NEUROSURGERY VOLUME 64 | NUMBER 6 | JUNE 2009 | 1183

LEGACY

Paula Eboli, M.D.Department of Neurosurgery,University of Illinois at Chicago,Chicago, Illinois

James L. Stone, M.D.Department of Neurosurgery,University of Illinois at Chicago,Chicago, Illinois

Sabri Aydin, M.D.Department of Neurosurgery,University of Illinois at Chicago,Chicago, Illinois

Konstantin V. Slavin, M.D.Department of Neurosurgery,University of Illinois at Chicago,Chicago, Illinois

Reprint requests:James L. Stone, M.D.,912 S. Wood Street,Chicago, IL 60612.Email: jlstone4@aol.com

Received, June 18, 2008.

Accepted, October 9, 2008.

Copyright 2009 by theCongress of Neurological Surgeons

Trigeminal neuralgia (TN) is a well knownclinical diagnosis, characterized by agoniz-ing, paroxysmal, and lancinating pain (7).The pain is perceived within 1 or more divisionsof the trigeminal nerve, is usually brief withrepetitive bursts every few seconds, and can betriggered by activities such as chewing, speak-ing, brushing the teeth, swallowing, or touchingthe face. A discrete trigger zone stimulated bytouch or even a breeze of air can set off a typicalparoxysm of pain. Characteristically, whenasked, the patient will point to this zone on theface avoiding direct touch to that area. The painis virtually always unilateral, with rare reports ofbilateral symptoms (17, 19).

HISTORICAL ASPECTSOF FACIAL PAIN

There have been many historical descriptionsof facial pain over the past several thousandyears. Hippocrates (circa 460377 BC) of ancientGreece is credited with being the first physicianto reject superstitions, supernatural beliefs, ordivine forces as the cause of illness and hasoften been called the Father of Medicine. He

greatly advanced the systematic study of clini-cal medicine, summarized the medical knowl-edge of previous schools, and advocated practi-cal and ethical physician practice through theHippocratic Oath and other works. Hippocratesmight have encountered TN, but unfortunatelyhis broad characterization of headaches as con-sisting of infinite forms, was too vague (12).The same is true of Aretaeus (150 AD) andGalen (circa 129200 or 216 AD), 2 of the mostcelebrated ancient Greek physicians. Theseauthors differentiated heterocrania (Galen)and hemicrania (Aretaeus), terms reflectingunilateral headache, from what they calledother head ailments or kephalalgia (16).

Aretaeus (4, 12, 21) of Cappodocia, a 2nd cen-tury AD physician who followed the method ofHippocrates, is believed to be the first todescribe hemicranial headaches as occurring inparoxysmal attacks, separated by pain- freeintervals, accompanied by a facial spasm, andfollowed by a fainting spell. However, furtheranalysis of the signs and symptoms described inhis patient would likely be more compatiblewith atypical TN or migraine (12).

In analyzing the history of facial pain, thereis an important error that has been copiedagain and again (12). It is the belief that theArabic medical school possessed knowledge

HISTORICAL CHARACTERIZATION OFTRIGEMINAL NEURALGIA

TRIGEMINAL NEURALGIA IS a well known clinical entity characterized by agonizing,paroxysmal, and lancinating facial pain, often triggered by movements of the mouthor eating. Historical reviews of facial pain have attempted to describe this severe painover the past 2.5 millennia. The ancient Greek physicians Hippocrates, Aretaeus, andGalen, described kephalalgias, but their accounts were vague and did not clearly cor-respond with what we now term trigeminal neuralgia. The first adequate description oftrigeminal neuralgia was given in 1671, followed by a fuller description by physicianJohn Locke in 1677. Andr described the convulsive- like condition in 1756, and namedit tic douloureux; in 1773, Fothergill described it as a painful affection of the face;and in 1779, John Hunter more clearly characterized the entity as a form of nervousdisorder with reference to pain of the teeth, gums, or tongue where the disease doesnot reside. One hundred fifty years later, the neurological surgeon Walter Dandyequated neurovascular compression of the trigeminal nerve with trigeminal neuralgia.

