Psychiatric Symptoms and Brain Tumors

HISTORY OF NEUROLOGY

SECTION EDITOR: CHRISTOPHER G. GOETZ, MD

Psychiatric Symptoms and Brain Tumors

A Brief Historical Overview

Adrian A. Jarquin-Valdivia, MD, RDMS

I ntracranial tumors with psychiatric symptoms are relatively uncommon but clinically im-portant events. How did we come to recognize brain tumors as clinical entities that couldmimic psychiatric symptoms? During the 16th and 17th centuries, the practice of perform-ing human autopsies for academic purposes eventually led to the link between brain tu-

mors and mental symptoms. Giovanni Battista Morgagni1 (1682-1771) was the first physician todescribe a patient with psychiatric symptoms and what may have been a brain tumor. Recognizingthis association was a slow process, mostly because of the paucity of practical ways to diagnoseand treat psychiatric illness and brain tumors until the late 1800s. The movement led by the Frenchphysician Philippe Pinel (1745-1826) influenced physicians to think of psychiatric patients as sickhuman beings who did not deserve to be physically restrained or mistreated.2 The creation of largepsychiatric hospitals that performed autopsies set the ground for the solid recognition of the as-sociation of brain tumors with psychiatric symptoms.

According to the Talmudic tradition, whenEmperor Titus (40-81 AD) landed on dryland after the destruction of the temple inJerusalem, a gnat flew into his nose, as-cended into his head, and knocked againsthis brain for 7 years. The pains drove himto the point of madness. After Titus died,physicians opened his skull and foundthere something that looked like a spar-row, “two selas in weight.”3 This is an earlydescription of symptoms brought on bybrain tumors, an association that did notencounter general acceptance and solidanatomical foundation until centuries later.Even more challenging was the associa-tion of psychiatric symptoms with braintumors.

Through the late Middle Ages and theRenaissance, it was held in popular beliefthat psychiatric symptoms were due to “astone” in the brain.4 Several depictions ex-ist of flagrantly deceptive physicians whoperformed operations to extract the “stoneof madness.”

Some of the early publications aboutphysical disease causing pains or alteredmental status symptoms date from the late1600s. Thomas Willis,5 in his book De animabrutorum (1672), describes the case of

a woman of about 50 years of age, after she hadborne for about 6 months, a most grievous painin the head, under the sagittal suture, trou-bling her almost continually, yielding to nomedicine or regime of treatments, finally intoa lethargy, with a partial alleviation of her symp-toms; from which being aroused by remedies,she awoke with the headache, as distressing asbefore. Within 2 or 3 weeks later, she de-parted this life. Her skull being opened therewas growing from the side of the sagittal si-nus, a scirrhrous tumor three finger broad,which united for a small area the dura materto the pia mater, and the venous tributaries,which should open here into the sinus, wereoccluded.5

In his chapter “Instructions and Pre-scripts for the Cure of the Delirium andthe Phrensy,” Willis remarks, “[I]n ana-tomical dissections I have commonly seenthe Meninges, nay sometimes also an out-ward circumference of the brain beset witha phlegmonous tumor; but the disease not

Author Affiliations: From the Departments of Neurology and Anesthesiology andthe Internal Medicine Division of Neurocritical Care, Vanderbilt UniversityMedical Center, Nashville, Tenn.

(REPRINTED) ARCH NEUROL / VOL 61, NOV 2004 WWW.ARCHNEUROL.COM1800

©2004 American Medical Association. All rights reserved.

Downloaded From: http://archneur.jamanetwork.com/ by a UB-Universitaets Landesbibliothek Dusseldorf User on 03/17/2014

affected with a phrensy, but on thecontrary with a drowsiness... and in-deed Reason plainly dictates thething to be thus, for inflam’d Me-ninges, and much more swollen,greatly compress the Brain, and stopthe passages of the Spirits.”6(p452) Theformer description seems that of abrain tumor (meningioma?) with ve-nous obstruction; the latter is notclearly that of a brain tumor and mayhave been an infectious process. Theclinical manifestation is not psychi-atric, but these descriptions repre-sent advances in the development ofclinicopathological correlations.

