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Salvarsanized Serum in Syphilitic Nervous Disease

SOME SALIENT FACTS: THE METHOD, THE DRUG, THE RESULTS

C. EUGENE R I GGS, A. M., M.D.

ST. PAUL

Repriuted from The Journal of the Ame1·ica11 Medical Association · Sept. 4, 1915, Vol. LXV, pp. 840-845

CoPYRIGHT, 1915 AM ERICAN MEDICAL AssociATION FivE HuNDRED AND TniRTY·FIVE NoRTH DEARBORN STREET C H I CAGO Q.Jv SALV ARSANIZED SERUM IN SYPHILITIC NERVOUS DISEASE

SOME SALIENT FACTS: THE MET HOD, THE DRUG, THE RESULTS *

C. EUGENE RIGGS, A.M., M.D. ST. PAUL

T he cl inical history of syphili s with its therapy is in the process of making, and is greatly in need of restat­ ing. Especially is this true of nervous syphilis. T he report of many investigators are so incomplete, so lackin g in scientific accuracy, as to cloud their findings and give rise to great confusion and difference of opini on. Paucity of experience, the failure to follow lines of procedure marked out by previous well-known and competent investigators, substituting therefor per­ sonal and theoretical mod ifications, are all important factors in the production of this deplorable condition. There are but few Noguchis or Marinescos, few Swifts and E llises. There must be mutual endeaYor; a cooperation of effort, so to speak, along definite lines among those in terested in the therapy of syphilitic nervous diseases, if order is to come out of chaos and definite and reli able data be obtained. Mattauschek found from the examin ation of 4,134 cases of syphilis that 3. 19 per cent. of the patients in fectecl sutferecl from ce rebrospin al syphilis. If we believe with Robertson and Klaudner that syphilis is a septicemia, that the organi sm is invaded by the spirochetes within a clay or so after in fection, that the nervous system is involved from the beginning, and that the majori ty of syphilitics a re essentiall y candi­ dates for nervous syphili s f rom the very outset, the all ­ important thing in the trea.tment of this disease is the

*Read be fore the Section on Nervous and Mental Diseases :tl th e Sixty- ixth Annual Session of th e American l\fedical Associat ion, San Francisco, June. 1915. 3 early recognition of the primary lesion: Th~ s is. readily nerves) , modification of sensibility, changes in the effected by the means _of da: k-ground 11lummat10n or_a reflexes, positive Babinski, pupils unequal and differing microscopic examinat10n ot the . exudate of the s?re, in their reaction, etc., are frequently demonstrable in be its resemblance to a huntenan chanc_re never so both stages. sli aht. This is the psychologic moment m the treat­ "The way the central nervous system is involved in m ~1t of syphilis. early syphilis," says Coriat, "is certainly surprising, Gibbard and H arrison have observed that r e l a p s ~ s and this is also borne out by the spinal fluid tests. I are more than doubled when medication is begun 111 am making complete neurologic examinations of all the secondary rather than the primary stage, and the_Y cases of constitutional syphilis, in all of its stages, with­ beli eve that by the employm_ent of ~11 o d e n;. th e r a p ~ utJ c out nervous complaints. " 1 methods syphilis may be ltm1ted t ~ 1ts earhe_st mamfes­ The neurologic findings may, or may not, be associ­ tati ons and that eventually congcmtal syphtl! s wtll cease ated with definite serologic changes. E ither one of to exist. A most valuabie addition to our knowledge these may exist independently of the other. Quincke of syphilis is the significa nt fact . that the . nerv_ous and Mayer consider that there is a parallelism between system is subject to an early sp1rochetal ~n vas 1_on . pleocytosis and the neurologic symptoms; the former Serology has enlightened us g r e~t l y on. tJ-: ts pomt: is believed to bear a relation to the severe headaches Ravaut has fo und an abnormal sp ma~ _flmd m ~7 p ~ r (Jeanse lme and Barbe) . If the serologic changes only cent. of his cases of secondary sy ph1l_1 s ;~D r eyt u s m are present we have what Ravaut call s the "preclinical" 80 per cent.; Robertson and Klaudner 1_n 10 pet: cent.: stage of nervous syphilis, which may last for months Gennerich in 90 per cent. ; Mattauschek m 80 per cent. . or years before the fi rst clinical sign