443 chest. The verbal I.Q.
score was
112, performance
score
and full scale score of 105. Further normal studies indued the SMA-12 chemical profile, complete blood-count, clood serological test, sedimentation rate, and thyroid profile. Since the patient had for 2 years received reserpine as part of her antihypertensive medication, it was considered that this might have contributed to the development of a hemiparkinsoman state. Reserpine was discontinued and a regimen of benzhexol, amantadine, and carbidopa begun. Within 24 h she was markedly improved, and noted that she could write better than she had been able to do in a long time, remarking "All the heaviness is gone". 1 month later, she was walking a mile a day, had no difficulty at all using her right hand, and had good facial expressivity. In walking she displayed only a mild reduction in right arm swing and a slightly flexed arm posture.
Discussion These two cases presented as progressive hemiparesis, raising the possibility of intracranial mass lesion. The patients suffered falls as a result of unilateral weakness. Tremor was inapparent, and a diagnosis of pseudohemiparetic parkinsonism could be made only on careful examination, particularly for mild cogwheel rigidity. Klawans and Topel3 have described eleven patients in whom parkinsonism presented as a "falling sickness," manifested predominantly by the loss of postural reflexes. However, none of their patients responded to anticholinergic medication, while my cases of pseudohemi-
paretic parkinsonism responded remarkably well to anticholinergic medication. Scott and Brody4 have described a slowly progressive unilateral Parkinson syndrome in youthful patients having a mean age of onset of 37 years. However, in contrast to our older patients, their patients were minimally incapacitated by their disease and did not present in a hemiparetic fashion. The pathology of unilateral Parkinson’s disease usually includes the depigmentation and loss of neurons in the substantia nigra and locus coeruleus predominantly on the contralateral side. There may also be neurofibrillary tangles and granulovacular degeneration in these nuclei.5 When a patient presents with tremor, rigidity, and akinesia, the diagnosis of Parkinson’s disease is readily made. If the patient’s gait is festinating and a pill-rolling tremor is present, there is rarely any difficulty in the diagnosis. When, however, the initial manifestation of Parkinson’s disease is falling, whether due to loss of postural reflexes as described by Klawans and Topelor to a pseudohemiparetic defect, then the diagnosis may be unusually difficult. Without careful neurological examination to disclose the presence of mild cogwheel rigidity, ! our patients might have been diagnosed as cerebrovascular disease, particularly when neurodiagnostic studies such as brain scan and electroencephalogram were nor,
,
mal. These patients were markedly incapacitated by their hemiparesis, while their prompt response to medication for Parkinson’s disease was such that they were ;eft with hardly any disability at all. How many similar patients may not be correctly diagnosed, and thus left untreated? I have seen two such cases within a 10-year
period. ,
These cases do differ fundamentally from those debribed by Klawans and Topel.3 Their cases all had bi:a:eral disease, and all had a positive glabellar reflex, e"tle my patients, having unilateral disease, not surpris-
lacked a glabellar reflex. Nine of their eleven patients also had a positive snout reflex, again showing bilateral cerebral involvement, while my patients lacked this sign. One very important similarity of their cases to mine is the fact that the diagnosis of parkinsonism had not been previously considered in any of these patients. The usual signs and symptoms of Parkinson’s disease were minimal. In their analysis of 856 patients with Parkinson’s disease, Hoehn and Yahrznoted that the diagnosis may be difficult when the full syndrome is not present, and especially when only tremor is present. In such cases there may be confusion between parkinsonism and essential tremor. It is the reverse situation which is presented here, where tremor is absent or almost entirely absent while hemiparesis predominates. Both cases displayed a markedly hemiparetic gait with dragging of the foot and ipsilateral facial weakness. The pathophysiological mechanism whereby a unilateral deficiency of basal ganglionic dopamine simulates pyramidal-tract disease is considered probably to relate to hemibradykinesia,6where an abnormally prolonged latency between the onset of muscular contraction and actual occurrence of limb motion is manifested as unilateral slowness in initiating movement resulting in pseu-
ingly
dohemiparesis. Requests for reprints should be addressed to G. J. G., 500 Pasadena South, St. Petersburg, Florida 33707, U.S.A.
Avenue
REFERENCE S
1. Parkinson, J. An Essay on the Shaking Palsy. London, 1817,. 2. Hoehn, M. M., Yahr, M. D. Neurology, Minneap. 1967, 17, 427. 3. Klawans, H. L., Topel, J. L. J. Am. med. Ass. 1974, 230, 1555. 4. Scott, R. M., Brody, J. A. Neurology, 1971, 21, 366. 5. Martinez, J., Utterback, R. A. ibid. 1973, 23, 164. 6. Brumlik, J., Boshes, B. ibid. 1966, 16, 337.