Intracranial tumors were re-ported in the early part of the 1700s,such as the case of a pineal tumor de-scribed in 1717 by Charles Drélin-court in his Theatrum Anatomicum.7

Later, in a book published in 1758 en-titled A Treatise on Madness by Wil-liam Battie (1704-1776), in “Sec-tion VIII: The Causes of Madness,”Battie begins by stating,

For as preternatural pressure upon thenerves is in human apprehension thenearest to delusive sensation thereby ex-cited; whatever injury creates such pres-sure must be a remoter cause of Conse-quential Madness. Under this headtherefore of remoter causes are to beranked the internal exostoses of the cra-nium, the induration of the Dura Mater,the fracture and intropression of the skulland concussion of the head, as also, if itwere of any service in the cure of mad-ness to enumerate them, the many andvarious accidents these delirious inju-ries may be owing to.8(p50)

Battie mentions “induration of theDura Mater” that may have been an-other of the earlier observations ofmeningiomas.

Morgagni, Chief Professor ofAnatomy at Padua, Italy, was prob-ably the first modern observer to de-scribe the finding of a brain mass ina person who had suffered associ-ated psychiatric symptoms. Theclinical case was that of

a virgin, of more than twenty years ofage, being extremely delirious and with-drawn into a nunnery, and being re-fused what she desired, her mind be-gan to be a little weak and unsteady, fromthe moment she heard the news of herrepulse: and very soon after, she beganto reason incongruously, which in-creased on her more and more every day;so that she frequently refused to takefood. Some months were thus passed, in

which time, beside a fever that at-tacked her many times by irregular re-turns, a more violent madness came on,without a fever; so that she endevoured[sic] to strike those who sat by her: andher strength decreasing by degrees, shedied.1(p144)

At her autopsy, Morgagni goes on toexplain,

The skull being opened, some little whitebodies were seen at the sides of the lon-gitudinal sinus, in the dura mater ex-ternally; some of which were round, oth-ers oblong, and some of a figure perfectlyirregular, but all soft in their consis-tence: Valsalva thought that they hadtheir origin from a concreted humor, forthis reason; because he had seen simi-lar bodies, from concretions of pus, stag-nating about the same membrane, in pa-tients that had died of wounds to thehead. But in that sinus was a slender pol-ypous concretion, which extended it-self through the whole length of the cav-ity. The brain was moist; and in its largerventricles was a little quantity of se-rum. However, in the plexus choroidspretty large glandular bodies were promi-nent, which had been indurated into asolid body, yellow, and somewhat globu-lar in form.. . .Valsalva had had as fre-quent opportunities of dissecting otherbodies of insane persons, as he had ofattending to their disorders while liv-ing; I doubt not but he would certainlyhave observed, what I have observed inall have hitherto examined, that is, a con-siderable hardness in the brain.1(p145)

However, it is not completely cer-tain that what Morgagni describes is

actually an intracranial neoplasticcondition. Other possibilities suchas tuberculosis or syphilis, both ofwhich were common in those years,cannot be reliably ruled out. In hisextensive descriptions of the manyautopsies performed, Morgagni de-scribes several other cases of braintumors.

FROM DIAGNOSISTO SURGERY

In 1865, 22-year-old Camillo Golgi(1843-1926) presented his gradu-ating thesis. It included a classifica-tion of the causes of psychosis. Neo-plastic conditions were not includedas potential causes. He writes thatthis “classification is the effort tobring some order into the great di-versity of phenomena observed inclinical practice”9(pp42-43) (Table).

In 1869, Golgi took care of an“active, upper class, 48-year-oldwoman who had become childish,and capricious, irreverent and foul-mouthed, unable to sustain atten-tion in the execution of even simpletasks, incapable of abstract think-ing, and devoid of concern and in-terest.” The patient fell from a bal-cony and died. At autopsy was found“an orange-sized fungoid mass aris-ing from the arachnoid layer of themeninges and severely compress-ing, without invading the left fron-tal lobe.” The histological study in

Table. Etiological and Phenomenological Classificationof the Psychosis According to Golgi, 18659

Disease Clinical Findings and Pharmacological Remedies

Heart psychosis Melancholia, disposition to suicide, and nightmares;tendency to relapse; positive response to digitalis, aconite,and arsenic

