Historical Vignette: Henri Parinaud (1844-1905): French Ophthalmologist and Pioneer in Neuroophthalmology Gill Roper-Hall, D.B.O.T., C.O., C.O.M.T.
INTRODUCTION Henri Parinaud was a French ophthalmologist whose name is well known to those who clinically examine patients with his eponymic syndrome and study the causative mechanisms. He had a great interest in neuroophthalmology and was one of the first physicians to practice in that specialty (Figure 1). EARLY YEARS Parinaud was born on May 1, 1844, in Bellac, in the Haute-Vienne region of central France. He was the oldest child in a family of modest means, his father being a locksmith. After attending elementary school, at thirteen he entered the local seminary to pursue higher studies. His father died when Parinaud was nineteen, leaving him the responsibility of caring for his mother and younger brothers. As a bright and determined young man, he earned money tutoring others while continuing his own education, and he was able Requests for reprints should be addressed to: Gill RoperHall, D.B.O.T., C.O., C.O.M.T., Department of Ophthalmology, Saint Louis University Medical Center, 1755 S. Grand Blvd., St. Louis, MO 63131.
FIGURE 1: Dr. Henri Parinaud and his signature. (Published in his obituary in the Annales d’Oculistique 1905; 133:320. Reprinted with permission from Elsevier-Masson.)
to provide for his family over the next few years. In 1865, at the age of twenty-one, he set off for Limoges to study medicine. He was awarded a merit prize in medicine in 1868.1-4 THE FRANCO-PRUSSIAN WAR After completing his studies in Limoges, Parinaud left for Paris in 1869 to continue his medical training. In 1870, the Franco-Prussian war broke out and he was called up to serve as an army medical officer (Figure 2). He was assigned to
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FIGURE 2: Army medical officer Henri Parinaud circa 1870 during the Franco-Prussian war. (Photographer unknown. Courtesy of Eye2blog.blogspot.com)
the Red Cross field ambulance service in Metz, where he saw action evacuating the wounded. He conducted himself courageously and was decorated for his bravery by French Prime Minister Léon Gambetta.4 ACADEMIC OPPORTUNITIES The war ended in 1871 and Parinaud returned to Paris to continue his training, first at the Hôpital des Enfants-Malades (Hospital for Sick Children) and later at the Hospice de la Salpêtrière.1-4 Paris at that time was a hotbed of neurological and medical discovery. While working at the Hôpital des Enfants-Malades, Parinaud observed that papilledema in children with meningitis was not caused by optic neuritis, but by obstructive hydrocephalus. He wrote a doctoral thesis on this topic in 1877, which attracted the attention of Professor Jean-Martin Charcot at the Salpêtrière.5 The Salpêtrière was recognized as a top teaching hospital where many famous physicians worked in collaboration, and it was a desired destination for those wishing to further their medical training. The famous Hospice de la Salpêtrière had been com-
American Orthoptic Journal
missioned by King Louis XIV in 1656. It was built on the grounds of a former gunpowder factory (salpêtrière or saltpeter being a constituent of gunpowder). It had a grim past, serving as a prison and institution to keep the mentally unstable, the criminally insane, epileptics, the poor, and other social “undesirables” off the streets.6 In the 1700s, the Salpêtrière was a dumping ground for women from all class backgrounds with “hysteria.” There was no humane treatment for this condition at the time, and once women were admitted, many lived out their remaining existences there. On the eve of the French Revolution, it was the largest hospital in the world, housing 10,000 patients, many of whom were considered criminally or violently insane. It did not fare much better until the middle of the nineteenth century, when mental illness was given its overdue recognition. Under the guidance of physician Philippe Pinel, more humane forms of treatment were introduced and the Salpêtrière developed as a psychiatric center. It was at this time that many neurological and neurophysiological disorders such as neurosyphilis, epilepsy, and stroke were recognized and the Salpêtrière quickly became a desired center of learning.5 Charcot, considered by many to be the founding father of neurology, enjoyed an international reputation and students came from all over Europe to hear his lectures at the Salpêtrière. Among them were Henri Parinaud and a young physician named Sigmund Freud! There is a famous painting by André Brouillet titled A Clinical Lesson at the Salpêtrière (displayed at Descartes University, Paris), which shows Charcot teaching in a classroom full of young doctors, one of whom is Parinaud. Other renowned neurologists in the painting include Joseph Babinski and Gilles de la Tourette. The hospital still enjoys international acclaim with experts practicing in most medical specialties. Numerous celebri-
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ties have been treated at the Salpêtrière, including some of the French presidents. Several notables have died there, including Josephine Baker in 1975 and Diana, Princess of Wales, in 1997. Charcot established a neurological service at the hospital, one of the earliest of its kind. His name is attached to over twenty-five different clinical entities, and he was the first to describe multiple sclerosis. He invited Parinaud to examine some of the ocular manifestations seen among his neurological patients. This was Parinaud’s first step into the world of neurology. He was appointed by Charcot as chief of ophthalmology of the neurology service at the hospital and this setting allowed him to develop and establish the discipline of neuroophthalmology.1-4 RESEARCH INTERESTS Charcot took Parinaud under his wing and introduced him to interesting and challenging neurological cases, particularly those pertaining to vision and the ocular motor system. This collaboration between Parinaud, Charcot, and other neurology colleagues led to studies and publications on multiple sclerosis, ophthalmoplegic migraine, ocular findings in hysteria, and disorders of eye movement. Parinaud was one of the first physicians to distinguish between central and peripheral causes of ocular paralysis, and he had a particular interest in supranuclear lesions affecting eye movements. He recognized what he referred to as “parallel and non-parallel” eye movements, now called conjugate and disjugate gaze, and deduced that there was a central system for conjugate eye movements.7 He examined and studied patients with disorders of horizontal and vertical eye movements, and those with convergence and divergence paralysis and convergence spasm.8, 9 Parinaud wrote two seminal papers that together form the basis for the syn-
