LONG-TERM
FOLLOW-UP
OF
100 CHILDREN
WHO
RECOVERED
FROM
TUBERCULOUS
MENINGITIS
John Lorber, M.D., M.R.C.P.
Department of Child Health, University of Sheffield, England
ADDRESS: The Children’s Hospital, West Bank, Sheffield 10, England.
778
I
T IS MORE THAN 13 years since strepto-mycin became available for the treat-ment of tuberculous meningitis. Since then treatment has become progressively more efficient and much less complicated.’Be-tween 1947 and the end of 1955, 170 chil-dren were treated for tuberculous menin-gitis by the Department of Child Health of the University of Sheffield. One hundred of these survived for 5 years or more.
The purpose of this paper is to review the long-term results in these 100 survivors, 33 of whom have been followed for more
than 10 years (Table I). Thirty children had been treated with streptomycin, 35 with streptomycin and aminosalicylic acid (PAS), and 35 with isoniazid, streptomycin
and PAS. All had intrathecal treatment with streptomycin, although the length of the intrathecal therapy and the number of in-jections was progressively reduced as the newer antibiotics were introduced. No child had less than 20 intrathecal injections.
At the beginning of their illness 47 were less than 5 years of age, 43 between 5 and
9, and 10 between 10 and 14 years of age (Table II). Thirty-one survivors were in the early stage of disease, 53 were in the intermediate and 16 in an advanced stage on admission. After discharge from the llospital they were all followed at regular intervals. In the follow-up period much stress was laid on the assessment of their
personality, their achievement, and their adjustment to life. During this period closer acquaintance with the parents and
their siblings helped in placing the pa-tients’ achievements and problems in per-spective. Independent intelligence tests were performed by the Sheffield Child
Guidance Clinic staff under the direction of Mr. Whilde, who used the
Terman-Merrill scale, or other appropriate tests in the case of deaf or blind children. The first test was usually performed within a year of recovery. Repeated and very help-ful school reports were obtained from
head-masters and headmistresses for children of school age. This allowed a comparison
be-tween the scholastic progress and behavior before and after the meningitis in those
children who had attended school before their illness.
The children underwent routine neuro-logic examinations, which included a study of the fundi. This was followed by routine and often repeated electroencephalography
(Dr.
J. W.
Warboys), by routine electric audiometry and repeated roentgenographic examination of the chest and the skull. Other investigations were performed when necessary.Among the 100 survivors 77 were sub-jectively normal and 23 had various physi-cal or mental sequelae. These sequelae range from a minimal facial weakness to the most profound intellectual and physical disorganization (Table III). Of the
chil-dren with sequelae, 11 had been treated with streptomycin alone (of 30 survivors),
7 with streptomycin and PAS (of 35) and
5 with isoniazid, streptomycin and PAS (of
35).
In this survey the intellectual and emo-tional aspects will be dealt with first and
the physical characteristics later, although it is realized that it is impossible to separate
these completely.
INTELLIGENCE
Formal intelligence tests were given to all children. The total number of tests was
250. Up to four tests, at not less than an-nual intervals, were given to any one child.
TABLE I
PERIOD OF OBSERVATION OF 100 CHILDREN \Viio
SURVIVED TUBERCULOUS MENINGITIS*
TABLE III
PHYSICAL CONDITION OF TIlE 100 CHILDREN
AT THE MOST RECENT ASSESSMENT
Length of Follow-np
(3/7)
Children (no.)
.5-7 37
8-9 29t
10-13 34t
Condition .Vumber
77 4 1 a
13
* As of December, 1960.
f One in each group died long after recovery from the
nieningitis.
The results of the last tests were very similar to the results in the preceding test, as shown in Table IV. It became apparent that there was a group of six children who
became profoundly retarded by their ill-ness. It was also seen that, apart from these six, the range of the I.Q. in the remainder was about the same as that of the general
population. There is little doubt, however, that the I.Q. of the group tended to be less than that of the general population, the majority (65 of 94) having an I.Q. of
100 or less (Fig. 1).
The patients in this study, however, were not a true sample of the general
popula-tion. The composition of the socioeconomic status of their families showed a heavy preponderance of semiskilled or unskilled workers. It is to be expected, therefore,
that the I.Q.’s of these patients should be
below that of the general population. Nevertheless, in the absence of objective
TABLE II
AGE OF THE 100 CHILDREN ON ADMISSION*
evidence it is not possible to say with any certainty that the meningitis did not ad-versely affect many or possibly all children.
Unfortunately it is impossible to secure adequate controls for a sample like this,
but it is possible to analyze the circum-stances in each case in an attempt to
de-termine whether any intellectual loss is
likely to have occurred as a result of the
meningitis. It is apparent from Figure 2 that the age at which children contracted meningitis was of vital importance to the subsequent development. All the severely
affected children were 2 years of age or less on admission, but beyond this age there is a normal scatter. The proportion with
superior intelligence approximates that of the general population.