Tuberculotic psychosis Aspecific clinical manifestation; lung signs; loss of weight;positive response to aconite, sea salt, and cod oil

Gastric psychosis Melancholia and anorexia; iperoralism, coprophagy, andbulimia; positive response to nux vomica, carbon,and bismuth

Herpetic psychosis Associated with skin erythema; positive response to sulfurand graphite

Uterine psychosis Erotic delirium; incurableGravidic psychosis Related to some of the above mentioned physical causesPellagral psychosis Growing stops and skin erythemaMalnutrition psychosis Alcohol, cretinism, and food deficiencyMoral psychosis Very few mental ailments are related to moral causes only;

16% of cases are related to interactions of moral causeswith inheritance

Congenital psychosis Skull alterations: microcephaly, brachycephaly, anddolichocephaly; intellectual deficit; hypogonadism; incurable




the preserved original specimenat the University of Pavia done in1993 demonstrated the mass to bea psammomatous meningioma.9

Although this case demonstratedfrontal symptoms and an eloquent,detailed, and more insightful de-scription of the clinical manifesta-tion, the case does not seem to havebeen considered that of a brain tu-mor with primarily psychiatric mani-festation, although the associationhad been made by Richard Bright inthe 1830s.2

Toward the end of the 1800s,changing ideas about diseases andtheir anatomical basis shifted the in-terface between neurology and psy-chiatry. Niemeyer10 wrote about theconnection between cerebral dis-ease and mental illness:

Indeed, it seems that the psychical func-tions of the brain only suffer when thecortical substance of both hemispheresis affected by organic disease, or by dis-turbance of circulation. The correct-ness of this view is proved by the pecu-liarities of those cases where the state ofthe psychical functions forms an excep-tion to the above. For the general men-tal ruin that we describe when speak-ing of abscess also occurs in cerebraltumors, when they are accompanied bychronic meningitis of the convexity, orwhen the cortical substance of bothhemispheres is the seat of numerous tu-mors (cysticerci), or when their capil-laries are compressed by encroachingtumor in both hemispheres, or by ex-tensive secondary effusions in theventricles.10(p242)

By the late 1800s, the influence ofthe localizationist movement was be-coming more accepted and was beingadvanced by scientists such as PierreBroca (1824-1880), Hughlings Jack-son (1835-1911), Eduard Hitzig(1838-1907), and others. Also, the in-troduction of anesthesia to medi-cine some 35 years earlier set theground for the first attempt at surgi-cal resections of brain tumors.

The first of such attempts oc-curred in July 1879 at the Hospitalfor Sick Children in Glasgow, Scot-land. The patient was a 14-year-oldgirl with headaches, seizures that be-gan on the right side, and swellingaround her left eye. On clinicalgrounds, it was concluded that theperiosteal tumor was present and ir-ritating the left frontal lobe. A large

trephination was performed anteri-orly on the left side, revealing a largetumor of the dura mater, which wasexercising pressure on the brain. Theentire tumor was removed. The pa-tient lived for another 8 years, sub-sequently dying of Bright disease. Atautopsy, no evidence of intracranialtumor was found. The surgeon wasWilliam Macewen (1848-1924), whoin the same year had performed thefirst surgery for evacuation of a ce-rebral hematoma.11

In 1879, Ernest Field12 pub-lished a case report of a 49-year-oldman admitted on October 13, 1874,to the St Luke’s Hospital for Luna-tics, London, England. His symp-toms were described as follows:

Incoherent; imagines he is not in his ownhouse; thinks he has been working hardwhen he has done nothing of the kind;believes he is some other person; gets outof bed and says he wants to go home;does not get up usually unless pressedto do so; says people are in the room, andothers have visited him whom he has notseen; fancies he is leading a gipsy [sic]life; loss of memory; semi-comatose. . .complained of a slight headache. Gradu-ally he lost power in his left side and be-came hemiplegic; lay in bed for days ina lethargic condition, with no pains, andexpressing himself as quite comfort-able. Finally, on November 23rd at-tended with squinting and unequalpupils; after a few hours he died. Nec-ropsy—A cancerous tumor of the size ofa pigeon’s egg was found on the right sideat the base of the brain, close behind thefissure of Sylvius, pressing extensivelyon all the parts around, and causing com-mencing absorption of the petrous por-tion of the temporal bone. No menin-gitis or effusion of the ventricles wasfound.12(p870)

