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“Centrencephalic” electroencephalographic patterns in precocious puberty
ELECTROENCEPHALOGRAPHYAND CLINICALNEUROPHYSlOLOGY
559
"CENTRENCEPHALIC" ELECTROENCEPHALOGRAPHIC PATTERNS IN PRECOCIOUS PUBERTY R. G. SCHERMAN, M.D. 1 AND K. ABRAHAM, M.D. Branch of Electroencephalography and Clinical A'eur~physioiogy, National Institute of Neurological Diseases and Blindness, National Institutes of Health, Bethesda, Md. (U.S.A.) (Received for publication: October 24, 1962)
INTRODUCTION This study was suggested by the incidental finding of 3-3.5/sec bilaterally synchronous spike and wave activity in the routine EEG of a girl referred with the clinical diagnosis of true precocious puberty, a This EEG pattern was of particular inte,~st since the patient was found to have an enlarged mamillary body on pneumoencephalography, The possibility that a lesion in this location might be related to both the endocrinopathy and the "centrencephalic"a discharge in the EEG appeared a reasonable assumption and a search for similar cases in the literature and in the files of our laboratory was undertaken, PATIENT MATEKIAL All cases referred to our EEG Laboratory Presently at Second (Cornell) Neurology Service, Bellevue Hospital, New York, N.Y. (U.S,A,) t Precocious puberty can be classified (Danowskt 1962) into true precocity and pseudo.precocity. The latter results from the production of excessive amounts of androBen or estro~n by the gonads or by the adrenal cortex in the absence of pituitary stimulation. In true precocity there is elevation of gonadotropic hormones as well as androBcns or estrogens approaching adult values at an earlier abe, which indicates premature pituitary~,¢tivity. True precocity can be sub.divided into : (a) constitutional type, where no etiology can be determin-
ed, and (b)cerebral type secondary to intracranial lesions, Mnerally in the area of the 3rd ventricle and hypothalamug. In this paper only true sexual precocity will be considered, a The term "centrencephalic" as used by Penfield and Jasper (1954) in "petit maP' epilepsy is referred to here to describe the specific electrographic pattern charactefized by bilaterally synchronous paroxysmal discharges of the more or less classical type (3/~ wave and spike complexes) without n__~es_ sarily referring to its clinical manifestations. For further details see Penfield and Jasper (1954), Ajmone Marsan and Lewis (1960) and the present discussion,
within the past 10 years with a verified, diagnosis of true precocious puberty were reviewed. Twelve such patients were found. In addition to the one already mentioned, two had bilaterally synchronous bursts of 2. 5-3. 5/sec spike and wave activity in their EEGs; the remainder had tracing which were considered normal for their age. An additional case of precocious puberty with a suggestive "centrencephalic" EEG pattern was found after reviewing the charts of 51 seizure cases with the discharge diagnosis of "subcortical" or "petit maP' epilepsy. This constitutes four cases, roughly one-third of a total of thirteen wherean EEG pattern of the "centrencephalic" type was associated clinically with precocio,.~s puberty. Of these thirteen cases three can be considered to be definitely, and one possibly, of cerebral origin and are included in the following case reports. The remaining nine cases in the absence of any apparent etiologic factor or
neurologic symptoms have probably to be classified as beiol~ging to the constitutional type, although no neuroradiologic procedures were performed and a small neurologically silent lesion could not be excluded with certainty in the genesis of their endocrinopathy. Since only a small number of reports on this subject have been published to date, a summary of case histories and EEG findings is presented. Pertinent data from our four casts and from three similar ones previously reported by others are shown in Table I. CASe ~EPORTI Case No. 1 (B.$.) This 7~-year-old white girl was the result of a normal pregnancy and delivery. Pubic hair and breast enlargement were first noted at the age of 16 months and were followed at 19 months Electwenceph. clin. NeurophysioL, 1963, 15:$59-~;67
560
R.G. SCHERMAN AND K. ABRAHAM
TABLE 1 Cases of precocious puberty associated with "centrencephalic" discharges
Authors
Age,
Clinicaldiqnosis
sex-race
Age onset of precocious
Lesion
Seizure
EEG
infundibuloma in
"Petit m a P '
Synchronousspike
anteriorhypothalamus*
and grand mal
and wave discharges
puberty Harm,
8t years I. Precocious
1957
(died) M-W
About
puberty,cerebral 4 months 2. Seizures
L ~ ~ u;.
iO ymrs i. i~7o~ious
About
Hamartoma, mid- Clinical
Atypical spike and
1958
F-W
2 years
line, extending from chiasm to upper pens, at-
myoclonic "petit maP'
wave discharges with left-sided predominance
"Petit mar' followedby short automatism and disorientation
Diffuse slow dysrhythmia; spikeand wave patternwhile dozing
puberty, cerebral 2. Brain tumor
tached to left mamillary body* MoCullagh al. 1960
6t years 1. Precocious F-W puberty
I year
et
Present
7~ years
Precocious
16 months
Series #1
F-W
.,.,...,.,v.,,,., ,J, ,,...k._,,I.......,,.
Tumor of tuber cinereum (astrocytoma) extending from infundibulum to upper pens*
Enlnrsexl mnmil. .
.
.
.
.
.
.
.
.
law body*"
(B. S.)
.
.
.
Nn hiatn.,'y nr
..,
seizures - ap-
and wave dis-
parent "absence" with bursts
charges
-
3 4 / ~ spike
.
.
.
.~.~.
w.
1_1 ¢/,~,,,,.,,,;t,,. . * * * * i ~
~jj~iA,
qw
~2 (O. U,)
6 years
Precocious
M-W
puberty,cerebral
~$ (O. O.)