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drome that carries his name. The first, “Paralysie des mouvements associés des yeux,” was published in 1883.7 The second, based on an 1885 publication simply called “Paralysie de la convergence,”10 was translated into English as “Paralysis of the Movements of Convergence of the Eyes” in 1886.11 ACADEMIC STANDING Although he had no formal academic appointment, Parinaud was well regarded by his colleagues and was an active member of various ophthalmology and neuroscience societies including the Paris Ophthalmology Society (La Societé d’Ophtalmologie de Paris) where he presented many scientific papers. He was a founding member of the French Ophthalmology Society (La Societé Française d’Ophtalmologie) and when the Neurological Society (La Societé de Neurologie) was founded in 1899, he served on the Council.1, 4 CLINICAL PRACTICE Despite his interest in neuroophthalmology, Parinaud was foremost an ophthalmologist. He treated ocular conditions such as iritis and lacrimal infections, and performed cataract, glaucoma, ptosis, and strabismus surgery.1, 2 He published articles on some of his more interesting ophthalmic cases and there are several clinical conditions that also bear his name: Parinaud oculo- glandular syndrome, caused by the same organism responsible for cat scratch disease, Parinaud conjunctivitis, and Parinaud dermo-lipomata.2, 9, 12 PERSONAL INTERESTS Parinaud was a generous and endearing person. Despite his humble beginnings, he was concerned about his fellow man and devoted much time to running a free clinic with his students.3 He was not in-
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terested in self-aggrandizement, and was always approachable and kind.2-4 He was quiet and unassuming, well respected by his peers. Parinaud was happily married and had three daughters. Despite his fondness for his family, and his dedication and industrious approach to his patients, research, and teaching duties, he somehow found time to compose music. This was published under the pseudonym of Pierre Erick.1, 2, 9 PUBLICATIONS Parinaud was a prolific writer. During his career, he published over seventy scientific articles and two books: La Vision; étude physiologique with 218 pages, published in 1898, and Le Strabisme et son Traitement with 197 pages in 1899.13, 14 With almost no exceptions, he published at least one article every year between 1877 and 1904 and often as many as four or more in the same year. In 1881, he published nine articles! These are listed in chronological order as an addendum to a long obituary in Annales d’Oculistique about his distinguished life.1 His first published article was the aforementioned thesis on optic neuritis in acute meningitis in childhood.5 His final two publications were on unrelated topics: stereoscopy and visual projection, and ptosis surgery, the latter based on a paper delivered before the Paris Ophthalmology Society on Feb 2, 1904, just a year before his death.15, 16 PARINAUD’S EPONYMIC SYNDROME Three important points should be made about Parinaud and the syndrome that carries his name. First, it should be emphasized that Parinaud did not name this syndrome—it was attributed to him by others. Ouvrier comments that he was a modest man and it would not have occurred to him to assume the credit for this.4
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A second consideration is that not all the features now known to be part of this syndrome were reported by him in his early description. Although Parinaud described vertical gaze paresis, he was not the first to do so. He gave credit for this in his article to Dr. Carl Wernicke (of Wernicke’s encephalopathy fame). Convergence retraction nystagmus and bilateral upper eyelid retraction were not observed as part of the syndrome. Neither Parinaud nor any of his contemporaries demonstrated that oculocephalic and vestibulo-ocular responses were usually normal in these cases.7, 11 The third important point was that Parinaud did not describe classic light / near dissociation of the pupils in any of his cases. A variety of responses were reported, but he observed pupillary abnormalities fairly consistently in which the near response was absent or poor and the responses to light were better or even normal. So what exactly did Parinaud report? He emphasized the difference between peripheral and central paralysis of eye movement and recognized central paralysis of convergence as distinct from the more commonly occurring convergence insufficiency. He classified organic convergence paralysis into two types: essential and combined. In essential convergence paralysis, the patient had diminished or absent convergence function, but retained full adduction of the “internal recti” on lateral movements. In combined cases, vertical gaze paralysis accompanied the convergence paralysis.7, 11 He described the ocular findings in ten patients in the French article in 1883, some of whom reappear among the eight case reports in the 1886 article translated into English. Most patients had convergence paralysis; one had divergence paralysis, and another had both. In others, there was an associated vertical gaze paresis.7, 11 The pupillary responses to light and
