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JNEUROSYPHILISA Review of Recent Literature
By W. D. NICOL, M.B., F.R.C.P.Physician and Lecturer in
Psychological Medicine, Royal Free Hospital; Physician
Superintendent, Horton
Hospital, Epsom
In this article it is proposed to review some ofthe work which
has been published during the lasttwo years, more especially with
reference toasymptomatic neurosyphilis, and the late
clinicalmanifestations, general paralysis of the insane,tabes and
optic atrophy.Asymptomatic NeurosyphilisBy the term 'asymptomatic
neurosyphilis' is
meant the condition characterized by the presenceof
abnormalities in the cerebrospinal fluid due tosyphilis,
unaccompanied by any clinical signs orsymptoms. It cannot be
stressed too often thatthe earlier treatment is instituted the
better theprospect of the arrest of the disease process, thebest
results of all being obtained in those casesbrought under treatment
in the asymptomaticstage.Hahn and Clark (I946) have made a
detailed
analysis of I8oo patients treated at the JohnsHopkins Clinic
between the'years 1914 and 1941.Out of these I8oo patients were
selected 533 withat least two cerebrospinal fluid examinations
and467 with at least two physical examinations. Theirwork affords
an excellent study, more especiallywith regard to the prognosis of
neurosyphilis. Theclassification of the type of abnormality of
spinalfluid is based upon that of Earle Moore. Thisgrouping is of
such paramount importance and souniversally used in America, that
it might be usefulto recapitulate here what is meant. Group I
fluidreveals a slight increase of cells 5-30, with normalprotein
content, a negative colloidal gold curveand a negative Wassermann.
In Group II thecells are similarly increased as in Group I,
proteinmay be raised from 30 to 75, the colloidal goldcurve is
variable and the Wassermann weaklypositive, while in Group III
fluid the cells are in-creased from o1 to 200, the protein from 50
to 200,the Wassermann is strongly positive and thecolloidal gold
curve exhibits what is known as theparetic formula, the first five
tubes being com-pletely decolourized. These authors, in
theiranalysis, make a sharp distinction between earlyand late
asymptomatic neurosyphilis: the early
form is confined to patients with a definite historyof 2 years
or less from the primary attack, whilein the late type the lapse of
time following theoriginal infection must be more than 2 years.
Of533 patients only 8.5 per cent. had received anytreatment prior
to diagnosis of asymptomaticneurosyphilis, not one had received as
many as atotal of 40 injections of trivalent arsenic and
heavymetal. The more strongly positive the spinalfluid on initial
examination, the more unfavourableis the prognosis with regard to
the final outcome.The longer the duration of the infection the
morestrongly positive and more resistant the cerebro-spinal fluid.
In respect of the relationship of thecerebrospinal fluid outcome to
the clinical out-come the authors state that the probability of
de-veloping clinical neurosyphilis at the end of fiveyears'
observation was i6.2 per cent. in patientswhose fluid became worse
or remained unchanged,contrasted with only 3.I per cent. in
patients whosefluid became negative or significantly improved:by
the tenth year these probabilities were 36.3per cent. and 6.8 per
cent. respectively. Theprobability of developing parenchymatous
neuro-syphilis increases directly in proportion to theseverity of
the initial spinal fluid involvement. Itshould be noted, however,
that in this large seriesonly 40 patients, over one-half of whom
had aninitial Group III fluid and most of whom provedresistant to
other types of therapy, receivedmalaria. Merritt (I945) presents a
useful analysisof 200 cases of asymptomatic neurosyphilis: IIomen,
go women. The sex incidence was relativelyequal, which is in sharp
contrast to that found inparenchymatous neurosyphilis, where the
male is amuch more frequent victim. Three quarters ofthe patients
had Group I abnormalities in thespinal fluid; none of these
patients developed theparenchymatous type of disease and only 4
percent. developed symptomatic neurosyphilis of themeningovascular