KEY WORDS: Facial pain, Historical review, Trigeminal neuralgia

Neurosurgery 64:11831187, 2009 DOI: 10.1227/01.NEU.0000339412.44397.76 www.neurosurgery- online.com

ABBREVIATIONS: TN, trigeminal neuralgia

of TN or tic douloureux. This is mainly the result of a misin-terpretation of an equivocal Latin translation of the Arabic text,The Canon of Medicine or The Law of Medicine, a 14-volumeArabic medical encyclopedia written by Ibn Sina (Avicenna;9801037) and completed in 1025. Ibn Sina, a Persian, was theforemost physician and Islamic philosopher of his time. Hediscussed what he called lakwat. In Latin, the title of thischapter was Tortura facei. The unfortunate choice of theword torturaequivalent to torture and distortionappar-ently produced the mistake. The Arabian expression wasindeed composed of the negation la and the substantivekuwwet, meaning strength, power, or nerve. Therefore,Lakwat means strengthlessness weakness or, in general,paralysis. The entity in question was more likely facialparalysis (12).

The first clear description of TN was provided in 1671. Thepatient was a well known physician, Johannes LaurentisBausch of Germany (16051665) (Fig. 1), founder and first pres-ident of the Imperial Leopoldian Academy of Natural Sciences,

who suffered from severe TNfor 4 years. The pain pre-vented him from eating anysolid food and he was almostunable to speak. Emaciationgradually occurred and led todeath from a stroke in 1665.Bauschs illness was detailedin his eulogy published in theAcademy volume coveringthe year 1671 (4, 8, 12, 21).

The well known philoso-pher and physician JohnLocke (16321704) providedthe first full description of TNand its treatment performedby a physician (15). While inParis in 1677, Locke was cal -led to see the wife of the Eng -lish Ambassador, the count-ess of Northumberland, who

was suffering an excruciating pain in the face and lower jaw (13,14). Two teeth had been removed without relief. In letters to hisfriend Mapletoft, he described her suffering in detail and out-lined his treatment, which included a thorough purging of thelady (1315).

The recognition of TN as a definite clinical entity is credited toNicolaus Andr in 1756 (1, 3, 21) (Fig. 2). Andr was a French sur-geon who conceived the illness in terms of convulsions. He fol-lowed the methods used by Aretaeus and Caelius Aurelianus(5th century Roman physician) to establish a differential diagno-sis between true tonic convulsions, tetanus, and spasm cinique(lip retraction as in smiling). He concluded the convulsivemovements that disturbed his patients could not be describedunder spasm cinique but were more appropriately designatedtic douloureux. The term tic douloureux was used to imply facialwincing, grimacing, and contortions that accompanied the violent

and unbearable pain (1, 3, 4).Andr reported 5 cases, thefirst of which he saw in 1732.Of the 5 patients reported indetail, only the second andthird cases were true TN.Andr believed that the causewas a local disease process orvicious nervous liquids thatirritated the affected nerveand caused painful shocks.Using this reasoning, he fol-lowed the proposal of Mar -chal, contemporary surgeonto Louis XIV, and ap pliedcaustic substances to theinfraorbital nerve at its infra-orbital foramen over a periodof days until the nerve wasdestroyed (4).

Approximately 17 yearsafter Andrs description inFrench, the English physicianJohn Fothergill (Fig. 3) de -cribed the condition in his1773 book Medical Obser -vations and Inquiries. Fother gillwrote of a painful affectionto the face, a disease thatwas not a convulsive disorder(9). He said that this conditionaffected people of advancedage, women more than men,and that it could be related totumors. He des cribed thepain as sudden and excruci-ating, lasting a short time,

and returning at irregular intervals. He also stated that, to hisknowledge, this was a newly described condition.