Superior Intelligence (Table V)
Seven children had an I.Q. of approxi-mately 120 or more. The striking feature
TABLE IV
INTELLIGENCE QUOTIENT OF THE 100 CHILDREN*
Age (yr)
Children (no)
0-4 47
<1 5
I 15
8
3 13
4 6
.5-9 43
10-14 10
I
.Q. Children
(no)
<50
50-70
71- 80
81- 90 91-100
101-110
111-120
121-130
>130
6
0
15
24
26
18
6
3
2
* There were 47 boys and 53 girls. * Terman-Merrill scale.
Subjectively normal Deaf
Blind
Fits
Facial weakness
z
., s, ‘ , &, , 100 110 130 I I.Q.
.
‘Si
‘Si
P4
P1
S 50
96-P
ioo i0i105 110 111-I115
116-( 121-I 1243-I 120 125 1O IO+[
:::::-‘--:; ---S
S_SSS%SSS__SSSS___SSS__
55
-SS----S---S---.SS-S-.S-SS---SSS---S
--- --S
-5---5---5-
5-5- 555-5
---5--____SS__-____
-::::.S5---
---,---S
#{149}
S
S
S
S
:
SS S
S I 2 5 5 5
S
S S S 55 5 5
S S S
S S
S 55
a
a:
:
:
a
S S S S S S
S 55
a
a
55
:
55 5 .:
S S
S S 2S S S
I.Q.’s of children with tuberculous meningitis
related to age on admission.
(1947-1955); results of last test
FIG. 1. Distribution of I.Q.’s of 94 children as
com-pared with a normal distribution for the same mean I.Q. of 97.5 and the same standard
devia-tion of 13.9.
in this group is that they were all fully
conscious on admission and throughout their treatment. In five the diagnosis of the meningitis was made at a very early stage. There was no apparent falling off in
alert-ness as a result of the illness; six children became excellent scholars. This group
in-eludes one boy who is an engineering stu-dent at a University; a deaf girl left school
after having won many prizes.
Average and Borderline Intelligence
Most of the children had average intel-ligence. A detailed consideration of back-ground, the history of early development and the occasional knowledge of previous
I.Q. and scholastic progress indicates that in the majority the meningitis did not cause
a detectable loss of intelligence. There is some evidence, however, that several chil-dren within the normal range did suffer intellectual deterioration as a result of the illness. Table VI gives data for the six
children with no neurologic sequelae but who probably suffered some intellectual loss as a result of the meningitis.
Among these, S.F. was just 1 year old when she developed meningitis. She was one of the first treated patients and re-quired very prolonged treatment, including
134 intrathecal injections of streptomycin. She became completely deaf. Her I.Q. of 71 was barely more than an approximation,
as she could not co-operate adequately dur-ing testing. This child died at another
hos-10-14
9
8
7
‘3
S
4
3
2
I
0-1.
* Degree of abnormality.
tDied.
TABLE V
DATA OF SEVEN CHILDREN WITH SUPERIOR INTELLIGENCE
Initials
Age, in Years .
Stage of Disease
Ofl Admission
I.Q. after Illness
Scholastic Achievement S S
Admission Follow-up Most Recent HighestS
L.C.
M.O’D. Ly.C. P.(;.
s.j.
A.J.K.E.
2 I 2
11
6
9
6
12 10
7 18
14
20
19
Intermediate
Early Early Early Early Early Intermediate
119 120
129 127
130
130 140+
121 Fair
124 Good .. Excellent
. Retained Grammar School place
154 Grammar school; very good
136 Sixth form; university
.. Prize winner; deaf school
pita! from pyogenic meningitis 8 years after veloped a block at the exits from the fourth
her recovery. ventricle, with resulting gross
hydroceph-RH. was a twin. He was in a very ad- alus, which was demonstrated by
pneumo-vanced stage of disease on admission and encephalography and ventriculography. The remained in coma for months. He developed cerebrospina! fluid pressure within the yen-a gross internal hydrocephalus. On recov- tnicles was very high, and frequent
yen-ery he at first appeared to have amentia, tricular punctures were necessary to relieve but gradually he improved. His I.Q. in- it. At the lowest point in his illness he had creased steadily to 78, but he remained gross papilledema, was blind, and had much duller than his twin. The most re- hemiplegia. Nevertheless he recovered with-cent encephalogram showed only minimal out any neurologic lesion and has cood abnormality, consisting of a big build-up eyesight. The block at the base of his brain on over-breathing. The degree of his re- persisted after recovery, and for some years
covery was remarkable in view of the orig- every time he had a sore throat, an upper ma! condition and the available methods of respiratory tract infection or any feverish
treatment in the early days. disease, the intracranial pressure increased
F.Z.’s history is very unusual. He de- sharply. This was shown by two large
TABLE VI
1)ATA OF SIX CHILDREN WIThOUT NEuRoIoGIc DEFECT BUT OF Low INTELLIGENCE PROBABLY
DUE TO MENINGITIS
S S Initials
Age, in I5ears
Stage of Disease S S
on Admission I.Q.