type. In those patients who hadGroup III fluid, parenchymatous
neurosyphilisdeveloped in 20 per cent. In a much wider
surveyMerritt found the incidence of asymptomaticneurosyphilis
present in 9.5 per cent. of 2263
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26 POST GRADUATE MEDICAL JOURNAL January 1948
patients who gave a history of syphilis of five yearsor more. On
the other hand, abnormalities in thecerebrospinal fluid are
increasingly prevalent,reaching a peak incidence of 35 per cent. of
allsyphilitics i8 months after the original infection.Treatment
recommended is firstly so-called routinewith trivalent arsenic and
bismuth, secondly try-parsamide, and thirdly fever. In patients
whohave received 30 or more injections of arsenic, andin whom the
findings of the spinal fluid remainabnormal, recourse to other
methods should beimmediately sought.General Paralysis of the
Insane
Arieti (1945) gives a critical review of the liter-ature of
senile G.P.I. together with a clinical andpathological description
of six cases. Patients inwhom symptoms appear for the first time at
theage of 60 or over are regarded as being senile casesof general
paralysis. The incidence for the decade1932-I941 in the New York
State hospital wasIo.58 per cent.; there was a tendency for
thenumbers to increase and the disproportion betweenmale and female
was even more pronounced insenility. The symptomatology was that of
anorganic psychosis and neurological signs were in-distinguishable
from those seen in cerebralarteriosclerosis. The irregularity of
the findings ofthe cerebrospinal fluid makes diagnosis
difficult;the course of the disease is rapid, with
progressivedeterioration.
Reynolds and Moore (1946) in a review ofrecent literature on
syphilis refer to a point of diag-nostic interest in general
paralysis. Thompsondescribes the palmomental reflex, which is
elicitedby stroking the thenar eminence from the base ofthe thumb
to the wrist: in a positive response theskin on the chin on the
ipsilateral side near themid line dimples and moves laterally and
upwards.This phenomenon, he claims, is one of the firstphysical
signs to appear and though occurringsometimes in other neurological
disorders, it isfar more common in the paretic.Electroencephalogram
in Neurosyphilis
Greenblatt and Levin (I945) describe theelectroencephalographic
abnormalities met within neurosyphilis. Investigations were carried
outin 330 cases, of whom 233 were selected; againstthis group was a
control of 240 from medical,nursing and other auxiliary hospital
staff. Amongstthe latter group were recorded o per cent. ab-normal
E.E.G.s. In the neurosyphilitic series50 per cent. E.E.G.s were
abnormal (46 per cent.abnormal slow; 44 per cent. abnormal fast,
andio per cent. paroxysmal). The incidence of ab-normality
according to clinical types was highestin meningovascular syphilis
(60 per cent.), in
general paresis it was 55 per cent., optic atrophy44 per cent.,
and tabes 14 per cent.; the tabeticswere not significantly
different from the controlgroup. It is noted, however, that 20 per
cent. ofthe total gave positive histories of cerebral seizures.In
the group of general paretics the highest in-cidence of abnormal
E.E.G. occurred in thosecases with seizures, the next highest in
the groupwith marked tremors and dysarthria, so that thereis some
correlation between the E.E.G. abnorma-lity and the clinical
condition. No correlation wasfound with regard to the presence of
pupillarychanges, delusions or hallucinations. The highincidence of
abnormality found in optic atrophy is amystery. These authors found
that the healingof these brain lesions after therapy reflected
animprovement in the electrical pattern of the E.E.G.Callaway and
his co-workers (1945) report thestudy of E.E.G. before and after
penicillin therapyin 38 patients (33 general paresis and
taboparesis).They agree that improvement in the E.E.G. isuseful in
determining the influence of penicillintherapy, but there is no
correlation between theseverity of the neurosyphilitic disorder and
thepresence or absence of E.E.G. abnormalities. Theyadvanced the
theory that the abnormality is an'expression of local anoxia and a
generalized orlocalized cerebral inflammation.'
