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NITROGEN-OXYGEN SATURATION THERAPY IN DECOMPRESSION SICKNESS
782 SUMMARY OF
29
CASES OF WERNICKE-KORSAKOFF SYNDROME
(CASES OF CHRONIC ALCOHOLISM EXCLUDED)
DETECTED AT NECROPSY
The ages of the 15 were males.
patients ranged
from 12
to
78 years. 14
were
females,
The hypothalamic lesions referred to by Wallis et al. as the of hypothermia may also be expected to give rise, at least occasionally, to the syndrome of inappropriate secretion of antidiuretic hormone. I have evidence for this in one patient and would like to know others’ experience. cause
regimen recommended by the European Undersea Biomedical Society that was publishedbefore the option of nitrogenoxygen saturation therapy had been proposed.4 Joint pain due to compressed-air decompression sickness which, Dr Hanson suggests,3 fails to improve in response to 18 m (60 ft) breathing oxygen, followed by 2 h at 50 m (165 ft) in compressed air, would be no ordinary "mild" limb bend but one which would deserve consideration for the longer treatment which we propose, if only to reduce the hypothetical possibility of subsequent osteonecrosis. The letters from Dr Brookings and Dr McIver and Dr James and his colleagues, 1which refer to helium as an alternative inert gas for the treatment of compressed-air decompression sickness, are from correspondents currently associated with commercial helium-oxygen diving. Such diving is performed predominantly in waters deeper than 50 m which is the depth limit for compressed-air diving. They discuss the treatment of compressed-air decompression sickness in those few places where helium mixtures are more readily available than nitrogen. In such special circumstances the change of oxygen diluent from, nitrogen to helium can be a useful option yet it is one which might aggravate the clinical status of the patient, possibly by counterdiffusion of inert gases in the tissues. When one of us was consulted by your correspondents in their first case’ he recommended that the chamber atmosphere be changed at depth from compressed air to helium-oxygen, despite this consideration. The slow-layering technique by which they could replace the atmosphere of compressed air around the patient with minimal wastage of the limited helium-oxygen available was described in detail. Similar atmosphere exchange techniques were first used by the Royal Navy8 and may continue to have a place in the treatment of commercial divers. They will have only a limited application because most compressed-air divers swim in waters that are shallower than 50 m (165 ft), possibly thousands of miles from any helium, and would be treated in a conventional compressed-air chamber. Hence our paper.
’
Institute of Naval Medicine, Alverstoke, Hampshire
T. G. SHIELDS
Shell International, The Hague, Netherlands
D. H. ELLIOTT
_
Division
of Neuropathology,
Department of Morbid Anatomy, University of Groningen,
Groningen, Netherlands
EBEL
J.
EBELS
SIR,-The major thrust of discussion 1in your columns has NITROGEN-OXYGEN SATURATION THERAPY IN DECOMPRESSION SICKNESS on our joint paper of July 22 from those discussion,from those who would broaden the issues2 and from others3 invite detailed reply. This is welcome, but we would point out that we limited our paper4to just one aspect of decompression illness: the occasional inadequacy of the published recompression tables when in treatment of a compressed-air diver in a conventional chamber, especially the clinical problems that may arise if these tables have been misinterpreted. In these circumstances we proposed that the potentially aggravating decompression of, for example, a quadriplegic diver could be postponed indefinitely without incurring the risk of pulmonary oxygen toxicity.
SIR,--Comments
who
want more
Thus the communication did not review the treatment of mild joint pain or other portions of the binary decision-tree, much of which has been presented for discussion elsewhere. 16 One basis for this simple diagramatic guide was the treatment 1. Brookings, C. H., Mclver, N. K. I., Lancet, Aug. 26, 1978, p. 468. 2. James, P. B., Hills, B. A. Holland, R. H. ibid. p. 469. 3. Hanson, R. de G. ibid. Sept. 16, 1978, p. 635. 4. Miller, J. N., Fagraeus, L., Bennett, P. B., Elliott, D. H., Shields, T. G., Grimstad, J. ibid. July 22,1978, p. 169. 5. Fagraeus, L., Miller, J. N, Bennett, P. B. Undersea biomed. Res. 1977, 4, A23. 6. Miller, J. N., Fagraeus, L., Bennett, P. B. Méd. aeronaut. spatiale, med. subaqu. hyperbare, 1978, 17, 74.
