Journal of Neuro-Ophthalmology, September 1989, Volume 9, Issue 3

Septo-optic dysplasia (SOD) or DeMorsier syndrome.

The historical evolution of the DeMorsier syndrome is reviewed. As the emphasis shifted from the eye findings to endocrinological defects and as the syndrome was further expanded through more frequent and easier radiological examination, the concept appears to have expanded, raising questions as to the nature of the disease and its clinical expression. To determine pathogenesis and better define the extent of the disease, further observations are needed, including postmortem studies on patients with septo-optic dysplasia and related disorders.

[ lJUmal or eil/ lleal Nc" ro- ol'htJlIllmolos.~ 9( 3): 156- 159, 1989 © 1989 Raven Press, Ltd., New York Septa- optic Dysplasia ( SOD) or DeMorsier Syndrome Uros Roessrnann, M. D. The historical evolution of the DeMorsier syndrome is reviewed, As the emphasis shifted from the eye findings to endocrinological defects and as the syndrome was further expanded through more frequent and easier ra­diological examination, the concept appears to have ex­panded, raising questions as to the nature of the disease and its clinical expression. To determine pathogenesis and better define the extent of the disease, further ob­servations are needed, including postmortem studies on patients with septo- optic dysplasia and related disor­ders. Key Words: DeMorsier- Hypopituitarism- Optic nerve hypoplasia- Septo- optic dysplasia- eNS malforma­tions. From the Divisiun of Neuropathology, Institute of Pathology, Case Western Reserve Universltv, C1evl'land, Ohill. Address corrl" p" ndenc,' an, i repnnt requests to Dr. U. P., : 1 iii':' rl, dh'llllg\', ( Lhl' Wt-!~ tern Reserve Uni- 1-", I ( If I 44JOh, USA 156 The absence of the septum pellucidum and optic atrophy were well recognized before DeMorsier in 1956 ( l) first called attention to the coincident oc­currence of the two findings in the same patient. He reviewed 36 cases of defects of the septum pel­lucidum from the literature: 12 had been recog­nized at autopsies and 24 by radiological examina­tion, 9 of which also showed optic system " malformations." His own case concerned an 84­year- old woman who died with a pelvic abscess, pyelonephritis, purulent bronchiolitis, and recent thrombosis of the cavernous sinus. She had expe­rienced no visual deficit during life. The brain at the autopsy showed a rudimentary septum and a dilated anterior third ventricle that resulted in ab­normal orientation of the optic chiasm and a di­vided left optic nerve. The profession was thus alerted to the condition called septo- optic dyspla­sia ( SOD) and, by 1973, Bruyn ( 2) had found 20 case reports. The number of reported cases has since increased almost exponentially, and there are now more than 200 cases on record. The definition of the syndrome and the understanding of the pathogenetic mechanisms have changed with the additional reports but still remain uncertain. The first impediment to clarification arises from the fact that several organs are involved. The interest in the subject first came from oph­thalmologists who studied many cases of optic nerve hypoplasia, some of which also involved le­sions of the brain, including septal defects. The studies were primarily oriented to findings in the eye, Optic nerve hypoplasia became well defined, and the septal defect, when present, fit with the definition of the syndrome as proposed by De­Morsier. An important report by Kaplan et al. in 1970 ( 3) described six patients with hypopituita­rism. Four had pneumoencephalographic studies and three showed absence of the septum pellu­cidum, thin optic nerves, abnormal fornices, irreg­ular lamina terminalis, and an abnormally shaped SEPTO- OPTIC DYSPLASIA OR DE MORSIER SYNDROME 157 third ventricle. The authors postulated that a dien­cephalic defect resulted in hypothalamic dysfunc­tion in association with a congenital malformation of the prosencephalon including 500. In the fol­lowing years, it became clear that the septo- optic defect is frequently associated with pituitary dys­function or, conversely, that septo- optic dysplasia is a common finding among patients with congen­ital hypopituitarism. The focus in the literature shifted from the ophthalmologic to the pediatric and endocrine journals. The third impetus came from new radiological techniques that became available in the early 1980s