9 years Precocious F~W puberty,cerebral
7 years
Left frontal astrocytom, extending across midline, removed at ago 6
#4
8 ye~t~
I. Precocious
6t y e a r s
None***
(L, C,)
F-W
puberty, constltu-
"absence"
rhythmia and
tional(?) 2, Sulgortical
with staring and ri$idity
2-3/se¢paroxysreal slow activity with suRmtion of a
4]i y e a r s
seizures
Enlargedpineal**
and wave discharles A. Generalized Leftfrontal focus with risht.sided and 2~3,$/sec predominance bilaterallysyn. B. Clinical ¢htonousspike "petit maP' and wave discharges Clinical Diffuse slow dys-
spike component * Autopsied case ** D i a l l n ~ by pneumoencephalowaphy *** No neuro-radiologie studiu
of age by intermittent vaginal bleeding, On her first admission at the age of' 28 months, patient showed breast enlargement, pubic hair, a palpa, ble uterus and a bone age of 6 years, Further admissions confirmed these findings and she continued to Brow in advance of' her chronologic
age, The remainder of her history was unremarkable; she had no symptoms referable to the central nervous system and had no seizures. During her most recent admission in 1962 at the age of' 7]~, she was a pleasant adolescent with behavior appropriate for her age. Examina-
F_.lectroenceple. elin. Neuropkysiol., 1963, 15:559-567
561
CENTRENCEPHALIC PATTERNS
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tion was unremarkable except for well developed sexual characteristics. Neurologic examination was normal. Laboratory studies revealed normal hemogram, urinalysis, and blood chemistries for the age. Endocrine studies over a period of several years revealed urinary gonadotropins ranging from IO-65 mouse units; urinary corticolds 4.8-7 mg per 24 h; urinary 17-ketosteroids 2.5 mg per 24 h. x A fractional pneumoencephalogram performed at age 6~ years revealed a 1 cm mass in the interr~ duncular cistern somewhat to the right of the midline felt to represent an
enlargement or tumor of the mamillary body. Carotid arteriograms were normal. Her IO was 110. The patient had a total of seven EEGs. Those records taken at the age of 2 and 4 were considered within normal limits for the age. The subsequent records have been consistently abnormal, showing a background activity of well developed and regular 8-10/see alpha activity, low voltage anterior fast activity and transients in the theta frequency range which appeared bilaterally and symmetrically. In addition, there were occasional bvrsts of high amplitude t The normal range of values established in the Clini- rhythmical and bilaterally synchronous diffuse 3-cal Patholo~ Department of the ClinicalCenter for the 3.5/seespike and wave complexes which were of age Ip'oup of both sexes included in this paper is: gonado- maximal amplitude posteriorly, varying in tropins' less than 10 mouse uni~/24 h; 17-ketosteroids: duration from 3-5 sec. Minor shifting asymmetry 0.8-2.6 rag/24 h; 17.hydroxy corticoids: approximately 2-10 m8/24 h above the age of 2 (values are based on of these discharges was noted. Some of these limited number of normal controls), bursts were elicited by eye closure. During photic Electroenceph. din. Neurophysiol., 1963, 15:559-567
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R, O. SCHERMAN AND K. ABRAHAM
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stimulation them was slight driving and, at faster rrequenct., high amplitude symmetrical bursts identical to those occurring during the resting record were activated (Fig. 1). The patient appeared to have brief' lapses of consciousness during the bursts of spike and wave activity, without other ictal manifestations. Hyperventilation produced no activation. Sleep patterns were normal. These records were interpreted as showing a normal background activity for the age with paroxysmal activity of "centrencephalic" type.
or ejaculations, his voice did not change and no facial hair appeared. There was no history of seizuresand the remainder of his medical history was non-contributory. Physical examination was negative except for striking secondary sexual characteristics as manif'ost~ by profuse growth of hair over his legs and pubic area, enlargementof the penis and testes and unusual. ly prominent muscular development for his age. His height and weight were above the 100thpercentile for his age. Neurologic examination was normal. Hemobram, urinalysis, and blood chemistries were within normal limits for Case No. 2 (G.U.J the age, Skull films wero normal and bone age This 6-year-old white boy was admitted was I1½ years. Spinal fluid was normal. Pneu~ u s e or precocious puberty. Pubic hair was moencephalograms showed definite enlargement first noted at 4~ years of' age and was £ollowed or the pineal gland with normal filling of the by further development of' secondary sexual 3rd ventricle, Carotid arteriograms were normal. chara~ristics, He did not have any erections Endocrine studies: 24-h gonadotropin titer FJectroe,ceph. ¢1i~;. ,~,'¢~ror,h:,'~,,do, !963, 15:559-$67
563
CENTRENCEPHALIC PATTERNS
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greater than 10 mouse units on several occasions; urinary 24-h 17.ketosteroids varied between 2 and 4 m8 and 17.hydroxycorticoids between 3 and 9 mg per 24 h; protein bound iodine 6.6 /48 percent. The remainder of the laboratory studies were normal. The patient had three EEGs all characterized by a normal background activity for the age. The tirst tracing showed several bursts of diffuse, bilaterally synchronous high amplitude 3.54/see spike and wave activity with minor, shifting asymmetries particularly following eye closure (Fig. 2) and during photic stimulation at 15 flashes per sec. During hyperventilation there were several bunts of 3--4/sec high amplitude sinusoidalslow activity with larvalaccompanying spikes; several similar bursts occurred after hyperventilation. The subsequent records did not show paroxysmal activity. The first EEG was interpreted as showing paroxysmal activity
of the "centrencephalic" type with an otherwise normal background.
Case No. J (G.G.) This 9.year-old white girl was seen at the Clinical Center in 1959 because of seizures. In 1956,at the age of 6, she had several generalized convulsions, and in February, 1957, a left frontal astrocytoma was removed at another hospital. This lesion extended across the midline at the base of the frontal lobe and "had to be dragged out". Subsequently she has had a right spastic hemiparesis, dysphasia and blindness of the left eye. One year after the removal of the tumor seizures recurred and consisted of two types: (I) generalized convulsions with right.sided predominance; (2) blank stares and unresponsiveness with drooping of the head for about 30 see, occurring a n~ :~ber of times daily without other Electroenceph. din. Ncuroph~,alol., 1963, 13:559.-$67
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R.G. SCHERMAN AND K. ABRAHAM
convulsive movements or post-ictal confusion, At this time she developed secondary sexual characteristics and, shortly thereafter, began to ,~.~,.,,~+= "~ . . . . . . . . :..+i+. of her history was unremarkable. On examination, the patient was a healthy girl with well developed secondary sexual characteristics. Neurologic examination showed a mild organic mental syndrome, dysphasia, left optic atrophy, a right superior quadrantic visual field defect and a right spastic hemiparesis, Hemogram, urinalysis and blood chemistries were within normal limits. Skull films revealed evidence of a left craniotomy. Pneumoencephalograms showed marked bilateral ventricular dilatation, left more than right, with a slight shift of the midline structures to the left• The 3rd ventricle appeared sliahtlv dilated on tomegrams. Carotid arteriography revealed no apparent residual tumor. Endocrine studies showed urinary gonadotropins greater than 10 mouse units and less than 50 mouse units (borderline value); 17-ketosteroids 4.3 mg/24 h; urinary corticoids7.4mg/24h. Lumbar puncture revealed normal pressure and protein with no cells, A total of ten EEGs was performed over a period of 3 years. The background was well formed and organized for the age with a domi. nant frequency of ~8/sec activity of slightly larger amplitude over the left side. Fairly high voltage slow wave activity in the delta and theta frequency range appeared abundantly on the frontal, prefrontal and fronto-central regions, more pronounced over the left side. Almost continuous 2-3.5/sec poorly formed slow spike and wave activity was seen in the left frontal area with spread to the corresponding right side. In addition, 2--3.5/sec spike-wave discharges occurred bilaterally and synchronously over both hemispheres with maximal amplitude in the frontal regions and, occasionally, with slightly higher amplitudes over the right side (Fig. 3). Hyperventilation produced occasional runs of synchronous and symmetrical high voltage 23/see spike and wave activity which was maximal in the left frontat area. Photic stimulation had no effect. This record was interpreted as showing an epileptogenic focus in the left frontal area, as well as occasiolml bursts of bilaterally synchronous spike and wave activity either repre, 61a~
