Folia Psych ia t r i a et Neurologica Japonica. Vol. 12, No. 2, 1958

FAMILTAI, PARALYSIS AGITANS JUVENILIS. A CLINICAL, ANATOMICAL AND

GENETIC STUDY

BY Yukio Ota and Sawako Miyoshi

Neuro-Psychiatr ic D e p a r t m e n t , Osaka Red Cross Hosp i t a l (D i rec to r : 1'. O t u ) .

Osamu Ueda

S e u r o - P s y c h i a t r i c Depar tmen t . K y o t o IJnivers i ty Schoo l of hledicinr . K y o t o (Di rec to r : Prof. Af. dfzrruknmi)

Torayoshi Mukai and Akio Maeda

Neuro-Psych ia t r i c Depar tmen t . O s a k a C i ty Un ive r s i ty Scliool o f Medicine. Osaka I P rof . S. 'YuRu)

A s a rule, pa ra ly i s ngitans is one of the d.i.;eases of presenile nvd smile n!ge, not developping among !.oung people. l lut ;: few cases of a jurcni le typc

agitans have heen reported. Willige (12 cases), Hunt (1 cases), Hall, Tromner. van Bogaert, Biondi, Oesterreich, and Ueda h a w reparted a jul.enilc t!.pe of parkinsonian and parkison-like cascs. Rut. as Gampev has mentioned. no postencephalitic parkinsonism \\.as known a t Willige's time and his pathological-anatomical considerztions were too old-fashioned to he acceptable tod;i!.. Cases of Hall, Tromner, Oesferveich, a d Ueda are lacking autops!. I t seems rather advisable to lenve these cnscs o c t of consideration, because some extrap! raniidal diseascs. such as Wilson's dixasc. ma!- he confused with paralysis agitans \vhen judged merely on n (1inic::I bnsis. Biondi's case is atypical in clinical and anatomical aspects. Hunt 112s recorted 4 cases, three of which, hon.ever, are without autopsy. 'I'hcrcforc. strictly speaking. on!!- 2 cases of Hunt and van Bogaerf arc justified t J belwik into the categor!' of juvenile paralrsis agitans. Hut, thcsc 2 c ; x s might possihly be due to a latent enceplia- litis, hecnusc they are solitar!. i nc t f ; m i l i n l I cascs. l h e present report deals \vith juvenile t!.Fe of paralysis agitans developed in a family followed by anatomical and cenetic studies.

Case Heports

Case I. '4. Shinrizrr. o fernale, bo rn in 1909. has been under o u r obse rva t ion since May . 15, 1954. At 13 years of a g e she began t o h a v e difficulty in w a l k - ing. bccause legs became stiff. A t 1 4 yea r s of age h e r r ight leg began t o s h a k e ; a t 70 yea r s of age he r a r m s became t remulous, too. T h e n , stiffness a n d t r e m o r g rew worse. I n he r t h i r t i e s she had much difficulty in walking

Received f o r publ icat ion March 6, 1958.

113 Fa mi 1 i a 1 Para 1 y s i s a g i t an s j u v c n i 1 is

a n d Littering w o r d s ; s ince t h e beginning of fou r t i e s she h a s been compel led t o s t a y in bed.

Phys ica l e x a m i n a t i o n (1954): Rig id f r o m head t o feet , s h e showed a t y p i c a l advanced pa rk inson ian f ace w i t h immobi le , mask-like express ion a n d r h y t h m i c a l t r emor i n t h e limbs. T h e f inge r s were in p i I l - ro l l ing t r e m o r a n d t h e f ee t in a pos i t ion of pes equinovarus . She could no t sit and s t and f o r herself . She showed a seve re d i s tu rbance of myo ton ic n a t u r e i n a r t i cu la t ion , bcsides s ia lor rhoea . - I t pass ive movemen t of t h e ex t r emi t i e s t h e so-called cog-wheel phenomenon o f Negro was observed. T h e pup i l s were no rma l in size and f o r m a n d reac ted well t o l i gh t , h a v i n g a good accommod- a t ion . Kaiser-Fleischer’s cornea l r ing failed. T h e eyeba l l s moved well w i thou t nys tagmus . I n n e r v a t i o n o f f ac i a l ne rve was symmetr ica l . T h e tongue look- ed tri:mulous, b u t w i thou t any s ign of paresis, n o r t h e r e was a n y pares i s of t h e so f t palate. T h e tendon and per ios ta l reflexes of a r m s were weaker t h a n normal , whi le t h e knee-jerk and Achilles j e rk were normal . T h e p l a n t e r reflexes showed a flexor response. No a b n o r m a l i t y was seen in t h e sense of t o u c h , pa in , musc le , t empera tu re , and jo in t and stereognosis. Phys ica l e x a - mina t ion revealed no abnorma l i t i e s i n t h e h e a r t , lungs, and abdomina l viscera. Psychologica l ly . marked b radyphren ia was seen wi thou t a n y s ign of de t e r io ra t ion of mind a n d intell igence.