John Hunter (17281793) (Fig. 4), the foremost British ana -tomist and surgeon of his time, credited as being theFounder of Scientific Surgery, had a profound and originalunderstanding of functional anatomy and physiology. Hethought that any sensory stimulation carried to excess couldresult in pain, and when a large nerve is compressed, themost acute sensation (pain or numbness) will be some dis-tance below the compression (20). Hunter did not adhere tothe then- popular concept that nerves function as hollow tubesconveying a fluid. He knew that inflammatory pain arosefrom the nerve endings of a diseased part, but that pain of thenervous kind arose from the nerves themselves beingaffected, with the parts that these nerves lead to being unaf-fected. He clearly described what we call forms of referredpain today (20).

Nervous problems and pain were of much interest to Hunter.In 1778, he wrote the Natural History of the Human Teeth with a

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EBOLI ET AL.

FIGURE 1. Portrait of JohannesLaurentis Bausch (16051665).

FIGURE 2. Portrait of NicolausAndr (170418th century).

FIGURE 3. Portrait of John Fother -gill (17121780).

pertinent chapter entitledNervous Pains in the Jaws(10). In the monographspreface, he states he hadbeen aware of most of theseconditions be fore 1755 andhad lectured on these topicsin his ana tomy and surgerycourse since that time:

There is one disease ofthe jaw which seems inreality to have no con-nection with the teeth,but of which the teethare generally suspectedto be the cause . . . atooth is often suspectedand it is drawn out; butstill the pain contin-ues. . . . It is then sup-

posed that the wrong tooth was ex tracted where- uponthat in which the pain now seems to be in is drawnbut with as little benefit. I have known cases of thiskind where all the teeth of the affected side of the jawhave been drawn out, and the pain has continued inthe jaw; in others . . . the sensation of pain hasbecome more diffused, and has at last, attacked thecorresponding side of the tongue. Hence it shouldappear that the pain in question does not arise fromany disease in the part, but it is entirely a nervousaffection (10, pp 6162).

John Hunters early contribution to TN seems to have beenoverlooked in previous reviews (4, 8, 12, 21).

After descriptions by Andr, Fothergill, and Hunter, occa-sional cases of the condition were reported. In 1782, Thouretconsidered it to be an affection of the nerves of the face, espe-cially in the distribution of the infraorbital, but also implicatingthe lower jaw (4). In 1802, Chaussier classified the variousforms of tic douloureux according to the 3 trigeminal divisions,but included the VIIth nerve as well (4). Very little was addedto the above clinical descriptions, but it was Fothergills greatnephew Samuel Fothergill who more definitively labeled thesite of the lesion as the trigeminal nerve in his Concise andSystematic Account of a Painful Affection of the Nerves of theFace Commonly Called Tic Dolourex. Consequently, TN hasbeen called Fothergills disease (18).

Nevertheless, the facial grimacing accompanying ticdouloureux led many to believe that the condition involvedboth the trigeminal (V) and facial (VII) nerves as a unit. It wasnot until the 1820s, when Charles Bell (17741842) character-ized the separate functions for these 2 nerves, that ticdouloureux or TN was truly considered localized to the trigem-inal nerve (2, 6). However, as late as 1919, prominent physiciansin England and France, im pressed with the convulsive facialspasms, thought that tic douloureux was an epileptiform

neuralgia signifying a spasmof muscle that was painful,rather than a pain of spas-modic character (11, 22).

In the 1930s, while perfor -ming partial sectioning of thetrigeminal root for typical TNby way of a posterior fos sa ap -proach, the neurological sur -geon Walter Dandy (18861946) (Fig. 5) noted that, Thesensory root is frequentlyindented, lifted up or bent atan angle by the artery (5, p450). This I believe is thecause of tic douloureux (6, p170). By this time, with accu-mulated surgical knowledge,it was also appreciated that

an occasional tumor in the cerebellopontine angle could impingeupon the trigeminal nerve and cause a similar or atypical TN.