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near stimuli were equal in two patients, normal in one, and slightly diminished but equal in the other. In the remaining six patients, the pupillary response to attempted convergence was either absent or diminished, whereas the response to a light stimulus was normal in four patients and diminished in two.7, 11 With this constellation of pupillary abnormalities and gaze disorders, he postulated that the location of the lesion was in the corpora quadrigemina, a fact that was supported until recent years. Parinaud’s description of the pupillary responses in his cases has drawn criticism from later authors, because he did not describe typical light/near dissociation pupillary responses. By contrast, he described several different responses, including a poor or absent pupillary response to a near stimulus, but with better pupillary responses to light. This finding is rare, but is sometimes seen in patients with complete convergence paralysis. There is a poor or absent pupillary response to a near stimulus, but normal light responses may be retained. Since many of Parinaud’s reported cases had convergence paralysis without vertical gaze involvement, this may explain why he described pupillary responses that were the opposite of what most observers report in dorsal midbrain syndrome.7, 11 Although convergence retraction “nystagmus” is a common finding with lesions occurring in the dorsal midbrain, Parinaud did not mention this feature in his well-known article. This unusual eye movement affecting both eyes was described separately by Hermann Koerber, Robert Salus, and Anton Elschnig, all of whom published their observations after Parinaud wrote his landmark article.17-19 In fact, this led some to call the collective findings of vertical gaze paresis and convergence retraction nystagmus the Koerber-Salus-Elschnig syndrome.2, 20-22 Upper eyelid retraction was not mentioned
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by Parinaud or any of the other earlier authors. In an article on midbrain syndromes, Liu et al. discuss the heritage of early researchers’ work in developing a modern understanding of clinical conditions and their pathophysiology.23 Eponymic syndromes often help to organize scientific information. Clinical localization, as practiced by the nineteenth century neurologists, is still valuable today and in many instances their neuroanatomical correlations, without modern investigative tools, was surprisingly accurate. OTHER NAMES FOR THIS SYNDROME Still named after Parinaud in most modern texts, the condition is known by a variety of other monikers: Parinaud syndrome, Parinaud ophthalmoplegia syndrome, Parinaud vertical ophthalmoplegia, Koerber-Salus-Elschnig syndrome, Parinaud- Koerber- Salus- Elschnig syndrome, sylvian aqueduct syndrome, nystagmus retractorius syndrome, pretectal syndrome, dorsal midbrain syndrome, Parinaud dorsal midbrain syndrome, and more recently, the posterior commissure syndrome.2-4, 20-22, 24, 25 Parinaud syndrome is still the best known of these. CURRENT UNDERSTANDING OF PARINAUD SYNDROME This syndrome, by any of its names, is caused by a disturbance in the dorsal midbrain that results in a supranuclear vertical gaze paresis.22 It is differentiated from other vertical gaze palsies, which can occur as isolated neurological events, by its accompanying clinical features. These are distinctive clinical signs affecting pupillary responses, lid function, and attempted upward gaze. These findings are recognized as major elements of the syndrome, and may be pres-
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ent in varying degrees.22 These are, respectively, light / near dissociation on pupillary testing, upper eyelid retraction known as Collier sign, and convergence-retraction nystagmus. Additional minor elements include convergence and accommodation paresis, and pseudo-abducens palsy (or thalamic esotropia) and may be present in some cases.20-22 Other ocular motility deficits may accompany the vertical gaze paresis and its associated elements. These include convergence paralysis and occasional convergence spasm as reported by Parinaud, skew deviation, third or fourth cranial nerve palsies, internuclear ophthalmoplegia, and rare cases of see-saw nystagmus. These additional clinical features occur when the lesion disrupts adjacent structures.7, 11, 20-22
saccades. When upward gaze is absent, saccades may be tested from below the horizontal meridian to the primary position, but are usually slow.20 To elicit the phenomenon, the patient first fixates an object in the midline or just below with both eyes open, and is asked to look quickly upward to another target held above midline. On attempted up-gaze, the eyes can be seen to converge rather than elevate, and the globes are noted to retract inward at the same time. The retraction can be confirmed by viewing the movement from one side. The response is particularly well demonstrated when using an optokinetic tape or drum with the stripes rolling downward. This stimulates repeated upward saccades and produces a movement that is perhaps erroneously called “nystagmus” as there is no true slow phase. It is a supranuclear sign.
VERTICAL GAZE PARESIS LIGHT / NEAR DISSOCIATION The vertical gaze disorder in this syndrome may present as an isolated up-gaze deficit or in combination with down-gaze paresis, depending on the location of the lesion. Greater involvement of up-gaze usually occurs with lesions affecting the posterior commissure, whereas greater down-gaze paresis results from more ventral lesions.21, 22 It is now known that Parinaud syndrome affects both voluntary saccades and pursuit movements with preservation of vestibulo-ocular or oculocephalic reflexes in most cases.8, 9, 20-22 CONVERGENCE-RETRACTION NYSTAGMUS Convergence- retraction nystagmus is induced when a patient makes an upward saccade. It may be noticed in casual conversation by an astute observer—for example, at the bedside or while history taking when a patient glances up—but is best elicited formally by testing upward