makes its appear­ N onne and Mantoux in 40 per cent. ; \tV 1le a n~ Stokes ance. I have now under observation two cases in m from 60 to 70 per cent., and t~1~ latter ~eh eve that which fifteen years elapsed between infection and the in every case of seco ndary syph!lts there 1s more or first manifestation of nervous symptoms. Serology less involvement of the nervous system. We c h s ~l. mann enables us to recognize this preclinical period in its states that in the ma jority of cases _of syphths the in cipiency when treatment is most effective. spinal fluid shows an _in c r ea~e d prot ~m c~nt e nt: A ~ examination of the sp111al flmd of 221 p a tl ~nt s 111 the T HE M ETHOD early stages of syphilis by_ yVechsel_mam: , vV2lhelm and As to the best method for the use of salvarsan in Dinkelacker, showed pos1t1ve fi ndm g~ 111 b ~ , and of nervous syphilis, the profession is hopelessly at vari­ these there were nervous symptoms 111 98; 1:1 the 63 ance. There have been too many contributions by neaative cases there were nervous symptoms 111 32. men whose training and acquaintanceship with the S imilar investigations of the primary peri?d h_ave more delicate methods of diagnosis were too faulty to elicited equally interesting resL:lts. A path?loglC spmal permit of their drawing reliable neurologic conclu­ fluid is common ; an increase 111 the a lbum~n a ~d glob­ sions. "The stage of temperate and critical criticisms ulin content, with or without p l ~ocy ~ os 1 s, IS often of results," says Schwab, "has evidently not yet been obse rved. The \Vassermann react10n IS the _l east ~ o reached." There are two modes of treatment that be relied on; a negative spinal _flui_d i ~ of d1agnosttc merit serious consideration, viz., the intensive and the value only when all symptoms _md!Cattve of n e r y ot~ s intraspinal methods. The former, when given intra­ involvement are absolutely laclong: One of Knda ~ venously and combined with the intramuscular injec­ patients, with a chancre on_ the ltps of hyo weeks tions of mercury, is of unquestioned value; some duration, showed a marked mcreased protem content believe that the results are in every way equal to those in the spin al flui d. obtained by the intraspinal methods (Sachs, Strauss Certain neuroloaic fi ndings, such as headache, and Kaliski ) . This procedure, when practiced by the in Yo h·ement of the "'second and eighth nerves (the lat­ 1. Dr. Co riat' s work :-t long thi s line will app ~a r wh en he and Dr. ter accordina to Benario, bein g more fr e qu e n~l y Sa nborn publish their results of th e treatment of nervous syphilis in ~o l Ye d in ea~·l y syphilis than any of the other cramal b2. sed on over 700 injections. 4 5 injection of salvarsan at the upper part of the nates. of clinical and biologic fact. I can best make clear in the loose tissues between the subcutaneous fat and the present status of intraspinal medication by a brief fascia ( in unctions or inj ections of mercury ~eing giv_en review of its literature and by a few excerpts from in the intervals), may be harmless and practically pam­ personal communications to me from representative less, but in the light of the studies of Tilney and vVoo~­ American workers. sey in vital staining with s~ luttm: s of trypan blue, IS Ehrlich, in his address on chemotherapy before the clearly inefficient. Th~se mv est t ga t_o~ s have shown International Medical Congress, August, 1913, referred that if solutions of thts agent are mJ ected subcuta­ to the intraspinal use of salvarsanized serum as prac­ neously or intra-arter_ially, tl:e skir~ and thoracic and ticed at the Rockefeller Institute, as being "not only abdominal viscera stam readtly whtle the ce ntr ~ l ner­ novel but suitable in so far as it obviates all possible vous system absolutely escap~s. If the solutwn be ill effect on the sensitive central nervous system, by injected intravenously, the stam reaches the dur~ and employing a serum obtained from the patient himself, pia mater, ~ut d?es 1:ot penet~ate th~ nervous ttssue. while at the same time it is possible to apply the cura­ vVhen the lllject!On IS gtven mtraspmally, the mem­ tiYe agent in sufficient quantities." branes are affected as before and the dye penetrates Drs. P urves Stewart and Harry Campbell both the nervous