Vet Path ol 28:536-538 (1991)

Myeloencephalopathy with Rosenthal Fiber Formation in a Miniature Poodle

J. A.

RICHARDSON,

K.

TANG , AND

D. K.

B URNS

Key words: Alexander's d isease; dogs; myeloenceph alopath y; Rosenth al fiber.

In 1949, W. Stewart Alexander desc ribed a degen erative di sorder o fas trocy tes in an 18-m onth-old child.' Th e subpial, subependy ma l, and peri vascular astrocytes co nta ined prominent , hom ogen eou s, eos ino philic, fibrinoid deposits. Lat er stud ies established that th e dep osit s were histochemi cally and ultram icros copi cally identical with Rosenthal fibers. Th e eponym " Alexander' s di sea se" is used for cases in which large numbers of Rosenthal fibers develop in a subpial, sub epcn d ym al, and perivascular distribution. In human beings, th e di sease is divided int o infantil e, j uve nile, and adult form s." T he di sease has been report ed in a shee p; two Labrad or Retri evers," and a Scott ish Terri er. v"Th is co m munication is the fi rst report of the formati on of ence phalopathy with Rosenthal fibers in th e Miniature Poodl e. At 3 months o f age, th e fema le Min iature Poodl e in th is rep ort develop ed trem or s and ataxia . Th e clin ical signs progressed slowly, and by 6 months, the dog had prominent pos terior weakness. Cra nial nerves were una ffected , and the dog remai ned br ight and alert. Cerebrospinal fluid was normal. T he dog was eutha na tized at 6 months of age, and the cerebrum, midbrain, cerebellum, and sectio ns of cervica l cord were submi tte d for path ologic exa m ina tio n. Sections were embedded in paraffin, sectio ned at 5 ~m and stai ned with hematoxylin and eos in. For electron m icrosco pic exa mi nation, tissues were embe dded in Epon/ Araldite cut at 80 nm sta ined with uran yl acetate and Reynold 's lead citrate. Grossly th e brain was unr em ark abl e. Histopath ologic cha nges were dominated by prominent , eosino philic, refractile bodi es with morphologic findings consistent with th ose of Rosenthal fibers. Th ey were most abundant in th e pons and midbrain , forming di stin ct, brightl y eosinophilic, perivasc ular, subpial, and subependy ma l zones (Fig. I). Rosenth al fibers were found in sma ller numbers in th e white matt er o f th e cerebru m, cerebellum, and in th e gray and whit e matt er ofth e cervica l cord. Th ere was mild rarefaction ofthe myelin , especially where Rosenthal fibers were most num erou s. Th e myelin rar efaction was acco mpanied by m ild-t o-m oderate gem istocy tic astro cytic gliosis. No Gi tte r cells were associ ated with the myelin loss. Electro n m icroscopi c exa mi na tion revealed osmio philic, dense, gra nular, aggregates within the cytop lasm ofastrocytic processes adjace nt to vessels (Fig. 2). Th e aggregates were surrounded by bundles of glial filame nts ran ging in diam eter from 7.5- 10 nm , a size and morph ology co nsistent with that of glial fibrillary acid protein. T he aggregates were not mem bran e-b ound and were int im ately assoc iated with th e glial fil am ent s (Fig. 3). Rosenth al fibers ar e not restri cted to Alexander's di sease but can develop in glial tum or s or scars ." Th eir origin is not clear, but it is believed that th ey repr esent a prim ary astro cytic abnorma lity.' On e hypoth esis is that th ey consist of

breakd own products of glial fibrillary acid prot ein , altho ugh Rosenthal fibers fail to consistently react to antibodies again st glial fibrillary acid protein.' Recentl y a 22 kD prot ein , a major co m pone nt of Rosenthal fibers, has been isolat ed and found to be a B-crystallin Y Th e role of a ll-crystallin in extralenticular tissue s is not established , but in path ologic cond itions astrocy tes accum ulate mas sive amo unts of th is protein into refractil e inclusions. Whether a ll-crystallin accum ulates beca use of excessive production or inadequat e degradation is not esta blished. T he origin of myelin loss, which may be quite variable in both human and an imal cases , is unclear. If the pathologic findin gs of this di sease are ind eed relat ed to a primary astrocytic abnorma lity, then in light of the role played by astrocytic foot processes in maintaining the integrity of the cere bra l ca pillary endo thelium 10 and thu s th e blood-brain

Fig.1. prom inent efied, and HE. Bar =

Medulla; Poodl e. T he vesse l (V) is surro unded by accumulation s of Rosenthal fibers. Myelin is rar gem istoc ytic astrocy tes (arrows) are prominent. 50 ~ m .

