The administration of vitamin B1 by intraspinal injection

THE ADMINISTRATION

OF VITAMIN INJECTION

OBSERVATIONS

AND DEDUCTIONS

THEODORE R. Consulting

Neurologist, EAST

I

B, BY INTRASPINAL

ROBIE,

New Jersey

ORANGE,

1938 a United Press reN January, lease appeared in the newspapers concerning a report read before the Pan-American Congress describing a new method of treating chronic neurologic disorders. The item was pIayed up for news vaIue and accorded the handIing that most scientific or medica subjects receive when brought to the attention of the Iaity. For exampIe, one metropoIitan newspaper captioned the reIease with this headIine : “ Sp ine is Made Youth Fountain by Vitamin ~1,” and the item itseIf informed readers that “the vaIue of the method (spina injection) has been proved cIinicaIIy in & Iarge number of different types of nervous disorders, decided symptomatic improvement being noted in cases of hopeIess cancer, beriberi, muItipIe scIerosis, aIcohoIic neuritis, sciatica, von ReckIinghausen’s disease, and infantile paraIysis.” particuIarIy Physicians, neuroIogists, who faiIed to read the reIease or who were in the habit of acquiring information concerning the Iatest advances in medicine from other sources than the newspaper were soon made aware of their shortcomings. PracticaIIy a11 patients whom we were treating for muItipIe ScIerosis had read the release and urgently requested that they be given this highIy promising treatment at once. In this fashion our attention was directed to the intraspina1 injection of vitamin ~~ for the treatment of chronic neuroIogic disorders and we uItimateIy evaIuated the treatment in a series of cases under our observation with resuIts which wiII be described Iater. Our group of patients had the foIIowing

NEW

M.D.

Orthopedic

HospitaI

JERSEY

disorders : muItipIe scIerosis, poIiomyeIitis, IateraI encephaIitis, and amyotrophic scIerosis. AI1 cases were chronic, and the majority were cases of muItipIe scIerosis. AI1 patients receiving treatment were kept under observation for at Ieast six months, and some for an even Ionger period of time. Prior to our cIinica1 evaIuation of the administration of vitamin ~~ by intraspina1 injection, the Iiterature on vitamin Bl, particuIarIy that which pertained to its cIinica1 use, was surveyed and reviewed. It is not the purpose of this report to attempt a compIete description of vitamin ~~ based upon the review of the literature, nor even to review the literature on the appIication and the vaIue of vitamin Bl in neuroIogic disorders. However, certain facts which in our opinion seemed pertinent to the evaIuation might warrant mention. Vitamin ~~ seems to be concerned in two important processes of the Iiving organism : (I) oxidation in the tissues, and (2) the breakdown and utiIization of carbohydrates by the body. Both processes may be more properly cIassified as portions of the genera1 metaboIism. Peters and his associates have deveIoped these concepts in their discussion of the basic roIe of vitamin ~~ in the human economy. Vitamin ~~ deficiency produced in the experimenta anima1 or encountered in the beriberi patient is characterized by excessive amounts of pyruvic acid or the pyruvates in the bIood. Peters, in describing a study of pigeons suffering from ~1 deficiency, apparentIy regards the impaired powers of the centraI nervous system of these birds to carry out norma oxidation of the carbohydrates as the “biochemica1

398

NEW SERIESVOL. XLVIII, No. z

Robie-SpinaI

Iesion ” of By deficiency, and significantly mentions the accumuIation of the pyruvates in the blood of his experimenta fow1 and of beriberi patients. The biochemical Iesion can be abolished in vivo or in vitro by the addition of crystalhne vitamin B]. Continuation of the deficiency in the experimenta fow1 is foIIowed by convuIsions of centra1 nervous system origin. The condition of animals in experimental B1 deficiency and that of patients suffering from beriberi (the manifestation of By deficiency in human beings) are remarkably similar. Symptoms referable to impairment of the neuraI tissues are prominent features in both instances. Beriberi, the condition caused by extreme or complete ~~ deficiency, is fortunately of rare occurrence in western countries. The question concerning the existence of B1 deficiencies of Iess marked degree which couId produce cIinica1 manifestations is not so readiIy answered. The preponderance of indicates that subevidence, however, chnica1 ~~ deficiencies are not uncommon. The summary of the Iiterature on vitamin By by WiIder and WiIbur states that CogwiII estimates the daiIy Bl requirement of the average aduIt to be about 300 internationa units; Harris and Leong estimate the daiIy requirement to be 230 to 500 internationa1 units. The summary continues that Baker and Wright reemphasize the fact that vitamin B1 is not abundant in most foods. Fresh foods, on an average, contain about I international unit per gram, but the content varies considerabIy and is further diminished during the preparation and cooking of food for human consumption. FinaIIy the vitamin content of the diet does not whoIIy enter the body, as much of it may be Iost during the process of digestion and absorption of food in the aIimentary tract. It seems reasonabIe therefore to state that the fairIy high daiIy requirements of vitamin By and the factors of varying food content, destruction during preparation of food for human consumption, and Ioss of the dietary vitamin B] during digestion and