Malaria TherapyA debt of gratitude should be accorded to
Bruetsch (1946) for releasing a document writtenby
Wagner-Jauregg in I935 on the' History of theMalaria Treatment of
General Paralysis,' whichhitherto had not been published. This is a
docu-ment of considerable historical interest. Wagner-Jauregg
describes how he had the idea of givingmental patients malaria or
erysipelas as far backas I887. The idea was not pursued as far
asmalaria was concerned; erysipelas was tried withpoor effect, but
in any case was not given to anyparetics. He then turned his
attention to Tuber-culin and reported in i909 with great caution
somemoderate success in cases of general paralysis;moreover he
maintained that the elevated temper-ature was not the fundamental
factor in treatment.Tuberculin treated cases were liable to relapse
andagain Wagner-Jauregg was attracted by the ideaof using malaria.
It was in June 1917 that ' asign of destiny' presented itself. A
woundedsoldier returned from the Balkan front had anattack of
malaria and this was reported by Wagner-Jauregg's assistant,
quinine was withheld, thediagnosis confirmed, and the blood of this
soldierwas used for scarifying the arms of three
general*paralytics; two developed fever, and so the firstcases on
record received malaria therapy.
Read, Kaplan and Becker (1946) published a
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January 1948 NICOL : Neurosyphilis 27
useful paper dealing with complications duringmalaria therapy.
The species of malaria employedwere Benign Tertian (P. Vivax) and
Quartan (P.Malariae). Their analysis comprises 300 cases, ofwhom 21
received Benign Tertian, the remainderbeing inoculated with quartan
malaria. The chiefcomplications referred to are jaundice,
oedema,and mild renal damage. Jaundice in 50 per cent.of cases
appears to be due to excessive haemolysis.This is of interest and
is a pointer to the need forcarrying out parasite counts on
patients duringmalaria therapy. The haemolysis is undoubtedlythe
result of a heavy parasitaemia. At the HortonMalaria Therapy
Centre, where a series of over2000 cases have been treated, it has
occurred veryrarely. This is probably attributable to the factthat
when parasite counts, which are done daily,show a high
parasitaemia, fever is temporarilyinterrupted. Care is needed in
arresting othermanifestations such as oedema and renal damage.Other
complications referred to are very rare,such as purpura, urticaria,
hyperlipaemia andspontaneous splenic rupture. Reference is alsomade
to two cases exhibiting an unusual form ofsevere respiratory
distress with cyanosis, bothbeing relieved by transforming a
quotidian type offever into a true tertian by the administration
ofthiobismol. No mention is made of those alarm-ing cases,
fortunately few, who show signs of peri-pheral failure. The use of
Thio-Bismol in malariatherapy was first described in America by
Schwartz(I939) and in this country by Whelen and Shute(I943). The
action of this drug in convertingquotidian fever into tertian in a
very high pro-portion of cases treated with benign tertianmalaria
is of great therapeutic importance, andin our experience has
rendered the treatmentcomparatively safe. Kaplan and others
(1946)have reported its use in Quartan malaria. Thereis much work
to be done in this direction, but theymake the interesting
observation that the usualmaximum dose of 0.2 gm. was ineffective
in casesshowing an unusually high parasitaemia.From the Malaria
Therapy Centre at Horton
Nicol (1946) made a careful comparison betweenthe results of
malaria plus tryparsamide andmalaria alone. Each group comprised
217 cases,127 men and go women. With the exception of44
taboparetics, all patients were suffering fromgeneral paralysis.
The follow up extended overten years and results were assessed
clinically andserologically. Definitely better results were
ob-tained in cases treated by malaria plus tryparsamidethan by
malaria alone. The trial of penicillin wasadvocated as being
possibly superior to and lessdangerous than tryparsamide.
The Serological Follow UpFrom the same Centre, Whelen (1946)
reported
a detailed analysis of the serological follow up ofover 500
cases. The work was based largely onDattner's premises, so well
advocated in his book'The Management of Neurosyphilis ' (944).
