areas stimulated over a 90° field using digital stimulus projection. Of the 5221 investigations 146 (3%) had reliability index in one or both eyes below the tolerance of 70%. 48 (<1%) investigations were terminated before completion due to poor patient compliance. 4190 (80%) investigations confirmed or improved localisation of pathology to a retinal defect. 731 (14%) provided complementary information to discount an outer/ mid retinal cause for visual dysfunction. In 106 (2%) investigations results remained inconclusive. Conclusions: Wide field multifocal electroretinography is well tolerated in a routine ophthalmic clinical service setting. In addition, these results indicate it is an important addition to the electrophysiological investigations available for the early detection and monitoring of visual dysfunction. doi:10.1016/j.clinph.2006.07.035
CS10.3 Central disorders of visual processing G. Celesia Neurovision, USA Background: Many diseases of the CNS produce visual deficits that are often not recognized, particularly when they produce complex perceptual deficits due to lesions of the ‘‘higher visual centers’’. Objective: a pragmatic classification of central disorders of visual processing (CDVP). Results: Central disorders of visual processing are classified into (1) disorders of visual sensory pathways, (2) disorders of visual integration, and (3) undetermined disorders of visual integration. Disorders of visual sensory pathways are due to lesions of the pathways from the optic nerve to the striate cortex. They produce spatially specific or retinotopic perception defects proportional to the amount of tissue destroyed (scotomas, hemianopias, visual anosognosia, cortical blindness, etc.) Disorders of visual integration are related to lesions upstream from the striate cortex and pro-
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duce complex disturbances of visual processing including attention disorders (hemineglect, Balint’s syndrome, etc.) and disorders of visual gnosis (achromatopsia, prosopagnosia, visual agnosia, etc.). Undetermined disorders of visual integration represent disorders not easily classified in the two former categories and of uncertain pathophysiology. They are represented by positive spontaneous visual phenomena (PSVP) including photopsias, phospenes, metamorphopsia, visual hallucinations, etc. Clinical neurophysiology from electrophysiology to psychophysical testing has a crucial role in the diagnosis and classification of these disorders. Examples of the three kinds of disorders will be presented. Conclusions: Comprehensive classification of CDVP is possible and permits a workable framework for further elucidation of the physiopathology of vision. doi:10.1016/j.clinph.2006.07.036
CS11.1 Cognitive assessment of non-communicative patients using event-related potentials J. Connolly Dalhousie University, Department of Psychology, Canada Background: Impaired communication in patients is a common consequence of brain injury often leading to restricted or withheld therapeutic interventions due to the difficulty or impossibility of obtaining accurate measures of their cognitive abilities. Over the last decade studies have demonstrated the ability of cognitive ERP to be recorded within the context of computerized neuropsychological test administration with ERPs providing performance markers in lieu of verbal or motor behavior. This method has been able to demonstrate the existence of residual cognitive function in vegetative state/persistent vegetative state patients leading, in some cases, to successful treatment interventions. Objectives: The research described here extended earlier work by examining stroke patients, and coma and VS/PVS patients. Also, proof of principle (POP) data for new tests was collected. Methods: A series of ERP-based neuropsychological tests were presented to patients to assess a range of cognitive processes ranging from ’automatic’ attention allocation to ’controlled’ semantic and memory mechanisms requiring volition or intentional processing. Patient results were compared to those obtained in the POP studies. Results: Results for some patients indicated intact cognitive processes despite co-existing inabilities to offer overt verbal or motor responses. POP studies supported the ability of these methods to obtain measures of cognitive function that correlated highly with the traditional test version when presented in the standard fashion. Discussion: These findings indicate that some patients with severe communication problems rendering traditional
Clinical Symposia / Clinical Neurophysiology 117 (2006) S5–S17