Vitamin

BI

AmericanJournalofSurger.y

399

absorption, may work together to resuIt in a higher incidence of miId to moderate By deficiencies productive of cIinica1 symptoms, than is commonIy reaIized. The “ biochemica1 lesion” of ~1 deficiency is majored in neura1 tissues, so many neuroIogic disorders, acute or chronic, might be due in part or entirely to ~~ deficiency. The medica Iiterature Ieaves no doubt but that vitamin By is an important factor in certain nervous disorders and merits the titIe of “the antirreuritic vitamin.” JoIIiffe, CoIbert, and Joffe considered the reIationship of diminished ~~ intake to neuritic symptoms to be definite. In their study of forty-two aIcoho1 addicts, every alcoholic who deveIoped poIyneuritis had an inadequate vitamin B intake, whiIe those whose intake was adequate did not deveIop poIyneuritis. They beIieve “that aIcoho1 has no direct toxic action on the peripheral nerves but that vitamin ~~ deficiency causes poIyneuritis.” JoIIiffe and CoIbert came to the same conclusions after a study of twenty-four alcohol addicts with polyneuritis. Seven patients on a borderIine diet neither improved nor deteriorated. Eight patients on a moderate ~~ intake improved. Nine patients whose ~~ intake was approximateIy four times their estimated requirement improved rapidIy and markedIg. Two patients on the border diet responded quickIy to the intravenous injection of crystahine By. Theobald treated neuritic patients in the last trimester of pregnancy with dietary measures; the symptoms in four were completely relieved by the addition of ~1 to the diet. The fifth apparently suffered from other vitamin deficiencies, and required A and D medication in addition to nl. Strauss and McDonaId, on the basis of their experience with vitamin ~~ in four cases of poIyneuritis of pregnancy, concIuded that the prophyIactic use of vitamin ~1 is indicated. Their first patient deveIoped vomiting in the fourth month of pregnancy which increased in severity. After therapeutic termination of the pregnancy in the seventh month, a cIear case of muItipIe

400

AmericanJournalofSurgery

Robie-SpinaI

neuritis deveIoped. The second patient aIso had muItipIe neuritis and vomiting of pregnancy. Miscarriage occurred and the patient grew steadily worse. Improvement foIIowed the administration of iron and a diet rich in vitamins. The third patient had a typica poIyneuritis of pregnancy with a macrocytic and hypochromic anemia. Improvement of the nervous disorder and of the bIood occurred within ten days, and a heaIthy chiId was deIivered at term. The mother was abIe to waIk without diffIcuIty shortIy after the birth of the chiId. Fouts, Gustafson, and Zerfas report a critica case of vomiting of pregnancy in which poIyneuritis deveIoped. Vitamin B therapy was instituted, and the patient soon showed definite improvement. The parentera administration of vitamin ~1 is recommended in a11 such cases as a prophyIactic against the deveIopment of poIyneuritis. Vorhaus has pointed out that the neuritides most often seen are the sciatic, sacroiIiac, and shouIder-girdIe group. Such cases are frequentIy associated with foca1 infection and improvement has foIIowed remova of tonsiIs, teeth, etc. However, cures are few in comparison with disappointments over the resuIts of such procedures. Vorhaus uses vitamin ~~ in these conditions and observed marked improvement in a Iarge number of cases even in the presence of a focus of infection. There are many other informative reports describing the use of vitamin ~~ in the treatment of poIyneuritis, but a suffnIcient number have been cited to demonstrate the resuIts obtained from ~~ therapy in this disorder. The vaIue of vitamin ~~ or the status of B1 deficiency in other neuropathies is not so definite or we11 defined. Wexberg, however, after studying forty-seven patients suffering from craniaI, spina1, or periphera1 nerve disease, stated that in a11 such cases evidences of vitamin By deficiency shouId be Iooked for. He found definite or strongIy suggestive evidence of Bl deficiency in a11 of his cases, and secured definite improvement from the use of vita-

Vitamin

B1

MAY, ,940

min By in patients with subacute combined degeneration of the cord, chronic progressive poIyneuritis, and aIcohoIic poIyneuritis. Vorhaus, in an evaIuation of ~~ therapy, stated that with the exception of beriberi, neuritis is the onIy cIinica1 entity in which vitamin ~~ may be said to be of unquestionabIe vaIue. AIthough studies of the reIationship of vitamin ~~ and the susceptibiIity of experimenta animaIs to herpes virus were inconcIusive, Vorhaus used vitamin By in postherpetic paresthesias and anesthesias and found that residua1 symptoms disappeared more quickIy and that fewer patients had persistent anesthesias in the group receiving vitamin BI than in the untreated patients comprising the contro1 group. Widenbauer reported vitamin R to be of vaIue in the treatment of miId chorea and in a Iater paper described the use of vitamin ~~ by intramuscuIar injection in ten cases of spasmophiIia. After one or two injections, the symptoms disappeared within tweIve to seventy hours in eight of the ten cases. Pfaffenberg and MieIke found that the cord symptoms in pernicious anemia were definiteIy reIieved by Iarge doses of vitamin By. The vitamin therapy was suppIementary to the usua1 anti-anemia measures. These investigators, however, caI1 attention to the fact that the neuroIogic symptoms in pernicious anemia have not been proved to be caused by neura1 Iesions referabIe to BI deficiency. In a11 of the cIinica1 studies mentioned thus far, vitamin By was administered either oraIIy, intramuscuIarIy, or intravenousIy. In reviewing the Iiterature, reference to the intraspinaI administration of vitamin By was discovered, but consrderation of the report was deferred unti1 compIete information regarding the influence of vitamin BI had been obtained, regarding its rBIe in the physioIogy of the body, the lesions produced by Bl deficiency (particuIarIy in nerve tissues), and the value of vitamin BI in at Ieast some of the neuropathies (by ora1, intramuscular, or intravenous therapy). The data on these points, as has been