from those involved with commercial helium-oxygen divin offshore situations, at depths in excess of 50 m (165 ft). However, most compressed-air decompression accidents occur in water that is shallower than 50 m (165 ft), where heliumoxygen saturation diving systems are not commonly available. The letter from Dr James and his colleagues2 could confuse the reader unfamiliar with diving techniques. For instance, except perhaps after a "blow-up" from deeper than 50 m (165 ft), any diver in whom symptoms of decompression sickness arise after surfacing, would be treated in a chamber using compressed air for pressurisation, and, in most cases, oxygen by mask for respiration. At this stage helium-oxygen would not be used, even if it happened to be available after a helium dive. In practice any change from air to helium-oxygen is usually made around 50 m (165 ft) and, at that selected depth, the change from nitrogen to helium is indeed isobaric. It was the purpose of the isobaric experiment’ referred to in our joint paper of July 22, to assess the risk of such switches at 132 and 198 ft (40 m and 60 m) from air to helium, and, in laboratory animals, this change led to overt manifestations. .James et al. are wrong to say that there are no proven therapeutic tables beyond 50 m (165 ft) for 1-Lh (e.g., R.N. table 54 and U.S.N. table 4). The unrelated quotation at the end of come
ing
Bennett, P. B. The Treatment Offshore of Decompression Sickness (U.M.S. report no. 4-9-76). Undersea Medical Society, Inc., Bethesda, Maryland. 8. Barnard, E. E. P., Elliott, D. H. Br. med. J. 1966, ii, 809. 7.
783 their letter from a paper9 cited by us for other reasons concerns patients who were refractory to air treatment after helium-oxygen dives. This therefore is similar to the case8 cited in our paper, and, together, these two articles illustrate the potential complexities of changing inert gases during treatment, again possibly related to counterdiffusion. Initially, the nitrogen-oxygen saturation therapy was proposed to reduce pulmonary oxygen toxicity while prolonging the duration at depth when a patient failed to improve after conventional oxygen and compressed-air treatment, and thus to postpone the potentially harmful decompression. As a result of the experience gained with the first case (case 1 in our joint paper), where the technique used was to avoid further deterioration of the patient, the clinical rationale for subsequent cases was extended to take maximum advantage of both raised atmospheric pressure and time within a safe oxygen environment; and thus, to enhance the possibilities for further improvement. If Dr Brookings and Dr McIver’ think that our aim was the complete resolution of the manifestations of decompression sickness they surely misunderstand our intent, for our experience has consistently shown the folly of such expectations. In any given case of decompression sickness the outcome of therapy is not predictable. Moreover, spontaneous resolution of paretic manifestations does happen (e.g., our case 3), a fact that will continue to make it difficult to evaluate any new treatment.
Space precludes extensive discussion of the adjuvant meaemployed (e.g., high fluid loading, low-molecular-weight dextran, steroids, and low-dose heparin) which are valuable but do not provide a complete cure. The use of such measures is based upon current practice in managing extensive trauma especially with microvascular and central-nervous-tissue involvement. We must emphasise that the treatment proposed is experimental; it should be supervised directly by an experienced diving medical officer and used only after conventional oxygen and recompression therapy has failed. Such difficult cases are rare, but we have lately seen another case which further demonstrates the value of prolonged time at a convenient depth at a safe oxygen partial pressure, and shows that the paralysed sports diver, can be offered a chance of recovery after the failure of other recompression treatment. A 24-year-old female sports diver in the Bahamas sustained a massive cerebral air embolism while performing a training manoeuvre breathing compressed air in shallow water. She sures
remained unconscious and areflexic after immediate recompression to 50 m (165 ft) (U.S.N. table 6A). On a second recompression, all signs and symptoms resolved only after 2 h at 50 m (165 ft) breathing compressed air. Soon after surfacing from that treatment she had pain and weakness in one knee which responded well to oxygen therapy at 18 m (60 ft; U.S.N. table 6). Some hours later more extensive weakness developed which again responded to oxygen therapy at 18 m (60 ft), but a pattern of escalating recurrences was already established. She subsequently had to be recompressed on two further occasions, each time with more severe symptoms than during the previous seemingly successful conventional recompressions. Finally, she was transferred to Duke University Medical Center by jet air ambulance pressurised at 1 bar. Physical examination upon arrival revealed a significant spinal-cord lesion involving L2-S3 spinal segments mainly on the left side, with severe pain of the right knee, both shoulders, left elbow, and wrist. Venous blood taken for platelet and coagulation studies revealed early signs of disseminated intravascular coagulopathy following recompression to 50 m ft). Repeated physical examination revealed complete relief of all symptoms and signs only after 2 h. Therefore, and because of the history of escalating recurrences and her coagulopathy, we decided to adopt the more conservative approach by using the saturation nitrogen-oxygen procedure. Adjuvant therapy in-
cluded intravenous fluids, dexamethasone, and low-dose heparin, but not dextran. Repeated blood studies done after 24 h at 30 m (100 ft) indicated that all coagulation variables had returned to normal. There was no further recurrence of symptoms. Saturation decompression was then accomplished successfully with no further sequelae. F. G. Hall Environmental Laboratory, Duke University Medical Center, Durham, North Carolina 27710, U.S.A.
