MULTIPLE SCLEROSIS IN CHILDREN

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ARTICLES

MULTIPLE

SCLEROSIS

IN

CHILDREN

A

Clinical

Study

of 40 Cases

with

Onset

in Childhood

By John C. Gall, Jr., M.D., Alvin B. Hayles, M.D., Robert G. Siekert, M.D.,

and Haddow M. Keith, M.D.

Sections of Pediatrics and Neurology (R.G.S.), Mayo Clinic and Mayo Foundation

(Submitted September 10, accepted November 13, 1957.)

The Mayo Foundation, Rochester, Minnesota, is a part of the Graduate School of the University of

Minnesota.

ADDRESS: (H.M.K.) Rochester, Minnesota.

703

PEDIATRIcs, May 1958

Ped

iui rics

VOLUME 21 MAY 1958 NUMBER 5

T

HE OCCURRENCE of multiple sclerosis in children has been the subject of

recur-ring discussion for more than 30 years.

Wechsler,1 in 1922, rejected the majority of

cases reported up to that time, but admitted

that authentic cases, though they are rare,

do occur. He placed the incidence of

multi-ple sclerosis with onset in childhood at about 2% of all cases. Since 1922, reports of sporadic cases and several series of cases

of multiple sclerosis in children have ap-peared in the literature.2 Some authors have expressed doubt that multiple sclerosis

actually occurs before the age of 15 years.

In order to investigate this problem further,

it was felt worth while to review our

ex-perience at the Mayo Clinic with respect to

the occurrence of multiple sclerosis in

chil-dren.

PATIENT MATERIAL

The files of the clinic from 1920 to 1952,

inclusive, were reviewed. In this 33-year period

40 patients fulfilled the criteria established for

inclusion in the study.#{176} Eight children were

less than 15 years of age when the diagnosis of multiple sclerosis was entertained on the

basis of manifest acute neurologic abnormalities and previous history (or subsequent course if

seen again) of appropriate neurologic

symp-toms and signs. Thirty-two patients were be-tween 15 and 20 years of age when the

diag-nosis of multiple sclerosis was made; these

32 patients gave histories of neurologic

symp-toms prior to the age of 15 years that appeared to be characteristic of multiple sclerosis. Pa-tients with multiple sclerosis who were more

than 20 years of age with a history of neuro-logic difficulty prior to the age of 15 years were arbitrarily excluded.

#{176}While we are not attempting to provide a true

picture of incidence, it is interesting to note that

11 of the 40 patients (about a third) were observed

during the 10-year period, 1940 to 1949, inclusive.

(2)

OGir1:Z6

D

Bo:14

Total

:40

i1flflA

H

Fic. 1. Distribution of cases by age at onset. The chief diagnostic criteria used in

select-ing cases for inclusion in the study were symp-toms and signs due to scattered lesions of the

central nervous system. Lesions were scattered

in regard to both time and space. In all in-stances at least two episodes of neurologic dysfunction occurred with a period of

rela-tive remission between them; objective evi-dence of multiple lesions in the central nervous system was observed in every patient. Patients

with retrobulbar neuritis but no other findings

were not included. Particular attention was given to exclude other diseases such as

post-infectious encephalomyelitis, encephalomyelop-athy of specific (infectious) etiology, and the heredofamilial and demyelinizing degenerative

diseases of progressive course.

It should be clearly noted that this is a

clinical study based on clinical criteria.

Patho-logic material of the patients who died was

not available for review. As a consequence,

questionable or borderline cases were excluded. Follow-up data were available on 32 of the 40 patients.

A family history of neurologic disease was absent in all of these cases except a few

in-stances in which a convulsive disorder may

have existed.

10

8

6

4

2

OBSERVATIONS

Sex Distribution

Of the 40 patients 26 were girls and 14 were boys, a ratio of about 2:1. This is

roughly in accord with the findings of

M#{252}l-ler3 who noted 35 girls and 11 boys in a

series of 46 children. In adults, on the other

hand, the sex ratio for large series is quite

close to unity.4 Significant sex-related

dif-ferences in the symptoms, signs, or course

of the disease were not noted.