Preliminary Communication DRUG-BASED PREVENTION OF PRESSURE-SORES MARY BARTON A. A. BARTON Pressure Sore Unit, Nunnery Fields Hospital, Canterbury
A double-blind clinical trial was carried in 85 patients undergoing surgery to the upper shaft of the femur and to the hip-joint. In the control series, 27% developed pressure-sores before discharge from hospital. In the group in which 80 I.U. of corticotrophin (A.C.T.H.) in gelatin solvent was administered, only 12% developed pressure-sores. 19% of the patients with fractures to the upper shaft of the femur developed sores because accurate timing was not always possible. Prevention was complete in the case of totalhip replacement which is an elective procedure where A.C.T.H. can be administered at the right time to prevent disruptive damage to the microcirculation. It is suggested that the administration of A.C.T.H. should form part of the management of all high-risk surgical situations.
Summary
out
INTRODUCTION
PRESSURE-SORES occur in areas of anoxic necrosis where blood has been excluded from the skin and subcutaneous tissues by sustained pressure, or where occlusion
444 of the microcirculation by platelets has been produced by disruptive forces which cause the dislocation of endothelial cell junctional complexes. 1Z In animals a single injection of corticotrophin (A.C.T.H.) in gelatin solFREQUENCY OF PRESSURE-SORES FOLLOWING OPERATION
administered four hours before trauma stabilises the junctions and prevents cell separation. Platelet thrombosis does not occur and there is marked reduction in the frequency of pressure-sores.3 This paper describes the prevention of pressure-sores which occur in patients subject to operation, who carry a high risk of pressure-sores.
vent
MATERIALS AND METHODS
The trial was conducted in a double-blind form and stratified. A total of 85men and women over the age of sixty-five were admitted, all of whom gave their informed consent. There was no clinical evidence of pressure-sores at the time of operation. The operations to be undergone were those associated with surgery to the upper shaft of the femur and to the hip joint. As part of the pre-medication procedure, 80 LU. of A.C.T.H. in gelatin solvent (’Acthar’ gel) or a placebo consisting of the gelatin solvent alone was administered intramuscularly four hours before operation. This was done in a random fashion. The statistical significance of the results was determined
using Fischer’s test.
without risk to the patient. It is of especial use in the busy understaffed ward, and in the field or casualty situation. Two factors must be borne in mind. Firstly, that the inhibitory effect is a "once only" phenomenon associated with disruptive damage and does not occur where necrosis is due to pressure alone where there is no endothelial cell separation.5 Secondly, optimum cortisol levels following the injection of A.C.T.H. have to be reached by the time that the endothelial cell separation begins to occur.67 If the drug is given too late, no harm is done but there is no inhibitory effect. Sustained treatment, as in the case of long-term corticosteroid therapy, 8 causes pressure-sores to deteriorate. Total-hip replacement is an elective procedure where the reduction in the frequency of pressure-sores, by the technique described, is statistically significant due to the fact that correct timing is possible. In the case of operations for fractured neck of femur, the results were without precedent in this hospital. There were, however, periods of up to four days where sustained pressure was applied to the sacral tissues and sores due to anoxic necrosis did occur. Correct timing of the administration of A.C.T.H. to prevent disruptive damage was not possible, As there were no complications in the administration of a single injection of 80 l.U. A.C.T.H. in gelatin solvent, we suggest that this should form part of standard premedi cation treatment. grateful to Mr T. G. Thomas for allowing us to study the in his care and to the staff of the Buckland Hospital, Dover, for their invaluable assistance. Also to Armour Pharmaceutical Co. Limited, who supplied the material used in the trials and analysed the statistical significance of the results. We
are
patients
Requests for reprints should be addressed to A.A.B., Nunnery Fields Hospital, Canterbury, Kent CT1 3LP. REFERENCES
RESULTS
be seen from the table that 43 patients received gelatin solvent alone. Of these, 12 developed pressuresores, an overall frequency of 27% which was typical of the orthopaedic wards of this hospital chosen for the trial. Five sores occurred in the 16 patients who received a total-hip replacement (31%) and occurred in the area of skin where a sand-bag had been placed to provide support during the operation. Of 27 patients operated on for fractures of the upper shaft of the femur (nail and plate, Thompson, Austin-Moore, McLaughlin) 7 developed sores (26%), a figure comparable to that reported by Campbell.4 These were of generalised sacrococcygeal It
can
distribution. 42 patients received the active compound (acthar gel). 5 developed sores (12%). Although this figure was without precedent on the orthopaedic wards of this hospital it was not statistically significant using Fischen’s test. Of the 16 patients who had a total-hip replacement none developed sores. This was statistically significant. Of 26 patients who were operated on for fractured neck of femur, 5 developed pressure-sores (19%). Neither in this trial nor in another series was any complication observed in any of the patients who received a single dose of 80 i.u. of A.C.T.H. in gelatin solvent. DISCUSSION
The drug-based prevention of pressure-sores by the use of a single preoperative injection of A.C.T.H. in gelatin solvent has provided a useful cost-effective procedure
1. Barton, A. A., Barton, M. Aust. J. exp. Biol. med. Sci. 1968, 46, 166. 2. Barton, A. A. Bedsore Biomechanics (edited by R. M. Kenedi, J. M. Cowden, and J. T. Scales); London, 1976.