reported, warranted investigation of the intraspinaI administration of vitamin By. Friedeman apparentIy was the first to report the resuIts obtained by the intraspinal administration of vitamin By. Two patients suffering from marked Korsakow’s SJ ndrome, severe dementia, and complete paralysis, and one patient with cerebrospina syphilis and compIete paraIysis of the muscuIature of the extremities and abdomen, were given intraspina1 injections of vitamin B1. In a11 three cases, the patients regained muscuIar activity in about four months. Even the dementia improved so that the patients became compIeteIy oriented as to time and environment. A dose of 500 international units of ~~ was given by epidura1 injection once a week. Later endoIumba1 injections were given. The time interva1 was graduaIIy increased so that finaIIy onIy one endoIumbaI injection was made in three weeks. The procedure was we11 torerated. Byeffects were observed onIy twice and consisted of nausea on the day of injection, and slight maIaise and headache persisting for four days. In neither instance was it necessary to administer any drugs for relief. Stern pubIished a detaiIed study on the intraspinal administration of vitamin By. The cases treated included inoperabIe cancer, ten; von Reckinghausen’s disease, one; muItipIe scIerosis, two; degeneration of the pyramida system of unknown etiology, one; thrombo-angiitis obIiterans with pregangrenous condition of feet, one; duodenal uIcer with puImonary tubercu losis, one; aIcohoIic neuritis of the supraorbita nerve, one; neuritis of the sciatic nert-e, one; cardiac decompensation with uremia and anuria, one; tabes dorsaIis, one; hypertrophic spondyIitis, two; osteoporosis of the spine, one; Paget’s disease, one; intractable pruritus ani and vuIvae, two; beriberi, one; and acute poIiomyeIitis, one. The warranty for the intraspina1 administration of vitamin By according to Stern is that “avitaminotic nerve fibers seem to have an urgent hunger for this

vitamin . . . which acts as a catalytic agent and which is essentia1 for carbohydrate metaboIism . . . after intravenous injection, the vitamin appears to be quickIy eIiminated in the urine, while after intraspina1 injection, the eIimination is found to be spread over a longer period ot From his observations in these time.” twenty-eight cases, Stern concIuded that “many chronic or incurabIe conditions of the central and periphera1 nervous system may respond favorabry to the intraspinal subarachnoid injection of synthetic \+tamin By. It shouId prove of particuIar \-aIue in cases of muItipIe scIerosis, encephaIitis, syphiIis and poliomyelitis.” Retarded eIimination of \Gtamin By wouId obviousIy be advantageous, as it wouId remain avaiIabIe for use bv the nerve ceIIs over an extended period of iime. It has been shown that folIowing ora1, intramuscuIar, or intravenous administration, vitamin ~1 is so rapidIy eIiminated that correction of a pronounced deficiency requires many doses at frequent intervals. Stern’s favorabIe concIusions from his observations in the series of twenty-eight cases would indicate that the intraspinal administration of vitamin By offers, among retarded eIimination. other advantages, We were unabIe, however, to Iocate data that, in our opinion, demonstrated sufhcient retardation of eIimination as to be responsibre for any material change in the cIinica1 resuIts. We were also unable to find information in the detaiIs regarding the patients’ responses to treatment which enabIed us to regard the therapy as being of vaIue. Improvement in many of the cases couId, in our opinion, be as well ascribed to other factors as to the intraspina injections of vitamin By. For esample, the marked improvement observed in the two cases of muItipIe sclerosis after four and five injections respectively could have been due to spontaneous temporary remissions which are known characteristicaIIy to occur in muItipIe scIerosis, or to psychic response (suggestion) on the part of the patient without organic improvement.

402

American

Cast

,Sex

JournaI

of Surgery

Robie-SpinaI

%e

1

Diagnosis

History

B1

MAY,

r9q.o

CHART I

-

-

Vitamin

T

Treatment

Reaction

ResuIt

-IF

55

F

14

M

35

F

54

F

- _

1First exam. I I /I 3/37. Onset 2 yrs. previous, pain in knees on walking. Unsteady on feet, and stiffness of Iegs. Urgency and incontinence. 1First exam. g/27/36. dragging Spastic, gait, extreme stiffness of Iegs. TypicaI neurologic findings.

1First exam. 2/r8/38. Onset I+$ yrs. previous with stiffness in left ankIe growing steadily worse. Now had stiffness of both Iegs, and knees ache. Continuous IibriIIary twitching of shoulder, girdIe and pectoral muscIes. Grew progressively worse months during 3 under treatment and had to discontinue. 1First exam. 319136. Onset one year previous with pain in Iegs and weakness in Ieft Ieg and some Ioss of sensation of arms and hips, and tendency to give out when walking. Right foot dragged in wa1 king. Numbness over right hip. Frequent backaches. NeuroIog ic findings positive. 1First exam. 6/14/38. Pain and numbness in knees for I yr., worse past month. not walk CouId straight, or manage feet right. Weak.