ti ssues through the walls of the veins and advise the treatment of nervous syphilis by intraspinal capillaries, affecting even th~ el?ithelium o ~ the latter. injections. "It is too early to claim," says the former; These experiments would mdtcate _that. mtravenous ·'that we possess a cure for tabes or general paralysis. inj ections of salvarsan are not sufficient m p a_re n c h~ ­ but we can, in suitable cases, do a good deal toward matous syphili s, however valuable they may be mluet1c arresting both diseases; time alone can tell whether meningitis, endarteritis and gumma. I~ has also bee_n such arrests are permanent." "In parenchymatous demonstrated that diseases of the menmges and _the1r syphilis," says the latter, "the intrathecal treatment is adjacent nervous tissues are best therapeutically mflu­ the only one yet devised which is capable of arresting enced by the employment of i~1tr asp i1:o': s methods. If, the morbid process." as Mott states, the cerebrospmal flmd ts the lyn~p_h of Mott, in his address before the section of Neurology the nervous system (and it has never been postttvely and Psychological Medicine of the British Medical shown that it does not reach the most remote nervot~s Association at its last annual meeting, said that "the tissues by way of the subarachnoid sp~ce~ and th e ~r late degenerative forms of syphilis of the nervous communicating canalicular system), tt 1s by th~ s system (and I refer especially to general paralysis) medium and through its channels ~hat therape';lttc have not been cured nor even greatly benefited by any agents can best be conveyed to the lestons deeply sttu­ treatment with salvarsan or neosalvarsan, whether ated in the cortex. administered intravenously or intrathecally." He Since affections of the meninges, such as influenza!, admitted, however, that his personal experience did not pneumococcic, and epidemic cerebrospinal meningiti_s, warrant his speaking authoritatively. In the ensuing are not responsive to any other than s u~~r.achnmd discussion McDonagh stated that he had observed somP. therapy, it would seem to follow ~hat syphthttc affec­ remarkable results from the intraspinal injection o£ tions of the membranes and thetr adJacent nervo us salvarsanized serum in cerebrospinal syphilis, but no tissues can best be treated by the intraspinal adminis­ better than he had obtained from inunctions of mer­ tration of spirocheticidal drugs. cury and intravenous inj ections. Intraspinal medication is one of the most no_tarsenic as to the antibodies cases if a sufficient number of treatments are given. it liberate~ . According to .Shil:mer, it is very difficult There are four kinds of intraspinal medication: fi rst, to cl etermme whether ant1bod1es play any additional the inj ection of mercurialized serum, as advocated by therapeutic role ; the good effects of the se rum he thinks, are clue, not to free salvarsan, but rathe'r to 2. The citations made from Drs. Cotton, Coria!, Jelliffe and Sanborn some oxidation products which by heating are sepa- g.re from personal communications to the writer. 8 9 rated from their loosely synthetic combination and whereas neosalvarsan gave 33.3 per cent., and they again become active. think salyarsan should always be used if one wi shes to Cotton advocates a more s tr ~nuou s therapy in the giY e hi s patients the best possible results in the shortest future than in the past. The small amount of salvarsan possible time. "Salvarsan is the most potent remedy," given. intraspinally every two weeks he regards as say Craig and Collins, "in our armamentarium in the effective only for a few days. It does kill some spiro ­ treatment of syphilis of the nervous system." They believe it to be much more potent than neosalvarsan. chetes; then in ~h~ inte~ve ning time the progress goes on and the remammg spirochetes continue to be active. \iV echselmann thinks that salvarsan alone should be During all this period the patient is deteriorating. used in the treatment of syphilis, and this conclusion is based on the obse rvation of 45 ,000 injections of this vVhen ~nally ~he bi~logi c reactions become negative drug. E hrlich and Dreyfus prefer old salvarsan to the subject IS 111 a mildly demented state from which recovery does not appear probable. He