3. Barton, A. A., Barton, M. J. Path. Bact. 1968, 96, 345. 4. Campbell, A. J. Age Ageing, 5, 102. 5. Willms-Kretschmer, K., Majno, G. Am. J. Path. 1969, 54, 327. 6. Glick, I. W., Friedman, M. Thorax, 1969, 24, 415. 7. Barton, A. A., Barton, M. Br. J. Pharmac. 1969, 36, 219. 8. Barton, A. A., Barton, M. Age Ageing, 1973, 2, 55.
Hypothesis RELATION BETWEEN CARP
(MULTIPLE-SCLEROSIS ASSOCIATED) AGENT AND MULTIPLE SCLEROSIS D. H. ADAMS Medical Research Council Demyelinating Diseases Unit, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE
It is suggested that the Carp (multiple sclerosis associated and scrapie associated) agents may be the V-R.N.A. form of slow (D.N.A. viruses which are the ætiological agents of the two dis
Summary
eases.
INTRODUCTION
THERE has
recently been an upsurge of interest in the
transmissible factor found by Carp and co-workers’
I
score was
112, performance
score
and full scale score of 105. Further normal studies indued the SMA-12 chemical profile, complete blood-count, clood serological test, sedimentation rate, and thyroid profile. Since the patient had for 2 years received reserpine as part of her antihypertensive medication, it was considered that this might have contributed to the development of a hemiparkinsoman state. Reserpine was discontinued and a regimen of benzhexol, amantadine, and carbidopa begun. Within 24 h she was markedly improved, and noted that she could write better than she had been able to do in a long time, remarking "All the heaviness is gone". 1 month later, she was walking a mile a day, had no difficulty at all using her right hand, and had good facial expressivity. In walking she displayed only a mild reduction in right arm swing and a slightly flexed arm posture.
Discussion These two cases presented as progressive hemiparesis, raising the possibility of intracranial mass lesion. The patients suffered falls as a result of unilateral weakness. Tremor was inapparent, and a diagnosis of pseudohemiparetic parkinsonism could be made only on careful examination, particularly for mild cogwheel rigidity. Klawans and Topel3 have described eleven patients in whom parkinsonism presented as a "falling sickness," manifested predominantly by the loss of postural reflexes. However, none of their patients responded to anticholinergic medication, while my cases of pseudohemi-
paretic parkinsonism responded remarkably well to anticholinergic medication. Scott and Brody4 have described a slowly progressive unilateral Parkinson syndrome in youthful patients having a mean age of onset of 37 years. However, in contrast to our older patients, their patients were minimally incapacitated by their disease and did not present in a hemiparetic fashion. The pathology of unilateral Parkinson’s disease usually includes the depigmentation and loss of neurons in the substantia nigra and locus coeruleus predominantly on the contralateral side. There may also be neurofibrillary tangles and granulovacular degeneration in these nuclei.5 When a patient presents with tremor, rigidity, and akinesia, the diagnosis of Parkinson’s disease is readily made. If the patient’s gait is festinating and a pill-rolling tremor is present, there is rarely any difficulty in the diagnosis. When, however, the initial manifestation of Parkinson’s disease is falling, whether due to loss of postural reflexes as described by Klawans and Topelor to a pseudohemiparetic defect, then the diagnosis may be unusually difficult. Without careful neurological examination to disclose the presence of mild cogwheel rigidity, ! our patients might have been diagnosed as cerebrovascular disease, particularly when neurodiagnostic studies such as brain scan and electroencephalogram were nor,
,
mal. These patients were markedly incapacitated by their hemiparesis, while their prompt response to medication for Parkinson’s disease was such that they were ;eft with hardly any disability at all. How many similar patients may not be correctly diagnosed, and thus left untreated? I have seen two such cases within a 10-year
period. ,
These cases do differ fundamentally from those debribed by Klawans and Topel.3 Their cases all had bi:a:eral disease, and all had a positive glabellar reflex, e"tle my patients, having unilateral disease, not surpris-