35

-

-

MuItipIe rosis

scle-

6/r/38 IO mg. 6/g/38 10 mg. 6/r5/38 30 mg. (intraspinaIIy)

MuItipIe rosis

scIe-

3/3o/38 ro mg. 4/r3/38 30 mg. 4/2o/38 30 mg. 5/4/38 30 mg. 5/r r/38 30 mg. 5/25/38 30 mg. (intraspinaIIy)

Amyotrophic IateraI scIerosis

3/23/38 ro mg. 3130138 30 mg. 416138 30 mg. 5/4/38 30 mg. 5/rr/38 30 mg. 5/r8/38 30 mg. 6/r r/38 30 mg. (intraspinaIIy)

MuItipIe rosis

scle-

IO mg. daily from

MultipIe rosis

scIe-

Severe headache after each treatment and more waIking diffrcuIty after Iast one; refused further injections. severe headaches and felt weaker after each treatment. After a z wk. interva1 refused to continue after 6 injections. Unable to lift Iegs at a11after some treatments, severe headaches after some. Discomfort so severe refused to come for treatment between third and fourth injections and on another occasion refused to come for 2 weeks. None

3/9/38 to 6/10/38, then 3 times per week for 2 months, then every third day for one (intramonth. muscuIarIy)

7/6/3g 10 mg. 7/r3/38 20 mg. 7/2o/38 30 mg. 7127138 30 mg. 3/3/38 30 mg. S/10/38 30 mg. s/16/38 30 mg. s/24/38 30 mg. 3/7/38 30 mg. 3/r4/38 30 mg. 3/2 r/38 30 mg. ?/28/38 30 mg. ro/r2/38 30 mg. ro/r9/38 30 mg. (intraspinally)

Ii

2 r e w progressiveIy weaker, with temporary minor remissions-in spite of taking the injections religi0usIy e v e r y week. Refused to Iet herself compIain of any discomfort, hoping for a cure.

Jnimproved (subjectiveIy worse).

Jnimproved (must have support in walking).

Lecame progressively weakercompIete paraIysis of extremities with incontinence (S/16/38).

lecame progressiveIy weaker (lost 5 Ibs. during treatment).

Jnimproved (unable to waIk without s u p port).

SFRIES Var. XLVIII.

Yru

No. 2

Robie-SpinaI

Vitamin

B1

CHART I (Continued) I Cast

I Sex

Agc

F

6

History

Diagnosis

Treatment

1

Result

Reaction

I

0

7

I

WI

0

iL1

57

3fi

Born with bilateral cIubfeet. Supernumright IittIe erary toe. Only a trace of power in either caIf and IittIe in hamstrings. Extensors of hands and feet powerless. Onset at 2 yrs.weakness of back with difficulty in from getting up p r 0 n e position. Marked hypertrophl of caIves of legs. In March 1938 was unable to walk. EntireIy heIpIess and deveIoping contracturcs. onset was CIaimed sudden following a fright 4 months before. Pain in left Ieg first, with later spasticity and then weak. nrss in Irgs and diffrwaIking. cuIty in Very suggestible individual. NeuroIogic findings positive. ,Onset 3 years previous genera1 weakness, particuIarIy in legs, staggering gait for past year. Tired from waist down, Ioses baIance on turn. ing quickly. A most coijperative patient a11 in compIeting treatment no matter how unpIeasant. NeuroIogic findings , posrtrve.

Onset vious birth,

Spina bifida or chronic poIiomyeIitis

I mg. daily for 7 weeks--then 2 mg. daiIy for 7 weeks. (intramuscuIarIy)

Progressive muscular dystrophy

z mg. daily from

years preafter chiIdwith difflcuIty

i

G r c w w o r s e I atrophy in~ creased).

UuItipIe rosis

3130138 10 mg. $16138 30 mg. ~113138 30 mg. l/20/38 30 mg. 4127138 30 mg. 514138 30 mg. $11 r/38 30 mg. 5/l/38 30 mg. $ntraspinaIIy)

Some headache after treatment and feet weaker for 2 days after each one.

10 mg intramuscuIarIy daiIy

and I nsomnia throbbing pains in back followed a11treatments of 30 mg. dosage, but IO mg. did not cause discomfort.

41though anxious to be heIped showed no sustained improvement after 48 daily intramuscuIar injections foIIowed by 49; months of intraweekIy spinal injections. Legs twitch and pound in walking.

TerribIe headache with vomiting a n d sweating

Unimproved. Refused to take treatfurther

I

MuItipIe rosis

MuItipIe rosis

II

None

scIe-

scIe-

scle-

317138 to hl27138. (intramuscularly)

2125138 to 4/13/38then: 1/13/38 10 mg. ~/20/38 20 mg. $127138 30 mg. $14138 30 mg. ~111138 30 mg. 511138 IO mg. S/8/38 IO mg. S/15/38 IO mg. 5122 138 10 mg. 716138 10 mg. 7113138 10 mg. 7120138 IO mg. 7127138 IO mg. 313138 10 mg. 3110138 10 mg. S/16/38 10 mg. 3124138 IO mg. a/7/38 10 mg. a/14/38 10 mg. (intraspinaIIy) 712138 10 mg. 7128138 10 mg. (intraspinally)

Unimproved.