advises a com­ neosalvarsan, but use the latter when a mild, nonirri­ bination of the Swift and Ellis method and the Oai!vie tating action is desired, although frequently the treat­ modification, using the former one week and on ~Iter­ ment is begun with neosalvarsan ( Conzelman). Many nate weeks the latter. Smith has recently reported medical men advise that mercnry be administered in twelve cases in which he had used the Swift and Ellis the intervals between the injections. Collins refers to with a modified Ravaut method ; the latter was fol­ potassium iodid as a "blighting delusion" and to the lowed by unfortunate complications after the second administration of mercury by the mouth as a " futility.'' inj ection, and was di scontinued. He now injects as high The relative merits of mercurialized and salvarsan­ ized serum, are still sub judice. The cases in which the as_ 30 c.c. of undiluted serum weekly ( Svvift and Ellis) fo rmer have been tried have been too few and the with a more speedy response and no ill results. time too short to warrant any express ion of opinion. . The true role of_ subdural therapy in nervous syphilis As to salvarsanized serum much can be said. Accord­ I S one of prevent10n rather than cure. The frequent ing to Hough : "The researches of Ehrlich and others occurrence of changes in the nervous system and spinal have shown that salvarsanized serum has a distinct ~uid in early syphilis cannot be too strongly empha­ spirochetacidal power, a power greater than that exer­ sized. cise d by salvarsan itself" (Siebert). Swift and Ellis Hauptmann says that a positive Wasermann in believe that "there is definite evidence that this form the cerebrospinal fluid in secondary syphilis is an of treatment has a curative action on the syphilitic expression of a true syphilitic cerebrospinal disease. process." A neurologic and laboratory examination should ne In the light of all the evidence the diversity of made in every _case,. for ~nly by an early recognition opinion that still exists regarding the utility of salvar­ of the nervous mvas10 n with prompt and radical treat­ san is most surprising. This seems to be almost as ment can subsequent inflammatory and deaenerative marked as when Ehrlich in 1909 first announced his changes be guarded against. b discovery of this truly remarkable synthetic substance.

THE DRUG THE LANGE COLLOIDAL GOLD REACTION "Salvarsan," says Wassermann, "is m my opinion Dr. Hammes and I have studied the colloidal gold the mightiest weapon in medicine." Gibbard and Har­ reaction3 in sixty cases. Eleven paretics gave the rison state that when mercury alone was used there typical paretic curve, namely, a complete decoloriza­ were 83 per cent. of clinical relapses, but with the tion in the first three or four tubes with some changes use of salvarsa n and mercury, only 3.9 per cent. had in the next four-5555443200. In one paretic with an recurred. They prefer it to neosalvarsan, as they acute maniacal onset the colloidal gold solution decol­ regard it as much more active in corresponding doses. orized completely in every dilution up to the tenth tube. According to Nelson and Haines, salvarsan has given 3. I am greatly indebted to Dr. Archibald L eitch for his pains· them in nine months 64 per cent. of negative serums, taking care in the investigation of the Lange colloidal gold reaction. 10 11

In_ one ca~e of clinical paresis with negative blood and THE RESULTS spmal flmd, the colloidal aold reaction was neaative · . 0 b ' The recent statements of Schwab that "clinical one case of taboparesis gave the curve for paresis. In improvement in paresis as a result of this treatmen~ ten cases of tabes the curve was somewhat variable [Swift and Ellis method] is a thing that no one ot seeming to bear a distinct relation to the intensity of recoanized standing has as yet asserted," and of Ravine the Wassermann reaction. that o salvarsanized serum administered in traspinally . In ~wo cases of typical clinical tabes all reactions, (Swift and E llis) gives only laboratory improvement; b10log1e and colloida! gold,_ were _n_egative. Five (50 that its chief asset is the original intravenous injection; per cent. of our tabetlcs) w1th pos1tive blood and spinal that clinical recoveries are not reported; that patients