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This is the term given when the pupils react poorly to a focused light source, but demonstrate a better or normal response to a near stimulus. This is also a supranuclear sign as the same efferent pathways allow miosis to occur from one stimulus, but not another due to interruption of the afferent pupillary fibers in the pretectal area. The pupils are often partially dilated to the mid-position.26 Because this disorder is associated with lesions in the dorsal midbrain these are often called “midbrain pupils.” The reaction to light may be subtle, and some authors recommend quantitative pupillography to document the responses.27 COLLIER SIGN Sometimes called posterior fossa stare, or Collier tucked lid sign, the presence of bilateral lid retraction is a recognized sign of a midbrain lesion and invariably accompanies Parinaud syndrome.20-22
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LOCATION OF LESION Midbrain lesions causing vertical eye movement disturbances arise from damage to the posterior commissure, the efferent pathways of the rostral interstitial nuclei of the medial longitudinal fasciculus (MLF), or the interstitial nucleus of Cajal (INC).9, 20 A lesion in the posterior commissure appears to be critical in producing the major elements in the pretectal syndrome.22 Destruction of the superior colliculi is no longer considered to be the mechanism causing this syndrome.20 Pineal tumors produce the dorsal midbrain syndrome either by direct compression of the posterior commissure or by causing obstructive hydrocephalus.21 LATER YEARS Throughout his life, Parinaud continued to see patients and teach his students at the hospital and in his free clinic. He was generous and concerned about his fellow man.1-4 He maintained a steady flow of clinical research and still published his observations late into his career. Following the death of his beloved wife in September 1904, Parinaud became severely depressed. Never having had a very strong constitution, he contracted bronchopneumonia and died 6 months later on March 23, 1905, at the age of 61. He left behind three daughters, Ebba, Ellen, and Karen, who were tutored after his death by famous French neurologist, Joseph Babinski (of “Babinski sign” fame).1, 3, 4 HIS LEGACY Although Parinaud is recognized, particularly in Europe, for his other eponymic ophthalmologic syndromes, he is best remembered for the supranuclear disorder affecting vertical gaze that bears his name. Being a humble man, it is doubtful that he
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would ever have expected the syndrome to be named after him. There are conflicting descriptions in the literature regarding which clinical components comprise this syndrome, including what Parinaud himself described. Some have advocated removing the name Parinaud from the syndrome and renaming the condition after the clinical features or the location of the pathology, such as the dorsal midbrain syndrome21 or the pretectal syndrome.24 Ouvrier was doubtful that the name Parinaud would go away, and in his opinion, it should not.3 Parinaud was described as a “reliable and devoted friend so perfectly sound and professionally correct that one could not find a better example. He was for all his confrères the kindest and most respected advisor.”1, 3, 4 Ouvrier wrote that “perhaps it would be much better for mankind if people were remembered for characteristics such as these, rather than for a few clinical details.”3 REFERENCES 1. H. Parinaud (1844-1905) [obituary]. Annales d’Oculistique 1905; 133:321-337. 2. Duke-Elder S. System of Ophthalmology, Volume XII: Neuro-Ophthalmology. St. Louis: C.V. Mosby Co.; 1971, pp. 827-829. 3. Ouvrier R: Henri Parinaud and his syndrome. Med J Austr 1993; 158:711-712. 4. Ouvrier R: Henri Parinaud (1884-1905). J Neurol 2011; 258:1571-1572. 5. Parinaud H: Étude sur la névrite optique dans la méningite aiguë de l’enfance [Study of optic neuritis in acute meningitis of childhood]. Thèse de Paris, number 9, 1877 (thesis). 6. http: // Wikipedia.com / saltpetriere 7. Parinaud H: Paralysie des mouvements associés des yeux. Archives de Neurologie; Clinique Nerveuse 1883; 5:145-172. 8. Wilkins RH, Brody IA: Parinaud’s syndrome. Arch Neurol 1972; 26:91-93. 9. Pearce JM: Historical note: Parinaud’s syndrome. J Neurol Neurosurg Psych 2005; 76:99. 10. Parinaud H: Paralysie de la convergence. Bulletin de la Societé Française d’Ophtalmologie 1885; 23. 11. Parinaud H: Paralysis of the movements of con-
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12.
13. 14. 15. 16. 17.
18.
19. 20.
21.
22.
vergence of the eyes [translated by Henry Juler, FRCS]. Brain 1886; 9:330-341. Parinaud H: Conjunctivite infectieuse paraissant transmise à l’homme par les animaux. Societe d’Ophtalmologie de Paris 1889; (Feb) 5. Parinaud H. La vision; étude physiologique. Paris: Octave Doin; 1898. Parinaud H. Le strabisme et son traitement. Paris: Octave Doin; 1898. Parinaud H: Stéréoscopie et projection visuelle. Annales d’Oculistique 1904; 131:241. Parinaud H: L’Operation du ptosis. Annales d’Oculistique 1904; 131:161. Koerber H: Über drei Fälle von Retraktionbewegung des Bulbus (Nystagmus retractorius). Ophthalmologische Klinik 1903; 7:65-67. Salus R: Über erworbene Retraktionbewegungen der Augen. Archiv für Augenheilkunde 1911; 68:61-76. Gamper E, Kubik J: Zur Frage des Nystagmus retractorius. Medizinische Klinik 1933; 29:1134. Miller NR, Newman NJ, eds. Walsh & Hoyt’s Clinical Neuro-Ophthalmology, Vol. 1, 6th ed. Philadelphia: Lippincott Williams and Wilkins; 2005, pp. 926-930. Leigh RJ, Zee DS, eds. The Neurology of Eye Movements, 4th ed. New York: Oxford University Press; 2006, pp. 437-438. Liu GT, Volpe NJ, Galetta SL, eds. NeuroOphthalmology: Diagnosis and Management, 2nd ed. St. Louis: Saunders Elsevier, Inc.; 2010, pp. 570-575.
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23. Liu GT, Crenner AM, Logigian EL, Charness, ME, Samuels MA: Midbrain syndromes of Benedikt, Claude, and Nothnagel: Setting the record straight. Neurology 1992; 42:1820-1822. 24. Keane JR: The pretectal syndrome: 206 patients. Neurology 1990; 40:684-690. 25. Bleeker GM: Parinaud’s vertical ophthalmoplegia. Ophthalmologica 1971; 163:44-45. 26. Liu GT, Volpe NJ, Galetta SL, eds. NeuroOphthalmology: Diagnosis and Management, 2nd ed., pp. 460-461. 27. Seybold M, Yoss RE, Hollenhorst RW, Moyer NJ: Pupillary abnormalities associated with tumors of the pineal region. Neurology 1971; 21:232-237.