Itwas found that most cerebrospinal fluids followingmalaria therapy
became negative within threeyears from the end of treatment. The
conditionof the fluid at the end of the first year was a
fairlyreliable indicator as to whether further treat-ment was
necessary or not. In over 90 per cent.of patients showing two
consecutive ' negatives'at an interval of six months or more, the
spinalfluid remained persistently negative-a point ofimmense
practical importance. The necessity foreducating the patient to the
need for serial lumbarpunctures following treatment is so
universallyrecognized now, that every effort to minimize anyafter
effects is essential.
L. J. Underwood (1946) presented a statisticalanalysis of 500
punctures. The incidence ofpost-lumbar puncture headache varied
betweeni per cent. and 40 per cent. of punctures accordingto
different workers. This wide range is difficultto explain, as also
is the report that cisternalpuncture (Kulchar) reduces the
frequency ofheadaches. Solomon has used Extract Pituitaryi c.c.
intramuscularly and relieved many patients.Guttmann is reported to
have produced completerelief with Ergotamine tartrate in 82.9 per
cent. of35 patients. In the report of Underwood, where a22 gauge
spinal needle was used, and 2 c.c. of 2per cent. novocaine locally,
the average amount offluid collected being 6-8 c.c. incapacitating
head-aches occurred in 19 per cent. of cases. He makesthe important
observation that rest in bed afterthe spinal puncture did not
reduce the incidenceof post-lumbar puncture headache. At theHorton
Clinic, where the Dattner needle withHarrison's modification (Down
Bros.) has beenemployed for dyer Io years, post-lumbar
punctureheadache has only been encountered very rarely.We attribute
this largely to the practice of allowingpatients to leave the
outpatient clinic almost im-mediately and not encouraging them to
lie downafterwards. Col. A. J. King, in a personal com-munication,
referred to this important point. Heexperienced considerable
difficulty in Army clinicsin Italy during the recent war, but found
the in-cidence of post-lumbar puncture headaches felldramatically
directly the recumbent position afterthe spinal puncture was
discontinued. This bearsout Levin's experience (U.S. Army Medical
De-partment) that by keeping patients active only 15patients (0.67
per cent.) reported severe headachesin a series of 2237 lumbar
punctures; he putforward the theory that intracranial
hypotension
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28 POST GRADUATE MEDICAL JOURNAI January 1948and lowered spinal
fluid pressure and hyper-tension with resultant headache are
overcome bymoderate exercise.
PenicillinFor the past two years the literature on neuro-
syphilis, as indeed in many other branches ofmedicine, has been
dominated by penicillintherapy.THE ACTION OF PENICILLIN:
Frazier and Frieden (1946) review the availableevidence and the
theories put forward as to themode of action of penicillin on the
spirochaete.Both experimental and clinical observations
arediscussed. Experiments in vivo are reported byDunham and Rake,
who put forward the theorythat penicillin probably destroys the
reproductivecapacity of the spirochaete without destroying itspower
of motility. Frazier and Frieden them-selves found changes in the
structure of spiro-chaetes as a result of penicillin therapy.
Thelength of the spirochaete altered considerably,there being an
increase in long forms (I4 to 22microns); these long froms were
less motile thanthe short forms, an indication in their opinion
ofexcessive growth of the organism eventually lead-ing to its
death. Though these initial studies wereconfined to reports on only
5 patients under treat-ment for syphilis, the findings were
constant.