None

:

~Improvement ! walking. j

in DCcrease in spasticity of legs. (Rrmission?)

404

American

Journal

oFSurgery

Robie-SpinaI CHART

- - - -

I (Continued)

I

Cast

Se3:

History

tkf

Diagnosis

/

_-

-

F

(Inset 8 years before with graduaIIy progressing pain and weakness of Iower back foIlowed by body generalized weakness and ataxia. AIso emotional upsets, intention tremor of hands, urinary incontinence, dipIopia and nystagmus, drags right spastic, leg, faIIs spontaneNeuroIogic ously. signs positive. )nset IO years before, graduaIIy progressive spastic paratysis of legs. Now constantly spastic in extreme degree-bedridden. Condition present since birth. MarkedIy tremuIous speech. Legs and arms extremeIy spastic, very unstable, wide-based gait. Makes grimaces spontaneousIy. Foot drop biIateralIy with spontaneous right Babinski, and pains in Iegs for Iast year. Generalized body tremors exaggerated in Romberg test. ( Inset followed “grippe” in 1933. PartiaI numbness of both forearms with graduaIIy increasing weakness of both, with tremor and hypertonicity. Masked fascies. PropuIsive gait.

27

16

M

38

M

-

-

-

AuItipIe rosis

IMuItipIe rosis

-

weakness of right upper extremity for 2 years. Shooting

Treatment

scIe-

m/23/38

IO mg.

3130138 30 mg. s/6/38 ro mg. +/13/3S 30 mg. i/20/38 30 mg. ?/rr/38 30 mg. WV38 30 mg. (intraspinaIly)

scIe-

Received IO mg. on 2 occasions (one week interva1). (intraspinaIIy)

spastic quadriplegia

$1’3138

to

Reaction

ResuIt

folIowed second intraspinal treatment. Symptoms persisted 5 days, foIlowed by 3 weeks of prostration. Jo reaction to 10 mg. but 30 mg. did cause pervomitsistent ing, headaches. Had to remain in bed. Because of such reactions Iong periods intervened between injections

merits.

Grew progressively worse. Fe11 off chair, fractured thumb during third month of treatment. Now confined to bed, incontinent.

reaction jevere after each injection. Refused treatfurther ments.

1’Vo

improvement.

‘Jane

11 Vo

improvement.

e/15/38 given IO mg. daiIy for

one month. (intramuscuIarIy)

Post-encephalitic syndrome

i/23/38 ro mg. 3/3o/3S 30 mg. 1/h/38 30 mg. I/27/38 30 mg.

(srowing worse. In third month felt right arm weaker. In fourth month cramps in arm. After seven months diffrcuIty in drinking or moving lips.

\Jone Patient

a stoic)

i/4/38 30 w. i/1 1/38 30 mg. i/1/38 30 mg. i/8/38 30 mg. i/15/38 i/22/38

<;raduaIIy progressive

$7

T I-

in waIking. SIowly getting worse. UnabIe to walk unassisted (6/27/3@. Legs spastic. Other neuroIogic findings positive. II

Vitamin B1

1myotrophic :-atera <$cIerosis

-

30 mg. 30 mg.

:intramuscuIarIy: IO mg. daiIy for nine weeks beginning 3/4/39. :intramuscuIarIy:

-

I\Jo improvement. I:ingers more painfu1. Pain in neck deveIoped.

he iSex

10

Age

A’1

1listory

I

Diagnosis

pains, and pins and needles sensation in same member. Atrophy of muscles of intcrossei and Iumbritalcs (right). SimiIar complaints to less extent in Ieft upper extremity. Atrophy of both deltoids. FibriIlary twitchings in tfre pectoralis, biceps and triceps. Walks with wide base. Bedridden spastic paralysis (quadriplegia) with incontinence. Duration 7 years. Marked speech and general bodiIy tremor, gradually progressive Ioss of sensation in hands. AI1 neuroIogic signs positivc.

35

Treat mcnt

27

29

--LI

I

Result

Spontaneous twitchmuscIe ings frequent.

MuItipIe rosis

scle-

-

No improvement. Remains bedridIncontiden. nence more frequent.

Very coiiperative. 318138 to Minimized his 3/18/38 10 mg. daily intravendiscomfort but ousIy and IO mg. had one or two intramuscularly. uncomfortabIe Then: IO mg. indays after each tramuscuIarIy intra-spinal daiIy for 7 treatment. weeks. Then IO mg. first dose and thereafter 30 mg. intra- ’ spinaIIy for 3 months. Very cooperative. r/31/38 to z/10/38 IO mg. Minimized disdaiIv intravencomfort, but had ously 10 mg. inreacrepeated tramuscuIarIy. tions of severe back pain foIz/10/38 to _ injeclowing 3/3r/38 ro mg. intravenousIy tions. daiIy. 3/3 I /38 to 6/8/38 30 mg. intraspinalIy at 3 day intervals (first dose IO

Onset gradua1 begin- 1MuItipIe sclening 8 years before rosis with facial paIsy (right). Later diplopia. Weakness in Iegs with spasticity past 3 years, unable to get up and down stairs. SIow, deIiberate speech. Tremors of legs (coarse) in waIking. FeeIing of generalized trembling. Nemologic signs positive. GraduaIIy progressive ‘I MuItipIe scIerosis weakness in lower extremities. Duration 8 years. Numbness after sitting, diffrcuIty climbing stairs, occasiona Ieg twitching. NeuroIogic signs positive. Tremor in right arm 1PoIiomyeIitis Residual PadeveIoped 8 years raIysis (Possiafter auto accident. PoIiomyeIitis I $5 bIe encephaIomyeIitis) years before, Ieaving weakness and atrophy of Ieft hand, arm

32

Reaction

No improvement. DistinctIy worse a year after treatstarting ment.

mg.).