and that made exami­nation of the central nervous system ( CNS) in vivo much easier and sufficiently detailed to recognize many of the changes that may be part of the syn­drome. Many cases are now reported in the radiologic literature based on the computed tomographic ( CT) or magnetic resonance images of the subjects' brains. It is easy to perceive that different groups of patients are described based on the various viewpoints and that the scope of the reports varies greatly. As each specialty group surveys the cases, the " complete" or " pure" syndrome becomes dif­ficult to find. The original concept of OeMorsier of a defect of septum pellucidum and optic nerve hy­poplasia has been expanded and modified. A sig­nificant number of patients exhibit optic hypopla­sia, septal defect, or hypopituitarism, either singly or variously combined. Furthermore, many of the cases present with additional lesions of the CNS, such as malformations of the midline and a variety of destructive changes. The questions that now arise are: Does SOD, or OeMorsier syndrome, exist in pure form? How many of the cases described in the current litera­ture are really part of the syndrome? Is there more than one syndrome? And, last but not least, what is the pathogenesis of the various lesions that are being considered in this complex? An answer to the last question in particular at present seems impossible because of the extreme paucity of the anatomical observations. In a recent review ( 4), we surveyed the literature and found only eight reports, including the original one by OeMorsier. Of these, five are brief to the point of not being useful. Since that writing, our attention has been called to a report of agenesis of the ver­mis with associated SOD and other anomalies ( 5). This leaves four' complete anatomical studies, each of which presents a different picture. OeMorsier ( 1) described small and malformed optic nerves with a rudimentary septum; other findings in­cluded a hypoplastic olfactory system and hetero-topia of the gray matter. Patel et al. ( 6) described a case with normal optic nerves and a normal sep­tum pellucidum, but they found evidence of hy­pothalamic damage and absence of the posterior lobe of the pituitary; in addition, there was a defi­cient anterior segment of the corpus callosum, mi­crogyria, and heterotopias. The case described by Zaias and Becker ( 7) had absent septum pellu­cidum, but normal optic nerves; they also found destructive lesions in the hypothalamus and in the left cerebral hemisphere. Michaud et al. ( 5) found absence of the septum pellucidum and a hypoplas­tic optic system; a posterior pituitary was also ab­sent in addition to agenesis of the vermis with fu­sion of the cerebellar hemispheres. The three cases that we reported ( 4) had hypoplastic optic nerves, but only one of the three had no septum pellu­cidum. Likewise, only one showed hypoplasia of the neurohypophysis, but all three had definite le­sions of the hypothalamus and other evidence of destructive changes in the cerebral hemispheres. Should one adhere to the strict definition of the OeMorsier syndrome, only his original case and that reported by Michaud et al. ( 5) could be truly defined as belonging to the " pure" septo- optic dysplasia. It is not clear how the rest should be classified. Can a clinically defined syndrome be found in the absence of a pathological definition? Review of the reports shows that the ophthalmologic litera­ture deals with optic nerve hypoplasia, which may be unilateral or bilateral. The " double ring sign" is described as pathognomonic for the condition; yet it is not certain that all of the authors report the same finding or that they adhere strictly to the definition. Earlier surveys were completed when the radiological examination necessary to detect septal or other CNS defects meant pneumoen­cephalogram, an arduous and not easily under­taken procedure. Even in the more recent reports, however, the incidence of septal defects in patients with optic nerve hypoplasia still varies between 25 and 100%. Moreover, the recorded findings again include a great variety of additional changes in the brain. The surveys of the populations with hypo­pituitarism give the span for the associated SOD as between 29 to 100%. The expression of the pitu­itary dysfunction ranges from panhypopituitarism to single hormonal dysfunction. The most extensive survey is that by