Electroen-
cephalo-.
graphic Findings*
Comment Admission Follow-up
S.F.
R.H.
F.Z.
MM.
R.E.
S.S.
1
I
4
5 5 5
9t
14
14
16
12
16
Early
Advanced Intermediate
Intermediate Early Intermediate
(?)71
78
80 81 8890 ..
1+
2+ Normal Normal1 +
Deaf; died
Twin; hydrocephalus
Obstructive hydrocephalus; headaches Progressive decrease in I.Q. Tuberculosis of spine; loss of schooling
TABLE VII
I)ATA OF ChILDREN WITII MAJOR NEUROLOGIC OR ENDOCRINE DEFECTS BUT WIThOUT Guoss
INTELLE-rUAL DEFECT
Initials
Age, in Years
-
-
Stage ofDisease.ldmission Follow-up--- #{176}.ldmission
---1.Q.
---
-
Electroenee;halo--Defect graphic Findings* W.M. K.F.
T.R.
C.P. P.B. A.H. 5 3 2 6 6 <1 17 15 13 13 13 7 Advanced Advanced Advanced Intermediate Advanced Early 93 90 90 75 78 1(X)* Degree of abnormality.
Optic atrophy; sexual precocity Hemiplegia on left; partial deafness Paraparesis; ectopic ossification
Hemiparesis on right
Hemiparesis on right; tuberculosis of spine
Flaccid nionoplegia; (?)poliomyelitis
2+ 1+ 3+ 2+ 2+ Normal TABLE VIII
* Degree of abnormality.
“horns,” cerebral herniations, through the
original bur-holes. He was admitted
sev-eral times to hospital in deep coma and was apparently moribund. A ventricular
puncture would immediately relieve the pressure and he would sit up within a mm-ute and demand food. Ten years after his illness he was still subject to headaches, and a myelogram confirmed that the basal
block
was still present. He was the onlychild in the series who was subject to head-aches. His I.Q. of 80 was well below the general level of intelligence of his family, and the promise of his earlier achievements.
S.S.’s parents were of good middle class
origin and conducted a successful business.
She was an only child who had a stormy illness complicated by bulbar palsy, hemi-plegia, gross hydrocephalus and papill-edema. Although she recovered from these
physical disabilities, her developmental his-tory indicates that her intelligence before the meningitis was higher than her pres-ent I.Q. of 90.
Intelligence and Neurologic Sequelae
Twelve children who survived had major neurologic or endocrine sequelae, exclud-ing isolated deafness, blindness or convul-sions. Six of these had I.Q.’s within the normal range (Table VII). It is likely, how-ever, that the intelligence of three was less
DATA OF Six CHILDREN WITH GROSS INTELLECTUAL DEFECT
Initials
Age, in Years Stage of
Disease on . S .ldmzssion .4pprox-imate I.Q.
Main Physical Defects
Electroen- cephalo-S graphic Findings* .4dmis.,ion Follaw-up
T.R.
D.W. A.B. H.A. C.D.T.H.
I 2 2 I I2
13 13 13 11 10 7 Advanced Intermediate Advanced Advanced Intermediate Advanced 46 34 25 0 0 45 HemiplegiaHemplegia; convulsions; deaf
Hemiplegia; paraplegia; ectopic
ossifica-tions; colivulsions; optic atrophy;
sex-ual precocity
Quadriplegia; torsion spasms; blind; sexual precocity
Hemiplegia on right; torsion spasms on left; I)lind convulsions; dwarf
Flaccid quadriplegia; optic atrophy
TABLE IX
EDUCATION OF THE 100 CHILDREN
* Thirty-one children left school subsequently.
than might have been expected from the family background and their earlier ac-complishments. This is particularly
notice-able in the case of P.B., whose I.Q. was only 78, and whose father was a deputy county librarian. All three with probable
intellectual deterioration were in an ad-vanced stage on admission, and all had ab-normal electroencephalographic findings
after recovery.
Severe Retardation
Six children were profoundly retarded and also had major neurologic sequelae (Table VIII). All were very young on
ad-mission, none were in an early stage when treatment was started, and five had grossly
abnormal electroencephalographic patterns. Three were treated with streptomycin alone, two with streptomycin and PAS, and
only one with isoniazid streptomycin and PAS. Except for T.H., all had gross hydro-cephalus demonstrated by pneumoence-phalography.