10mg. daiIy for 6 None weeks begun 3/g/38. (intramuscularIy)

No improvement.

i 1

No improvement.

10 mg. first dose Severe headaches and then 30 mg. I for 2 days-had weekly for 61 t 0 remain away weeks. (intrafrom his work. spinaIIy)

I

-

I

1 -

American Journd of Surgery

406 - Case

(

F

-

-

B1

CHART I (Continued) Diagnosis

History

Vitamin

T

Treatment

MAY. r9.w

ResuIt

Reaction

-

-

20

-

- -

Sex 1he

Robie-SpinaI

36

-

and shouIder, constant tremor of right hand persists. fenerahzed pains Iike : 1UcohoIic poIyneuritis “toothache” particuIarIy in hands and Iegs deveIoped in ApriI with 1938, some numbness. On ApriI z I, neurologic exam. showed: biIatera1 foot drop, absent knee and ankle jerks compIete Ioss of motor power (both legs) gIove and stocking anesthesia, tremor and weakness both hands, positive Romberg. Ptosis right. History of excessive induIgence in aIcoho1 -

In view of the r8Ie of vitamin B1 in the metaboIism in the nerve tissues, the improvement which foIIows its use in the neuritides, the frequent occurrence of ~~ hypovitaminosis in many of the neuropathies, the nature of the nervous symptoms occurring in beriberi, and the favorabIe opinions of the investigators who had used and reported the intraspina1 injection of vitamin By, we arranged for cIinicaI evaIuation of this procedure with the hope of confirming its vaIue in the degenerative neuroIogica1 disorders. The investigation was conducted in the NeuroIogicaI CIinic of the New Jersey Orthopedic HospitaI (Orange, New Jersey). Various types of organic disorders are seen in this CIinic which accepts patients from the northern haIf of the State. Vitamin By* was administered by intraspina1 subarachnoid injections. The dose, the time interva1 between doses, and the duration of treatment are shown in Chart I. The tabIe aIso incIudes * AcknowIedgment is made of the courtesy of Hoffmann-La Roche, Inc., Nutley, New Jersey who provided generous supplies of berocca (synthetic vitamin BI) for use in this study.

IO mg. b.i.d. intramuscuIarIy for 6 weeks, then daiIy for 6 weeks. SubsequentIy 5 mg. oraIIy b.i.d.

1None

Vumbness decreased in IO and disdays appeared in 20 days. AbIe to waIk with heIp after 7 weeks and aIone after IO weeks. Jan. I g3p-is attending dancing schoo1 weekIy.

-

data regarding the sex, the age, a digest of the pertinent facts of the history pertaining to the neuroIogic disorder, reactions (byeffects) caused by the treatment, and the rksuIts. It was pIanned to administer vitamin ~~ oraIIy, intramuscuIarIy, and finaIIy intraspinaIIy, interrupting the therapy at any point if improvement was such that further treatment seemed unnecessary. The patients were easiIy interested in the treatment. AIthough most of them had tried many different remedies without improvement during a period of months or years, they had deveIoped a “grasping for and were wiIIing to a straw” phiIosophy, try anything which offered hope. The compIete progressive course of therapy couId not aIways be appIied in every case as is evident from inspection of the tabIe. The reasons wiII be discussed Iater. A series of twenty patients was started on the course of therapy which was pIanned to incIude the ora1, intramuscuIar, and intraspinal administration of vitamin ~1 in each case. The foIIowing conditions were treated : muItipIe scIerosis, tweIve; amyotrophic IateraI scIerosis, one; postencephaIi-

NEW SERVESVOL. XLVIII,

No. 2

Robie-SpinaI

tic syndrome, one; spastic quadripIegia, one; poliomyeIitis, one; progressive muscular dystrophy, one; spina bifida (or chronic poliomyelitis), one; and aIcohoIic poIyneuritis, one. Complete recovery was obtained in onIy one case-the case of alcoholic polyneuritis. Three of the tweIve patients with muhiple sclerosis refused to continue treatment on account of the pain and discomfort caused by the intraspinal injections of vitamin nl; no improvement was observed in these patients from the beginning of treatment to the time when they discontinued treatment. Seven of the patients with muItiple scIerosis who continued with the treatment as Iong as requested failed to secure sustained improvement. Two of the patients with mu ItipIe scIerosis, having been treated with intramuscurar injections of vitamin By for a period of two to four months without improvement, were not given the intraspinal injections. Our observation of the seven patients who had received the injections without improvement made us reluctant to subject the patients to the discomfort, particuIarIy since the intramuscular injections had effected no improvement. In the remaining seven cases of various neurologic disorders, intensive vitamin ~1 therapy, administered intramuscuIarly or intraspinaIIy, was not folIowed by sustained improvement. Other investigators may be abIe to confirm the findings of Friedeman and Stern that the intraspinal injection of vitamin ~1 in chronic neurologic disorders brings about improvement. In our series of cases the procedure proved of no vaIue. Deficiency of vitamin ~~ may also be shown in the future to be a factor, or even the basic cause, of multiple scIerosis or other degenerative neuroIogic disorders. Our results, however, indicate that if the nerve degeneration has reached the stage of irreversibIe change, return of motor or sensory function will not occur even though massive doses of vitamin ~~ are injected intraspinally over a long period of time. Considering the number of patients in our group and the