J. N. MILLER L. FAGRAEUS
MEASLES VACCINE AND THE COURSE OF SUBACUTE SCLEROSING PANENCEPHALITIS
SIR,-Dodson et aLl describe a patient with subacute sclerosing panencephalitis (S.S.P.E.) who had a rapidly deteriorating clinical course after receiving measles vaccine. This child had had natural measles as an infant and then received live, attenuated measles (rubeola) vaccine about a year after onset of s.s.P.E. symptoms. Dodson et al. suggest that the vaccine may have accelerated the course ofs.s.p.E. We have reviewed the records from the National Registry for S.S.P.E., which are maintained at the University of Tennessee for Health Sciences, Memphis, and at the Center for Disease Control, Atlanta, Georgia. The records of nine patients indicated that they had received live and/or inactivated measles vaccine after the onset of S.S.P.E. The diagnosis of S.S.P.E. was confirmed in all nine by the presence of measles-
specific haemagglutination-inhibiting or complement-fixing antibodies in the cerebrospinal fluid, by characteristic electroencephalogram, or by brain biopsy. Four of the nine patients have died, at an average of 3.6 years (range 2.4-6.5 years) after onset of S.S.P.E. symptoms and 2.4 years (range 0.8-4.4 years) after measles vaccination. The interval from s.s.P.E. onset to death in these S.S.P.E. patients is unusually long. In a review of one hundred and forty-nine S.S.P.E. deaths, the average interval from onset of symptoms to death varied from 9 to 30 months, depending 2 upon the age at onset. The five patients who are still alive have survived 10 5 years (range 7.3-12.2 years) after onset of S.S.P.E. symptoms and 9.3years (range 6.8-9.8years) after vaccination. At least three of these patients received multiple doses of live and/or inactivated measles vaccines, with one receiving a total of twelve vaccinations. There is no evidence to indicate that measles vaccine accelerated (or decelerated) the disease process in any of these patients. The variability of the clinical course in S.S.P.E. makes it difficult to evaluate therapeutic measures in this disease,3-7 and it is just as hard to identify any one factor that might be associated with a deleterious effect on the clinical course. We ,feel that Dodson et al. arrived at an incorrect conclusion in attributing the rapid progression of S.S.P.E. to the administration of measles vaccine. Immunisation Division, Bureau of State Services, Center for Disease Control, Atlanta, Georgia 30333, U.S.A.
NEAL A. HALSEY WARREN SCHUBERT
Department of Neurology, University of Tennessee Center for Health Sciences, Memphis
J.T. JABBOUR
Immunisation Division, Bureau of State Services, Center for Disease Control
STEPHEN R. PREBLUD
(165
9.
Fagraeus, L., Miller, J. N., Bennett, A48.
P. B. Undersea biomed.Res.
1977, 4,
1. 2.
Dodson, W. E., Pasternak, J., Trotter, J. L. Lancet, 1978, i, 767. Modlin, J. F., Halsey, N. A., Eddins, D. L., Conrad, J. L., Jabbour, J. T., Chien, L, Robinson, H. J. Pediat. (in the press). 3. Freeman, J. M. ibid. 1969, 75, 590. 4. Jabbour, J. T., Garcia, J. H., Lemmi, H., Ragland, J., Duenas, D. A., Sever, J.L.J. Am. med Ass. 1969, 207, 2248. 5. Scully, R. E., McNeily, B. U. New. Engl. J. Med. 1975, 297, 141. 6. Landau, W. M., Luse, S. A. Neurology, 1968, 8, 669. 7. Cobb, W. A., Morgan-Huges, J. A. J. Neurol, Neurosurg. Psychiat. 1968, 31, 115.