CONCLUSION

Reports of facial pain have been progressively described inthe literature from Hippocrates (circa 400 BC) to the presenttime. The understanding and characterization of this conditionhas evolved through the years to be known as TN, either typi-cal or atypical. Thus, our accumulated information on ticdouloureux or TNa fascinating and challenging conditionapproximates much of the period of recorded medical literatureand yet is certainly not complete. So often, medical knowledgeyields more questions for future generations than answersyet, by nature, we continue in pursuit.

REFERENCES

1. Andr M: Practical observations on urethral diseases, and factual information onconvulsive facial contortions with principles for cure of associated gangrenous andcancerous conditions by use of various solvents and caustics. College of the RoyalAcademy [in French]. Paris, De Chir.rue S. Jacq. A lOlivier, 1756.

2. Bell C: On the nerves; giving an account of some experiments on their struc-ture and functions, which lead to a new arrangement of the system. PhilosTrans R Soc 111:398424, 1821.

3. Brown J, Coursaget C, Preul M, Sangvai D: Mercury water and cauterizingstones: Nicolas Andr and tic douloureux. J Neurosurg 90:977981, 1999.

4. Cole CD, Liu JK, Appelbaum RI: Historical perspectives on the diagnosisand treatment of trigeminal neuralgia. Neurosurg Focus 18:E4, 2005.

5. Dandy WE: Concerning the cause of trigeminal neuralgia. Am J Surg24:447455, 1934.

6. Dandy WE: Lesions of the cranial nerves. Lewis Pract Surg 12:167202, 1954.7. Eller JL, Raslan AM, Burchiel KJ: Trigeminal neuralgia: Definition and classi-

fication. Neurosurg Focus 18:E3, 2005.8. Fields WS, Lemak NA: Trigeminal neuralgia: Historical background, etiology

and treatment. BNI Q 3:4756, Spring 1987.9. Fothergill J: On a painful affliction of the face. Med Observ Inquiries 5:129

142, 1773.10. Hunter J: Nervous pain in the jaw, in Hunter J: The Natural History of the

Teeth: Explaining Their Structure, Use, Formation, Growth and Diseases. Part II.London, J. Johnson, 1778, ed 2, pp 6163.

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FIGURE 4. Portrait of John Hunter(17281793).

FIGURE 5. Photograph of WalterDandy (18861946).

various forms of pain and came so clearly to conclusion that TN was itsown unique entity. The extraction of teeth to cure this disorder clearlydid not work; the description was provided more than 230 years ago,yet this error in treatment still persists. The authors have provided uswith a wonderful and most insightful article on this historical disorder.

James T. GoodrichBronx, New York

The authors recount and attempt to reconstruct the historical aspectsof TN and our current understanding of this disorder. They makethe interesting observation that the Persian scholar Ibn Sina may bewrongly credited with a description of this disorder, owing in largepart to mistranslation, from the original Arabic text, of a word thatwas thought to signify pain, but which more likely means paralysis.They recount observations from the British and French schools in the17th century as the landmark contributions to the modern notionsunderlying TN. The contributions of John Hunter, an 18th centuryanatomist and surgeon, to the understanding of the pathophysiology ofTN are particularly interesting, since previous reviews have notacknowledged his work.

Curiously, the observations of Ismail Al-Jurjani are not mentioned inthis article. This Persian physician, a protg of Ibn Sina, likely diddescribe TN in the following passage of his book, Zakhireh-i-Khwarazm-shah (Thesaurus of the Shah of Khwarazm): There is a type of pain whichaffects the teeth on one side and the whole of the jaw on the side whichis painful (1). Although it is, of course, impossible to know with cer-tainty that he was referring to TN, Jurjani was prescient in his explana-tion: The cause of spasm and anxiety is the proximity of the artery tothe nerve (1).