EDUCATION
Table IX gives information about the schooling of these children. One girl was
15 years old on recovery and did not re-turn to school; 6 remained ineducable. Seventeen children under 11 years of age
attended junior schools. Of the 70 children
who reached 11 years of age and were
not suffering from physical handicaps ne-cessitating attendance at special schools,
7 attended grammar schools,* 60 attended
secondary modern schools, and 3 attended schools for educationally subnormal
chil-dren. One child attended a school for the blind, and 5 were in schools for the deaf.
One child, with an I.Q. of 140, in a school for the deaf was of grammar school
stand-ard. The proportion of children of gram-mar school standard (10%) is less than the usual figure of approximately one in five, but the sample is too small for valid
corn-0 In England children of 1 1 years of age are
sent to Grammar Schools if their I.Q. is 120 or
more and to secondary modem school if their I.Q.
is below that level but the normal range.
Type of School Number of
Children5
Infant and junior 17
Secondary modern 60
Grammar 7
Deaf 5
Blind 1
Special 3
Left school on recovery 1
Ineducable 6
parisons. It is remarkable that many chil-dren were able to attend ordinary schools
in spite of severe physical handicaps such as hemiplegia, and in spite of prolonged
absence from school on account of their illness. It is probable that teaching in the wards by qualified teachers, as soon as the children were ready for it, contributed to these favorable results.
Thirty-one children subsequently left school and entered some form of useful employment. Most of the girls became shop assistants. Six girls and one boy married.
Several had children.
Detailed information is available about
the scholastic progress of all the children. Broadly speaking, and within their appro-priate environment, about one-third were making excellent progress, and one-third were of average ability, and another third
were dull and making poor progress. As would be expected, children who missed a
great deal of schooling found it difficult to catch up with their contemporaries, and
many had to join the classes with younger children. Those with lower I.Q.’s usually remained with their juniors throughout, or
were placed in the lower stream of multi-stream classes; but those with higher
in-telligence progressed well and joined
chil-dren of their own age.
A correlation between I.Q. and scholastic achievement was remarkably consistent.
ex-TABLE X
PERSONALITY DIs0IIDEIts IN CHILDREN WITH I.Q.’s GREATER THAN 70
Initials
.
Age, in Years
Admission Follow-up t.Q.
Physical Handicap
Electroen-
cephalo-graphic Findings*
Personality
S.F. B.D.
T.R.
S.B.t
V.G. CF.
1
12
2
7
11 11
7
21
13
18
20
18 71
100
90
86
88
93 Deaf Deaf Paraparesis;
hydrocephalus
Convulsions
.. . .
S Normal
3+
3+
Normal 2+
Inability to adjust
Initially resentful and morose Very shy; aloof
Outbursts of violent temper; extreme changes of temperament
Petty thieving; recovery on marriage Nocturnal enuresis; moral problems;
thieving
S Degree of abnormality.
t Considerable domestic stress.
pected from their I.Q. There was only one child whose teacher noticed a striking de-terioration in effort and achievement after meningitis.
CHARACTER AND BEHAVIOR
There was no apparent change in the
behavior of 88 children. In this large group there were pleasant friendly children,
eas-ily managed children and difficult,
temper-amental children. Usually they had a similar
character pattern before the illness, and the pattern was similar to that of one or both parents. Some were quiet, shy and
in-troverted; others were more open and frankly extroverted, as one would expect
in a normal population of children. Only
6 of the 94 children whose intelligence was within the normal range showed some
tem-porary personality disorder. In four the dis-orders were associated with a physical handicap; in the other two there were no
physical handicaps, and the disorders were not related to the meningitis. Two among the physically handicapped (Table X) be-came totally deaf. S.F. became deaf in in-fancy and could not adjust to this. She was of low intelligence, and her parents were
of poor intelligence and lacked understand-ing. The child was difficult, restless and
disobedient-a stranger in the world of
speaking people. She died of purulent men-ingitis at 7 years of age.
B.D. became very resentful as a result
of deafness and did not become settled for a long time, but he eventually acquired a good job and worked well.
T.R. was the most severely affected. He had a huge hydrocephalus, had been blind
for a long time, and had paraplegia in flexion, with ectopic ossification in his thighs. As a result of all this he was in hospital for several years. He made an astounding recovery but became aloof and very self-conscious because of gross
disa-bility resulting from the ossifications.
S.B., an epileptic girl, is subject to out-bursts of violence. She is moody and swings from profound depression to manic activ-ity. Her home life was very unhappy. Her
father, who from time to time suffered from hysterical paralysis or hemoptyses, hated her; there was constant fighting in the home. He would not allow her to sit at the the same table with him. Even when she was still at school she had to work during weekends and school holidays to help her mother care for a large family of many
children, because the father refused to work. Eve’nually the parents separated. S.B. spent 2 years in a training center for
SImpossible to test.
a stable occupation later. She had ample
reason to be disturbed even without her history of meningitis.
