An Investigation Into Post-Encephalitic Parkinsonism

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THESI S.

AN INVESTIGATION INTO POST-ENGEPHALITIG PAEKINSONISM

BY

AEGHIBALD MGPHATEE,

M .B ., Ch.B.(HN1VERSITY Off GLASGOW). 1936.

ProQuest Number: 13849819

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Pag© 1•

AN INVESTIGATION INTO F03T-ENGEPHALITIC PAEKINSONISM.

FOBEViPBD. The la y o u t o f t h i s t h e s i s i s g iv e n in th e forew ord so t h a t th e c o n t in ­ u i t y may be a s com p lete as p o s s i b l e . F i r s t l y ,th e r e i s a g e n e r a l in t r o d u c t io n g iv in g th e h is t o r y o f th e d is e a s e E n c e p h a litis L e th a r g ic a .

This ch a p ter t r a c e s th e d is e a s e from th e a cu te

ep id em ics to th e c h r o n ic s t a g e s o f th e d is e a s e w ith s p e c i a l r e fe r e h c e t o P o s t - e n c e p h a lit ic P ark in son ism and i s rounded o f f by th e b ib lio g r a p h y r e ­ l a t i n g to i t . S econ d ly th e r e i s a b r i e f ch a p ter on th e s e d im e n ta tio n r a te o f th e red b lo o d c o r p u s c le s which was one o f th e t e s t s u sed i n th e i n v e s t i g a t i o n .

This ch a p ter

i s a ls o fo llo w e d by i t s own b ib lio g r a p h y T h ir d ly th e r e i s a ch a p ter on th e ex a m in a tio n o f th e c e r e b r o - s p in a l f l u i d which was th e o th e r l i n e o f i n v e s t i g a t i o n .

The b ib lio g r a p h y a ls o f o llo w s t h i s

c h a p te r . F o u r th ly , b e fo r e g o in g on to th e a c t u a l c a se r e s u l t s , a resume o f th e scop e o f th e i n v e s t i g a t i o n i s g iv e n . Again th e b ib lio g r a p h y fo llo w s i t s r e le v a n t c h a p te r • F i f t h l y th e c a se r e s u l t s are g iv e n one page b e in g a l l o t t e d to each c a s e .

The

sed im e n ta tio n r a t e s b ein g g iv e n g r a p h ic a lly and th e c e r e b r o -s p in a l f l u i d r e ­ s u l t s i n ta b u la r form . S ix t h ly th e r e s u l t s o f a c o n t r o l s e r i e s o f c e r e b r o - s p in a l f l u i d i s . giV en i n ta b u la r form .

Again t h i s i s fo llo w e d by a b ib lio g r a p iiy .

The c a se r e s u l t s are th en summarised w ith r e le v a n t b ib lio g r a p h ie s appended and th e t h e s i s com p leted by a ch a p ter g iv in g th e c o n c lu s io n s drawn from th e s e sum m aries•

Page 2 . GENERAL INTRODUCTION. During th e G reat War o f 1914/1913 i t was i n e v i t a b l e , w ith th e unnatur­ a l l i v i n g c o n d it io n s ,t h a t i n f e c t i o n s o f a l l ty p e s sh o u ld become more p re­ v a le n t.

Of th e s e in f e c t i o n s p rob ab ly th e m ost im p ortan t was in f lu e n z a w ith

i t s a tte n d a n t d is e a s e E n c e p h a litis L e th a r g ic a . This t h e s i s d e a ls w ith th e P o s t - e n c e p h a lit ic Syndrome o f Parkinsonism * 1 In th e month o f A p r il, 1917* V ien n a, Von Economc d e s c r ib e d c a s e s o f a new d is e a s e w ith th e s ig n s and symptoms o f a d if f u s e b r a in i n f e c t i o n . Then 2 N e t t e r , th e fr e n c h n e u r o lo g i s t , d e sc r ib e d s im ila r c a s e s i n a m ilit a r y base h o s p it a l in P ra n ce. Prom t h i s s p o r a d ic b e g in n in g th e d is e a s e to o k on an ep id em ic form and f i n a l l y became pandem ic, sp rea d in g to a l l co rn er s o f th e e a r th i n a s h o r t sp ace o f tim e . A lthough d e sc r ib e d by Von Economo and N e t t e r as a new d is e a s e th e r e i s h i s t o r i c a l e v id e n c e t h a t a d is e a s e w ith s im ila r c h a r a c t e r i s t i c s had been ch ron i c a l e d s e v e r a l tim e s a s w i l l be se e n from th e f o llo w in g h i s t o r y . 3 In 1580 th e r e i s record o f a s e r io u s ep id em ic a f f e c t i n g th e whole o f Europe which was d e s c r ib e d a s " Morbus ep id em icu s p er totam f e r e Europa S c h la fk r a n k h e it d ic t u s ” ,non tarn l e t a l i s n i s i a ccid en ta l a l i o rnorbo"•

Again in

London from 1673 to 1&75 th e r e m s an ep id em i* o f a d is e a s e which Sydenham d e s c r ib e s as " fe b r is com atose” , t h i s d is e a s e was o f t e n a s s o c ia t e d w ith s in g u lt u s . The n e x t reco rd o f a d is e a s e c h a r a c te r is e d by som nolence and nerve symp­ toms i s by A lbrech o f H ild esh eim in 1695*

T his was an i s o l a t e d c a s e d esc r ib e d

by him under th e t i t l e o f " de fe b r e le t h a r g ie a i n strab ism o u tr iu s q u e o c u l i d e s in e n t e ” which would a g ree w ith th e modern som nolent o p h th a lm o p leg ic form o f th e d i s e a s e • The n e x t m ention o f f e b r i l e d is e a s e w ith som nolence was a t Tubingen i n 1712 b u t th e r e i s d u b ie ty ab ou t th e occu rren ce o f som nolent s t a t e s in t h i s d is e a s e . From 1723 t o 1727 an epidem ic occu rred in London d e sc r ib e d as " fe b r is sop orosa e t a p o p le c t ic s " .

Then i n 17&3 hepecq de l a C lotu re d e sc r ib e d a

11 coma somnolentum" o c c u r r in g during an in f lu e n z a epidem ic i n Rouen, and a g a in from i~]3Q to 1732 th e r e was an in f lu e n z a ep id em ic w ith marked c e r e b r a l m a n ife s ta tio n s .

Prom 1330 to 1833 th e r e was an in f lu e n z a epidem ic in P a r is

c h a r a c te r is e d by som nolen ce.

Page 3 . The p r e v io u s ly m entioned d is e a s e s c h a r a c te r is e d by f e v e r , som nolence and o th e r c e r e b r a l m a n ife s ta tio n s a re o n ly put forw ard h y p o t h e t ic a lly aa b e in g E n c e p h a litis L a th a r g ic a , but i n 1346 th e r e was d e sc r ib e d by D ubinni th e e l e c t r i c ch orea i n N orth ern I t a l y which i s g e n e r a lly r e c o g n ise d as h avin g been m yoclon ic e n c e p h a l i t i s .

Again from 1839 to 1390 th e r e was an epidem ic 4 o f in f lu e n z a in I t a l y and from 1390 to 1991 th e d is e a s e c a l l e d "Nona" was se e n in I t a ly :

t h i s had many o f th e c h a r a c t e r i s t i c s o f E n c e p h a lit is L eth a r­

g ic a • The f i r s t name a s s o c ia t e d w ith th e modern ep id em ic o f E n c e p h a litis L eth a rg ica i s t h a t o f C o n sta n tin Von Economo o f V ien n a.

In th e w in ter o f

1916/1917 th e r e came to th e Vienna P s y c h ia t r ic C lin ic many c a s e s which cou ld n o t be c l a s s i f i e d under any d e f i n i t e h ead in g b u t a l l o f which showed le th a r g y combined w ith o c u la r p a r a ly s e s which le d him t o a s s o c ia t e i t w ith th e d is e a s e "Hona" which had occu rred i n N orthern I t a l y i n th e n i n e t i e s o f th e p rev io u s c e n tu r y .

This knowledge o f "Nona" was d eriv ed from th e f a c t t h a t he had

sp e n t h is you th i n Southern A u str ia where t a l e s o f t h i s d is e a s e were o t i l l p r e v a le n t • A lthough Von Economo was th e f i r s t to c l a s s i f y t h i s d is e a s e as Ence­ p h a l i t i s L a th a r g ic a , C ruchet i n P ra n ce, claim ed to have se e n c a s e s in th e w in te r o f 1915/1916 and U rech ia o f Eoumania d e s c r ib e d s im ila r o a se s b ut d id n o t a s s o c ia t e them w ith any record ed d i s e a s e .

More c a s e s co n tin u ed to be de­

s c r ib e d b u t i t was n o t t i l l a f t e r th e in f lu e n z a ep id em ic o f 1913 th a t Ence­ p h a l i t i s L e th a r g ic a assumed a pandemic form in s t e a d o f l o c a l i s e d e p id e m ic s • A fte r th e pandemic s t a g e o f th e d is e a s e had p a ssed o f f l o c a l i s e d e p id 5,& 6 em ics a g a in made t h e ir a p p earan ce, th r e e o f such b e in g , a t S h e f f ie l d i n 1924, 7,& 3. a t S t. Louis in America during 1933 » p r e s e n t , th e d is e a s e in th e a cu te form i s o n ly se e n i n sp o r a d ic c a s e s , b u t w ith th e advent o f w orld-w ide h o s t i l i t i e s and th e p o s s i b i l i t y o f s im ila r c o n d itio n s to th o se o f th e War o f 1 9 1 4 /1 9 1 8 , t h e r e i s th e f e a r o f s p o r a d ic c a s e s o f E n c e p h a litis L eth a rg ica becom ing l o c a l i s e d ep id em ics or even pandem ic. D uring th ey ep id em ic and pandemic s t a g e s o f E n c e p h a litis L eth a rg ica i t i t was f i r s t thou ght to be an a cu te inflam m atory d is e a s e which su b sid ed by i n th e r e c o v e r in g c a s e s , b u t a s tim e p a ssed and th e a f t e r e f f e c t s became more o b v io u s , th e r e were two s c h o o ls o f th ou gh t as to th e ca u se o f th e a fte r e ffe c ts .

Pago 4 . The f i r s t s c h o o l o f thought s t a t e d th a t th e s e a f t e r e f f e c t s were due to con seq u en t d eg en era tio n fo llo w in g damage done i n th e a cu te s ta g e and la b ­ e l l e d th e a f t e r e f f e c t s s e q u e lla e ,

In 1924, d is c u s s in g th e s e s e q u a lla e , Ivy

9

M ackenzie s t a t e d th a t in h is o p in io n , th e r e was no a c t iv e in flam m ation b u t changes bore a resem blance to Inflammation in th e b a s a l n u c le i o f th e b r a in .

10 Abro i n Beaumont’ s t e x t book o f m ed icin e r e f e r s t o c h ro n ic c a s e s , but sa y s th ey 11 are due to th e p r e v io u s d e s t r u c t io n o f n erve c e l l s . The M in istr y o f H e a lth , in a memorandum p u b lish ed in 1929* d e s c r ib e d th e a f t e r e f f e c t s as s e q u a lla e and n o t as ch ro n ic i n f e c t i v e p r o c e s s e s . The secon d s c h o o l o f th ou ght fa v o u r s th e th eo ry o f a s t i l l a c t iv e i n f e c t ­ io n i n a ch ro n ic s t a g e .