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senting a subcurtical discharge or resulting from a secondary bilateral synchrony mechanism• Ca.~'eNo. 4 (L C ) This 9-year-old girl was admitted in 1959 because of seizures. At the age of 6½ years she developed irritability, crying spells, behavioral problems and a voracious appetite. Five months prior to admission she had the onset of almost daily seizures described as unresponsiveness, with a wide-eyed stare andfrightenedexpression, lasting less than 2 min. She also had frequent nocturnal seizures characterized by sudden rigidity followed by opening of the eyes, flexion of the neck, flushed face with a terrified facial expression and unresponsiveness lasting 1-2 sin, with a brief post-ictal confusion. She did not rp~pcmd t,~ ~ number , , r o,,+;....... ~o~-. drugs. At age 7 she developed pubic and axillary hair as well as enlargement of the breasts, with. out menstruation. The remainder of her history was unremarkable. Physical examination was normal except for moderately well developed secondary sexual characteristics withoutenlargementoftheclitoris. The uterus appeared slightly enlarged. Neuro. logic examination was normal, Hemogram, urinalysis, and blood chemistries were within normal limits for the age. Endocrine studies showed 24 h urinary gonadotropins greater than 10 and less than 50 mouse units (borderline);24hurinary17.ketosteroidsbetwecn 2.7andS.0mg.SkullX-rayswerenormal, Doneage was 10-11 years. No neuroradiologic procedures were carried out. In the hospital she had one seizure characterized by unresponsiveness, staring with deviation of the head and eyes to the right, salivation, right-sided tonic-clonic movements involving the face and neck muscles lasting 1 min, followed by brief confusion. Seven EEGs were performed over a 3 year period. The first four records taken at ages 8 and 9 showed a somewhat disorganized background with a dominant frequency of 7-7.5/sec over the posterior areas intermixed with theta frequencies and high voltage symmetrical synchronous waves at 3-4/sec. Infrequent sharp transients were noted. Occasional bursts of bilaterally synchronous and high voltage rhythmical 2-3/sec slow activity, with a suggestion •
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CENTRENCEPHALIC PATTERNS
565
of a spike component, of 1-3 sec duration ap- experience would suggest that the routine use peared maximally in the posterior regions with of activating procedures and, particularly, numinor shifting asymmetry, .....Hyperventilation merous seria! recordings would probably have - ~ s i 0 n a i l y enhancedthe discharges, No symp- increased the likefihood of detecting such abtoms accompanied these bursts. Photic stimula- normalities. tion had no effect, The subsequent three tracings In reviewing Table I, it becomes apparent showed background alpha activity with diffuse that, with the exception of patient 4ofthepresent symmetrical slow waves in the theta frequency series, in whom no neuroradiologic procedures range, Occasional runs of symmetrical and syn- were performed, all cases ~f precocious puberty chronous 3-4/sec slow activity without spikes are clearly of the cerebral type. The patients of were occasionally seen. No activation was noted Listetal.(1958),Hann(1957)andMcCullaghetal. with hyperventilation and photic stimulation. (1960)revealedtumorsatautopsyimpingingonthe These records were interpreted as showing a hypothalamic area and our first two cases showed diffuse slow dysrhythmia as well as paroxysmal definite abnormalities in the area of the 3rd discharges suggestive of subcortical involvement, ventricle on pneumoencephalography. NoneAlthough aware of the fact that these discharges theless, neither of these two patients had any are not as typical as those observed in the other clinical evidence of central nervous system patients, we feel justified i~t includit~g this case derangement due to space occupation or to in our series since there were also seizures of increased intracranial pressure. The neurologic the "absence" type associated with the preco- findings and contrast studies in case 3 suggested cious puberty, that surgical removal ofthe tumor, which extended across the midline, resulted in damage to the DISCUSSION area of the chiasm and the floor of the 3rd Only three cases of precocious puberty with ventricle. "centrencephalic" EEG patterns have been A further point of interest is the incidence found in a review of the literature and these of seizures, both "petit mal" and "grand mar', are summarized in Table 1. In contrast to these in such cases. Lange-Cosack (1951), in reviewisolated eases, the majority of EEG studies in ing 18 cases of precocious puberty associated other series of patients with constitutional and with tumors of the hypothalamus, reported cerebral precocious puberty have been reported clinical seizures in eight. Lowrey and Brown as normal (Lowrey et al. 1951; Piotti 1952; (1951), in a study of 30 eases of precocious Boudin et al. 1954; Giraud et al. 1954; Jolly puberty, found eight of the cerebral type, with 1955; David et al. 1957; Bruton et al. 1961). convulsions in three who had other manifestaSome showed slow dysrhythmias or focalepilepti- tions of central nervous system disease as well. form potentials, particularly in cases of deep- In contrast no seizures were recorded in Jelly's seated tumors. For example, David et al. (1957) (1955) series of 34 cases of constitutional and report six cases of precocious puberty due to five cases of cerebral (tumoral) precocious cerebral tumor. Although several of their EEGs puberty. These representative reports suggest that were abnormal none was described as showing seizures are a relatively common occurrence in any paroxysmal activity of the"centrencephalic" precocious puberty of the cerebral type, partictype. Furthermore, in their literature review of ularly when associated with tumors. The data 55 tumors of the 3rd ventricle and 31 tumors of presented in Table 1 confirm this impression. the pineal gland associated with precocious If one includes case I of our series, who had puberty, the presence of this pattern was not apparent "absences" coincident with spike an~! mentioned in any patient on whom EEGs had wave discharges, the total number with ictal been performed. The reason for the obvious manifestations increases to six out of seven cases discrepancy between the relative paucity of who had"centrencephalic" discharges. Only case reports of"centrencephalic" discharges and the 2, with enlargement of the pineal body (by high proportion found in the present series pneumoencephalography) and spike and wave (4 out of 13 cases) is not clear. However, our discharges, had no history of clinical seizures. Electroeneeph. din. Neurophysiol., 1963~ .,'5:559-567
566
R.G. SCHERMAN AND K. ABRAHAM
Thus, despite the paucity of cases reviewed, their analysis i~dicate~ :,~at bilateral ~plke and wave discharges, particularly when associated with seizures, may be a not u n c o m m o n finding in precocious puberty of the cerebral type. Furthermore it is worth re-emphasizing that this EEG pattern may occur with structural lesions in proximity to the 3rd ventricle, even in the absence of other neurologic manifestations, Another factor that may influence seizure activity is the effect of relatively elevated hormone levels. An increase in the frequency of seizures in idiopathic epilepsy at the time of menarche and menstruation, when gonadotropic and estrogen levels are high, is an established obeervatt .t (Laidlaw 1956). Logothetl.s et al. (1959) have shown an activating effect of estrogent on the EEG both experimentally and in epileptic women. However, neither paroxysmal discharges nor seizures accompany constitu, tional and pseudo-precocious puberty, whose gonadal-hormone levels are equally elevated (Lowrey and Brown 1951; Jolly 1955). Th,refore, whether elevated gonadotropin and andxogen or estrogen levels may act synergistically with certain critically located subeortical lesions, particularly in the immature CNS ofchildren, remains a speculation, The significance of the association of precociout puberty of cerebral origin with "centren. cephalic" EEG patterns is evident if one takes into consideration the still controversial opinions of various investigators on the origin of the 3/see spike and wave patterns. Although the term "centrencephalon" has gained a certain recognitio~x since first used by Penfield and Jasper (1954) it is not a clearly established concept and refers to a rather ill-defined anatomical area located in midline subcortical structures, This area is considered by some investigators as the possible "origin" for 3/see spike and wave discharges, despite the paucity of, and at times contradicting, experimental evidence (Jasper 1947; Williams 19$3;Bickfordetal. 1955;Ogden et~. 195~1956; lngvar 1955, 1959).The dimculty in r e p r o d ~ this pattern experimentally and the ~ t e d number of depth electrode studies in cases ofcentrencephalic seizuresare ~ggravated by the lack of histopathological changes at autopsy in this type of epilepsy. Ajmone Marsan -
- .