T h e cerebrospina l fluid was no rma l in co lour , p ressure , ce l l coun t , and g lobul in reactions. Wassermann reac t ion in blood and cere- brospina l fluid was nega t ive . Cu and Fe in t h e blood were 125r/d!and 103r/ d’, re5:pectively. A de ta i led examina t ion of t h e func t ion of l iver revea led no i m p o r t a n t abnormal i t ies . Biopsy of t h e l i ve r was per formed, demonst ra - t i ng en t i r e ly no rma l findings ( S t a i n i n g w i t h hematoxyl in-eos in) .

Case 11. H. Shiinizu, t h e e lder s i s te r of case I , bo rn in 1907, had been cont inuous ly observcd since Oct . 10, 1954 t i l l h e r d e a t h wh ich occurred on 16 Auzus t , 1956. A t t h e beginning of t w e n t i e s s h e began t o n o t e some diffi- c u l t y n p e r f o r m i n g de l i ca t e movements , such a s s ewing ; a t 22 yea r s of age she became s t i f f , h a v i n g t roub les in wa lk ing ; a t 23 yea r s of age she was ope ra t ed o n (p re sumab ly s y m p a t h c c t o m y ) wi thou t any c l in ica l improvement . . I t t h e s a m e i ime h e r r igh t hand began t o shake. T r e m o r a n d stiffness g r e w worse.

Phys ica l examina t ion (1954): S h e w a s of sma l l s t a t u r e and undernou- r i shed , present ing typ ica l pa rk inson ian s y m p t o m s which were s l i gh te r t h a n in case I. S h e became rigid f r o m head t o fee t , w i t h t y p i c a l pa rk inson ian immobi l e face , ga i t , a n d a t t i t ude . T h e r e was a t y p i c a l pa rk inson ian t r emor all ove r he r f o u r l imbs ; w i t h f ee t in a pos i t ion of pes equinus. T h e cog-wheel phenomenon of Nepro was observed in t h e ex t remi t ies . T h e pup i l s were n o r m a l in size a n d f o r m and reac ted well to l igh t w i t h a good accommodat ion . Kuiser- Fleisclier’s r ing failed. T h e eyeba l l s moved well w i t h o u t nys t agmus ; i nne rva t ion of fac ia l nerve was symmet r i ca l . T h e tongue was t remulous , bu t w i thou t a n y s ign of paresis. s ign of pares i s f a i l i ng i n t h e so f t pa la te . T h e tendon and per ios ta l reflcxes of t h e a r m s were no rma l , so were knee- je rk a n d A,-hilles jerk. T h e p l a n t a r reflexes showed a flexor response. N o abnor - ma l i t i c s were seen in t h e sense of t ouch , pa in , t empera tu re , muscle, and jo in t and stereognosis. A phys ica l examina t ion revea led n o abnorma l i t i e s i n t h e h e a r t , I u ngs, and a b d o m in a 1 was marked . w i thou t sign of de t e r io ra t ion o f mind a n d intell igence. Biopsy of the l iver was made , demons t r a t ing en t i r e ly no rma l findings.

In J u n e 1956 she developed f eve r ( a b o u t 38°C) w i t h nausea a n d vomi t - ing. Var ious k inds of t r e a t m e n t s were not successful. S h e died on 16 Augus t , 1956. .%utopsy was pe r fo rmed by Dr. Kawai wi th t h e e s t ab l i shmen t of a n ana toni ica l d iagnos is of “acu te monocy t i c leukemia”.