Prom th e l i t e r a t u r e t h i s has a g r e a t e r f o llo w in g , and

th e p ro o f o f t h i s can be grouped under th r e e h e a d in g s : - c l i n i c a l , p a t h o lo g ic a l and e p id e m io lo g ic a l. 12 to 19 20 21 22 23 24 On th e c l i n i c a l s id e Von Economo, Wimmer, H a ll, MciNalty, Duncan, G ross25 26 man, and Preeman su p p ort th e view t h a t th e i n f e c t i o n i s s t i l l a c t i v e , b u t in a 2 7 , 23 c h ro n ic s t a t e . In a d d it io n , s e v e r a l o f th e o b se r v e r s lik e n ch r o n ic E n c e p h a litis L e th a rg ica to G eneral P a r e s is o f th e In sa n e , which i s a d e f i n i t e l y proven chron­ i c i n f e c t i v e E n c e p h a litis due to th e p resen ce o f th e S p iro ch a eta P a llid a in 29 th e b ra in t i s s u e . A lso , one o b serv er f in d s a s i m i l a r i t y betw een ch ro n ic E n c e p h a litis L e th a r g ic a , G eneral P a r e s is and D issem in a ted S c l e r o s i s , which i s a ch ro n ic E n c e p h a litis c h a r a c te r is e d by rec u r r e n c e s o f a c t i v i t y .

30, 31 P a t h o lo g ic a lly , many are found to su p p ort th e ch ro n ic i n f e c t i v e th eo ry ;

32

33

34

33

36

th e s e in c lu d e M uir, M eA lpine, V egni, C arm ich ael, Preeman, Hunt & C ornw all,

37 ^Reynolds & S l a t e r .

T h eir fin d in g s are a l l based on h is to p a th o lo g y and are th e

r e s u l t s o f post-m ortem exam in ation s on P o s t - E n c e p h a lit ic c a s e s a t v a ry in g i n ­ t e r v a l s o f tim e from th e f i r s t a t t a c k . The e p id e m io lo g ic a l ev id e n c e i s s c a r c e r than e i t h e r th e c l i n i c a l o r p a th -

33

o l o g i c a l , b u t Preeman w r itin g in th e J o u rn a l ©f th e American M edical A s s o c ia tio n , q u o tes seven c a s e s o f p rob ab le co n ta g io n o f E n c e p h a litis L a th a rg ic a from p a t­ i e n t s s u f f e r in g from p o s t- E n c e p h a lit ic P a rk in so n ism .

S t e i f l e r s u g g e s ts th a t

a cu te e x a c e r b a tio n s o f a ch ro n ic c a se o f E n c e p h a litis L eth a rg ica may be a so u rce o f new i n f e c t i o n s . Prom th e s e paragraphs th e ev id en ce would seem to p o in t to th e p e r s is t e n c e o f E n c e p h a litis L eth a rg ica as a ch ro n ic i n f e c t i o n , and t h i s paper i s b ased on work done w ith t h i r t y such c a s e s o f p o st-E n c e p h a litis* P arkinsonism o v er a p eriod o f s i x months, in an e f f o r t to prove t h a t th e i n f e c t i o n was s t i l l i n e x is t e n c e in th e s e c a s e s .

The in v e s t ig a t i o n was d ir e c t e d , f i r s t l y to th e sed im en ta tio n

/s e d im e n ta tio n r a te o f th e red b lood c o r p u s c le s and to an exam in ation o f th e c e r e b r o -s p in a l f l u i d .

In th e c e r e b r o -s p in a l f l u i d s , s p e c ia l a t t e n t io n was

p a id to th e a lb u m en -g lo b u lin r a t i o .

B efore p ro ceed in g to th e a c t u a l i n v e s t i ­

g a t io n , i t was found n e c e s s a r y to stu d y th e l i t e r a t u r e on th e sed im en ta tio n r a te o f th e red b lo o d c o r p u s c le s and to p r a c t ic a l methods o f a n a ly s in g ce r e b r o ­ s p in a l f l u i d s ;

th u s th e f o llo w in g n o te s on th e h is t o r y and a p p lic a t io n o f th e

red b lood c o r p u s c le se d im e n ta tio n r a te t o i n f e c t i v e p r o e e s s e s and th e im p o rt­ ance o f th e a lb u m en -g lo b u lin r a t io i n th e c e r e b r o - s p in a l f l u i d o f c a se s o f nervous d is e a s e became e s s e n t i a l l y a p a r t o f th e i n v e s t i g a t i o n .

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2*

N etter.

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3.

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6.

M ed ical R esearch C o u n cil: S p e c ia l R eport S e r ie s No. tOS. The S h e f f ie l d O utbreak o f E n c e p h a litis in 1924.

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New York.

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19* M in istr y o f H ealth R e p o r ts. R ep orts on P u b lic H ealth and M edical S u b j e c t s . P .P .1 3 9 * 2 0 . Von Economo C.

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25«Grossman M.

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Heineman 1 9 2 4 .

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Freeman •

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27*

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23*

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29*

E d it o r i a l N o te .

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33-

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33.

C arm ichael.

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37*

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33.

Freeman.

Chronic E n c e p h a lit is ,L e t h a r g ic a . J o u r n a l o f th e American M edical A s s o c ia t io n . S o l . 37 p .p . t601 •

L ancet V o.2 1927* p .p .361.

J o u rn a l o f American V o l. 37 p .p .l 6 0 1 .

V o l. 6 (VI) p .p . 2 6 9 . 1927*

P*P* 323*

1924.

p .p .727'

Page 3 . THE SEDIMENTATION SATE OF THE HEP BLOOD CORPUSCLES. A iie f i-n it io n o f th e se d im e n ta tio n r a te o f th e red b lood c o r p u s c le s i s 1 d i f f i c u l t to g iv e b u t t h a t g iv e n by Panton i s c o n c is e " a non s p e c i f i c t e s t f o r th e p r e se n c e o f an a c t iv e i n f e c t i o n * . A lthough th e c l i n i c a l a p p lic a t io n o f th e t e s t i n i t s p r e s e n t form i s co m p a ra tiv ely r e c e n t se d im e n ta tio n has a lo n g h is t o r y w ith i t s b eg in n in g s i n th e w r itin g s o f H ip p o cra tes and A r i s t o t e l e s , who h e ld t h a t th e fo u r funda­ m entals o f l i f e were

A ir , Water, F ir e and E a r th .

io n s composed a l l th in g s l i v i n g and d ead.

These i n v a ry in g p ro p o rt­

S im ila r ly i n th e human body th e r e

were fo u r flu id s ? in t im a t e ly mixed form in g th e c o n te n ts o f th e b lo o d v e s s e l s and th e body f l u i d s .

The A it corresp on d s t o th e b lo o d , Vfeter to phlegm , F ir e

to y e llo w b i l e and th e E arth to b la c k b i l e .

These f l u i d s were known as th e

Humours• This th eo ry o f fo u r Humours was su p p orted by v e n e s e c tio n which was th e o n ly method o f b lo o d ex a m in a tio n th en known.

The shed b lo o d ,a f t e r sta n d in g ,

d i f f e r e n t i a t e d i t s e l f in t o s e v e r a l l a y e r s , th e dark co lo u r ed lo w er p o r tio n ; o f th e b lood c l o t r e p r e se n te d th e b la c k b i l e , th e red p o r tio n r e p re se n ted in th e upper p a r t o f th e c l o t was th e b lo o d proper w h ile th e y e llo w b i l e was the serum e x p ressed from th e c l o t .

F i n a l ly , in p a t h o lo g ic a l b lo o d s th e phlegm

c o l l e c t e d as a w h itis h la y e r above th e b lo o d c l o t and was c a l le d th e "Febria* c o n te n t .

Thus t h i s w h it is h la y e r was ta k en as an ev id e n c e o f th e p resen ce o f

fe v e r . In th e r a p e u tic v e n e s e c t io n i t was custom ary to measure th e amount o f phlegaaa in th e!sh e d * b lo o d and to b a se th e p r o g n o sis on th e amount p r e s e n t . The p resen ce o f phlegm i n th e b lood o f p a t ie n t s who were i l l le d to i t phlegm) b ein g regarded a s th e c a u s a l a g en t o f d i s e a s e .

(th e

Thus i n th e G recian

th eo ry o f m ed icin e phlegm was h e ld t© be th e m ost im p ortan t c a u s a l f a c t o r in d is e a s e .

G alen gave th e name "Buffy Coat" to t h i s la y e r o f phlegm .

U n til th e ad vent o f P a r a c e lsu s i n th e s ix t e e n t h cen tu ry t h i s fcheory h eld sw ay.

He s t a t e d th a t th e in c r e a s e o f phlegm was th e r e s u l t and n o t th e c a u sa l

fa c t o r o f th e i l l n e s s b u t h is th eo ry d id n o t r e p la c e th e o ld o n e .

In th e seven ­

te e n th cen tu ry H a rv ey 's d is c o v e r y o f th e b lood c i r c u la t io n i n l6 2 8 and M a lp ig h i’ s d is c o v e r y o f th e c a p i l l a r i e s and red b lood c o r p u s c le s a ls o h elp ed to undermine th e o ld th eo ry b u t d id n o t co m p lete ly r e p la c e i t . Sydenham (1 6 2 4 /1 6 3 9 ) b e lie v e d that" i^lammation;;Of:t1^i«Sr/]tJl©©J,1was th e b a s is o f d is e a s e and th e two s ig n s o f t h i s were f e v e r and th e form ation o f a "buffy

/ b u f f y c o a t"1 i n th e v e n e s e c te d b lo o d . th e o r y on th e C on tin en t o f E urope.

Boerhaave (1663/173^ ) spread t h is

John Hunter (1 7 2 3 /1 7 9 3 ) th ou ght t h a t th e

’’b u ffy c o a t ” was i n th e n a tu re o f a p r e v e n ta tiv e r e a c t io n w h ile s t i l l con­ s id e r in g th e b lo o d to be th e so u rce o f a l l d i s e a s e s . P r io r y (1794/1 3 7 9 )> a French p h y s ic ia n , a g a in brought th e ’’b u ffy c o a t ” in t o prominence and c o n s id e r e d th a t th e r e was an in c r e a s e o f i t in th e b lood and th a t i t was a ls o d e p o s ite d a t th e s i t e o f d is e a s e by th e b lo o d . The f i n a l s tr o n g h o ld o f t h i s humoral p a th o lo g y was i n V ienna under R okitan sk y b u t its.L d o w n fa iiiw a s brou gh t by Virchow (1821-1902 )the founder o f c e l l u l a r p a th o lo g y .

S in ce th e ’’b u ffy c o a t ” was one o f the c e n t r a l f e a t u r e s

o f th e o ld humoral p a th o lo g y i t was in v e s t ig a t e d i n th e new r e a c tio n a r y method and th u s began th e modern c o n c e p tio n o f th e ”b u ffy c o a t ” • The f i r s t name in t h i s modern c o n c e p tio n o f th e ”b u ffy c o a t ” i s t h a t 2 o f B ie r m c k i who in 1394 p u b lish e d a work which showed th e r e la t io n s h ip o f th e ”b u ffy c o a t ” to th e s in k in g v e l o c i t y o f red b lo o d c o r p u s c le s i n shed b lo o d tr e a te d w ith an a n t ic o a g u la n t .