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Brief Comm unications and Case Reports

537

Fig. 2. Electro n mi cro graph . Medulla; Poodl e. Not e th e os m io phi lic aggregates (arro ws) within th e as trocytic pro cesses surro undi ng a ca pilla ry co nta ining eryt hrocytes (whi te a rrow). Bar = 2 J.L m. Fig. 3. Electron mi cro grap h. M ed ulla; Poodl e. T he os m iophi lic bod y co nsists of non- membran e- bou nd , gra n ular , aggrega tes int im ately associated with glia l filaments. Bar = 500 n m.

barrier, th e o ligode ndroglia m ay be a ffected seco ndari ly. Herndon " sugges ts th at ab norma lities in m yelin a rc es pecia lly p ro minent in th e infa ntile form du e to th e fact that ea rlyo nset di sea se would inte r fere m or e severe ly with po stn atal m yelin ati on . Wh ether th e as trocy tic a bno rma lity is due to a gene t ica lly in he rite d enzy me deficien cy is not ye t kno wn . Th e di sea se is rare a nd hen ce no gene tic pa tterns ha ve been esta blis he d in huma n beings o r animals. T he he terogenic ity not ed in th e clinical and m orphol ogic pa tterns of th e di sease rai ses the possibility of homozygou s a nd het ero zygo us p hen ot ypes. In the two o ther rep orts in th e dog .v" th e subjects were m al e. Three of four m ale litt crmat cs of o ne of th e cases we re euth an ati zed pri or to 6 m onths of age becau se of ce ntra l nervou s sys te m di sea se but were not necropsied . T he litt erm at es of th e Poodl e in th e curre nt rep ort and m ember s o f subse qu ent litt er s had no clin ica l abn ormalities o f th e ce ntra l nervo us sys te m .

References Alexander WS: Pro gressi ve fibri no id d egen er at ion of fibrilla ry as t rocy tes associate d with men ta l ret ardat io n in a hydrocepha lic infa nt. Bra in 72:373-381,1 949 2 Borrett D, Beck er LE: A lexa nde r's di sea se: a di sea se of ast ro cytes. Bra in 108:367-385, 1985

3 Cox N R, Kwapicn RP , So rjone n DC, Braund KG: M yeloen cephal opath y resembling A lexa nder's di sease in a Sco tt ish T er rier d og. Ac ta Neuropath ol (Berl) 71: 163-

166, 1986 4 Fan kha use r R, Fa tzer R, Best etti G, Deruaz J P, Perentes E: Ence p ha lopathy with Rosenthal fibre formati on in a shee p. Ac ta Ne uro pa tho l (Berl) 50:57-60, 1980 5 Go ld ma n l E, Corbin E: Isol ati on o f a m aj or co mponen t of Rosenthal fibers. A m 1 Path ol 130(3):569- 578,

1988 6 Hernd on RM , Ru bin stein LJ, Free man 1M , Ma thieso n G : Light and electro n mi cro scopic observatio ns o n Rose ntha l fiber s in A lexa nde r's d isea se and in multiple scle rosis. 1 Ne uro pa tho l Exp Ne uro l 29:524-551 , 1970 7 Iwaki T , Kum c-Iwak i A, Liem RKH , Gold ma n l E: cy Bcrysta llin is exp ressed in non-lenticul ar tissues and accum ula tes in A lexa nder's di sea se brain . Ce ll 57:71-78, 1989 8 M cGrath IT: Fibrinoi d leukod yst roph y (A lexa nde r's D isea se). I n: Sp ontan eou s Ani mal M od els of Hu m an D isease, ed . A ndrews El , Wa rd Be. and A lta man N H, vo l. 2, pp. 147- 148. Aca de mic Press In c, New York, N Y, [980 9 Sorj on en DC, Cox NR , Kwapien RP : M yeloen cephalopath y wit h eosi no p hilic refractil e bo d ies (Rose n tha l fi-

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Brief Communicatio ns and Case Report s

bers) in a Scottish Terrier. J Am Vet Med Assoc 190(8): 1004-1006, 1987 10 Stewart PA, Wiley MJ: Dev eloping nervous tissue induces formation of blood-brain barrier characte ristics in invad ing endo thelial cells: a study using quail-chi ck transpl ant ati on chime ras. Dev BioI 84: 183-1 92, 1981

Requ est reprints from Dr. J. A. Richardson , Department of Pathology, Div ision of Comparative Medicine, Uni versity ofTexas Southwestern Medical Center at Dallas, 5323 Harry Hin es Blvd. , Dallas, T X 75235 (USA).

Vet PathoI28:538-540 (1991)

Giant Cell Glioblastoma in a Syrian Hamster H.

ERNST, D.

K ey words:

L.

G. F.

WALTER,

C.

DUNGWORTH, AND

DASENBROCK,

U.

MOHR

G lioblasto ma; hamsters; immunoperoxidase.