NEUROLOGICAL
LESIONS
AND
OTHER
PHYSICAL
DEFECTS
Neurologic lesions were frequently asso-ciated with intellectual or psychologic de-viations from the normal. All the children who showed definite intellectual
deteriora-tion also had neurologic sequelae. Alto-gether, 23 children had neurologic sequelae (including isolated deafness) and resulting subjective disability. However, several other children who did have gross
neuro-logic lesions during the active phase of their disease made a complete recovery. Oc-casional objective physical signs remained, such as extensor plantar response.
Outstand-ing among these signs was optic atrophy, not associated with any visual defect.
Hearing (Table Xl)
All mentally normal children underwent routine electric audiometric testing as soon
as they were old enough to co-operate during testing. In older children each ear was separately tested. In younger children
binaural hearing was assessed by the peep-show technique. The tests were repeated in the younger children to increase the ac-curacy of the observations and also in
chil-dren who were found partially deaf or whose ability to hear had apparently a!-tered during the follow-up period. The six
severely affected children could not be
tested this way, but rough tests indicated that the hearing was not grossly affected. Among the remaining 94, 84 had normal hearing at follow-up. The 84 included 3
children who had been deaf for a long pe-nod after their recovery. Two of them
were of school age and had actually
at-tended a school for the deaf. Their hear-ing gradually returned, and all three
even-tually could attend ordinary schools with-out difficulty and without use of a
hear-ing aid.
Six children had partial nerve deafness; five were able to attend an ordinary school, and only one attended a school for the
deaf. The latter child heard perfectly well for more than a year after recovery, but she then developed a tuberculous pleural effusion for which she was again treated
with streptomycin at another hospital. Fol-lowing this she became completely deaf in
one ear and moderately deaf in the other.
She derived great benefit from a hearing aid. It is clear that her hearing loss was
due to the repeated streptomycin treat-ment.
Four children were completely deaf. In
three the deafness was of the inner ear
TABLE XI
HEARING ABILITY OF THE 100 ChILDREN
S
Category of hearing Children(no ) Comments
Normal 84 Includes 3 children who recovered from deafness
Partial nerve deafness Attended ordinary school Attended deaf school
5
1
TWO required hearing aids; 2 unilateral (?) 1)elayed onset
Complete nerve deafness 3 Psychologic upset in one
Middle ear deafness I Due to recurrent otitis
TABLE XII
OPHThALMOLOGIC ASPECTS IN CHILDREN WITh
TIJBERCULOUS MENINGITIS
S S
Optw Lesion
Patient.s (no.)
.4ssoeiated Defects
Atrophy with blihidness 2 2+
Atrophy with good visioi i 2+
Complete blindness with re-covery
I 2+
2 .
Partial blindness with recovery ‘2 .
Persistant choroidal tuhercles 31 .
type and was the sequel of the meningitis or its treatment. One child suffered from recurrent attacks of otitis media of nontu-berculous origin before, during and after meningitis. These led to destruction of the eardrums and loss of the ossicles. Table III,
dealing with the physical condition of the survivors, lists four deaf children-the three who had complete nerve deafness and the one who had partial nerve deafness and
attended a school for the deaf. The hearing loss of the others was either not severe enough to constitute much disability or was not due to the tuberculosis or its treat-ment.
Vision and Ophthalmologic Aspects
(Table Xli)
There were three blind children, and all three had complete optic atrophy. Two of these had amentia, with multiple
neuro-logic defects, and the blindness is of no clinical importance. One child, however, was normal in every other way and was a good scholar in a school for the blind. He had some residual peripheral vision.
He developed extensive intracranial cal-cifications at the site of the chiasma. He suffered a relapse of meningitis 6 years after
recovery from the first attack and died very quickly. At necropsy there was an exten-sive calcifying tuberculous mass at the base
of the brain in which the optic tracts and
optic nerve were so completely embedded that they could not be identified
sepa-rately.
There were four other patients in whom optic atrophy was and remained complete as judged by ophthalmoscopic examination,
yet their vision was normal both
subjec-tively and on expert testing of visual fields and visual acuity. Two of these had
asso-ciated sequelae. Both were girls with preco-cious sexual development. The third was a boy who made a complete recovery from
spastic paraplegia. The fourth was a girl who recovered from spastic hemiplegia.
The latter two became subjectively normal in every respect.
Three children recovered completely
from total blindness associated with pa-pilledema, and two recovered from partial blindness. One of these was a large girl
with a homologous hemianopia. Although
this was the only proven case of hemianopia in this series, it is possible that its true
in-cidence was higher. It would be impossible
to make such a diagnosis in small children with variable degrees of clouding of
con-sciousness. Brief case histories of two of the
children who regained vision have already been given. The history of the third illus-trates how difficult it is to give a prognosis even in a situation that seems beyond all hope.