His i n t e r e s t i n t h i s phenomen co n tin u ed 3 and i n 1397 he p u b lish e d a n o th er paper i n which he a p p lie d th e phenomen to c l i n i c a l p r a c t ic e and p u b lish e d f in d in g s i n many d is e a s e s in c lu d in g pneu­ m onia, t u b e r c u lo s is , rh eu m atic a r t h r i t i s and an aem ia. Again in 1906 he pub4 l i s h e d a fu r th e r paper g ifrin g a s im p le r te c h n iq u e . In th e s e l a s t two p u b lic ­ a t io n s he a d v o ca tes t h a t th e c l i n i c a l a p p lic a t io n o f th e t e s t be used a s a p r o g n o s tic g u id e . In sp ir e d by B ie r n a c k i’ s work to c o r r e la t e th e s in k in g v e l o c i t y o f th e 3 red b lood c o r p u s c le s w ith th e c l i n i c a l c o n d it io n Marcano record ed h is f in d in g s in many d is e a s e s and a ls o th e f a c t t h a t th e s in k in g v e l o c i t y o f th e red b lo o d

6 c o r p u s c le s was in c r e a s e d i n women d u rin g m e n str u a tio n .p cB elo b u t , w h ile i n ­ v e s t ig a t in g b lo o d changes i n r e l a t io n to th e b lo o d p r e s s u r e , in c lu d e d th e s in k in g v e l o c i t y o f th e red b lood c o r p u s c le s as p a r t o f a com p lete b lo o d ex ­ a m in a tio n . G on tin u ih gp th e c l i n i c a l in v e s t ig a t i o n o f t h e ”B ie rn a ck i phenomenon n 1 Fahreus i n 1921 p u b lish ed a rev iew and gave th e name ’’su sp e n sio n s t a b i l i t y ” to th e phenomenon.

He p u b lish e d a s e r i e s o f c a s e s w ith th e r e s u l t s o f t e s t s

i n pregnant women and found pithkt th e ’’su sp e n sio n s t a b i l i t y ” was d ecrea sed i n t h e i r b lo o d , t h a t i s , th e c o r p u s c le s o f th e shed b lood sank f a s t e r than 8 th o se o f non pregnant women. In th e same yaar W estergren p u b lish e d h is

Page 1 0 .

/ h i s method and th e f in d in g s in pulmonary t u b e r c u lo s is ; he con clud ed th a t th e " su sp en sio n s t a b i l i t y ” was d ecrea sed i n pulmonary t u b e r c u lo s is and th a t t h i s te s t- gave an in d ic a t io n o f a c t i v i t y even i f no p y rex ia was p r e s e n t . S in c e th e s e r e s u l t s were p u b lish ed th e ’’su sp e n sio n s t a b i l i t y ” o f th e red b lo o d c o r p u s c le s has become a r o u tin e t e s t in th e i n v e s t i g a t i o n o f ch ro n ic d is e a s e where th e r e i s l i t t l e p y r e x ia l r e a c t io n . In th e p o s t - E n c e p h a lit ic syndrome o f P ark in son ism th e r e i s l i t t l e p y r e x ia l r e a c t io n and so th e " su sp en sio n s t a b i l i t y ” o f th e red b lo o d co r­ p u s c le s was u sed a s a more d e li c a t e means o f d e t e c t io n f o r e v id e n c e o f a c t ­ iv ity . 9 & 10 The o r i g in a l W estergren te ch n iq u e f o r d eterm in in g " su sp en sio n s t a b i l ­ it y " was u s e d .

T his i s more f a m il ia r ly known a s th e " S ed im en ta tio n Rate"

o f th e red b loo d c o r p u s c le s

DESCRIPTION OF METHOD. The apparatus req u ir ed i s 1.

:-

W estergren se d im e n ta tio n tu b es o f a d ia m eter 2*5 nan. and grad u ated from

above downwards i n m illim e t r e s from 0 to 2 0 0 . 2.

W estergren s y r in g e .

T his has two m arkings on th e b a r r e l, one a t 0 . 4 c c .

and th e o th e r a t 2 .0 c c . c o a g u la n t which i s 3

This i s u sed to d i l u t e th e b lo o d w ith th e a n t i ­ sodium c i t r a t e s o lu t io n i n s t e r i l e w a ter.

3«

S t e r i l e sodium c i t r a t e s o lu t io n 3

i n w a ter.

4.

Wooden stan d to h o ld th e W estergren tube v e r t i c a l w ith a s p r in g c l i p a t

th e to p and a f l a t rubber pad a t th e b a s e .

TBCHNIQUE. The s y r in g e i s f i l l e d to th e 0 .4 c c . mark w ith s t e r i l e sodium c i t r a t e s o lu t io n and venous b lood drawn up to th e 2 . 0 cc mark, c a r e f u l ly a v o id in g th e in tr o d u c tio n o f a i r b u b b le s.

A s la c k to u r n iq u e t i s u sed to c o n g e s t th e v e i n s .

The m ixtu re o f b lo o d and c i t r a t e i s th en t r a n s f e r r e d to a s m a ll t e s t tu b e and c a r e f u l ly marked. Within an hour t h i s b lo o d i s drawn up in t o one o f th e W estergren tu b es to th e mark 200 and f i x e d i n the stan d w ith th e t i p on th e rubber pad. Readings o f th e c le a r f l u i d column which appears w ith th e s e t t l i n g o f th e c o r p u s c le s a re ta k en a t th e ®nd o f one and two hours from th e tim e o f s e t t i n g up th e tube in th e s t a n d . To en su re u n ifo r m ity o f r e s u l t s and to make th e a ccu ra cy a s g r e a t aar

Page 11 / a s p o s s ib le th e f o llo w in g p r e c a u tio n s were ta k e n s 1.

Tubes were s e t up w ith in an hour o f w ithdraw ing th e b lo o d .

2.

Specimens were a l l ta k en a t th e same tim e o f d ay, in th e foren oon mid­

way betw een m e a ls • 3*

Any specim en showing h a em o ly sis or a g g lu t in a t io n were d isca rd ed *

4,

The s ta n d , w ith tu b e s i n p la c e , was alw ays s e t up on th e same bench i n

th e la b o r a to r y o u t o f d ir e c t s u n lig h t* 5.

The tu b es were e x a c t l y p e r p e n d ic u la r .

These p r e c a u tio n s were ta k en i n v iew o f th e c o n s id e r a b le d if f e r e n c e s 11 to 1 5 . e x e r te d by a p p a r e n tly t r i v i a l f a c t o r s as i s m entioned in th e lite r a tu r e .? ,;!

BIBLIOGRAPHY. The S ed im en ta tio n R ate o f th e Red Blood C o rp u scles.

•

1*

Panton P .N .

S ed im en ta tio n R ate o f Red Blood C orpusO les. M edical Annual. 1939* P»P« 431.

2*

B ie m a c k i E .A .

Wiener M e d iz in isc h e V b c h e n s e h r ift. 1 3 94.

p.p*36*

D eu tsch e M e d iz in isc h e W o ch en sch rift. V o l. XX111 1397*

p . p . 769.

3* B ie rn a ck i E .A .

4 . ' B ie m a c k i E .A .

Wiener K lin is c h e V /o ch en sch rift.

5.

Marcano G.

J o u rn a l de p h j?® ib logie e t de P a th o lo g ie G en era le. 1901. v o l. 3 p .p .167.

6.

Holobut T.

7.

Fahreus R.

3.

W estergren

9*

W estergren A.

10.

’Whitby & B r it t o n .

Wiener K lin is c h e W och en sch rift

A.

1906.

Vol.3CtX. . , J, p . p . 53 9 .

D eer. 7 t h . I9 U5 .

A cta M edica S c a n d in a v ic a .

1 9 21. V o l.3 5 .

p .p .1

A cta Medica S c a n d in a v ic a .

1-921. V o l .3 4 .

p .p .247.

A cta Medica S c a n d in a v ic a .

1 9 2 1 . V o l. 54-.

p .p .247.

D iso r d e r s o f th e B lo o d .

2nd. Ed. 1937•

p . p . 541.

I t . S ed im en ta tio n S a t e .

J o u rn a l ©f L ab oratory and C lin ic a l M ed icin e. V o l.11 p .p . 1 0 45.

12* S ed im en ta tio n R a te .

J o u rn a l o f L aboratory and C li n i c a l M ed icin e. V o l. 1 3 . p . p . 327*

13« Walton A .C.R.

J o u rn a l

o f L ab oratory and C l i n i c a l M ed icin e. V o l . 13. p .p . 7 1 1 .

1 4 . S ch u ster N.H.

L a n cet.

1 5 . Fahreus R.

P h y s io lo g ic a l R eview .

V ol.1

1939.

p .p . 8 7 2 . V o l. 9

p .p . 2 41.

THE EXAMINATION OF THE CEREBRO-SPINAL FLUID. On c o n s u lt in g th e standard monographs reg a rd in g th e c e r e b r o -s p in a l 1 . 2 /JL f l u i d in ch r o n ic E n c e p h a lit is L eth a rg ica th e r e appear to be v ery few ab­ n o r m a litie s c o n s t a n t ly p r e s e n t , so i t m s d ecid ed to co n c e n tr a te th e i n v e s t i ­ g a t io n on th e p r o te in c o n te n t w ith s p e c i a l r e fe r e n c e to th e A lb u m en -glob ulin 4 & 5 r a t i o . Other t e s t s perform ed were th e Lange C o llo id a l Gold R e a c tio n , a C e ll count and th e Pandy T e s t .

As a m a tter o f r o u tin e a l l f l u i d s on f i r s t

exam in ation had a Wassermann t e s t p erform ed. R e a lis in g t h a t th e ex am in ation o f a s in g le f l u i d i n each c a se was n ot s u f f i c i e n t i t was d ecid ed to examine a s p in a l f l u i d from each c a se every month over a p erio d o f s i x m onths.

In a c t u a l p r a c t ic e , how ever, t h i s was

d i f f i c u l t to ca rry o u t and th e c a s e s had to be grouped in t o th r e e c l a s s e s . \m

Those p a t ie n t s who were i n i n s t i t u t i o n s and p e r m issio n was o b ta in a b le to

p rocu re a f l u i d ev ery month. 2.

Those p a t ie n t s where p e rm issio n f o r w ith d raw al o f a s i n g l e f l u i d was

o b ta in a b le * b u t where a s e r i e s was im p o s s ib le . 3.

Those p a t i e n t s where i t was im p o s s ib le to o b ta in p erm issio n f o r w ith ­

drawal o f f l u i d and i n th o s e i n v e s t i g a t i o n was c o n fin e d to th e se d im e n ta tio n r a te o f red b lo o d c o r p u s c le s . In a d d itio n to th e fo r e g o in g d i f f i c u l t i e s th e r e were t e c h n ic a l d i f f i c u l ­ t i e s i n th e w ithdraw al o f c e r e b r o -sp $ n a l f l u i d b eca u se o f th e r i g i d i t y p r e s e n t­ ed by p a t ie n t s w ith P a rk in so n ism ; an o th er d i f f i c u l t y met w ith was th e a c c id e n t ­ a l con tam in atio n o f th e s p in a l f l u i d w ith b lo o d from one o f th e t h e c a l v e s s e l s . These axe n o t m entioned to e x p la in th e gap s i n th e s e r i e s b u t were found to be v ery r e a l i n a c t u a l p r a c t ic e . The c e l l c o u n t, th e Pandy t e s t and th e Lange c o l l o i d a l g o ld cu rve were done a s d e s c r ib e d by M e r r itt and Fremont Sm ith, th e te ch n iq u e b e in g uniform th roughout a l l e x a m in a tio n s.