fluid gave wha~ mig!1t be ca ~l e~ a t~b et ic ~ur ve, _namely, have been made decidedly worse, and that fatalities 3444432000, w1th slight vanat10ns 111 the mtens1ty. An have occurred are in the light of the following facts atypical case, in which the symptoms were most stw­ gest i_v~ _of an incipient tabes or paresis, reacted in tl~e most amazing. In speaking of intraspinal therapy (Swift and E llis) syph 1~1tl c zone. Three tabetics gave the characteristic paret1c curve. as used in nine cases, Barrett says: The curve in our cerebrospinal syphilis cases, six in number, was such as occurs in the syphilitic zone. In Enough time has not elapsed to warrant passing final judgment: . . . but the improvement, or at least the o_ne case of clinic~ ! cerebrospinal syphilis with a posi­ increase in the proportionate number and length of remis­ ttYe ~iV assennann 111 th ~ blood :'lnd spinal fluid, the gold sions, has been encouraging and justifies the undertaking of solutiOn reacted negatively; 111 another similar case this treatment in all early cases. the se robi~logic findings were all negative, while the gold solutiOn reacted in the syphilitic zone. In two Dr. Blumer states that "thirteen cases of general cases o~ t ub er~ul ~t~s meningitis and one case of pneu­ paresis, taboparesis and tabes have been treated with mococcic menmg1tis the curves were similar namely 0123343210. In one case of pneumococcic n;eninaitis salvarsanized serum with euconragiug resnlts.'' a_ssociated with spinal syphilis of three months' d~ra­ 1-Iough, according to Vvardner, s um ~.· t_tp the work of tion, the curve was similar to that observed in our Swift and E llis at the Rockefeller Inst1tute, Myerson cases of acute meningitis. of the Psychopathic Hospital, Boston, and Asper of _Two c~~es of syphilitic endarteritis and apoplexy Baltimore, as follows: w1th _po sitive blood and spinal fluid gave a typical paret1c curve. A case of tabes associated with cere­ There has been marked improvement in the syphilitic inflammatory processes and in many cases the patients with brospinal syphilis gave an atypical curve su0agestive tabes especially have shown pronounced clinical improve- of both. Two cases of spinal cord tumor one a fibro­ my~oma in the ~e~vical region, one a cyst in the lumbar ment. reg10n, gave s1mtlar curves: 0000001233. V.,Te have Taylor of Boston, in referring to the results obta i ~1ed found in the following conditions no reaction: a case by the Swift and E llis method in the N eurolog1cal of transverse n:yeliti_s, three of multiple sclerosis, five Department of the Massachu_setts General Hospital cases of essential eptlepsy, one of involutional melan­ and in a limited number of pnvate cases, says: cholia, three normal spinal flu ids, two cases of Syden­ h_am's chorea, Of.!e s ub ~c ut e degeneration of the poste­ In otherwise obstinate cases of tabes the results have been nor . columns w1th pnmary anemia, one Friedreich's encouraging. It is believed that a certain modification in atax1a, one I? rogress1ve muscular dystrophy (Erb ), and the course of general paralysis may result if taken early. two alcohohcs. At times it appears that cerebrospinal syphilis yields more Treatment_ has produced no change worth recording promptly to this than to other forms of treatment; several on the coll01dal gold curve except in three cases of cases suggest the possibility of complete cure; no perma­ tabes. nent ill effects thus far have been experienced. 13 12 had delusions of grandeur, thought he was the best agent . Dr. Hammes an? I haYe administered over 200 injec­ in the country, etc.; at times became greatly excited and had tiOns of sa l var~an t zed serum ( th~ Swift and Ellis pro­ to be put in restraint. Physical examination negative. Neu­ cedure). Thet e have been no Ill effects aside from rologic examination: Pupils respond sluggishly to light and one case of aseptic chemical meningitis in' which there accommodation; marked increase of knee jerks; otherwise negative. The blood serum and spinal fluid gave a posi­ was speedy recovery. Ou~· r_esults are very similar to tive Wassermann; the latter showed increased pressure with thos~ of Dr. Taylor. RemiSSions occurred in three out globulin excess and 12 lymphocytes to the cubic millimeter. of etght