873
LETTERS to the EDITOR
P300 as a predictor of recovery from
coma
SiR,—The prognosis for patients in coma still cannot be established with certainty. Clinical assessments such as the Glasgow coma scale (GCS) are poor predictors of outcome,’ even in conjunction with imaging techniques such as magnetic resonance imaging or computed tomography (CT), which provide anatomical but not functional information. Prognosis might be improved by the use of measures of brain function, especially those that assess brain activities related to consciousness and cognition. The P300 component of the auditory event-related brain potential reflects such cognitive processes.2 P300 is typically elicited by a rare tone which is randomly presented within a sequence of different tones to subjects instructed to attend to the rare stimulus; however, it can also be recorded passively if the difference between frequent and rare stimuli is salient enough.3 We have used a passive P300 protocol in 8 comatose patients, with GCS scores of 3-11. We recorded from a 19-electrode montage, presenting tone pips at 95 decibels (dB) (85 % at 1000 Hz, 15% at 1500 or 3000 Hz). Event-related brain potentials were averaged separately to each frequency and plotted as waveforms and as topographical maps of voltage distribution. Of the 8 patients, 6 produced no P300 component. 4 died within a week of the recording session; the remaining 2 survived in a persistent vegetative state without any clinical improvement. By contrast, 2 patients showed a P300 to the rare stimuli, but not to the frequent stimuli. These 2 patients showed substantial clinical improvement in the following weeks and months. 1 patient, a 66-year-old woman who had had a brainstem infarct, had a GCS of 3 at the time the P300 was recorded, 1 week after evacuation of a posterior fossa haematoma. She had no right comeal reflex, no doll’s eyes reflex, and no response to deep pain, yet produced a broad symmetrical P300 with a delayed latency of 430 ms. She began to open her eyes spontaneously and respond to commands 25 days later. She was subsequently discharged to a local rehabilitation facility with a GCS of 12, although the long-term prognosis is uncertain because of her advanced age. The second patient was a 26-year-old man who had fallen from a height of three storeys. CT showed evidence of bilateral frontal and temporal contusions, left parietal contusion, right basal ganglia haemorrhage, and multiple basilar skull fractures. His GCS was 8 when a clear P300 with a latency of 325 ms was recorded (figure). Despite his initially poor neurological status, he began to respond to commands 2 weeks after the recording, and thereafter steadily improved. He is now fully alert and oriented; although unable to speak, he communicates well with an alphabet board, recognises friends and family, and demonstrates a good basic knowledge and clear sense of humour. These observations suggest that P300 could indicate the integrity of brain systems that mediate cognitive functions, even in the
absence of consciousness or overt behavioural responses.4 P300 may thus be a valuable adjunct to clinical examinations and anatomical imaging techniques in the evaluation of patients in coma or
persistent vegetative states. Departments of Psychiatry, Neurological Surgery and Otolaryngology, University of California, San Francisco, CA 94143-0984, USA
stupor and coma, 3rd ed. Philadelphia: FA Davis Company, 1982. 2. Hillyard SA, Picton TW. Electrophysiology of cognition. In: Plum F, ed. Handbook of physiology, vol V. Higher functions of the brain. Bethesda, Maryland: American Physiological Society, 1987. 3. Polich J. P300 from a passive auditory paradigm. Electroenceph Clin Neurophysiol 1989; 1. Plum F, Posner JB. The diagnosis of
74: 312-20. BM, Linke DB. P300 and coma. In: Maurer K, ed. Topographic brain mapping of EEG and evoked potentials. Berlin: Springer-Verlag, 1989: 192-96.