A co m p a ra tiv ely new method f o r d eterm in in g th e

p r o te in c o n te n t and th e a lb u m en -g lo b u lin r a t io was u sed and s in c e t h i s en ­ t a i l e d much rea d in g a h is t o r y o f p r o te in e s t im a t io n in c e r e b r o - s p in a l f l u i d i s g iv e n fo llo w e d by a d e t a ile d d e s c r ip t io n o f th e method u s e d . Three main methods f o r e s tim a tin g th e p r o t e in c o n te n t o f c e r e b r o - s p in a l f l u i d are i n u s e : 1.

The s im p le s t and l e a s t a ccu ra te b e in g th e p r e c i p it a t io n o f th e p r o t e in i n

a s p e c i a l l y grad u ated c e n t r if u g e tu b e and m easuring th e d e p o s it a f t e r c e n t r i ­ fu g in g f o r a f ix e d tim e a t a f ix e d speed*

Page 13* The s c a le on th e c e n t r if u g e tu b e i s p r e v io u s ly determ ined by c a l c u l­ a t in g a p r o t e in p r e c i p it a t e by th e K je ld h a l method and from s e v e r a l o f th e s e e s t im a t io n s th e tube i s g ra d u a ted .

A dvocates o f t h i s method are

6 Youn^ and B en n ett who u sed a c e t i c a c id , a lc o h o l and h ea t to p r e c ip it a t e th e 7 p r o te in * C h r is t le ib and Myers u sed T su ch ia y a ’s method o f p r e c i p it a t in g th e p r o te in w ith p h o sp h o tu n g stic a c id , h y d r o c h lo r ic a c id and h ea t* 2*

The second method o f e s tim a tin g th e p r o te in c o n te n t o f c e r e b r o - s p in a l

f l u i d i s by th e u se o f a tu r b id im e te r .

The p r o t e in s are put in t o a c o l l o i d a l

s t a t e by means o f s u l p h o s a l i c y l i c a c id and com paring th e d egree o f t u r b id it y w ith th a t o f a known p r o t e in s o l u t i o n . The names a s s o c ia t e d w ith t h is method 9 to 11 are D en is and A yer, D aly and Fremont S m ith , and Hempel and G eise who u sed a lc o h o ls to produce th e t u r b i d i t y .

A s im ila r tu r b id im e tr ic method u sin g

d if f e r e n t r e a g e n ts to produce th e c o l l o i d a l s u sp e n sio n i s rep o rte d by Exton 12 and Bose • 3.

The th ir d method o f e s t im a t in g th e p r o t e in c o n te n t o f c e r e b r o -s p in a l

f l u i d depends on th e e s t im a t in g o f th e t y r o s in e c o n te n t as compared w ith th e ty r o s in e c o n te n t o f a known s o lu t io n by means o f a c o lo u r in d ic a t o r and a 13 & 21 c o lo r im e te r . The te c h n iq u e was e v o lv e d from //u’ s method o f e s tim a tin g th e plasm a p r o t e in s .

The f i r s t

a d a p ta tio n was d e s c r ib e d b y H ew itt, in t h is th e 15 & 1 6 . in d ic a t o r was th e p henol r ea g e n t o f F o lin and D e n is . A fu r th e r advance was 17 13 made by J o h n sto n and G ibson who u sed th e F o lin - Q io c a lt e u r e a g e n t in p la c e o f th e phenol r e a g e n t u sed by H ew itt* In t h i s paper th e method u sed i s an a d a p ta tio n o f t h a t o f J oh n ston and G ib son .

The main d if f e r e n c e s from t h e i r method b e in g th a t 20^ t r i c h l o r a c e t i c

a c id was used in s t e a d o f y], t ammonium su lp h a te was used in s t e a d o f sodium su lp h a te f o r th e f r a c t i o n a t i o n in t o albumen and g lo b u lin and th e tim e a llo w ed f o r th e c o lo u r r e a c t io n to d ev elo p e was in c r e a s e d t o tu e n ty m inutes in s te a d o f th e te n m in u tes recommended.

This l a s t d if f e r e n c e m s judged n e c e s s a r y

b ecau se o f th e slo w developem ent o f th e c o lo u r r e a c t io n .

DESCRIPTION OF METHOD. In t h i s th e t o t a l p r e t e in was e s tim a te d , th en th e albumen co n ten t and f i n a l l y by s u b t r a c t io n ;th e g lo b u lin c o n te n t was fo u n d . A.

T o ta l P r o t e in . Take 2 m l. c e r e b r o - s p in a l f l u i d in t o a c le a n ,d r y , ta p ered 15 n l* c e n t r i­

fu g e tu b e . Add 2 m l. 20^ t r i c h l o r a c e t i c a cid *

Page 1 4 . C lose w ith rubber sto p p er and in v e r t s e v e r a l t im e s , a llo w to sta n d o v er­ n ig h t , Immerse in b o i l i n g w ater b a th f o r i m in u te . Cool by sta n d in g i n c o ld w a te r . C en trifu g e f o r h a lf - a n - h o u r . Pour o f f th e su p ern a ta n t f l u i d and remove f i n a l t r a c e s o f li q u i d w ith a p ie c e o f c le a n , washed g a u z e . Add 0*25 m l. o f 10f0 sodium h yd roxid e and p la c e i n a b o ili n g w ater b ath f o r te n m in u te s. Add 3*75 m l. o f d i s t i l l e d w ater and 0 . 5 m l. o f F o lin - C io c a lt e u co lo u r r e a g e n t. Add 1*5 m l. s a tu r a te d sodium carb on ate s o l u t i o n . Mix c o n te n ts o f tub©: by c l o s i n g w ith th e thumb and in v e r t in g s e v e r a l tim e s . Do n o t u se a rubber bung a s t h i s m ight a f f e c t th e c o lo u r . Leave f o t tw en ty m in u tes b e fo r e com paring .with th e stand ard s o lu t io n in the c o lo r im e te r • B.

Albumen. Take 2*5

c e r e b r o - s p in a l f l u i d i n a c le a n , d ry , ta p ered 15 m l. c e n t r i ­

fu g e tu b e . Add 2 .5 m l. s a tu r a te d s o lu t io n o f ammonium s u lp h a t e . C lose w ith a rubber s to p p e r and in v e r t s e v e r a l t im e s , a llo w t o sta n d o v er­ n ig h t • C en trifu g e f o r h a lf - a n - h o u r . D ecant th e su p ern a ta n t f l u i d and p ip e t t e 4 m l. o f th e d ecan ted f l u i d to an­ o th er c le a n , dry 15 nil* c e n t r if u g e tu b e . Add 4 m l. 20fo t r i^ o h lb r o c e tic a c i d . P ut i n b o i l i n g w ater b a th f o r 1 m in u te. C en trifu g e f o r h a lf - a n - h o u r . Pour o f f th e w u p ern atan tt f l u i d • Add 0 .2 5 m l. o f tO^c sodium hyd roxid e s o l u t i o n . P la c e in b o i l i n g w ater b a th f o r 10 m in u te s. Add 0 .5 m l, ©f F o lin - C io c a lt e u c o lo u r r e a g e n t. Add 1 .5 m l. ©f s a tu r a te d sodium carb on ate s o l u t i o n . Mix c o n te n ts by in v e r t in g s e v e r a l tim es w ith thumb o v er th e end* Leave f o r tw en ty m in u tes t i l l c o lo u r d^w»b©pes*

Page 1 5 . C.

Standard T yroaine S o lu t io n s .

In to th r e e t e s t tu b es p ip e t t e r e s p e c t i v e ly 0*5 m l ., 1 ,0 m l ., and 2*0 m l. N o f an 0 . 02^ s o lu t io n o f t y r o s in e in 101 h y d r o c h lo r ic a c id . Make th e vollttme^up to 8 m l. by adding r e s p e c t i v e ly 7 . 5 m l., 7 .0 m l., and 6 .0 m l. o f d i s t i l l e d w a te r . Add to each t e s t tube 1 m l. ©f F o lin - C io c a lt e u r e a g e n t and 3 *al* o f sa tu r a te d sodium carfeoilate s o l u t i o n . Mix a l l tu b es th o r o u g h ly . Leave f o r tw en ty m inutes t i l l th e c o lo u r d e v e lo p e s . A lthough d e sc r ib e d a s th r e e s e p a r a te p ie c e s o f work i t w i l l be se e n th a t th e f i r s t two o p e r a tio n s ,A and B ., c o in c id e from th e p o in t where th e c e n t r i­ fu g e tu b es a re put in t o th e b o ili n g w ater b ath f o r 1 minute and t h a t th e p re­ p a r a tio n o f th e t y r o s in e s ta n d a r d s, o p e r a tio n C ., c o in c id e from th e a d d itio n o f th e F o lin -C io c a lt e u c o lo u r r e a g e n t.

Thus a l l th r e e o p e r a tio n s can be com­

b in ed to have th e c o lo u r rea g e n t added to th e f i n a l s o lu t io n a t th e same tim e , and so a llo w in g th e c o lo r im e t r ic rea d in g s to be done c o n s e c u t iv e ly . S e v e r a l t e c h n ic a l p o in ts cropped up in d oin g t h i s s e r i e s o f f l u i d s .

The

f i r s t o f t h e s e b e in g a t th e p o in t when t r e a t i n g th e p r o te in p r e c ip it a t e w ith th e h o t sodium h yd roxid e th e whole o f th e p r e c i p it a t e must be d is s o lv e d ; i f t h i s does n o t happen th e specim en must be d isc a r d e d and h a l f th e amount o f c e r e b r o -s p in a l f l u i d u sed making up th e req u ir ed volume w ith

d i s t i l l e d w a te r .

In th e p r e s e n t s e r i e s o n ly a few req u ired to be done i n t h i s

way where th e pro­

t e i n c o n te n t was h ig h .

The second p o in t b e in g th e u se o f c le a n , washed gauze

to remove f i n a l drops o f f l u i d a f t e r d e c a n tin g , t h i s i s n e c e s s a r y as f i l t e r 19 paper absorbs p r o t e in . The f i n a l p o in t i s th e m ixing o f th e tu b es a f t e r th e c o lo u r in d ic a t o r has been added where th e thumb i s used to c lo s e th e tube i n ­ s t e a d o f a rubber sto p p er a s t h i s d is c o lo u r s th e s o l u t i o n . The c a lc u la t io n s a re based on th e t y r o s in e e q u iv a le n ts g iv e n by J oh n ston 20 and G ibson, nam ely t mgm. t y r o s in e i s e q u iv a le n t to 11 .1 mgrn. albumen. t ngm. t y r o s in e i s e q u iv a le n t to 1 1 .4 mgm. t o t a l p r o t e in . I t was found t h a t th e standard ty r o s in e s o lu t io n c o n ta in in g 1 m l. o f N an 0 .0 2 $ s o lu t io n o f t y r o s in e i n 10 h y d r o c h lo r ic a c id made up to 3 m l. w ith d i s t i l l e d w ater m s th e b e s t to u s e . cup b ein g 10 mfn,..