.
.
.
.
and Lewis (1960) reviewed thirteen cases ofbrain tumo,~ a~ociated.-~:~ith 3/sec spike and wave complexes and discussed the controversy relati . ~ to the ,,~+t,. . . . . :~ and ~~'~+~--^+ . U a LUILLXV ~.p .~ ., ~.=.L ~ V Lh;~. ~L~ origin of this EEG abnormality. They concluded that "the large predominance of subtentorial or midline localizations in tumors accompanied by this characteristic electroencephalographic pattern is suggestive of a primary brain-stem role in the mechanism of production of the pattern itself". The two subsequent cases of Millichap et al. (1962), one with a right temporal (deep and midline) astrocytoma, the other with a lipoma of thecorpuscallosum, both with"centrencephal. ic" EEG patterns, are in agreement with this view. Since the structural lesions etiologically linked with precocious puberty have their anatomic localization in the area of the 3rd ventricle and hypothalamus, a region likely included in the hypothetical "centrencephalic" center, their association with 3/see spike and wavecomplexes lends further clinical support to the role of these regions in the pathophysiological mech. anisms and the origin of these patterns. " ~ O
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SUMMARY
Four cases of precocious puberty with EEG patt©rns of a "centrencephalic" type have been described, together with three similar cases reported in the literature. It would appear that the association of these characteristic EEG patterns with precocious puberty, either with or without clinical seizures or neurologk: signs, is suggestiveof the cerebral etiology of true precocious puberty. Since the lesions linked with precocious puberty are located in proximity to the 3rd ventricle and hypothalamus, their association with such EEG patterns lends further clinical-pathological support to the role of these midline subcortical structures in the genesis of these patterns. The authon wish to express their appreciation to Dr. Cosimo Ajmone Marsan for his encouragement and editorial assistance. R~CES A~MoNzM,,,a.~N,C.and L~wm,W. It. Patholosicflndinss in patients with "centgencephaHc" electmm,cephalographicpatterns. Nomo/aS,y (MImm~.), 1960, 10: 922-93o. Electroe~mei~. dim. Newo~stol., 1963, 15:559-567
CENTRENCEPHALIC PATTERNS
567
BICKFORD, R. G., KErYH, Fi. M. m-~ MACCARTY,C.S. Lp~r,C. F., DOW~N, C. E., BAc,cm, B. and Be.raN. J. Some observations on the mechanism of"petit real". Po~erinr h:.~ot.~-..A..~,fi~; h~a~tomas and gangliaTram. Amer. NeUral. Ass.,8OthMeet.,19S&-13 ~15~....... gliomas causing precocious puberty. Neurology BOUDnq, G., ~ e T , J. et I.~neT, R. L'association (Minneap.), 19~, 8: 164-174. ~.nilepsie-e_nd__~.O~em__L~e;~,pi.tepsicd'o~.~'Ic profonde LOOOTtmTm,J., HARNF.R,R., MOmmLL,F. and Tourm, F. avec Lra~ ¢~pileptique de type petit real et endocrinoThe role of estrogen in catamenial exacerbation of pathie d ' o ~ ~enc~phalique. Rev. neurol.,19S4, 91: epilepsy. Neurology ( Minneop.) , 1959, ~: 352-360. 330-.~16. L o w ~ , G. H. and BROWN, T. G. Precocious sexual BacrrON, O. C., M~xTz, D. C. and Gt:aARD, E. S. Predevelopment: a study of 30 cases. J. Pediat., 1951, 38: cocious puberty due to secretory chorionepithelioma 325-340. (teratoma) of brain. J. Pediat., 1961, 39: 719-725. MCCULLAGH,E. P., ROSENBERG,H. S. and NORMAN,N. DANOWSKI, T. S. Clinical Em~ocrinology. Williams and Tumor of tuber cinereum with precocious puberty: Wiikins Co., Baltimore, 1962, Vol. 1, 357-371. case report with hormone a ~ y s . J. clin. Endocr., DAVID, M., DIE AJURIAOUIERILA, J. et BONIS, A. Les 1960, 20: 1286-1293. pubert~ pnkocu des tumeurs c~r~brales. Sam. HOp. MILLICHAP,J. G., BICKFOItD, M. B., MlttJEit, M. D. Paris, 195"/, 33: 3935--3958. and BACKUS, R. E. The electroencephalogram in Gtt~UD, P., OitatSl, A., BADeTTt, L. et Loucticr, E. children with intracranial tumors and seizures. Pubert6 pr6coce et ¢omitialit6. Marseille.Med., 19~, Neurology (Minneap.), 1962, 12: 329-336. 91: 571-574. OODeN,T. E., AtRD,R.B. and GAROUTTe,B. D. Studies on HANS, J. "Petit maP' seizures in pubertas praecox from the nature ofbilateral and synchronous cerebral spiking. hypothalamic orifm. L Int. Cong. Neural. Sciences, Trans. Amer. Neural. Ass., 80th Meet., 195S, 149-153. Pergamon Press, Brussels, vol. HI, 1957, p. 701-704. OODeS,T. E., Amp, R. B. and GAROtrrre, B. D. The naINGVAa, D. H. On the patho-physiology of the threeture of bilateral and synchronous cerebral spiking.
per-so:and spike-and-wave epilepsy. Electroeneeph. olin. Neurophyslol., 1959o I i: 187.
Acta psychiat, stand., 1956, 31: 273-284. PeNFieLD,W. and JASPER,H. Epilepsy and the functional
JOLLY, H. Sexual Precocity. C. C. Thomas, Springfield, i11., 195~ 276 p. LAIDLAW, J. Catamenial epilepsy. Lancet, 1956, 271:
anatomy of the human brain. Little, Brown and Co., Boston, 1954, 896 p. PtOTTI, A. Pubert.as praecox bei Tumor der Regio hypothalamica und Neurofibromatose Recklinghausen. Acta endocr. (Kbh.), 1952, I0: 66-85. WiLLiAMS,D. A study of thalamic and cortical rhythms in petit reel. Brain, 1953, 76: 50-69.
1235-12Y/. LANoe-Coe~cg, H. Vemchiedene Gruppen der hypothalamiachen Pubertaa praecox. Dtsch. Z. Nervenbatik., 19510 166: 499-$45.
Reference: SC~l~tLe.t,m,R. G. and AnAm~M, k..,Centrencephalic" electroencephalolpraphic patterns in precocious puberty. Eleetroeneeph.olin. Neurophyslol., 1963, l.T: 559-567.