Case 111 K. Shimizir (F ig . I ) , t h e younger b r o t h e r of case I and 11, born i n 1918, h a s been under o u r obse rva t ion s ince Nov. 20, 1954. A t 12 yea r s of a g e h e became du l l i n action. He was ope ra t ed on (p re sumab ly sympa thec -

Lnbora to ry t e s t s :

S h e could no t s t and and walk , bu t could sit f o r herself .

v i sc e r a. Psycho 1 o g ic a 11 y , brad y p h re n i a

114 Y. O t a e t 0 1 :

F i g . 1 . Case 111.

t o m y ) a t 12 y e a r s of a g e , vc i thout a n y c l i n i c a l i m p r o v e m e n t . A t 20 y e a r s of age s h a k i n g s r t o n t h e l e f t leg. t h e n . o n r i g h t leg a n d h a n d . T h e s e s y m p - ton is g r e i r w o r s e t o w a r d s t h e e n d of t w e n t i e s . w h e n h e h a d diff icul ty i n r a t i n g a n d u t t e r i n g words .

i c a l e x a m i n a t i o n (1954): H e s h o w e d a t y p i c a l f a c e of p a r a l y s i s a n d r h y t h m i c a l t r e m o r in h i s l o w e r l i p a n d t o n g u e . T h e r e w e r e

t y p i c a l p a r k i n s o n i a n a t t i t u d e a n d g a i t w i t h r h y t h m i c a l t r e m o r in t h e f o u r e x t r e m i t i e s s h o w i n g p i l l - r o l l i n g t r e m o r in f ingers a n d p e s e q u i n o v a r u s p o s i t i o n in f e e t . S y m p t o m s i n h i m w e r e t h e m o s t s e r i o u s a m o n g 3 s i b l i n g s ; h e c o u l d n o t t u r n o v e r i n b e d , a t t h e s a m e t i m e s h o w i n g a m a r k e d d i s t u r - 1)anct. in a r t i c u l a t i o n . ;I c o g - w h e e l p h e n o m e n o n of .Vegro was o b s e r v e d a t p a s s i v e m o v e m e n t s of f o u r l imbs . T h e p u p i l s w e r e n o r m a l i n s ize a n d f o r m a n d r e a c t e d wel l t o l i g h t w i t h g o o d a c c o m m o d a t i o n . T h e Kaiser-Fle isrher’s r i n g f a i l e d ; e y e b a l l s m o v e d w e l l w i t h o u t n y s t a g m u s ; f a c i a l i n n e r v a t i o n p r o v e d n o r m a l . T h e t o n g u e w a s t r e m u l o u s b u t w i t h o u t a n y s i g n of p a r e s i s ; t h e s o f t p a l a t e m o v e d n o r m a l l y . T h e t e n d o n a n d p e r i o s t a l re f lexes of t h e a r m s . k n e e - j e r k a n d A c h i l l e s j e r k w e r e n o r m a l . T h e p l a n t a r re f lexes s h o w e d a n o r m a l response . No a b n o r m a l i t i e s w e r e seen i n t h e s e n s e of t o u c h , p a i n , t e m p e r a t u r e , m u s c l e , a n d j o i n t a n d s t e r e o g n o s i s . T h e p h y s i c a l e x a m i n a t i o n r e v e a l e d n o a b n o r m a l i t i e s i n t h e h e a r t . l u n g s . a n d a b d o m i n a l v i scera . Psy- c h o l o g i c a l l y m a r k e d b r a d y p h r e n i a w a s s e e n b u t t h e r e f a i l e d s igns of d e t e - r i o r a t i o n of m i n d a n d i n t e l l i g e n c e . B i o p s y of l i v e r w a s m a d e . d e m o n s t r a t i n g e n t i r e l y n o r m a l f indings.

Patho-Anatomical Findings of Case 11 A% p l e u r a l a d h e s i o n of lesser e x t e n t w a s f o u n d i n t h e r i g h t p l e u r a .