lacked a glabellar reflex. Nine of their eleven patients also had a positive snout reflex, again showing bilateral cerebral involvement, while my patients lacked this sign. One very important similarity of their cases to mine is the fact that the diagnosis of parkinsonism had not been previously considered in any of these patients. The usual signs and symptoms of Parkinson’s disease were minimal. In their analysis of 856 patients with Parkinson’s disease, Hoehn and Yahrznoted that the diagnosis may be difficult when the full syndrome is not present, and especially when only tremor is present. In such cases there may be confusion between parkinsonism and essential tremor. It is the reverse situation which is presented here, where tremor is absent or almost entirely absent while hemiparesis predominates. Both cases displayed a markedly hemiparetic gait with dragging of the foot and ipsilateral facial weakness. The pathophysiological mechanism whereby a unilateral deficiency of basal ganglionic dopamine simulates pyramidal-tract disease is considered probably to relate to hemibradykinesia,6where an abnormally prolonged latency between the onset of muscular contraction and actual occurrence of limb motion is manifested as unilateral slowness in initiating movement resulting in pseu-
ingly
dohemiparesis. Requests for reprints should be addressed to G. J. G., 500 Pasadena South, St. Petersburg, Florida 33707, U.S.A.
Avenue
REFERENCE S
1. Parkinson, J. An Essay on the Shaking Palsy. London, 1817,. 2. Hoehn, M. M., Yahr, M. D. Neurology, Minneap. 1967, 17, 427. 3. Klawans, H. L., Topel, J. L. J. Am. med. Ass. 1974, 230, 1555. 4. Scott, R. M., Brody, J. A. Neurology, 1971, 21, 366. 5. Martinez, J., Utterback, R. A. ibid. 1973, 23, 164. 6. Brumlik, J., Boshes, B. ibid. 1966, 16, 337.
Preliminary Communication DRUG-BASED PREVENTION OF PRESSURE-SORES MARY BARTON A. A. BARTON Pressure Sore Unit, Nunnery Fields Hospital, Canterbury
A double-blind clinical trial was carried in 85 patients undergoing surgery to the upper shaft of the femur and to the hip-joint. In the control series, 27% developed pressure-sores before discharge from hospital. In the group in which 80 I.U. of corticotrophin (A.C.T.H.) in gelatin solvent was administered, only 12% developed pressure-sores. 19% of the patients with fractures to the upper shaft of the femur developed sores because accurate timing was not always possible. Prevention was complete in the case of totalhip replacement which is an elective procedure where A.C.T.H. can be administered at the right time to prevent disruptive damage to the microcirculation. It is suggested that the administration of A.C.T.H. should form part of the management of all high-risk surgical situations.
Summary
out
INTRODUCTION
PRESSURE-SORES occur in areas of anoxic necrosis where blood has been excluded from the skin and subcutaneous tissues by sustained pressure, or where occlusion
444 of the microcirculation by platelets has been produced by disruptive forces which cause the dislocation of endothelial cell junctional complexes. 1Z In animals a single injection of corticotrophin (A.C.T.H.) in gelatin solFREQUENCY OF PRESSURE-SORES FOLLOWING OPERATION
administered four hours before trauma stabilises the junctions and prevents cell separation. Platelet thrombosis does not occur and there is marked reduction in the frequency of pressure-sores.3 This paper describes the prevention of pressure-sores which occur in patients subject to operation, who carry a high risk of pressure-sores.
vent
MATERIALS AND METHODS
The trial was conducted in a double-blind form and stratified. A total of 85men and women over the age of sixty-five were admitted, all of whom gave their informed consent. There was no clinical evidence of pressure-sores at the time of operation. The operations to be undergone were those associated with surgery to the upper shaft of the femur and to the hip joint. As part of the pre-medication procedure, 80 LU. of A.C.T.H. in gelatin solvent (’Acthar’ gel) or a placebo consisting of the gelatin solvent alone was administered intramuscularly four hours before operation. This was done in a random fashion. The statistical significance of the results was determined
using Fischer’s test.