paretics. One patient relapsed after four The colloidal gold reaction was typical of paresis. He was months; the other two are apparently perfectly normal. given eleven inj ections of salvarsanized serum (Swift and ~he blood serum and cytochen~ical reactions were prac­ E llis); his mental condition became normal after the fifth; tlca~ly norm~!; the sp111al flUld only remained mildly after the eighth the vVassermann in the blood became nega­ positive. Ltke Dr. Sanborn we have thus far been tive. When he left us the spinal fluid still reacted posi­ unable to get a negative spinal fluid in paresis. tively; its pressure was normal; there were seven lympho­ In 75 per c_ent. of our tabetics the spinal fluid has cytes to the cubic millimeter and the Noguchi was mildly become negative and all but two out of twenty-two positive. ~ases have bee_n be_ttered_ cl inically. The gait has I have under my care at present a paretic who was tmproved, the ltghtn111g pa111s have lessened or di sap­ acutely maniacal; after the second injection of salvar­ peared, the bl~dder symptoms have cleared up, ·while sanized serum the excitement disappeared and now he at t~e same time there has been a decided change appears perfectly normal, his elation and grandiose physically for the better. ideas have also disappeared. . All of ot~r. cases of cerebrospin~l syphilis have CASE 2.-C. was seen first June 12, 1914: 29 years old, n:~proved cltmc_a ll y~ cyt~ch emica lly and biologically, news agent; family history negative. Personal history nega­ \\·tth one e_xceptwn 111 which treatment seemed to have tive with the exception of gonorrhea in 1914; denies syphilis. no benefictal effects. Pr e~e nt trouble began about one year ago with occasional Dr. Cott01: says that his statistics . show that SO per attacks of shooting pains; for the past three months there cent . . (paretlcs) make tremendous Improvement and has been a tottering gait with difficulty in starting the flow that tncludes all cases treated, many of them. in the of urine. After a strong laxative the bowels and bladder last stages. Of the favorable cases, and by that he evacuated involuntarily. For the past three months sexual power has been markedly impaired. During April, 1914, means the new ca_se~, at least 75 per cent. have shown he noticed a feeling of tightness around the waist which has ~e ry nw~·ke d re1111sswns. About sixty patients are liv- gradually disappeared; he also felt numbness in both feet. 111g outst?e of the hospital. There have been several Physical examination negative. Neurologic examination: relapses 111 _cases which were pretty far advanced and Pupils respond to li ght and accommodation, but are irregu­ seemed to Improve wonderfully at first. He has had lar, the right being larger than the left; marked Ro mb~rg ; no untowa~·d symp~on~s! but he reports several cases ataxia of both upper extremities; loss of knee and Acl11 lles o~ mechamcal men111gi~IS, such as I described a year jerks; impaired muscle sense of both lower extremities; a.\>o bef?re the _Amencan Neurological Association. blood and urine normal; blood serum and spinal fluid gave 1 he patients qUJckly recovered. a positive vVassermann. There was increased pressure of Of the three f~l l_owing cases, one is paresis in which the spinal fluid with a positive globulin and 42 lymphocytes !h~ ~ental condttton became normal after the fifth to the cubic millimeter. After the third intraspinal inj ecti on ~nJectwn; the o!h~r two are tabetic cases in which the hi s blood became negative, and the spinal fluid after the tmprovement chmcally and serobiologically is notable. seventh; cytochemically it was also normal. His gait greatly improved, as did also his bladder functioning; the lightning CASE 1.-B. was first s_een Aug. 19, 1914. Insurance agent, pains have disappeared and he has gained 16 pounds in 34 years old, fam1ly h1story negative. Personal history: weight. When I last saw him he was walking without a Uses tobacco and alcohol moderately; gonorrhea in 1904 · cane. denies syphilis. Present complaint began about June 1, 1914, CASE 3.