Another vexed question has been the problemof the transfer of
penicillin into the cerebrospinalfluid. McDermott and Nelson (I945)
ask whetherit is necessary in the treatment of neurosyphilisfor an
effective concentration of any particularchemotherapeutic agent to
be present in thecerebrospinal fluid. They argue that there is
noproof that an effective concentration of penicillinis not
achieved in the tissues of the central nervoussystem merely because
little or no penicillin isdetectable in the cerebrospinal fluid,
followingparenteral administration. Using dilution tech-niques of
bioassay these workers found no peni-cillin demonstrable in the
spinal fluid from 70patients being treated for neurosyphilis. On
theassumption that in neurosyphilis, even wheremeningitis is
present, the rate of infection is re-latively slow, the continued
presence of minuteamounts is probably all that is necessary
foreffective therapy. This is in contrast to the moreacute rapid
purulent form of meningitis of non-specific origin, where
parenteral administrationonly might prove dangerously
inadequate.Dosage of PenicillinIn the early reports of the American
clinicians
the dosage in neurosyphilis was in the region of2 mega units,
but the general consensus of opinion
now is to give at least 4 mega units. Reynolds andMoore (1946)
in their review of recent literaturequote Raiziss' experiments in
rabbit syphilis,where syphilitic infections were cured by
40,000Oxford units of penicillin per kilogram bodyweight over a
period of 8 days. On this basis fora human adult of 60 kg. weight
the total dose re-quired would be 2.4 mega units. Since, how-ever,
larger doses produced more rapid healing,these workers recommended
doubling the dose,making a total of 4.8 mega units. Rose andSolomon
(i947) draw the conclusion that 3 megaunits of penicillin,
supplemented by a short courseof therapeutic fever, are
insufficient in the treat-ment of late neurosyphilis. The reason
for thisassertion was the need for re-treatment in onethird of
their cases after one year's follow up andsince 1945 they have
recommended a course of 6mega units of penicillin.Methods of
AdministrationThe usual method is by intramuscular injection,
3 hourly throughout the 24 hours, in '50,000 unitdoses for a
period of 7 to 0o days. Weickhardt(1946) describes 5 cases where
introthecal peni-cillin was given, doses being gradually
increasedfrom 25,000 to ioo,ooo units; he maintains thatthough in
the experimental stages the method issafe. This author quotes
reports from otherworkers, which are certainly not encouraging.
Inview of the excellent results obtained by the in-tramuscular
route, it would appear that intrathecaladministration is
unnecessary, if not harmful.Even intramuscular injections at
repeated intervalsthroughout the 24 hours must be very trying
forthe patient. In this country Lloyd Jones (1946)and his
colleagues obtained good results in thetreatment of primary and
secondary syphilis withintramuscular injections (300,000 units)
oncedaily. Similarly Lourie (I945) and others advocateambulatory
treatment of early syphilis by threedoses of 600,000 units at
hourly intervals givenon 5 successive days. In the treatment of
thelater manifestations of neurosyphilis it has beenthe practice at
the Horton Malaria TherapyCentre to give intramuscular penicillin,
300,000units, once a day for 14 days, making a total of4.2 mega
units. In the work referred to above,penicillin was administered in
aqueous solution.Kirby and others (i945) discuss the use of
peni-cillin in beeswax peanut oil, with a view to delayingits
absorption. They used a mixture of 4.8 percent. beeswax and 300,000
units of penicillin percubic centimetre daily for 8 days. The
authorsconsidered the method safe and there was evidencethat the
action of the drug was prolonged. Febrilereactions accompanied by
convulsions have beenreported by various workers in association
with
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January 1948 NICOL: Neurosyphilis 29
penicillin therapy. These phenomena are gener-ally accepted as
Herxheimer reactions. Callaway(1946) tried to minimize the effects
by the use ofgraduated doses of penicillin; patients received5
injections of Io,ooo units, after which they weregiven 79
consecutive injections of 50,000 units.In spite of this febrile
Herxheimer reactions werefrequent, but were not sufficiently severe
to inter-fere with the completion of the course of therapy.Koteen
and his colleagues (I947), using 4 megaunits (25,000 units
intramuscularly 2 hourlythrough the 24 hours), report febrile
reactions in17 patients out of a total of I I I under review.