T he prevalence o f naturally-occurring tumors of the central vasc ular proliferation with hyperpl astic endot helial and periner vous system in human beings, dom estic ani mals, and in vasc ular cells (Fig. 4). Immunoh istochemi cal inves tigations, most species o f laboratory animals is below 1.5%.4- Th e rat which were performed on formal in-fixed and paraffin-emis an exception, with a brain tumor incidence of up to 7%.6,7 bedded tumor tissu e usin g the alkalin e phosph ata se-anti alIn contrast, primary brain neoplasm s in the Syrian ham ster kalin e ph osphatase meth od. ' confirmed the glial nature of ar e extreme ly rare. T wo astrocy to mas ha ve been record ed in the tum or. A strong reaction to glial fibrillary acid ic protein th e data of th e Na tiona l Toxicology Program ." A va riety of (rabbit-anti hum an G FAP [Medac, Hamburg, Germa ny]) was brain tumors have been experime nta lly induced in ham sters obs erve d in the bett er d ifferentiated tum or cells with glial by vario us viruses and chem ical carcinogens, however, in- processes and in most of the giant cells (Fig. 5). Th e reactive cluding multiform gliobla stoma, medulloblastom a, epen- astrocy tes in the no rmal cere bral tissue adja cent to th e tum or dymoma and pineocytorna, '> but as far as we know there were also G FAP-positive. Th e neuronal markers neur onhas been no published report on naturally-occurring brain specific enolase (mouse-anti human NSE [Inn ogeneti cs, Anttum ors in ham sters up to now. werp, Belgium]) and neu rofilam ent prot eins (mo use-a nti huT his paper describes a giant cell glioblasto ma in a 6-mo nth- man N FP [Dako, Hamburg, Ge rma ny]); mo use-anti bovin e old male Syrian ham ster (stra in Han :AURA) that serve d as NFP (M ilab, Hamburg, Germa ny) gave no reaction withi n control animal in a chro nic toxicity study. T he ham ster was th e tum or , but were positi ve in the unaffected brain tissue. Sum marizing the morphologic findin gs, the present case submitted for necrop sy with clinica l sym pto ms ofprogressive weight loss du e to diarrhea , ataxia, dyspn ea , and bilateral shows a striking resemblance to human giant cell glio blasda cryorrhea. At necropsy, the diameter of th e left cerebra l toma. Th e World Health Organi zati on classification of brain hem isph ere was enlarged to twice th e diameter of th e right tum ors in human beings categorizes th e giant cell glioblashem isphere. T here was a large area of reddis h discolorati on tom a as an undifferent iated (em bryo nal) neuroepithelial tuon th e lat eral as pect of the left hemi sph ere with indi stin ct mor, whic h is a va ria nt o f the multiform gliob lasto ma. " Th is tran sit ion to th e grayis h-w hite surro unding bra in tissue. The classi ficatio n is based primarily on cyto logic and histologic co nsistency of the enlarged hem isph ere was slightly firmer characteristics. Since most gliobl astom as in human beings th an that o f th e right. Gross sectioning of fixed brain revealed have some degree of astrocytic differenti ati on , as evi de nced an indistinctly circumscribed mass that occupied most of the by the expression of G FAP , th ey ma y not only arise from left hem isph ere. Th e mass di stort ed and obliterated the lu- the neopl astic transformati on o f glial precur sor cells but also men and boundaries of the left lateral ventricle and caused develop by ded ifferentiation o f a preexisting astrocyto ma.v di stension of the right lat eral ven tricle (Fig. I, inse t). His- T he mark ed G FAP-reactivity in the astrocyte-like tumor cells tologically, th e tum or was characterize d by sma ll, fusifo rm of the ham ster glio blasto ma sup ports this view. In the labor pleom orph ic tum or cells, some with glial processes, re- oratory rat , a positi ve GFAP sta in has only been reported sem bling gem istocytic astrocytes, and intermingled with for normal and reacti ve astrocy tes but not for spo nta neo us clusters of large giant cells (Figs. I, 2). The giant cells had glial tum or s.'> single or multiple large vesicular nucl ei with prominent nucleoli and a hyalin e, eos ino philic, and hom ogene ous cytoReferences plasm. Occas ional mit ot ic figur es were present and were usually atypical (Fig. 2). Th e tum or center had foci of hem orrhage Cardesa A, Rustia M, Mohr U: Tumor s of the nervo us as well as necrot ic areas th at were surrounde d by pseud osyste m. In: Pathology of Tumors in Lab orat ory Animals: pall isaded tum or cells (Fig. 3). Th ere was also a moderat e T umo urs of th e Ham ster , ed . Tu rusov VS, vol. 3, pp . 4 I3-

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Myeloencephalopathy with Rosenthal fiber formation in a miniature poodle.

Vet Path ol 28:536-538 (1991) Myeloencephalopathy with Rosenthal Fiber Formation in a Miniature Poodle J. A. RICHARDSON, K. TANG , AND D. K. B...
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