559
"CENTRENCEPHALIC" ELECTROENCEPHALOGRAPHIC PATTERNS IN PRECOCIOUS PUBERTY R. G. SCHERMAN, M.D. 1 AND K. ABRAHAM, M.D. Branch of Electroencephalography and Clinical A'eur~physioiogy, National Institute of Neurological Diseases and Blindness, National Institutes of Health, Bethesda, Md. (U.S.A.) (Received for publication: October 24, 1962)
INTRODUCTION This study was suggested by the incidental finding of 3-3.5/sec bilaterally synchronous spike and wave activity in the routine EEG of a girl referred with the clinical diagnosis of true precocious puberty, a This EEG pattern was of particular inte,~st since the patient was found to have an enlarged mamillary body on pneumoencephalography, The possibility that a lesion in this location might be related to both the endocrinopathy and the "centrencephalic"a discharge in the EEG appeared a reasonable assumption and a search for similar cases in the literature and in the files of our laboratory was undertaken, PATIENT MATEKIAL All cases referred to our EEG Laboratory Presently at Second (Cornell) Neurology Service, Bellevue Hospital, New York, N.Y. (U.S,A,) t Precocious puberty can be classified (Danowskt 1962) into true precocity and pseudo.precocity. The latter results from the production of excessive amounts of androBen or estro~n by the gonads or by the adrenal cortex in the absence of pituitary stimulation. In true precocity there is elevation of gonadotropic hormones as well as androBcns or estrogens approaching adult values at an earlier abe, which indicates premature pituitary~,¢tivity. True precocity can be sub.divided into : (a) constitutional type, where no etiology can be determin-
ed, and (b)cerebral type secondary to intracranial lesions, Mnerally in the area of the 3rd ventricle and hypothalamug. In this paper only true sexual precocity will be considered, a The term "centrencephalic" as used by Penfield and Jasper (1954) in "petit maP' epilepsy is referred to here to describe the specific electrographic pattern charactefized by bilaterally synchronous paroxysmal discharges of the more or less classical type (3/~ wave and spike complexes) without n__~es_ sarily referring to its clinical manifestations. For further details see Penfield and Jasper (1954), Ajmone Marsan and Lewis (1960) and the present discussion,
within the past 10 years with a verified, diagnosis of true precocious puberty were reviewed. Twelve such patients were found. In addition to the one already mentioned, two had bilaterally synchronous bursts of 2. 5-3. 5/sec spike and wave activity in their EEGs; the remainder had tracing which were considered normal for their age. An additional case of precocious puberty with a suggestive "centrencephalic" EEG pattern was found after reviewing the charts of 51 seizure cases with the discharge diagnosis of "subcortical" or "petit maP' epilepsy. This constitutes four cases, roughly one-third of a total of thirteen wherean EEG pattern of the "centrencephalic" type was associated clinically with precocio,.~s puberty. Of these thirteen cases three can be considered to be definitely, and one possibly, of cerebral origin and are included in the following case reports. The remaining nine cases in the absence of any apparent etiologic factor or
neurologic symptoms have probably to be classified as beiol~ging to the constitutional type, although no neuroradiologic procedures were performed and a small neurologically silent lesion could not be excluded with certainty in the genesis of their endocrinopathy. Since only a small number of reports on this subject have been published to date, a summary of case histories and EEG findings is presented. Pertinent data from our four casts and from three similar ones previously reported by others are shown in Table I. CASe ~EPORTI Case No. 1 (B.$.) This 7~-year-old white girl was the result of a normal pregnancy and delivery. Pubic hair and breast enlargement were first noted at the age of 16 months and were followed at 19 months Electwenceph. clin. NeurophysioL, 1963, 15:$59-~;67
560
R.G. SCHERMAN AND K. ABRAHAM
TABLE 1 Cases of precocious puberty associated with "centrencephalic" discharges
Authors
Age,
Clinicaldiqnosis
sex-race
Age onset of precocious
Lesion
Seizure
EEG
infundibuloma in
"Petit m a P '
Synchronousspike
anteriorhypothalamus*
and grand mal
and wave discharges
puberty Harm,
8t years I. Precocious
1957
(died) M-W
About
puberty,cerebral 4 months 2. Seizures
L ~ ~ u;.
iO ymrs i. i~7o~ious
About
Hamartoma, mid- Clinical
Atypical spike and
1958
F-W
2 years
line, extending from chiasm to upper pens, at-
myoclonic "petit maP'
wave discharges with left-sided predominance
"Petit mar' followedby short automatism and disorientation
Diffuse slow dysrhythmia; spikeand wave patternwhile dozing
puberty, cerebral 2. Brain tumor
tached to left mamillary body* MoCullagh al. 1960
6t years 1. Precocious F-W puberty
I year
et
Present
7~ years
Precocious
16 months
Series #1
F-W
.,.,...,.,v.,,,., ,J, ,,...k._,,I.......,,.
Tumor of tuber cinereum (astrocytoma) extending from infundibulum to upper pens*
Enlnrsexl mnmil. .
.
.
.
.
.
.
.
.
law body*"
(B. S.)
.
.
.
Nn hiatn.,'y nr
..,
seizures - ap-
and wave dis-
parent "absence" with bursts
charges
-
3 4 / ~ spike
.
.
.
.~.~.
w.
1_1 ¢/,~,,,,.,,,;t,,. . * * * * i ~
~jj~iA,
qw
~2 (O. U,)
6 years
Precocious
M-W
puberty,cerebral
~$ (O. O.)
9 years Precocious F~W puberty,cerebral
7 years
Left frontal astrocytom, extending across midline, removed at ago 6
#4
8 ye~t~
I. Precocious
6t y e a r s
None***
(L, C,)
F-W
puberty, constltu-
"absence"
rhythmia and
tional(?) 2, Sulgortical
with staring and ri$idity
2-3/se¢paroxysreal slow activity with suRmtion of a
4]i y e a r s
seizures
Enlargedpineal**
and wave discharles A. Generalized Leftfrontal focus with risht.sided and 2~3,$/sec predominance bilaterallysyn. B. Clinical ¢htonousspike "petit maP' and wave discharges Clinical Diffuse slow dys-
spike component * Autopsied case ** D i a l l n ~ by pneumoencephalowaphy *** No neuro-radiologie studiu
of age by intermittent vaginal bleeding, On her first admission at the age of' 28 months, patient showed breast enlargement, pubic hair, a palpa, ble uterus and a bone age of 6 years, Further admissions confirmed these findings and she continued to Brow in advance of' her chronologic
age, The remainder of her history was unremarkable; she had no symptoms referable to the central nervous system and had no seizures. During her most recent admission in 1962 at the age of' 7]~, she was a pleasant adolescent with behavior appropriate for her age. Examina-
F_.lectroenceple. elin. Neuropkysiol., 1963, 15:559-567
561
CENTRENCEPHALIC PATTERNS
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tion was unremarkable except for well developed sexual characteristics. Neurologic examination was normal. Laboratory studies revealed normal hemogram, urinalysis, and blood chemistries for the age. Endocrine studies over a period of several years revealed urinary gonadotropins ranging from IO-65 mouse units; urinary corticolds 4.8-7 mg per 24 h; urinary 17-ketosteroids 2.5 mg per 24 h. x A fractional pneumoencephalogram performed at age 6~ years revealed a 1 cm mass in the interr~ duncular cistern somewhat to the right of the midline felt to represent an
enlargement or tumor of the mamillary body. Carotid arteriograms were normal. Her IO was 110. The patient had a total of seven EEGs. Those records taken at the age of 2 and 4 were considered within normal limits for the age. The subsequent records have been consistently abnormal, showing a background activity of well developed and regular 8-10/see alpha activity, low voltage anterior fast activity and transients in the theta frequency range which appeared bilaterally and symmetrically. In addition, there were occasional bvrsts of high amplitude t The normal range of values established in the Clini- rhythmical and bilaterally synchronous diffuse 3-cal Patholo~ Department of the ClinicalCenter for the 3.5/seespike and wave complexes which were of age Ip'oup of both sexes included in this paper is: gonado- maximal amplitude posteriorly, varying in tropins' less than 10 mouse uni~/24 h; 17-ketosteroids: duration from 3-5 sec. Minor shifting asymmetry 0.8-2.6 rag/24 h; 17.hydroxy corticoids: approximately 2-10 m8/24 h above the age of 2 (values are based on of these discharges was noted. Some of these limited number of normal controls), bursts were elicited by eye closure. During photic Electroenceph. din. Neurophysiol., 1963, 15:559-567
50,2
R, O. SCHERMAN AND K. ABRAHAM
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stimulation them was slight driving and, at faster rrequenct., high amplitude symmetrical bursts identical to those occurring during the resting record were activated (Fig. 1). The patient appeared to have brief' lapses of consciousness during the bursts of spike and wave activity, without other ictal manifestations. Hyperventilation produced no activation. Sleep patterns were normal. These records were interpreted as showing a normal background activity for the age with paroxysmal activity of "centrencephalic" type.