Age Distribution

In eight patients, six girls and two boys, the age at onset was 10 years or younger.

Significant differences in the course of the

disease in these eight patients were not

noted,

as compared to the remaining 32

with onset between the ages of 11 and 14

years (Fig. 1).

Mode of Onset

In the majority of cases constitutional

symptoms were not present at the onset of

the

disease;

the

patient

simply

became

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8

9

10

11

12

13

14

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705

aware of the gradual or sudden appearance of an impairment of neurologic function.

Usually the patient or parents were able

to recall that symptoms had begun on a

given day or even at a definite moment, but

in a few cases the development of weakness

and clumsiness in a limb occurred so

gradu-ally that no definite date of onset could be

determined. In seven cases the initial

epi-sode was accompanied by one or more of

the following symptoms: mild headache, nausea and vomiting, dizziness or true

ver-tigo, or excessive drowsiness. Fever was not found to be present in any case at the

onset, possibly because of the method of selection. Convulsive episodes occurred at or near the onset in one patient. This pa-tient had a convulsive episode at

7

years of age, 5 years prior to our examination, at

which time he had some headache and

presumably unilateral optic neuritis (ele-vated disk and blindness). A ventriculogram revealed only slight dilatation of the lateral

ventricles.

In most patients the initial episode lasted from a few days to several months. They were then symptom-free, or nearly so, for periods as long as 5 years. When the initial episode was severe and prolonged,

however, new symptoms appeared on a

background of chronic neurologic

dysfunc-tion.

Symptoms Occurring During Initial Episode

MOTOR.

The

initial complaint in 22 cases was a disturbance in function of a limb.

Although a

sharp

distinction could not al-ways be made between in-co-ordination and

muscular weakness, ataxia seemed to pre-dominate in most cases. Numbness or

tin-gling was present in the affected limb in 9

of the 22 patients. In cases in which an upper extremity was involved, the patient or his parents reported difficulty buttoning buttons, combing the hair, handling eating utensils and so forth. Any combination of limbs might be involved in any sequence.

VISUAL. Disturbance of vision was an

initial complaint in 16 cases. In seven

pa-tients this took the form of a relatively sud-den haziness or partial blindness in one

eye. In two patients both eyes were affected

at the onset. In three cases diplopia was associated with blurring as an initial

symp-tom and in two cases it occurred alone. In six cases a subsequent episode of blurring

occurred, while nine patients who had not had visual symptoms at the onset of their

illness later experienced an episode of

blurred vision. Combined motor and visual symptoms occurred initially in four pa-tients. Altogether 34 patients had either

mo-tor or visual symptoms, or both, initially.

The initial episode of blurred vision

im-proved after periods varying from 1 week to as long as 6 months; in some cases re-covery was apparently complete, but more often a degree of residual visual

involve-ment persisted.

MISCELLANEOUS. Numbness and tingling of a limb occurred in nine cases in conjunc-tion with weakness or clumsiness of the

in-volved limb. Isolated sensory deficit was an initial complaint in only one case.

Objective vertigo was an initial symp-tom in five cases; dizziness, headache, and

vomiting accompanied the initial symptoms in seven cases. Somnolence was present

initially in three cases; it was an isolated initial symptom in only one case and its reliability in this case may be doubted. One patient noted recurrent tinnitus during an initial episode of ataxia. In one patient transient binaural loss of hearing was the

initial symptom. Unilateral facial weakness was the first symptom in

one

patient

and

accompanied other initial symptoms in

an-other patient. In one patient an initial epi-sode of retrobulbar neuritis was

accom-panied by urinary and fecal incontinence.

Symptoms Occurring Within Period of Study (Table I)

MOTOR.

The specffic

complaint

of

muscle

weakness occurred at some point in the

course of illness in all

but

five

patients.