OTHER RESOURCES: http: // wikipedia.com www.whonamedit .com (Dictionary of Medical Eponyms) www.eye2blog.blogspot.com / Parinaud www.pitiesalpetriere.aphp.fr
Key words: Henri Parinaud, Parinaud syndrome, dorsal midbrain syndrome, pretectal syndrome, posterior commissure syndrome, convergence retraction nystagmus, light-near dissociation, Collier sign
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INTRODUCTION Henri Parinaud was a French ophthalmologist whose name is well known to those who clinically examine patients with his eponymic syndrome and study the causative mechanisms. He had a great interest in neuroophthalmology and was one of the first physicians to practice in that specialty (Figure 1). EARLY YEARS Parinaud was born on May 1, 1844, in Bellac, in the Haute-Vienne region of central France. He was the oldest child in a family of modest means, his father being a locksmith. After attending elementary school, at thirteen he entered the local seminary to pursue higher studies. His father died when Parinaud was nineteen, leaving him the responsibility of caring for his mother and younger brothers. As a bright and determined young man, he earned money tutoring others while continuing his own education, and he was able Requests for reprints should be addressed to: Gill RoperHall, D.B.O.T., C.O., C.O.M.T., Department of Ophthalmology, Saint Louis University Medical Center, 1755 S. Grand Blvd., St. Louis, MO 63131.
FIGURE 1: Dr. Henri Parinaud and his signature. (Published in his obituary in the Annales d’Oculistique 1905; 133:320. Reprinted with permission from Elsevier-Masson.)
to provide for his family over the next few years. In 1865, at the age of twenty-one, he set off for Limoges to study medicine. He was awarded a merit prize in medicine in 1868.1-4 THE FRANCO-PRUSSIAN WAR After completing his studies in Limoges, Parinaud left for Paris in 1869 to continue his medical training. In 1870, the Franco-Prussian war broke out and he was called up to serve as an army medical officer (Figure 2). He was assigned to
© 2014 Board of Regents of the University of Wisconsin System, American Orthoptic Journal, Volume 64, 2014, ISSN 0065-955X, E-ISSN 1553-4448
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FIGURE 2: Army medical officer Henri Parinaud circa 1870 during the Franco-Prussian war. (Photographer unknown. Courtesy of Eye2blog.blogspot.com)
the Red Cross field ambulance service in Metz, where he saw action evacuating the wounded. He conducted himself courageously and was decorated for his bravery by French Prime Minister Léon Gambetta.4 ACADEMIC OPPORTUNITIES The war ended in 1871 and Parinaud returned to Paris to continue his training, first at the Hôpital des Enfants-Malades (Hospital for Sick Children) and later at the Hospice de la Salpêtrière.1-4 Paris at that time was a hotbed of neurological and medical discovery. While working at the Hôpital des Enfants-Malades, Parinaud observed that papilledema in children with meningitis was not caused by optic neuritis, but by obstructive hydrocephalus. He wrote a doctoral thesis on this topic in 1877, which attracted the attention of Professor Jean-Martin Charcot at the Salpêtrière.5 The Salpêtrière was recognized as a top teaching hospital where many famous physicians worked in collaboration, and it was a desired destination for those wishing to further their medical training. The famous Hospice de la Salpêtrière had been com-
American Orthoptic Journal
missioned by King Louis XIV in 1656. It was built on the grounds of a former gunpowder factory (salpêtrière or saltpeter being a constituent of gunpowder). It had a grim past, serving as a prison and institution to keep the mentally unstable, the criminally insane, epileptics, the poor, and other social “undesirables” off the streets.6 In the 1700s, the Salpêtrière was a dumping ground for women from all class backgrounds with “hysteria.” There was no humane treatment for this condition at the time, and once women were admitted, many lived out their remaining existences there. On the eve of the French Revolution, it was the largest hospital in the world, housing 10,000 patients, many of whom were considered criminally or violently insane. It did not fare much better until the middle of the nineteenth century, when mental illness was given its overdue recognition. Under the guidance of physician Philippe Pinel, more humane forms of treatment were introduced and the Salpêtrière developed as a psychiatric center. It was at this time that many neurological and neurophysiological disorders such as neurosyphilis, epilepsy, and stroke were recognized and the Salpêtrière quickly became a desired center of learning.5 Charcot, considered by many to be the founding father of neurology, enjoyed an international reputation and students came from all over Europe to hear his lectures at the Salpêtrière. Among them were Henri Parinaud and a young physician named Sigmund Freud! There is a famous painting by André Brouillet titled A Clinical Lesson at the Salpêtrière (displayed at Descartes University, Paris), which shows Charcot teaching in a classroom full of young doctors, one of whom is Parinaud. Other renowned neurologists in the painting include Joseph Babinski and Gilles de la Tourette. The hospital still enjoys international acclaim with experts practicing in most medical specialties. Numerous celebri-
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ties have been treated at the Salpêtrière, including some of the French presidents. Several notables have died there, including Josephine Baker in 1975 and Diana, Princess of Wales, in 1997. Charcot established a neurological service at the hospital, one of the earliest of its kind. His name is attached to over twenty-five different clinical entities, and he was the first to describe multiple sclerosis. He invited Parinaud to examine some of the ocular manifestations seen among his neurological patients. This was Parinaud’s first step into the world of neurology. He was appointed by Charcot as chief of ophthalmology of the neurology service at the hospital and this setting allowed him to develop and establish the discipline of neuroophthalmology.1-4 RESEARCH INTERESTS Charcot took Parinaud under his wing and introduced him to interesting and challenging neurological cases, particularly those pertaining to vision and the ocular motor system. This collaboration between Parinaud, Charcot, and other neurology colleagues led to studies and publications on multiple sclerosis, ophthalmoplegic migraine, ocular findings in hysteria, and disorders of eye movement. Parinaud was one of the first physicians to distinguish between central and peripheral causes of ocular paralysis, and he had a particular interest in supranuclear lesions affecting eye movements. He recognized what he referred to as “parallel and non-parallel” eye movements, now called conjugate and disjugate gaze, and deduced that there was a central system for conjugate eye movements.7 He examined and studied patients with disorders of horizontal and vertical eye movements, and those with convergence and divergence paralysis and convergence spasm.8, 9 Parinaud wrote two seminal papers that together form the basis for the syn-