M o n o c y t i c - l e u k e m i c c h a n g e s w e r e o b s e r v e d i n t h e l i v e r . k i d n e y s . b o n e m a r - r o w s . s p l e e n . a n d p h a r y n x . T h e l i v e r w a s s o m e w h a t e n l a r g e d on a m a c r o s c o p i c e x a m i n a t i o n . h l i c r o s c o p i c a l l y , t h e r e w e r e o b s e r v e d a s l i g h t d e g r e e of c o n g r s t i o n a n d m o n o c y t i c i n f i l t r a t i o n . O t h e r w i s e . n o p a t h o l o g i c a l , e s p e c i a l l y c i r r h o t i c . c h a n g e s w e r e o b s e r v e d in t h e l i v e r ( F i g . 2).

,%facroscopical e x a m i n a t i o n of t h e b r a i n : N o a t r o p h i c c h a n g e s w e r e s e e n o n t h e s u r f a c e of c e r e b r a l h e m i s p h e r e s ;

t h e m e n i n g e s l o o k e d e n t i r e l y n o r m a l . O n t h e c o r o n a l s e c t i o n no a t r o p h y w a s o b s e r v e d in t h e b a s a l g a n g l i a . On t h e c r u s c e r e b r i , c u t a t r i g h t a n g l e s to t h e d f e y n e r t ’ s a x i s , t h e s u b s t a n t i a n i g r a d e m o n s t r a t e d a m a r k e d d i s c o l o r a - t i o n .

l\ficroscopircll examination rf t h e brain : 1 ) M e n i n g e s : T h e r e was n o p i a l t h i c k e n i n g n o r c e l l i n f i l t r a t i o n . 2 ) C o r t e x c e r e b r i : G e n e r a l l y , c e l l a r c h i t e c t u r e s t o o d n o r m a l . No p a t h o l o -

Familial P i r z lys i s agitans juvenilis 115

Fig. 2, Live r

gical changes were seen in t h e nerve cells, especially in Betz’s g ian t cells. ’The gl ia cells showcd n o increase in number.

3) Of t h e basal gang l i a : a ) P u t a m e n : T h e large gangl ion cel ls showed decrease in n u m b e r ; w i t h neu ronophag ia seen i n some of them. T h e nuclei were s i t ua t ed eccentr ic and AiszI-substance appea red paler in t h e g rea t e r pa r t of t h e l a rge gang l ion cells. No pa tho log ica l finding was obtained in t h e sma l l gangl ion cells, whi le t h e gl ia cells showed a s l ight increase in number.

Disappearance of gangl ion cells was observed in t h e l a t e ra l p a r t of i n t e rmed ia t e divis ion of globus pal l idus [Fig. 3). I n the

b) Globus pal l idus:

Fig. 3. Globus pall idus

remaining cell bodies so-called ‘* zersprungene ” ’‘ wabige ” col lapsc toge the r w i th s imple a t r o p h y was seen. T h e gl ia cells showed a s l ight increase in number. T h e r e was observed calcification of t h e blood vessels and of capi l - lar ies on t h e median division 1 Kossa-methode).

c ) Nucleus c a u d a t u s : A phenomenon of neuronophagia was seen in t h e large gangl ion cells.

d ) T h a l a m u s op t i cus : T h e r e were seen a number of gangl ion cells w i t h 2 nuclei.

e) Hypo tha lamic gangl ia and f ) T h e ansa l en t i cu la r i s : ’There was n o pathological change.

4) Subs tan t i a n i g r a : T h e melanin-containing cells decreased in number

T h e gl ia cel ls showed a n increase in number.

116 Y. O t a et a l :

r emarkab ly in t h e zona compac ta (F ig . 4 a. b.), whi le the r ema in ing cel ls possessed sh runken bodies, melanin pigments c l inging to cel l bodies. S o m e of t h e m were on the b r ink of col lapse (Fig. 5). T h e cel ls d i sappea red in g roups i n t h e rostra1 p a r t m o r e t h a n in caudal . Among ce l lg roups t h e r e

Fig. 4 , a. Substant ia nigra of Case 11.

Fig. 4, b. Normal substant ia nigra ( t h e same por t ion n i t h Fig. 4. a )

Fig. 5.

Familial Paralysis agi tans juvenilis 117

were observed some wi th cells re la t ively well preserved. T h e gl ia cel ls showed a s l i gh t increase in number wi thou t a marked increase of gl ia fibers.