-A., 43 years old, married; family history nega- w_1th l a~k of mental concentration and inabil'ity to handle tive; seen fir st Jan. 11 , 1915. Personal his tory: No alcohol h1s busmess. Gradually became disoriented and confused, 15 14 logically and serobiologicall_Y, and if there be found but tobacco in excess. Denies venereal disease, but admits exposure; one child living and well; wife has had no mi s­ any symptoms of. nervou_s n~volv e n~ent ?r. an. abnor­ carriages. Illness began about twelve years ago with pain mality of the spmal fhud, mtra~pmal n~Jectwr: s. of and soreness in joints of the feet and both heels, reli eved salvarsanized serum should be gtven u_nttl a. c hmc~ l by potassium iodid and inunctions of mercury. These con­ and laboratory cure is effected. Bern s t~m adv1 es thts ditions would recur every year or so and were relieved by procedure as a prophylactic m~a s ur e 111 all cases of this treatment. Almost two years ago he noticed that the syphilis, particularly 111 the pnmary and secondary feet were numb and were awkward and clumsy ; about six stage. . . bl · d · months ago numbness developed in both hands and up to 2. Lange's colloidal gold solutwn 1s a valu~ e at 111 the elbows, also around the scrotum. Bladder and sexual diagnosis, possessing a co rro?orattv_: value.: functions normal. Occasional lancin ating pain s. Physical n:a~k ed examination negative. Neurologic examination: Light Paresis gives a characten stlc curve ( 111 over 90 pe, response sluggish in both eyes. accommodation normal, left cent. of our cases) so constant, say Grulee and Moody, pupil larger than right ; marked Romberg, no ataxia of that "one may venture a diagnosis without_ othe~ fi_nd­ upper extremities and deep refl exes normal. Lower extremi­ ings, either clinical or laboratory." Th~re 1s a chstmc­ ties: knee and ankle jerks lost, superficial reflexes normal, tive tabetic curve wh1 ch was present m 5_0. per ~ent. impaired tactil e sense extending from feet to knees with of our cases. The colloidal gold r eact ~ on dtffer ~ 1_1t1ates loss of muscl e sense. Blood and urine normal. The blood cl early between paresis and ce r ~brospmal sy~hth s . In serum and spinal fluid gave a positive \i\Tassermann , with tuberculous meningitis the collotdal gold s_olutwn : eacts increased pressure in the spinal fluid, Noguchi positive, 18 lymphocytes per cubic millimeter. After the second inj ec­ markedly. N onsyphilitic cases sometnne_s g1ve a tion the Wassermann in the blood became negativ e; after vague di scoloration which may or may _not _mv_ade the the fourth inj ection the vVassermann in the spinal fluid syphilitic zone, bnt ~~ hic!t has n? specwl s~gmficance . became negative in 0.7 c.c.; Noguchi mildly positive, four 3. Intraspinal medtcatton ( wtft and E~hs method) lymphocytes per cubic millimeter. H e has received fiv e is a sane and safe form of therapy, _and 111 the hands inj ections of salvarsanized serum intraspinally. There has of competent men is practically dev01d of danl?er. In been a decided improvement in the li ghtning pains and in cerebrospinal syphilis and tabes, results ?btamed ~y the gait; the numbness has left the upper extremities and is very much better in the lower; there is a great improve­ conse rvative workers are most encouragmg, a~ d m ment in the general health. some cases little less than marvelous. vVhen parests. can be treated in the early, the toxic, stage, before senous Treatment is usually regarded as contraindicated in deaeneration of nervous tissue has ensued, an arrest cases of clinical tabes in which the biologic and cyto­ of 0 the di sease may reasonably be expected. Is it too chemical reactions are negative. Recently Dr. Hammes much to hope for a cure? and I have each had such a case in which the intra­ 1019 Lowry Building. spinal use of salvarsan ized serum produced very cleciclecl improvement. The spinal fluid in my patient reacted positively after the first injection. ·while in some patient there is a definite periodicity in the pains following an inj ection, in others their occurrence is mo t erratic; sometimes, but rarely, there will be no pain at all, at others they will vary in their manifestation from fifteen minutes to fi ve hours. The cessation of tabetic pain Craig and Collins regard as the single gre.atest benefit following the use o f salvarsan. CO NCLUSIONS 1. Every patient with constitutional syphili s, espe­ ciall y in the earl y stages, should be examined neuro-