29
CASES OF WERNICKE-KORSAKOFF SYNDROME
(CASES OF CHRONIC ALCOHOLISM EXCLUDED)
DETECTED AT NECROPSY
The ages of the 15 were males.
patients ranged
from 12
to
78 years. 14
were
females,
The hypothalamic lesions referred to by Wallis et al. as the of hypothermia may also be expected to give rise, at least occasionally, to the syndrome of inappropriate secretion of antidiuretic hormone. I have evidence for this in one patient and would like to know others’ experience. cause
regimen recommended by the European Undersea Biomedical Society that was publishedbefore the option of nitrogenoxygen saturation therapy had been proposed.4 Joint pain due to compressed-air decompression sickness which, Dr Hanson suggests,3 fails to improve in response to 18 m (60 ft) breathing oxygen, followed by 2 h at 50 m (165 ft) in compressed air, would be no ordinary "mild" limb bend but one which would deserve consideration for the longer treatment which we propose, if only to reduce the hypothetical possibility of subsequent osteonecrosis. The letters from Dr Brookings and Dr McIver and Dr James and his colleagues, 1which refer to helium as an alternative inert gas for the treatment of compressed-air decompression sickness, are from correspondents currently associated with commercial helium-oxygen diving. Such diving is performed predominantly in waters deeper than 50 m which is the depth limit for compressed-air diving. They discuss the treatment of compressed-air decompression sickness in those few places where helium mixtures are more readily available than nitrogen. In such special circumstances the change of oxygen diluent from, nitrogen to helium can be a useful option yet it is one which might aggravate the clinical status of the patient, possibly by counterdiffusion of inert gases in the tissues. When one of us was consulted by your correspondents in their first case’ he recommended that the chamber atmosphere be changed at depth from compressed air to helium-oxygen, despite this consideration. The slow-layering technique by which they could replace the atmosphere of compressed air around the patient with minimal wastage of the limited helium-oxygen available was described in detail. Similar atmosphere exchange techniques were first used by the Royal Navy8 and may continue to have a place in the treatment of commercial divers. They will have only a limited application because most compressed-air divers swim in waters that are shallower than 50 m (165 ft), possibly thousands of miles from any helium, and would be treated in a conventional compressed-air chamber. Hence our paper.
’
Institute of Naval Medicine, Alverstoke, Hampshire
T. G. SHIELDS
Shell International, The Hague, Netherlands
D. H. ELLIOTT
_
Division
of Neuropathology,
Department of Morbid Anatomy, University of Groningen,
Groningen, Netherlands
EBEL
J.
EBELS
SIR,-The major thrust of discussion 1in your columns has NITROGEN-OXYGEN SATURATION THERAPY IN DECOMPRESSION SICKNESS on our joint paper of July 22 from those discussion,from those who would broaden the issues2 and from others3 invite detailed reply. This is welcome, but we would point out that we limited our paper4to just one aspect of decompression illness: the occasional inadequacy of the published recompression tables when in treatment of a compressed-air diver in a conventional chamber, especially the clinical problems that may arise if these tables have been misinterpreted. In these circumstances we proposed that the potentially aggravating decompression of, for example, a quadriplegic diver could be postponed indefinitely without incurring the risk of pulmonary oxygen toxicity.
SIR,--Comments
who
want more
Thus the communication did not review the treatment of mild joint pain or other portions of the binary decision-tree, much of which has been presented for discussion elsewhere. 16 One basis for this simple diagramatic guide was the treatment 1. Brookings, C. H., Mclver, N. K. I., Lancet, Aug. 26, 1978, p. 468. 2. James, P. B., Hills, B. A. Holland, R. H. ibid. p. 469. 3. Hanson, R. de G. ibid. Sept. 16, 1978, p. 635. 4. Miller, J. N., Fagraeus, L., Bennett, P. B., Elliott, D. H., Shields, T. G., Grimstad, J. ibid. July 22,1978, p. 169. 5. Fagraeus, L., Miller, J. N, Bennett, P. B. Undersea biomed. Res. 1977, 4, A23. 6. Miller, J. N., Fagraeus, L., Bennett, P. B. Méd. aeronaut. spatiale, med. subaqu. hyperbare, 1978, 17, 74.