In

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TABLE I

SYMPTOMS IN MULTIPLE SCLEROSIS WITh ONSET IN CmLDIIooD

(40 cases)

Muscular weakness One or both legs One or both arms Facial weakness (unilateral) 35 23 6 35 In-co-ordination One or both legs One or both arms Tremor Altered speech 40 34 8 16 40 Sensory changes Numbness of arms Numbness of legs Numbness of other areas Paresthesia 23 21 6 18 33 Visual Diplopia Blurred vision 27 26 34 Sphincter involvement Urinary Anal incontinence Constipation 21 4 12 26 Other

Dizziness or vertigo Headache

14 12

eventually involved. In 12 patients a single arm or hand was involved, and in 11, both upper extremities were weak at one time

or another. Five patients had involvement

of one arm and leg only. Unilateral facial

weakness was a complaint in six patients,

two of whom had facial numbness also.

IN-CO-ORDINATION. This symptom

in-cluded disturbances of motor function vari-ously described as clumsiness or unsteadi-ness of arms or legs, as well as references

to specific disability such as inability to button buttons, comb hair, ride a bicycle

and

so forth. All 40 patients complained of these or similar disturbances at some time.

In 35 cases both legs were involved, in 5 only one leg. Both arms were involved in 26, one arm only in 8, and neither arm in

6 patients. Sixteen patients had noted

al-terations of speech, such as dysarthria or

alteration in rhythm.

Visuu. COMPLAINTS. Thirty-four patients had disturbance of vision. Twenty-seven

patients had double vision and 26 had

blurred vision in one or both eyes. Sixteen patients had both blurred vision and

diplo-pia, though not necessarily at the same time. In eight patients decreased vision was

noted in only one eye.

SENSORY DISTURBANCES. Disturbances of

sensation were reported in 33 patients. The term “numbness” was used in 27 cases; in 23 of these one or both of the patients’ arms

were affected and in 21, one or both legs.

In four cases loss of sense of touch was

noted specifically. Four patients reported loss of sense of temperature. One patient experienced numbness of the abdomen and another, numbness of the back radiating into the leg. Numbness or loss of taste in

the tongue was reported in three cases, and numbness of the face was reported in three cases. No patient complained of facial pain (trigeminal neuralgia). Paresthesias of one or several limbs were reported in 18

cases; “tingling” was used descriptively in a third of these cases. One patient had paresthesias over the right scapula, and one had transient paresthesias over the right side of the face. One patient noted a tin-gling sensation in his body on flexing the

neck (Lhermitte’s sign).

SPHINCTER DISTURBANCES. Twenty-one patients reported transient disturbances of urinary function, including urinary incon-tinence, hesitancy, and urgency. Twelve

patients complained of constipation and four gave histories of fecal incontinence.

In all, 26 patients had some disturbance of

sphincter function; in 10 both bladder and bowels were affected.

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TABLE II

Nauaoioaic ABNORMALITIES IN MULTIPLE Sci.msosis

WITH ONSET IN CHILDHOOD (40 Cases)

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ARTICLES 707

OTHER SYMPTOMS. Vomiting (occurring

in nine patients) tended to occur every morning for several days, weeks, or even

months early in the illness. Dizziness oc-curred in seven patients, and in another seven a specific history of vertigo was

elicited.

Vomiting, dizziness or vertigo, and men-tal alterations were present in some cases

(Table I).

Five patients reported difficulty in swal-lowing, and six patients complained of jerk-ing muscles. Two patients noted vasomotor disturbances such as blueness, coldness, or increased perspiration of limbs affected by motor dysfunction. In five patients an

epi-sode suggesting a convulsion had occurred.

One of these has been mentioned. Each

of the other four had only one or two sei-zures; apparently they were not associated

with any other neurologic deficits at the

time of the seizure.

Physical Findings (Table II)

MUSCLE WEAKNESS. Muscle weakness was

observed in 26 patients. In 16 both legs were involved and in 5 only one leg. Both arms were weak in 11 cases, and only one arm in 8. Unilateral facial weakness (of

peripheral type) was noted in seven cases.

