HISTORICAL CONTRIBUTIONS TO PEDIATRIC PATHOLOGY

Sturge-Weber Syndrome

VENITA JAY

Division of Pathology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8

I have no intention of going into the difficult ques-

tion of the pathology of port-wine mark. The point to

which I wish to call particular attention is the prob-

able relationship between the mark and the fits . . . .

From the nature of the fits, and from their mode of

onset, I think there can be no doubt that they are due

to some cause external to the nerve-tissue . . . and

this external cause is in all probability to be found in

the presence of a “port-wine mark” on the surface of

the right side of the brain, just as we have found it in

the skin, mucous membranes, and retina of that

side.

William Allen Sturge, 1879

The compilation of clinical observations of a mul-titude of physicians helped to elucidate the fullclinicopathological spectrum of the Sturge-Webersyndrome. Despite recognition of the clinical, ra-diological, and pathological features, and advancesin functional imaging, the condition continues toremain an enigma in terms of its etiopathogenesis.The astute clinicians of yesterday uncovered theassociation between the port-wine stain and theseizure disorder. But the inciting forces that stim-ulate this abnormal vascular proliferation in theface, choroid of the eye, and leptomeninges of thebrain still remain shrouded in mystery.

Dr. William Allen Sturge (1850–1919) and Dr.Frederick Parkes Weber (1863–1962) made semi-nal contributions to separate facets of the Sturge-Weber syndrome, in reports published some 43

years apart. The name of Dimitri, who described aroentgenographic shadow in a case of angioma ofthe brain in a presentation to the NeurologicalSociety of Argentina, has also been associatedeponymously with this condition.

William Allen Sturge was born in Bristol,England, in 1850. He was the eldest son of Wil-liam Sturge, a wealthy land surveyor. His parentswere members of the Religious Society ofFriends (Quakers). While in school, the youngSturge sustained a soccer injury. Sturge stayedwith his physician uncle while recuperating—thissparked an interest in medicine and led him tochoose a medical career, contrary to the wishes ofhis father, who wanted him to pursue the familybusiness.

Sturge obtained his medical training at Bris-tol Medical School and at University College Hos-pital, London. His keen sense of observation andoriginal reasoning set him apart, even in his schooldays. He completed his M.D. in 1875. After servingas a physician’s assistant and resident officer, Dr.Sturge became a registrar at the National Hospitalfor Paralysis and Epilepsy. Here he became en-grossed in the study of neurological disorders, andpursued this interest further in Paris. At the time,this would have been a natural destination for anyaspiring young neurologist, as the Salpetriere wasa mecca for neurologists, with none other than thelegendary Charcot as its Chair of Neurology. Withhis astute clinical sense and acumen, Dr. Sturge

Pediatric and Developmental Pathology 3, 301–305, 2000

DOI: 10.1007/s100249910040

Pediatric and Developmental Pathology

© 2000 Society for Pediatric Pathology

left a lasting impression even on Charcot, thefounding father of neurology.

While in Paris, Dr. Sturge also pursued stud-ies in pathology and general medicine. He was alsoclosely affiliated with Fournier, who, like Charcot,was also extremely impressed with Sturge. WhenDr. Sturge returned to London, he was appointedphysician and pathologist to the Royal Free Hos-pital and was a lecturer at the Women’s MedicalSchool. A liberal and strong advocate of women’seducation, Dr. Sturge himself was married to adistinguished physician, Dr. Emily Bovell.

Besides his description of the condition thatis eponymously associated with him, Dr. Sturgedid notable work on muscular atrophies, erythro-myalgia, and other miscellaneous disorders. As aphysician, Dr. Sturge was exceedingly humane. Hereserved the deepest regard for his patients, espe-cially those suffering from chronic nervous disor-ders. When his wife Emily’s health was in declinedue to tuberculosis, seeking a milder climate forher sake, Dr. Sturge spent considerable time inNice. Here his practice catered to many interna-tional visitors to the French Riviera, includingQueen Victoria, who regarded him with high es-teem.

Emily Bovell died in 1885. The following year,Dr. Sturge married Julia Sherriff, who was hisnurse in Nice. It was during his travels that Dr.Sturge became greatly interested in archaeologyand started collecting Greek vases and paleolithicflint implements.