This article makes for a concise and interesting narrative of our under-standing of TN throughout history. It is humbling to realize that themodern concepts of pathophysiology of this disorder are not vastly dif-ferent from observations and speculations that are nearly 1000 years old.

Oren SagherAnn Arbor, Michigan

1. Ameli NO: Avicenna and trigeminal neuralgia. J Neurol Sci 2:105107, 1965.

In this brief but entertaining review, Eboli et al. trace the history ofTN through the ages, as the signs and symptoms that characterizethe disease emerged from increasingly detailed descriptions. Onelesser-known contribution to this narrative is that of the famousScottish surgeon John Hunter, who described pain in the jaw thatwas not related to the teeth. Although Hunters cursory description ofthe disorder falls far short of Fothergills, he did state in his 1778treatise that Neuralgia of the fifth pair of nerves may arise fromteeth that are perfectly sound (1), thus making the connectionbetween this mysterious pain syndrome and the fifth cranial nerve.Illustrative of the times, Hunters treatment recommendations were atleast far more benign than carbamazepine, radiofrequency lesioning,or microvascular decompression: Sea bathing has been in some casesof singular service (1).

Jaimie M. HendersonStanford, California

1. Hunter J: The Natural History of the Teeth: Explaining Their Structure, Use,Formation, Growth and Diseases. London, J. Johnson, 1778.

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11. Hutchinson J: Epileptiform neuralgia: Its course and symptoms, in On FacialNeuralgia and Its Treatment. New York, William Wood, 1919, pp 4548.

12. Lewy FH: The first authentic case of major trigeminal neuralgia and somecomments on the history of this disease. Ann Med Hist 10:247250, 1938.

13. Locke J: Letters to Dr. Mapletoft: Letter VII, Paris, 9th August 1677; Letters IX,X, Paris, 4th December 1677. The European Magazine, February 1789, pp 8990,March 1789, pp 185186.

14. Locke J: Letter to Dr. Mapletoft, in Stookey B, Ransohoff J: Trigeminal Neuralgia:Its History and Treatment. Springfield, Charles C. Thomas, 1959, pp 810.

15. Pearce JM: John Locke and the trigeminal neuralgia of the Countess ofNorthumberland, in Fragments of Neurological History. London, ImperialCollege Press, 2003, pp 280283.

16. Pearce JM: Migraine. Eur Neurol 53:109110, 2005.17. Ropper A, Brown R: Adams and Victors Principles of Neurology. New York,

McGraw- Hill Professional, 2005, ed 8, pp 161167, 11781190.18. Rose FC: John Fothergill, in Rose FC (ed): A Short History of Neurology: The

British Contribution 16601910. Oxford, Butterworth-Heinemann, 1999, pp8892.

19. Rowland L: Cranial and peripheral nerve lesions, in Rowland L (ed): MerrittsNeurology. Baltimore, Lippincott Williams & Wilkins, 2005, ed 11, pp 527529.

20. Stone J, Goodrich JT, Cybulski GR: John Hunters contribution to neuro-science, in Whitaker H, Smith CUM, Finger S (eds): Brain, Mind and Medicine:Essays in Eighteenth Century Neuroscience. New York, Springer, 2007, pp 6784.

21. Stookey B, Ransohoff J: Historical background of the trigeminal nerve andtrigeminal neuralgia, in Trigeminal Neuralgia: Its History and Treatment.Springfield, IL, Charles C Thomas Publisher, 1959, pp 332.

22. Trousseau A: Treatise on therapeutics. Clin Med Htel Dieu 2:156, 1885.

COMMENTS

This review of the history of trigeminal neuralgia (TN) reminds us ofthe benefit of careful, unbiased observation and reporting of med-ical phenomena and the unique role that a neurosurgeon may have asa result of his/her ability to see not only the clinical presentation of adisease but also the operative anatomy in a living patient.