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drome that carries his name. The first, “Paralysie des mouvements associés des yeux,” was published in 1883.7 The second, based on an 1885 publication simply called “Paralysie de la convergence,”10 was translated into English as “Paralysis of the Movements of Convergence of the Eyes” in 1886.11 ACADEMIC STANDING Although he had no formal academic appointment, Parinaud was well regarded by his colleagues and was an active member of various ophthalmology and neuroscience societies including the Paris Ophthalmology Society (La Societé d’Ophtalmologie de Paris) where he presented many scientific papers. He was a founding member of the French Ophthalmology Society (La Societé Française d’Ophtalmologie) and when the Neurological Society (La Societé de Neurologie) was founded in 1899, he served on the Council.1, 4 CLINICAL PRACTICE Despite his interest in neuroophthalmology, Parinaud was foremost an ophthalmologist. He treated ocular conditions such as iritis and lacrimal infections, and performed cataract, glaucoma, ptosis, and strabismus surgery.1, 2 He published articles on some of his more interesting ophthalmic cases and there are several clinical conditions that also bear his name: Parinaud oculo- glandular syndrome, caused by the same organism responsible for cat scratch disease, Parinaud conjunctivitis, and Parinaud dermo-lipomata.2, 9, 12 PERSONAL INTERESTS Parinaud was a generous and endearing person. Despite his humble beginnings, he was concerned about his fellow man and devoted much time to running a free clinic with his students.3 He was not in-
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terested in self-aggrandizement, and was always approachable and kind.2-4 He was quiet and unassuming, well respected by his peers. Parinaud was happily married and had three daughters. Despite his fondness for his family, and his dedication and industrious approach to his patients, research, and teaching duties, he somehow found time to compose music. This was published under the pseudonym of Pierre Erick.1, 2, 9 PUBLICATIONS Parinaud was a prolific writer. During his career, he published over seventy scientific articles and two books: La Vision; étude physiologique with 218 pages, published in 1898, and Le Strabisme et son Traitement with 197 pages in 1899.13, 14 With almost no exceptions, he published at least one article every year between 1877 and 1904 and often as many as four or more in the same year. In 1881, he published nine articles! These are listed in chronological order as an addendum to a long obituary in Annales d’Oculistique about his distinguished life.1 His first published article was the aforementioned thesis on optic neuritis in acute meningitis in childhood.5 His final two publications were on unrelated topics: stereoscopy and visual projection, and ptosis surgery, the latter based on a paper delivered before the Paris Ophthalmology Society on Feb 2, 1904, just a year before his death.15, 16 PARINAUD’S EPONYMIC SYNDROME Three important points should be made about Parinaud and the syndrome that carries his name. First, it should be emphasized that Parinaud did not name this syndrome—it was attributed to him by others. Ouvrier comments that he was a modest man and it would not have occurred to him to assume the credit for this.4
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A second consideration is that not all the features now known to be part of this syndrome were reported by him in his early description. Although Parinaud described vertical gaze paresis, he was not the first to do so. He gave credit for this in his article to Dr. Carl Wernicke (of Wernicke’s encephalopathy fame). Convergence retraction nystagmus and bilateral upper eyelid retraction were not observed as part of the syndrome. Neither Parinaud nor any of his contemporaries demonstrated that oculocephalic and vestibulo-ocular responses were usually normal in these cases.7, 11 The third important point was that Parinaud did not describe classic light / near dissociation of the pupils in any of his cases. A variety of responses were reported, but he observed pupillary abnormalities fairly consistently in which the near response was absent or poor and the responses to light were better or even normal. So what exactly did Parinaud report? He emphasized the difference between peripheral and central paralysis of eye movement and recognized central paralysis of convergence as distinct from the more commonly occurring convergence insufficiency. He classified organic convergence paralysis into two types: essential and combined. In essential convergence paralysis, the patient had diminished or absent convergence function, but retained full adduction of the “internal recti” on lateral movements. In combined cases, vertical gaze paralysis accompanied the convergence paralysis.7, 11 He described the ocular findings in ten patients in the French article in 1883, some of whom reappear among the eight case reports in the 1886 article translated into English. Most patients had convergence paralysis; one had divergence paralysis, and another had both. In others, there was an associated vertical gaze paresis.7, 11 The pupillary responses to light and