The depth o f s o lu t io n i n th e c o lo r im e te r

Page 1 6 . CALCULATION. P ercen ta g e s tr e n g th o f t y r o s in e s o l u t i o n * i s 0 .0 2 $ . 100 c c . t y r o s in e s o lu t io n c o n ta in 0 .0 2 gm s. t y r o s in e . 1 c c . s o lu t io n c o n ta in 0 .0 0 0 2 gm s. t y r o s in e . C o n cen tra tio n i s 0 .0 0 0 2 gm s. in 8 c c . s o l u t i o n . P ercen ta g e s tr e n g th in 8 c c . s o lu t io n i s

( 0 .0 0 0 2

=

X tQO

0 . 0025$ .

When th e c o lo u r s match in th e c o lo r im e te r S

x

X

*

U

x

T.

Where S i s depth o f stand ard s o l u t i o n . X i s c o n c e n tr a tio n o f stand ard s o l u t i o n . U i s depth o f unknown s o l u t i o n . T i s c o n c e n tr a tio n o f unknown s o l u t i o n . The standard i s a t 10 mm. d ep th . S

x X

=

0 .0 0 2 5 x 10

0.025 $

*

U

x Y X

=

0 .0 2 5 $

=

.(.Q_*Q2.5, 1 ^

c o n c e n tr a tio n o f unknown.

1 c c . o f unknown c o n ta in ( O.Q2'5 ) ___

( T o o u l e“s -

*

ftr ig o e ?

gm s.

0*25

mg.

u

4 c c . o f unknown s o lu t io n c o n ta in 1 0 .2 5 x 4 ) (

U

t y r o s in e .

*

2 c c . o f unknown ( i . e . o r i g i n a l C .S .P .} c o n ta in | 0 12 1 jx 4 l

=

- i

^

ty r o a In®.

mgm. t y r o s in e .

100 c c . o f o r i g i n a l C .S .P . c o n ta in

50 mgm. t y r o s in e . U

b u t 1 mgm. t y r o s in e i s e q u iv a le n t t o 1 1 ,4 ngm. t o t a l p r o t e in . .52. fflgm. ty r o s in e i s u

e q u iv a le n t to 1.1 -4 x 5u u m

mgm. t o t a l

p r o t e in ,

mgm. t o t a l p r o t e in .

S im ila r ly f o r albumen th e v a lu e i s

555 where 1 mgm. t y r o s in e i s e q u iv a le n t U

Page 1 7 . /e q u iv a le n t to 11.1 mgm. albumen.

T herefore th e r e s u lt o f th e s e c a lc u la t io n s

i s i n m illigram m es o f t o t a l p r o te in o r albumen per 100 c c .

The g lo b u lin con­

t e n t i s o b ta in ed by sim p le s u b tr a c tio n o f albumen c o n te n t from t h a t o f t o t a l p r o te in c o n te n t . Thus from th e s e two e s t im a t io n s th e r e was fo u n d :1.

T o ta l p r o te in in mgm. p er 100 c c . o f c e r e b r o - s p in a l f l u i d .

2.

Albumen c o n te n t i n mgm. per 1u0 c c . o f c e r e b r o - s p in a l f l u i d .

3.

G lo b u lin c o n te n t in mgm. per 1u0 c c . o f ce r e b r o -sp in a }, f l u i d .

4.

The a lb u m en -g lo b u lin r a t io o f th e specim en o f c e r e b r o - s p in a l f l u i d exam ined.

BIBLIOGRAPHY. The C e r e b r o -sp in a l F lu id and f r a c t i o n a l e s t im a t io n o f th e c e r e b r o - s p in a l ________________________ f l u i d p r o t e in d .___________________________________ t.

Levinson •

The C ereb ro -S p in a l f l u i d .

2nd. E d it .

1923*

2.

G r e e n fie ld &C arm ich ael.

The C e r e b r o -sp in a l F l u i d .i n C l i n i c a l D ia g n o s is . M cM illan & Coy. 1925*

3.

M errit and Fremont S m ith . The C e r e b r o -sp in a l F l u i d .

4.

M errit & Fremont S m ith .

The C ereb ro -S p in a l F lu id .

5.

Cruikshank J .

B r i t is h J o u rn a l o f E xp erim en tal P a th o lo g y . V o l. 1 1920. p .p . 7 1 .

6.

Young A.G. and B en n ett A.E. S tu d ie s on th e Q u a n tita tiv e E stim a tio n o f th e T o ta l P r o te in o f th e C ereb ro -S p in a l F lu id . American J o u rn a l o f th e M ed ica l S c ie n c e s . V o l. 1 7 2 . p .p . 2 4 9 /2 5 5 .

7.

Young A .G ., B en n ett A .E ., A rch iv es o f N eu ro lo g y and P s y c h ia t r y . C h r is t le ib J .M ., & Myers J .T . V o l. 2 3 . P»P* 542. t931*

S.

Bauer A.E. &Schahk H .P.

9.

D enis &A yer.

Saunders & Coy. 1937* Saunders & Coy. 1937• p .p . 270

J o u r n a l o f L ab oratory and C l i n i c a l M e d ic in e . V o i.t 6 . p .p . 1 0 9 0 . 1 9 3 1 . A rch iv es o f I n t e r n a l M ed icin e. V o l. 2 6 .

p .p . 4 2 6 .

1 0 . A yer, D aly & Fremont S m ith . T o ta l P r o te in in C ereb ro -S p in a l F l u i d . A rch iv es o f N eu ro lo g y and P s y c h ia t r y . V o l. 2 6 . p .p . 1033. 11.

Hempel&G e is e .

1 2 . Exton W.G. & Rose A .S.

13*

14.

Wu H.

H e w itt.

1920.

1931*

Method o f E stim a tin g C erebro-SpinaJ. F lu id P r o t e in . K lin is c h e W o ch en sch rift. V0I . I 5 . p .p .t 6 4 3 . 1 9 3 6. F r a c tio n a tio n o f C ereb ro -S p in a l F lu id P r o t e in s . J o u rn a l o f th e American M ed ical A s s o c ia t io n . V o l. 9 6 . p .p . 3 6 . E stim a tio n o f Plasm a P r o t e in s . J o u rn a l o f B io l o g ic a l C h em istry. V o l. 1 0 0 .

'

p .p . 7 7 9 . 1933.

D eterm in a tio n o f C ereb ro -S p in a l F lu id P r o t e in s . B r i t is h J o u rn a l o f E x p erim en ta l P a th o lo g y . V o l. 3 . p .p . 3 4 . t9 ? 7 •

Page 1 8 . 15.

F o lin 0 . & D en is YV.

Two C olour R ea g en ts. J o u r n a l o f B io lo g ic a l C hem istry. V o l. 12 p .p . 239*

1912.

16.

Lloyd D.G. & Shore A.

The C hem istry o f th e P r o t e in s . (Monograph) p .p . 1 2 6 .

17*

J o h n sto n D.vY. & G ibson R.B. D eterm in a tio n o f th e C ereb ro -S p in a l F lu id American J o u rn a l o f T e c h n ic a l Supplement

13.

F o lin 0 . & C io c a lte u .

J o u rn a l o f B io l o g ic a l C hem istry. V o l. 7 3 . p .p . 6 2 9 .

19.

R o b iso n .

J o u rn a l o f B io l o g ic a l C hem istry. V o l. 1 2 0 . p .p . 4 3 1 .

Blood Plasma and th e P r o t e in s . C lin ic a l P a th o lo g y . N o .2 . p .p . 2 2/31* J a n /1938.

1937.

20.

Joh n ston D.VY. & Gibson R.B. D eterm in a tio n o f th e Blood Plasm a and the C ereb ro -S p in a l F lu id p r o t e in s . American J o u rn a l o f C lin ic a l Pkfch&Logy. T ech n ic a l Supplem ent N o .2 p .p . 2 2 /3 1 . J a n /1 9 3 3 *

21.

R ein er M. & Sobotha H.

T y ro sin e and C y stin e C ontent o f Serum P r o t e in s . J o u rn a l o f B i o l o g i c a l C hem istry. V o l. 100. p .p . 7 7 9 . 1 9 33.

SCOPE OF PRESENT INVESTIGATION. The b lood and c e r e b r o - s p in a l f l u i d o f t h i r t y (30) c a s e s o f P o s t E n c e p h a litic P ark in son ism was in v e s t ig a t e d i n an attem p t to d eterm ine w hether o r n ot th e i n f e c t i o n was a c t i v e . In th e b lo o d th e h o u rly and tw o -h o u rly se d im e n ta tio n r a t e s were found by th e W estergren m ethod.

This was done w eekly o v er a p e r io d o f s i x m onths.

As d is c u s se d i n th e c h a p ter on s e d im e n ta tio n r a t e s t h i s was tak en as th e most 1 s e n s i t i v e t e s t f o r th e a c t i v i t y o f an i n f e c t i v e p r o c e s s . In th e c e r e b r o - s p in a l f l u i d th e f o llo w in g t e s t s were c a r r ie d o u t : 1*

The t o t a l p r o te in c o n t e n t .

2.

The albumen c o n t e n t .

3.

The g lo b u lin c o n t e n t •

4..

The a lb u m en -g lo b u lin r a t i o .

5,

The c e l l c o u n t.

6.

The Pandy t e s t .

7*

The Lange c o l l o i d a l g o ld c u r v e . I t was attem p ted in each c a s e to o b ta in a c e r e b r o - s p in a l f l u i d f o r

exam in ation each month f o r a p e r io d o f s i x months . These i n v e s t i g a t i o n s on th e h lo o d and c e r e b r o - s p in a l f l u i d were c a r r ie d o u t o v e r th e same p e r io d o f s i x m onths.

Owing to th e d i f f i c u l t i e s m entioned

i n paragraphs 2 and 3 o f th e ch a p ter on th e ex a m in a tio n o f th e c e r e b r o -s p in a l f l u i d th e c a s e s f i n a l l y r e s o lv e d th em selv es in t o fo u r groups A.

Gases where th e b lo o d ex a m in a tio n s were made w eek ly o v e r th e s i x months

and a ls o c e r e b r o - s p in a l f l u i d was examiiaed m o n th ly . B.

Cases where th e b lo o d ex a m in a tio n s were made w eekly o v e r th e s i x months

b u t where o n ly one o r two c e r e b r o - s p in a l f l u i d s were o b ta in e d . C.

Gases where th e b lo o d ex a m in a tio n s were made w eekly o v er th e s i x months

b u t no c e r e b r o - s p in a l f l u i d s were o b ta in e d . D.

Gases who d ied o f in t e r c u r r e n t d is e a s e d u rin g th e i n v e s t i g a t i o n . In c a te g o r y A. th e r e were tw e lv e (12) c a s e s , i n c a te g o r y B. th e r e were

te n (10) c a s e s , in c a te g o r y C. s i x £6 ) c a s e s and i n c a te g o r y D. two (2) c a s e s . The e a s i e s t way to p r e s e n t a l l th e r e s u l t s f o r one c a s e on one page was by making a g ra p h ic r e p r e s e n t a t io n o f th e se d im e n ta tio n r a te w ith th e number o f weeks p lo t t e d h o r iz o n t a lly and th e s e d im e n ta tio n r a t e s v e r t i c a l l y .