IN-CO-ORDINATION. Ataxic gait was ob-served in 28 patients. In 11 patients

in-co-ordination was so severe as to preclude walking. Other typical signs of

in-co-ordina-tion of limbs, such as terminal tremor and adiadochokinesia also were noted. In-co-ordination in the upper extremities was noted in 30 of the 40 patients; only one

upper limb was involved in 8 patients. REFLEXES. Babinski’s reflex was present

in 36 cases. It was present bilaterally in 30 and unilaterally in 6. Ankle clonus was present in 17 cases. Abdominal reflexes were absent bilaterally in 22 cases and uni-laterally in 3; they were diminished in 7. In two cases they were stated to be normal

and in five cases no record was made. Mus-cle stretch reflexes were increased bilater-ally in 29 cases, unilaterally in 5. They were diminished in three cases.

Muscular weakness One or both arms One or both legs

21 19

26

In-co-ordination One or both legs One or both arms Altered speech ‘39 30 14 40 Reflex changes Babinski’s reflex

Increased muscle stretch reflexes Absent abdominal reflexes

36

34 25

38

Disturbances of visual apparatus Pallor of optic disks Nystagmus

Scotomas

Sheathing of retinal veitis

19 28 7 5 35 Sensory changes

l)iminished vibratory sense in legs l)iminished position sense in legs Tactile sensory deficit

Pain and temperature sensory deficit 23 11 6 10 26

I)isturbances of sphincter function 5

Vesical Anal

VISUAL. Thirty-five patients exhibited

ab-normalities of the visual apparatus. Tern-poral pallor of the optic disks was present in 19 patients. Seven of the nineteen

pa-tients had central or paracentral scotornas on perimetry. In another patient a defect was noted in the upper quadrant of the left visual field. Sheathing of

the

retinal

veins

was present in five cases; perhaps it was

present in more but was not recognized since many cases antedated Rucker’s re-port,5 in 1945, of this valuable sign. Paresis of convergence or of conjugate gaze was present in five patients. Nystagmus was present in 28 patients. In 25 patients

hori-zontal nystagmus on lateral gaze was

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Laboratory Studies

Studies on the cerebrospinal fluid were performed in 30 patients. The pressures,

in-cluding response to compression of the

jugular vein, were normal in each instance. The fluid was normal in only one instance

TABLE III

rotary. In half of the patients both hori- (as to cells, protein or gold curve).

zontal and vertical varieties of nystagmus The fluid in all 30 cases contained one

were present. Weak pupillary response to or more leukocytes. Eight specimens had

light was noted in three cases, and in two one, two, or three lymphocytes each.

Nine-cases the pupils were unequal. teen specimens contained from 4 to 25

SENSORY. Sensory deficits were noted in cells; three specimens contained more than

26 patients. Loss or depression of vibratory 25 cells. The highest was 70 cells.

sensibility in the lower extremities was The fluid from 14 patients contained

ab-noted in 23, and decrease in joint sensibility normal amounts of protein : 2 had positive in the toes in 11, 10 of whom had positive results to Nonne and globulin tests; no de-results to the Rhomberg test. Tactile sen- termination of the concentration of protein

sory loss was recorded in four patients. Hy- was made; 12 had more protein than 40

peresthesia was noted in two patients. rng/100 ml of fluid. Ten of the twelve had

SPmNcTERs. Objective evidence of in- 41 to 80 mg/100 ml and the other two had

volvement of a sphincter at the time of 110 and 200 rng/100 ml, respectively.

examination was scanty. Three patients Gold sol or benzoin curves were

abnor-were incontinent of urine and one had an mal in 22 instances: 16 specimens had a first

“automatic” bladder. Two of these four also zone curve, and 6 had a midzone type

had fecal incontinence, curve.

MENTAL STATE. In nine cases a note of

altered mental state was made. In four Course

cases euphoria was mentioned; four

pa-tients were described as “giggly,” “de-pressed,” or “emotionally unstable.” One patient was confused and semistuporous on

the first day of examination but had recov-ered normal alertness within a few days.

In 15 patients only one episode occurred during childhood, and the full-blown

clini-cal picture did not appear until the later teens. In most of these 15 patients, the

na-ture of the initial episode in retrospect was quite suggestive of multiple sclerosis.

In the remaining 25 patients more than one episode with varied symptoms had

oc-curred by the age of 14 years. Eight of these patients were observed while still in the pediatric age range; they displayed

evidence of scattered involvement of the central nervous system.