without risk to the patient. It is of especial use in the busy understaffed ward, and in the field or casualty situation. Two factors must be borne in mind. Firstly, that the inhibitory effect is a "once only" phenomenon associated with disruptive damage and does not occur where necrosis is due to pressure alone where there is no endothelial cell separation.5 Secondly, optimum cortisol levels following the injection of A.C.T.H. have to be reached by the time that the endothelial cell separation begins to occur.67 If the drug is given too late, no harm is done but there is no inhibitory effect. Sustained treatment, as in the case of long-term corticosteroid therapy, 8 causes pressure-sores to deteriorate. Total-hip replacement is an elective procedure where the reduction in the frequency of pressure-sores, by the technique described, is statistically significant due to the fact that correct timing is possible. In the case of operations for fractured neck of femur, the results were without precedent in this hospital. There were, however, periods of up to four days where sustained pressure was applied to the sacral tissues and sores due to anoxic necrosis did occur. Correct timing of the administration of A.C.T.H. to prevent disruptive damage was not possible, As there were no complications in the administration of a single injection of 80 l.U. A.C.T.H. in gelatin solvent, we suggest that this should form part of standard premedi cation treatment. grateful to Mr T. G. Thomas for allowing us to study the in his care and to the staff of the Buckland Hospital, Dover, for their invaluable assistance. Also to Armour Pharmaceutical Co. Limited, who supplied the material used in the trials and analysed the statistical significance of the results. We
are
patients
Requests for reprints should be addressed to A.A.B., Nunnery Fields Hospital, Canterbury, Kent CT1 3LP. REFERENCES
RESULTS
be seen from the table that 43 patients received gelatin solvent alone. Of these, 12 developed pressuresores, an overall frequency of 27% which was typical of the orthopaedic wards of this hospital chosen for the trial. Five sores occurred in the 16 patients who received a total-hip replacement (31%) and occurred in the area of skin where a sand-bag had been placed to provide support during the operation. Of 27 patients operated on for fractures of the upper shaft of the femur (nail and plate, Thompson, Austin-Moore, McLaughlin) 7 developed sores (26%), a figure comparable to that reported by Campbell.4 These were of generalised sacrococcygeal It
can
distribution. 42 patients received the active compound (acthar gel). 5 developed sores (12%). Although this figure was without precedent on the orthopaedic wards of this hospital it was not statistically significant using Fischen’s test. Of the 16 patients who had a total-hip replacement none developed sores. This was statistically significant. Of 26 patients who were operated on for fractured neck of femur, 5 developed pressure-sores (19%). Neither in this trial nor in another series was any complication observed in any of the patients who received a single dose of 80 i.u. of A.C.T.H. in gelatin solvent. DISCUSSION
The drug-based prevention of pressure-sores by the use of a single preoperative injection of A.C.T.H. in gelatin solvent has provided a useful cost-effective procedure
1. Barton, A. A., Barton, M. Aust. J. exp. Biol. med. Sci. 1968, 46, 166. 2. Barton, A. A. Bedsore Biomechanics (edited by R. M. Kenedi, J. M. Cowden, and J. T. Scales); London, 1976.
3. Barton, A. A., Barton, M. J. Path. Bact. 1968, 96, 345. 4. Campbell, A. J. Age Ageing, 5, 102. 5. Willms-Kretschmer, K., Majno, G. Am. J. Path. 1969, 54, 327. 6. Glick, I. W., Friedman, M. Thorax, 1969, 24, 415. 7. Barton, A. A., Barton, M. Br. J. Pharmac. 1969, 36, 219. 8. Barton, A. A., Barton, M. Age Ageing, 1973, 2, 55.
Hypothesis RELATION BETWEEN CARP
(MULTIPLE-SCLEROSIS ASSOCIATED) AGENT AND MULTIPLE SCLEROSIS D. H. ADAMS Medical Research Council Demyelinating Diseases Unit, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE
It is suggested that the Carp (multiple sclerosis associated and scrapie associated) agents may be the V-R.N.A. form of slow (D.N.A. viruses which are the ætiological agents of the two dis
Summary
eases.
INTRODUCTION
THERE has
recently been an upsurge of interest in the
transmissible factor found by Carp and co-workers’
I