4. Reuter
Adverse reactions to monosulfiram SIR,-Dr Blanc and Dr Deprez (May 26, p 1291) note that the disulfiram-like reaction in their patient with scabies has only rarely been observed. From the references cited the belief could arise that this reaction only follows the imbibing of alcohol, contrary to recommendations. However, hearsay evidence suggests that this reaction is underreported by both patients and doctors. I have investigated a scabies outbreak in a nursing home, during which some patients and staff had been treated with 25% monosulfiram in alcohol (’Tetmosol’) diluted for use. I found that, apart from the high treatment failure rate, one member of staff (an otherwise healthy woman aged 32) had shown a disulfiram-like reaction soon after treatment, with flushing, sweating, and tachycardia. She had not consumed alcohol in the previous 24 h and seemed to have reacted only to the alcohol base of the formulation passing through the skin. She usually had facial flushing after ingestion of alcohol, as seen in 5-10% of caucasian people.’ Such flushing is believed to be due either to an abnormal alcohol dehydrogenase isoenzyme (ADH2) or to deficient aldehyde dehydrogenase (ALDH).2 In either case acetaldehyde accumulates, producing the reaction. Monosulfiram is not an efficient scabicide and often needs several applications. If it causes a prolonged inhibition of ALDH in the same way as does disulfiram3 then the chances of a reaction to the treatment are enhanced, even in healthy individuals, with each application. Such a reaction is potentially serious in children, for whom monosulfiram is prescribed most often. Consequently it should be used with care, especially since other more efficient and potentially less toxic scabicides are available. Medical Entomology Centre at The University of Cambridge, Austin Building, New Museums Site, Cambridge CB2 3DX, UK
100ms
Note P300
(arrow)
in
response to
rare tone
rare tone
I. BURGESS
1. Wolff P. Ethnic differences in alcohol sensitivity. Science 1972; 125: 449-51 BR, Saunders JB, Williams R, Hopkinson DA. Hepatic ADH and ALDH isoenzymes in different racial groups and in chronic alcoholism. Pharmacol Biochem Behav 1983; 18 (suppl 1): 61-65. 3. Tottmar O, Hellstrom E. Aldehyde dehydrogenase in blood. a sensitive assay and inhibition by disulfiram. Pharmacol Biochem Behav 1983; 18 (suppl 1): 103-07.
2. Ricciardi
Response at vertex to frequent tone (dashed line) and (solid line) from patient with GCS of 8.
CHARLES D. YINGLING YOSHIO HOSOBUCHI MARGARET HARRINGTON
LETTERS to the EDITOR
P300 as a predictor of recovery from
coma
SiR,—The prognosis for patients in coma still cannot be established with certainty. Clinical assessments such as the Glasgow coma scale (GCS) are poor predictors of outcome,’ even in conjunction with imaging techniques such as magnetic resonance imaging or computed tomography (CT), which provide anatomical but not functional information. Prognosis might be improved by the use of measures of brain function, especially those that assess brain activities related to consciousness and cognition. The P300 component of the auditory event-related brain potential reflects such cognitive processes.2 P300 is typically elicited by a rare tone which is randomly presented within a sequence of different tones to subjects instructed to attend to the rare stimulus; however, it can also be recorded passively if the difference between frequent and rare stimuli is salient enough.3 We have used a passive P300 protocol in 8 comatose patients, with GCS scores of 3-11. We recorded from a 19-electrode montage, presenting tone pips at 95 decibels (dB) (85 % at 1000 Hz, 15% at 1500 or 3000 Hz). Event-related brain potentials were averaged separately to each frequency and plotted as waveforms and as topographical maps of voltage distribution. Of the 8 patients, 6 produced no P300 component. 4 died within a week of the recording session; the remaining 2 survived in a persistent vegetative state without any clinical improvement. By contrast, 2 patients showed a P300 to the rare stimuli, but not to the frequent stimuli. These 2 patients showed substantial clinical improvement in the following weeks and months. 