5) Cerebel lum: No pathological changcs were demons t r a t ed in t h e nucleus dentatus . I n t h e small p a r t of cerebel lar co r t ex near t o medul- l a ry body, g ranu le cells of g ranu la r l aye r were found decreased in number. No pathological changes were seen in Purkinje’s cells and molecular layer. No demyelinat ion was observed in Weil-stain as l i t t l e a s pathological changes in Holzer-st a i n.

6) T h e o l iva ry nuclei and t h e red nucleus were ent i re ly normal. 7) Locus coeruleus: -4n axonal react ion ( “Pr imare Reizung Nissl’s”) was

observed in t h e melanin-containing cells (Fig. 6).

Fig. 6. T h e melanin-containing cells of locus coeruleus.

Resume of Clinical and Anatomical Findings

I n thc present thrce cases. the disease develops before 20 years of age, with muscular rigidity as the initial symptom. Three to eight years later tremor develops. Muscular rigidity and tremor become worse, finclly resulting in serious defect. Pathological finding is missed here in pyramidal tract, in sense sphere and in mental state cxceFt niarkcd brzdyphrenia. Histological examination of the punctuatccl tissues of livcr r;i;cals an entirely normal finding in all three cases ; postmortem examinztion of thc hepatic tissues of case I 1 is equally free from any sign of cirrhosis An anatomical examination of the brain of the latter case reveals the following findings :

1) Discoloration of substanti:. nigra is observed even on macroscopical exami- nation. 2) RIany melanin-containing ncrve cells of substantia nigra are atrophic, some of them even effaced. T h e fact that there are some cell-groups with relatively well preserved nerve cclls seems to speak against assumption of posten- cephalitic parkinsonism <Hallevvorden). 3 ) Nerve cells of locus coeruleus a re atrophic, some of t h e n showing c picture of “Primiire Keizung of Nissl”. 4) Nerve cells of pallidurn and large ncrve cells of neostriatum are slightly atrophic. 5) Disappcarance of Cranulc ccll.; is obscrved in the small par t of ccrebellar cortex. According to Lewy, disaplzcarznce of granule cells and Purkinje’s cells of cere- bellar cortex is one of common findings in classical paralysis agitans.

Comments on Anatomical Findings

A t present there a re some disagreements among authors about the patho-

118 Y . O t a et a l :

anatomical changes of classical paral!.sis azitans. Foix and Nicolesx have pointed out that pathological changes in pallidurn and substantia nigr: are the most important for paralysis agitans. T h e y found some pathological changes in the cells of nucleus vagi dorsalis, formatio cupuliformis, and formntio reticul- aris, too. Hassler has reported tha t chanLes in zona compacta of substantia nigra a re the most important for parnlj-sis agitans. He found Fzthological changes in locus coeriileus, nucleus vagi dorsalis, and substantia innominzta. t30,

while he attached no importance to pallidum. Klaue has regarded the pitholo- gicnl changes in black zone ischivarze Zone) of substantia nigra :s the most important in the patholog! of paralysis agitans. He attached no irrportznce to pallidurn either. According to these 3 authors, 7.11 these changes are of ztrophic nnturr . l.‘rom the abol-e-mentioned review, the pathological changes in substmtia nigra shall be looked upon as the most important for the Fatholog!- of c!assiial paraI!.sis agitans.

T \ v o cases of juvcnile t j - x of paralysis agitans with autopsy have been reported in cases of Hurt and oan Bogaevt. I n Hunt‘s case tremor began to drvelop a t 15 years of age. followed by serious and typical picture of paralysis agitans. Nerve cells of globus pallidurn and largr ce!ls (cells of pallidal type’) of neostriatum w e r e diminished in nuniher and the grcater part of the reiraining cells showed various stages of atroph!., together ivith atrophic ch:inges in the nerve cells of nucleus basalis of Meynert . There was a moderate increase of the glia cells in globus Fallidus, putanien, and caudate nucleus in number. in contrast with entirely intact subs- tantia nigra. l l a n y cells of dorsal \-aLal nucleus were deeply pigmented and some of them were densely filled up tvith dark brown pigment granl:!es. T h e strio-hj.pothalamic radiations presented slight hut definite signs of atrophy.