or ejaculations, his voice did not change and no facial hair appeared. There was no history of seizuresand the remainder of his medical history was non-contributory. Physical examination was negative except for striking secondary sexual characteristics as manif'ost~ by profuse growth of hair over his legs and pubic area, enlargementof the penis and testes and unusual. ly prominent muscular development for his age. His height and weight were above the 100thpercentile for his age. Neurologic examination was normal. Hemobram, urinalysis, and blood chemistries were within normal limits for Case No. 2 (G.U.J the age, Skull films wero normal and bone age This 6-year-old white boy was admitted was I1½ years. Spinal fluid was normal. Pneu~ u s e or precocious puberty. Pubic hair was moencephalograms showed definite enlargement first noted at 4~ years of' age and was £ollowed or the pineal gland with normal filling of the by further development of' secondary sexual 3rd ventricle, Carotid arteriograms were normal. chara~ristics, He did not have any erections Endocrine studies: 24-h gonadotropin titer FJectroe,ceph. ¢1i~;. ,~,'¢~ror,h:,'~,,do, !963, 15:559-$67
563
CENTRENCEPHALIC PATTERNS
GG 61-0804
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C3 P3
O,
A2
P4 D
Fill. 3 EEG in cax 3 showin8 brief bursts of bilaterally synchronous, slightly uymmetri~l 2-2.$/sec spike and wave complexes. In this sample, these are of slightly larger amplitude on the right side. There is slowing of backuound in left fronto.central area.
greater than 10 mouse units on several occasions; urinary 24-h 17.ketosteroids varied between 2 and 4 m8 and 17.hydroxycorticoids between 3 and 9 mg per 24 h; protein bound iodine 6.6 /48 percent. The remainder of the laboratory studies were normal. The patient had three EEGs all characterized by a normal background activity for the age. The tirst tracing showed several bursts of diffuse, bilaterally synchronous high amplitude 3.54/see spike and wave activity with minor, shifting asymmetries particularly following eye closure (Fig. 2) and during photic stimulation at 15 flashes per sec. During hyperventilation there were several bunts of 3--4/sec high amplitude sinusoidalslow activity with larvalaccompanying spikes; several similar bursts occurred after hyperventilation. The subsequent records did not show paroxysmal activity. The first EEG was interpreted as showing paroxysmal activity
of the "centrencephalic" type with an otherwise normal background.
Case No. J (G.G.) This 9.year-old white girl was seen at the Clinical Center in 1959 because of seizures. In 1956,at the age of 6, she had several generalized convulsions, and in February, 1957, a left frontal astrocytoma was removed at another hospital. This lesion extended across the midline at the base of the frontal lobe and "had to be dragged out". Subsequently she has had a right spastic hemiparesis, dysphasia and blindness of the left eye. One year after the removal of the tumor seizures recurred and consisted of two types: (I) generalized convulsions with right.sided predominance; (2) blank stares and unresponsiveness with drooping of the head for about 30 see, occurring a n~ :~ber of times daily without other Electroenceph. din. Ncuroph~,alol., 1963, 13:559.-$67
5~
R.G. SCHERMAN AND K. ABRAHAM
convulsive movements or post-ictal confusion, At this time she developed secondary sexual characteristics and, shortly thereafter, began to ,~.~,.,,~+= "~ . . . . . . . . :..+i+. of her history was unremarkable. On examination, the patient was a healthy girl with well developed secondary sexual characteristics. Neurologic examination showed a mild organic mental syndrome, dysphasia, left optic atrophy, a right superior quadrantic visual field defect and a right spastic hemiparesis, Hemogram, urinalysis and blood chemistries were within normal limits. Skull films revealed evidence of a left craniotomy. Pneumoencephalograms showed marked bilateral ventricular dilatation, left more than right, with a slight shift of the midline structures to the left• The 3rd ventricle appeared sliahtlv dilated on tomegrams. Carotid arteriography revealed no apparent residual tumor. Endocrine studies showed urinary gonadotropins greater than 10 mouse units and less than 50 mouse units (borderline value); 17-ketosteroids 4.3 mg/24 h; urinary corticoids7.4mg/24h. Lumbar puncture revealed normal pressure and protein with no cells, A total of ten EEGs was performed over a period of 3 years. The background was well formed and organized for the age with a domi. nant frequency of ~8/sec activity of slightly larger amplitude over the left side. Fairly high voltage slow wave activity in the delta and theta frequency range appeared abundantly on the frontal, prefrontal and fronto-central regions, more pronounced over the left side. Almost continuous 2-3.5/sec poorly formed slow spike and wave activity was seen in the left frontal area with spread to the corresponding right side. In addition, 2--3.5/sec spike-wave discharges occurred bilaterally and synchronously over both hemispheres with maximal amplitude in the frontal regions and, occasionally, with slightly higher amplitudes over the right side (Fig. 3). Hyperventilation produced occasional runs of synchronous and symmetrical high voltage 23/see spike and wave activity which was maximal in the left frontat area. Photic stimulation had no effect. This record was interpreted as showing an epileptogenic focus in the left frontal area, as well as occasiolml bursts of bilaterally synchronous spike and wave activity either repre, 61a~
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senting a subcurtical discharge or resulting from a secondary bilateral synchrony mechanism• Ca.~'eNo. 4 (L C ) This 9-year-old girl was admitted in 1959 because of seizures. At the age of 6½ years she developed irritability, crying spells, behavioral problems and a voracious appetite. Five months prior to admission she had the onset of almost daily seizures described as unresponsiveness, with a wide-eyed stare andfrightenedexpression, lasting less than 2 min. She also had frequent nocturnal seizures characterized by sudden rigidity followed by opening of the eyes, flexion of the neck, flushed face with a terrified facial expression and unresponsiveness lasting 1-2 sin, with a brief post-ictal confusion. She did not rp~pcmd t,~ ~ number , , r o,,+;....... ~o~-. drugs. At age 7 she developed pubic and axillary hair as well as enlargement of the breasts, with. out menstruation. The remainder of her history was unremarkable. Physical examination was normal except for moderately well developed secondary sexual characteristics withoutenlargementoftheclitoris. The uterus appeared slightly enlarged. Neuro. logic examination was normal, Hemogram, urinalysis, and blood chemistries were within normal limits for the age. Endocrine studies showed 24 h urinary gonadotropins greater than 10 and less than 50 mouse units (borderline);24hurinary17.ketosteroidsbetwecn 2.7andS.0mg.SkullX-rayswerenormal, Doneage was 10-11 years. No neuroradiologic procedures were carried out. In the hospital she had one seizure characterized by unresponsiveness, staring with deviation of the head and eyes to the right, salivation, right-sided tonic-clonic movements involving the face and neck muscles lasting 1 min, followed by brief confusion. Seven EEGs were performed over a 3 year period. The first four records taken at ages 8 and 9 showed a somewhat disorganized background with a dominant frequency of 7-7.5/sec over the posterior areas intermixed with theta frequencies and high voltage symmetrical synchronous waves at 3-4/sec. Infrequent sharp transients were noted. Occasional bursts of bilaterally synchronous and high voltage rhythmical 2-3/sec slow activity, with a suggestion •