Twotabetics died within two weeks of treatment. Ina communication
to a joint meeting of the Frenchand British neurologists, held in
April 1947, at theRoyal Society of Medicine, Nicol and Whelen(I947
in the Press) reported their limited ex-perience of the use of
penicillin in the HortonMalaria Therapy Centre. In a series of 60
casesof general paresis so treated, no Herxheimer re-actions were
encountered, nor was any preparatorycourse of a heavy metal and
potassium iodidegiven.Results of Penicillin Therapy
It is indeed fortunate that several clinics haveconfined
themselves to the use of penicillin alone,so that we are at any
rate in some position toevaluate the efficacy of this drug, without
havingresults masked by the supplementary use ofmalaria or other
fever therapy. Results may begrouped under two headings-clinical
and sero-logical.
Clinically there seems to be general agreementthat patients gain
weight and feel quite differentin themselves. Heyman (I947) refers
to the sub-jective improvement, especially the asymptomaticgroup,
who described themselves as' one hundredper cent. different.' Nicol
and Whelen (videsupra) reported the marked clinical
improvement,particularly in patients who were confused and inpoor
physical condition, seen during the actualcourse of penicillin,, a
phenomenon rarely en-countered during malaria therapy. The
improve-ment in the tabetic is difficult of assessment dueto the
large subjective element. Gammon andStokes (vide supra) report on
lightning pains in 40tabetic and taboparetic patients. Some degree
ofimprovement following penicillin therapy wasnoted in 82 per
cent.; on the other hand, 4 of 15patients in whom no pain had been
present,developed pain during and after penicillin, whichthe
authors attribute to a Herxheimer reaction.Koteen (1947: vide
supra) and his colleagues re-port considerable improvement of
lightning painsin I7 out of 24 patients and also improvement
ofataxia in half the series; no improvement of
gastric crises was observed. These same workersrecord a striking
improvement in, a case of severeoptic neuritis, who before
receiving penicillin,had had intensive chemotherapy without
inter-ruption for the previous five years.
Serological results are of much easier assay andafford more
accurate data as to the efficacy ofpenicillin therapy. O'Leary,
Brunsting andOckuly (I946) are unconvincing regarding the useof
penicillin and exercise extreme caution inadvocating the use of
penicillin alone. Thiscertainly does not seem to be the view held
byother workers. Gammon and Stokes (1946) usedpenicillin alone in
I6I cases of neurosyphilis;since May 1945 the dose employed was 4.8
megaunits. Decision to retreat was based on failure ofspinal fluid
to become normal, failure of reversiblesymptoms to respond and a
serological relapse.They advocate penicillin as the first choice
oftreatment for neurosyphilis, though this statementmay be
qualified in the case of severe paretics.Koteen (I947) and his
co-workers are satisfiedwith 300,000 daily (in 25,000 unit doses)
over atwo week regimen and conclude that an increaseof the daily
total dosage would not increase theeffectiveness of the therapy.