Arslanian et al. ( 8), who found 16 children with septo- optic dysplasia among 96 followed for hypopituitarism. In the majority of cases studied, the diagnosis of septo- optic dysplasia was established before the patients were studied for endocrine problems. The I Clin Neuro- ophthalmol. Vol, 9, No. 3, 1989 158 U. ROE55MANN presence of hypopituitarism was established at an average of 31/ 2 years after that of septo- optic dys­plasia. The authors also systematically searched for the septum, establishing the largest group of recorded examinations. They found agenesis in one- half of their patients, compared with 75% for the cases collected from the literature in which the results of pneumoencephalography were re­corded. A different aspect of the problem was studied by Costello and Gluckman ( 9), who collected 12 pa­tients with neonatal hypopituitarism " whether or not the diagnosis was established at that time." Six were diagnosed as having SOD; all had optic hy­poplasia ( five were observed on ophthalmologic examination and one showed small optic nerves on CT scan); four also had septal defect. Two of the six died and the postmortem examinations showed, in addition to the optic and septal lesions, gliosis of the hypothalamus and hypoplasia of the posterior pituitary, aplasia of the olfactory bulbs and tracts, and hydrocephalus secondary to the aqueductal occlusion in one and aplasia of the ol­factory system and hypoplasia of the posterior hy­pophysis in the other. It is apparent that the clinical expressions vary greatly ( spectrum is the word used in several cur­rent titles). Furthermore, there often is discor­dance between the clinical and radiological find­ings ( 10). To pose the question again- Is there a " pure" form of septo- optic dysplasia that con­forms to the definition of DeMorsier- one can an­swer that there probably is, but it must be very rare. The majority of patients have only partial ex­pression, optic hypoplasia being the most fre­quent, pituitary hypofunction next, and septal de­fect the least common. Any combination of the three major findings may, and frequently does, co­incide with additional CNS defects that can be di­vided into two major groups. The first group con­sists of apparent morphogenetic malformations, usually of the midline type and most often involv­ing the cerebellum; the second group appears to be destructive and usually involves the region around the anterior third ventricle, including the hypo­thalamus, the septal region, and the anterior por­tion of the corpus callosum. Each set of findings implies a different pathogenetic mechanism and a different timing. The second group overlaps in its expression with another syndrome, that of the ab­sent septum pellucid urn with porencephalies. A number of cases have been reported under that name ( 11- 13); they show absence of the septum peJlucidum along with porencephalic defects, car- I ,.;". 1fi, lI:' lc optic system de-feets. The syndrome is considered an entity sepa­rate from the septo- optic dysplasia because its clearly clastic lesions determine the clinical picture, which usually includes significant mental or motor dysfunction, and because of the optic atrophy that presumably results from destruction of a well­formed optic system through lesions occurring af­ter its development is already advanced. Morgan et ai. ( 14) reported a case that clearly overlaps both of these syndromes, as the patient showed optic hypoplasia, absence of septum pellucidum, and porencephaly. Many of the cases reported under SOD show cortical changes similar to those described above. One may ask whether these two syndromes are two distinct entities or whether there is a continu­ity- a spectrum of changes that simply differ in the intensity of the clinical expression and are due to the same or a similar pathogenetic mechanism, with the differences being due to the different stages of development at which the noxious stim­ulus has been active and the different intensity of its activity. It is likely that most of the reported cases included clinically under the title of SOD should not be considered as such and that the term has become a collecting point for a variety of man­ifestations. None of the questions raised in this review can be resolved from past observations. Many of the reports up to now fail to describe the optic findings in sufficient detail to enable one to distinguish be­tween atrophy