I n oan Bogaevt’s case tremor began to develop a t 7 years of age, growing tvorse up to 30 years of age. The re were tremor of parkinsonian tyFe znd other ex t rapyramidal h! Fe r k ines is, complic a tcd with park insonian a t tit ude ciissing in muscular rigidit!.. I n autopsy the globus pallidiis \\-as found the most seriously damaged, many cells therein standing in \-nrious stages of atroph::. Now, in neostriatum atrophic changes of large ce!ls was observed, in corpus Luysi degenerative changes of nerve cells, and in substantia nigra a reduction in cell number and cell atroph!-, still never so seriJus as in senile and postencephalitic parkinsonian syndrom. Various kinds of degenerative changes were observed in the strio-hypothalamic radiations.

13rietl!- speaking, patholozical change; :re the most serious in pallidum in the above-mentioned 2 CaSCj. though lesion of substantia nigra, considered as the most important in classical parkinsoni2.n >!-ndroni a t present, is lacking in Hunt’s case as well as altogether unimFortant in van Bogaert’s case. Th i s discordance hetw.een the present case and the exes oi Ilunt and van Bogaert might possibly he explained through dissimilarity in the clinical findings, as van Bogaert’s case proceeded without rigidit!. and in Hunt’s case tremor made out an initial symp- tom. An!-horv, it seeins reasonable to maintain that the present case bears much more similarity to classical parkinsonian syndrom than the cases of Hunt and van Bogaert both in clinical and Fath:>logid findings.

Pallidum come second in demand.

T h e case dicd from exhaustion and heart failure.

Comments on Heredity

A t present there are some disagreements among authors about the etiolog!. of classical paralysis agitans. so far as a number of authors consider paralysis agitans as one of the hereditary diseases. Comprehensive studie; on the

Familial Paralysis agi tans juveinlis 119

heredity of paralysis agitans have been made by Kehrer and Mjijnes. Kehrer has reported that paralysis agitans is one of the heredodegenerative diseases at least in its central group and that a dominant mode of heredity is most probable. According to Mjones, paralysis agitans, except solitary cases, is one of hereditary disease; which is transmitted by a mode of monohybrid autosomal dominance. Really, Mjones has found 12 cases of paralysis agitans with juvenile onset (before 20 years old). All these patients belong to families in whkh the onset occurs a t the later age.

I

+ r ~ f + ?

-ad Pa ra lys i s ag i t ans Those personal ly examined in detai l T w i n cases

/’ Fig 7. pedigree of c u r cases

The re were only brief descriptions about the family history in cicej of Hzrnt and van Bogaert. Hunt described “ T h e family history as f a r a5 known \*-as negative: his parents, brothers and sisters a r e all alive and well. No other members of the family have had any disease remotely resembling that from n hich he suffers”. van Bogaert described. ‘’ Issue de p6re tuberculeux, il avait deux fr6res dont un Gtat suspect de tuberculose et une soeur bien portant . . .”

Therefore. these two cases are not analysed sufficiently in detail f r o p a genetic view-point. As stated before, in the above mentionde solitary c a x s an objection can be raised that these cases might possibly- be dealt with a latent encephalities (Klauej .

T h e present study covered 60 relative; of the above three cases studied in detail. Eighteen of them were examined Fersonally in detail from a neuro-psy- chiatric vieH- point (Fig. 7). I n remaining members a detailed descriFtion of mental and physical states is obtaind from their own o r their parents o r siblin_:s. T h e protocol of cach member has been obtained from a t least 2-3 deFendable sources. A thorough study has revealed the results aj follows:

1 ) Th ree were suffering from the same type of disease among 1 1 siblings. 2) Their parents went through the first cousin marriage. 3 ) Their father died of gastric ulcer at 55 years of age. According to Mjo-

nes. the average age of onset of paralysis agitans except solitary case; is 49 2

120 Y. Ota e t a l :

1.4 !.ears. Therefore, they survived a lower borderline for the morbid risk period. 4 1 I n their relatives there is no ca<cs which is suspected to have paralysis

agitans and other extrap!-ramidal diseases. T h e above-mentioned findings demonstrate u i t h a high probability that the

disease is inhcrited in a recessive mode in the family. ?‘his result is inconsistent \I-ith that of Kehrer and Mjones about the classical paralysis agitans. Ru t the same abntrrmal character ma!. be dominant in one pedigree, rcccssivc in another and sex-linked in a third (Ga tes ] . I t is a grneral rulc of genetics that the recessive form of disease is the most virulcnr, the dominant forms the mildest, and the sex-linked forms intermediate (Gates 1 .