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near stimuli were equal in two patients, normal in one, and slightly diminished but equal in the other. In the remaining six patients, the pupillary response to attempted convergence was either absent or diminished, whereas the response to a light stimulus was normal in four patients and diminished in two.7, 11 With this constellation of pupillary abnormalities and gaze disorders, he postulated that the location of the lesion was in the corpora quadrigemina, a fact that was supported until recent years. Parinaud’s description of the pupillary responses in his cases has drawn criticism from later authors, because he did not describe typical light/near dissociation pupillary responses. By contrast, he described several different responses, including a poor or absent pupillary response to a near stimulus, but with better pupillary responses to light. This finding is rare, but is sometimes seen in patients with complete convergence paralysis. There is a poor or absent pupillary response to a near stimulus, but normal light responses may be retained. Since many of Parinaud’s reported cases had convergence paralysis without vertical gaze involvement, this may explain why he described pupillary responses that were the opposite of what most observers report in dorsal midbrain syndrome.7, 11 Although convergence retraction “nystagmus” is a common finding with lesions occurring in the dorsal midbrain, Parinaud did not mention this feature in his well-known article. This unusual eye movement affecting both eyes was described separately by Hermann Koerber, Robert Salus, and Anton Elschnig, all of whom published their observations after Parinaud wrote his landmark article.17-19 In fact, this led some to call the collective findings of vertical gaze paresis and convergence retraction nystagmus the Koerber-Salus-Elschnig syndrome.2, 20-22 Upper eyelid retraction was not mentioned
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by Parinaud or any of the other earlier authors. In an article on midbrain syndromes, Liu et al. discuss the heritage of early researchers’ work in developing a modern understanding of clinical conditions and their pathophysiology.23 Eponymic syndromes often help to organize scientific information. Clinical localization, as practiced by the nineteenth century neurologists, is still valuable today and in many instances their neuroanatomical correlations, without modern investigative tools, was surprisingly accurate. OTHER NAMES FOR THIS SYNDROME Still named after Parinaud in most modern texts, the condition is known by a variety of other monikers: Parinaud syndrome, Parinaud ophthalmoplegia syndrome, Parinaud vertical ophthalmoplegia, Koerber-Salus-Elschnig syndrome, Parinaud- Koerber- Salus- Elschnig syndrome, sylvian aqueduct syndrome, nystagmus retractorius syndrome, pretectal syndrome, dorsal midbrain syndrome, Parinaud dorsal midbrain syndrome, and more recently, the posterior commissure syndrome.2-4, 20-22, 24, 25 Parinaud syndrome is still the best known of these. CURRENT UNDERSTANDING OF PARINAUD SYNDROME This syndrome, by any of its names, is caused by a disturbance in the dorsal midbrain that results in a supranuclear vertical gaze paresis.22 It is differentiated from other vertical gaze palsies, which can occur as isolated neurological events, by its accompanying clinical features. These are distinctive clinical signs affecting pupillary responses, lid function, and attempted upward gaze. These findings are recognized as major elements of the syndrome, and may be pres-
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ent in varying degrees.22 These are, respectively, light / near dissociation on pupillary testing, upper eyelid retraction known as Collier sign, and convergence-retraction nystagmus. Additional minor elements include convergence and accommodation paresis, and pseudo-abducens palsy (or thalamic esotropia) and may be present in some cases.20-22 Other ocular motility deficits may accompany the vertical gaze paresis and its associated elements. These include convergence paralysis and occasional convergence spasm as reported by Parinaud, skew deviation, third or fourth cranial nerve palsies, internuclear ophthalmoplegia, and rare cases of see-saw nystagmus. These additional clinical features occur when the lesion disrupts adjacent structures.7, 11, 20-22
saccades. When upward gaze is absent, saccades may be tested from below the horizontal meridian to the primary position, but are usually slow.20 To elicit the phenomenon, the patient first fixates an object in the midline or just below with both eyes open, and is asked to look quickly upward to another target held above midline. On attempted up-gaze, the eyes can be seen to converge rather than elevate, and the globes are noted to retract inward at the same time. The retraction can be confirmed by viewing the movement from one side. The response is particularly well demonstrated when using an optokinetic tape or drum with the stripes rolling downward. This stimulates repeated upward saccades and produces a movement that is perhaps erroneously called “nystagmus” as there is no true slow phase. It is a supranuclear sign.
VERTICAL GAZE PARESIS LIGHT / NEAR DISSOCIATION The vertical gaze disorder in this syndrome may present as an isolated up-gaze deficit or in combination with down-gaze paresis, depending on the location of the lesion. Greater involvement of up-gaze usually occurs with lesions affecting the posterior commissure, whereas greater down-gaze paresis results from more ventral lesions.21, 22 It is now known that Parinaud syndrome affects both voluntary saccades and pursuit movements with preservation of vestibulo-ocular or oculocephalic reflexes in most cases.8, 9, 20-22 CONVERGENCE-RETRACTION NYSTAGMUS Convergence- retraction nystagmus is induced when a patient makes an upward saccade. It may be noticed in casual conversation by an astute observer—for example, at the bedside or while history taking when a patient glances up—but is best elicited formally by testing upward
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This is the term given when the pupils react poorly to a focused light source, but demonstrate a better or normal response to a near stimulus. This is also a supranuclear sign as the same efferent pathways allow miosis to occur from one stimulus, but not another due to interruption of the afferent pupillary fibers in the pretectal area. The pupils are often partially dilated to the mid-position.26 Because this disorder is associated with lesions in the dorsal midbrain these are often called “midbrain pupils.” The reaction to light may be subtle, and some authors recommend quantitative pupillography to document the responses.27 COLLIER SIGN Sometimes called posterior fossa stare, or Collier tucked lid sign, the presence of bilateral lid retraction is a recognized sign of a midbrain lesion and invariably accompanies Parinaud syndrome.20-22