Aside from his notable medical achievements,Dr. Sturge will be cherished for his passionatecontribution to prehistoric archaeology. The SturgeCollection is an extraordinary two-volume illus-trated selection of stone implements bequeathed toThe British Museum by Dr. Sturge in 1919 andauthored by Reginald A. Smith. The first volume ofthis extraordinary collection includes a collectionof flints from Britain, amassed chiefly on Dr. Stur-ge’s visits to England from Nice and after his re-tirement in Icklingham Hall, a village in Suffolk.Icklingham Hall was a haven for the collector inSturge, as the area was rich in Stone Age relics. Dr.Sturge and his second wife collected many thou-sands of specimens, not only on their own but alsoin acquiring material from other collectors. In thesecond volume of The Sturge Collection, there are

detailed descriptions of stone implements from farcorners of the world, including Asia, Africa, Eu-rope, and Australia.

Dr. Sturge was one of the founders and thefirst presidents of the Society of Prehistoric Ar-chaeology of East Anglia. His writings in the fieldare extensive and his generosity unparalleled, as hebequeathed the extraordinary collection of morethan 100,000 pieces to public museums. His largecollection of prehistoric flint implements were do-nated to the British Museum, while his collectionof Greek vases and bronzes became part of thecollection of the Royal Ontario Museum in To-ronto. Dr. Sturge died on March 27, 1919, leavingbehind a rich legacy in medicine and archaeology.

There have been but few nonagenarians inthe history of medicine who can match the vitalityand vigor of Dr. Frederick Parkes Weber. He wasborn in London on May 8, 1863. His father was thecelebrated Sir Hermann Weber, whose practice in-cluded the royal family and several prime minis-ters. Frederick Parkes Weber thus had the singularfortune of being affiliated with some of the greatestminds in medicine from his childhood on.

In 1886, Parkes Weber entered St. Bar-tholomew’s Hospital in London and graduatedwith a M.B., Ch.B degree in 1889. He obtainedfurther training in Paris and Vienna. He obtainedhis M.D. in 1892, and became a Fellow of the RoyalCollege of Physicians in 1898. After residency po-sitions at St. Bartholomew’s Hospital, Dr. Weberjoined the German Hospital, Dalston, a profes-sional association that continued for more thanhalf a decade. He also served as physician to theMount Vernon Hospital for diseases of the chest.

Dr. Weber was a voracious writer. Not all hiswritings were devoted solely to medical themes, asdivulged in his books, entitled, Some Thoughts of aDoctor, and More Thoughts of a Doctor and anothernotable work, Aspects of Death and Correlated As-pects of Life in Art, Epigram, and Poetry. Dr. Webershared his father’s interest in climatology andother matters; one such father-and-son collabora-tion involved research on spas and mineral watersof Europe.

Dr. Weber held a wide range of interests. Hewas a prominent member of the Society of Anti-quaries and the Archaeological Society. Coins wereanother consuming passion for him, and he was

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elected to the Numismatic Society. It is indeed afortuitous coincidence that both names associatedwith the Sturge-Weber syndrome shared a passionfor archaeology. In one extraordinary instance re-counted by Dr. Weber, a fine Panathenaic am-phora, once owned by Dr. Weber, ended up in Dr.Sturge’s collection, later becoming a part of theSturge collection at The Royal Ontario Museum inToronto.

Besides the Sturge-Weber syndrome, Dr. We-ber’s name is also immortalized in the eponymsOsler-Weber-Rendu disease, Weber-Christian dis-ease, and Weber’s disease. Dr. Weber’s remarkablemedical writings were donated to the WellcomeHistorical Medical Library in 1958. His specialpassion for dermatology is reflected in two of theconditions eponymously associated with him andin the fact that Dr. Weber made a monetary dona-tion of 3000 pounds to the Royal College of Physi-cians for the advancement of dermatology.

In 1921, Dr. Weber married Dr. Hedwig Un-ger-Laissle. He was honored by the Royal Collegeof Physicians with the Moxon Gold Medal in 1930.Dr. Weber suffered from visual difficulties in hisfinal years, but his zest for medicine and for liferemained uncompromised. Dr. Weber died onJune 2, 1962.