group. Two forms have been recognised in hyperekplexia; a major and a minor form. The major form of hyperekplexia is characterised by excessive startle reflexes, startle-induced stiff falls and continuous stiffness in the neonatal period. The cause of the major form is mainly genetic with mutations in the a1 subunit of the glycine receptor or related genes. Patients with the minor form suffer from excessive startle reflexes without signs of stiffness. The cause of the minor form is not genetic and largely unknown. Additional brainstem abnormalities point toward a symptomatic minor form, but in patients with a nonsymptomatic minor form the cause is difficult to establish. A startle-EMG study should be performed to determine whether the excessive response can be classified as a startle reflex. Neuropsychiatric startle disorders form the second group. In this group of patients excessive startling as well as behavioural features occur. Examples include culture-specific disorders such as the ’Jumping Frenchmen of Maine’ and anxiety disorders. Startle motor patterns have not been investigated in detail and therefore, neuropsychiatric startle syndromes can currently not be identified on specific features. The third group is formed by disorders in which startling stimuli can induce responses other than startle reflexes, for example startle-induced epilepsy and reticular reflex myoclonus. The phenomenology and pathophysiology of stimulus-induced disorders is diverse. Further electrophysiological studies of startle disorders are required and will lead to improved discrimination between the groups. doi:10.1016/j.clinph.2006.07.033
CS10.1 Visual electrophysiology in retinal and optic nerve and cortical disorders G. Harding Aston University, Neurosciences Research Institute, UK Visual electrophysiology, particularly the electroretinogram (ERG) and visual evoked potentials (VEP) can be used to highlight the location of lesions in the visual system. Monocular ERGs can indicate the integrity of rod, cone and ganglion systems in the retina utilising scotopic photopic and 30 Hz stimulation. Pattern ERG allow the separation of reception and ganglion function using the P50 and N95 responses. More recently, multifocal ERGs allow detailed analysis of separate retinal locations combining the detail of static perimetry with objective responses from the retina. Visual evoked potentials to flash and pattern stimulation have been used for 40 years to locate post-retinal lesions. By combining monocular stimulation with multichannel recordings it is possible to locate lesions as prechiasmal or optic nerve, chiasmal and post-chiasmal. The combination of these two techniques, the ERG and VEP allow lesions to be located at all levels of the visual system and allow objective evidence of functional visual loss. Combined ERGs and VEPs provide good indications of
outcome when traumatic injuries to the visual system occur. The ERG is indicative of a variety of retinal conditions including retinitis pigmentosa, cone-dystrophy, retinal detachment, occlusive retinal vascular disease and other conditions affecting the layers of the retina. Combined with VEP they are helpful in diagnosing macular degeneration and central serous retinopathy although in the latter case multifocal ERGs are better. The VEP has been used for many years for diagnosing acute optic neuritis or demyelinating disease although its pre-dominant value has been overtaken by improvements in MRI scanning. It must be remembered however that MRI reflects anatomy whereas evoked potentials represent function. More central conditions such as localised trauma to the occipital regions are represented in asymmetric responses, correlating with field defects. Other diffuse but discrete cortical changes, such as those in Alzheimer’s disease also affect the VEP delaying the flash response but preserving the latency of the pattern reversal response. Recently a novel antiepileptic drug, vigabatrin, has been shown to be associated with peripheral visual field losses which appear permanent and irreversible. Using ERGs, it has proved possible to separate the effects of receiving the drug from those correlated with the field defect. Cone-ganglion function has been shown to be affected and reflected in the amplitude of the 30 Hz response. In spite of findings of microvaculation in the myelin sheath of animals VEPS were unaffected and there is no evidence in anatomical studies that humans are affected. Other antiepileptic drugs also affect the ERG. The lack of affect of vigabatrin on the VEP became fortuitous in assessment of visual function in patients too young to be examined by perimetry. By utilising a divided pattern stimulus with separate reversal rates for central and peripheral fields it is possible to test children as young as three years for preservation of peripheral field function. Compliance with this test is extremely high, and the test has high sensitivity and specificity. The development of detailed visual stimuli such as the multifocal stimulus will increase the utility of both the ERG and the VEP. In addition the temporal resolutions of these techniques give them a massive advantage over the slow functional MRI. doi:10.1016/j.clinph.2006.07.034
CS10.2 Multifocal ERG in assessment of retinal disorders D. Keating, S. Parks Gartnavel General Hospital, ElectroDiagnostic Imaging Unit, UK Background: In recent years, multifocal electroretinography (mfERG) has added a new dimension to objective investigation of retinal disorders. The technique uses simultaneous stimulation of multiple retinal sites to obtain spatial information on retinal function. The stimulation sequence also contains multiple frequency components
Clinical Symposia / Clinical Neurophysiology 117 (2006) S5–S17