They do, however,raise the question as to whether penicillin
plusfever therapy might not be superior to the use ofeither agent
alone. Nicol (1946) recommendedthe substitution of penicillin for
tryparsamide asan adjuvant to malaria therapy in the treatment
ofparenchymatous forms of neurosyphilis. Roseand Solomon (I947) in
a useful summary of afollow up of Ioo cases over one year or more
givea comparison of different modes of therapy; peni-cillin plus
malaria, penicillin plus fever cabinet,and penicillin alone. Where
penicillin was sup-plemented by other therapy, the amount ofmalaria
was reduced to 4 to 6 paroxysms of feverand the time in the fever
cabinet to 20 hours at105° F. The amount of penicillin given was
3mega units at first, but since 1945 penicillin dosagewas increased
to 6 mega units. In most cases thecell count returned to normal
earlier than theprotein content, a decrease in the
Wassermannoccurred but was less rapid. Results generallywere most
favourable with penicillin plus malaria;to quote these authors,
they write ' after two yearsexperience with penicillin our
enthusiasm hasbeen tempered and we have become aware of
thelimitations\ of this treatment as well as theadvantages.'Heyman
(1947) in a follow up of 141 cases
treated with doses of penicillin ranging from 1.2to 6 mega units
reports that with the use of 4 megaunits penicillin will arrest the
neurosyphiliticprocess in 85 per cent. of cases. He adds acautious
note, however, that longer periods of
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30 POST GRADUATE MEDICAL JOURNAL January I948
observation are necessary before evidence ofserological relapse
becomes evident. The criterionof relapse was based entirely on the
cell count.For early and late asymptomatic neurosyphilispenicillin
therapy is probably adequate, provideda careful follow up is
observed. In late sympto-matic neurosyphilis penicillin is not
recommendedas replacing fever therapy.The introduction of
penicillin to the armen-
tarium against syphilis and its later manifestationshas produced
a spate of literature and it is im-possible in our present state of
knowledge to bedogmatic as to its use. Earle Moore and Mohr(1946)
in a review of 4.I patients with early andlate asymptomatic
syphilis, while their resultswere encouraging (only 4 patients had
a serologicalrelapse within the limits of a six month to oneyear's
follow up) sound a note of warning andstate that a minimum of five
years' study and thetreatment of many more patients are
necessarybefore we can reach any definite conclusion.Dattner (i947)
is of the opinion that so far peni-cillin, when given in adequate
doses, is at least aseffective in the treatment of neurosyphilis as
com-bined fever and specific therapies. He adds aword of caution,
however, in that we are ignorantof the ' optimal relationship of
dose and time toobtain the maximal therapeutic success.'
Whilepenicillin may well supersede other forms oftherapy in the
treatment of asymptomatic neuro-syphilis, is it going to displace
malaria or artificialfever therapy for late symptomatic
neurosyphilis,more especially general paresis ? At present,opinions
of various observers are conflicting.Stokes, Steiger, and their
co-workers (1946) lookforward to the replacement of malaria therapy
bypenicillin; their observations are based on thefollow up of 283
cases of neurosyphilis. Reynolds,Mohr and Earle Moore (1946), on
the other hand,advocate the use of concurrent penicillin-malariaas
the treatment of choice for cases of generalparesis. Rose, Trevett
and others (1945) in aseries of Io6 patients with symptomatic
neuro-syphilis, employing penicillin plus malaria or fevercabinet,
reduced by half the amount of feverusually accepted as optimal.
It was several years before malaria was acceptedas an
established therapeutic measure; it is now30 years since
Wagner-Jauregg introduced it, andit is still in vogue as the
treatment par excellence forcertain types of neurosyphilis.
Penicillin is fullof promise, but it will be many years before
adefinite conclusion can be arrived at. We have yetto find the
optimum dosage, whether it should be
given concurrently with malaria, or before orsupplementary to
it, or, indeed, without malariaat all.
ConclusionsIf our therapeutic endeavours could be confined
to the asymptomatic cases of neurosyphilis, thelater crippling
disabilities of symptomatic neuro-syphilis would never be
witnessed. The socialand economic implications of general
paresisalone are almost without bounds. Iskrant (i945)gives an
estimate of the cost to the community ofhospitalization of paretic
patients in institutions inNew York State and the consequent loss
or im-pairment of productive capacity. When one learnsthat there is
an estimated annual loss of workingyears of life due to general
paresis amounting to75,729 man years and approximately 112
milliondollars loss in income, it is indeed time for avigorous
campaign to enable every possible meansof antisyphilitic
prophylaxis to be carried out.While these patients present
themselves for treat-ment, it is incumbent on us to make every
econo-mic use possible of our discharges as advocatedby Whelan and
Bree (I946) who make a plea fora wider conception of the promotion
of optimumhealth.
BIBLIOGRAPHYARIETI, S. (I945), Am. Journ. Psych., Iox,
585.BRUETSCH, WALTER J. (I946), J.A.M.A., 130, 14.BRUETSCH, WALTER
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