Historically, recognition of the Sturge-Webersyndrome emerged through individual observa-tions dating back to the second half of the previouscentury. In 1860, Rudolf Schirmer published abrief account of a case of facial vascular nevus inassociation with buphthalmos, but made no men-tion of neurological associations. In a meeting ofthe Clinical Society of London in 1879, Dr. WilliamAllen Sturge described a 6.5-year-old girl with ahemangioma of the right side of the face, buph-thalmos, and focal seizures. While Dr. Sturge didnot have the benefit of pathological examination ofhis patient, he correctly predicted the presence of a“port-wine mark” on the surface of the right side ofthe brain. His prediction was to be proved accuratein later years by postmortem examinations byKalischer and other investigators.

In a report entitled, “A case of partial epi-lepsy, apparently due to a lesion of the vasomotorcentres of the brain,” which was read before theClinical Society of London and published in itstransactions in 1879, Dr. Sturge described his first

encounter with the syndrome. The patient, AdaBrook, was born with a very extensive “mother’smark,” which was most evident on the right side ofthe head and face, but with a more widespreaddistribution. The mark was “everywhere of a deeppurple colour, the colour partially disappearing onfirm pressure.” The right eye was affected in asimilar way “both in its superficial and deep struc-tures.” It was larger than the left eye, and the scleramore vascular than usual. With the ophthalmo-scope, it was obvious that the retina and choroidwere involved. The choroid of the right eye wasmarkedly darker and redder. Without the benefit ofpathologic examination, Dr. Sturge stated: “Thedifference is not what we should expect if it weredue to the pigment being more abundant in oneeye than the other; it is suggestive of venous orvenous and capillary hypertrophy like that on theskin.”

At 6 months of age, the child began to haveseizures affecting the left side; in time, the rightside was also involved. Under the influence of bro-mide of potassium, the patient had “considerablyimproved.” In his summation of this rare form ofepilepsy, Dr. Sturge drew attention to the fact thatthe fits were partial and confined to the left side fora long time, and to the probable relationship be-tween the facial mark and the fits. He felt that acause external to the nerve tissue rather than aninherent instability of the gray matter was respon-sible for the fits and predicted that the surface ofthe right side of the brain would have a “port-winemark” similar to that in the skin, mucus mem-branes, and retina on the same side.

In 1897, Kalischer made an interesting pre-sentation to the Medical Society of Berlin. Hispatient was a 1.5-year-old child with a left-sidedfacial nevus and initially right-sided seizures thatlater also involved the left side. At postmortem,there was angioma of the skin as well as the me-ninges of the left cerebral hemisphere. In 1901,Kalischer described the histology of the vascularmalformation in this patient, but did not observecalcifications in this case. In 1910, Durck describedcerebral calcification and a “racemose pial angi-oma” in a patient with severe epilepsy, right-sidedhemiplegia, and a left facial nevus. In 1913, Hebolddescribed three cases of facial and meningeal an-giomatosis with contralateral hemiplegia; two of

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his three cases showed grossly “lime salt” depositsat autopsy. Around the same time, Volland de-scribed intracortical calcifications underlying themeningeal angioma by postmortem examination.

In 1921, Wissing presented before the Radio-logical Society of Copenhagen a roentgenogram ofthe skull of a young man; the image had an un-usual shadow, localized to the right occipital lobe.This shadow and its sinuous form suggested theconsideration of calcification of the piamater, butWissing did not publish his observations until1929.

In 1922, Dr. Weber reported a 22-year-oldwoman with an extensive cutaneous angioma,spastic hemiplegia with hemihypotrophy, glau-coma, and buphthalmos. This communication, en-titled, “Right-sided hemi-hypotrophy resultingfrom right-sided congenital spastic hemiplegia,with a morbid condition of the left side of thebrain, revealed by radiograms,” was published inthe Journal of Neurology and Psychopathology. Dr.Weber’s patient had a very widespread vascularnevus (not restricted to the face), chiefly of thesuperficial “port-wine-stain” type, and more exten-sive on the left side. The patient was blind in theleft eye, which was larger than the right, owing tocongenital glaucoma.