and hypoplasia. The descriptions of the changes in the brain, either radiological or from the postmortem examinations, are insuffi­cient to provide grounds for firm conclusions. To obtain true answers, it is necessary to study these problems prospectively. Since it is the eye abnor­mality that is detected first in most of the cases, it is incumbent on ophthalmologists to examine and describe the eyeground exactly and to initiate fur­ther studies to detect lesions in the brain and to evaluate the pituitary function in every child with optic hypoplasia. This is not just of academic in­terest; pituitary hypofunction can be treated and timely replacement therapy can significantly im­prove the well- being of the patient and prevent much of the morbidity related to these syndromes. The significance of the diagnosis for the anesthe­siology has been pointed out ( 15). Much of the nec­essary information can be readily obtained with the available modern radiological methods. It is, however, highly important to realize that the res­olution power of these methods is not sufficient to give us insight into the morphogenetic aspects of the lesion. SEPTO- OPTIC DYSPLASIA OR DE MORSIER SYNDROME 159 It is further incumbent on all the professionals who treat these patients to assure that a postmor­tem examination be undertaken upon death of the subjects in order to help determine the nature of the lesions and to enable us to arrive at some con­clusions as to the timing, extent, and nature of the causative agent( s). It is only in this way that we will be able to answer the questions posed above and to conclude the work begun by Prof. DeMor­sier. REFERENCES 1. DeMorsier G. Etudes sur les dysraphies cranio- ence­phaliques. III. Agenesie du septum lucidum avec malfor­mation du tractus optique. La dysplasie septo- optique. Sch­weiz Arch Neurol PS1{ chiatr 1956; 77: 267- 92. 2. Bruyn GW. Agenesis septi pellucidi, cavum septi pellucidi, and cavum vergae and cavum veli interpositi. In: Vinken PJ, Bruyn GW, eds. Handbook of clinical neurology; vol 30: Congenital malformation of the brain and skull, Part I. Amster­dam: North Holland, 1977: 299- 336. 3. Kaplan SL, Grumbach MM, Hoyt F. A syndrome of hypo­pituitary dwarfism, hypoplasia of optic nerves and malfor­mation of prosencephalon: report of 6 patients. Pediatr Res 1970; 4: 480- 1. 4. Roessmann U, Velasco ME, Small EJ, Hori A. Neuropathol­ogy of " septo- optic dysplasia" ( de Morsier syndrome) with immunohistochemical studies of the hypothalamus and pi­tuitary gland. J Neuropathol Exp NeuroI1987; 46: 597-{ j08. 5. Michaud J, Mizrahi EM, Urich H. Agenesis of the vermis with fusion of the cerebellar hemispheres, septo- optic dys-plasia and associated anomalies: report of a case. Acta Neu­ropathol 1982; 56: 161-{ j. 6. Patel H, Tze WJ, Crichton JU, et al. Optic nerve hypoplasia with hypopituitarism: septo- optic dysplasia with hypopitu­itarism. Am J Dis Child 1975; 129: 175- 80. 7. Zaias B, Becker D. Septo- optic dysplasia: development or acquired abnormality? A case report. Trans Am Neural Assoc 1978; 103: 273- 7. 8. Arslanian SA, Rothfus W, Foley TP Jr, et al. Hormonal, metabolic, and neuroradiologic abnormalities associated with septo- optic dysplasia. ~ Acta Endocrinol ( Copenh) 1984; 107: 282-- 8. 9. Costello JM, Gluckman PD. Neonatal hypopituitarism: a neurological perspective. Dev Med Child Neurol 1988; 30: 190- 9. 10. Wilson DM, Enzmann DR, Hintz RL, et al. Computed to­mographic findings in septo- optic dysplasia: discordance between clinical and radiological findings. Neuroradiology 1984; 26: 279-- 83. 11. Aicardi J, Goutieres F. The syndrome of absence of the septum pellucidurn with porencephalies and other devel­opmental defects. Neuropediatrics 1981; 12: 19- 29. 12. Menezes L, Aicardi J, Goutieres F. Absence of the septum pellucidum with porencephalia: a neuroradiologic syn­drome with variable clinical expression. Arch Neurol 1988; 45: 542- 5. 13. Shimozawa N, Ohno K, Takashima S, et al. The syndrome of the absence of a septum pellucidum with porencephaly. Brain Dev 1986; 8: 632-{ j. 14. Morgan SA, Amsellem HA, Sandler JR. Absence of the sep­tum pellucidum: overlapping clinical syndrome. Arch Neu­roI1985; 42: 769- 70. 15. Sherlock DA, McNicol LR. Anaesthesia and septo- optic dysplasia: implications of missed diagnosis in peri­operative period. Anaesthesia 1987; 42: 1302- 5. , Clin Neuro- ophthalmol, Vol. 9, No. 3, 1989