The

h ou rly se d im e n ta tio n r a te p lo t t e d i n b la c k in k , tw o -h o u rly r a t e i n g r e e n in k j w h ile two red h o r iz o n t a l l i n e s in d ic a t e d th e normal a v erage rea d in g f o r th e

Pago 20*

/ t h e h o u rly and tw o -h o u rly r e a d in g s . To c o r r e la t e th e c e r e b r o - s p in a l f l u i d r e s u l t s w ith th e graph o f th e se d im en ta tio n r a t e s a t a b le o f th e s e was drawn b elow th e graph w ith an arrow in d ic a t in g th e week i n w hich i t had been ta k e n . Below t h i s combined r e p r e s e n ta tio n o f th e c a s e r e s u l t s was p r in te d a few s e n te n c e s c o r r e la t in g th e r e s u l t s and n o t in g any o u tsta n d in g abnormal­ ity . CONTROL SERIES. No c o n t r o l s e r i e s o f b lood s e d im e n ta tio n r a t e s m s co n sid e r e d n e c e ssa r y 2 a s a l l th e stand ard r e fe r e n c e s gave f in d in g s w hich are u n iv e r s a ll y rec o g n ise d a s b ein g th o s e o f normal h e a lt h . With th e c e r e b r o - s p in a l f l u i d th e r e v e r s e was found a s even th e mono­ graphs d id n o t g iv e r e s u l t s o f any g r e a t number o f c a s e s o f P o s t - E n c e p h a lit ic P ark in son ism .

T h erefore a c o n tr o l s e r i e s had to be found and th e b e s t source 3 .4 .& 5 . fo r t h is was found to be S ch izo p h ren ic p a t ie n t s a s a l l th e r e fe r e n c e s c o n su lted agreed th a t th e c e r e b r o - s p in a l f l u i d s o f such c a s e s was norm al.

T w enty-tw o(22}

such c a s e s had a c e r e b r o - s p in a l f l u i d exam ined to p ro v id e a c o n tr o l s e r i e s . A ll th e c a s e s , b oth o f P ark in son ism and th e c o n tr o l s e r i e s , had a Wassermann R ea ctio n done on th e b lo o d and c e r e b r o -s p in a l f l u i d as a r o u tin e m easure•

BIBLIOGRAPHY. 1.

Panton P.M.

S ed im en ta tio n R ate o f Red B lood C o r p u sc le s. M ed ical A nnual. 1939• P*P* 43 1 .

2.

Whitby & B r it t e n .

D is e a s e s o f th e B lo o d . 2nd. E d it . 1 9 37.

P-P« 3 4 1 /5 4 2 .

P s y c h o lo g ic a l M ed icin e. 4 th . E d it . 1 9 26.

p .p . 1 24.

3*

4.

5*

C raig & B ea to n .

M e r r itt & Fremont S m ith . The C e r e b r o -sp in a l F lu id . 1 s t . E d it . 1937* G r e e n fie ld & C arm ich ael.

P*P* 138.

The C ereb ro -sp in a l F lu id in C lin ic a l D ia g n o s is . 1 s t . E d it . 1925* P*P* *93 *

t

______

* * -------- ---- ------------

Sedimentation Graph. This graph over the whole period of six months was within normal limits, (indicated by the horizontal red lines, ezcept for the sixth week where both the hourly and two-hourly readings were slightly greater than normal.

D uring t h i s

week there was a coryzal infection. Gerebro-Spinal Pluid results• Here five complete results were obtained in addition to two specimens which contained franx blood. The evaluation of these results is not attempted here, with £he small space available, but is consolidated in the pages following the case results. This applies to all the cases where cerebro-spinal results are quoted.

Page 2 2 .

Case 2 .

Ill

_ qTJi

i i M i

Et

zm

®o 0\ o\o \0

Sedimentation Graph. In all aspects this graph gave a completely normal picture, over the whole period of six months. Cerebro-spinal fluid results. Five complete results were obtained and two specimens which had sufficient fluid only for a cell-count and Pandy test and Lange colloidal gold curve.

Page 23•

Case 3.

Sedimentation Graph. This graph showed high readings over the first three months, a chronic bronchitis was present and showed some activity during this period. Cerebro-spinal fluid results. Five complete results were obtained and two specimens which had suffic­ ient fluid only for a cell count, Pandy test and Lange colloidal gold curve.

Sedimentation Graph. In all aspects this graph gave a completely normal picture over the whole period of six months. Gerebro-spinal fluid results. Six complete results were obtained and one specimen which had suffic­ ient fluid only for a cell count, Pandy Test and Lange colloidal gold curve.

^age 2 5 .

1

Sedimentation Graph# This graph showed high readings over the first three and a half months, a pyelitis was present and also increased hilar markings in an X-ray plate of the chest. Gerebro-spinal fluid results.

Seven com plete r e s u lt s were o b ta in e d .

Sedimentation Graph* This graph showed high readings over the first six weeks, a coryza followed by an acute bronchitis was present during this period. Ccrebro-spinal fluid results# Pour complete results were obtained and one specimen which had suffic­ ient fluid only for a cell count, Pandy test and Lange colloidal gold curve#

Page 2 7 .

Case 7 to

Sedimentation Graph» In all aspects this graph gave a completely normal picture over the whole period of six months• Cerebro-spinal fluid results* Five complete results were obtained in addition to one specimen which contained frank blood.

Pag*

Sedim entation Graph* This graph showed high readings over the first four weeks, an acute bronchitis was present over this period#

C_erebro~sp in al f lu id r e s u l t s . F iv e com plete r e s u l t s were o b ta in ed i n a d d itio n to one sp ecim en w hich co n ta in ed fra n k b lo o d .

Pag© 2 9 .

Gas© 9

Uo

6-A

Sedimentation Graph, In all aspects this graph gave a completely normal picture over the whole period of six months. Gerebro-spinal fluid results.

F iv e com plete r e s u l t s were o b ta in ed in a d d itio n to one specim en which co n ta in ed fra n k b lo o d .

Page 30

r

It

Sedimentation Graph. This graph showed high readings over the whole period of six months, a chronic bronchitis complicated by moderately acute exacerbations was present, Cerebro-spinal fluid results.

Pour com plete r e s u lt s were o b ta in e d .

Page 3 1 •

Case 11

m

Sedimentation Graph. In all aspects this graph gave a completely normal picture over a period of five months. Cerebro-spinal fluid results,. Pour complete results were obtained in addition to one specimen which contained frank blood*

Page

32

Case 1 2 .

Sedimentation Graph, This graph showed high readings over the first three months, a chronic bronchitis with acute exacerbations was present. Gerebro-spinal fluid results.

Three com plete r e s u lt s were o b ta in ed in a d d itio n to one specim en which c o n ta in e d fran k b lo o d .

Page 33

Case 13*

Sedimentation Graph. The sedimentation rate was raken over only a period of two months, as an acute respiratory infection culminating in broncho-pneumonia and death developed. Gerebro-spinal fluid results. Two complete results were obtained.

Page 34 *

Gase. 14

XX -1X

n

/O 7

Sedimentation Graph. The sedimentation rate was taken only over a period of two months as an acute respiratory infection, culminating in broncho-pneumonia and death developed. Gerebro-spinal fluid results* Two complete results were obtained#

Page 35*

.

1

Sedimentation Graph, In all aspects this graph gave a completely normal picture over the whole period o f six months• Cerebro-spinal fluid results* Two complete results were obtained.

Sedimentation Graph* This graph showed high readings practically over the whole period of six months as a chronic bronchitis was present complicated by an acute ex­ acerbation during the first month. Gerebro-spinal fluid results* Two complete readings were obtained.

Page 37

Case 17

LC\

•A

^ ----------- —---------------------

'

...,--V -.:V!-v-W,.!a»-

.

•

Sedimentation Graph* In all aspects this graph gave a completely normal picture over the whole period of six months. Gerebro-spinal fluid results. Two complete results were obtained.

vL

------ —---------------------------- =====----------

**—

—

--------------

Sedimentation Graph* In all aspects this graph gave a completely normal picture over the whole period of three months# Cerebro-spinal fluid results# Two complete results were obtained#

t

Sedimentation Graph. In all aspects this graph gave a completely normal picture over the whole period of six months • Sgrebro-apinal fluid results. One complete result m s obtained#

.

Page 40

Gase 20 *

u

± □

*

J.

I..

I___

L 4#rx u

/;/ j*:P *|/;p

i i i i

Sedimentation Graph. This graph showed a high reading over the first two months as a bronchitis present, Qgribro*spinal fluid results. One complete result was obtained.

Page 41

Case 21•

444

h -

Sedimentation Graph* In all aspects this graph gave a completely normal picture over the whole period of six months • Cerebro-spinal fluid results.

One com p lete r e s u l t was ob tain ed *

Page 4 2 .

Case 22*

O',

M

I i0/a /. ^ ci'l iU*4i

Sedimentation Graph* This graph showed high readings over the first month, a chronic bronchitis was present. Cgrebro-spinal fluid results.

One com p lete r e s u l t 'was o b t a in e d .

Sedimentation Graph. In all aspects this graph gave a completely normal picture over the whole period of six months* _Oerebro-spinal fluid results. One complete result was obtained*

,

hOiCt i

Sedim entation Graoh. This graph showed high readings over the first month, an acute bronchitis was present.

i

Gereb ro-sp in al f l u i d r e s u l t s . One com p lete r e s u l t was o b ta in e d . ■

.Page 45 •

Sedimentation Graoh. This graph showed high readings over the first month, an acute bronchitis was present. Cflrebro-soin.al fluid results. Cases 23 to 30 had no serebro-spinal fluid examinations.carried out.

Sedimentation Grapn. In all aspects this graph gave a completely normal picture over the whole period of six months*

Case 27

.

,

Sedimentation Graph* In all aspects this graph gave a completely normal picture over the whole period of six months*

Sedimentation Graph* In all aspects this graph gave whole period of six months•

Sedimentation Graph* This graph showed high readings in the second month, a coryza with bronchitis was present.

Page JO.

Case* 30

t

-

4

Sedimentation Graph* In all aspects this graph gave a completely normal picture over the whole period of six months*

Page 51 •

CONTROL SERIES OF CEREB5Q-SPINAL FLUIDS TAKEN FROM GASES OF SCHIZOPHRENIA. For the control series of eerebro-spinal fluids twenty-two (22) cases of Schizophrenia were chosen. people were unobtainable.

This was necessary as fluids from normal

In the references consulted the cerebro-spinal

1. 2.

&3 .

fluid was considered to be normal in cases of Schizophrenia, the defect in them being regarded as purdly functional. The results are arranged in similar tables to those used for the cases of Post-Encephalitic Parkinsonism.

Case 1.

Case 2*

Total Protein. Albumen. Globulin•

34*03

A lb u m en -glob ulin r a t i o .

4.3/1 R.B.C. Neg.

52.43 33.16 14.32 2.7/1

Cell count. Pandy Test. Lange colloidal gold curve*

Total Protein. Albumen. Globulin• Albumen-globulin ratio. Cell count. Pandy Test. Lange colloidal gold curve,

Total Protein. Albumen•

G lob u lin * Albpmen-globulin Ratio. Cell count. Pandy Test. Lange colloidal gold curve.