MULTIPLE SCLEROSIS WITH ONSET IN CHILDHOOD: STATUS OF PATIENTS AT LAST REPORT

Total Duration

of Illness (yr)

No Follow-up (number of

patients)

Followed (number of patients)

Dead Bedfast Ambulatory Total

0-4 6 ‘3 0 1 4

5-9

10-19

20 and over

Total

1

0

8

1 2 4 7

6 7 4 17

2 1 1 4

(7)

ARTICLES

Follow-up data were available by letter on 32 patients. Ten were still ambulatory, 10 were bedfast and 12 had died, presuma-bly from this illness or its complications

(Table III), which were often recorded as

pneumonia.

The average duration of life of the 12

pa-tients known to have died was 14 years after onset of symptoms. One died 3 years after onset of symptoms and two survived for 29 years. Most of the patients who died

were bedfast several years terminally. The

youngest patient to die was 16 years of age.

COMMENT

The data presented indicate that from a

clinical standpoint multiple sclerosis does

occur in children and that it appears

simi-lar to the disease as seen in adults. By the

very nature of the disease process the

varia-bility in the clinical findings is immense. In children, however, just as in adults, evi-dence of weakness of limbs or

in-co-ordina-tion, visual disturbances such as retrobul-bar neuritis, diplopia and nystagmus, ab-normalities of speech, and involvement of “posterior column” sensibilities are present in the majority of instances. The course is

likewise variable and therefore prognosis is difficult to ascertain.

Confronted with a patient manifesting

evidence of multiple neurologic lesions, the physician must consider multiple sclerosis. If this is the first episode, the diagnosis may

be suspected but by definition, it cannot be established conclusively. The possibility of other diseases also must be considered carefully. If specific treatment of multiple

sclerosis becomes available, however, early diagnosis would appear to be important.

SUMMARY

Forty cases of disease of the central nerv-ous system, characterized by several

epi-sodes and disseminated lesions, with onset

in childhood and clinically typical of

multi-ple sclerosis, were studied.

The disease as it occurs in children does not appear to differ clinically from the

disease as observed in adults, in respect to mode of onset, symptoms, physical findings, and changes in the spinal fluid. In the Mayo

Clinic series, however, almost twice as

many girls as boys were affected.

A pediatrician confronted with a child showing evidence of scattered neurologic

deficits that remit, particularly a disturb-ance of vision and co-ordination, should

consider the possibility of multiple sclerosis.

REFERENCES

1. Wechsler, I. S. : Statistics of multiple scle-rosis; including a study of the infantile, congenital, familial and hereditary forms and the mental and psychic symptoms. Arch. Neurol. & Psychiat., 8:59, 192. 2. Low, N. L., and Carter, S. : Multiple

scle-rosis in children. PEDIATRICS, 18:24, 1956.

3. Muller, R. : Studies on disseminated scle-rosis; with special reference to symptoma-tology, course and prognosis. Acta med. scandinav., suppl. 222, p. 5, 1949. 4. McAlpine, D., Compston, N. D., and

Lums-den, C. E.: Multiple Sclerosis. Baltimore, Williams & Wilkins, 1955, p. 34 5. Rucker, C. W.: Sheathing of the retinal

veins in multiple sclerosis. J.A.M.A., 127: 970, 1945.

SUMMARIO IN INTERLINGUA

Multiple Sclerose In Patientes Pediatric Un Studio Clinic De 40 Casos

Esseva studiate 40 casos de morbo del sys-tema nervose central, characterisate per plure episodios e lesiones disseminate con declaration a etates juvenil e manifestationes clinic typic de multiple sclerose.

In su occurrentias in juveniles le morbo non pare differer clinicamente ab su forma obser-vate in adultos, tanto con respecto al moclo de declaration, al symptomas, e al constatationes physic como etiam con respecto a alterationes

in le fluido spinal. In le serie studiate al Clinica Mayo, ii habeva, tamen, quasi duo vices plus

pueras que pueros.

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1958;21;703

Pediatrics

John C. Gall, Jr., Alvin B. Hayles, Robert G. Siekert and Haddow M. Keith

Childhood