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LOCATION OF LESION Midbrain lesions causing vertical eye movement disturbances arise from damage to the posterior commissure, the efferent pathways of the rostral interstitial nuclei of the medial longitudinal fasciculus (MLF), or the interstitial nucleus of Cajal (INC).9, 20 A lesion in the posterior commissure appears to be critical in producing the major elements in the pretectal syndrome.22 Destruction of the superior colliculi is no longer considered to be the mechanism causing this syndrome.20 Pineal tumors produce the dorsal midbrain syndrome either by direct compression of the posterior commissure or by causing obstructive hydrocephalus.21 LATER YEARS Throughout his life, Parinaud continued to see patients and teach his students at the hospital and in his free clinic. He was generous and concerned about his fellow man.1-4 He maintained a steady flow of clinical research and still published his observations late into his career. Following the death of his beloved wife in September 1904, Parinaud became severely depressed. Never having had a very strong constitution, he contracted bronchopneumonia and died 6 months later on March 23, 1905, at the age of 61. He left behind three daughters, Ebba, Ellen, and Karen, who were tutored after his death by famous French neurologist, Joseph Babinski (of “Babinski sign” fame).1, 3, 4 HIS LEGACY Although Parinaud is recognized, particularly in Europe, for his other eponymic ophthalmologic syndromes, he is best remembered for the supranuclear disorder affecting vertical gaze that bears his name. Being a humble man, it is doubtful that he
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would ever have expected the syndrome to be named after him. There are conflicting descriptions in the literature regarding which clinical components comprise this syndrome, including what Parinaud himself described. Some have advocated removing the name Parinaud from the syndrome and renaming the condition after the clinical features or the location of the pathology, such as the dorsal midbrain syndrome21 or the pretectal syndrome.24 Ouvrier was doubtful that the name Parinaud would go away, and in his opinion, it should not.3 Parinaud was described as a “reliable and devoted friend so perfectly sound and professionally correct that one could not find a better example. He was for all his confrères the kindest and most respected advisor.”1, 3, 4 Ouvrier wrote that “perhaps it would be much better for mankind if people were remembered for characteristics such as these, rather than for a few clinical details.”3 REFERENCES 1. H. Parinaud (1844-1905) [obituary]. Annales d’Oculistique 1905; 133:321-337. 2. Duke-Elder S. System of Ophthalmology, Volume XII: Neuro-Ophthalmology. St. Louis: C.V. Mosby Co.; 1971, pp. 827-829. 3. Ouvrier R: Henri Parinaud and his syndrome. Med J Austr 1993; 158:711-712. 4. Ouvrier R: Henri Parinaud (1884-1905). J Neurol 2011; 258:1571-1572. 5. Parinaud H: Étude sur la névrite optique dans la méningite aiguë de l’enfance [Study of optic neuritis in acute meningitis of childhood]. Thèse de Paris, number 9, 1877 (thesis). 6. http: // Wikipedia.com / saltpetriere 7. Parinaud H: Paralysie des mouvements associés des yeux. Archives de Neurologie; Clinique Nerveuse 1883; 5:145-172. 8. Wilkins RH, Brody IA: Parinaud’s syndrome. Arch Neurol 1972; 26:91-93. 9. Pearce JM: Historical note: Parinaud’s syndrome. J Neurol Neurosurg Psych 2005; 76:99. 10. Parinaud H: Paralysie de la convergence. Bulletin de la Societé Française d’Ophtalmologie 1885; 23. 11. Parinaud H: Paralysis of the movements of con-
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12.
13. 14. 15. 16. 17.
18.
19. 20.
21.
22.
vergence of the eyes [translated by Henry Juler, FRCS]. Brain 1886; 9:330-341. Parinaud H: Conjunctivite infectieuse paraissant transmise à l’homme par les animaux. Societe d’Ophtalmologie de Paris 1889; (Feb) 5. Parinaud H. La vision; étude physiologique. Paris: Octave Doin; 1898. Parinaud H. Le strabisme et son traitement. Paris: Octave Doin; 1898. Parinaud H: Stéréoscopie et projection visuelle. Annales d’Oculistique 1904; 131:241. Parinaud H: L’Operation du ptosis. Annales d’Oculistique 1904; 131:161. Koerber H: Über drei Fälle von Retraktionbewegung des Bulbus (Nystagmus retractorius). Ophthalmologische Klinik 1903; 7:65-67. Salus R: Über erworbene Retraktionbewegungen der Augen. Archiv für Augenheilkunde 1911; 68:61-76. Gamper E, Kubik J: Zur Frage des Nystagmus retractorius. Medizinische Klinik 1933; 29:1134. Miller NR, Newman NJ, eds. Walsh & Hoyt’s Clinical Neuro-Ophthalmology, Vol. 1, 6th ed. Philadelphia: Lippincott Williams and Wilkins; 2005, pp. 926-930. Leigh RJ, Zee DS, eds. The Neurology of Eye Movements, 4th ed. New York: Oxford University Press; 2006, pp. 437-438. Liu GT, Volpe NJ, Galetta SL, eds. NeuroOphthalmology: Diagnosis and Management, 2nd ed. St. Louis: Saunders Elsevier, Inc.; 2010, pp. 570-575.
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23. Liu GT, Crenner AM, Logigian EL, Charness, ME, Samuels MA: Midbrain syndromes of Benedikt, Claude, and Nothnagel: Setting the record straight. Neurology 1992; 42:1820-1822. 24. Keane JR: The pretectal syndrome: 206 patients. Neurology 1990; 40:684-690. 25. Bleeker GM: Parinaud’s vertical ophthalmoplegia. Ophthalmologica 1971; 163:44-45. 26. Liu GT, Volpe NJ, Galetta SL, eds. NeuroOphthalmology: Diagnosis and Management, 2nd ed., pp. 460-461. 27. Seybold M, Yoss RE, Hollenhorst RW, Moyer NJ: Pupillary abnormalities associated with tumors of the pineal region. Neurology 1971; 21:232-237.
OTHER RESOURCES: http: // wikipedia.com www.whonamedit .com (Dictionary of Medical Eponyms) www.eye2blog.blogspot.com / Parinaud www.pitiesalpetriere.aphp.fr
Key words: Henri Parinaud, Parinaud syndrome, dorsal midbrain syndrome, pretectal syndrome, posterior commissure syndrome, convergence retraction nystagmus, light-near dissociation, Collier sign
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