from those involved with commercial helium-oxygen divin offshore situations, at depths in excess of 50 m (165 ft). However, most compressed-air decompression accidents occur in water that is shallower than 50 m (165 ft), where heliumoxygen saturation diving systems are not commonly available. The letter from Dr James and his colleagues2 could confuse the reader unfamiliar with diving techniques. For instance, except perhaps after a "blow-up" from deeper than 50 m (165 ft), any diver in whom symptoms of decompression sickness arise after surfacing, would be treated in a chamber using compressed air for pressurisation, and, in most cases, oxygen by mask for respiration. At this stage helium-oxygen would not be used, even if it happened to be available after a helium dive. In practice any change from air to helium-oxygen is usually made around 50 m (165 ft) and, at that selected depth, the change from nitrogen to helium is indeed isobaric. It was the purpose of the isobaric experiment’ referred to in our joint paper of July 22, to assess the risk of such switches at 132 and 198 ft (40 m and 60 m) from air to helium, and, in laboratory animals, this change led to overt manifestations. .James et al. are wrong to say that there are no proven therapeutic tables beyond 50 m (165 ft) for 1-Lh (e.g., R.N. table 54 and U.S.N. table 4). The unrelated quotation at the end of come
ing
Bennett, P. B. The Treatment Offshore of Decompression Sickness (U.M.S. report no. 4-9-76). Undersea Medical Society, Inc., Bethesda, Maryland. 8. Barnard, E. E. P., Elliott, D. H. Br. med. J. 1966, ii, 809. 7.
783 their letter from a paper9 cited by us for other reasons concerns patients who were refractory to air treatment after helium-oxygen dives. This therefore is similar to the case8 cited in our paper, and, together, these two articles illustrate the potential complexities of changing inert gases during treatment, again possibly related to counterdiffusion. Initially, the nitrogen-oxygen saturation therapy was proposed to reduce pulmonary oxygen toxicity while prolonging the duration at depth when a patient failed to improve after conventional oxygen and compressed-air treatment, and thus to postpone the potentially harmful decompression. As a result of the experience gained with the first case (case 1 in our joint paper), where the technique used was to avoid further deterioration of the patient, the clinical rationale for subsequent cases was extended to take maximum advantage of both raised atmospheric pressure and time within a safe oxygen environment; and thus, to enhance the possibilities for further improvement. If Dr Brookings and Dr McIver’ think that our aim was the complete resolution of the manifestations of decompression sickness they surely misunderstand our intent, for our experience has consistently shown the folly of such expectations. In any given case of decompression sickness the outcome of therapy is not predictable. Moreover, spontaneous resolution of paretic manifestations does happen (e.g., our case 3), a fact that will continue to make it difficult to evaluate any new treatment.
Space precludes extensive discussion of the adjuvant meaemployed (e.g., high fluid loading, low-molecular-weight dextran, steroids, and low-dose heparin) which are valuable but do not provide a complete cure. The use of such measures is based upon current practice in managing extensive trauma especially with microvascular and central-nervous-tissue involvement. We must emphasise that the treatment proposed is experimental; it should be supervised directly by an experienced diving medical officer and used only after conventional oxygen and recompression therapy has failed. Such difficult cases are rare, but we have lately seen another case which further demonstrates the value of prolonged time at a convenient depth at a safe oxygen partial pressure, and shows that the paralysed sports diver, can be offered a chance of recovery after the failure of other recompression treatment. A 24-year-old female sports diver in the Bahamas sustained a massive cerebral air embolism while performing a training manoeuvre breathing compressed air in shallow water. She sures
remained unconscious and areflexic after immediate recompression to 50 m (165 ft) (U.S.N. table 6A). On a second recompression, all signs and symptoms resolved only after 2 h at 50 m (165 ft) breathing compressed air. Soon after surfacing from that treatment she had pain and weakness in one knee which responded well to oxygen therapy at 18 m (60 ft; U.S.N. table 6). Some hours later more extensive weakness developed which again responded to oxygen therapy at 18 m (60 ft), but a pattern of escalating recurrences was already established. She subsequently had to be recompressed on two further occasions, each time with more severe symptoms than during the previous seemingly successful conventional recompressions. Finally, she was transferred to Duke University Medical Center by jet air ambulance pressurised at 1 bar. Physical examination upon arrival revealed a significant spinal-cord lesion involving L2-S3 spinal segments mainly on the left side, with severe pain of the right knee, both shoulders, left elbow, and wrist. Venous blood taken for platelet and coagulation studies revealed early signs of disseminated intravascular coagulopathy following recompression to 50 m ft). Repeated physical examination revealed complete relief of all symptoms and signs only after 2 h. Therefore, and because of the history of escalating recurrences and her coagulopathy, we decided to adopt the more conservative approach by using the saturation nitrogen-oxygen procedure. Adjuvant therapy in-
cluded intravenous fluids, dexamethasone, and low-dose heparin, but not dextran. Repeated blood studies done after 24 h at 30 m (100 ft) indicated that all coagulation variables had returned to normal. There was no further recurrence of symptoms. Saturation decompression was then accomplished successfully with no further sequelae. F. G. Hall Environmental Laboratory, Duke University Medical Center, Durham, North Carolina 27710, U.S.A.