Field’s report ends stating, “But itwill be evident that such a case. . .could with perfect ease and propri-ety have been treated at home, hadhis family wished to be spared thedistress of believing that one of theirnumber had gone ‘out of his mind’and died in a lunatic asylum.”12(p871)

Shortly after this, other sur-geons began resecting tumors withinthe brain. Rickman Godlee at theHospital for Epilepsy and Paraly-sis, Regents Park in London, En-gland, performed the first paren-chymal brain tumor surgery inNovember 1884.13,14 The patient, MrHenderson, a native of Dubfries, was

a 25-year-old man who had focal sei-zures of the Jacksonian type, head-aches, and papilledema with hem-orrhages. No psychiatric symptomswere described.15 The tumor wasclinically localized as follows: “prob-ably of limited size involving the cor-tex of the brain and situated at themiddle part of the fissure of Ro-lando.”14 Surgery was performed,and the tumor was found in the ex-pected location. The patient had anexcellent immediate postoperativecourse but succumbed to wound in-fection 4 weeks later.14

The first primary brain tumor op-eration in the United States was per-formed at the German Hospital inSan Francisco, Calif, by Joseph O.Hirschfelder and William F. Morsein February 1886. This surgery wasperformed on a 33-year-old womanwith headaches and seizures, whoseclinical condition was deteriorat-ing. The anesthetic used was ether.The patient had a “dramatic recov-ery” shortly after surgery but died8 days later because of a woundinfection, although the surgeonswere devoted to Lister’s aseptictechniques.11,14

TEXTBOOK DESCRIPTIONS

Sir Byron Bramwell’s 1888 book In-tracranial Tumours16 demonstrateshow physicians had become moreaware of brain tumors and theirsubtle psychiatric manifestations:

In the later stages of those cases of tu-mours in which the mental deteriora-tion is extreme the patient may make nocomplaints, and symptoms of “coarse”lesion may be so little marked as to passunnoticed. It is obvious that under suchcircumstances the condition may be mis-taken for ordinary dementia. . . . Again,in those rare cases of intracranial tu-mour in which maniacal symptoms aredeveloped, unless the previous historyand course of the case are known to thephysician, the presence of a tumour maybe unsuspected.16(pp9,16)

In the same year, William Gow-ers,17 in a lucid and erudite para-graph, describes the state of knowl-edge regarding brain tumors andtheir symptoms. Further, he drawsattention to the “many errors ofdiagnosis in such cases; the unmis-takable symptoms of hysteria havecaused the physician to overlook




the symptoms of organic dis-ease.”17(p886)

Tumors with psychiatric symp-tomatology were more frequentlyconsidered in the differential diag-nosis but were not necessarily em-phasized. In the chapter on brain tu-mors in The Principles and Practiceof Medicine, Sir William Osler18

(1849-1919) wrote the book’s onlysentences regarding mental symp-toms in patients with brain tumors:“The patient may act in an odd, un-natural manner, or there may be stu-por and heaviness. The patient maybecome emotional or silly, or symp-toms resembling hysteria maydevelop.”18(p919) And in the samechapter, when discussing tumorsof the prefrontal region, Oslerwrites, “The most striking feature ofgrowths in this region is mental tor-por and gradual imbecility.”18(p920)

The first book dedicated to thetopic of brain tumors and their psy-chiatric manifestations was writtenby I. W. Blackburn,19 pathologist tothe Government Hospital for the In-sane, Washington, DC: Intracra-nial Tumors Among the Insane, pub-

lished in 1903. Although this bookbriefly describes some clinical cases,its focus was anatomical, patho-logic descriptions using pictures anddrawings of the brain tumors of allthe 29 cases found among 1642 au-topsies from 2807 deaths across 18years (1885-1903) (Figure). Ex-cluded from publication were smalltumors that at the time were deemednot to cause mental disturbance.