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Electroenceph. din. Neurophysiol., 1963, 15:559-567
CENTRENCEPHALIC PATTERNS
565
of a spike component, of 1-3 sec duration ap- experience would suggest that the routine use peared maximally in the posterior regions with of activating procedures and, particularly, numinor shifting asymmetry, .....Hyperventilation merous seria! recordings would probably have - ~ s i 0 n a i l y enhancedthe discharges, No symp- increased the likefihood of detecting such abtoms accompanied these bursts. Photic stimula- normalities. tion had no effect, The subsequent three tracings In reviewing Table I, it becomes apparent showed background alpha activity with diffuse that, with the exception of patient 4ofthepresent symmetrical slow waves in the theta frequency series, in whom no neuroradiologic procedures range, Occasional runs of symmetrical and syn- were performed, all cases ~f precocious puberty chronous 3-4/sec slow activity without spikes are clearly of the cerebral type. The patients of were occasionally seen. No activation was noted Listetal.(1958),Hann(1957)andMcCullaghetal. with hyperventilation and photic stimulation. (1960)revealedtumorsatautopsyimpingingonthe These records were interpreted as showing a hypothalamic area and our first two cases showed diffuse slow dysrhythmia as well as paroxysmal definite abnormalities in the area of the 3rd discharges suggestive of subcortical involvement, ventricle on pneumoencephalography. NoneAlthough aware of the fact that these discharges theless, neither of these two patients had any are not as typical as those observed in the other clinical evidence of central nervous system patients, we feel justified i~t includit~g this case derangement due to space occupation or to in our series since there were also seizures of increased intracranial pressure. The neurologic the "absence" type associated with the preco- findings and contrast studies in case 3 suggested cious puberty, that surgical removal ofthe tumor, which extended across the midline, resulted in damage to the DISCUSSION area of the chiasm and the floor of the 3rd Only three cases of precocious puberty with ventricle. "centrencephalic" EEG patterns have been A further point of interest is the incidence found in a review of the literature and these of seizures, both "petit mal" and "grand mar', are summarized in Table 1. In contrast to these in such cases. Lange-Cosack (1951), in reviewisolated eases, the majority of EEG studies in ing 18 cases of precocious puberty associated other series of patients with constitutional and with tumors of the hypothalamus, reported cerebral precocious puberty have been reported clinical seizures in eight. Lowrey and Brown as normal (Lowrey et al. 1951; Piotti 1952; (1951), in a study of 30 eases of precocious Boudin et al. 1954; Giraud et al. 1954; Jolly puberty, found eight of the cerebral type, with 1955; David et al. 1957; Bruton et al. 1961). convulsions in three who had other manifestaSome showed slow dysrhythmias or focalepilepti- tions of central nervous system disease as well. form potentials, particularly in cases of deep- In contrast no seizures were recorded in Jelly's seated tumors. For example, David et al. (1957) (1955) series of 34 cases of constitutional and report six cases of precocious puberty due to five cases of cerebral (tumoral) precocious cerebral tumor. Although several of their EEGs puberty. These representative reports suggest that were abnormal none was described as showing seizures are a relatively common occurrence in any paroxysmal activity of the"centrencephalic" precocious puberty of the cerebral type, partictype. Furthermore, in their literature review of ularly when associated with tumors. The data 55 tumors of the 3rd ventricle and 31 tumors of presented in Table 1 confirm this impression. the pineal gland associated with precocious If one includes case I of our series, who had puberty, the presence of this pattern was not apparent "absences" coincident with spike an~! mentioned in any patient on whom EEGs had wave discharges, the total number with ictal been performed. The reason for the obvious manifestations increases to six out of seven cases discrepancy between the relative paucity of who had"centrencephalic" discharges. Only case reports of"centrencephalic" discharges and the 2, with enlargement of the pineal body (by high proportion found in the present series pneumoencephalography) and spike and wave (4 out of 13 cases) is not clear. However, our discharges, had no history of clinical seizures. Electroeneeph. din. Neurophysiol., 1963~ .,'5:559-567
566
R.G. SCHERMAN AND K. ABRAHAM
Thus, despite the paucity of cases reviewed, their analysis i~dicate~ :,~at bilateral ~plke and wave discharges, particularly when associated with seizures, may be a not u n c o m m o n finding in precocious puberty of the cerebral type. Furthermore it is worth re-emphasizing that this EEG pattern may occur with structural lesions in proximity to the 3rd ventricle, even in the absence of other neurologic manifestations, Another factor that may influence seizure activity is the effect of relatively elevated hormone levels. An increase in the frequency of seizures in idiopathic epilepsy at the time of menarche and menstruation, when gonadotropic and estrogen levels are high, is an established obeervatt .t (Laidlaw 1956). Logothetl.s et al. (1959) have shown an activating effect of estrogent on the EEG both experimentally and in epileptic women. However, neither paroxysmal discharges nor seizures accompany constitu, tional and pseudo-precocious puberty, whose gonadal-hormone levels are equally elevated (Lowrey and Brown 1951; Jolly 1955). Th,refore, whether elevated gonadotropin and andxogen or estrogen levels may act synergistically with certain critically located subeortical lesions, particularly in the immature CNS ofchildren, remains a speculation, The significance of the association of precociout puberty of cerebral origin with "centren. cephalic" EEG patterns is evident if one takes into consideration the still controversial opinions of various investigators on the origin of the 3/see spike and wave patterns. Although the term "centrencephalon" has gained a certain recognitio~x since first used by Penfield and Jasper (1954) it is not a clearly established concept and refers to a rather ill-defined anatomical area located in midline subcortical structures, This area is considered by some investigators as the possible "origin" for 3/see spike and wave discharges, despite the paucity of, and at times contradicting, experimental evidence (Jasper 1947; Williams 19$3;Bickfordetal. 1955;Ogden et~. 195~1956; lngvar 1955, 1959).The dimculty in r e p r o d ~ this pattern experimentally and the ~ t e d number of depth electrode studies in cases ofcentrencephalic seizuresare ~ggravated by the lack of histopathological changes at autopsy in this type of epilepsy. Ajmone Marsan -
- .