Vitamin

B1

American Journal of Surgery

407

youth of many of them, it wouId seem that there would be some in whom nerve degeneration had not reached the stage of irreversible change. In these cases (if vitamin ~~ deficiency caused the disorder) definite and sustained improvement such as return of function in a partially paralyzed arm or Ieg, should have occurred. In the one case of muItiple sclerosis in which improvement occurred, a number of factors have to be considered in evaluating this response. The patient, formerly a hardy and robust man, was most anxious to improve and therefore was extremely suggestible. The improvement, including the neuroIogic signs, was stiII apparent two months after concIusion of the intraspinal injections. After the passage of another two months, however, he went to another clinic where his condition was again diagnosed as a very evident case of multipIe sclerosis. In our opinion, the improvement was probabIy due to a spontaneous and temporary remission, entirely unreIated to the intraspinal injections of vitamin By. The intramuscular injections of vitamin ~1 caused no discomfort other than the pain usuaIIy experienced in any intramuscular injection from insertion of the needle. This part of the treatment, as well as the oral treatment, therefore, was not disturbing to the patients. The intraspinal injections, however, were painfu1 even though a Iocal anesthetic was used, and very frequentIy reactions such as headache or vomiting deveIoped afterward and Iasted as long as two days. Some patients refused to even start the treatment when these facts were made known to them by their fellow Other patients, although they patients. started treatment enthusiastically, couId not be persuaded to continue treatment after experiencing one or two reactions. This was the experience with six of our patients. Goodhart and JoIIiffe, and WechsIer have estabhshed beyond question the fact that function can and frequentIy does return in paraIytic conditions caused by a true vitamin ~~ deficiency. This response was

408

American

Journal

of Surgery

Robie-SpinaI

observed in the Iast case I&ted in the accompanying tabIe. The patient, a 36 year oId woman, had a typical case of so-caIIed aIcohoIic poIyneuritis (which in the future may be more properly named avitaminotic poIyneuritis). AIthough a bed-ridden invaIid previous to treatment, she recovered normaI function of her paraIyzed arms and Iegs and compIete return of sensory function after Iess than three months of vitamin ~~ therapy administered intramuscuIarIy. She is now heaIthy, normaIIy ambuIatory, and, according to most recent reports, taking dancing Iessons reguIarIy. Due to the observations of McCormick, we incIuded the case of poIiomyeIitic residual paraIysis in our series. McCormick pointed out the simiIarities between poIiomyeIitis and beriberi and posed the question whether the susceptibiIity of chiIdren to poIiomyeIitis was reIated to decreased reserves of vitamin ~1 caused by increased physica activity in the summer months. If decreased vitamin ~~ reserves are responsibIe, this neatIy expIains both the greater severity and the higher incidence of the disease during the summer. WhiIe there is insistence upon an adequate intake of vitamins A, c, and D in the growing chiId, the concomitant need for vitamin ~1 is Ieft in the background. The reIativeIy recent synthesis of vitamin By has made it readiIy avaiIabIe for therapeutic use and refocussed attention on its possibIe raIe in the resistance to poIiomyeIitis. The disabiIity in our patient was of one and one-haIf years’ duration and therefore irreversibIe changes probabIy had occurred in the neura1 tissues. Other than the residua1 symptoms, the patient’s condition was exceIIent. As was expected, the intraspinaI injection of vitamin ~1 over a period of weeks faiIed to bring about improvement. Notwithstanding the resuIts in this case, further intensive study of vitamin ~1 therapy in poIiomyeIitis seems warranted. PresumabIy, the vitamin shouId be administered intravenousIy or intramuscuIarIy, immediateIy after the condition has been diagnosed.

Vitamin

B1

MAY,

IWO

SUMMARY

The widespread pubIicity given by the daiIy press to the inaccurate, optimistic accounts of medica research frequentIy arouses faIse hopes in those afKcted with the disorders which happen to be the subjects of the scientific investigation unfortunateIy expIoited for sensationa news vaIue. Our attention was directed to the intraspinaI injection of vitamin By in the treatment of chronic neuroIogic disorders by patients who had such disorders and who had Iearned of the injections through the accounts in their newspapers. A survey of the medica and scientific Iiterature indicated that there was a reIationship between vitamin ~1 and metaboIism in the neura1 tissues, that a “biochemica1 Iesion” in the centra1 nervous system was caused by By hypovitaminosis, that the cIinica1 manifestations of beriberi incIuded (absoIute By hypovitaminosis) nervous symptoms now acknowIedged to be remarkabIy simiIar to those seen in degenerative neuroIogic disorders, and that the use of vitamin ~1 in some disorders of the periphera1 nerves, for exampIe the neuritides, brings about improvement. The intraspinaI injection of vitamin BI, in the Iight of the survey, seemed to merit consideration, particuIarIy since reports of improvement following such therapy appeared in the medica literature. The administration of vitamin ~~ by intraspinaI injections (and other avenues as weI1) was evaIuated in a group of patients suffering from chronic neuroIogic disorders. Our experience with this type of therapy has Ied to severa concIusions. CONCLUSIONS I. IntraspinaI injections of vitamin B1 in a series of nineteen cases of chronic degenerative neuroIogic disorders and one case of aIcohoIic poIyneuritis faiIed to bring about sustained improvement in the chronic degenerative disorders. The aIcohoIic poIyneuritis apparentIy was cured by intramuscuIar injections of vitamin ~1; this