with the composite multifocal ERG waveform containing information on temporal processing or retinal adaptation. Aims/Objectives: There are many variables which influence the multifocal ERG response. These variables include, stimulus luminance, method of stimulus delivery, length of stimulation sequence, field of view and recording bandwidth. These parameters were systematically investigated to produce a robust method for performing multifocal ERG in a routine clinical setting. Methods: The parameters listed above were investigated to optimise the signal to noise ratio of the multifocal ERG records. A protocol for clinical testing was formulated based on the results. Since 1994, 5221 patients have been tested using the clinical protocol. Results: The chosen recording protocol included an 8 min recording period with 61 areas stimulated over a 90° field using digital stimulus projection. Of the 5221 investigations 146 (3%) had reliability index in one or both eyes below the tolerance of 70%. 48 (<1%) investigations were terminated before completion due to poor patient compliance. 4190 (80%) investigations confirmed or improved localisation of pathology to a retinal defect. 731 (14%) provided complementary information to discount an outer/ mid retinal cause for visual dysfunction. In 106 (2%) investigations results remained inconclusive. Conclusions: Wide field multifocal electroretinography is well tolerated in a routine ophthalmic clinical service setting. In addition, these results indicate it is an important addition to the electrophysiological investigations available for the early detection and monitoring of visual dysfunction. doi:10.1016/j.clinph.2006.07.035
CS10.3 Central disorders of visual processing G. Celesia Neurovision, USA Background: Many diseases of the CNS produce visual deficits that are often not recognized, particularly when they produce complex perceptual deficits due to lesions of the ‘‘higher visual centers’’. Objective: a pragmatic classification of central disorders of visual processing (CDVP). Results: Central disorders of visual processing are classified into (1) disorders of visual sensory pathways, (2) disorders of visual integration, and (3) undetermined disorders of visual integration. Disorders of visual sensory pathways are due to lesions of the pathways from the optic nerve to the striate cortex. They produce spatially specific or retinotopic perception defects proportional to the amount of tissue destroyed (scotomas, hemianopias, visual anosognosia, cortical blindness, etc.) Disorders of visual integration are related to lesions upstream from the striate cortex and pro-
S15
duce complex disturbances of visual processing including attention disorders (hemineglect, Balint’s syndrome, etc.) and disorders of visual gnosis (achromatopsia, prosopagnosia, visual agnosia, etc.). Undetermined disorders of visual integration represent disorders not easily classified in the two former categories and of uncertain pathophysiology. They are represented by positive spontaneous visual phenomena (PSVP) including photopsias, phospenes, metamorphopsia, visual hallucinations, etc. Clinical neurophysiology from electrophysiology to psychophysical testing has a crucial role in the diagnosis and classification of these disorders. Examples of the three kinds of disorders will be presented. Conclusions: Comprehensive classification of CDVP is possible and permits a workable framework for further elucidation of the physiopathology of vision. doi:10.1016/j.clinph.2006.07.036
CS11.1 Cognitive assessment of non-communicative patients using event-related potentials J. Connolly Dalhousie University, Department of Psychology, Canada Background: Impaired communication in patients is a common consequence of brain injury often leading to restricted or withheld therapeutic interventions due to the difficulty or impossibility of obtaining accurate measures of their cognitive abilities. Over the last decade studies have demonstrated the ability of cognitive ERP to be recorded within the context of computerized neuropsychological test administration with ERPs providing performance markers in lieu of verbal or motor behavior. This method has been able to demonstrate the existence of residual cognitive function in vegetative state/persistent vegetative state patients leading, in some cases, to successful treatment interventions. Objectives: The research described here extended earlier work by examining stroke patients, and coma and VS/PVS patients. Also, proof of principle (POP) data for new tests was collected. Methods: A series of ERP-based neuropsychological tests were presented to patients to assess a range of cognitive processes ranging from ’automatic’ attention allocation to ’controlled’ semantic and memory mechanisms requiring volition or intentional processing. Patient results were compared to those obtained in the POP studies. Results: Results for some patients indicated intact cognitive processes despite co-existing inabilities to offer overt verbal or motor responses. POP studies supported the ability of these methods to obtain measures of cognitive function that correlated highly with the traditional test version when presented in the standard fashion. Discussion: These findings indicate that some patients with severe communication problems rendering traditional