Total Protein. Albumen• Globulin• Albumen-globulin ratio* Cell count. Pandy Test. Lange colloidal gold curve.

Total Protein.

Albumen » Globulin. Albumen-globulin ratio. Cell count. Pandy Test. Lange colloidal gold curve.

23.16

>93

0000000000

1. Neg.

1112210000

Case 3 .

Case 4 .

37.67 29.70

32.90 23.90

7.97 3 .7 /1 1

9.00 2 .7/1

Neg.

R.B.C. Tr*ce.

0011100000

0112211000

Case 5.

Case 6 .

46.70 30.30 16.40 1 .3/1

2 5.60 19.20

1 Neg.

6.40

3 -0 /t 4 Neg.

00o 121000u

1 122l000-u0

Case 7 .

Case 8 .

24*30 19.20 5 .30 3 .6/1

26.90 2 3 .3 0 3 .60

S.B.C. Neg.

6 . 5/1 6

1112220000

Neg. 11221OO0Q0

Case 9 «

Case 10.

33.30 27.50

41 .70 23.50

6*30 4.4/1

10 Neg.

1122210000

13.20 2 . 3/1 R.B. C. Neg. 11111QOuQu

Page 5 2 .

Total Protein. Albumen. Globulin. Albumen-globulin ratio. Cell count. Pandy Test. Lange colloidal gold curve.

C ase 11 .

C ase 1 2 .

3 0 .7 0 2 2 .3 0

34.40

2 7 .2 0 7 .2 0

3.40 2.7/1

3

0 Neg.

1111ouoooo

Total Protein. Albumen. Globulin. Albumen-globulin ratio• Cell count. Pandy Test. Lange colloidal gold curve,

111100000O

Case 13.

Case 14.

42.20

33.30

3 1 .00

2 5 .5 0

11.20

3 .3 0

.

2 8 /1

3.1/1

0

0

Neg.

Total protein. Albumen. Globulin. Albumen-globulin ratio. Cell count. Pandy Test. Lange colloidal gold curve.

1111100000

Neg. 11110000O0

Case 1 3.

Case 16.

35*oo

31 .00

2 6 . Go 9 .0 0 3 . 0/1

2 3 .0 0 3.00 2 .9/1

0 Neg.

Total Protein. Albumen. Globulin. Albumen-globulin ratio. Cell count. Pandy Test. Lange colloidal gold curve

Total Protein. Albumen. Globulin. Albumen-globulin ratio. Cell count. Pandy Test. Lange colloidal gold curve

0

0000000000

Neg. 11 10000000

Case 17.

Case 13.

29 .Go

39.00

21 .00

7 1 .0 0

3.00 2.3/1 0 Neg, 0001 110000

13.00 4.0/1

’ 1111222000

Case 19.

Case 2 0 .

33.00

33-00

2 7 .0 0 6 .0 0

2 6 .0 0

R.B.C. Neg.

7.00

4.5/1

Total Protein. Albumen. Globulin. Albumen-globulin ratio. Cell count. Pandy Test. Lange colloidal gold curve.

.3 / 1

0 Neg.

1 Neg.

3.3/1 0 Neg.

0001110000

0001100000

Case 21.

Case 2 2 .

2 7 .0 0 2 2 .0 0

42.00

3 6 .0 0

5.00

6.00 6 . 0/ 1 1

4.4/1 0 Neg.

Neg.

oooooooooo

oooooooooo

BIBLIOGRAPHY. Psychological Medicine. 4th. Ed* 1926. p.p.1?4«

t.

Craig & Beaton.

2.

Merritt & Fremont Smith. The Cerebro-spinal Fluid. 1st. Ed.

1937*

p.p. 133.

3.

Greenfield & Carmichael.

The Cerebro-sp§inal Fluid in Clinical Diagnosis.

1s t . Ed.

1 9 25.

P*P* 1 93.

Page 53 •

SUMMARY OP SEDIMENTATION RATE GRAPHS. O nly f o u r r e f e r e n c e s to t h e s e d i m e n t a t i o n r_^te o f t h e r e d b l o o d c o r ­ p u s c l e s i n c a s e s o f P o s t - B n c e p h a l i t i c P a r k i n s o n i s m were f o u n d .

The f i r s t was

1

by L o r e n z

w r i t i n g i n t h e Deut-sche M e d iz in is c h © v / o c h e n s c h r i f t , b u t t h e s e c a s e s

were in an a c u te s ta g e and the f in d in g s are n o t comparable w ith th o se in the 2 p r e s e n t wotk. The seco n d , by P a u lia n and T om ovici,found d ecrea sed sed im en t­ a tio n r a te s in P o s t— E n c e p h a litic xJa rk in so n ism .

The t h ir d , by Lorenz and B erger, 4 found in c r e a se d r a te s in some c a s e s and normal in o t h e r s . F i n a l ly , Hachez, who found s im ila r r e s u l t s to Lorenz and B erger. These r e fe r e n c e s g iv e very l i t t l e in d ic a t io n as to what th e f in d in g s in a la r g e s e r i e s o f se d im e n ta tio n r a te s i n c a s e s o f P o s t—E n c e p h a litic P ark in son ­ ism would be and th e summ arising o f r e s u lt s was undertaken w ith an open mind. A s c r u t in y o f th e r e s u lt s in d ic a t e d a method whereby th e graphs cou ld be d iv id e d in t o th r e e t y p e s , nam ely:1.

Graphs which in a l l a s p e c ts gave a c o m p le te ly normal p ic tu r e over th e

w hole p e r io d o f s i x m onths.

This group com prised t h ir t e e n (13) c a s e s .

To t h i s group was added th e c a s e s where th e p eriod was l e s s than s ix months b u t where th e graph was in a l l a s p e c ts co m p letely normal ov er th e p erio d in v e s tig a te d .

This group com prised fo u r c a s e s .

Thus group one co n ta in ed se v e n te e n (17) c a s e s . 2.

Graphs which gave in c r e a se d sed im en ta tio n r a t e s o v er v a ry in g p e r io d s o f

tim e during th e s i x months but where an a c t iv e in te r c u r r e n t i n f e c t i o n was p re­ se n t.

T his group com prised t h ir t e e n (13) c a s e s .

These in te r c u r r e n t i n f e c t i o n s

were m ain ly r e s p ir a t o r y in ty p e , v a ry in g from a sim p le coryza to an a cu te bronch­ i t i s , i n one ca se a p y e l i t i s was p r e s e n t in a fem ale c a s e .

This h ig h in c id e n c e

o f in te r c u r r e n t i n f e c t i o n in a r e l a t i v e l y sm a ll s e r ie s o f c a se s i s e x p la in e d by the f a c t t h a t th e y were in an advanced s t a t e o f Parkinsonism and, w ith the e x c e p tio n o f a very few c a s e s , were b e d -r id d e n .

Another f a c t o r c o n tr ib u tin g to

r e s p iisa to r y i n f e c t i o n was the r i g i d i t y o f th e whole s k e l e t a l sy stem , in c lu d in g th e c h e s t , p resen ted by th e s e c a s e s .

The s i x month p erio d during which a l l c a s e s

were in v e s t ig a t e d began in January and so r e s p ir a t o r y i n f e c t i o n s were more com­ mon during th e e a r ly p a r t o f th e p e r io d .

Many o f th e c a s e s showed a c h ro n ic

b r o n c h it is a s th ey had been b ed -rid d en f o r many y ea rs and had had a r e s p ir a to r y i n f e c t i o n each w in te r .

The two c a s e s which d ied d id so from Broncho-pneumonia

which i s th e commonest term in a l e v e n t in th e l i f e o f a c a se o f P o s t - B n c e p h a lit ic P a rk in so n ism .

3*

This group t h e o r e t i c a l l y c o n ta in s th o se c a s e s where a d istu rb a n ce o f s e d i­

m en tation r a te e x is t e d in th e absence o f an a c t iv e in te r c u r r e n t i n f e c t i o n . No such c a s e s were o b se r v e d . From tn e above th ree paragraphs i t w i l l be seen t h a t , i n t h i s s e r i e s o f t h i r t y (3*^) c a s e s o f P o s t - E n c e p h a lit ic P ark inson ism th e blood se d im en ta tio n r a t e was normal e x c e p t in th o se c a s e s where an a c t iv e in te r c u r r e n t i n f e c t i o n was p r e s e n t .

In each sjich ca se th e in f e c t i o n was s u f f i c i e n t to e x p la in th e

in c r e a se d b lood se d im en ta tio n r a t e . For i n t e r e s t , a su rv ey a t one in s t it u t io n ,w h ic h a d m itted c a s e s o f P o s tE n c e p h a litic P a rk in so n ism ,to determ ine the cau se o f d eath ,w as c a r r ie d o u t . Out o f tw en ty (20) c a s e s e ig h t were c la s s e d as dying from Broncho-pneum onia, n in e gave no o th e r cau se o f d eath than P c s t - E n c e p h a lit ic P ark in son ism , w h ile th r e e c a s e s d ied from c a r d ia c f a i l u r e .

BIBLIOGRAPHY. 1.

Lorenz H.F.

S ed im en ta tio n R ate i n E n c e p h a lit is . D eutsche M ed izin iscn e V /o ch en sch rift. V o l. 50 1924. p .p . 752/753*

2.

P a u lia n & Toraovici.

S ed im en tation T e sts in P o s t-E n c e p h a litic P a rk in so n ism . J o u rn a l o f the American M edical A s s o c ia tio n . V o l. 81 p .p . 2067.

3.

Lorenz & B erg er.

S ed im en ta tio n T ests i n Epidem ic E n c e p h a lit is . J o u rn a l o f th e American M edical A s s o c ia t io n . V o l. 33 p .p . 15s *

4.

Hachez E.

S ed im en ta tio n Rate in E n c e p h a litis L e th a r g ic a . D eutsche M ed izin isch e W o ch en sch rift. No. 7 1923* p .p . 2 1 7 .

SUMMARY OF TOTAL PROTEIN CONTENT RESULTS. For p u rposes o f a n a ly sin g th e t o t a l

p r o te in

co n ten t o f th e

examined two stan d ard s were u se d ,

nam ely,

th e average o f

flu id s

c e r e b r o -s p in a l

the c o n tr o l 1 s e r i e s r e s u l t s and th e normal f ig u r e s as g iv e n by M e r r itt & ^remont S m ith ,

These r e s u lt s were 1. 2.

C ontrol s e r i e s ; average t o t a l p r o te in c o n te n t Average normal t o t a l p r o te in c o n te n t

-

- 3 4 ,9 0 mgm. p er

100 c c . C .S.F

4 5 ,0 0 mgm. p er

100 c c , C .S .F

S in ce th e s e two r e s u lt s agree M e r r itt and Fremont S m ith 's c l a s s i f i c a t i o n was fo llo w e d as under : A.

Norm al.

- 4 5 mgm. p er 100 c , c . C .S .F . o r l e s s ,

B.

S l i g h t l y in c r e a s e d .

- 4 5 /7 5

C.

M oderately in c r e a s e d .

-

B.

G rea tly in c r e a s e d .

- 100/500 mgm. per 100 c . c . C .S .F .

E.

Very g r e a t l y in c r e a s e d .

- 5 ^ 0 /3 * 5 ^ mgm. per 100 c . c . C .S .F .