condition is recognized to be due to ~~ hvpovitaminosis. 2. The intraspinal injections were very frequently followed by such severe reactions that a substantial number of even the most enthusiastic and hopeful patients discontinued treatment. Since the injections, in our experience, are valueless, discontinuation of treatment was a matter of no concern, except for the disappointment :I nd the needless discomfort. 3. The lack of improvement indicates that By hypovitaminosis is not the basic cause of the degenerative disorders and probably- not even an important factor in their development or rate of progress. 4. The value of vitamin By in some of the disorders of the periphera1 nerves, for example the neuritides, suggests that it may prove of value in onIy those conditions in which nervre degeneration has not reached the stage of irreversible change. On this premise, treatment of poliomyehtis in its earlier stages with vitamin ~~ warrants further investigation. Poliomyelitis in the later stages or residual symptoms following an acute attack of poliomyelitis wiII proba kly not be improved by treatment with \.itamin B1. 3. Newspaper pubhcity of medica research, particularly in the field of therapeusis, is deplored. False hopes are aroused in patients who insist upon prolonged and frequently painful treatment of dubious or unproved value. The discontent and disappointment caused by faiIure of the treatment are a menace to the patient’s general weIfare. REFERENCES PI:~EKS, RYDIN, and THOE~IPSON:Brain respiration. A chain of reactions as reveaIed by experiments upon

catatorulin effect. Biochem. J., 29: 53, 1935. The retation of pyruvic acid in brain to certain tissue poisons. Biochem. J., 29: 63, 1935. PETERS. The biochemica1 lesion in vitamin B! tlcIicienc~-. Lancer, I: 1161, 1936. WILDER and ~Z~LBCR: Diseases of metabolism and nutrition. Review of certain recent contributions. Arch. Int. Med., 59: 512, 1937. HARRIS and LEON<;. The excretion of vitamin n, in human urine and its dependence on the dietar? intake. Lancet, I : 886, 1936. BAKER and WRIGHT. The vitamin By content of foods. Btocbem. J., zg: 1802, 1935. JOLLIFFE, COLBEKT, and JO~FE. Observations on the ctiologic relationship of vitamin ts (RI) to poJvneuritis in the alcohol addict. Am. J. 31. SC., 1g1 : 515, 1936. JOLLIFIX and COLBEKT. The etiology- of polyneuritis in the aIcohoI addict. J. A. ,bf. A., IO-: 642, 1936. THEOBALD. Neuritis in pregnancy successfully treated with vitamin BI. Lancet, I : 834, 1936. STRAUSS and MCDONALD. Polyneuritis of pregnancy. J. A. M. A., 200: 1320, 1933. FOUTS, GGST.~~;SOX, and ZERFAS. SuccessfuI treatment of a case of poIyneuritis of pregnancy. Am. J. Oh-t. @ Gynec., 28: 902, 1934. VORHAUS. The present evaluation of vitamin n, therapy. Am. J. &es. Dis. P+ Nut&ion, 3: 915, ‘937. WEXBERG. Diseases of the nervous system caused by nutritiona deficiency. South. 1\/1. J., 30: 334, 1937. WIDENBALER. Die Behandlung der Spasmophille mit krystalhsiertem Vitamin 81. :~onafscilw. J’. Kinder/J., 70: 82, 1937. PFAFFEKBERG and .\IIELKE. Zur VitaminbehandIung funikulaerer Spinalerkrankungen. K/in. Il’chnscbr., r6: 919, ‘937. FRIEDEMAKN. Epidural and endoIumba1 administration of vitamin B,. Schweiz. Arch. j. Neural. u. P.ychiut., SupPI., 39: 236, 1937. STERN. The intraspinal (subarachnoid) injection of vitamin B, for the relief of intractable pain, and for the inffammatory- and degenerative diseases of the centra1 nervous system. Preliminary report. Am. J. Surg., 39: 495, 1938. STERN. Intraspinal (subarachnoidj injection of vitamins n1 and c in acute poliomyelitis. C/in. .Lfed. P hrh’., 45: 108, 1938. GOODHART and JOLLIFK. Effects of vitamin n (ui) therapy on the polyneuritis of alcohol addicts. J. A. hf. A., 110: 414. 1938. WECHSLER. MuItipIe periphera1 neuropathy versus multipIe neuritis. J. A. hf. A., IIO: 1910, 1938. MCCOR~UCK. Poliomyehtis: vnamin I~ deficiency a possible factor in susceptibility. Canatl. :21. A. J., 38: 260, 1938.