J. N. MILLER L. FAGRAEUS
MEASLES VACCINE AND THE COURSE OF SUBACUTE SCLEROSING PANENCEPHALITIS
SIR,-Dodson et aLl describe a patient with subacute sclerosing panencephalitis (S.S.P.E.) who had a rapidly deteriorating clinical course after receiving measles vaccine. This child had had natural measles as an infant and then received live, attenuated measles (rubeola) vaccine about a year after onset of s.s.P.E. symptoms. Dodson et al. suggest that the vaccine may have accelerated the course ofs.s.p.E. We have reviewed the records from the National Registry for S.S.P.E., which are maintained at the University of Tennessee for Health Sciences, Memphis, and at the Center for Disease Control, Atlanta, Georgia. The records of nine patients indicated that they had received live and/or inactivated measles vaccine after the onset of S.S.P.E. The diagnosis of S.S.P.E. was confirmed in all nine by the presence of measles-
specific haemagglutination-inhibiting or complement-fixing antibodies in the cerebrospinal fluid, by characteristic electroencephalogram, or by brain biopsy. Four of the nine patients have died, at an average of 3.6 years (range 2.4-6.5 years) after onset of S.S.P.E. symptoms and 2.4 years (range 0.8-4.4 years) after measles vaccination. The interval from s.s.P.E. onset to death in these S.S.P.E. patients is unusually long. In a review of one hundred and forty-nine S.S.P.E. deaths, the average interval from onset of symptoms to death varied from 9 to 30 months, depending 2 upon the age at onset. The five patients who are still alive have survived 10 5 years (range 7.3-12.2 years) after onset of S.S.P.E. symptoms and 9.3years (range 6.8-9.8years) after vaccination. At least three of these patients received multiple doses of live and/or inactivated measles vaccines, with one receiving a total of twelve vaccinations. There is no evidence to indicate that measles vaccine accelerated (or decelerated) the disease process in any of these patients. The variability of the clinical course in S.S.P.E. makes it difficult to evaluate therapeutic measures in this disease,3-7 and it is just as hard to identify any one factor that might be associated with a deleterious effect on the clinical course. We ,feel that Dodson et al. arrived at an incorrect conclusion in attributing the rapid progression of S.S.P.E. to the administration of measles vaccine. Immunisation Division, Bureau of State Services, Center for Disease Control, Atlanta, Georgia 30333, U.S.A.
NEAL A. HALSEY WARREN SCHUBERT
Department of Neurology, University of Tennessee Center for Health Sciences, Memphis
J.T. JABBOUR
Immunisation Division, Bureau of State Services, Center for Disease Control
STEPHEN R. PREBLUD
(165
9.
Fagraeus, L., Miller, J. N., Bennett, A48.
P. B. Undersea biomed.Res.
1977, 4,
1. 2.
Dodson, W. E., Pasternak, J., Trotter, J. L. Lancet, 1978, i, 767. Modlin, J. F., Halsey, N. A., Eddins, D. L., Conrad, J. L., Jabbour, J. T., Chien, L, Robinson, H. J. Pediat. (in the press). 3. Freeman, J. M. ibid. 1969, 75, 590. 4. Jabbour, J. T., Garcia, J. H., Lemmi, H., Ragland, J., Duenas, D. A., Sever, J.L.J. Am. med Ass. 1969, 207, 2248. 5. Scully, R. E., McNeily, B. U. New. Engl. J. Med. 1975, 297, 141. 6. Landau, W. M., Luse, S. A. Neurology, 1968, 8, 669. 7. Cobb, W. A., Morgan-Huges, J. A. J. Neurol, Neurosurg. Psychiat. 1968, 31, 115.