.
.
.
.
and Lewis (1960) reviewed thirteen cases ofbrain tumo,~ a~ociated.-~:~ith 3/sec spike and wave complexes and discussed the controversy relati . ~ to the ,,~+t,. . . . . :~ and ~~'~+~--^+ . U a LUILLXV ~.p .~ ., ~.=.L ~ V Lh;~. ~L~ origin of this EEG abnormality. They concluded that "the large predominance of subtentorial or midline localizations in tumors accompanied by this characteristic electroencephalographic pattern is suggestive of a primary brain-stem role in the mechanism of production of the pattern itself". The two subsequent cases of Millichap et al. (1962), one with a right temporal (deep and midline) astrocytoma, the other with a lipoma of thecorpuscallosum, both with"centrencephal. ic" EEG patterns, are in agreement with this view. Since the structural lesions etiologically linked with precocious puberty have their anatomic localization in the area of the 3rd ventricle and hypothalamus, a region likely included in the hypothetical "centrencephalic" center, their association with 3/see spike and wavecomplexes lends further clinical support to the role of these regions in the pathophysiological mech. anisms and the origin of these patterns. " ~ O
V ~ ' s x v ~
~'i-gt'~la
SUMMARY
Four cases of precocious puberty with EEG patt©rns of a "centrencephalic" type have been described, together with three similar cases reported in the literature. It would appear that the association of these characteristic EEG patterns with precocious puberty, either with or without clinical seizures or neurologk: signs, is suggestiveof the cerebral etiology of true precocious puberty. Since the lesions linked with precocious puberty are located in proximity to the 3rd ventricle and hypothalamus, their association with such EEG patterns lends further clinical-pathological support to the role of these midline subcortical structures in the genesis of these patterns. The authon wish to express their appreciation to Dr. Cosimo Ajmone Marsan for his encouragement and editorial assistance. R~CES A~MoNzM,,,a.~N,C.and L~wm,W. It. Patholosicflndinss in patients with "centgencephaHc" electmm,cephalographicpatterns. Nomo/aS,y (MImm~.), 1960, 10: 922-93o. Electroe~mei~. dim. Newo~stol., 1963, 15:559-567
CENTRENCEPHALIC PATTERNS
567
BICKFORD, R. G., KErYH, Fi. M. m-~ MACCARTY,C.S. Lp~r,C. F., DOW~N, C. E., BAc,cm, B. and Be.raN. J. Some observations on the mechanism of"petit real". Po~erinr h:.~ot.~-..A..~,fi~; h~a~tomas and gangliaTram. Amer. NeUral. Ass.,8OthMeet.,19S&-13 ~15~....... gliomas causing precocious puberty. Neurology BOUDnq, G., ~ e T , J. et I.~neT, R. L'association (Minneap.), 19~, 8: 164-174. ~.nilepsie-e_nd__~.O~em__L~e;~,pi.tepsicd'o~.~'Ic profonde LOOOTtmTm,J., HARNF.R,R., MOmmLL,F. and Tourm, F. avec Lra~ ¢~pileptique de type petit real et endocrinoThe role of estrogen in catamenial exacerbation of pathie d ' o ~ ~enc~phalique. Rev. neurol.,19S4, 91: epilepsy. Neurology ( Minneop.) , 1959, ~: 352-360. 330-.~16. L o w ~ , G. H. and BROWN, T. G. Precocious sexual BacrrON, O. C., M~xTz, D. C. and Gt:aARD, E. S. Predevelopment: a study of 30 cases. J. Pediat., 1951, 38: cocious puberty due to secretory chorionepithelioma 325-340. (teratoma) of brain. J. Pediat., 1961, 39: 719-725. MCCULLAGH,E. P., ROSENBERG,H. S. and NORMAN,N. DANOWSKI, T. S. Clinical Em~ocrinology. Williams and Tumor of tuber cinereum with precocious puberty: Wiikins Co., Baltimore, 1962, Vol. 1, 357-371. case report with hormone a ~ y s . J. clin. Endocr., DAVID, M., DIE AJURIAOUIERILA, J. et BONIS, A. Les 1960, 20: 1286-1293. pubert~ pnkocu des tumeurs c~r~brales. Sam. HOp. MILLICHAP,J. G., BICKFOItD, M. B., MlttJEit, M. D. Paris, 195"/, 33: 3935--3958. and BACKUS, R. E. The electroencephalogram in Gtt~UD, P., OitatSl, A., BADeTTt, L. et Loucticr, E. children with intracranial tumors and seizures. Pubert6 pr6coce et ¢omitialit6. Marseille.Med., 19~, Neurology (Minneap.), 1962, 12: 329-336. 91: 571-574. OODeN,T. E., AtRD,R.B. and GAROUTTe,B. D. Studies on HANS, J. "Petit maP' seizures in pubertas praecox from the nature ofbilateral and synchronous cerebral spiking. hypothalamic orifm. L Int. Cong. Neural. Sciences, Trans. Amer. Neural. Ass., 80th Meet., 195S, 149-153. Pergamon Press, Brussels, vol. HI, 1957, p. 701-704. OODeS,T. E., Amp, R. B. and GAROtrrre, B. D. The naINGVAa, D. H. On the patho-physiology of the threeture of bilateral and synchronous cerebral spiking.
per-so:and spike-and-wave epilepsy. Electroeneeph. olin. Neurophyslol., 1959o I i: 187.
Acta psychiat, stand., 1956, 31: 273-284. PeNFieLD,W. and JASPER,H. Epilepsy and the functional
JOLLY, H. Sexual Precocity. C. C. Thomas, Springfield, i11., 195~ 276 p. LAIDLAW, J. Catamenial epilepsy. Lancet, 1956, 271:
anatomy of the human brain. Little, Brown and Co., Boston, 1954, 896 p. PtOTTI, A. Pubert.as praecox bei Tumor der Regio hypothalamica und Neurofibromatose Recklinghausen. Acta endocr. (Kbh.), 1952, I0: 66-85. WiLLiAMS,D. A study of thalamic and cortical rhythms in petit reel. Brain, 1953, 76: 50-69.
1235-12Y/. LANoe-Coe~cg, H. Vemchiedene Gruppen der hypothalamiachen Pubertaa praecox. Dtsch. Z. Nervenbatik., 19510 166: 499-$45.
Reference: SC~l~tLe.t,m,R. G. and AnAm~M, k..,Centrencephalic" electroencephalolpraphic patterns in precocious puberty. Eleetroeneeph.olin. Neurophyslol., 1963, l.T: 559-567.