1 patient, a 66-year-old woman who had had a brainstem infarct, had a GCS of 3 at the time the P300 was recorded, 1 week after evacuation of a posterior fossa haematoma. She had no right comeal reflex, no doll’s eyes reflex, and no response to deep pain, yet produced a broad symmetrical P300 with a delayed latency of 430 ms. She began to open her eyes spontaneously and respond to commands 25 days later. She was subsequently discharged to a local rehabilitation facility with a GCS of 12, although the long-term prognosis is uncertain because of her advanced age. The second patient was a 26-year-old man who had fallen from a height of three storeys. CT showed evidence of bilateral frontal and temporal contusions, left parietal contusion, right basal ganglia haemorrhage, and multiple basilar skull fractures. His GCS was 8 when a clear P300 with a latency of 325 ms was recorded (figure). Despite his initially poor neurological status, he began to respond to commands 2 weeks after the recording, and thereafter steadily improved. He is now fully alert and oriented; although unable to speak, he communicates well with an alphabet board, recognises friends and family, and demonstrates a good basic knowledge and clear sense of humour. These observations suggest that P300 could indicate the integrity of brain systems that mediate cognitive functions, even in the
absence of consciousness or overt behavioural responses.4 P300 may thus be a valuable adjunct to clinical examinations and anatomical imaging techniques in the evaluation of patients in coma or
persistent vegetative states. Departments of Psychiatry, Neurological Surgery and Otolaryngology, University of California, San Francisco, CA 94143-0984, USA
stupor and coma, 3rd ed. Philadelphia: FA Davis Company, 1982. 2. Hillyard SA, Picton TW. Electrophysiology of cognition. In: Plum F, ed. Handbook of physiology, vol V. Higher functions of the brain. Bethesda, Maryland: American Physiological Society, 1987. 3. Polich J. P300 from a passive auditory paradigm. Electroenceph Clin Neurophysiol 1989; 1. Plum F, Posner JB. The diagnosis of
74: 312-20. BM, Linke DB. P300 and coma. In: Maurer K, ed. Topographic brain mapping of EEG and evoked potentials. Berlin: Springer-Verlag, 1989: 192-96.
4. Reuter
Adverse reactions to monosulfiram SIR,-Dr Blanc and Dr Deprez (May 26, p 1291) note that the disulfiram-like reaction in their patient with scabies has only rarely been observed. From the references cited the belief could arise that this reaction only follows the imbibing of alcohol, contrary to recommendations. However, hearsay evidence suggests that this reaction is underreported by both patients and doctors. I have investigated a scabies outbreak in a nursing home, during which some patients and staff had been treated with 25% monosulfiram in alcohol (’Tetmosol’) diluted for use. I found that, apart from the high treatment failure rate, one member of staff (an otherwise healthy woman aged 32) had shown a disulfiram-like reaction soon after treatment, with flushing, sweating, and tachycardia. She had not consumed alcohol in the previous 24 h and seemed to have reacted only to the alcohol base of the formulation passing through the skin. She usually had facial flushing after ingestion of alcohol, as seen in 5-10% of caucasian people.’ Such flushing is believed to be due either to an abnormal alcohol dehydrogenase isoenzyme (ADH2) or to deficient aldehyde dehydrogenase (ALDH).2 In either case acetaldehyde accumulates, producing the reaction. Monosulfiram is not an efficient scabicide and often needs several applications. If it causes a prolonged inhibition of ALDH in the same way as does disulfiram3 then the chances of a reaction to the treatment are enhanced, even in healthy individuals, with each application. Such a reaction is potentially serious in children, for whom monosulfiram is prescribed most often. Consequently it should be used with care, especially since other more efficient and potentially less toxic scabicides are available. Medical Entomology Centre at The University of Cambridge, Austin Building, New Museums Site, Cambridge CB2 3DX, UK
100ms
Note P300
(arrow)
in
response to
rare tone
rare tone
I. BURGESS
1. Wolff P. Ethnic differences in alcohol sensitivity. Science 1972; 125: 449-51 BR, Saunders JB, Williams R, Hopkinson DA. Hepatic ADH and ALDH isoenzymes in different racial groups and in chronic alcoholism. Pharmacol Biochem Behav 1983; 18 (suppl 1): 61-65. 3. Tottmar O, Hellstrom E. Aldehyde dehydrogenase in blood. a sensitive assay and inhibition by disulfiram. Pharmacol Biochem Behav 1983; 18 (suppl 1): 103-07.
2. Ricciardi
Response at vertex to frequent tone (dashed line) and (solid line) from patient with GCS of 8.
CHARLES D. YINGLING YOSHIO HOSOBUCHI MARGARET HARRINGTON