From the numbers suggested byBlackburn’s book, the rate of autop-sies at their institution for psychi-atric patients was 58.5%, and theprevalence of brain tumors in psy-chiatric patients was 1.76%. Thesefigures can be compared with laterseries such as that of the Boston State(mental) Hospital, Boston, Mass,where 2430 autopsies were per-formed from 1930 to 1950, with100% including examination of thebrain.21 Their prevalence of brain tu-mors was 3.5% (or 86 tumors).

CONCLUSIONS

The history of brain tumors andtheir psychiatric or mental clinical

manifestations has been summa-rized with a series of highlights andexamples characteristic of eachcentury. The association was slowto be recognized but has closelyfollowed the path of the evolutionof medicine, psychiatry, pathology,and surgery.

Accepted for Publication: May 18,2004.Correspondence: Adrian A. Jarquin-Valdivia, MD, RDMS, 2100 PierceAve MCS308, Vanderbilt Univer-sity Medical Center, Nashville, TN37212 ([email protected]).

REFERENCES

1. Morgagni GB. The Seat and Causes of Diseases.Alexander B, trans. Book 1. New York: New YorkAcademy of Sciences; 1769.

2. Weiner DB. Philippe Pinel’s “Memoir on Mad-ness” of December 11, 1794: a fundamental textof modern psychiatry. Am J Psychiatry. 1992;149:725-732.

3. Preuss J. Biblical and Talmudic Medicine. Ros-ner F, trans. New York, NY: Sanhedrin Press; 1978.

4. Babiloni F, Babiloni C, Carducci F, Cincotti F, Rossini

Figure. Case 774 from Blackburn’s Intracranial Tumors Among the Insane,19 the first book dedicated to brain tumors from autopsies from a psychiatric hospital.The depiction is that of a large spindle-celled endothelial sarcoma, later to be known as meningioma (term introduced by Harvey Cushing20 in 1922).




PM. ‘The stone of madness’ and the search forthe cortical sources of brain diseases with non-invasive EEG techniques. Clin Neurophysiol. 2003;114:1775-1780.

5. Hughes JC. Thomas Willis: the first Oxfordneuropathologist. In: Clifford FC, ed. Neurosci-ences Across the Centuries. London, England:Smith-Gordon & Co; 1989:87-96.

6. Willis T. The London Practice of Physick. Lon-don, England: The Classics of Medicine Library;1685.

7. Borit A. History of brain tumors of the pineal region.Am J Surg Pathol. 1981;5:613-620.

8. Battie W. The Causes of Madness. London, En-gland: Fleet Street; 1758:50-58.

9. Liberini P, Spano P. From the mind to the brain:

an unusual pathway. J Hist Neurosci. 2000;9:41-45.

10. Niemeyer FV. Text-Book of Practical Medicine.Humphreys GH, Hackley CE, trans. Vol 2. 7th ed.New York, NY: D Appleton & Co; 1870.

11. Pierce J. The First Attempts at Removal of BrainTumors. New York, NY: Raven Press; 1982.

12. Field E. Cerebral tumour, producing mentalsymptoms. The Lancet. 1879;870-871.

13. Kirkpatrick DB. The first primary brain-tumoroperation. J Neurosurg. 1984;61:809-813.

14. Keller T. The first primary brain tumor operationin America. Surg Neurol. 1996;45:463-466.

15. Trotter W. A landmark in modern neurology.Lancet. 1934;1207-1210.

16. Bramwell B. Intracranial Tumours. Philadel-

phia, Pa: JB Lippincott Co; 1888.17. Gowers WR. A Manual of Diseases of the Ner-

vous System. American ed. Philadelphia, Pa:P Blackiston, Son & Co; 1888.

18. Osler W. The Principles and Practice of Medicine.New York, NY: Appleton and Co; 1894.

19. Blackburn I. Intracranial Tumors Among the Insane.Washington, DC: Government Printing Office; 1903.

20. Wang H, Lanzino G, Laws ER Jr. Meningioma, thesoul of neurosurgery: historical review. SeminNeurosurg. 2003;14:163-168.

21. Raskin N. Intracranial neoplasms in psychotic pa-tients: survey of 2,430 consecutive complete au-topsies performed at the Boston State Hospital dur-ing the period 1930-1950. Am J Psychiatry. 1956;112:481-484.




Documents

Psychiatric Symptoms and Brain Tumors