A. C. was admitted in April, 1953, at the age of 2 years 5 months. She was drowsy and irritable, and in spite of full antibiotic treatment her condition steadily deterio-rated and she became more and more deeply unconscious. Three months after
ad-mission she was deeply unconscious and was in a state of decerebrate rigidity; she
was blind and deaf. In view of the absence of response to treatment and in consulta-tion with her parents all treatment was suspended at their request. She was dis-charged home.
She unexpectedly started to make steady and progressive improvement. This im-provement was so striking after 5 months
ARTICLES
treatment and make sure that she would
not suffer a relapse. Eventually she made a complete recovery both physically and
mentally, and from an emaciated uncon-scious decerebrate child she became a nor-ma! person.
By the time she was 6 years old she had normal vision and normal hearing. She had no abnormal neurologic signs. Roent-genograms of the chest revealed normal
findings. A roentgenogram of the skull showed calcification above the sella. Her I.Q. in November, 1956, was 101. Her
school progress, according to her teacher, was amazingly good.
Electroencephalo-graphic findings remained abnormal.
Choroidai Tubercies (Table Xii)
Choroidal tubercies were commonly seen at the beginning of treatment and
mdi-cated associated miliary tuberculosis.8 It has often been stated that these tubercles disappear on recovery, but this is rarely
true in my experience. In this series tu-bercies of the choroid were still present at the last examination in 31 children in whom
they were found at the beginning of the illness. It is true that in cases of multiple small tubercles, some become virtually im-possible to locate again, as they become
very small scars indeed, but in most of the others there is little difficulty in locating them even without sedation or dilatation of the pupils, provided an accurate map was made of their position. In the latest and presumably permanent stages they ap-pear as dead white scars with either a mod-erate amount of black pigment scattered largely around the periphery, or with masses of black pigment almost completely
covering it.
Convulsions
Convulsions are a common feature of
tu-berculous meningitis during the active phase, but they persisted after recovery in only eight children (Table XIII). In five the convulsions were the only sequelae and
were well controlled by drug therapy. It is likely that one girl’s convulsions are not
due to the meningitis at all. On her ad-mission she was in an early stage of
men-ingitis, and she had no convulsions dur-ing her illness, which was uneventful. She had a normal electroencephalogram after recovery. Her first and only convulsion oc-curred 6 years later, and the electroen-cephalogram then showed a typical
epi-leptic pattern. She had a family history of
epilepsy. One of the other four in this group was a boy with well-controlled
con-vulsions associated with a large calcified intracranial tuberculoma and focal electro-encephalographic changes. Three children
suffered from recurrent grand ma! attacks. These three were among the six physically
and mentally most severely affected chil-dren. One of these, and another child who
had no grand mal seizures, exhibited
uni-lateral torsion spasms. These are unusual manifestations following tuberculous
menin-gitis. All the children with epileptic man-ifestations had abnormal electroencephalo-graphic patterns. I have not seen petit mal following tuberculous meningitis.
Paraiytic Lesions
There were 12 survivors with paralytic
manifestations of various types, often asso-ciated with other features already described (Tables VII and VIII). One boy had an isolated facial palsy. Seven suffered from spastic hemiplegia of varying severity, and one of these had residual paraplegia as well. There were two children with residual
TABLE XIII
INCIDENCE OF CoNvuIsIoNs IN CHILDREN VITH
TITBERCtTLOITS MENINGITIS
Electroen-Type of Cases . Associated
S cephalographie
Convulsions (no. ) . . * Dfecls
thil(ihili
Grand ma!
Frequent 3 3+ 3+
Occasional or
controlled S 2+ .
Torsion spasnit 2 3+ 3+
Petit ma! 0 .. .
* l)egree of al)norrnality.
Initials
Ageon Stage of
A dmission Disease on (yr) Admission
Site of Ossification
Neurologic Lesion
Comments
T.R.
A.B.
T.N.
2 Advanced
2 Advanced
5 Advanced
Ileopsoas and adductors, bilaterally
Ileopsoas tendons below pelvis, bilaterally
Ileopsoas tendons below pelvis, bilaterally
Paraplegia, with re-covery
Paraplegia, with great improvement
Paraplegia, with full recovery
Re-formed afteroperations; gross disability; osteot-omies
Moderate limitations of flexion; osteotomies
Tendency to spontaneous
absorption; no disability
TABLE XIV
EcroPhC OSSIFICATION AROUND THE HIPJ0INTS
paraplegia of moderate degree and one
child with spastic quadriplegia. In two
chil-dren the motor defect was of the lower motor neurone type.