P©r 100 c , c . C .S .F . ragm. per 100 c . c . C .S .F .

The c a s e s were d iv id e d in t o f i v e groups as ab ove.

Any r e s u lt showing red

b lo o d c o r p u s c le s (R. B. C. ) in the c e l l count was n o t c o n s id e r e d . Group A.

Those c a s e s i n which a l l c e r e b r o -s p in a l f l u i d s were norm al. Those c a s e s numbered n in e te e n ( t 9) *

Group B.

Those c a s e s i n which one or more specim en c e r e b r o -s p in a l f l u i d showed r e s u l t s from 45 to 75 cigm. per 100 c . c , C .S .F , Those c a se s numbered fo u r ( 4 ) •

Group C.

Those c a s e s i n which one or more specim en c e r e b r o -s p in a l f l u i d showed r e s u l t s from 75 to 1o0 mgm. p er 100 c . c . C. S. F. Those c a s e s numbered one ( 1 ) .

Groups D. & E. c o n ta in e d no c a s e s . From th o se r e s u l t s o n ly f i v e t o t a l p r o te in c o n te n t.

(5 ) c a s e s showed an abnormal p ic tu r e in th e

Those c a s e s were Case 1, 3>

23> and ca se 5»

I n none

o f th o se c a s e s was th e in c r e a s e o f t o t a l p r o te in co n ten t very marked.

BIBLIOGRAPHY. 1,

M e r r itt & Fremont S m ith .

The C e r e b r o -sp in a l F lu id .

1 s t . E d it .

1937-

p .p . 3 0 .

Page 5 6 • SUMMARY OF ALBUMEN CONTENT RESULTS. For p u rposes o f a n a ly sin g r e s u lt s o f th e albumen c o n te n t o f th e cereb ro­ s p in a l f l u i d sp ecim en s, one standard was used ;

t h i s was th e average albumen

c o n te n t o f th e c o n tr o l s e r i e s which was tw enty seuen (27) mgm. per 100 c c . C. S. F. This d iv id e d th e c a s e s in t o two g ro u p s, th o se above and th o se b elow the average o f c o n tr o l s e r i e s . Group 1 .

Those c a s e s in which the albumen c o n te n t was l e s 3 than th a t o f the average o f th e c o n tr o l s e r i e s .

Group 2 .

This group co n ta in ed n in e (9) c a s e s .

Those c a se s in which th e albumen c o n te n t o f one o r more c e r e b r o -s p in a l f l u i d s was g r e a t e r than th e average o f th e c o n tr o l s e r i e s . co n ta in ed f i f t e e n

This group

(1 5 ) c a s e s .

Any r e s u l t showing red b lood c e l l s

(R. B. C. ) in th e c e l l

count was n ot

c o n s id e r e d • From th o se r e s u l t s f i f t e e n c a s e s ( 1 5 l showed an abnormal p ic tu r e in th e albumen c o n te n t a s compared w ith th e c o n tr o l s e r i e s average r e s u l t .

The h ig h e s t

r e s u l t i n th e c o n tr o l s e r i e s , h avin g ig n o red th e r e s u lt s which showed red blood c e l l s ( R. B . C . ) , was 3& nqgm. P©r 100 c c . C. S. F.

Taking t h i s f ig u r e as th e upper

l i m i t o f ab n orm ality group 2 . r e s o lv e d i t s e l f in t o a fu r th e r two c a t e g o r ie s as u n d er:A.

Those r e s u l t s w ith in th e h ig h e s t normal f ig u r e in th e c o n tr o l s e r i e s . Those numbered tw e lv e (12) c a s e s .

B.

Those r e s u l t s above th e h ig h e s t normal f ig u r e i n th e c o n tr o l s e r i e s . Those numbered th r e e (3) c a s e s . From th o se r e s u l t s o n ly th r e e c a s e s showed a d e f i n i t e l y abnormal p ic tu r e

i n th e albumen c o n te n t o f th e c e r e b r o -s p in a l f l u i d . and ca se 7 »

Those c a s e s were Case 5> 6

Page 5 7 .

SUMMARY OF GLOBULIN CONTENT RESULTS. For th e purposes o f a n a ly sin g r e s u lt s o f th e g lo b u lin c o n te n t one sta n d ­ ard was used;

t h i s was th e average g lo b u lin c o n te n t o f th e c o n tr o l s e r i e s w h i c h

was 7 .6 5 mgm. per 100 c c . C. S. F. This d iv id e d th e c a s e s in t o two g ro u p s, th o se above and th o se below the average o f th e c o n tr o l s e r i e s . Group 1•

Those c a s e s in which th e g lo b u lin was l e s s than th a t o f th e average o f th e c o n tr o l s e r i e s .

This group co n ta in ed fo u r (4) c a s e s .

Group 2 . Those c a s e s in which the g lo b u lin c o n te n t o f one or more c e r e b r o -s p in a l f l u i d s m s g r a a te r than th e average o f th e c o n tr o l s e r i e s .

This group

co n ta in ed tw en ty ( 2 0 ) c a s e s . Any s id e r e d . The c c . C.S.F..

r e s u l t showing rod blood c e l l s ( P. B. C. ) in th e

c e l l count wo.sn ot con­

T his reduced group 2. to n in e te e n (19) c a s e s . h ig h e s t g lo b u lin co n ten t in th e c o n tr o l s e r ie s Taking t h i s r e s u lt as

was 1 6 .4 0 mgm.per 100

the upper l i m i t o f n o rm a lity group 2 . was

fu r th e r su b d iv id ed in t o a fu r th e r two c a t e g o r ie s . A.

Those c a s e s in which th e r e s u lt s o f g lo b u lin co n ten t were w ith in t h i s upper l i m i t o f n o r m a lity . Those c a s e s numbered s ix t e e n ( 1 6 ) .

B.

Those c a s e s in which one or more c e r e b r o -s p in a l f lu id s showed h ig h er g lo b u lin c o n te n t than th e h ig h e s t g lo b u lin c o n te n t o f th e c o n tr o l s e r i e s . Those c a s e s numbered th ree (3 )• From th o se r e s u l t s o n ly th r e e c a s e s showed an abnormal p ic tu r e in th e g lo b u ­

l i n c o n te n t o f the c e r e b r o -s p in a l f l u i d .

Those c a s e s were Case 4 , 5 an^ ©a se 13*

SUMMARY OF ALBUMEN-GLOBULIN RATIO RESULTS. For purposes o f a n a ly sin g r e s u lt s o f th e alb u m en -g lo b u lin r a t io one s ta n ­ dard was u sed ;

t h i s was tne a v era g e-a lb u m en -g lo b u lin r a t io o f th e c o n t r o l s e r i e s ,

which was 3 *59/ 1 • This d iv id e d th e c a s e s In to two g ro u p s, th o se above and th o se below th e average o f th e c o n tr o l s e r i e s . Group t •

Those c a s e s which th e a lb u m en -g lo b u lin r a t io was l e s s than t h a t o f the average o f th e c o n tr o l s e r i e s .

Group 2 .

This group co n ta in ed e ig h t (3) c a s e s .

Those c a se s i n which th e a lb u m en -g lo b u lin r a t io o f one or more cereb ro ­ s p in a l f l u i d s was g r e a te r than th e average o f th e c o n tr o l s e r i e s .

This

group co n ta in ed s ix t e e n ( 16) c a s e s . Any r e s u lt showing red b lood c e l l s (R. B. C. ) i n th e c e l l count was n o t con­ s id e r e d . The h ig h e s t a lb u m en -g lo b u lin r a t io in th e c o n tr o l s e r ie s was 6 . 5/ 1 .

Taking

t h i s r e s u l t as th e upper l i m i t o f n o r m a lity , group 5 was fu r th e r su b d iv id ed and th o se r e s u lt s above t h i s f ig u r e r e ta in e d as b e in g abnorm al. A.

Those c a s e s in which r e s u lt s o f alb u m en -g lo b u lin r a t io were w ith in t h i s upper l i m i t o f n o r m a lity . Those c a s e s numbered fo u r te e n ( 1 4 ) .

B.

Those c a s e s in which one or more c e r e b r o -s p in a l f lu id s showed a h ig h e r albumeng lo b u lin r a t io than th e h ig h e s t a lb u m en -g lo b u lin r a t io o f th e c o n tr o l s e r i e s . Those c a s e s numbered two ( 2 ) . From th o se r e s u lt s o n ly two c a s e s showed an abnormal p ic tu r e i n th e albumen-

g lo b u lin r a t io o f th e c e r e b r o -s p in a l f l u i d .

Those c a se s were Case 5 anc* ca se 19*

SUMMARY OF CELL COUNT RESULTS. For p u rposes o f a n a ly s in g the o e l l cou n t o f th e c e r e b r o -s p in a l f l u i d s in t h i s s e r i e s o f c a s e s , th e b a s is was p a r t ly the r e s u lt s found in the c o n tr o l s e r i e s and p a r t ly th e fin d in g s g iv e n in th e standard monographs.

From th o se

so u rces th e c a s e s were d iv id e d in t o th r e e g ro u p s. Group 1•

Those c a s e s in which th e c e l l counts were between 0 and 5 c e l l s per c . m.m.

Group 2 .

Those c a se s in which one or more c e r e b r o -s p in a l f l u i d s showed a c e l l cou h t between 5

Group 3*

10 c e l l s per c u . m.m*

Those c a s e s in which one or more c e r e b r o -s p in a l f l u i d s showed a count o f o v er 10 c e l l s per c u . m.m. Group 1. c o n ta in ed tw en ty -o n e (21) c a s e s .

Group 2. con tain ed th ree (3) c a s e s . Group 3* c o n ta in e d no c a s e s . Any r e s u l t w hich showed red b lood c e l l s

( S . B. C. ) in th e c e l l count was not

c o n s id e r e d . In th e c o n tr o l s e r i e s th e h ig h e s t c e l l count was 10 c e l l s per cu.m .m . Taking t h i s as th e upper l i m i t o f n o rm a lity none o f the c a s e s under i n v e s t ig a t i o n was abnormal in r e s p e c t o f the c e l l c o u n t.

T his a g rees w ith M e r r itt & Fremont

1 Smith

who c o n s id e r 3 to 10 c e l l s p er cu.m.m . s u s p ic io u s and o v er 10 c e l l s as 2 pathognomonic o f an a c t iv e l e s i o n o f th e b ra in o r m en in ges. L evinson a g ree s

a ls o w ith th o se sta n d a r d s. As judged by th e c e l l count none o f th e s e r i e s o f th e o a se s showed ev id en ce o f an a c t iv e l e s i o n o f th e b r a in .

BIBLIOGRAPHY.

1.

M erritt & Fremont Sm ith.

The C ereb ro-sp in al F lu id .

2.

L evinson .

The C erebro-spin al

1 s t . E d it. 1937P .? * 57-

F lu id . 3 rd . E d it. 1929* p . p . 136.

SUMMARY OF PANDY TEST RESULTS. For th e purposes o f a n a ly sin g th e Pandy t e s t r e s u lt s two group o f o a ses were form ed. Group 1 .

NEGATIVE. (a)

Gases which showed n e g a tiv e Pandy t e s t s throughout a l l cereb ro ­ s p in a l f l u i d s exam ined.

(b) Group 2 .

Cases which showed,,trac