Ronald BrismanNew York, New York

TN is clearly a miserable disorder to have, and it has only beenwithin the past 30 years that we have had any form of reasonablemethod, either surgical or medical, to treat it. What a delight it was toread of this disorders most interesting historical background. Startingwith the ancients, Eboli et al. have reviewed early writings, looking fordocumentation of TN. Although I would have thought that principalslike Hippocrates and Galen were likely to have written on the subject,it is not clear that they were aware of this disorder.

The authors have provided a notable service to the historical com-munity in correcting errors in the literature dealing with Avicenna andhis supposed description of TN; the authors point out that he waslikely describing facial paralysis and not facial pain. The first cleardescription appears to be that by a physician who suffered from thedisorder, Johannes Laurentis Bausch, who was so debilitated by the dis-order that he died from a stroke.

In treating patients with TN, it is very common to see them aftermultiple tooth extractions and root canals, all with no relief of the pain.Therefore, it was interesting to read John Lockes 1677 report of seeinga noblewoman treated in Paris with extractions. Locke provided a cleardescription of this painful disorder. Unfortunately for this lady, thetreatment was purginga treatment that clearly would not have anybenefit, except for a placebo effect.

The authors present a number of historical vignettes on TN. One Iparticularly enjoyed concerned John Hunter. It was just amazing tome to see the clarity of thought in Hunters mind as he sorted out the

The authors provide a concise and informative review of the longhistory of this very important neurological malady. The fact thatthis condition is diagnosed by the clinical history allowed TN to be rec-ognized in ancient times, but it is interesting to note that it was not welldescribed as a separate clinical syndrome until a few hundred yearsago. It is also very appropriate to note Professor Walter Dandys sem-inal observation of the vascular compression etiology of TN. It is help-ful for modern neurosurgeons and neurologists to know that surgeryfor TN was prominent at the origins of modern neurosurgery, even ata time when the mortality of cranial operations was quite high. This isa testament to the misery provoked by this condition, as well as thesuccess of trigeminal nerve transection/ablation (and subsequent vas-cular decompression operations).

Robert R. GoodmanNew York, New York

This article deals with TN, one of the neurological diseases that,although benign, have challenged the quality of life of patientssince ancient times. It suggests a new classification of the differenttypes and pathology of facial pain, in which TN is included.

This concept is very important in a time of evidence-based medicine.Indeed, the comparison of different therapeutic methods and techniquesis possible only if the clinical picture of a disease is recognized and clas-sified, avoiding the so-called apples and oranges comparison.

The historical report of the descriptions, by various authors, of thisdisease is quite interesting. It gives an idea of the difficulty, during theEnlightenment period, of accepting the concept that pain could arisefrom a structure that is different from the one in which the pain isreferred (e.g., the teeth instead of the nerve in TN). Nevertheless, theproposed classification does not consider the possibility of a doublepathologyagain, this is an event contrary of our positivistic and sim-plistic approach to disease. Our experience with typical TN and mul-tiple sclerosis (1) is witness to that concept: more than 50% of patientswere cured with a technique that the magnetic resonance imagingrationale suggested should be avoided.

The authors have reported on the historical contributions of out-standing surgeons of the past. They were deprived of modern imagingstudies but guided by clinical expertise, i.e., the rigorous analysis ofsymptoms and anatomopathological knowledge.

Giovanni BroggiMilan, Italy

1. Broggi G, Ferroli P, Franzini A, Servello D, Dones I: Microvascular decompres-sion for trigeminal neuralgia: Comments on a series of 250 cases, including 10patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 68:5964,2000.

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Mouse brain cryosection. Axons were labeled with Vybrant DiI cell-labeling solution (Cat. no. V22885). Neuron cell bodies werestained with NeuroTrace 500/525 green fluorescent Nissl stain (Cat. no. N21480). Nuclei were stained with DAPI (Cat. no. D1306,D3571, D21490). Copyright 2009 Life Technologies Corporation. See Khalessi et al., pp 10151028.

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