One of the latter two (A.H., Table VI)
was less than 1 year of age when she
de-veloped tuberculous meningitis. She was in the early stage on admission and made good progress until she suddenly lost the use
of her leg and was subsequently left with a flail. short, small and cold limb. It is very likely that this girl had associated poliomyelitis, although this was not proved
by laboratory evidence. This girl had no
other sequelae and was the only child with a paralytic lesion who had a normal elec-troencephalographic pattern.
The other child with flaccid paraplegia (T.H., Table XIII) had severe flaccid
quad-riplegia with involvement of the abdomi-nal muscles and all the muscles of her back. She was severely retarded, but could speak, remember and sing nursery rhymes, yet she could not lift her head and was
un-able to move her limbs. Hydrocephalus was a constant feature of the badly paralyzed cases,1#{176}except for this last one.
It is noteworthy that the I.Q. of six of
the severely paralyzed children was below
50, four others had an I.Q. between 75 and 90, and only one (the girl with the flaccid monoplegia) had an I.Q. as high as 100.
Ectopic Ossification of the Hip Joints
An unusual source of disability was the occurrence of bilateral ectopic ossifications
of
the iliopsoas tendons and inthe
ad-ductors of the thighs.11 This occurred in three survivors (Table XIV), none of whom
were treated with isoniazid; all were in the advanced stage on admission, and at one time all had paraplegia in flexion.
The first child, T.R., was in coma for several months with paraplegia; when he recovered consciousness he was blind for a long time and had a low I.Q. At this stage roentgenograms of the hips showed rather ill-defined ossifications in both thighs,
although by then the neurologic signs of paraplegia had disappeared. Several oper-ations were performed and the ossifications were removed. The results were disastrous as the child rapidly developed further and even more dense lesions. After many years
the situation was improved by osteotomies of the femur, which largely corrected the flexion deformities and the alignment of his feet. He became able to walk, but had dif-ficulty in sitting and so remained severely
disabled.
The early history of the second child,
A.B., was similar, but the ossifications around her hip joint were confined to the
iliopsoas tendon below Poupart’s ligament. Her general recovery was far less corn-plete, and she retained a degree of para-plegia; no surgical attempt was made to remove the ectopic bone. Osteotomy of the
femur greatly improved the functional effi-ciency, and she became able to walk and
sit without undue difficulty.
The history of T.N., the last child in this group, is perhaps as remarkable as any.
S Degree of abnormality.
and remained so for a long time. At first he had gross papilledema, followed by
optic atrophy that persisted after 10 years; yet his vision became normal. He had a complete paraplegia in flexion and became
emaciated almost beyond description. At this stage he developed his bilateral ectopic ossffications. Eventually he made a corn-plete physical and mental recovery. He be-came a friendly sturdy youth with an I.Q. of 102, a good school report, and no trace of paralysis. The ossifications in his psoas tendons underwent considerable absorption, and he retained no disability from these.
Endocrine Disorders
Endocrine disorders following tubercu-bus meningitis are much less common than neurologic disorders. The only obvious and
gross endocrine disorder encountered in this series was sexual precocity’2 in three girls (Table XV). All three were in the advanced stage of disease on admission; all developed gross hydrocephalus; all had gross neurologic lesions. None was treated with isoniazid. One made an excellent
re-covery in spite of having a large cyst in the frontal lobe, in addition to hydroceph-alus. All three developed secondary sexual
characteristics at the age of 7 or 8 years; all started to menstruate soon after. All
three were very much above the 95th per-centile in height and weight at that stage of their development. One girl, W.M., re-tained the psychologic outlook of her
chron-ologic age and was not disturbed by her
rapid physical development. The other two were grossly retarded children. A fourth
girl reached sexual maturity at 9% years of age, but this could be within the
physio-logic range. I am not aware of any re-corded instances of male sexual precocity following tuberculous meningitis.
The other very rare endocrine disturbance that has been described is diabetes insipi-dus.13 There have been no such cases in this series, but I investigated two boys who were referred from other hospitals be-cause of gross polyuria and polydipsia fol-lowing tuberculous meningitis. We were able to confirm without a doubt vasopressin (Pitressin)-sensitive diabetes insipidus.
Eiectroencephaiographic Findings
In co-operation with Dr.
J.
%V.War-boys,14 all our survivors have been studied
by serial electroencephalography, with use
of a bipolar technique. I shall only briefly summarize the findings. As is shown in Table XVI, abnormal
electroencephalo-graphic tracings were almost constant in children with either persistent neurologic
sequelae, or in children who had had gross neurologic lesions (including coma) but from which they recovered, and also in children who had post-meningitic convul-sions. Of 34 such children, only 7
eventu-ally had normal electroencephalographic
tracings. The incidence of persistently ab-normal tracings was remarkably high (23) among 66 children who never had gross
neurologic lesions, who never had lost
con-TABLE XV
ENDOCRINE DISORDERS RESL-LTING FROM TUBERCULOUS MENINGITIS
Initials
Age on Admission
(1/F)
Age at Follow-up
(zi’)
Stage of Disease on Admission
I.Q.