-411un has studied a relationship het\r-een the mode of inheritance and severity of diseases in retinitis pigmentosa (1937 I and peroneal atrophy (1938). He (1937) has reported that there are three tl-pes of inheritance : in retinitis pigmentosa dominant. recessive, and sex-linked. Those suffering from a dominant retinitis pigmentosa usually become aware of night blindness bet\I-een the age of 25 and 50, sometimes earlier, with the degeneration gradually progredient. But, of the 38 affected persons in the 2 pedigrees, on[!- one becomes too blur-sighted to work after 50 years of age. In the pedigree \\.hich shows a recessive trait , the affected menihers become blind hefore the age of 25 !-ears. T h e pedigree, in which retinitis pigmentosa has been inherited, as sex-linkcd recessive trait , suggests that this type o f inheritance occupies a place midwal- hetween dominant and recessive inheritance i n the severit!. of the disease. Hence, outbreak of the same phenotypic ahnor- malitics can he due to different genotypes. Among them the dominant form is the mildest, and the recessive the most serious, the latter al\va!s starting in earlier decade. Aflan’s finding seems to explain the disagreement ahout the mode of inheritance hetir-ecn the present pedigree and those of Mjones and Kehrer. Aljiines has reported that his cases of juvcmile paral!.sis agitans belong to families in which onset of the disease took placc: in later age. l l u c h seems still to be left ahout this discordance, hecause the juvenile cases of Illjones are bvithout nutops! and lacking in a detailed clinical description.

Summary

l’hree familial cases of juvenile tyFe of paral! sis agitans have hecn reported

1 I ‘4 parkinsonian s!mdrom not due to a latcrit encephalitis can develop bcfore

2 ) Its clinical and anatomical findings are \-er!. similar to that of classical

31 By a detailed genetic stud!- i t is dcrnonsrrated that the disease is inhcrited

with the foIlo\c.ing results :

20 !-ears of age.

paral! sis agitans.

in a recessive modc.

T h e au tho r ’ s hea r t f e l t t h a n k s are due t o Prof . A!litsudo, Prof . I’oshida. a n d Dr. Kaunai f o r t h e i r kind advice in genet ics a n d p a t h o l u g i c a l a n a t o m y in comple t ing th i s report .

Literature 1 ) ; l l / n n : Arch. of Ophthal . , 18, 1937. .:) :Il /un : Eugenic. News, 23. 1938. 3) B i o n d i : Z. Neur.. 140. 1932. 4) Fozx ef Nirolesco: Les N o y a u x Gri s C e n t r a u x e t la Region Mesencephalo-

sousopt ique, 1925, Paris.

Familial Paralysis agitans juvenilis 121

Camper : Gates: Human Genetics, 1948, N e w York. H a l l : Hassler: J. Psychol. u. Neur.. 48, 1938. Hallervorden : Scholz's Handbuch d. Spez. Pathol. Anatornie. Bd. 8. 1957, Berlin. Hunt : Brain, 40 1917-191f3. Kehrer: Arch. f. Psychiatr., 91, 1930. KZaue: Arch. f. Psychiatr.. 111. 1940. L e w y : -Mjd'nes: Paralysis agitans. Suppl., Act. Psychiatr . Neur. Scand.. 1919. Oesterreich : 'Med. Klin., 32, 1936. TrBmner: Zbl. f. Neur. u. Psychiatr . . 43. 1926. Ueda : Neur. e t Psychiatr . Jap,. 58, 1956 (Japanese). van Bogaert: Revue Neur., 37, f i , 1930. Will ige: 2. Neur., 4. 1911.

Bumke-Foerster's Handbuch de r Neurologie, 16, 1936.

La DCgCnBrescense Hepato-Lenticulaire, 1924, Paris.

Die Lehre von Tonus und d e r Bewegung. 1923, Berlin.