Dr. Weber reproduced crude skiagrams of theabove patient’s skull and became the first to pub-lish a roentgenogram of the intracranial calcifica-tion in this condition. Thus, although Wissing wasthe first to obtain a radiographic picture of thecalcification in this condition, Weber was the firstto publish an abnormal radiograph in his report of1922. In the two skiagrams taken, one showing theside view and the other, the anteroposterior view,the left half of the brain appeared sclerosed andmore opaque, giving a somewhat deeper shadowthan the right half of the brain. In his summationof this extraordinary case, Dr. Weber concluded:“The abnormal consistence of the left cerebralhemisphere is doubtless due to sclerotic changesor meningeal abnormalities. It is highly probablethat the congenital cerebral disease is in some wayconnected with the presence of the vascular naevusof the meinges or brain on the left side—of thesame nature as the extensive vascular naevus of thepatient’s body.”

In his publication of 1922, Dr. Weber citedother authors who had encountered similar clini-cal situations. In 1922, Greig had described a boywith right hemiplegia, right-sided convulsions, acutaneous nevus of the face, and a meningeal vas-cular nevus of the contralateral cerebral hemi-sphere. Also in 1922, Campbell and Ballance pub-lished a report of a 23-year-old man with mild lefthemiplegia and left-sided convulsions with a ve-nous angioma of the brain on the opposite side.

With the aid of better radiographic technique,Dimitri demonstrated the gyriform pattern of thecalcification in 1923. His report mentioned thecharacteristic double contoured intracranial shad-ows interlacing in ribbon-like formations, whichhe and many others after him interpreted to becalcified blood vessels in the meningeal angioma.Radiographic demonstration of unilateral cerebralchanges also came from several other authors, in-cluding Marque, Brushfield, Wyatt, and Sheldon.Marque published two cases in 1927, with radio-graphic shadows in the occipital lobes. The sameyear, Brushfield and Wyatt reported a similar casein a young girl of 11 years. In 1929, Moore de-scribed a 12-year-old boy with defective vision inthe left eye. He had a nevus of the left half of theface, right homonymous hemianopsia, and a large,wedge-shaped shadow on the roentgenogram,which turned out to be an angioma primarily in theoccipital lobe.

Dr. Weber reported his famous patient againin 1929, this time in the Proceedings of the RoyalSociety of Medicine; this report included better andmuch improved radiographs, which revealed atro-phy of the entire left cerebral hemisphere: “Theshadowing, apparently due to calcareous deposit,does not extend beyond the tentorium cerebelli,and there is no radiographic sign that the cerebel-lum is affected.” By this time, there was greaterawareness in the medical community of this con-dition, with several reports, including those ofKalischer, Lannois, Bernoud, Strominger, Cock-ayne, Mouriquand, Bernheim, Symonds, Brush-field, Wyatt, and Aynsley. The legendary HarveyCushing also had his encounter with this novelcondition. Cushing’s first case was a 4-year-old boywith an extensive capillary nevus of the right sideof the face, right-sided buphthalmos, and left-sidedspastic hemiplegia. At autopsy, the right cerebral

304 V. JAY

hemisphere was smaller than the left one, and themeninges covering it was unduly vascular, whichDr. Cushing felt was “in all probability represent-ing a nevoid condition similar to that present onthe skin.”

In 1934, Krabbe showed that the counterpartof the double contoured radiographic shadow wascortical calcification, and not calcified blood ves-sels in the leptomeningeal angioma. Thus Krabbecorrected the persisting erroneous belief that theradiographic abnormality was due to calcifiedmeningeal vessels.

Thus, historically, there have been numerouscontributors who helped to elucidate the clinicalspectrum of this syndrome, some of whom havebeen alluded to in this brief overview. In 1936,Bergstrand proposed the designation “Sturge-We-ber’s disease” for this condition. In a communica-

tion to the British Medical Journal the same year,the extraordinary Dr. Weber disclaimed a place forinclusion of his name for the designation of thecondition—adding that addition of Kalischer’sname would be more appropriate! Subsequently in1955, Dr. Weber advocated the use of the terms“encephalo-trigeminal angiomatosis” or “en-cephalo-facial haemangiomatosis.” But as allwould agree, the title of Sturge-Weber syndromeseems well deserved, and the legacy of Dr. Sturgeand Dr. Weber lives on.

A C K N O W L E D G M E N T

A few biographical details on the life of Dr. SturgeWeber were derived from information kindly pro-vided by The Sturge-Weber Foundation, Mt. Free-dom, NJ, USA.

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