Neurologic Lerion
Ekctroen- cephalo-graphic Findings5
Endocrine Disorder
W.M.
A.B.
H.A.
S
1
17
13
1 1
Advanced
Advanced
Advanced
93
(?)25
0
Optic atrophy; hydrocephalus Gross, multiple
Gross, multiple
3+
3+
(not done)
Sexual maturity at 7
years
Sexual maturity at 8
years
Sex development at 7
S Three children had both types of calcifications.
TABLE XVI
ELECTROENCEPHALOGRAPHIC FINDINGS AS RELATED
TONEUROLOGIC LESIONS
S Neurologw
Disorder
Total Number
Electroencephalographic
Pattern
Normal Abnormal Not
Done
Persistent lesions
Temporary
grosslesions
Persistent
convulsions Total No gross
neuro-ologic
dam-age at any
time
14
15
5
34
66
3
4
.
7
49
10
11
5
26 (79%)
15 (23%)
1
..
5.
1
2
sciousness and who recovered without sequelae. There are, however, qualitative differences. Table XVII shows the various
electroencephalographic patterns we have seen. One child had a normal resting
rec-ord but produced a big build-up on over breathing. The commonest abnormality found was generalized dysrhythmia (28 cases). Of these, 15 had no focal abnormali-ties. The children in this sub-group were either normal or not severely affected.
Thirteen, however, had additional focal
ac-tivity. In this group were several of the
TABLE XVII
ELECTROENCEPIIALOGRAPHIC PATTERNS OF
97 PATIENTS
Pattern Cases
(no.)
Normal 56
Abnormal
Normal resting record, abnormal build-up
on over-breathing 1
General dysrhythmia
Without focal lesions 15
With focal lesions 13
Paroxysmal general slow activity 7
Focal abnormality alone 5
more severely affected children; seven had persistent neurologic sequelae or convul-sions. Only two had no neurologic lesions at any time.
Paroxysmal general slow activity was seen in seven children. This group included two of the worst affected children, but also
one of the brightest children with no se-quelae. Focal abnormalities alone were seen in five children, four of whom had no
Se-quelae.
It is apparent that by and large there
was good correlation between the incidence of residual electroencephalographic abnor-malities and the incidence of neurologic lesions. Major electroencephalographic ab-normalities tended to coincide with the
TABLE XVIII
INTRACRANIAL CALCIFICATIONS RELATED TO NEuaoi.sxuc LESIONS
Type of Case
Cases (no.)
Intracranial Calcification
Roenigeno-grams not
Taken
None Meningeal Cerebral
-______
Total
. .
rosit ire
Persistent neurologic lesions Temporary gross neurologic lesions Persistent convulsions
14
15
5
6
9
1
6
6
1
1
0
2
7
6
3
1
.. .
34 17 13 3 16 1
No gross neurologic lesions at any time 66 37 22 10 29 ..
791
major physical defects, although there were some important exceptions, and several
normal survivors still had grossly abnormal tracings at the most recent examination.
intracranial Caicifications (Table XVIII)
An interesting feature of children who
recovered from tuberculous meningitis is the high incidence of intracranial
calcifica-516 These calcifications most corn-monly became demonstrable between 2 and
3 years after the onset of the disease, but occasionally they were not seen for up to 5 years. These calcffications were common-est in the basal meninges and much less common in the substance of the brain itself. In this series intracranial calcifications were demonstrated in 45 of 99 children who had serial roentgenograms of the skull.
Three children had both meningeal and cerebral calcifications. Of the 34 children who had either permanent or temporary neurologic lesions or had post-meningitic
convulsions, 13 had meningeal
calcifica-tions, as compared to 22 of 66 or who had no such complications. These differences in incidence are not significant, nor is there any significant difference between the
in-cidence of all types of calcifications. Very gross calcified masses may be seen on roentgenograms of the skull of perfectly
normal children. Often there is no
calcifi-cation at all in children with the most
ex-tensive neurologic damage. There is little doubt now that tuberculous meningitis must be the commonest cause of pathologic intracranial calcification in children.
SUMMARY AND CONCLUSIONS
A fairly complete report is given of 100
consecutive children who recovered from tuberculous meningitis. Although the va-riety of sequelae is very large the number of children seriously afflicted as a result
of the illness is relatively small. This is particularly true of the psychologic aspects. If we consider the whole background of these children, we may be reasonably sat-isfied with the end-results of treatment.
There is no doubt, however, that with
ear-her diagnosis and with modern treatment the incidence of serious sequelae could well be reduced to negligible levels.
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